Housestaff Manual

July 2024 - June 2025

Department of Medicine
Massachusetts General Hospital
Harvard Medical School
Boston, MA

Editors
Elizabeth Gay, MD
Noemie Levy, MD
MGH Housestaff Manual Preface
It is an honor to present the 30th Edition of the MGH Department of Medicine Housestaff Manual. We submit this manual, which
we view as a great tradition of the Internal Medicine Residency Program, to function as a resource for medical residents and other
clinicians at MGH. We hope that it exemplifies the energy, compassion, and spirit of growth with which MGH medical residents
approach their training and their profession.

The Housestaff Manual shares lessons from our clinical experiences on the medical services, including our annual review of the
literature. Each year, this book reflects the diligent work of the residents, whose contributions join them with past generations of
house officers.

We extend our gratitude to those residents who contributed their time and expertise to edit entire sections of this manual. Multiple
sections have had significant updates and there are several new articles this year.

Cardiology: Will Pohlman & Sourik Beltran Endocrinology: Mirai Matsuura & Bryan Holtzman
Pulmonology & Critical Care: Sanjeethan Baksh & Joyce Zhou Rheumatology, Allergy & Immunology: Marissa Savoie
Gastroenterology: Hanna Erickson & Eric Barash Psychiatry: Richard Seeber
Nephrology: Kyle Saysana Primary Care: Unyime-Abasi Eyobio
Infectious Disease: Christopher Radcliffe & Matthew Adan Radiology: Rachel E. Grenier & Eric L. Tung
Hematology & Oncology: Hatem Ellaithy & Catherine Gutierrez Procedures: Max Quinn
Geriatrics & Palliative Care: Jade Connor

We would like to thank the many faculty, fellows, and administrators who assisted with this book. In addition, we are grateful to the
residents in the ENT, General Surgery, Neurology, Ophthalmology, Radiology, and Urology programs who lent their expertise to the
relevant sections.

Our work would not be possible without the countless hours of work by the previous editors of the MGH Department of Medicine
Housestaff Manual. We hope we have lived up to their example.

1994 Albert Shaw & Ravi Thadhani 2011 Kerry Massman & Vilas Patwardhan
1995 Barry Kitch 2012 Michelle Long & Mihir Parikh
1996 Sam Hahn 2013 Molly Paras & David Sallman
1998 Marc Sabatine 2014 Zaven Sargsyan & George Anesi
2000 Sherri-Ann Burnett & Bill Lester 2015 Ang Li & Jehan Alladina
2001 Jose Florez 2016 Nino Mihatov & Tessa Steel
2003 Andrew Yee 2017 Michael Abers & C. Charles Jain
2004 Ishir Bhan 2018 Kelsey Lau-Min & Jonathan Salik
2005 Aaron Baggish & Yi-Bin Chen 2019 Melissa Lumish & Shilpa Sharma
2006 Bobby Yeh & Eugene Rhee 2020 Jacqueline Henson & Alexandra Wick
2007 Rajeev Malhotra 2021 Leslie Chang & Daniel Gromer
2008 Maha Farhat & W. Steve Sigler 2022 Mitu Bhattatiry & Sirus Jesudasen
2009 David Dudzinski & Elizabeth Guancial 2023 Hannah Abrams & Alexandra Doms
2010 Roby Bhattacharya & Paul Cremer

None of this would be possible without the support of the Department of Medicine. We extend special thanks to Gabby Mills, Libby
Cunningham, Rachel Peabody, and Paula Prout. We also thank our Chief Residents – Blair Robinson, Sara Char, Josephine Fisher,
and Darshali Vyas– as well as Jay Vyas, William Kormos, Joshua Metlay, and Jose Florez for their devotion to the housestaff and
our education.

It has been an incredible honor to edit the Housestaff Manual. We look forward to the contributions of future generations of authors
and editors in the years to come.

Elizabeth Gay, MD & Noemie Levy, MD

Department of Medicine, Massachusetts General Hospital
June 2024

As with any other medical reference, this manual is not intended to provide specific clinical care decisions in any individual case and
should not substitute for clinical judgment. Please continue to consult your colleagues and supervisors, as well as the primary
literature, whenever possible. We hope to provide guidance in the form of peer education and a forum for future experts to share
their knowledge and hone their teaching craft for the benefit of their colleagues. We encourage you to use the manual, not only as a
quick reference, but also as a teaching tool, a source of relevant publications, and a jumping-off point for personal exploration.
Although we have reviewed every page, errors may exist. Please inform next year’s editors here to ensure these errors are
corrected.
MGH Housestaff Manual Table of Contents
CARDIOLOGY NEPHROLOGY Adrenal Insufficiency 182
ACLS: Cardiac Arrest & TTM 1 Acute Kidney Injury 96 Pituitary Disorders 183
ACLS: Bradycardia 3 Glomerular Disease 98 Calcium Disorders 184
ACLS: Tachycardia 4 Chronic Kidney Disease 99 Osteoporosis & Vitamin D 185
ACLS: Defibrillation/Cardioversion/Pacing 5 Dialysis & Transplant 100 Thyroid Disorders & Male Hypogonadism 186
EKG Interpretation 6 Advanced Diuresis 101 ALLERGY & IMMUNOLOGY
Narrow Complex Tachycardia 8 Acid-Base Disorders 102 Drug & Contrast Allergy 188
Wide Complex Tachycardia 9 Sodium Disorders 104 Angioedema & Anaphylaxis 190
Atrial Fibrillation & Flutter 10 Potassium Disorders 105 Mast Cell Disorders 191
QTc Prolongation 12 Magnesium & Phosphorus Disorders 106 Primary Immunodeficiency 192
Chest Pain 13 IV Fluids & Electrolyte Repletion 107 NEUROLOGY
Acute Coronary Syndrome 14 Urinalysis & Nephrolithiasis 108 Altered Mental Status 193
MI Complications 16 INFECTIOUS DISEASE Dementia 194
Cardiac Catheterization 18 Empiric Antibiotics & Antibiogram 109 Headache & Vertigo 195
Non-Invasive Cardiac Testing 19 Multidrug Resistant Organisms 112 Stroke & TIA 196
Echocardiography 21 Community Acquired Pneumonia 113 CNS Emergencies 198
Inpatient Heart Failure 22 HAP/VAP & Aspiration Pneumonia 114 Seizures 199
Right Ventricular Failure 25 Viral Respiratory/Head & Neck Infections 115 Weakness & Neuromuscular Disorders 200
Mechanical Circulatory Support 26 Urinary Tract Infections 116 Neuroprognostication 201
Pulmonary Artery Catheterization 27 Skin & Soft Tissue Infections 117 PSYCHIATRY
Cardiac Devices: PPM, ICD, & CRT 28 Osteomyelitis 118 Consent & Capacity 202
Valvular Heart Disease 29 Bloodstream Infections & Endocarditis 119 Agitation 203
Pericardial Disease 31 Meningitis & Encephalitis 120 Delirium 204
Aortic Disease 32 C. Difficile Infection 121 Psychosis 205
Syncope 34 Invasive Fungal Infections 122 Catatonia, NMS, & Serotonin Syndrome 206
Severe Asymp. HTN & Emergency 35 Tuberculosis 123 Depression 207
Peripheral Artery Disease 36 HIV/AIDS & Opportunistic Infections 124 Anxiety Disorders 208
Cardio-Oncology 37 Transplant ID 125 Alcohol Use Disorder & Withdrawal 209
Outpatient CV Health 38 STIs & Travel Medicine 126 Opioid Use Disorder & Withdrawal 212
Anti-Arrhythmic Medications 41 Tick-Borne Diseases 127 Other Substance Use & Drug Testing 213
Telemetry and Physical Exam 42 Mpox & Ectoparasites 128 PRIMARY CARE
PULMONARY & CRITICAL CARE Fever of Unknown Origin 129 Health Screening & Maintenance 215
Respiratory Distress 43 Rare Diseases at MGH 130 Transgender Health 217
Hypoxemia & Hypercapnia 44 Infection Control 131 Women’s Health 218
Noninvasive Oxygenation/Ventilation 45 Antimicrobial Dosing 132 Men’s Health 221
Interpretation of Chest Imaging 46 HEMATOLOGY Sleep Medicine 222
PFTs & Asthma 47 Pancytopenia & Anemia 133 HEENT Concerns 223
COPD 48 Sickle Cell Disease 135 Nodules 225
Bronchiectasis & Hemoptysis 49 Thrombocytopenia 136 Musculoskeletal Pain 226
Interstitial Lung Disease 50 Eosinophilia 137 Immigrant & Refugee Health 228
VTE Diagnostics 51 Coagulation Disorders 138 Climate Change & Health 229
VTE Management 52 Anticoagulation Agents 139 Health Equity & Insurance 230
Pulmonary Hypertension 53 Anticoagulation Management 140 Disability Competent Care 231
Mechanical Ventilation 54 Transfusion Medicine 141 CONSULTANTS
ARDS 56 Transfusion Reactions 143 Calling Consults 232
ECMO 58 Peripheral Smear Interpretation 144 Perioperative Medicine 233
Sedation 59 ONCOLOGY Dermatology 235
Shock 61 Acute Leukemia 145 Surgery 238
Sepsis 62 Lymphadenopathy & Lymphoma 147 Urology 239
Vasopressors 64 Plasma Cell Disorders 148 ENT 240
Toxicology 65 MDS & MPN 149 Ophthalmology 241
GASTROENTEROLOGY Hematopoietic Cell Transplantation 150 OB/GYN 242
Upper GI Bleeding 67 CAR T-cell Therapy 153 RADIOLOGY
Lower GI Bleeding 68 Solid Organ Malignancies 154 Radiology Basics 243
Abdominal Pain 69 Immune Checkpoint Inhibitors 156 Contrast 244
GERD & Peptic Ulcer Disease 70 Oncologic Emergencies 157 Protocols 245
Functional Dyspepsia 71 Febrile Neutropenia 158 Interpretation of Common Studies 247
Nausea & Vomiting 72 Inpatient Leukemia & Lymphoma Regimens 159 PROCEDURES
Diarrhea 74 GERIATRICS & PALLIATIVE CARE Ultrasound Basics 249
Constipation, IBS, & Colonic Disorders 75 Pain Management 161 Ultrasound-Guided Peripheral IV 251
Esophageal and Upper GI Disorders 77 Adv Care Planning & Code Status 163 Central Line 252
Inflammatory Bowel Disease 78 End of Life & Pronouncement 165 Arterial Line 254
Intestinal Disorders 80 Comfort Focused Care & Hospice 166 Intraosseous Line 255
Nutrition & Feeding 81 Geriatric Assessment & Frailty 167 Paracentesis 256
Pancreatitis and Pancreatic Mass 82 Polypharmacy & Elder Abuse 168 Lumbar Puncture 257
Weight and Weight Loss 83 RHEUMATOLOGY Thoracentesis 258
Liver Chemistry Tests 84 Approach to Rheumatologic Disease 169 Pericardial Drain 259
Biliary Disease 85 Arthritis 170 Fluid Analysis 260
Acute Liver Injury & Failure 86 Connective Tissue Diseases 172 Tube Management 261
Viral Hepatitis 87 Vasculitis 173 Exposures & Needle Sticks 264
Alcohol-Related Liver Disease 88 Miscellaneous Rheumatologic Diseases 175 LOGISTICS
MASLD 89 Autoantibodies 176 Monitoring & Prophylaxis 265
End Stage Liver Disease 90 Rheumatologic Medications 177 Peri-Procedural Anticoagulation 266
Hepatorenal Syndrome 94 ENDOCRINOLOGY Senior On Encounters 267
Liver Transplant 95 Outpatient Type 2 Diabetes Mellitus 178 Post-Acute Care 268
Inpatient Diabetes Mellitus Management 180 Bias, Patient-Directed Discharge, ICE 269
DKA/HHS 181 MGH Directory 270
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Cardiology ACLS: Cardiac Arrest & TTM

Maternal Code Blue Algorithm: AHA 2020
UNRESPONSIVE PATIENT START CARDIOPULMONARY AHA 2023 Guideline (Circ 2024;149:e254)
Check circulation (pulse), RESUSCITATION ILCOR 2023 Guidelines (Circ 2023;148:e187)
airway and breathing (C-A-B) start compressions
No definite pulse within 10 sec.
Call CODE BLUE (x6-3333, blue button on wall)
Call for defibrillator, backboard, ambu bag
CODE TASKS Monitoring: tele, defib pads, cont O2, BP cuff
MGH CODE ROLES
- Access (IV>>IO), Airway
- Code leader: Senior On
- Backboard Compress 2-2.4” deep, 100-120BPM,
- Code Whisperer:
- Compression quality / Code minimize interruptions & allow full recoil
AM = Consult SAR
status (always confirm) Without ETT: 30:2 compressions to mask vent
PM = Units NT
- Defibrillator, Drips With ETT:  compressors q2min, breaths q6-8s
- Pulse: SDU JAR
- ECMO/Embolus Early:
- Compressions: Interns
o page <10min of coding Rhythm check as soon as pads are on
- Bring Lucas: MICU
o Consider Tenecteplase Initial Defib if shockable, Epi if non-shockable
Intern
- Family (call HCP)
- Run tele + meds REVERSIBLE
QUICK GUIDE: DOSING PEA / CAUSES (H&Ts)
VT / VF
Asystole
- DEFIB: Biphasic (MGH) vs. - Hypovolemia
Mono (360J), if unknown, use SHOCK! - Hemorrhage
max setting. repeat shocks @ Biphasic - Hypoxia
same or ↑dose. If no ROSC w/ 120-200J - H+ ion (acidosis)
3 shocks consider AP pad EPI 1mg q3-5m
(MGH) - Hypokalemia,
placement and double hyperkalemia
sequential defib NO pulse - Hypothermia
EPI 1mg q3-5m
- AMIODARONE: 1st dose = 300 continue CPR - Thrombosis,
mg, 2nd dose = 150 mg +/- AMIO, LIDO coronary (ACS) &
PULSE / RHYTHM MgSO4 pulmonary (PE)
- LIDOCAINE: 1st dose: 1-1.5
CHECK - Tension
mg/kg, 2nd dose: 0.5-0.75mg/kg
q2 minutes pneumothorax
- MGSO4: if TdP 2g - Tamponade
- HYPERKALEMIA: 1g CaCl2, (cardiac)
Return of spontaneous
bicarb 1-2 amp IV, D50W 1-2 - Toxins (drugs,
circulation (ROSC) criteria: Go to post-arrest
amp, insulin 10u IV accidents)
(1) Pulse + BP
- NALOXONE: minimum 2 mg IV care/TTM evaluation
(2) Sustained ETCO2 > 40
if pulseless, if apneic but has (3) Spontaneous waves on a-line MATERNAL CODE:
pulse, 0.2-1 mg IV ABCDEFGH
Code Cart Medications

ACLS LOGISTICS & UPDATES

- ACCESS: try IV first, IO if necessary or IV not feasible; c/f reduced drug delivery esp with pre-tibial placement (AHA 2020 ACLS)
- STAT LABS: ABG with K & Hgb, CBC, BMP, LFTs, lactate, T&S, coags, fibrinogen, cardiac enzyme
- MONITORING: recommend wave capnography during CPR, keep ETCO2 at least >10mm H20, ideally >20
- PROGNOSTICATION: ETCO2 <10 mmHg in intubated pts after 20min CPR ~90% sensitive for no ROSC
- PREGNANT WOMEN: Apply left lateral uterine displacement, IVs above diaphragm, if receiving IV Mg, stop and give CaCl,
resuscitative hysterotomy if no ROSC within 5min, TTM should still be considered with ROSC

Thrombolysis for Known/Suspected PE During Code ECMO for Cardiac Arrest (ECLS, ECPR)
• Tenecteplase (TNK - preferred over tPA in PE Code) • STAT page “ECMO Consult MGH” or use “MGH STAT” app to
Given as IV push over 5 seconds call consult and for MGH ECMO guidelines ideally <10
- <60 kg: 30 mg minutes from code initiation.
-60 to <70 kg: 35 mg • Indications: Age<75, no ROSC w/in 5 min, EtCO2 >10 mmHg
-70 to <80 kg: 40 mg • Contraindications: BMI>45, EtCO2<10, lactate>18, pH<7.0,
-80 to <90 kg: 45 mg PaO2<50 on ABG, severe aortic regurgitation, aortic dissection,
-90 kg: 50 mg uncontrollable hemorrhage.
• If TNK is not available: Alteplase (tPA) 50mg IV over 2 • Significant medical comorbidity should be discussed with
minutes. Can give a second dose in 15min if no ROSC ECMO team
• Continue CPR for at least 15 minutes post lysis • Favorable if initial shockable rhythm, shorter low-flow time
• Contraindications (absolute): prior ICH, ischemic • Evidence: (Lancet 2020;396:1807; JAMA 2022;327:737, NEJM
stroke, head trauma (3mo), intracranial neoplasm or 2023; 388:299)
AVM, suspected aortic dissection, active bleeding • See ECMO
• Heparin gtt after lysis when PTT falls to <2x normal

Chris Schenck
1
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Cardiology ACLS: Cardiac Arrest & TTM

Initial Post-ROSC Evaluate for Reversible Consider Targeted Neuro-
Stabilization Causes Temp Mgmt (TTM) prognostication

Hemodynamics: MAP>65 - Obtain 12-lead EKG Is patient able to follow Multimodal eval at
(NEJM 2022;387:1456) - Consider other H&Ts commands? minimum of 72h,
- Norepinephrine 1st line off of sedating meds
pressor
No -Serial Neuro Exam
Oxygenation: SpO2 92-98% - If STEMI criteria on post-ROSC ECG - cEEG ASAP
(NEJM 2022;387:1467) activate Cath Lab (Call 6-8282)
- Page Stroke/ICU - bMRI >48-72h
o Ventilation: PaCO2 35-45 - Consider emergent CAG if c/f ischemic - SSEP>48h
Neuro (p20202)
(NEJM 2023;389:45) etiology (ischemic ECG changes, recent -NSE at 24h, 48h, 72h
- See TTM below
PCI/CABG, VT/VF arrest) (Neurocrit Care
- Preparation: Consider
Hypothermia not a contraindication for PCI 2023;38:533)
NCHCT, CVC, a- line
(Resusc 2010;81:398)

TARGETED TEMPERATURE MANAGEMENT AFTER CARDIAC ARREST

Rationale: Fever is associated with worse neurological outcomes and neuronal damage due to inflammatory changes and biochemical
cascades that develop following ischemia and reperfusion injury associated with cardiac arrest (Arch Intern Med 2001). Goal is to avoid
fever for neuroprotection and to be aggressive about diagnosing/treating infections.

Causes of fever: Inflammatory response to global ischemia-reperfusion; Infection (high risk of aspiration/pneumonia, global ischemia ->
gut ischemia -> bacterial translocation). Pan-culture and consider aggressive antibiotic treatment. Drug fever

*Importantly*: Per MGH policy, default strategy is maintenance of normothermia ≤37.5 C/≤99.5 F for at least 72 hours, w/central
temperature monitoring (bladder preferred), and placement of temperature control device in all patients (eg Arctic Sun)

TTM options if patient is not following commands (patient needs to be stable enough to wean sedation and paralysis for this exam):
• Normothermia (≤37.5 C)
o Allow passive rewarming until patient achieves T 37 C
o Arctic Sun or other temperature control device to maintain T 37 C for 72 hr Hypothermia (33°C)
• Mild Hypothermia (T 33-36 C)
o Individualized patient selection for mild hypothermia (T 33-36 C) decided by primary team
o Temperature control device placed as soon as possible with goal of achieving target temp within 4h of ROSC
o Maintain mild hypothermia for 24 hr, followed by normothermia for 48hr for total 72 hr
o For pts treated with mild hypothermia, Re-warming should occur at a target rate of 0.25°C/h till normothermia
achieved.
o Monitor blood glucose/electrolytes closely
o Relative Contraindications to Mild Hypothermia: Recent head trauma, active bleeding, major surgery (<14d), refractory
hypotension

Evidence:
- Targeted hypothermia (T 33 C) did not reduce 6-month mortality or survival with good neurologic outcome compared to targeted
normothermia (T<37.5 C) (NEJM 2021;384:2283)
- Whether certain subgroups benefit from targeted hypothermia is uncertain (e.g., initial non-shockable rhythm (NEJM 2019;381:2327))

Sedation and Analgesia:

- Patients should undergo continuous sedation/analgesia if undergoing TTM w/mild hypothermia. Propofol is preferred sedative agent,
dilaudid (or fentanyl) is preferred analgesic

Shivering:
- Stepwise approach to shivering in pts undergoing TTM (1st line: acetaminophen 650q6, Mg >3, 2nd line: skin counterwarming +
dexmedetomidine OR propofol OR hydromorphone boluses, 3rd line: propofol + hydromorphone gtt, consider buspirone 30q8, 4th line:
NMBA) (Neurocrit Care 2011;14:389)

Neuro-prognostication see Neurology section

Chris Schenck
2
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Cardiology ACLS: Bradycardia

Bradycardia with Pulse Bradycardia Diagnostic Algorithm
HR<60 bpm and symptomatic Are P waves present? *=Wide QRS
Circ 2020 Evidence Review | ACC/AHA Brady 2018 Bold = needs
Yes No pacemaker

1. Sinus arrest w/ junctional

ASSESS PATIENT escape OR ventricular escape
• Focused exam  vitals, mental status, pupils, [idioventricular]*
pulmonary edema, murmurs, warm/cold, other sx 2. A fib/flutter w/ slow/variable
• Review recent ECG, tele & labs, current meds, Regular P-P interval? conduction
recent dose changes
• Obtain 12-Lead ECG, have pacing pads available
• IV Access: BMP, Mg, lactate ± trop Yes No
• Monitor BP freq., keep O2 > 92%, maintain airway
1. Sinus pause/sinus
arrhythmia
2. Wandering pacemaker
IF PATIENT IS UNSTABLE: Regular P-R interval? 3. Non-conducting
Any of the following present? PACs
o Hypotension/shock
o Altered mental status Yes No
o Ischemic chest discomfort
o Acute heart failure/pulmonary edema 1. Sinus bradycardia (# 1. Mobitz I (# of P > # of QRS)
of P = # of QRS) 2. CHB w/ junctional escape
2. Mobitz II (# of P > # OR ventricular escape* (P
of QRS) unrelated to QRS)
Trial medications, low threshold to pace
If pulseless arrest develops
 ACLS PEA/Asystole
RHYTHM PEARLS
ATROPINE* TRANSCUTANEOUS PACING - If grouped beats  look for Mobitz I & II
1mg bolus | q3-5mins - See pacing page for details - In 2nd degree AV block with 2:1 conduction, it is not
(max 3g); 2hr half-life - Basics: Emergent 2mg possible to differentiate Mobitz I vs. Mobitz II
do not give s/p heart transplant lorazepam + 2mg dilaudid OR - Always remember to consider hyperkalemia!
avoid with AV block Mobitz II or RICU for fentanyl/midazolam +/-
CHB intubate  turn to PACER 
SET RATE: 100 BPM + SET ETIOLOGIES OF SINUS BRADYCARDIA AND/OR CHB
OUTPUT: 100 mA  turn Italic = sinus brady, Bold = CHB
output down to minimum
- Meds, esp. in - Inc. vagal tone - Ischemia/ACS
needed to capture  adjust rate
liver, renal dz - Elevated ICP (inferior MI, 2/2 SA
DOPAMINE IV infusion down
- SSS - Hypothermia vs AV nodal artery
5-20mcg/kg/min - Degenerative, - Carotid dz + lesion)
TRANSVENOUS PACING WIRE
OR calcific recent stent - Endocarditis
- Wire placed by cardiology
EPINEPHRINE IV infusion conduction dz - Infiltrative dz - Lyme carditis,
- Indications: 1) need for
2-10mcg/min - Elderly - Hypothyroidism myocarditis
transcutaneous pacing despite
- Hypoxia - Nocturnal/sleep - Pericarditis
meds, 2) unstable rhythm with
& ANTIDOTES BY CAUSE - Autoimmune/ apnea - Hyperkalemia
no quickly reversible cause
Infectious CM - Athlete - s/p septal
- s/p TAVR - Drugs/toxins ablation
IF PATIENT IS STABLE:
Monitor + Assess for reversible causes
- Mobitz II & CHB with wide QRS  always gets pacing wire even if SPECIFIC ANTIDOTES BY CAUSE
stable, call cards + ensure prepared to pace - Beta blocker: glucagon 3-10mg IV (if no response,
repeat bolus, if response, infusion at 3-5mg/h)
- HOLD nodal blockers/anti-HTN if applicable - Calcium channel blocker: glucagon as above, calcium
gluconate 3-6g q10-20min or gtt, insulin 1U/kg bolus
ATROPINE & AV BLOCKS with 0.5U/kg gtt
Take-home message: Atropine will not help in the setting of CHB and - Digoxin: dig immune FAB vial, 1 vial binds ~ 0.5mg
Mobitz II digoxin, administer over 30min
o Ineffective for blocks below AV node (response to atropine in pt with - Opioids: naloxone 0.4-0.8mg IV, consider gtt
AVB; Resuscitation 1999;41:47) - Organophosphate: atropine 2-5mg IV (double dose
o Potential worsening of Mobitz II 2/2 HR (Am J Card 1974;33:333) q5min until effect), pralidoxime 1-2g IV over 15-30min

Tom Sommers
3
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Cardiology ACLS: Tachycardia

Tachycardia with Pulse ACUTE DRUG DOSING
HR>120 bpm and symptomatic • Adenosine: 6mg rapid IV push (followed by NS flush) + arm raise,
can repeat x1  12mg if required, central line = ½ peripheral dose,
ACLS Guidelines 2020 relative contraindication in pts s/p heart transplant
• Amiodarone: 150mg IV over 10min (may repeat x1); then infusion at
ASSESS PATIENT 1mg/min x6h followed by 0.5mg/min x18h (max 2.2g/24h)
• Focused exam  vitals, MS, pulmonary edema, • Diltiazem: 0.25mg/kg IV bolus over 2min  gtt @ 5-10mg/h
murmurs, warm/cold, pupils, other sx • Lidocaine: 1.0-1.5mg/kg IV bolus (usually 100mg), refractory 
• Review: most recent ECG, tele, labs, meds, events repeat 0.5-0.75mg/kg IV push q5-10min PRN, max 3mg/kg 
• Obtain: 12-Lead ECG, Defib + pads maintenance infusion at 1-4mg/min; preferred agent if QTc
• IV Access: BMP, Mg, lactate ± trop if c/f ischemia • Metoprolol: 2.5-5 mg over 2 min; repeat q5 min; max dose 15mg
• Monitor BP frequently • Procainamide: 20-50mg/min or 100mg q5min until any of the
• O2: supplement to >94%, maintain airway following: arrythmia terminates, BP, QRS prolongs by 50% from
baseline, or total 17mg/kg given  maintenance infusion at 1-4mg/min
(adjusted for CrCl), avoid with QTc
• Sotalol: 1-1.5mg/kg IV over 5 min; then maintenance infusion at
10mg/min, contraindicated with QTc & caution in pts w/ ↓EF
IS THE PATIENT UNSTABLE? YES SYNCHRONIZED CARDIOVERSION VS.
Any of the following present? DEFIBRILLATION
o Hypotension / shock Analgesia (1-2mg dilaudid)
o Altered mental status Rhythm Mode Dose (J) *
+ sedation (2mg lorazepam)
o Ischemic chest discomfort / angina Narrow & Regular Sync 50-100
o Acute heart failure / pulmonary edema If narrow & Narrow & Irregular Sync 120-200
regular, can trial Wide & Regular Sync 100
adenosine
NO Wide & Irregular Defib 120-200
*Biphasic (MGH)
MEDICATIONS DETERMINE QRS WIDTH (> or <120 ms) & REGULARITY

NARROW NARROW WIDE WIDE

& REGULAR & IRREGULAR & REGULAR & IRREGULAR

Vagal IV BB or Dilt* Amiodarone Lido + 2g Mg (over 15min) &

Maneuvers (OK for VT or SVT) treat myocardial ischemia
 b/l QTc nml b/l QTc
If persists
Adenosine* EF >40%: Lidocaine, Sotalol,
Amiodarone (rhythm,rate)** Torsades (TdP) Non-TdP
Procainamide, Metoprolol
Digoxin (rate) 2-4g Mg & HR 2nd line =
EF <40%: Lidocaine
IV BB or Dilt** consider empiric 2g Mg (overdrive pacing, Amiodarone,
Amio/Procainamide isoproterenol) procainamide
------------
*avoid if HFrEF Suspect SVT + conduction abnl ------------
*avoid post OHT **possible cardioversion,  can trial vagal + adenosine Pre-Excited SVT  Procainamide
**avoid if HFrEF consider AC status (will not worsen VT) (nodal agents contraindicated)

DDx: ST, AT, DDx: AF + RVR, MAT, DDx: monomorphic VT, SVT DDx: PMVT (TdP & non-TdP),
orthodromic AVRT, Aflutter/AT + variable with aberrant conduction, AFib/Aflutter/AT + pre-excitation vs
AVNRT, Aflutter block, ST + freq PACs antidromic AVRT, aberrancy
Consider chronicity/AC preexcitation, meds &
If difficult to discern P status prior to giving electrolyte abnormality Lido generally safe 
waves, adenosine can rhythm control for effective for all PMVT and will
slow rate to differentiate Afib/Aflutter not worsen pre-excited rhythms

VAGAL MANEUVERS:
- Unilateral Carotid Massage: supine with neck extended  steady pressure to carotid sinus (inferior to angle of the mandible at level of
thyroid cartilage near carotid pulse), avoid if prior TIA/CVA in past 3mo, and those with carotid bruits; 5%-33% success
- Modified Valsalva Maneuver: semi-recumbent  blow forcefully into a 10cc syringe x10-15 seconds  reposition to supine and
passively raise legs at 45° for 15 seconds; 43% effective in breaking SVTs vs 17% with standard Valsalva (Lancet 2015;386:1747)
- Also consider: cold ice face immersion or ice-water bag to face (diving reflex, more effective in children); 17% success.

Roger Zhou
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Cardiology ACLS: Defibrillation/Cardioversion/Pacing

EXTERNAL DEFIBRILLATION/CARDIOVERSION/TRANSCUTANEOUS PACING
• About the device: the Zoll R Series is on all code carts & ICUs at MGH. This device allows for external defibrillation, cardioversion, and
pacing with additional benefits (e.g. display ET-CO2, CPR quality feedback, & upload rhythm strips into Epic)
• Additional supplies/resources: Ambu bag, intubation equipment, RICU staff, backboard, suction
• Medications: use procedural sedation (typically 50mcg fentanyl  2mg midazolam) when possible, requires Cardiac Anesthesia/RICU.
In emergent situations, Dilaudid 1-2mg  lorazepam 2mg are reasonable alternatives (often readily available).

DISPLAY/OPERATION OF ZOLL R SERIES

• Remove all clothing covering the patient’s chest. Dry chest if necessary. If the patient has excessive chest hair, shave it to ensure proper
adhesion of the electrodes. Can rip off hair with extra set of pads if razor not readily available in acute situations.
• Attach hands-free therapy electrodes in anteroapical position (pictured) or anteroposterior position

Pearls:
• CPR ok to perform while pacing, take
R-sided pulses (L not reliable)
• Failure to capture? Increase output,
ensure pads are in correct location
(avoid bony structures), consider ddx
(barrel chest, COPD, hypoxia,
Manual tamponade/pericardial effusion,
pneumothorax, acidosis, hyperK,
obesity, MI, cardiac drug tox [dig, anti-
arrhythmic])
• Failure to sense? Only happens with
synchronous pacing – can switch to
asynchronous pacing, reposition pads
Defibrillation Synchronized Cardioversion Transcutaneous Pacing
Indications: pulseless VT or VF Indications: Unstable SVT or VT Indications: Unstable bradycardia
FIRST turn the Selector Switch to ON. Then press Manual (bottom left soft key) to change to ALS
1. PACER appears as an option on the
1. Select the desired energy using the up and
Selector Switch. Turn to PACER
down arrow keys on the front panel
• Narrow, regular: 50-100 J (atrial flutter 2. Set the PACER RATE (BPM) to a value
often converts with 50 J) 20 bpm higher than the patient’s intrinsic
• Narrow, irregular: 120-200 J (atrial heart rate. If unknown or absent intrinsic
fibrillation typically requires 150 J) rate, use 100 bpm
• Wide, regular: 100 J • Observe the pacing stimulus
1. Default energy selection is 120 J. • Wide, irregular: 150-200 J (defib dose) marker on the display and verify
Initial dose 120-200 J. Use Energy that it is well-positioned in diastole
2. Press the Sync On/Off button
Select (UP) & (DOWN) arrow keys
to change the energy. • Confirm that a Sync marker () appears 3. Increase PACER OUTPUT (mA) until
on the monitor above each detected R- the paced beats demonstrate capture
2. If there is a shockable rhythm on wave to indicate where discharge will (“threshold”); the output value is displayed
the pulse/rhythm check, press occur on the screen.
Charge. Continue CPR while • If necessary, use the LEAD and SIZE • Capture = widened QRS complex +
charging. buttons to establish settings that yield the loss of underlying intrinsic rhythm
best display • Confirm mechanical capture with
3. Once charged, the red shock
pulse check and/or by observing
button illuminates. Shout “Clear!” 3. Press the CHARGE button on the front
ventricular contraction w/ US
then press and hold the illuminated panel. Ensure patient is “clear”
Shock button at the top right of the 4. Set the PACER OUTPUT to the lowest
console. 4. Press and hold the illuminated SHOCK setting that maintains consistent capture
button on the front panel. The defibrillator • Usually ~10% above threshold
4. Resume CPR for 2 minutes will discharge with the next detected R wave (typical threshold: ~40-80 mA)
before the next pulse/rhythm check
5. If additional shocks are necessary, increase • Pressing and holding the 4:1 button
the energy level as needed temporarily withholds pacing
• Confirm that a Sync marker () appears stimuli, thereby allowing you to
above each R-wave; you may need to observe pt’s underlying EKG
press Sync between shocks rhythm & morphology
• Treat underlying cause and/or
6. Anticoagulation required for at least four weeks
pursue transvenous/permanent
after cardioversion
pacing

Daniel Restifo

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Cardiology EKG Interpretation

Approach all EKGs systematically. Note rate, rhythm, QRS axis, intervals, complexes, chambers, ischemia/infarction. Compare with prior EKG.
R A T E (atrial, ventricular)
• If regular, 300 / #large boxes between each QRS (60,000/rate = R-R interval in ms)
• If irregular, count # of QRSs on EKG and multiply by 6 (printout = 10 sec)
• Normal 60-100bpm; <60 = bradycardia, >100 = tachycardia

R H Y T H M (regular or irregular; sinus vs non-sinus) 1 small box = 40 ms

• Sinus rhythm = P before every QRS and QRS following every P, regular w/ rate 60-100, normal P wave axis
• P waves/morphology: determine 1) if P wave is present (best leads to visualize P wave are II and V1), 2) atrial rate (100-180: sinus tachycardia;
140-220: atrial tachycardia, AVNRT, AVRT; 260-320: atrial flutter), and 3) axis (Normal axis: P wave upright in I/II, biphasic in V1)
• QRS morphology: narrow (<120 ms) = supraventricular origin; wide (>120 ms) = aberrant supraventricular conduction or ventricular origin
• P wave/QRS complex association: if not 1:1, determine if number of P>QRS (AV block) or P<QRS (AV node, His-Purkinje, or ventricular rhythm). If
P precedes QRS, evaluate PR interval. If P after QRS, evaluate RP interval. Determine if PR or RP interval is fixed or variable
o AVB: first degree (PR >200ms); second degree Mobitz I/Wenckebach (PR progressively longer until dropped QRS); second degree Mobitz
type II (sudden dropped QRS without PR lengthening); third degree (dissociation of P and QRS)

Q R S A X I S (use direction of QRS complex)

Axis Deviation Lead I Lead II Lead aVF Differential Diagnosis
Normal (-30 to +90º) ⊕ ⊕ ⊕/-
Normal variant, mechanical shifts, LVH, LBBB, LAFB,
Leftward
⊕ - - congenital heart disease, emphysema, hyperK,
(-30 to -90º)
ventricular ectopic rhythms, WPW, inferior MI, pacing
Normal variant, mechanical shifts, RV strain, RVH,
Rightward
- ⊕ ⊕ LPFB, dextrocardia, ventricular ectopic rhythms,
(+90 to +180º)
WPW, lateral MI (RBBB rarely causes RAD)
Extreme/Northwest Lead transposition, ventricular ectopic rhythms,
- - -
(180 to -90º) hyperK, artificial pacing, severe RVH
• Clockwise/counterclockwise rotation (“R wave progression”): R wave amplitude typically increases from V1 to V5, amplitude of R becomes greater
than S at V3 or V4. Early or late R wave progression is nonspecific and can be normal (Am Heart J 2004;148:80)
o CCW (“early R wave progression”): R>S prior to V3. Causes: RVH, WPW, LAFB, posterior MI.
o CW (“late R wave progression”): R>S after V4. Causes: cardiomyopathy, LVH, LBBB, anterior MI.
• Low voltage: average QRS amplitude <5 mm in I, II, III and <10 mm in precordial leads
o DDx: obesity, pericardial effusion, PTX, COPD, PE, restrictive or infiltrative CM (particularly amyloidosis), severe hypothyroidism, or anasarca

C O M P L E X E S A N D I N T E R V A L S (Circ 2009;119:e241)
• P wave: right and left atrial depolarization. Normal: duration <120ms, voltage ≥ 0.1mV in I, area (1/2 duration x voltage in II) ≤ 4 (Circ Arrhythm
Electrophysiol. 2022; e010435)
• PR interval: atrial depolarization, AV node and His-Purkinje conduction. Normally 140-200ms, changes with rate (shortened at faster rates, longer at
lower rates) d/t autonomic effects on AV nodal conduction
• QRS: ventricular depolarization. Normal duration 60-110ms, not influenced by HR. QRS 100-120ms = incomplete BBB or intraventricular conduction
delay (IVCD). QRS >120ms = BBB, ventricular activation (PVC, VT, fusion beats, WPW, paced beats), hyperK, Na channel poisoning, aberrancy,
hypothermia.
RBBB: QRS >120, rSR’ in V1 or V2, LBBB: QRS >120, wide negative
LAFB: left axis deviation, LPFB: right axis deviation, wide qRS in V6, S>R duration in I, QS in V1, wide tall R in I, aVL, V5,
QRS <120, qR in I, aVL and QRS <120, rS in I, aVL and V6. Causes: infection (myocarditis), V6. Causes: primarily dilated
rS in II, III, aVF. Common, qR in II, III, aVF. Rare in infarction, increased RV pressure cardiomyopathy (ischemia, infection,
nonspecific. isolation, usually w/ RBBB. (PE, Cor Pulmonale). valvular, infiltrative).

Bifascicular: RBBB + LAFB or LPFB

• ST segment: normally isoelectic plateau of ventricular potentials
• T wave: ventricular repolarization, with a slow upstroke and a rapid return to the isoelectric line after peaking. Usually asymmetric and in the same
direction as the QRS. Should have smooth contours (bumps in T are usually buried P waves)
• U wave: occurs in the same direction as the T wave, rate-dependent (shorter at faster rates); DDx: bradycardia, hypoK/Mg/Ca, hypothermia
• QT interval: ventricular depolarization and repolarization. Excludes U wave unless fused with T wave. Rate-dependent (shortened at faster rates).
Normal <440ms (M) and <460ms (F). Reassuring if QT is less than half R-R interval with normal HR

C H A M B E R E N L A R G E M E N T (Circ 2009;119:e251) all have low Sn and Sp

• LVH: Sokolow-Lyon criteria: S in V1 + R in V5 or V6
≥35mm OR R in aVL ≥11mm. Cornell criteria: S in V3 LAE RAE
+ R in aVL >28mm (M) or >20mm (F). For non-voltage
based criteria consider Romhilt-Estes score
• RVH: R>S or R ≥7mm in V1, S ≥7mm in V5 or V6
• LAE: P wave duration ≥120ms (>2.5mm), widely
notched P (≥40ms), negative component of P in V1 >1mm wide and deep
• RAE: P wave height >2.5mm in II (“P-pulmonae”), initial positive P wave in V1/V2 ≥1.5mm
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Cardiology EKG Interpretation

S T S E G M E N T A N D T W A V E C H A N G E S (JACC 2009;53:1003)
• Analyze abnormalities along the vectors of ventricular depolarization and repolarization (QRS-ST-T)
• T wave abnormalities: hyperacute, symmetric T waves can be found within minutes of ischemia, followed by T wave inversions (≥1mm in 2
contiguous leads). TWI normal if only in aVR, V1 or III. Isolated TWI in aVL may indicate mid-LAD lesion vs inferior MI (J Emerg Med 2014;46:165)
o TWI DDx: myocardial ischemia (symmetric), prior MI, acute PE (RV strain pattern: TWI V1-V4, II, III, aVF, RBBB, ↑Sp/↓Sn: S1Q3T3, TWI
III+V1 high PPV for PE > ACS (Am J Card 2007;99:817)), apical HCM (TWI V1-V6), arrhythmogenic right ventricular cardiomyopathy (TWI V1-
3), intracranial pathology (“cerebral T waves”, asymmetric), myocarditis, pericarditis, BBB pattern, V-paced, LVH with “strain”, normal variant,
digoxin effect (biphasic w/ initial neg. predominance), Type 1 Brugada (TWI V1-V2), athlete’s heart. (World J Cardiol. 2015; 7(2): 86-100).
o De Winter’s T waves: 2% of STEMIs present with tall, symmetric T waves + >1mm STD at J point in precordial leads + 0.5-1mm STE in aVR
c/w acute LAD occlusion (NEJM 2008;359:2071)
• ST depression: suggests subendocardial injury, ≥0.5mm below the baseline (PR segment), measured 80ms after the J point in 2 contiguous leads
o Downsloping or horizontal = more ominous. STD do not localize to territories (Circ Res 1998;82;957)
o Always look for STE to rule out reciprocal STD. STD in V1-V3 can be posterior MI (check posterior leads)
• ST elevation: suggests transmural ischemia, ≥1mm in leads except for leads V2-V3 (≥2mm in M ≥40y, ≥2.5mm in M ≤40y, ≥1.5mm in F), use PR
segment (isoelectric interval), measured at the J point (Circ 2018: e618-e651). Differential diagnosis:

Diagnosis w/ STE Characteristic ECG Findings (NEJM 2003;349:2128; Annals 2004;141:858; NEJM 2004;351:2195)
Acute STEMI STE in ≥2 contiguous leads in coronary distribution (see table), reciprocal STD
LVH Concave STE in V1-V3 with STD and TWI in I, aVL, V5-V6, voltage criteria as above
LBBB Concave STE in V1-V3, discordant with negative QRS
Acute pericarditis Diffuse STE (usually <5mm), PR depression, amplitude of STE:T wave (in mm) >0.26 is specific
Printzmetal’s angina/vasospasm Transient STE in coronary distribution as in STEMI
Acute PE STE in inferior and anteroseptal leads, mimics acute MI, complete or incomplete RBBB
Stress-induced cardiomyopathy (Takotsubo’s) Diffuse STE in precordial leads w/o reciprocal inferior STD, STE followed by deep TWI
Ventricular aneurysm Persistent STE after MI, often with abnormal Q waves
Early repolarization J point elevation ≥1mm in 2 contiguous leads (esp V4), amplitude of STE:T wave (in mm) <0.25
Brugada syndrome rSR’ and downsloping STE in V1-V2 (see below)
Male pattern 1-3mm concave STE, often highest in V2
Normal variant STE in V3-V5, TWI, short QT, high QRS voltage
Cardioversion Marked (often >10mm) and transient following DCCV
Coronary Distribution Modified Sgarbossa Criteria:
EKG Lead Territory Coronary Vessel To diagnose acute MI w/ LBBB
V1-V2 Anteroseptal Proximal-mid LAD (does not apply to pacers). Below =
V5-V6 Apical Distal LAD, Distal LCx, RCA traditional version (need 3pts)
I, aVL Lateral LCx (proximal) • Concordant STE >1mm in any
II, III, aVF Inferior RCA (85%), LCx lead = 5 points
V7-V9 Posterior LCx > RCA • Discordant STE >5mm in any
V4R RV RCA, LCx lead = 2 points
aVR L main or 3vD • STD >1mm in V1-V3 = 3 points
• Q wave: usually a marker of scar, pathologic Q waves must be deep (>1mm), 25% height of QRS, and 40ms long. More likely 2/2 prior MI if inverted
T wave in same lead. Small “septal” Q physiologic in V5, V6, I, aVL
Wellens Type A Wellens Type B
• Wellens Syndrome: sign of critical proximal LM or LAD lesion, 75% MI in <2w. Often pain free with h/o
angina. Normal/slightly elevated troponin. Type A: 25% biphasic (up then downsloping morphology) T waves in
V2 and V3. Type B: 75% symmetric, deeply inverted precordial T waves. Isoelectric or minimally elevated (<1mm)
ST segment. No precordial Q waves (Am J Emerg Med 2002;20:7; Am Heart J 1982;103:730)

OTHER
• J-Point Elevation Syndromes: J point is when QRS transitions to ST segment.
o Early repolarization pattern: benign STE in absence of chest pain, terminal QRS slur, or terminal QRS notch
 Suspicious features: FH sudden cardiac arrest or early unexplained death, workup c/f channelopathy,
h/o unheralded syncope suggestive of arrhythmogenic pathogenesis (Circ 2016;133:1520)
o Brugada Pattern: Syndrome only if symptomatic.
Autosomal dominant SCN5A loss of function in 10- Brugada Syndrome: Type 1 Epsilon wave
30%, M>F, common to have nocturnal cardiac arrest,
p/w VT/VF or sudden cardiac death (Circ Arrhythm
Electrophys 2012;5:606)
o Osborn wave: hypothermia T<93ºF, elevation of J
point height ~ proportional to degree of hypothermia in
II, V2-6. More dome-shaped than Epsilon wave.
o Epsilon wave: found in arrhythmogenic right ventricular cardiomyopathy (ARVC;
inherited, age 10-50, fibro-fatty replacement of RV myocardium → ventricular arrhythmias [Circ
2005;112:3823]), most Sp in V1 (30% with ARVC), low frequency, positive terminal deflection in V1-V3.
• Electrolyte Abnormalities
Abnormality Characteristic ECG Findings
Hypokalemia Prolonged QT, ST depression, flattened T wave, prominent U wave, higher amplitude P wave, prolonged PR
Hyperkalemia Peaked, symmetric T wave → flat P → prolonged PR ± AVB → widened QRS ± BBB (severe) → sinusoidal
Hypocalcemia Prolonged QT, unchanged T wave
Hypercalcemia Shortened QT (if severe, T-wave can merge with QRS and mimic STE)

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Cardiology Narrow Complex Tachycardia

NARROW COMPLEX TACHYCARDIA (QRS <120MS)
(NEJM 2012;367:1438; Mayo Clin Proc 1995;70:371)
Diagnostic approach & general principles:
1. Determine the width of the QRS complex
2. Determine if the rhythm is regular or irregular
3. Assess for the presence of P waves (noting location, axis and morphology)
4. Compare to baseline ECG
5. Treatment (See ACLS: Tachycardia and Atrial Fibrillation/Flutter)
• If unstable  synchronized cardioversion
• If stable  vagal maneuvers (carotid massage/valsalva/ice water on face).
Adenosine can resolve diagnostic dilemmas and treat AVNRT and AVRT
(adenosine is blocked by theophylline/caffeine & potentiated by dipyridamole)
• Acute treatment for all others is BB, CCB or amiodarone (use caution with
pharmacologic cardioversion and consider ruling out intra-atrial clot if pt has
been in Afib/flutter for > 48 hours and has not been anticoagulated for 3 weeks prior to cardioversion)
Regular, narrow complex tachycardias Irregular, narrow complex tachycardias
Sinus Tachycardia (rate >100, maximum HR = 220-age) Multifocal Atrial Tachycardia (MAT) (rate ~100-150)
Gradual onset Discrete P waves present, of ≥3 morphologies
Most important to determine underlying cause: hypovolemia, Irregular due to varying PP, PR, and RR intervals
hemorrhage, withdrawal (EtOH, BZD, opiate, BB), intoxication, Seen in COPD, pHTN, CAD, electrolyte disarray,
fever/infection, pain, hypoxemia, PE, anemia, tamponade, aminophylline/theophylline use
dissection, endo (hyperthyroidism, adrenal insufficiency, pheo)
Atrial Fibrillation (AF)
Focal Atrial Tachycardia (AT) (atrial rate 100-200) No coordinated atrial activity (P wave absent), irregular,
Due to abnormal automaticity at a single atrial focus other than the fibrillatory waves present
SA node, or due to a reentrant circuit within the atria Arises from numerous re-entrant tracts in atria or
Discrete P waves present, but of abnormal morphology +/- axis (i.e. pulmonary veins
p wave inverted in inferior leads) If associated with pre-excitation, the result is an
Classic digoxin toxicity is AT w/ variable AVB irregular, WCT
Usually seen in otherwise normal hearts
Atrial Flutter (AFL) (P wave rate 250-300)
Junctional Tachycardia Arises from true (isthmus-dependent, typical) or
Due to increased automaticity within the AV node (or reentrant functional (isthmus-independent, atypical) re-entry in R
rhythms, e.g., AVNRT) atrium
P waves may be absent (e.g. buried within the QRS complex), May be regular (e.g. 2:1, 3:1, 4.1, etc.) or irregular (if
inverted and/or retrograde variable AV block)
Atrioventricular Nodal Re-entrant Tachycardia (AVNRT) (rate Counterclockwise: negative flutter waves in II, III, aVF
150-250) Clockwise: positive flutter waves in II, III, aVF
Arises from functional re-entry within AV node No isoelectric baseline, atrial rate ~300 (always >250)
P wave, if visible, is retrograde (may be seen as a pseudo R-wave usually with 2:1 conduction but can have variable
in lead V1, or pseudo S wave in lead II) – note that retrograde P conduction
waves appear earlier in AVNRT than in AVRT AVRT
Short RP (when conducting fast-slow), however more commonly no Note: blue arrows =
RP (when conducting slow-fast) retrograde P waves
Trigger PAC (slow-fast) > PVC (fast-slow)
Young adults, F>M, usually arises within structurally normal hearts

Orthodromic Atrioventricular Re-entrant Tachycardia (AVRT)

(rate usually 150-250)
Ventricular depolarization occurs via the AV node, however an
accessory tract allows for retrograde conduction to the atria (if
ventricular depolarization occurs via the accessory tract, the
resultant QRS is wide and is termed “Antidromic, see “WCT”)
Retrograde P waves may be present (if so, they appear later than
those seen in AVNRT)

Junctional Tachycardia

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Cardiology Wide Complex Tachycardia

WIDE COMPLEX TACHYCARDIA (QRS ≥120MS)
DDx = VT (80%), SVT with aberrant conduction, pre-excitation syndrome, or pacemaker-mediated tachycardia
Features that Favor VT (note: absence does NOT rule out VT) Features that Favor SVT with Aberrancy
• Very wide QRS (>160 ms), Rate > 120 (if <120, consider Na channel • Known BBB: ventricular conduction delay
toxicity or VT in someone already on significant antiarrhythmics) (RBBB, LBBB, IVCD) with similar morphology
• New northwest (aka extreme) axis (leads I and II negative) and axis as seen on prior / baseline ECG
• AV dissociation (often V rate > A rate): pathognomonic for VT • Evidence of His conduction: QRS has sharp
initial deflection (suggests initial use of His-
• Concordance: all QRS in V1-6 are completely (+) or completely (-)
Purkinje system followed by aberrancy)
• Partial (fusion beat) or complete (capture beat) depolarization of His-
Purkinje by a competing supraventricular (atrial / junctional) rhythm • Pre-excitation on baseline ECG  supports
• Basel algorithm = VT likely if ≥2 of 3 present: (1) high risk substrate (prior antidromic AVRT or pre-excited atrial fibrillation
MI, EF<35, prior VT/has ICD), (2) lead II time to first peak >40ms (1 small • R wave peak time < 40msec (measured in lead
box), (3) aVR time to first peak >40ms (1 small box). II and aVR)
 Very effective: 93% sensitive & 90% specific [similar to other algorithms]
but faster diagnosis [36s vs 105s with Brugada] (JACC 2022;7:831).
Other important considerations:
• Hyperkalemia, antiarrhythmic drugs (digoxin, class IA or IC, amiodarone), TCA overdose
• Pacemaker-mediated/endless loop tachycardia: retrograde VA conduction of V-paced beat misidentified as native A-beat  V-
pacing. ECG shows V pacing at upper rate limit
• Sensor induced tachycardia: inappropriate sensing of nonphysiologic stimuli (vibrations, electrocautery, etc.) and pacing.

MANAGEMENT OF V T (also see ACLS: Tachycardia)

• Often no way to confidently distinguish VT or SVT with aberrancy. If there is any doubt, treat like VT
• Consider underlying processes: active ischemia, CAD with scar, electrolyte derangement (low K, low Mg), indwelling lines
• Check and replete electrolytes (K>4, Mg>2)
• Review baseline ECG for evidence of long QT or pre-excitation
Monomorphic VT Polymorphic VT Torsades de Pointes
DDx: ischemia, structural heart disease, idiopathic DDx: ischemia (acute, CAD, ICM) vs. prolonged QTc

1. Non-sustained VT (>3 complexes, <30 secs) 1. Evaluate for ischemia & need for Polymorphic VT that occurs
Asymptomatic  monitor, treat underlying cardiac revascularization with underlying prolonged
comorbidities (e.g., CAD, HF) 2. Stable  magnesium 2-4g over 10-15min, QTc (congenital or acquired).
Symptomatic  nodal blockade (BB>CCB), then AADs HR (isoproterenol, overdrive pacing), QTc Can be prompted by PVC
2. Stable and sustained (>30 seconds)  antiarrhythmic (lido), avoid bradycardia (amio, CCB/BB) falling on T wave of previous
agent (e.g. amiodarone, lidocaine, procainamide [WPW]) 3. Unstable  defibrillation beat (R on T phenomenon)
3. Unstable  synchronized cardioversion (100J) if Note: isoproterenol = pure
pulse; defibrillation if pulseless chronotrope will reduce RoT
VT Storm: ≥3 sustained episodes of unstable VT within 24 hours
• Lido bolus (preferred if prolonged QTc), Amio bolus (careful if long QT), co-admin propranolol 60mg q6 [JACC 2018;71:1897])
• Anti-tachycardia pacing (ATP): overdrive pacing at a faster rate than VT
• Treat / minimize ischemia: revascularization, IABP to improve coronary perfusion, reduce preload / afterload
• Reduce autonomic tone: intubation and sedation, stellate ganglion block/cardiac sympathetic denervation
• Call EP +/- MCS/Shock Team
• Catheter ablation (VANISH trial, NEJM 2016;375:111)

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Cardiology Atrial Fibrillation & Flutter

ATRIAL FIBRILLATION
Epidemiology (Heart Rhythm 2012;9:632) New AF Classification (Circ 2024; 149: e1-e156)
• RF: age, obesity, HTN, smoking, EtOH, DM, previous MI, HF, OSA Stage I: At-risk Presence of modifiable and non-
• Recurs in majority of cases due to secondary precipitant (surgery, for AF modifiable RFs
infection, MI, thyrotoxicosis, acute alcohol, PE) Structural or electrical findings that
• Often co-exists with atrial flutter (Circ Arrythmia EP 2009;2:393) Stage II: Pre-AF predispose to AF (atrial enlargement or
• Racial, ethnic, and gender inqeuities persist in AF screening and ectopy etc.)
management (Circ 2024; 149: e1-e156) Spectrum including paroxysmal (3A,
Clinical Evaluation of New-Onset AF Stage III: AF <7d), persistent (3B, >7d), long-
Spectrum standing persistent (3C, >12mo), or s/p
• H&P: presence & timing of sx, HTN, DM, valve dz, HF, angina,
successful AF ablation (3D)
congenital heart disease, OSA, FH of AF, acute precipitants (e.g.
EtOH, thyrotoxicosis, sympathomimetic drugs, surgery, MI, Stage IV: Decision is made to no longer pursue
myocarditis, PE, acute pulmonary disease, infection) Permanent AF rhythm control
• ECG: absence of discernible p waves, irregularly irregular R-R intervals (if regularized, may represent escape rhythm and CHB)
• TTE: LV function, enlarged LA/RA size, valve function, pulmonary HTN, LA thrombus (better visualized with TEE)
• CXR: evaluate for pulmonary parenchymal processes, pulmonary vasculature/edema
• Labs: TFTs, LFTs, BUN/Cr, CBC, NT-proBNP, BMP (K,Mg)
• May also need longer term rhythm monitoring (Holter, Zio patch). Consider stress test if signs/sx of ischemic heart disease.
• Smartwatch notification has PPV 0.84 for AF on subsequent simultaneous EKG in patients > 65 (NEJM 2019; 381:1909-1917)
Acute Management of AF with Rapid Ventricular Response
Hemodynamically stable?

Stable (SBP >90) Peri-stable (SBP 80-90) Unstable (SBP<80)

Rate control (IV if HR >130 or sx, follow with PO If borderline BP, carefully attempt Usually HR >150, signs of shock
agent once rates controlled) low dose BB or CCB (can try (AMS, cool ext.), refractory
concomitant IVF if pulm edema pulmonary edema or angina
- Magnesium: 2-4 g empiric IV Mg + nodal agents ↑
not a concern)
success of rate and rhythm control (JACC 2021;
78:375-381) Synchronized cardioversion:
Consider BP-sparing agents: start with 150J (Biphasic)
- Beta blocker: metoprolol preferred in most cases
(weigh risk of pharmacologic
- IV: bolus 2.5-5mg over 2min, repeat prn q5min,
cardioversion if not on AC) If pressors needed:
max dose 15mg
- Amiodarone: 150mg IV over 10 phenylephrine is first-line given
- PO: fractionated, up to 400mg total daily dose
min, can repeat x1 if needed and reflex bradycardia
- Caution if severe bronchospasm and w/ rapid
start gtt at 1mg/min
escalation in pts w/ ADHF
- Digoxin: 0.5mg IV followed by Higher HRs (>140) more likely to
- Calcium channel blocker: diltiazem
0.25mg IV q6h x2, total load 1mg. cause HoTN alone; lower HRs
- IV: bolus 0.25mg/kg (average dose 10-25 mg)
Check level s/p load. Careful in may cause HoTN if systolic or
over 2min, repeat prn q10-15min
renal impairment, contraindicated diastolic dysfxn, or decreased
- PO: fractionated, up to 360 mg total daily dose
if accessory pathways preload (“loss of atrial kick”)
- Reduce dose with hepatic or renal impairment
- Avoid in pts with LVEF<40% and in ADHF
Correct underlying etiology whenever possible once stable (e.g. infection, volume, PE, EtOH, PTX, PNA, MI, pericarditis)
Cardioversion (ALWAYS consider high risk of embolic stroke if any interruptions in AC for 3 weeks prior)
• Indications: Urgent: ischemia, end-organ hypoperfusion, symptomatic hypotension, severe pulmonary edema; Elective: new-onset
AF or unacceptable symptoms from persistent AF
• Synchronized Electrical Cardioversion (DCCV): start with 150J (biphasic),↑energy if NSR not achieved. See ACLS: Cardioversion.
• Chemical Cardioversion: success rate significantly higher for acute (<7d) compared with longer duration AF
o Pill-in-pocket (flecainide, propafenone) + BB or CCB
o Ibutilide (most effective) or Dofetilide or Procainamide
o Amiodarone (IV infusion weakly effective for cardioversion, PO load over 3-4w, 27% rate of cardioversion)
• Anticoagulation (applies to BOTH chemical and electrical)
o Pre-cardioversion: if definitive new onset <48h: may proceed without anticoagulation. If Afib onset >48h or unclear:
anticoagulate for 3w prior to cardioversion or obtain TEE immediately prior to cardioversion (NEJM 2001;344:1411)
o Post-cardioversion: anticoagulate for at least 4 weeks after cardioversion (risk of myocardial stunning and AF recurrence, but
unproven efficacy). Anticoagulation beyond 4 weeks after reversion to NSR is based on CHA2DS2-VASc and HAS-BLED scores

Risk Assessment (Risk scores DON’T account for the complete spectrum of RFs - Individualize AF management)
• CHA2DS2-VASc: 1pt for CHF, HTN, Age 65-74, DM, female Sex, Vascular disease; 2pt for Age≥75, Stroke/TIA. CHA2DS2-VASc >
CHADS2 in “truly low risk” subjects (Thromb Haemostasis 2012;107:1172)
o Score 0 = no AC or ASA; Score 1 (2 in women)= no AC vs AC based on clinical judgment, generally lean towards AC initiation;
Score ≥2 (≥3 in women) = AC
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Cardiology Atrial Fibrillation & Flutter

o NOT used to guide decision making for HOCM or mitral stenosis (MS) with moderate severity or greater.
• HAS-BLED: risk stratification of bleeding risk w/ oral AC. HTN (SBP>160); abnl renal function (CrCl<50); liver disease (cirrhosis or Bili
2x ULN or AST/ALT/AlkPhos 3x ULN); stroke; bleeding history; labile INR (<60% in Rx range); elderly (>65y); antiplatelet meds (ASA,
NSAID); alcohol (>8 drinks/w) or other drug use. Score ≥3 suggests caution and regular follow-up
• SPARCtool can aid in risk/benefit assessment and choice of anticoagulation

Anticoagulation (AHA/ACC/HRS: Circ 2024; 149: e1-e156 ; Stroke 2010;41:2731)

• Consider AF burden when estimating stroke risk (JAMA Card 2018; 601-608). Subclinical AF is also associated w/ increased
stroke/systemic embolism (NEJM 2012;366:120). In these pts, AC reduces the risk of ischemic stroke but increases the risk of major
bleeding, thus AC decision should be individualized. (Circ 2023; 123:067512)
• DOACs vs warfarin: DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) recommended > warfarin in all except w/ mod-severe
mitral stenosis, HOCM, or mechanical valve. Warfarin may be > rivaroxaban in rheumatic heart dz (NEJM 2022;387:978-988).
DOACs: risk of stroke, mortality, & ICH, risk of GIB (Lancet 2014;383:955), apixaban lowest GIB risk (Annals 2022:175:1515-1524)
• Dosing: see Anticoagulation Agents for dosing. Dose-reduce apixaban to 2.5mg BID if 2/3: Cr ≥1.5, Wt ≤60kg, age ≥80
• Renal impairment: for pts w/ CrCl<15 or on dialysis, can use either warfarin or apixaban
• Bridging AC: see Anticoagulation Management

• Left Atrial Appendage Occlusion (LAAO) - LAA is the source of at least 90% of thrombi in pts with CVA and AF
• Watchman device: in non-valvular AF, device placement  comparable stroke prevention to warfarin with bleeding risk & improved
mortality (JACC 2017;70:2964). Consider if contraindication to long-term AC. AC can be discontinued 6w after LAAO, per MGH protocol.
• Surgical occlusion: decreases risk of stroke and systemic embolism. Grade 1A recommendation for pts with CHA2DS2-VASc ≥2
undergoing cardiac surgery in addition to continued AC (Circ 2024; 149: e1-e156).
Long-Term Rate vs Rhythm Control
• Traditionally, rate control considered noninferior to rhythm control for AF sx, CV mortality, & stroke risk (AFFIRM, RACE, PIAF, STAF,
HOT CAFÉ, AF-CHF). Latest guidelines shifted with benefit of early rhythm control and reducing AF burden. (Circ 2024; 149: e1-e156)
• Rhythm control (antiarrhythmics and AF ablation) superior to usual care (rate control) for patients with recently diagnosed AF (within
1 year) and concomitant CV conditions in decreasing CV mortality, stroke, and hospitalization for HF or ACS (EAST-AFNET 4)
o Consider rhythm control if persistent AF sx impairing quality of life, age <65, or comorbid HF (esp if systolic dysfxn)
o Restoration of NSR may lead to increased quality of life & exercise performance (NEJM 2005;352:1861; JACC 2004;43:241)
• Rate Control
o BB > CCB in achieving rate control (70% vs 54%), either alone or in combination with digoxin
o Digoxin alone is moderately effective in controlling V-rate at rest (time to onset 3-6 hrs), ineffective w/ high adrenergic tone
 Long-term digoxin a/w increased mortality in AF patients (JACC 2018;71:1063)
o Targets: lenient rate control (resting HR <110) non-inferior to strict (HR <80) w/ similar outcomes in CV death, stroke, bleeding,
arrhythmia, & hospitalization for HF (RACE II). Strict HR (or rhythm) control may be beneficial in younger pts or pts w/ HF
o Contraindications/Warnings: evidence of pre-excitation on ECG (in these patients, IV procainamide is 1st line), cautious use in
high-degree AVB. CCB should not be used in pts with LVEF <40% given negative inotropy
• Rhythm Control (Circ 2012;125:381)
o Choice of Agents:
 No structural heart disease: “pill-in-pocket” (flecainide/propafenone), dofetilide, dronedarone, sotalol, amiodarone
 Structural heart disease: CAD: dofetilide, dronedarone, sotalol, amiodarone; HF or LVH: amio, dofetilide
o “Pill-in-Pocket”: for pts with recent pAF and infrequent and well-tolerated episodes, ppx may have risk>benefit. PRN flecainide
or propafenone + BB or CCB at sx onset is safe and effective (NEJM 2004;351:2384)
o Catheter ablation (pulmonary vein isolation [PVI]): long-term AF recurrence rate vs AADs in both pAF (MANTRA-PAF, RAAFT-2)
& persistent AF (EHJ 2014;35:501). Ablation in pts w/ HF morbidity/mortality (CASTLE-AF). Ablation improves psychological
distress. (JAMA 2023; 925-933)
o AV nodal ablation with PPM: indicated when pharmacologic rate/rhythm control not achievable (JACC 2014;64:2246)

A T R I A L F L U T T E R (AFL, less prevalent but often coexists with or precedes AF)

• ECG: “sawtooth” P waves (F waves), atrial rate typically 250-300bpm w/ 2:1 conduction (~V-rate 150), though can be variable block,
3:1, or 4:1. 1:1 conduction can briefly precede VT/VF
o Type 1 (typical): reentrant loop in RA via cavo-tricuspid isthmus
 Counterclockwise: more common, inverted flutter waves II, III, aVF + upright flutter waves V1
 Clockwise: less common, upright flutter waves in II, III, aVF + inverted flutter waves in V1
o Type 2 (atypical): does not meet criteria for Type 1; is often faster and refractory to ablation
• Anticoagulation: risk of thromboembolism lower than AF (J Stroke Cerebrovasc 2018;27:839) but
anticoagulation management is similar to AF (Chest 2012;141:e531S)
• Rate control: similar strategies (BB, CCB) to AF, but more difficult to successfully rate-control vs. AF
• Rhythm control: Ablation > AAD. Cavo-tricuspid isthmus (CTI) ablation for typical flutter >90%
effective at 1y (Circ Arrhythmia EP 2009;2:393). However, prophylactic CTI ablation during PVI for AF pts
without documented AFL fails to reduce incidence of AFL or recurrence of AF (Arryth EP Rev 2022;
e10).

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Cardiology QTc Prolongation

D E F I N I T I O N (Circ 2009; 119: e241)
• QT interval correlates with repolarization time of ventricles
• Normal: ≤460ms; Borderline (adult): 460-479ms (female), 450-459ms (male)
• Measure from beginning of QRS to end of T wave in a lead with T wave > 2mm
(best in II, V5), define end point using tangent from peak of steepest slope to
isoelectric line; can use ECG or caliper function on telemetry
• QTc is QT corrected for HR; linear (i.e., Hodges/Framingham) formulas are
recommended by AHA (J Electrocardiology 2004;37:81)
• Can be calculated using MDCalc or with formulas below:
Framingham = QT + 0.154 * (1-RR) | Fridericia = QT/3√RR | Hodges = QT + 1.75
* (60/RR-60) | Bazett = QT/√RR | Rautaharju = QT * (120+HR)/180
o Framingham and Fridericia provide best rate correction and mortality prediction (JAHA 2016;5:e003264)
A S S E S S M E N T O F Q T C W I T H U N D E R L Y I N G W I D E Q R S (Heart Rhythm 2014;11:2273)
• Wide QRS (BBB/V-paced) lengthens QT interval; calculate using Mayo calculator, or with rough estimate using QT - (QRS-120)
o JT prolongation index = JT * (HR + 100)/518 where JT is distance between J point and end of T, with a JTI ≥112 identifying
repolarization prolongation in all ventricular conduction defects (J Electrocardiology 1992;25;131)
CONGENITAL LONG-QT SYNDROMES
• Majority of pts are asymptomatic, often discovered on ECG or QTc prolonged more than should be expected by drugs, etc.
• Sx: presyncope/syncope, hemodynamic compromise, sudden cardiac death; triggered by exercise, stress
• Tx: beta blockers, ICD if previous cardiac arrest and expected survival >1y (Circ 2006;114:e385)
D R U G - I N D U C E D P R O L O N G E D Q T I N T E R V A L (Heart 2003;89:1363; NEJM 2004;350:1013)
• Drugs inhibit IKr causing prolonged ventricular repolarization & exaggerate heterogeneity in repolarization times in different layers of
myocardium leading to reentry and tachyarrhythmia
Danger of prolonged QT = increased risk of Torsades de Pointes (TdP), which can degenerate into VF
Longer QT increases risk for “R on T” phenomenon and development of TdP (higher risk if PVCs)

Risk factors for TdP in Hospitalized Pts QT-Prolonging Drugs: [common, high-risk, (low-risk)]
Class of Drug
(Circ 2010;121:1047) (Br J Clin Pharm 2010;70:16; Circ 2020:142:e214)
Elderly, female, CLASS IA/C: quinidine, disopyramide, procainamide,
congenital LQTS, flecainide, propafenone
Demographics
anorexia/starvation, Antiarrhythmics CLASS III: sotalol, dofetilide, ibutilide, dronedarone,
hypothermia amiodarone - oral amiodarone rarely associated w/ TdP
Renal failure, hepatic due to uniform delay in repolarization across myocardium
dysfunction (or drug-drug ANTIBIOTIC: azithromycin, erythromycin, clarithromycin,
Comorbidities interactions impairing levofloxacin, moxifloxacin, (ciprofloxacin),
liver metabolism), HF, (metronidazole)
MI, LVH, hypothyroidism Antimicrobials
ANTIFUNGAL: fluconazole, voriconazole, (ketoconazole)
QTc >500ms, ANTI-MALERIAL: quinine, quinidine, chloroquine,
bradycardia (sinus, AV (hydroxychloroquine)
Rhythm-related
block, ectopy causing haloperidol IV, thioridazine, chlorpromazine, ziprasidone,
pauses), PVCs Antipsychotics quetiapine, risperidone, olanzapine, haloperidol oral,
Hypomagnesemia, clozapine
Electrolytes hypokalemia, Clomipramine, imipramine, citalopram, escitalopram,
hypocalcemia Antidepressants
(fluoxetine), (sertraline), (trazodone), (mirtazapine)
QT-prolonging drugs
Medication- (esp. IV infusions, >1 Anti-emetics ondansetron IV>oral, droperidol, (metoclopramide)
related concurrently), diuretic Methadone, propofol, hydroxyzine, (loperamide),
Others
use, beta blocker use (albuterol), (donepezil)

MONITORING FOR QT/QTC PROLONGATION

• Check QTc before and 12h after initiation/increased dose of QT-prolonging drug. Continue monitoring if prolongation is seen.
o Check QTc 2h post loading-dose of sotalol or dofetilide
• Class I indications for QTc monitoring with ECG (Circ 2004;110:2721)
o Initiation of QT-prolonging medication and dose changes q8-12h
o Overdose of proarrhythmic drug
o New bradyarrhythmia
o Severe hypokalemia or hypomagnesemia Illustration: Modified from Circ EP 2019;12:12

MANAGEMENT OF ACQUIRED LONG QT

• Stop offending drug if QTc >500ms or increase in QTc of >60ms
• ECG should be checked for bradyarrhythmias & signs of impending TdP (R on T, above). Stop drugs causing bradycardia.
• Check electrolytes & consider repleting (K >4, Mg >2). Supratherapeutic repletion (K: 4.5-5, Mg: 2-2.5) can be if risk of TdP

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Cardiology Chest Pain

HISTORY PHYSICAL EXAM
Stable Assess: Characteristics and duration of
symptoms, associated symptoms, provoking • Distress, diaphoresis
Angina/ACS Likelihood Ratios for ACS
(Circulation factors, and CVD risk factors. • New S4, MR (ischemia)
(JAMA 2015;314:1955)
2021;22;e368) • CHF (crackles, +S3, JVP,
Classic angina triad*: (1) substernal Low Risk
Pleuritic (0.3) Syncope (0.5)
pedal edema)
chest pain, (2) worse w/ exertion, and (3)
relieved by rest or nitrate Intermediate Risk • Carotid, subclavian, &
Anginal Equivalents: Chest pain/ Radiation to left Diaphoresis abdominal bruit (indicates
pressure/tightness, discomfort in chest/ arm, neck, or (1.4); exertional vascular disease)
jaw (1.3-1.5) (1.5)
shoulders/arms/neck/back/upper abdomen/ • Bilateral femoral and radial
Pressure / Pattern change /
jaw, SOB and fatigue typical (1.9) 24h (2.0) pulses (document pre-cath)
*Symptoms are no High Risk • Frank’s sign: bilateral diagonal
longer described as Women, elderly and pts w/ DM may have
vague sx: palpitations, jaw/neck/back pain,
Similar to prior Pain radiating to earlobe crease (slight  in
atypical/typical, ischemia (2.2) both arms (2.6)
instead use cardiac, SOB, N/V, abd pain, (pre-) syncope, AMS likelihood of CAD in adults
Abnormal prior
possible cardiac, or PAD (2.7)
stress test (3.1) <60yrs)
noncardiac Antianginals: nitrates; avoid if preload • Less likely ACS: pleuritic,
(Circulation sensitive (HoTN, AS, recent PDEi); BB positional, reproducible by
2022;80(17)) (careful in ADHF, long PR, 2˚/3˚ AV block); N.B.: Significant racial/ethnic
disparities exist in dx of ACS. palpation (LR 0.28)
CCB if BB intolerant; ranolazine
Abrupt onset of tearing/sharp thoracic or abdominal pain BP variation >20mmHg between
Acute Aortic
RF: known aneurysm, Marfan syndrome, CTD, HTN, M:F 2:1, 60-80y, arms, pulse deficits, new diastolic
Syndromes
cocaine use, high-intensity exertion (weightlifting) murmur, focal neurologic changes
Friction rub (breath hold to
Acute Pleuritic, sharp, improves upon leaning forward
distinguish from pleural rub);
Pericarditis May have URI prodrome; consider bacterial pericarditis if high fevers
tamponade (pulsus >10 mmHg)
Sudden onset, dyspnea/hypoxemia, pleuritic Tachycardia, tachypnea,
PE RF: hx of cancer/recent surgery/immobility, hemoptysis, calf/thigh hypoxemia, calf/thigh erythema,
pain/swelling swelling, tenderness
Ipsilateral absence of breath
Sudden onset dyspnea; RF: 20-40y (more likely if tall), FH or personal
Pneumothorax sounds, contralateral deviation of
history, smoker, known emphysema, M > F, recent chest procedures/lines
trachea
Pneumonia, Sharp, pleuritic CP a/w fever/↑WBC, productive cough, recent radiation, Bronchial breath sounds, crackles,
Pneumonitis autoimmune (SLE, RA, drug-induced lupus, collagen vascular diseases) dullness
Cardiac: HOCM, AS, vasospasm (Prinzmetal’s, drug/toxin), Takotsubo; MSK: costochondritis, Zoster; GI: GERD,
Other
esophageal spasm (may be relieved by TNG), Boerhaave’s, PUD, biliary colic, pancreatitis; Psych: panic attack
BASIC CHEST PAIN ALGORITHM
ECG: compare w/ prior ECGs & check q10-15m if suspicious, but <50% Non-diagnostic
Sn for dx of acute MI. Check posterior (if STD in V1-3 or R>S in V1-2) CXR
or R-sided leads (if STE in II/III/AVF) to better evaluate LCx/RCA.
If b/l LBBB or ventricularly paced, use Sgarbossa criteria to dx acute MI.

PTX PNA

Pericarditis NSTEMI STEMI Signs of PE

Diffuse upsloping ≥0.5mm STD or New ≥1mm STE in RAD, new RBBB,
STE and PR TWI (consider any 2 consecutive TWI V1-4, Widened
S1Q3T3 Normal
depression, PR posterior infarct) leads (except V2/V3 mediastinum
elevation in aVR, [M: >2, F: >1.5]) suggestive of RV
CRP compared to prior strain (Sp, not Sn)
ECG or new LBBB

± hs-troponins
Consider PE, Consider non- Consider
valvulopathy, or cardiopulmonary Aortic
ACS Pathway myopathy etiology Dissection

Non-Invasive Tests CT
- For pts w/ resolved chest pain or Angiography
Echo- Useful to assess valvular
stable chest pain as outpatient - Emergently for STEMI dx, EF, & RV strain (Sn, Sp) CT-PE if c/f PE
- Stress test: r/o ACS if low- - Early for high risk NSTEMI in PE (J Am Soc Echo - NPV 60%/89%/96% for
intermediate risk - All pts with confirmed ACS 2017;30:714) high/intermediate/low risk PE
- Coronary CTA: 100% NPV in pt should undergo - TEE if evaluating prosthetic (PIOPED II)
w/o CAD. Esp useful for patients angiography. Use GRACE, MV, suspected proximal aortic
<65 (JAMA Cardiol 2020;5;193). No TIMI, HEART, & Mayo Clinic dissection (can eval aortic root CTA chest if c/f aortic dissection
Δ in LOS or ED d/c rate vs hs-Tn score for risk stratification and valvular function) - Sn 97-100%, Sp 83-100% for
(JACC 2016;67:16) AoD (NEJM 1993;328:35)

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Cardiology Acute Coronary Syndrome

DEFINITIONS AND EVALUATION
Myocardial injury: defined as any patient with troponin >99th percentile without evidence of myocardial ischemia (sx of ischemia, new
ischemic ECG changes, new wall-motion abnormalities, and/or acute coronary thrombus on angio). May be acute or chronic.
Myocardial infarction: myocardial necrosis (trop >99th percentile + ∆) w/ ischemia (4th universal def. of MI, types 1-5: JACC 2018;72:2231)
• Type 1 MI: spontaneous plaque rupture, erosion,intraluminal thrombus
• Type 2 MI: supply-demand mismatch that is not atherothrombosis – most commonly due to sepsis/infection, arrhythmias, severe
anemia, renal failure, surgery, hypertension, and heart failure; other causes include vasospasm, microvascular ischemia (e.g.
Takotsubo), thromboembolism (Circulation 2019;140:1661).
o Must have a clear precipitating factor. If not, treat as a type 1 MI until further evaluation
o 50-70% have obstructive CAD – reasonable to initiate ASA, BB, and high-intensity statin
Evaluation of CP with hsTnT
Emergency Department – CP onset ≥3h PTA Inpatient or Emergency – CP onset < 3h
Check hsTnT immediately and at 1h Check hsTnT immediately and at 3h
Rule in: hsTnT ≥10 (F) or ≥15 (M) AND 3h ∆Tn ≥7 from baseline
Rule in: hsTnT ≥52 OR ∆ ≥5 from baseline
AND sx or ECG changes or concerning imaging (CCTA, cath)
 consider ACS
 consider ACS
Rule out: hsTnT <10(F) or <12(M) AND ∆ <3 from baseline Rule out: no significant ∆ in 3h
 unlikely ACS  unlikely ACS
Intermediate: calculate HEART score, repeat hsTnT in 3h and apply inpatient criteria
STEMI NSTEMI Unstable Angina
• 1mm STE in two contiguous leads (if V2-V3: >2.5mm in M<40, 2mm
in M>40, 1.5mm in F) OR new LBBB AND ⊕ biomarkers
• If baseline LBBB, use Sgarbossa’s criteria: ≥1 mm concordant STE, 1 ⊕ ECG or hx, ⊕ ECG or hx,
mm STD V1-V3, ≥ 5 mm discordant STE
⊕ biomarkers ⊝ biomarkers
• Electrically Silent: LCx or RCA lesions. Consider posterior V7-V9
leads, in which STE>0.5mm is diagnostic. Other changes: large R in
V2-V3, STdep in anterior leads (mirror image effect)
Clinical Evaluation & Risk Stratification:
• Consider pt’s baseline CAD risk. Review prior stress test and cath
data. risk of MI w/ resp infxn (esp flu) (NEJM 2018;378:345)
• Treat secondary causes of myocardial demand
ECG: (NEJM 2003;348:993)
• Obtain serial tracings (q15-30min) if initial ECG non-diagnostic in pts
with compelling hx & sx
• Non-STE ischemic EKG changes: ≥0.5mm STD (horizontal,
downsloping), new TWI ≥1mm or normalization
(“pseudonormalization”) of prior TWI in s/o sx
Cardiac Biomarkers:
• hsTnT 99th %ile among normal subjects: M 15ng/L, F 10ng/L
• 75% of healthy individuals will have measurable hsTnT
• hsTnt peaks within 12-48 hrs, normalizes in 5-14 days
REVASCULARIZATION
STEMI
o Primary PCI (PPCI) recommended revasc strategy for pts w/STEMI <48h symptom onset
o PCI center: aim<60 min to wire crossing; non-PCI center: aim<90 min to wire crossing
o PPCI regardless of symptom onset if cardiogenic shock, malignant arrhythmia (recurrent sustained VT/VF), persistent STE and/or CP.
o PPCI>48h symptom onset not indicated in stable pts (NEJM 2006;355:2395)
o If PPCI not possible within 120 min FMC (and <24h symptom onset), fibrinolysis: Aim<10 min to lytic bolus (Tenecteplase preferred)
w/ immediate transfer to PCI center. Discuss antithrombotic therapy w/cardiology. Contraindicated in ↑bleeding risk (esp ICH),
suspected dissection, ischemic stroke <3 months prior, severe HTN
NSTE-ACS (NSTEMI/UA)
o Multiple risk models incl GRACE, TIMI, PURSUIT. GRACE score is based on predictors of 6mo mortality (age, HR, SBP, Cr, cardiac
arrest at admission, ST deviation, elevated trop) (BMJ 2006;333:1091)
o Four subgroups for urgency to revascularization (JACC 2014;64:e139)
1. Very high risk (“immediate invasive,” within 2h): refractory/recurrent angina, hemodynamic or electrical instability,
mechanical complications, recurrent dynamic ECG changes suggestive of ischemia
2. High risk (“early invasive,” within 24h): temporal change in troponin, ECG changes (transient STE, STD, TWI), high risk pt
(GRACE>140)
a. Conflicting results between TIMAC (NEJM 2009;360:2165) and VERDICT (Circ 2018;138:2741) trials about outcome benefit of
early cath. However, both show improved outcomes with early cath in patients with GRACE >140
3. Intermediate risk (“delayed invasive,” within 72h): none of above but risk factors at baseline (e.g. EF <40%, GFR <60)

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Cardiology Acute Coronary Syndrome

4. Low risk (“ischemia guided,” no cath): no risk factors, GRACE <109, TIMI 0-1 OR not good candidate for angiography
PCI vs CABG: Selection of revascularization strategy should be based on the acuity of the patient’s condition, the angiographic
characteristics of the culprit lesion, and the complexity of the patient’s anatomy and, when appropriate, should include a Heart Team
discussion (Guideline: Circulation 2022;145:4). CABG often preferred for 3VD (NEJM 2009;360:961), L main disease (Lancet 2016;388:2743;
NEJM 2016;375:2223), 2VD with prox LAD stenosis or EF <50%, DM + 2VD w/ involvement of LAD (NEJM 2012;367:2375).
Multivessel Disease PCI Strategies
o STEMI w/o cardiogenic shock: complete revascularization strategy (culprit + non-culprit) has risk of CV death and MI at 3y
(COMPLETE, NEJM 2019;381:1411)
o STEMI OR NSTE-ACS + cardiogenic shock: culprit-lesion only PCI has a risk of death/RRT (CULPRIT-SHOCK, NEJM
2018;379:1699). Consider staged complete revascularization
o NSTE-ACS w/o cardiogenic shock: complete revascularization strategy (BIOVASC, Lancet 2023;401:1172)
ADJUNCTS TO REVASCULARIZATION
Adjuncts at Presentation:
1. ASA: established mortality benefit, give to all pts in an immediate load/maintenance strategy (325mg/81mg) (Lancet 1988;2:8607)
2. Peri-Intervention Anticoagulation: start on Dx of ACS. Usually stopped after PCI if no additional indication for AC (eg Afib, PE). If
no PCI and medically managed, usually d/c at 48h if ECG changes improving and c/f ongoing ischemia resolved (BMJ 1996;313:652). If
chronically on warfarin/DOAC, discuss transition to short acting AC with pharmacy pre-cath.
o UFH: Standard. Start gtt w/ bolus and use low intensity PTT goal (63-83). No bolus if giving lytics or if on warfarin and INR<2
o LMWH: possible reduction in death w/ minimal evidence for major bleeding, trials vs UFH largely null (BMJ 2012;344:e553)
o Fondaparinux: preferred to UFH/LMWH if medically managed. Contraindicated in PCI catheter thrombosis/complications
(JAMA 2006;295:1519)
o GPIIb/IIa Inhibitors: eptifibatide (Integrilin) used at MGH. Initiated in cath lab if PCI high-risk (extensive thrombus)
o Bivalirudin/Argatroban: direct thrombin inhibitor, preferred for patients w/ HIT. Emerging evidence suggests benefit over UFH
in STEMI (BRIGHT-4 Lancet 2022;400:1847)
3. Statin: atorvastatin 80mg daily regardless of baseline LDL (NEJM 2004;350:1495)
o Early high-dose statin within 24-96h may reduce death/adverse cardiac events if given pre-PCI (JACC 2009;54:2157; JAMA
2018;319:1331). Early anti-inflammatory effect may stabilize plaque (JAMA 2001;285:1711; JAMA 2004;291:1071)
o If very high risk clinical ASCVD w/ LDL-c>70 mg/dL, add ezetimibe and consider PCSK9i (JACC 2019;73:3168)
4. Nitrates: TNG SL (0.3-0.6mg) x3, if refractory  gtt (start 5-10mcg/min titrate to chest pain free). Nitropaste and gtt have shorter
half-life than SL if c/f HoTN. No mortality benefit. Caution in inferior MI/RVMI, SBP<100, or PDEi use in last 48h. If refractory CP
indication for earlier cath.
5. Morphine: not recommended. Consider only if unacceptable level of pain refractory to TNG, careful if suspicious for inferior MI/RVMI
6. Discontinue NSAIDs: risk of mortality, re-infarction, HF, and myocardial rupture after ACS
Adjuncts to start within 24h or Post-Revasc
7. P2Y12 Inhibitors: Pre-cath load not done at MGH. Do not start w/o cards. Controversial benefit & may delay CABG by 5-7d
(Circulation 2022;145:4).
o Ticagrelor: mortality compared to clopidogrel w/o increasing major bleeding. Reversible with platelet transfusion. Side effect:
dyspnea (14-21%, often mild & transient, but can be severe enough to warrant discontinuation), risk of pneumonitis w/ alveolar
hemorrhage. Avoid in liver disease, prior CVA, oral AC (PLATO, NEJM 2009;361:1045).
o Prasugrel: death, MI, CVA compared to ticag (NEJM 2019;381:1524). Contraindicated if prior TIA/CVA, wt <60kg, or >75y
o Clopidogrel: death, repeat MI when load/maintenance with PCI (Lancet 2001;358:527I). Prodrug, metabolized by CYP219, less
effective in those with LOF allele (NEJM 2009;360:354). May benefit from PPI ppx for ↓UGIB (NEJM 2010;363:1909). ↓Bleeding
compared to ticagrelor and prasugrel but ↑ischemic events (Circulation 2020;142:150).
o Cangrelor: IV reversible inhibitor with immediate onset and return of platelet function in 1h. Used in pts with recent PCI who are
unable to take PO or are periprocedure, needs pharmacy approval
DAPT duration: Default 12 months after ACS. Use DAPT score to help risk stratify. Evolving movement to shorten DAPT duration
(TWILIGHT NEJM 2019;381:2032; TICO JAMA 2020:323:2407; STOPDAPT-2 JAMA 2019;321:2414; SMART CHOICE JAMA 2019;321:2428;
GLOBAL LEADERS Lancet 2018;392:940-949; MASTER DAPT NEJM 2021;385:1643-1655 HOST-EXAM Lancet 2021;397:2487).
Bottom line: In select patients, single agent P2Y12 inhibitor after 1-3 months (vs. longer duration DAPT) is non-inferior in
reduction of cardiovascular events, with reduced bleeding risk.
o If on longterm AC (eg AFib, PE): P2Y12 inhibitor + DOAC > triple therapy. bleeding and non-inferior for ischemic events
(AUGUSTUS NEJM 2019;380;1509; RE-DUAL PCI NEJM 2017;377:1513; NEJM 2016; 375:2423). (Guideline JACC 2021;77:629).
 Common example: initiate triple therapy (ASA/clopidogrel/AC) for 1-4wks and then d/c ASA  AC + clopidogrel
8. Beta Blockers: start within 24h (1B for STEMI, 1A for NSTE-ACS), mortality benefit. Consider early initiation if ischemic arrhythmias
present. Not indicated for stable ischemic heart disease s/p cath, but rec’d after CABG (Circulation 2022;145:4)
o Caution in decompensated HF, risk for cardiogenic shock (>70y, SBP <120, HR >110 or <60)
o Contraindications: shock, cocaine-induced MI, PR>240ms, 2nd or 3rd degree AVB, severe bronchospasm (Lancet 2005;366:1622)
9. ACEi or ARB: start ACE within 24h in all patients if BP/renal function normal (2a;LOE:A for STEMI) but mortality benefit (1; LOE:A) in
anterior STEMI; use ARB if intolerant of ACE. ARB > ACE in patients with HF or LVEF <40% (Circulation 2008; 117:269).
10. Aldosterone antagonist: s/p MI on ACE and BB, and have LVEF<=40 + DM or sx of HF (1;LOE:B) (Circulation 2008; 117:269)
11. Lifestyle: smoking cessation, BP <140/90 (if DM or CKD, <130/80), cardiac rehab (1; LOE:B), depression screening; Flu vaccination

M G H P 2 Y 1 2 S W I T C H I N G G U I D E L I N E S (Ellucid policy, does not apply to patients on triple therapy)

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Cardiology MI Complications
M E C H A N I C A L C O M P L I C A T I O N S (JACC 2013;61:e78; JACC Cardiovasc Interv 2019;12:1825)
Prevalence / Risk
Complication Timing / Clinical Signs Evaluation Treatment
Factors
 STEMI: 50% develop shock  TTE  Inotropes/pressors
 STEMI~6%, NSTEMI~3%
w/in 6h of MI, 75% w/in 24h  PAC (CI<2.2,  Emergent PCI/CABG (<75y
 Anterior MI, LBBB, prior
Cardiogenic Shock  NSTEMI: 72-96h after MI PCWP>18) + STEMI + shock w/in 36h
MI, 3VD, age, HTN, DM,
(see Inpatient HF)  New CP, cold/wet physiology,  End organ hypo- of MI). SHOCK trial (NEJM
mechanical complications
HoTN, tachycardia, dyspnea, perfusion (lactic 1999;341:625)
 50% of post-MI death
JVD, rales, new murmur acidosis, AKI)  IABP and other MCS
 0.01% STEMIs &
Myocardial Free NSTEMIs
 Emergent surgery for
EARLY COMPLICATIONS (Hours – Days)

Wall Rupture  Transmural MI, 1-vessel  TTE (pericardial

 40% w/in 24h, 90% w/in 2w resection of ruptured
(Pseudoaneurysm: MI, 1st MI (poor effusion w/ high
 Tamponade in 85% myocardium w/ primary
LV defect contained collaterals), anterior & acoustic echoes
 Electromechanical dissociation, reconstruction
by only pericardium, lateral MI, HTN, late indicating clot)
aberrant T wave evolution,  Fluids, inotropes and
scar, more prone to thrombolysis (>14h),  STAT cardiac
abrupt episodes of HR/BP pressors (for cardiogenic
rupture than true fibrinolysis>>PCI, NSAIDs, surgery consult
shock)
aneurysm) female, age >70
 10% post-MI death
Emergency surgery or
 0.21% STEMIs, 0.04% transcatheter closure
NSTEMIs  TTE w/ doppler (L to device if unstable, mortality
 Bimodal: 24h & 3-5d to up to 2w
 1st MI, 1-vessel MI (esp. R shunt, RV ~50%. Closure often
Interventricular from event
LAD), CKD, anterior overload) delayed if stable.
Septal Rupture  New, harsh holosystolic murmur
infarct w/ inferior STE due  RHC: increase in O2  Vasodilators (use
(VSD) (50% w/ thrill), S3, loud P2,
to wrap-around LAD, older sat from RA to PA cautiously) to decrease L
hypotension, BiV failure (R>L)
age, female >5, large V waves to R shunt (nitroprusside or
 5% of post-MI death nitroglycerin)
 IABP/MCS
 0.05% STEMIs, 0.01%  No reperfusion: 2-7d
NSTEMIs  With reperfusion: median 13h  TTE (MR)
 Posteromedial (supplied  Abrupt dyspnea, pulmonary  CXR: edema (can
 Aggressive afterload
by PDA, with inf. or post. edema, hypotension be asymmetric to
Papillary Muscle reduction (nitroprusside or
MI) >> anterolateral (dual  Hyperdynamic LV, holosystolic RUL if MR jet
Rupture (leading nitroglycerin)
blood supply by LAD and murmur at apex (radiates to directed at right
to acute MR)  IABP
LCx) LSB w/ posterior pap muscle pulmonary veins)
 Emergent surgery
 Poor collaterals, 1st MI, rupture), murmur may be  Tall c-v wave in
single vessel disease absent in torrential MR or PCWP tracing
 5% of post-MI death severe HF
LV Aneurysm  Days to weeks  Acute: management of
(discrete,  No reperfusion: 10-30%  Acute: diffuse, displaced PMI,  ECG w/ persistent CHF, ACEi, avoid
 Apical-anterior wall >> S3 and/or S4, MR murmur, STE NSAIDs/steroids, start
dyskinetic area of
inferior posterior CHF  TTE, other imaging heparin (if EF<35%)
LV with broad  Total occlusion of LAD  Chronic: HF, VT/VF, systemic (CMR, CT,  Chronic: ACEi, digoxin,
neck, rarely
LATE COMPLICATIONS (Weeks – Months)

 Steroids, NSAIDs embolization, may be ventriculography) diuretics, AC (if EF<35%)

ruptures) asymptomatic  Surgical repair
 Warfarin (INR 2-3); DOAC
 5% of AMI patients post-
 Can form 24-72h post MI may be a reasonable
PCI
 90% of thrombi are formed by alternative (Circ.
 Usually in LV apex
2w  TTE w contrast 2022;146:e205–e223)
LV Thrombus  Large infarct size, severe
 Embolization risk persists for  CMR or CT  When to stop AC unclear,
apical akinesis or
6mo but most by 3-4mo; risk check for resolution of
dyskinesis, LV aneurysm,
10% if not on AC thrombus on TTE at 3-
anterior MI
6mo
 Peri-MI pericarditis has  10% at 2-4d post-transmural MI
 ECG (diffuse STE,
decreased with use of  May be focal or  ASA + colchicine
PR depressions)
diffuseDressler’s syndrome (1-  Avoid NSAIDs and
Pericarditis reperfusion therapy
6wks): malaise, fever,
 TTE (effusion)
steroids post MI as can
 Friction rub within 2-3 days  CMR and/or cardiac
leukocytosis, late autoimmune impair infarct healing
post MI. Often large infarct CT
carditis, rare
 PCI
 Long term anti-platelet
 Highest risk is absence of
Coronary Artery  Most cases occur within 30d of  ECG therapy (prasugrel or
P2Y12 inhibitor
In-Stent  1% at 1 year, then ~0.2%
PCI irrespective of stent type  Biomarkers ticagrelor given higher
Thrombosis  ACS symptomatology (troponin/CKMB) potency) with monitoring of
per year thereafter
adherence to therapy
 DAPT minimum one year

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Cardiology MI Complications
U R G E N T A S S E S S M E N T O F P O S T - M I C O M P L I C A T I O N (page Cardiology)
• Assess VS for hemodynamic instability, focused physical exam (new murmur, pericardial friction rub, elevated JVP, crackles, access site/s)
• Stat labs (troponin, PT/INR, PTT, T&S, BMP, lactate), ensure adequate vascular access (≥2 PIVs)
• Run telemetry, repeat ECG, STAT TTE, consider STAT CTA if concern for RP bleed/aortic dissection, notify interventionalist

Circuit Coronary Vessel Supply

SA Node 60% from RCA, 40% from LCx
AV Node 90% from distal RCA, 10% from distal LCx
Bundle of His AV nodal artery (RCA), LAD septal perforators
RBB LAD septal perforators, collaterals from RCA/LCx
LBB LAD, collaterals from RCA/LCx
LAD septal perforators (single supply, sensitive to
LAF
ischemia)
AV nodal arteries proximally, distally dual supply from
LPF Ecgwaves.com
LAD/PDA septal perforators
ELECTRICAL COMPLICATIONS
Overview
• Bradyarrhythmia/conduction block: may be due to coronary artery occlusion (see below) or baroreceptor reflexes (Anes 2003;98:1250)
• Tachyarrhythmia: related to creation of re-entrant circuit from scar formation and/or automaticity from adrenergic surge
Arrhythmia Location/Mechanism Incidence/Timing Treatment/Outcome
Sinus  Inferior and posterior MI  Up to 40% of acute MI
 Atropine, pacing if unstable, dopa/epi if HoTN
bradycardia  Beneficial: myocardial O2 demand  Occurs early in STEMI
 Inferior: vagal tone or AV node
 If due to inferior MI, transient (vagal)
First degree AV ischemia (RCA), narrow QRS
 More common in inferior MI  Continue CCB or BB unless PR interval
block  Anterior: septal necrosis below AV
>240ms
node, RBBB, wide QRS
Bradyarrhythmia

Second degree  Usually inferoposterior MI (vagal

 Usually transient; observe
AV block: tone, narrow QRS) or AV node  Usually within first 24h of MI
 Atropine if symptoms or HR <45
Mobitz Type I ischemia
Second degree  Usually anterior MI with infranodal  Consider temporary pacing
AV block: conduction injury, wide QRS, HR  Usually within first 24h of MI  In infranodal block, atropine may paradoxically
Mobitz Type II often <30, 33% progress to CHB worsen AV block
 If inferior MI: intra-nodal lesion;  3-7% acute MI  Recovery 5-7d; temp pacing required
Third degree narrower QRS escape  Inferior: gradual, stable  Inferior: transient, resolves on own
AV block  If anterior MI: infra-nodal lesion;  Anterior: sudden, 12-24h  Anterior: carries high mortality rate (80%) and
wide, unstable escape rhythm after MI indicates extensive necrosis
 50% already present on first ECG,  Patients w/ BBB are more likely to have
Intraventricular may represent antecedent disease of comorbid conditions, less likely to have
 2-5% of MI
Conduction Blocks conduction syndrome received therapies, have larger area infarcts,
 Suggests more extensive infarct and have high mortality
 May be compensatory for LV  Undesirable as myocardial oxygen demand,
Sinus
Supraventricular

dysfunction, common in anterior MI  25% of acute MI diastole time causes coronary perfusion time
tachycardia
Arrhythmias

 Pain, anxiety, pericarditis, fever  Treat underlying cause

 A/w mortality, particularly if late (>30d) AF (Circ
 Early: may be transient due to
Atrial fibrillation,  6-8%, may be >30% of 2011;123:2094)
sympathetic; atrial ischemia
Atrial flutter acute MI  If unstable, cardioversion; consider BB,
 Late: due to atrial stretch/HF
amiodarone, digoxin, anticoagulation
Premature  Correct electrolyte deficits, BB. Do NOT treat
 Due to electrical instability and
Ventricular  Variable with anti-arrhythmics as can mortality (NEJM
increased sympathetic tone
Contraction 1991;324:781)
Accelerated  50-110bpm, higher V- vs A-rate; in  Up to 20% of STEMI  Do not treat unless symptomatic or
Ventricular Tachyarrhythmias

Idioventricular 40%, considered a reperfusion  Usually within 12-48h, can hemodynamically unstable, usually short
Rhythm (AIVR) rhythm occur after reperfusion duration & does not affect prognosis
 NSVT 1-7%, sustained VT  Antiarrhythmic agents (amio, lidocaine)
 Monomorphic VT <170bpm is
(2-3% of STEMI, <1%  Urgent revasc if due to ischemia
unusual early after STEMI, suggests
Ventricular NSTEMI)  Cardioversion/defibrillation to prevent VF and
pre-existing arrhythmogenic scar;
Tachycardia  Usually 48h post STEMI, restore hemodynamic stability
recurrent ischemia usually
late VT (>48h) has very poor  Correct underlying abnormalities (pH, K, Mg,
polymorphic VT
prognosis hypoxemia)
 Risk factors: age, prior MI (scar),
 ACLS/defibrillation
anterior MI, cardiogenic shock,
Ventricular  5% of STEMI  Anti-arrhythmic infusion (24-48h amiodarone
LVEF, CKD
Fibrillation  1% of NSTEMI post-defibrillation)
 VF >48h post-MI may indicate LV
 Maintain K>4, Mg>2.2
dysfunction

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Cardiology Cardiac Catheterization

• Note: RAO caudal: best overall view & best for LCx; LAO caudal: LM, prox LAD, prox LCx; LAO + RAO cran: mid+distal LAD
LEFT VS RIGHT HEART CATHETERIZATION
• LHC (often used to describe Cor Angio): Arterial access (radial, fem). Assess coronary anatomy/lesions, LV & Ao pressures. PCI.
• RHC: Venous access (IJ, fem). Assess hemodynamics (see Pulmonary Artery Catherization); cardiac biopsies (usually RV)
CORONARY ANATOMY
• LCA and RCA & their branches create two rings around the heart: RCA + LCX in AV groove; LAD + PDA in IV groove
• 80% of PDA arises from RCA (right dominant), thus inferior MI more likely due to RCA lesion; 10% from LCx; 10% co-dominant
PREPARATION FOR CATHETERIZATION
• NPO MN; INR<2 for radial, <1.8 for fem/IJ; monitor Cr, no ppx abx. Continue ASA (for planned PCIs, loading of 324 mg chewed ASA
should be given if pt not on daily ASA), statin, BB. Hold AC (ellucid guidelines): UFH gtt (hold when on call), LMWH (hold tx dose 24h
prior. DVT ppx 12h prior), DOACs >48hr or >72hr if CrCl<30. Hold metformin (1d pre-, 2d post-proc), may hold/delay starting ACEi
• Document b/l radial, femoral, popliteal, DP pulses, & Allen’s test. Check for bruits. Note history of HIT, PVD, Ao aneurysm/dissection
• Contrast allergy: pre-tx w/ steroids & benadryl if patient has documented allergy. See Contrast Allergy for MGH protocols.
• Respiratory distress: patient will need to lie flat; consider intubation if prohibitive hypoxemia/pulmonary edema
• Pre-hydration w/ crystalloids and NAC/bicarb have not been shown to prevent CIN in most patients with moderate CKD (Lancet
2017;389:1312; NEJM 2018;378:603); CIN risk calculator; See Contrast
PERCUTANEOUS CORONARY INTERVENTION CONSIDERATIONS
• Access: fewer bleeding/vascular complications if radial (vs femoral) esp for PCI iso ACS, possible death in ACS (JACC 2018;71:1167);
due to radial vasospasm, CCB and/or nitrogylcerin is administered along with UFH to prevent arterial occlusion
• BMS vs DES: in-stent thrombosis with DES with subsequent MI/revascularization andCV death; however, risk of late stent
restenosis so requires longer duration of DAPT (JAHA 2021;10:e018828; Lancet 2019; 393; 2503)
• Can identify HD significant lesions via: fractional flow reserve (FFR), Instant Wave Free Ratio (iFR), intravascular ultrasound (IVUS)
• Contraindications to stents: predicted DAPT non-adherence, anticipated major surgery within treatment time, elevated bleeding risk
• Antiplatelet: 81mg ASA indefinitely (Circ 2016;134:e123). P2Y12 inhibitor added after cath (prasugrel, ticagrelor or clopidogrel)
o Not high bleeding risk: ACS, 12mo DAPT (DES/BMS); stable IHD, ≥6mo DAPT if DES or ≥1mo if BMS
o High bleeding risk: ACS, 6mo DAPT (DES/BMS). In select patients, DAPT 1-3 months followed by P2Y12 monotherapy (NEJM
2019; 381:2032); stable IHD, ≥3mo DAPT if DES or ≥1mo if BMS (also consider 1-3mo DAPT followed by P2Y12 monotherapy)
o Triple therapy: see ACS. Usually, 1 wk triple therapy and transition to P2Y12 inhibitor + DOAC.
POST-PROCEDURE CARE
• Femoral access: 4-6h bedrest after procedure. Closure devices decrease time needed for bedrest
o Groin checks immediately, 6h, 8h post-procedure: check b/l pulses, palpate for pulsatile masses, auscultate for bruits
o Sheaths: usually removed when PTT<60, confirm with interventional fellow; only fellows remove
 Radial access: TR band for 4-6h. Driven by RN protocol; if paresthesias/numbness, examine, check finger sat probe for perfusion. Can
remove several mLs of air from band if necessary and if no complications. NOTE: if hematoma do not remove until fellow assesses.
POST-CATHERIZATION COMPLICATIONS
• Access site complications: always inform the interventional fellow who performed the procedure, diagnose by exam and US
o Hematoma: mass w/o bruit. Apply compression. If unable to control, may require Fem-Stop device to apply external pressure
o Pseudoaneurysm: pulsatile mass with bruit at access site. Tx w/ compression; if <2cm, may require thrombin injection or
surgery if >2 cm. Urgent US & Vascular Surgery consult
o AV fistula: continuous bruit with no mass. Evaluate w/ US. Surgical repair usually necessary
o Limb ischemia: from thrombus, dissection, or malpositioned closure device. Evaluate pulses, limb warmth, & PVR
o Retroperitoneal bleed: presents within hours post-cath, often with hemodynamic instability ± flank pain ± ecchymoses. STAT
CT A/P if stable. Transfuse, IV fluids, discuss with attending about stopping/reversing anticoagulation
• Other complications:
o Infection: more common in setting of vascular closure devices
o Atheroembolism: eosinophilia; livedo reticularis; blue toes; mesenteric ischemia; acute, subacute, or chronic renal dysfunction
o CIN: occurs within 24-72h with peak Cr 1-5d post contrast load, risk correlated with contrast load and initial GFR
o Tamponade: narrow PP, hypotension 2/2 coronary/cardiac perf. Check pulsus (>10 mmHg), STAT echo, page cath fellow.
o MI/CVA: due to in-stent thrombosis (MI) or distal embolization post-cath (CVA). Discuss all CP/neuro changes with cath fellow
o Radiation injury: more common in CTO cases. Occurs days to weeks after PCI. Ranges from erythema to skin ulceration
o Delayed Hemostasis: apply indirect pressure (several cm cranial to site of skin access) page gen cards fellow to discuss
escalation to cath fellow/vasc surg (see ellucid escalation pathway)

Ashvita Ramesh
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Cardiology Non-Invasive Cardiac Testing

BASICS
• Non-invasive cardiac testing includes stress/functional and anatomic testing.
• The best approach to testing depends upon: 1) the clinical question being asked, 2) symptom (often chest pain) acuity, 3) baseline
CVD risk/known CAD hx, and 4) patient-specific contraindications.

ROLE OF NON-INVASIVE CARDIAC TESTING IN CHEST PAIN EVALUATION

Source: 2021 ACC/AHA Guidelines for Evaluation and Diagnosis of Chest Pain (Circ 2021;144:e368-e454)

Deciding between CCTA (anatomic) and stress imaging in an intermediate-high risk patient:
• CCTA favored: Age<65y, to rule out obstructive CAD, to detect non-obstructive CAD, prior functional study w/o conclusive results, for
bypass graft assessment, known anomalous coronaries, parallel evaluation of aorta, pulmonary arteries, or left atrial appendage
desired.
• Stress imaging favored: Age>65y, if known >50% (obstructive) CAD to assess for specific areas of ischemia, prior CCTA w/o
conclusive results, parallel eval for scar or microvascular dysfunction (PET or CMR).

STRESS/FUNCTIONAL TESTING
• Indications:
o Diagnose CAD: Workup stable angina in pts with intermediate-high risk of CAD. Consider spectrum of non-invasive tests vs. cath
in intermediate-risk pts presenting with more acute sx. Not indicated in pts with no symptoms or at low risk.
o Evaluate new or changing sx concerning for ischemia in pts with known CAD.
o Post-revascularization: Evaluate pts with angina or asymptomatic pts if incomplete revasc or >2y post-PCI/5y post-CABG.
o Pre-op risk assessment: If indicated (see Perioperative Medicine).
o Other: Newly diagnosed HF or cardiomyopathy likely secondary to ischemia, functional capacity (for exercise prescription),
viability testing, valvular disorders, dobutamine stress echo in LFLG AS, quantify microvascular disease (PET).
• Contraindications: Untreated ACS, MI within 2d, high risk or LM CAD, uncontrolled arrhythmia, ADHF, severe AS or HOCM, recent
DVT/PE, acute myo-/peri-/endocarditis, aortic dissection, uncontrolled HTN.
• Approach to choice of test: See below for information on choosing a stressor and evaluation modality.
• Preparation: NPO 3h prior, longer if imaging or adenosine. Must reverse DNR/DNI for test.
o If the question is “Does the patient have CAD?”  hold BB and nitrates
o If the question is “How well are meds working in known CAD?”  continue BB and nitrates
o Hold BB >24h for dobutamine stress test; hold caffeine >12h for adenosine
 Positive test results: Optimize medical rx. Decision re: angiography/revascularization varies by pt (degree of sx,
known stenosis, current meds). In ISCHEMIA trial, initial revascularization vs. OMT did not reduce the risk of
ischemic CV events for pts with moderate to severe stable ischemic heart disease (NEJM 2020;382:1395).
• Caveats:
o Majority of vulnerable plaques are angiographically insignificant (<70% stenosis)  CCTA more sensitive for their detection
o Angiographically significant 3VD may produce false-negative vasodilator stress test  ”balanced ischemia”
 Can see transient ischemic dilatation (apparent enlargement of LV cavity during stress) which can occur in 3VD

Approach to choosing a stressor and evaluation modality:

• See Table 5 for full list of contraindications by test type (Circ 2021;144:e368-e454).
Choosing a stressor:
o Exercise: Preferred over pharmacologic testing if patient able to reach goal exertion. More relevant to real-world stress.
o Adenosine/Regadenoson:
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Cardiology Non-Invasive Cardiac Testing

 Mechanism: Vasodilation via cAMP, detect ischemia by coronary steal (stenosed coronary arteries are unable to further
dilate, creating a relative perfusion deficit in diseased vessels).
 Side effects: Wheezing, bradycardia, HoTN. Caution if ACTIVE bronchospasm, high grade AVB, SSS, severe AS
o Regadenoson (vs adenosine) has decreased respiratory/conduction side effects, is more cost-effective in obese pts,
but caution if seizure hx (reversal agent aminophylline seizure risk)
o Dobutamine:
 Mechanism: Positive inotropy and chronotropy via β-1 receptor agonism. Extremely high dose (up to 40 mcg/kg/min)
 Side effects: tachyarrhythmias. Caution if MI <48h, hx of malignant arrhythmia, severe AS, HOCM, severe HTN, severe
PAH, aortic dissection
Choosing an evaluation modality:
o ECG: Only used as stand-alone with exercise, though often still assessed alongside imaging.
o TTE:
 Can define ischemia severity and risk-stratify. Additional info on hemodynamics/valve disorders
 Do not use in pts with LBBB, V-pacing, or extensive wall motion abnormalities at rest
o Nuclear imaging (PET or SPECT myocardial perfusion imaging):
 Utilizes a radiotracer to detect areas of perfusion between rest and stress states. Can also measure LV function, transient
LV dilatation, myocardial blood flow reserve.
 More expensive than TTE & high amount of radiation (SPECT > PET)
 PET more Sn & Sp than SPECT with faster image acquisition. Less widely available & more expensive. Additional uses for
imaging in rheumatologic (i.e. cardiac sarcoid) and oncologic contexts (i.e. cardiac myxoma, metastases).
o Cardiac MRI (CMR):
 Localize ischemia and infarction, assess LV and RV function, determine myocardial viability. Can also detect microvascular
dysfunction, and has other uses (see Anatomic Testing).

Exercise Tolerance Test (ETT):

• Approach: ETT generally refers to exercise + ECG, though can perform imaging eval (TTE, SPECT) with exercise. Exercise ECG has
much lower sensitivity than exercise imaging, but is very cheap and available.
• Protocols: Bruce (large changes in workload between stages), modified Bruce (for less fit pts  adds stages of lower workload)
• Assess: exercise duration, METs, BP/HR response, HR recovery, double product (HR x SBP), Duke Treadmill Score (estimates risk of
CAD in pts w/ chest pain undergoing exercise stress testing (Circ 1998;98:1622)).
• Diagnostic if: >85% max-predict HR (220-age), peak double product (HRxBP) >20k, HR recovery (HRpeak – HR1min post-exercise) >12
• Increased probability of ischemia with:  # of leads with STD,  degree of max STD,  METs when ECG changes occur, ventricular
ectopy during recovery, increased time to recovery of ECG, failure of SBP to rise with exercise.

Viability testing:
• Indication: Determine viability of ischemic myocardium (assess for hibernating tissue) that may be salvaged w/ revascularization.
• Modalities: SPECT, PET, TTE, MRI with exercise or pharmacologic stress. Looking for metabolic or contractile reserve.

ANATOMIC TESTING
Coronary CTA (CCTA):
• Indications:
o Evaluate for the presence and extent of CAD. Primarily anatomc info, though offers plaque characterization and CT FFR.
o Asymptomatic pts: NOT for screening use. Low-risk pts with sx: high NPV (99%) for CAD rule-out (JACC 2008;52:1724). Moderate-
risk pts with sx: reasonable for risk stratification (especially after equivocal stress test).
• Preparation: Requires cardiac gating (goal HR 60-70, may need to give BB) and respiratory gating (breath hold for 5+ sec).
• Results:
o 2y ACS risk significantly elevated if high-risk plaque (16%) and/or stenotic disease (6%) (JACC 2015;28:337)
o Higher Sn & Sp for coronary stenosis compared to cMRI (Annals 2010;152:167)
• Caveats: Less useful in pts with extensive calcifications (older) or stented vessels due to “blooming” artifact (cannot eval patency).

Coronary Artery Calcium (CAC) Scan:

• Indications:
o Risk-assessment (CAC or Agatston) score for ASCVD risk stratification. Used to guide decision-making for primary
prevention/statin therapy in asymptomatic pts, ≥40y at intermediate-risk (7.5-19.9% 10y ASCVD risk). Do NOT use as a stand-
alone test in eval of sx of myocardial ischemia. Do NOT use in high-risk pts, including those with familial hypercholesterolemia
• Preparation: Non-gated, non-contrast (if done independent of CCTA) CT scan.
• Results: MESA score accounts for CAC score and is able to refine 10 year risk estimates
o If CAC score 0 and pt without significant risk factors, reasonable to defer statin therapy for up to 5 years (Circ 2019;140:496).
o If CAC score ≥100 or >75%ile for age & gender, independent of ASCVD risk recommend aggressive lifestyle changes, ASCVD
RF modification (BP, smoking cessation, diabetes treatment), & statin therapy (JACC 2019;73:285)

Cardiac MRI:
• Can be used in a stress test/ischemia eval, also is modality of choice for assessment of funtional & tissue properties of the heart that
cannot be adequately assessed with TTE or CCTA (inflammation, scarring, infiltration, cardiac tumors, pericardial disease)
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Cardiology Echocardiography
View/Description Position View*
Patient: lying on left side, with left arm under head
Probe: 2-3 inches left of sternum at 3rd-4th
PARASTERNAL LONG AXIS intercostal space, indicator at 10 o’clock (facing R
• LV size, function, wall thickness shoulder). Should see LA, LV, Ao, RV, and dAorta
(septum/posterior wall)
• MV/AoV function/flow (w/
Doppler)
• LVOT diameter, aortic root size

Patient: same as above

Probe: from long axis view, rotate probe clockwise
until indicator at 2 o’clock (facing L shoulder). Fan
PARASTERNAL SHORT AXIS probe to L hip until at level of papillary muscles.
• Cross-sectional views of the
heart from base to apex, at level
of AoV, MV and mid-
ventricle/papillary muscles

Patient: lying flat on back or left decubitus

APICAL 4 CHAMBER Probe: at PMI w/ probe indicator at 3 o’clock (to the
• RV/LV size, function, thrombus pt’s L). For 5-chamber view, fan probe cranially.
• TV/MV function/flow (w/
Doppler)
• Septal size/motion
• Pericardial effusion
• In 5-chamber view, can see AoV
and proximal ascending aorta

Patient: laying flat on back, can slightly bend legs

Probe: below xyphoid process, indicator to pt’s R

SUBXIPHOID (aka subcostal)

• RV/LV size, function
• Pericardial effusion

INFERIOR VENA CAVA Patient: same as above

• IVC diameter and respiratory Probe: rotate 90°, indicator to head. Fan L, rock up
variation gives estimate of
volume status and RA pressure
• Most helpful for extremes of
volume status measurement (i.e.
very dry or very wet)
*Images from: Soni, N. J., Arntfield, R., &amp; Kory, P.
(2020). Point of care ultrasound. Elsevier.

R E V I E W I N G T H E M G H R E P O R T : for questions or clarification of findings, call Echo Lab (x6-8871) or page on-call Echo Fellow
• Valvulopathy: stenosis/regurgitation (valve area, gradients, severity), leaflets, vegetations
Indications for STAT TTE:
• Structure/chamber dimensions: aorta, LVIDd & LVIDs (LV internal diameter in diastole, range: 42 – - Eval hemodynamic instability of
58mm & systole, range: 25 – 40mm), IVS (septum, 6-10mm), PWT (posterior wall thickness, 6-10mm,  suspected cardiac etiology
in LVH, diastolic dysfunction), LV volume (ULN: 74ml/m2 in men 61 in women, <40 suggest restrictive), - Eval for early MI complication
LA volume (ULN: 34ml/m , in MR/MS, diastolic dysfunction, AF)
2
- Suspected MI w/ non-diagnostic
• EF: “preserved” EF ≥50%, “borderline” EF 40-50%, “reduced” EF <40% biomarkers and EKG
• WMA: territory correlates w/ coronary vessels (anterior + septal = LAD, inferior = RCA, lateral = LCx). If - Identify cause of cardiac arrest
global WMA, r/o diffuse ischemia vs non-ischemic insult (sepsis, stress)
• RVSP: RVSP=4v2 + RAP. RAP assumed to be 10 mmHg and v = TR jet velocity. RVSP >35mmHg (<60yrs) and >40mmHg (> 60yrs) is elevated.
• Shunt detection: agitated saline contrast study (i.e. TTE w/ bubble) to detect PFOs, ASDs, and pulmonary arteriovenous shunts
CLINICAL QUESTIONS AND ASSOCIATED TTE FINDINGS
• Right heart strain in acute PE: RV WMA or hypokinesis, RV dilation (RV:LV ratio >1), interventricular septal bowing, IVC collapse, “D-sign”: septal
flattening, “McConnell’s sign”: RV free wall akinesia w/ normal RV apex motion (77% Sn, 94% Sp for acute PE)
• Tamponade: large effusion, swinging heart, R-sided chamber collapse, interventricular septal bowing, dilated IVC (no  w/ inspiration)
• ACS/mechanical complications of ACS: regional WMA, septal/free wall rupture, acute MR, LV thrombus
• Stress (Takotsubo) cardiomyopathy: LV apical ballooning and akinesis/hypokinesis; Heart failure: depressed EF, RV/LV hypertrophy and/or dilation
• Diastolic dysfunction: LA enlargement, E/e’ >14, LVH (note: diastolic dysfunction not typically called on MGH TTE reports)
• Constrictive pericarditis: thickened or hyperechoic pericardium, abnormal septal motion, respiratory variation in ventricular size, dilated IVC
• Cardiac amyloid: biatrial enlargement, increased LV and RV wall thickening, valvular thickening, diastolic dysfunction, paradoxical LFLG AS

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Cardiology Heart Failure

INITIAL WORKUP - NEW HEART FAILURE DIAGNOSIS
• Clinical syndrome with signs/symptoms consistent with
impaired cardiac function ± cardiomyopathy
• Echocardiography: TTE for all new presentations; obtain
thereafter only if concern for clinical/functional change
o HFrEF (EF ≤40%), HFmrEF (“mid-range” EF 41-
49%), HFpEF (EF ≥50%), HFrecEF (“recovered”)
• Ischemic workup: FHx, ECG, TnT, noninvasive or
invasive cardiac testing
• Non-ischemic workup: FHx, genetic testing, med hx,
alcohol use history, lipid panel, TSH, A1c, urine hCG,
iron studies, HIV, SPEP/SFLC w/ UFLC
o Consider: cardiac MRI/PET, ANA, T. cruzi
serologies, viral panel, antimyosin Ab, tox screen,
thiamine/carnitine/selenium, genetic testing,
ARVC, sarcoid, PYP scan/bone scintigraphy
(amyloid), cardiac masses; endomyocardial bx (if
serologic testing neg, new onset <6mo unexplained HF, unexplained HF <2wks and HDUS, major arrhythmias) to r/o myocarditis
• Consider high-output etiologies: anemia, thyroid dysfxn, liver failure, Paget’s, systemic infection, AV shunts
Dilated Cardiomyopathy
Etiologies: ischemic (most common cause, 50-75%), HTN/LVH, valvular (e.g. MR), myocarditis, stress-induced (Takotsubo),
tachyarrhythmia, infiltrative (as below), CTD, ARVC, LVNC (left ventricular non-compaction), HIV, cocaine/methamphetamines, EtOH,
chemotherapy, nutritional deficiency, cirrhosis, sepsis, peripartum, idiopathic/genetic
Condition Etiology and Management
Mechanism: associated with >80g/d EtOH (6 standard drinks) over >5y (toxic to myocytes via O2 free radicals +
defects in protein synthesis)
Alcohol-induced
Tx: abstinence + HF therapy
Prognosis: better/equivalent to idiopathic CM if <20g/d (<2 drinks) or abstinence, worse w/ continued EtOH use
Mechanisms: catecholamine surge from physical/emotional stress, coronary artery spasm, microvascular ACS
Stress-induced Presentation: may present like ACS with CP (most common), SOB, shock, syncope. If in shock, urgent TTE to
(Takotsubo) assess for LVOT obstruction
(JACC. Dx (need all 4): 1) transient dysfxn of LV mid-segments, WMAs extending beyond a single coronary distribution; 2)
2018;72:1955) rule out ACS/obstructive CAD (via cath); 3) new ECG ∆ (STE or TWI) OR TnT; 4) absence of pheo or myocarditis
Tx/Prognosis: remove stressor, ACEi (may improve survival), BB; most recover LV function in 1-4w

Hypertrophic Cardiomyopathy (HCM) (Circulation 2024 ;149)

Characteristics: LV and/or RV hypertrophy of various morphologies ± LVOT dynamic obstruction (HOCM), diastolic dysfxn, ischemia, MR;
risk of arrhythmia/SCD
Exam: SEM at LLSB/apex that augments with Valsalva or on standing (due to preload); S2 paradox split, S4
Dx: ECG (prominent voltages w/ depolarization abnormalities, large abnormal Q waves in inferior/lateral leads, LAD, giant negative T
waves in V2-V4 (apical HCM variant aka “Yamaguchi syndrome”)), TTE (unexplained LVH >15mm, SAM of MV, outflow tract gradient +/-
provocative testing), cMRI (late gadolinium enhancement [LGE] = fibrosis)
Clinical genetic testing (mutation in ~70%) helpful for family screening; not useful for dx or risk stratification
Tx: avoid volume depletion or high dose vasodilators (may worsen obstruction); phenylephrine is pressor of choice if no response to
IVF bolus for HoTN (afterload, stents open LVOT). Activity restriction, meds (BB > verapamil). Consider mavacamten if LVEF ≥ 55%
(VALOR-HCM); septal ablation or surgical myectomy for medically refractory sx, ICD (for high SCD risk, see below)
Risk factors for SCD/VT: prior VT/SCD/unexplained syncope; FHx of SCD in 1° relative; massive LVH (>30mm); NSVT on Holter;
abnormal BP response to exercise; burden of LGE on cMRI; h/o suspected cardiac syncope; EF<50%
Restrictive Cardiomyopathy (JACC 2010;55:1769) – conditions below may also manifest as Dilated CM
Etiologies: in addition to below, Löffler’s, radiation, metabolic storage disease, carcinoid
Tx: treat underlying disease and HF as below. For amyloidosis: tafamidis (TTR deposition) (NEJM 2018;379:1007)
Condition Presentation ECG Echo cMRI
- voltage, - Symmetric LV/RV wall
Amyloidosis - HF w/ other findings of amyloid - LGE in
pseudoinfarct pattern thickness, speckled
(AL, TTR) (renal, neurologic, hepatic dz) subendocardium
in inferolateral leads myocardium
- If hereditary: M >30yo; F >40yo
- SVT (ventricular
- If 2°: any age - Dilated LV with global - Iron overload with
Hemochromatosis conduction
- Abnl LFTs, arthralgias, DM, systolic dysfunction T2 protocol
abnormalities rare)
hyperpigmented skin
- Variable wall thickness, - Patchy
- Young adult w/ HF - Infrahisian block,
Sarcoidosis focal/global hypokinesis, enhancement of
(more commonly as DCM) atypical infarct pattern
LV aneurysm basal and LV walls
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INPATIENT ACUTE DECOMPENSATED HEART FAILURE (ADHF)

• Admission orders: tele, 2g Na restricted diet, daily standing weights, strict I/Os, DVT ppx
• SDU Admission: EF <25%, NTproBNP ≥ 2,500, arrhythmia-induced HF. Black & Latinx pts w/ HF are less likely to be admitted to
cardiology services, contributing to racial inequities in HF outcomes (Circ Heart Fail 2019;12:e006214).
• Avoid: CCB (esp. non-dihydropyridines), NSAIDs, flecainide
• Check NT-proBNP (& weight) on admission and at discharge
o ADHF unlikely if NT-proBNP <300 (NPV 98%), likely if >450 (>900 if age >50) (Am J Cardiol 2005;95;948)
o Difficult to interpret in CKD/dialysis. May be falsely low in obesity, HFpEF
• Screen for & treat iron deficiency in all HF pts independent of Hgb (JACC HF 2019;7:36)
o Dx: ferritin <100 or ferritin <300 + TSat <20% (JACC 2017;70:776); though some evidence that TSat ≤19.8% or serum iron
≤13µmol/L most predictive & ferritin may be less useful (Circ Heart Fail 2018;11:e004519)
o Tx: replete with IV iron (JACC 2018;71:782) to sx, functional capacity, QOL (FAIR-HF, NEJM 2009;361:2436); PO ineffective in
HF (JAMA 2017;317:1958)
ADHF MANAGEMENT – FLOOR/SDU
1. Identify hemodynamic profile & triage accordingly (JACC 2019;74:1966)
• Warm vs Cold: adequate vs inadequate tissue perfusion (AMS,
lactate, cool extremities, narrow PP)
• Dry vs Wet: presence vs absence of congestion
(JVD, crackles, pleural effusions, ascites, LE
edema, interstitial/alveolar edema on CXR)
• Evaluate for signs of pulmonary congestion on
exam. Pulm edema may be absent on CXR in
chronic HF due to lymphatic compensation (Chest
2004;125:669)
• ~80% of decomp HFrEF and nearly all decomp HFpEF pts will be warm and wet
2. History
• Identify precipitants: dietary/med non-adherence (~40%), new ischemia/infarction, uncontrolled HTN, arrhythmia,
inadequate diuretic dose, meds (NSAIDs, steroids, CCB, TZDs, anthracyclines), acute infection (URI, PNA, UTI), AKI, PE, toxins
(EtOH, cocaine), new/worsening valve disease, myocarditis
• Cardiac/HF history (last EF, dry weight, prior ischemic w/u, prior TTE, cardiologist); accurate PAML; social history
3. Early/Acute Management:
• Diuresis: CVP, PCWP to optimize Starling curve mechanics & relieve sx (NEJM 2017;377:1964; JACC 2020;75:1178)
o Initial tx: IV loop (furosemide, torsemide, bumetanide), start w/ 2-2.5x home dose (IV/PO). No difference b/w continuous gtt
vs bolus (NEJM 2011;364:797); furosemide & torsemide have same outcomes (JAMA 2023;329:214-223). See Advanced Diuresis
o Refractory diuresis: metolazone 2.5-5mg (or chlorothiazide 500mg IV) administered 30min before loop diuretic. May need
RHC to clarify hemodynamics or inotropes to augment diuresis. Acetazolamide (500mg daily) may also augment successful
decongestion (NEJM 2022;387:1185). Step-up pharmacologic therapy superior to RRT in the setting of cardiorenal
syndrome (NEJM 2012;367:2296)
o Worsening renal function: occurs in ~23% of pts treated for ADHF. Mild-mod “Cr bumps” are likely benign hemodynamic
changes, should not necessarily preclude further diuresis if pt still congested (Circ 2018;137:2016)
o Endpoints: target resolution of signs/symptoms of congestion. Daily weights & hemoconcentration are useful adjuncts
• If acute pulmonary edema, NIPPV may improve mortality and reduce need for intubation (Annals 2010;152:590)
• Vasodilators: arterial/venous dilation can relieve symptoms by afterload, PCWP and SV. Can acclerate early sx relief.
Consider esp. in severe HTN, acute MR, acute AR
o Floor: isosorbide dinitrate, hydralazine, nitropaste, captopril; SDU/CCU: nitro gtt, nitroprusside gtt
• Guideline-Directed Medical Therapy (GDMT): if not in cardiogenic shock or new AKI, continue ACEi/ARB/ARNi and βB during
ADHF (but do not newly initiate βB) (EHJ 2009;30:2186)
4. Pre-Discharge Optimization: Document d/c weight & NT-proBNP, appt in HF Transitions Clinic
• HFrEF (EF ≤40%) GDMT, including HFrecEF (recovered EF), prioritize initiation of low-dose quadruple therapy prior to d/c:
o Beta blockers: initiate, uptitrate evidence-based βB (carvedilol, metoprolol succ., bisoprolol) (COPERNICUS; MERIT-HF).
Caution if recently weaned from inotropes
o RAAS inhibitors: if renal fxn stable, initiate/titrate ARNI (sacubitril/valsartan) (PARADIGM-HF; PIONEER-HF), second line ACEi/
ARB (CONSENSUS; CHARM). Switch to ARNI from ACEi/ARB if no contraindications/cost concerns, 36h washout period for
ACEi prior to starting ARNI.
 Guidance for GDMT in advanced CKD: JACC HF 2019;7:371
o Mineralocorticoid receptor antagonist: initiate spironolactone or eplerenone if CrCl>30 (EMPHASIS-HF; RALES). Watch for
rebound hyperK after de-escalation of diuretics (check K, Cr within 72h of discharge)
o SGLT2i (dapaglifozin, empagliflozin): further reduce CV mortality & HF admissions regardless of DM (DAPA-HF;
EMPEROR-Reduced; EMPULSE; Lancet 2020;396:819 (see Outpatient Type 2 Diabetes)
o GDMT dosing - AHA/ACC/HFSA 2022 Guidelines (Circ 2022;145:895)
βB ARNi/ACEi/ARB MRA SGLT2i
metop succ carvedilol sacub/val lisinopril losartan spirono epler dapag empag
Initial Dose (mg) 12.5-25 qD 3.125 BID 49/51 BID 2.5-5 qD 25-50 qD 12.5-25 qD 25 qD 10 qD 10 qD
Target Dose (mg) 200 qD 25-50 BID 97/103 BID 20-40 qD 50-150 qD 25-50 qD 50 qD 10 qD 10 qD

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Cardiology Inpatient Heart Failure

• Diuretic plan: determine maintenance diuretic dose and provide specific instructions for taking additional rescue doses. Observe
on maintenance dose and decide if needs K replacement
• HFmrEF (EF 40-49%): treat with diuretics & consider adding GDMT agents for HFrEF (Curr Heart Fail Rep 2020;17:1)
• HFpEF (EF ≥50%): prevent volume overload, treat with diuretics, treat comorbidities (DM, HTN, AF)
o SGLT2i only agent found to CV death/hospitalizations in pt with EF ≥40% (EMPEROR-Preserved)
o Consider spironolactone if normal renal fxn/K, CV death/admits in N/S Am. sites in TOPCAT (Circ 2015;131:34)
o No proven benefit to BB (EHJ 2018;39:26), ACEi (PEP-CHF), ARNi (PARAGON-HF), ARB (CHARM-Preserved; I-PRESERVE)
• ICD indicated if: ischemic CM w/ EF ≤30 or ≤35% w/ NYHA II-III; CRT if: EF ≤35% & prolonged QRS ± LBBB & some w/ EF
≤50% (see Cardiac Devices: PPM/ICD & guidelines for specifics: JACC 2013;61:e6; EHJ 2016;37:2129)

O U T P A T I E N T H E A R T F A I L U R E (JACC 2021;77:772, Circ 2022;145:895)

Not comprehensive; assumes EF ≤ 40% (HFrEF), co-management by cardiology and/or heart failure specialist.
● At each visit: assess med/dietary/lifestyle compliance, document weight, detailed volume exam, assess symptoms and classify ACC
Stage/NYHA Class, review current GDMT, review ambulatory BP / HR measurements for GDMT titration targets
● Lab monitoring: BMP/Mg and 1-2 weeks following uptitration of ACE-i/ARB/ARNi; spironolactone requires close monitoring
● Goal: toleration of target doses of ACE/ARB/ARNI, β-blocker, aldosterone antagonist, and SGLT-2 inhibitor without symptomatic
hypotension or metabolic disarray. For β blockade, target resting HR < 70 without postural hypotension or unacceptable SE.
● Principles: start GDMT immediately on dx, often “quad therapy” at lower than target dosing is preferred over maxing out a single agent
● Diuretic: see Advanced Diuresis. Diuretic needs may change when SGLT-2i is added due to mild diuretic effect.
● Avoid: NSAIDs, CCBs, flecainide, steroids, OTC decongestants (e.g. Sudafed), Bactrim
● Special considerations/scenarios:
o Ivabradine: add if sinus rhythm & resting HR > 70 on max β blockade. Start at 2.5 mg – 5 mg qd
o Hydralazine/isosorbide dinitrate: add if SBP persistently > 130 on target GDMT; especially beneficial in AA patients
o Symptomatic hypotension on GDMT: consider over-diuresis or other offending prior to reducing GDMT
● Adjuvant care/ambulatory referrals to consider: cardiac rehab (often under-prescribed); nutrition consultation for assistance with
dietary adherence; patient-centered education is critical to enhance adherence

CARDIOGENIC SHOCK – CCU

• Definition: HoTN (SBP<90 for 30min or pressor req) + hypoperfusion (cold extremities, oliguria, lactate) + hemodynamics (CI <2.2,
PCWP >15) (EHJ 2019;40:2671)
• Etiology: acute MI ± mechanical complications, end-stage heart failure, acute myocarditis, acute MR/AR, myocardial contusion
• Evaluation: ECG, troponin to r/o acute MI. TTE to exclude tamponade/mechanical lesions/contraindications to MCS
• Monitoring: A-line, consider PA catheter for inotropes/pressors and MVO2 monitoring
Immediate Management:
• If c/f acute MI, activate cath lab for PCI (only intervention proven to improve outcomes in cardiogenic shock) (NEJM 1999;341:625)
• Consider early SHOCK consult (p11511). Escalating inotropes/pressors exacerbate myocardial supply/demand imbalance and are
associated with poor outcomes. Emerging evidence supports early initiation of MCS (Cath Cardio Interv 2019;93:1173)
• Stabilize MAP with norepinephrine PRN prior to obtaining PA catheter to guide tailored therapy
Tailored Therapy: uses invasive hemodynamic monitoring (i.e., PAC) to guide medical therapy
• Goals: tissue perfusion (CO, MAP), decongestion (CVP, PCWP), ventricular unloading (minimize myocardial O2 demand)
 Preload: LVEDV ∝ LVEDP ≈ PCWP; goal PCWP 14-18, PAD 16-20, CVP 8-12 → diuresis, UF with RRT, TNG
• Afterload: wall stress ∝ MAP (Laplace’s law); SVR = (MAP - CVP)/CO; goal MAP >60, SVR <800-1200
 Vasodilators: captopril, hydralazine, nitroprusside, TNG, isosorbide dinitrate
 Vasopressors: afterload, sometimes needed to MAP in mixed shock or to counteract vasodilatory effect of inodilators
 IABP: see Mechanical Circulatory Support
• Contractility: ∝ CO for given preload/afterload; goal CO>4, CI >2.0-2.2, MVO2 >65
 Dobutamine (inodilator): β1>β2 agonist (production of cAMP); initial dose 0.5-1 mcg/kg/min
• Watch for tachycardia, ventricular response to AF, arrhythmias, ischemia, HoTN, tachyphylaxis in infusions >24-48h
 Milrinone (inodilator): PDE-3 inhibitor (breakdown of cAMP); initial dose 0.125 mcg/kg/min
• Watch for tachycardia, arrhythmias, ischemia, HoTN. Compared to dobutamine, milrinone has longer half-life, greater
pulmonary vasodilatation, slightly less chronotropy
• Preferred in patients on βB and w/ RV failure. Renally cleared. Often choice for home inotrope for palliative therapy
 Epinephrine, norepinephrine, dopamine (inopressors): use if severe HoTN often in combination with inodilators
• Watch for tachycardia, arrhythmias, end-organ hypoperfusion
• Advanced: consideration of need for mechanical circulatory support or transplant
 Goal of mechanical circulatory support: improve systemic perfusion while reducing myocardial oxygen demand (in contrast
to inotropes which CO at the expense of increased oxygen demand); see MCS
• Limitations:
o CO approximated via thermodilution or Fick equation: CO = VO2/(13.4 x Hgb x [SpO2-MVO2]); CI = CO/BSA; VO2 = 125 x BSA
 Thermodilution: uses temp gradient between two points on PAC. Less reliable if shunt/valvular insufficiency (e.g., TR)
 Fick equation: assumes a VO2 (oxygen consumption) that in reality varies depending on physiologic state (e.g., infxn)

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Cardiology Right Ventricular Failure

PATHOPHYSIOLOGY
RV “death spiral”
• Normal RV function: governed by systemic venous return, PA pressure, pericardial
compliance, and native contractility of the RV free wall and interventricular septum
(where RV and LV are “tethered”).
o The RV is coupled to the high-compliance, low-resistance pulm circulation 
RV ejects blood at lower pressure compared to LV  RV is more afterload
sensitive than LV. RV can adapt to changes in volume > pressure.
• Acute RV Failure: RV & LV interdependent  failure of RV  failure of LV via: (1)
decreased LV preload, as RV output = LV preload & (2) septal bowing into LV,
causing diastolic impairment (“Diastolic Ventricular Interaction”)
o RV afterload (e.g. PE, hypoxia, acidemia), RV preload (e.g. LR shunt or
TV disease), or RV contractility (e.g. MI, myocarditis) all lead to increased
RV wall stress & resultant ischemia
• Chronic RV Failure: gradual RV afterload (from Pulmonary Hypertension /
Pulmonic Stenosis / Tricuspid Regurgitation) RV “death spiral” Eur Heart J 2020;41:543

C L I N I C A L F E A T U R E S A N D W O R K U P (Circ 2018;137:e578-e622)
• Exam: JVP, peripheral edema, RV heave, pulsatile liver, split S2, new TR (holosytolic murmur at LLSB with radiation to RLSB)
• Imaging: PA/lateral CXR; CT  RV/LV ratio >0.9 suggests RV strain
• Echo: measure RV size/function to elucidate underlying etiology. RVEF based on displacement of base towards apex; TAPSE =
tricuspid annular plane systolic excursion (normal ≥ 17 mm; reflects RV apex-to-base shortening, correlates with RVEF)
o RVSP: correlates w/ RHC but can vary up to 10mmHg (esp w/ chronic lung disease, PPV)
• RHC w/ placement of PA line: gold standard for measurement of ventricular filling pressures, CO, PA pressures
o RV function: CVP/PCWP ratio: normal = 0.5;  is sign of RV failure; PAPi: (PAs – PAd)/CVP <0.9 = RV failure, for pts w/ VAD <
1.85 = RV failure; RV stroke work index: (mPAP – CVP) x (CI/HR) x 0.0136 (normal 8-12 g/m/beat/m2)
• Labs: NT-proBNP, troponin, also Cr and LFTs secondary to venous congestion

M A N A G E M E N T (AHA: Circ 2018;137:e578)

• Treat reversible causes (pericardial disease, RVMI, PE, hypoxemia, infections)
• Preload (CVP goal 8-12mmHg): both hypo- and hypervolemia can CO
o Volume Depletion (PE, Tamponade, RVMI): judicious IVF (0.5-1L) in absence of CVP elevation (goal CVP 10-14 in RVMI)
o Volume Overload: IV diuresis to RV filling pressures, functional TR, and improve LV CO; consider UF/CVVH if refractory to IV
diuresis
• Afterload:
o Systemic: if pt hypotensive, start pressors – do not tolerate HoTN as propagates RV death spiral (CPP); Goal MAP>65 &
MAP>mPAP (EHJ Acute CV Care 2022;11:77) no clinical data regarding pressor of choice, but often choose vasopressin or
norepinephrine (vaso affects PVR less than norepi) (Crit Care Med 2007;35:2037)
o Pulmonary: remove factors that pulm vasc tone (e.g. hypoxemia, acidemia). Consider pulm vasodilators if evidence of PAH
(inhaled>oral to deliver vasodilators to ventilated vascular beds)
 Types: iNO, prostacyclin agonists (epoprostenol (Veletri), inhaled or IV), endothelin antagonists (e.g. bosentan,
ambrisentan), nitric oxide enhancers (e.g. PDE-5 inhibitors: sildenafil, tadalafil)
• Contractility: dobutamine or milrinone; milrinone: RV afterload by pulmonary vasodilation but risk of hypotension; epinephrine  RV
contractility and MAP
• Devices: if refractory RVF, consider RV MCS and/or biventricular support (ProtekDuo, Impella RP, VA-ECMO)

I N T U B A T I O N A N D M E C H A N I C A L V E N T I L A T I O N (Curr Heart Fail Rep 2012;9:228)

• RV preload is “extrathoracic” and afterload is “intrathoracic”  intubation & positive pressure ventilation  pulmonary vascular
resistance (PVR) and  RV afterload   RV dilation  “death spiral”
• IMV/NIPPV in RV failure precipitate risk for hemodynamic collapse & cardiac arrest; trial of HFNC for hypoxemic respiratory failure
preferred prior to IMV/NIPPV given minimal effect on RV afterload.
o Drugs commonly used in intubation (BZDs, propofol, muscle relaxants)  tendency towards vasodilation and negative inotropy
 decreased venous return  decreased LV preload  systemic hypoTN  propagates “death spiral”
o Consider RSI w/ hemodynamically stable induction agents (ketamine/etomidate >> propofol for induction) & push dose
epinephrine (5-20mcg) or phenylephrine if emergent intubation; have norepinephrine in line anticipating hypotension.
• Vent management: prevent hypoxemia & hypercarbia (PVR), consider moderate TV (~8cc/kg), low PEEP (<8 cm H2O), and
moderate plateau pressure goal (<30 mmHg) to help minimize RV afterload

R I G H T V E N T R I C U L A R M Y O C A R D I A L I N F A R C T I O N (ACC/AHA: Circ 2013;127:e362)

• EKG: check R-sided ECG leads in pts with inferior STEMI (10-15% have RV involvement)
o 1mm STE in V4R  88% Sn, 78% Sp in inferior STEMI; STE III>II suggests RCA > LCx and RVMI
o High-grade AV block seen in ~50% of pts with RVMI
• Management: pts with RVMI may initially benefit from fluid bolus; caution w/ TNG (preload) & BB

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Cardiology Mechanical Circulatory Support

M E C H A N I C A L C I R C U L A T O R Y S U P P O R T ( M C S ) (JACC HF 2020; 8(11):879 ; Heart Int 2022; 16(1):37)
Note: if inotrope-refractory cardiogenic shock, call SHOCK team (p11511) and/or HCICU attending (p29151). VAD Coordinator (p11045).
Selected MCS Modalities
Device Indications Support Provided Considerations Management Complications
Mechanism: balloon
inflation/deflation; LV support
- Bedside insertion (quick)
Minimal hemodynamic support
- Does not always require - Check CXR daily (tip 1- - Limb ischemia
(0.5 L/min), greater in ADHF than
- Refractory heart AC (when at 1:1) 4cm below aortic knob) - Vascular injury
IABP acute MI shock (Am J Card
failure (bridge to - No mortality in - Check waveform twice - Thromboembolism
(intra- 2019;124:1947)
durable MCS or cardiogenic shock (IABP- daily - Bleeding
aortic - LV afterload (deflation)-
transplant, bridge- SHOCK II, NEJM - Wean by  ratio (then - Infection
balloon improves forward flow in
to-bridge) 2012;367:1287) return to 1:1, stop AC, - Balloon leak/rupture
bump) MR/VSD
- Prevents mobility (if pull) (STAT c/s to attending
- Coronary perfusion
- Refractory femoral placement) - Pulse checks and vascular surg c/s)
(inflation)
ischemia - Least costly
- Requires native contractility &
stable rhythm
- Cardiogenic
- Ventricular unloading
shock/massive PE
- Requires AC (purge ±
Mechanism: axial flow continuous systemic) - P1 (lowest) to P9
- Refractory - Infection
pump - Allows pt mobilization (if (highest support)
malignant - Bleeding
Partial LV support (LV->Aorta) axillary placement) - Check urine color
arrhythmias - Limb ischemia
- Cath lab (percutaneous) - Longer-term support (days (hemolysis), LDH
- Thromboembolism
placement: Impella 2.5 (2.5 to weeks) - Check suction events
Impella - Support during - Thrombocytopenia
L/min), Impella CP (3.5 L/min) - complications comp ared (preload, RV failure,
high-risk - Vascular injury
- OR placement: Impella 5.0 (5 to IABP position)
procedures: - Position alarm
L/min) or 5.5 (6.5 L/min) - May  major adverse - Check ventricular
o Complex PCI (reposition under
Partial RV support (VC->PA) cardiac events, not arrhythmias (device
o Ablation of fluoro/echo)
- Impella RP (>4 L/min) mortality (PROTECT II, migration)
ventricular
Circ 2012; 126:1717–
arrhythmias
1727)
o Percutaneous
- Bedside and urgent
valve repair
insertion possible
- Short-term support
- Acute allograft Full bi-ventricular support (4-10
VA- (days/weeks)
failure L/min) + oxygenation & CO2 See ECMO
ECMO - Often requires Impella for
clearance
LV venting (prevent
complications such as
pulmonary edema)
Full LV support (10 L/min) - Mobility - BP via manual cuff w/
- Bridge to - HeartMate II - Long-term support doppler (goal MAP 70- - Acquired vWF
transplant - HeartMate 3 (years) 80); continuous flow deficiency
- Bridge to - HeartWare HVAD - Require lifelong device does not generate - Bleeding
candidacy anticoagulation pulse - Hemolysis (possible
Durable - Destination 48% reduction in all cause - If hypotensive: A-line pump thrombosis)
VAD therapy mortality with LVAD as compared - If unconscious, w/o hum - Ventricular arrhythmias
- Bridge to recovery to optimal GDMT in Class IV HF and unable to - Thromboembolism
(LV unloading can (REMATCH) troubleshoot OR - RV failure
be therapeutic) MAP<50: chest - AR
Off-label for RV support (RVAD) compressions - Driveline infections
or both (BiVAD) - TTE if any concern
Assessment of contraindications:
Refractory Cardiogenic Shock Technical/logistical, Patient/family wishes, Septic
Shock, Uncontrolled Bleeding, AR, Aortic
Aneurysm/Dissection, LV/LA Thrombus, Severe PAD or
Aortic Disease
LV Failure: Bi-Ventricular Failure:
Increasing Support

Increasing Support

• IABP • Dual Impella (e.g. CP/RP) RV Failure:

Increasing Support

• Impella (2.5, CP, 5.0, 5.5) • VA ECMO • Impella RP

• VA ECMO • BiVAD (extracorporeal for RV • VA ECMO
• LVAD (extracorporeal & acute or & extracorporeal or durable • RVAD (extracorporeal/
implanted & durable) for LV) acute)

Pulmonary Support:
• Add oxygenator to extracorporeal VAD
• Add VV ECMO cannulation

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Cardiology Pulmonary Artery Catheterization

OVERVIEW
• Indications: PA catheter (PAC) for tailored therapy; diagnose (1) etiology of shock (e.g. cardiogenic vs. distributive); (2) cardiogenic vs.
non-cardiogenic pulm edema; (3) LV vs RV failure; (4) etiology of PH; (5) L R shunting; (6) valve disease; (7) pericardial disease
• Efficacy: controversial - ESCAPE trial (JAMA 2005;294:1625) showed no mortality benefit to
empiric use of PAC in pts w/ ADHF not on inotropes. PACs are still standard of care and
guideline-recommended in carefully selected patients (e.g. cardiogenic/mixed shock on
inotropes/pressors or in pts w/ MCS)(Circulation 2022;145:e895–e1032)
• Line course: central vein (IJ/fem)SVC/IVCRARVPAdistal pulmonary arteriole
VENOUS WAVEFORMS (CVP/PCWP)
• a wave: atrial contraction; coincides with the QRS complex (on CVP tracing)
• c wave: bowing of TV into atrium during ventricular contraction; more visible in 1st degree
AV block.
• x descent: atrial relaxation (early x descent), downward movement of TV (late x descent)
• v wave: passive atrial filling (venous return) when TV/MV closed; coincides with T wave
o Prominent v waves seen in MR & TR
• y descent: rapid atrial emptying following opening of the TV (ventricular diastole)
o Prominent x+y descents seen in pericardial constriction; blunted y descent seen in
tamponade
OBTAINING PA LINE NUMBERS ON AM ROUNDS
1) Position patient supine with head-of-bed between 0-60°
2) Align transducer with mid-axillary line (4th intercostal space)
3) Zero transducer to air & assess waveform for dampness
4) Record PA systolic, PA diastolic, PA mean, CVP, & line position
5) Open the PA catheter balloon port & remove 1.5cc air
6) Inject 1.5cc air slowly until PCWP waveform observed (use minimum air required to
↓ risk of PA infarction/rupture) & record PCWP (limit balloon inflation <10 seconds)
7) Release safety syringe & allow balloon to deflate passively; verify balloon deflated
by visualizing the PA waveform
8) Troubleshooting: CXR to evaluate position
a. Arrhythmia: catheter may be in RVOT; consider repositioning
b. Dampened waveform: kinked tubing, air/thrombus, or catheter tip against
vessel wall; flush and/or withdraw catheter
c. No PCWP tracing: catheter tip is not far enough, balloon has ruptured, or
catheter is coiled in RV
d. Continuous PCWP: catheter tip is advanced too far
e. mvO2 resembles arterial O2: catheter tip is advanced too far
CALCULATING HEMODYNAMIC PARAMETERS
• Normal: “rule of 5s”  RA 5, RV 25/5, PA 25/10, PCWP 10, LV 125/10
• Cardiac output: TD better predicts mortality (JAMA Cardiol 2017:10:10)
o Fick = VO2 / (13.4 * Hgb * [SpO2 – MvO2]) [nml: 4-7 L/min]
 VO2 ≈ 250 ml/min OR 3*wt(kg) OR 125*BSA
o Thermodilution (TD): temp change (measured by thermistor in PA) is
proportional to LV CO (inaccurate if: TR, intracardiac shunt, very low CO)
• Cardiac index = CO/BSA [normal: 2.6-4.2 L/min/m2]
• SVR = (MAP-CVP) / CO x 80 [normal: 700-1200 dynes*s*cm5]
• PVR = (mPAP-PCWP) / CO [normal: <2 Woods units]
HEMODYNAMIC CONSIDERATIONS
• All quantitative pressure measurements (especially PCWP) should be made at end-expiration (when intrathoracic pressure is zero)
o Spontaneous respiration: RA & PCWP  with expiration  measure from the higher a waves (“patient = peak”)
o Positive pressure ventilation: RA & PCWP  with expiration  measure from the lower a waves (“vent = valley”)
• Measure RA & PCWP at end-diastole (i.e. just before the c wave)
• Correlate PCWP with PA diastolic pressure; if well correlated, can trend PAd as proxy for PCWP (allowing for less frequent wedging)
CLINICAL CONSIDERATIONS
• Placement: usually through RIJ Cordis. Advance ONLY with balloon inflated. Deflate balloon when withdrawing and at ALL other times.
Must have cardiology or pulmonary fellow present to place/advance at MGH.
o Cath lab if: severe PH (>70mmHg), large RV/RA, LBBB, PPM/ICD <6mo, temp wire, severe TR, prosthetic TV/PV, femoral access
• Contraindications: absolute – insertion site infection, RVAD, RA/RV mass/thrombosis, mechanical TV/PV, endocarditis (TV/PV)
• Position: on CXR, should be in middle 1/3 of the chest bilaterally; ability to wedge more important than CXR position
• Complications: infection, bleeding, PTX, VT, RBBB, CHB, PA rupture (place patient on side with the catheter “bleeding side down”, order
STAT CXR, CBC, coags, CT surgery consult), pulm infarct, PE, catheter knotting (difficult removal)
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Cardiology Cardiac Devices: PPM, ICD, & CRT

PERMANENT PACEMAKERS (PPM), IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS (ICD), &
CARDIAC RESYNCHRONIZATION THERAPY (CRT)
• Types: single chamber (RA or RV lead), dual chamber (RA + RV leads), biventricular (RV + coronary sinus ± RA leads)
• PPM: sense/pace the RA & RV to treat bradyarrhythmias (see tables for nomenclature and common modes)
• ICD: device with an RV lead capable of terminating re-entrant ventricular tachyarrhythmias via pacing, cardioversion, or defibrillation
• CRT: provides simultaneous RV + LV pacing in HFrEF pts w/ wide QRS to ↓dyssynchrony → LV reverse remodeling & ↑LVEF
o CRT-P = BiV ± RA pacing; CRT-D = CRT-P w/ ICD function
HARDWARE OVERVIEW
• System consists of pulse generator + leads.
Usually implanted SQ in upper chest (L>R) >> NASPE/BPEG Codes for Pacing Operating Modes
abdominal Position I Position II Position III Position IV
• Types: traditional (SQ pulse generator + Chamber(s) Paced Chamber(s) Sensed Response to Sensing Rate Modulation
intracardiac leads), leadless (Micra, pulse O = None O = None O = None O = None
generator directly implanted into RV; no pocket A = Atrium A = Atrium T =Triggered R = Rate Modulation
complications; when battery dies, device V = Ventricle V = Ventricle I = Inhibited
retrieval is rare), SQ ICD (no IV hardware; low D = Dual (A+V) D = Dual (A+V) D = Dual (T+I)
risk for infection but NO pacing capabilities)
Code Action Use Waveform
• Placement: RA lead → RA appendage; RV lead
Single Chamber Modes
→ RV apex; LV lead → coronary sinus
Atrial Demand; A-
→ branches of great cardiac vein paced, A-sensed, Isolated SN dysfxn,
• Interrogation: EP Technician (p16939) business AAI
atrial activity inhibits intact AV node
hours; EP fellow on call after-hours/weekend PM
• MRI compatibility: not all devices are MRI High-grade AVB,
compatible (find out device model), however, Ventricular Demand;
bradycardia; does
even non-MRI compatible devices may be safe V-paced, V-sensed,
VVI not track atrial
to scan after re-programming (NEJM ventricular activity
activity (i.e. chronic
2017;376:755). Case-by-case. inhibits PM
AF)
• Magnet response: PPM: asynchronous pacing AOO: Obsolete,
AOO/ Asynchronous; A- or
(DOO/VOO); ICD: suspends detection/treatment VOO: Temp wire
VOO V-paced, no sensing
of tachyarrhythmias (no effect on pacing) pacing
Dual Chamber Modes
P P M I N D I C A T I O N S ( C L A S S I ) (JACC
Tracking Modes
2019;74:e51) Synchronous; paces Allows coordination
Sinus Node Dysfunction: senses in A & V; of A- & V-pacing;
• Symptomatic sinus brady (± sinus pauses) or DDD atrial activity is most closely
chronotropic incompetence (after tx reversible tracked/triggers mimics intrinsic
causes, ensure symptoms temporally ventricular activity conduction system
correlated) Atrial Synchrony
o Recommend DDD for symptomatic SND Rarely used; high-
VDD Possible; V-paced, A-
with extension of AV interval to minimize grade AVB
& V-sensed
V-pacing; prefer physiologic pacing Non-Tracking Modes
• Symptomatic medication-induced bradycardia if AV Sequential; paces
there is no accepted alternative medication & senses in A & V;
• Permanent AF and symptomatic bradycardia SSS or sinus brady
atrial activity not
AV Block (AVB)/Conduction Disease: DDI with intermittent
tracked; atrial
• 3°AVB with or without symptoms atrial tachycardias
tachyarrhythmia does
• Symptomatic 2° AVB Mobitz I or II (conduction not trigger RVR
disease must correlate temporally w/ symptoms) Avoid sensing
• Permanent 2° AVB Mobitz II or intermittent 3° Asynchronous Fixed
electrocautery or
AVB (regardless of symptoms) DOO Rate; paces A & V,
electromagnetic
• Alternating bundle branch block no sensing
interference
Neurocardiogenic: only if syncope associated with Different pacing modes. LRL, Lower rate limit; P, intrinsic P wave; A, atrial paced event; R, intrinsic R wave; V, ventricular paced
marked cardioinhibitory or bradycardic event event; VAI, ventriculoatrial interval; PAV, paced atrioventricular interval; SAV, sensed atrioventricular interval.

I C D I N D I C A T I O N S ( C L A S S I ) (JACC 2018;72:e91, 2022 AHA HF Guideline)

• 1° prevention indicated for pts with HFrEF only if after re-assessment on optimal GDMT for ≥90d. All pts must have an estimated >1-year survival.
Primary Prevention Secondary Prevention
Ischemic CM: NYHA Class I: EF ≤30%, >40d s/p MI & ≥90d s/p revascularization
- Prior episode of cardiac arrest (VF/pulseless VT)
NYHA Class II/III: EF ≤35%, >40d s/p MI & ≥90d s/p revascularization
and unstable or sustained stable VT** in presence of
Other: EF ≤40%, >40d s/p MI + NSVT + inducible VT/VF
other heart disease/channelopathy or if no reversible
Non-ischemic CM*: EF ≤35% + NYHA Class II/III cause found
- HoCM with known arrhythmias or after risk stratification (Circ 2024;149) - Cardiac syncope w/ LVEF<35% OR cardiac
- Long QT syndrome refractory to ßB +/- cardiac denervation syncope w/ inducible VT/VF on EP study OR cardiac
- Arrhythmogenic right ventricular cardiomyopathy after risk modeling syncope where VT/VF is most likely etiology
- Cardiac sarcoid (LVEF ≤35% despite GDMT and immunosuppression) (Circ 2024;149)
Also considered in: Brugada syndrome, catecholaminergic pVT, channelopathies, and **Does not include patients who have VT/VF limited to
within 48h of MI
specific protein variants (LMNA/C, desmosomal proteins, phospholamban, Filamin-C)
*DANISH (NEJM 2016;375:1221) in pts w/ NICM, ICD ↓SCD, but no Δmortality; In SCD-HeFT (JACC 2020;76(4):405) no benefit from ICD in NICM subgroup
C R T I N D I C A T I O N S ( C L A S S I ) (2022 AHA HF Guideline)
• NYHA II-III or ambulatory IV + LVEF ≤35% + Normal Sinus Rhythm + QRS >150ms w/ LBBB
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Cardiology Valvular Heart Disease

AORTIC STENOSIS
• Etiology: Aortic sclerosis (calcification of the valve; increasingly common with age), bicuspid valve (most common cause <70yo),
rheumatic heart disease (leaflets fuse, often with concurrent MV disease), radiation-induced
• Clinical Manifestations: most important determinant of prognosis = sxs: 50% mortality at 5y if angina, 3y if syncope, 2y if HF
o Angina: afterload  LV pressures  LVH  O2 demand  supply-demand mismatch w/ exertion or tachycardia
o Syncope: exercise-induced vasodilation  inability to augment CO due to stenotic valve hypotension / transient hypoperfusion
o Heart failure (dyspnea): LVH  diastolic dysfunction (systolic dysfunction is a late finding)
o Acquired vWF def: 20% of severe AS, can worsen bleeding from GI AVMs “Heyde syndrome” (NEJM 2012;367:1954)
• Diagnosis:
o Physical exam: harsh crescendo-decrescendo murmur at RUSB radiating to carotids. If severe: murmur late-peaking, delayed
carotid upstroke (pulsus parvus et tardus), soft S2 (Am Heart J 1999;137:298); Pearl: soft murmur may indicate low flow!
o TTE: measure mean (not peak) gradient, valve area, & jet velocity; also, important to assess EF (gradient can be underestimated
with reduced EF  low flow, low gradient AS)
• Severe AS: peak AV velocity ≥4m/s, mean AV pressure grad ≥40mmHg, or AV area (AVA) ≤1cm2 (ACC/AHA: Circ 2021;143:e35)
o ECG: LVH, LAE, LAFB, LBBB
o Exercise stress testing: recommended in asymptomatic severe AS to assess for symptoms; do not perform in pts w/ sx
• Natural History: highly variable, but on average, AVA  ~0.1 cm2/y & mean gradient 8mmHg/y (JACC 1989;13:545). Patients with
bicuspid valves, advanced age, & those with severe leaflet calcification are at risk for more rapid progression
• Aortic Valve Replacement (AVR) (J Am Soc Echo 2018;31:117): determining indication for valve replacement is based on
evaluating: (1) presence of symptoms, (2) severity by TTE criteria, (3) LV function (EF)
o Symptomatic, severe AS (Stage D): prompt AVR indicated due to risk of sudden death
o Asymptomatic, severe AS (Stage C): AVR appropriate if LVEF<50%, if symptoms provoked with exercise testing, or undergoing
other cardiac surgery; for patients with asymptomatic very severe AS (AVA ≤0.75cm2) early surgery may have mortality benefit
(NEJM 2020;382:111)
o If suspect low-flow (LVEF <50%) & low-gradient (<40mmHg w/ AVA <1cm2): dobutamine stress TTE (DSE) to distinguish
between low-flow, low-gradient AS versus “pseudosevere AS” (Circ 2011;124:739)
 Low-flow/Low-gradient: if DSE = Vmax >4m/s or mean gradient >40mmHg while AVA remains <1cm2, AVR is indicated
 Pseudosevere AS: if DSE results in AVA >1cm2, AVR not indicated
o Bioprosthetic vs Mechanical: if contraindications to AC with VKA, must offer bioprosthetic; if pt <50 years of age without
contraindications to AC, SAVR w/ mechanical valve recommended (COR 1; Circulation 2021; 143:35); if >65 yrs of age,
bioprosthetic recommended (COR 2a); 50-65 years of age require shared decision making
o SAVR vs TAVI for bioprosthetic: pts <65y, SAVR recommended d/t increased durability; >80y TAVI recommended
o 65-80 yrs of age: depends on surgical risk (STS-PROM score), concomitant heart/vascular disease, valvular/vascular
anatomy that is amenable to TAVI (Circulation 2021; 143:35)
o TAVI is recommended for those at extreme surgical risk (compared to medical therapy, PARTNER); noninferior to
SAVR in those at high (NEJM 2011;364:2187), intermediate (PARTNER 2), & low surgical risk (PARTNER 3). Valve-in-
valve TAVI may additionally be beneficial in pts with surgical bioprosthetic AV failure (JACC 2017;69:2253)
o TAVI Evaluation: c/s structural cardiology, cardiac surgery. Obtain TTE, TAVI-protocol CT, dental clearance (Panorex)
o TAVI Complications: Valve: embolization, paravalvular leak; Stroke: embolic (first 48h), ischemic/hemorrhagic; Conduction:
HGAVB requiring PPM (Major RF: baseline RBBB, need for pacing or HAVB s/p TAVI; Minor: h/o AF, valve oversized >15%;
Card Fail Rev 2021; 7:e12); Bleeding; Access site complication; Hemodynamics: dynamic LVOT obstruction due to LVH (“suicide
LV”), HTN (sudden ↓ in obstruction after TAVI), hypotension (d/t ↓preload), tamponade (perforation, usually immediate); AKI
• Medical Management: AS is a surgical disease & medical management is only utilized for treatment of sx
o Treat HTN: reduce the “double load” on the ventricle. In theory, ACE-I may have beneficial effect on LV fibrosis. However, no
optimal regimen exists because anti-hypertensives can lead to hemodynamic issues. Bottom line: start low and go slow
o Control volume status: operate within a narrow preload range, prone to underfilling (low preload) & overfilling (volume overload)
• Anticoagulation after Valve Replacement:
o Bridging UFH or LMWH if AC interrupted only in mechanical MV or mechanical AV with RFs (Class I),
o RFs: AF, LV dysfxn, prior VTE, hypercoag, older gen mech AVR (Circ 2021;143:e35)
o Bleeding risk: mechanical > bioprosthetic (likely AC related). Reoperation risk: bioprosthetic > mechanical
o TAVI: ASA monotherapy non-inferior to DAPT for thrombotic events & associated with less bleeding (NEJM 2020;383:1447)
o If need AC for AF, DOACs similar outcome after TAVI, not approved for valvular MS (moderate+) (JAHA 2021;11:e023561)

Prosthesis Location Timing and Risk Factors for AC INR Class

Mitral Indefinitely 2.5-3.5 (+ ASA 81) I
Mechanical Indefinitely, (+) risk factors 2.5-3.5 (+ ASA 81) I
Aortic
Indefinitely, (-) risk factors 2.0-3.0 (+ ASA 81) I
First 3 months after placement, regardless of RFs 2.0-3.0 (+ ASA 81) IIa
Mitral
>3 months after placement ASA 81 IIa
Bioprosthetic
First 3 months after placement, regardless of RFs 2.0-3.0 (+ ASA 81) IIa
Aortic
>3 months after placement ASA 81 IIa
TAVI Aortic No AC; indefinite antiplatelet monotherapy ASA 81 or Clopidogrel 75 IIa
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Cardiology Valvular Heart Disease

AORTIC REGURGITATION (AKA INSUFFICIENCY)
• Etiology: Acute: aortic dissection, valve perforation (usually due to MI or endocarditis), traumatic valve leaflet rupture; Chronic: leaflet
abnormalities (bicuspid valve, endocarditis, RHD) or root dilation (secondary to HTN, CTD, dissection, syphilis)
• Pathophysiology: Acute: diastolic regurgitant flow  sudden LVEDP (w/o remodeling time)  CO  pulmonary edema; Chronic:
diastolic regurgitant flow  LVEDP  initial maintenance of SV/CO  progressive ventricular dilatation  failure
• Clinical/Exam: angina, L-sided HF. Acute: cardiogenic shock. Chronic: pulse pressure (bounding pulses, bouncing head/uvula, nail
bed capillary pulse; Int J Card 2006;107:421)
o Auscultation: high-pitched, blowing diastolic decrescendo murmur along LSB. Longer murmur = more severe/chronic. May hear
low-pitched diastolic murmur at apex secondary to regurgitant jet displacing anterior mitral leaflet
• Treatment:
o Acute: usually needs surgery. Nitroprusside to afterload; ino- and chronotrocpes to diastolic time. Do not use
vasoconstrictors or IABP (which worsen regurg) or beta-blockers (which block compensation and diastolic regurgitant time)
o Chronic: ACEi/ARB/Entresto first line, CCB or hydralazine/nitrates second line to reduce LV afterload. Proceed to AVR if:
symptomatic severe AR; LVEF<55%, LV end-systolic dimension >50mm, undergoing other cardiac surgery

MITRAL STENOSIS
• Etiology: 80% due to RHD (only 50-70% report h/o rheumatic fever). Also, endocarditis, annular calcification (rarely significant),
congenital, autoimmune valvulitis (SLE), carcinoid synd, endomyocardial fibroelastosis, XRT (e.g., 10-20y after Hodgkin’s tx)
• Pathophysiology: elevated LAP  pHTN, AFib (47%). Demand for CO precipitates symptoms. Valve narrows ~0.1cm2/y
• Clinical/Exam: dyspnea (most common), pulmonary edema, hemoptysis, VTE even w/o AFib (Am Heart J 2000; 140:658), RV failure
o Auscultation: loud S1, high-pitched opening snap (more severe if earlier, indicating higher LAP); low-pitched diastolic rumble at
apex and at end-expiration
• Treatment: Medical: warfarin if LA thrombus, AFib, prior embolism (Class I) or LA > 55mm (Class IIb). Beta-blockers if tachycardic or
dyspneic, diuresis if pulmonary vasc congestion. If rheumatic, secondary ppx against strep as below (Circulation 2021;143:e35)
o Intervention: generally, need to have severe MS (MV area ≤1cm2) + symptoms to be considered for intervention
 Rheumatic MS: symptomatic pts with severe rheumatic MS and favorable valve morphology (based on TTE, Wilkins Score)
 Percutaneous mitral balloon commissurotomy (PMBC) (COR 1, Circulation 2021;143:e35); consider if asymptomatic
and elevated pulmonary pressures (>50mmHg; COR 2a) or new AF (COR 2b)
 Nonrheumatic Calcific MS: because calcification involves the annulus and base of the leaflets without commissural fusion,
there is no role for PMBC or surgical commissurotomy; consider intervention only after discussion of high risk (COR 2b)
 Proceed to MVR if not PBMC candidate, PBMC fails, or undergoing another cardiac surgery (even if asymptomatic)

MITRAL REGURGITATION
• Etiology: dilated annulus (“functional MR”), MVP, ischemic papillary muscle dysfunction, ruptured chordae, endocarditis, RHD, CTD
• Pathophysiology: LA/LV volume overload  LV dysfxn, progressive enlargement of LV  dilated mitral annulus  regurgitation
• Clinical: Acute: flash pulmonary edema, hypotension, shock; Chronic: DOE, orthopnea, PND, AFib, pulmonary  periph edema
(pulmonary edema may be one-sided depending on jet direction)
• Exam: holosystolic murmur at apex radiating to axilla, S3, displaced PMI. If acute: early diastolic rumble and S3 may be only signs
• Treatment:
o Acute: afterload (e.g., nitroprusside), inotropes (dobutamine), diuresis. If hemodynamically unstable (esp. post-MI or
endocarditis), consider IABP and/or urgent surgical repair (NEJM 2012;366:2466). If ischemic, consider revascularization
o Chronic: GDMT for HF if applicable
 Severe primary MR: symptomatic w/ any EF OR asymptomatic w/ EF ≤ 60% or LVESD ≥ 40mm  MVR (Circulation
2021;143:e35); primary MR w/ high surgical risk, transcatheter edge to edge repair (M-TEER) (COR 2a; EVEREST II).
 Severe “functional MR”: if LVEF ≥50% OR unfavorable anatomy AND symptomatic on maximal GDMT OR undergoing
CABG  MVR; if LVEF <50% AND persistent symptoms on maximal GDMT AND anatomy favorable  M-TEER (COAPT).

TRICUSPID REGURGITATION
• Etiology: Primary: RHD, IE, iatrogenic (device leads, etc), congenital, trauma, carcinoid, drugs; Secondary: pulmonary HTN w/ RV
remodeling (“functional”), dilated annulus (associated with AF), dilated CM, RV volume overloadischemic papillary muscle dysfunction
• Pathophysiology: similar to mitral regurgitation, but involving RA/RV and tricuspid annulus
• Clinical: Right-sided heart failure: hepatosplenomegaly, ascites, peripheral edema, large V in JVP, pulsatile liver, substernal pulsation
o Ausculation: holosystolic murmur at left mid- or lower- sternal border that increases with inspiration, S3
• Treatment: Medical: Diuresis (COR 2a), management of underlying cause
o Tricuspid valve replacement: Consider if primary severe TR OR secondary severe TR with RV dilation/dysfx
o Primary severe TR: if: 1) at time of LV valve surgery, 2) R heart failure, 3) moderate TR with progressive RV dilation/dysfx
o Secondary severe TR if: 1) R heart failure poorly responsive to GDMT without ↑PAP or left HF (Circ 2021;143:e35).
o Progressive TR (Stage B): consider if undergoing L valve surgery OR tricuspid annular dilation >4 cm w/ R heart failure
o Transcatheter therapies are potential options but lack longterm outcomes and performance data (JACC 2018;71:2935)
GENERAL PRINCIPLES
• Rheumatic Disease: secondary ppx against streptococcus recommended for 10y or until 40 yrs old (whichever longer, COR I)
• AF and Valvular disease: w/o mechanical valve, DOAC reasonable VKA except in rheumatic MS, practice variable for nonrheum MS
• IE Prophylaxis: Reasonable in pts undergoing dental manipulation with 1) prosthetic heart valves, 2) prosthetic material used in valve
repair, 3) prior IE, 4) Unrepaired cyanotic CHD, or 5) s/p cardiac transplant with valve abnormality (COR 2a; Circulation 2021; 143:35)
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Cardiology Pericardial Disease

CARDIAC TAMPONADE
• Definition: hemodynamic insufficiency caused by impaired cardiac filling due to pericardial pressure due to effusion, leading to
intracardiac chamber pressures & eventually equalization of diastolic pressure in all 4 heart chambers
• Etiologies of pericardial effusion: idiopathic (20%), iatrogenic (16%), malignant (13%), uremic, infectious, HF, autoimmune (Am J Med
2000;109:95). Tamponade more likely in malignant, post-viral (including SARS-CoV-2), uremic, iatrogenic (i.e. post-cath) etiologies. Also
seen with prox. aortic dissection & myocardial wall rupture
Clinical Manifestation and Diagnosis: 5 Clinical Features Associated with
• Beck’s Triad: BP, JVP, muffled heart sounds; elevated BP does not rule out Tamponade (JAMA 2007;297:1810)
• Pulsus paradoxus (PP): exaggeration of normal decrease in SBP during inspiration (If Sign/Sx Sensitivity 95% CI
>10mmHg, ⊕LR=3.3. If ≤10 mmHg, ⊕LR=0.03) Dyspnea 87-89% n/a
1. Slowly deflate BP cuffnote pressure when systolic Korotkoff sounds Tachycardia 77% 69-85%
only heard during expiration (will sound irregular) (a)  continue slowly Pulsus
82% 72-92%
deflating BP cuff until Korotkoff sounds heard throughout; (b) PP = a – b paradoxus
2. Via A-line tracing (PP = height exp. – height insp. systolic waveform) Elevated JVP 76% 62-90%
o False-negative PP conditions: pre-existing disease w/ LVEDP (e.g., chronic Cardiomegaly 73-
HTN), regional tamponade, pericardial adhesion, acute MI, arrhythmia, 89%
on CXR 100%
ASD/VSD, severe AI, hypotension/shock, RVH)
o PP DDx: severe COPD/asthma, massive PE, hypovolemic shock, RVMI, constrictive
physiology, tense ascites CVP tracing in tamponade
• ECG: sinus tach, low QRS voltage (50%; limb ≤5mm, precordial ≤10mm), electrical alternans
(20%; precordial leads)
• TTE: inspiratory leftward septal shift, diastolic collapse of cardiac chambers (R > L-sided),
respirophasic changes in transvalvular velocities, IVC plethora. SIZE of effusion does NOT
predict tamponade – RATE of accumulation is more important
Treatment:
• Fluid resuscitation: administer volume urgently to increase intracardiac pressures (monitor
closely as overfilling can worsen tamponade), starting w/ 250-500cc bolus; greatest benefit for SBP < 100 mmHg (Circ 2008;117:1545)
• Inotropes: administer if IVF insufficient. Unclear benefit b/c endogenous catecholamines already at max level. Avoid BB
• PPV: avoid if possible as positive intrathoracic pressure will further impede ventricular filling
• Drainage: catheter pericardiocentesis, surgical pericardiectomy (if aortic/myocardial rupture), or HD (if uremic)
o Analysis of pericardial fluid: cell count, total protein, LDH, gram stain/cx, viral markers/cx (Coxsackie, HSV, CMV, EBV, HIV),
AFB smear/cx, ADA/IFN-gamma/lysozyme (if concerned for TB), cytology/tumor markers
o Removal of drain: when output <50cc/d, otherwise consider pericardial window (pleural>abdominal). See Pericardial Drain
PERICARDITIS ECG Evolution in Pericarditis (JACC 2020;75:76)
• Classification: acute (<6w), incessant (>6w w/o remission), recurrent (return
after symptom free interval of 4-6 wks), chronic (>3months)
• Epidemiology: 5% of pts in ED w/ non-ischemic chest pain, M > F
• Etiology: 80-90% idiopathic (usually viral/post-viral), bacterial, fungal, post-MI,
uremic, mycobacterial (TB), autoimmune (CTD, vasculitis), malignancy (e.g.
lung, breast), XRT, drugs (procainamide, hydral, INH) (NEJM 2014;371:2410)
Clinical Manifestations and Diagnosis:
• Symptoms: sudden onset, pleuritic, retrosternal CP relieved w/ sitting up & leaning forward (may radiate to trapezius muscles), ±
viral prodrome if infectious etiology. In uremic or CTD pericarditis, CP may be absent
• Exam: pericardial friction rub (~30% cases), best heard at LLSB w/ diaphragm of stethoscope at end-expiration w/ pt leaning forward
• ECG: 4 stages: (1) diffuse ST & PR (PR & ST in aVR/V1); (2) ST & PR normalize; (3) diffuse TWI; (4) TW normalize. May see
continual low-voltage or electrical alternans if effusion present. Uremic pericarditis: ECG can be normal b/c epicardium not inflamed
• Diagnosis: ≥2 of the following: (1) characteristic CP, (2) friction rub, (3) suggestive ECG changes, (4) pericardial effusion
o Workup: infectious w/u, BUN/Cr, ANA/RF/CCP, HIV, HCV, IGRA, ESR/CRP, troponin (elevated in ~30%, c/f myopericarditis)
o TTE: assess for presence/size/location of co-existent effusion and/or tamponade physiology
o Pericardiocentesis/Surgical Drainage: if (1) suspect malignancy or bacterial etiology (2) large effusion (>2cm) (3) tamponade
o Cardiac MRI: adjuvant test if dx uncertain or c/f myocardial involvement; +LGE has 94% Sn for pericarditis (JACC 2020;75:76)
Treatment: self-limited (days-weeks) in 70-90% of cases
• Hospitalize if: fever, WBC, large effusion (>2cm), immunocompromised, anticoagulated, trauma, troponin, unstable/signs of
tamponade, failure to respond to NSAIDs after 7d. Also consider hospitalization if subacute presentation
• 1st-line treatment: NSAIDs (e.g. ibuprofen 600-800mg TID; ASA 650-1000mg TID) ± colchicine 0.6mg BID (qd if pt <70kg)
o Colchicine sx at 72h, improves 1w remission and 18mo recurrence in acute idiopathic pericarditis (Circ 2005;112:2012; NEJM
2013;369:1522). No benefit w/ malignant or uremic cases
o ASA: preferred over NSAIDs if: post-MI, CAD, concomitant anti-platelet/anticoagulant therapy
o Activity restriction: avoid strenous activity until symptom resolution
• Glucocorticoids (prednisone 0.2-0.5mg/kg/d): preferred over NSAIDs if: sx refractory to 7d of NSAID treatment, recurrent (>2
episodes), uremic pericarditis, CTD pericarditis, or contraindication to NSAIDs. Associated w/ recurrence if first idiopathic episode
• Duration: NSAIDs: until sx resolve (1-2w), then taper (total 3-4w). Colchicine: 3mo. Glucocorticoids: 2w, then taper (3mo total)

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Cardiology Aortic Disease

A C U T E A O R T I C S Y N D R O M E S ( A A S ) (Nat Rev Cardiol 2015;12:103)(Lancet 2023;401;p773)
Definitions: three distinct processes with risk of rupture
• Aortic dissection (AD): intimal tear resulting in a false lumen
• Intramural hematoma (IMH): rupture of vasa vasorum causing
hematoma within aortic wall without tear
• Penetrating aortic ulcer (PAU): ulceration of atherosclerotic
plaque that penetrates into intima of aortic wall

Classification: Aortic Landing Zones

Source: (Circulation 2022)
• DeBakey: type I (ascending + descending aorta); type II
(ascending aorta only); type III (descending aorta only) Source: UpToDate 2023

• Stanford: type A (ascending ± descending); type B (descending only)

• Aortic Landing Zones: Classification used to guide intervention

Epidemiology:
• Prevalence: aortic dissection most common (62-88%), followed by IMH (10-30%) & PAU (2-8%)
• Risk factors: male, HTN, age 60-70 (if <40yo, think Marfan syndrome, Ehlers-Danlos Syndrome type IV, CTD, bicuspid valve),
atherosclerosis, prior cardiac surgery, aortic aneurysm, FHx of AAS, aortitis, trauma, pregnancy
• Aortic dissection prognosis:
o Type A: mortality at 3y among patients discharged alive: Medical: 31%, Surgical: 10% (Circ 2006;114:I350)
o Type B: Medical: 8% in-hospital mortality, 15% 1y, 24% 3y, 57% 10y (J Vasc Surg 2021;73:48)
• IMH will progress to complete dissection in 28-47% of cases. PAU will progress to aortic rupture in 42%.
Diagnosis:
• Clinical features: AD, IMH, & PAU cannot be distinguished by presentation alone
o Signs: AI murmur, pulse deficit, upper extremity BP differential (>20mmHg), decompensated heart failure
o Sx: chest or back pain (radiates to neck/jaw if ascending; back/abdomen if descending; may migrate as dissection propagates)
• Complications: syncope, shock, branch artery occlusion (MI, CVA, paraplegia, cold extremity, renal failure); aortic valve regurgitation,
pericardial effusion, cardiac tamponade, stroke
• Risk Score: Aortic Dissection Detection Risk Score (ADD-RS): d-dimer versus directly to CTA (Circ 2018;3;250)
• Labs: rule out if D-dimer <500ng/mL (96% NPV), troponin (can be ⊕ if dissection extends into coronaries), ↑MMP-9
• Imaging:
CXR - 50% with AAS have normal CXR; only 1/3 will have widened mediastinum

- Sn 95%, Sp 87-100%; first-line modality in pts w/ high clinical probability of AAS

CT-A
- Combined I+/I- (assess for IMH, mediastinum hemorrhage, or hemopericardium)

- Sn 73-100%, Sp 71-91%, least accurate of diagnostic imaging modalities

TTE
- Useful for identifying AV dysfunction, prox dissections extending to Ao root/pericardium

- Sn 99%, Sp 90-100%. Often used intra-op to confirm dx prior to surgery

TEE
- Invasive nature limits use; cannot detect pathology below the diaphragm

Management:
• Goal: “impulse control”  minimize aortic wall stress by LV ejection force (dP/dT): goal HR <60, SBP 100-120mmHg
• Agents:
o IV beta blockade (esmolol, labetalol); except if acute severe AI.
o If additional BP control required, consider IV nitroprusside, TNG, nicardipine. If refractory HTN, consider renal artery
involvement.
 NEVER use vasodilators for AA without AI without concomitant beta blockade  will increase wall stress via reflex
tachycardia, thereby increasing dP/dT. Opiate analgesia attenuates release of catecholamines (Lancet 2015;385:800)
• Urgent surgical consultation (CT surgery)
• Aortic Dissection:
o Type A: immediate open surgical repair 26% mortality vs >50% with medical management (JAMA 2000;283:897)
o Type B: uncomplicated: medical therapy (80% survival at 5y); complicated (compromise of renal/mesenteric vessels): TEVAR.
However, INSTEAD-XL showed improved outcomes with low-risk preemptive TEVAR in all Type B dissections
• IMH & PAU:
o Type A: urgent (i.e., within days) open surgical repair
o Type B: medical management or TEVAR
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Cardiology Aortic Disease

A O R T I C A N E U R Y S M S (Circulation 2022 ;146 ; e334)
Abdominal Aortic Aneurysm (AAA) Thoracic Aortic Aneurysm (TAA)
• M>F, mostly 50-70yo, 50% ascending Ao, 40%
Epidemiology • M>F; >65yo, mostly infrarenal
descending Ao, 10% arch
• Atherosclerotic: majority of cases, especially
descending Ao. RFs: smoking, HLD, HTN
• Structural/genetic: mostly root & ascending aorta.
• Usually due to atherosclerotic disease Causes: CTD (Marfan, Ehlers-Danlos, Loeys-Dietz),
Etiology • RFs: smoking, male sex, age, pre-existing Turner, bicuspid AoV, trauma
atherosclerosis, obesity, HLD, HTN, FHx • Infectious: 3° syphilis, mycotic aneurysm (most
common org: Staph spp., Salmonella spp.)
• Inflammatory: GCA (~10% have TAA), Takayasu, RA,
psoriasis, Behcet’s, Wegener’s, IgG4
• General population: not recommended
• Indications: at time of dx of Marfan, Turner, Loeys-
• ACC/AHA: one-time abdominal US in all men >60
Dietz, Takayasu or GCA. 1° relatives of pt w/ TAA,
w/ FHx of AAA & all men 65-75 who have ever
smoked dissection, bicuspid valve (even if no disease-causing
Screening / variant identified on genetic testing)
• Surveillance (J Vasc Surg 2018;67:2): interval
Surveillance • Surveillance: interval depends on presence of
depends on size
aneurysm etiology/location; primarily CT/MRI, TTE (if
• 3.0-3.9cm: q2-3y; 4.0-4.9cm: q12 months;
valvular disease) ranging from q6-12months
5.0-5.4cm: q6 months
• Associated aneurysm: screen for abdominal,
intracranial and lower extremity aneurysms
• Abdominal US: screening and surveillance of infrarenal AAAs. High Sn/Sp (>90%), operator-dependent
• CTA: high Sn/Sp, >>US for suprarenal AAA; ECG-gated CT (synced w/ diastole via ECG) increases resolution
Imaging
• MRI/MRA: good Sn/Sp, preferred for aortic root imaging & for imaging tortuous aortas
Modalities
• CXR: “enlarged aorta” nonspecific (tortuous aorta vs aneurysm)
• TTE: useful for root & proximal thoracic aorta; TEE: will visualize entire thoracic aorta but rarely used
Medical
• Reduce BP (SBP goal of 105-120)
• Meds: BBs (decrease TAA growth in Marfan pts),
ARBs (slows expansion in Marfan pts)(JACC
2014:64:1725), ACEi, statins (goal LDL<70)
Medical • Behavioral: Smoking cessation, avoid straining
• Smoking cessation (slows growth) • Avoid fluoroquinolones
(J Vasc Surg 2010:52:539)
• Reduce BP per ACC/AHA guidelines Surgical
• Meds: statins (reduce all-cause mortality in pts s/p • Root/ascending TAAs: ± concomitant AVR
surgery)(JAHA 2018:7:19) ; BBs (have not been • Intervention indicated at 5 cm (threshold
clearly shown to slow expansion)(J Vasc Surg lower in patients w/ heritable conditions)*
Treatment 2002:35:72); ACEi (controversial); low dose ASA • Arch/descending TAAs
(may slow growth); avoid fluoroquinolones
• Intervention indicated if diameter is ≥5.5 cm*
Surgical *Repair indicated earlier if rapid expansion (>0.3-0.5cm/yr)
• Men: >5.5cm OR growing >0.5cm/6mo or
>1.0cm/y OR symptomatic Genetic Testing
Women: >4.5-5cm (controversial) • Indicated in proband (first person in family in whom
• Open repair vs EVAR clinical concern is raised)
• Genetic counseling and cascade testing if pathogenic
or likely pathogenic variant detected
• Panels include FBN1, LOX, COL3A1, TGFBR1,
TGFBR2, SMAD3, TGFB2, ACTA2, MYH11, MYLK,
and PRKG1
• Rupture: devastating mortality. Risk factors: size, rate of expansion, female gender. Sx: triad of abd/back pain +
Acute pulsatile abd mass + HoTN  immediate OR
Presentations • Dissection: pain (chest/abdomen/back), occlusion of aortic vessels, thromboembolism, discrepant blood
pressure in upper extremities

Surgical • Endovascular Repair: Endoleak, graft failure, thrombosis

Complications • Open Repair: MI, embolization, AKI, ischemic colitis

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Cardiology Syncope
OVERVIEW
• Definition: transient (self-limited) loss of consciousness due to cerebral hypoperfusion that is associated with loss of postural tone,
followed by complete spontaneous recovery; excludes metabolic causes (e.g. hypoglycemia, hypoxia, intoxication)
• Risk assessment and need for hospitalization:
o High-risk symptoms: preceding palpitations, exertional syncope, bleeding, syncope while supine, lack of prodrome, trauma
o High-risk features: angina, CHF, mod-severe valvular or structural heart disease, ECG features of ischemia/arrhythmia, FHx of
SCD, preexcitation syndromes, high-risk occupation (e.g. airline pilot), facial trauma (lack of warning time)
o Risk calculators have high NPV (>95%) but do NOT replace clinical judgment
 San Francisco Syncope Rule (SFSR): admit pt if ≥1: ECG changes or non-sinus rhythm, dyspnea, Hct<30, SBP<90, HF
 Canadian Syncope Risk Score: predicts risk of 30-day serious adverse events associated w/syncope (arrhythmia, MI, etc.)
• Ddx: seizure, metabolic causes (hypoglycemia, hypoxia), intoxication/meds, vertebrobasilar TIA, fall, psychiatric, autonomic failure

E T I O L O G Y A N D D I A G N O S I S : (AHA/ACC/HRS: JACC 2017;70:e39)

Etiology Historical Features Diagnosis Treatment
Vasovagal: prodrome of dizziness,
• Avoid provocative stimuli
nausea, warmth, diaphoresis,
Reflex (60%) • Vasovagal: can dx w/ tilt table test, not • Isometric counterpressure
pallor; a/w intense emotion, pain,
necessary if clear dx by history (JACC maneuvers of the limbs (e.g.
• Vasovagal stress, or prolonged standing.
1996;28:263) leg crossing, hand grip, arm
• Situational Situational: cough, sneeze, laugh,
• Carotid sinus syncope: diagnose via carotid tensing, Valsalva, squatting)
• Carotid sinus micturition, defecation, post
sinus massage (if no underlying bruits or • Meds for select cases (i.e.
syncope exercise
CVA history) midodrine, fludrocortisone,
CSS: neck turning/
surgery/irradiation βB) (NEJM 2005;352:1004)
Prodrome of dizziness, nausea, • Orthostatic vital signs (systolic ≥20mmHg • Primary: fludrocortisone
warmth, diaphoresis, pallor or diastolic ≥10mmHg w/in 3min of (0.05-0.3mg qd), midodrine
Orthostasis (15%) Risk factors for autonomic failure: standing or on a head-up tilt test ≥60o)(Circ (2.5-10mg bid or tid),
- 1°: PD, Lewy body, MSA EP 2022;15:3) pyridostigmine, droxidopa
• Autonomic failure
(formerly known as Shy-Drager) - HR is NOT part of definition (for PD-associated
(1° or 2°)
- 2°: DM, amyloid, spinal cord - Variant: smaller, but symptomatic, orthostasis) (Circ EP
• Drug-induced
injury, chronic EtOH, Lyme, reduction in SBP when supine SBP is low (90- 2022;15:3)
• Volume depletion syphilis, B12 deficiency, meds 100mmHg) but drops well below this. • Secondary: treat underlying
(vasodilators, diuretics, BB, TCAs, • Consider: Hct, A1C, SPEP if c/f amyloid, etiology, replete volume, d/c
PD meds, opiates, α-blockers) RPR, B12 culprit meds
• Causes of cardiac syncope in young people
• VT- Therapy with ablation
(+ ECG signs):
and/or an implantable
1. WPW (delta wave)
cardioverter-defibrillator
2. HOCM (LVH, apical TWI)
(ICD) is indicated in most
3. Brugada (pseudo-RBBB with
patients (JACC
coved/saddleback pattern in V1-V2)
2017:70:e39)
4. Long QTc syndrome (QTc >500ms)
Cardiac (15%) • SVT (Less common)- If
5. ARVC (Epsilon wave)
evidence of accessory
• Arrhythmia • Consider cardiac monitoring on basis of
No prodrome, syncope while in pathway is found, should be
• Structural (AS, frequency and nature of syncope events
sitting or supine position, treated with catheter
LVOT obs.) (inpatient telemetry, Holter, Zio patch,
palpitations, FHx or personal ablation.
• Obstruction (e.g., implantable cardiac monitor)
history of heart disease • Bradyarrythmmias-
PE, tamponade) • TTE only if H&P suggestive of cardiac
Depending on etiology of
• Dissection cause (<1% yield if no underlying heart
bradycardia, pacemaker
disease and normal ECG)
therapy could be indicated
o ROMEO criteria: Sn 99.5%, Sp 15.4%
• AS- If all other sources of
(JHM 2018;13:823)
syncope are ruled out, AVR
• Consider PE if no other apparent cause 
may be indicated if patient is
identified in 17.3% hospitalized w/ 1st
a surgical candidate
syncope (& 25.4% w/ no other apparent
cause for syncope) (NEJM 2016;375:1524)

Seizure: lateral tongue biting (Sn • Seizure: EEG

Neurologic (<10%) 20-33%, Sp 96-100%), • Stroke: CT, MRI/MRA
• Based on etiology, consider
urinary/fecal incontinence (Sn • Steal: UENI w/ Dopplers (specify for
• Seizure neurology consult and follow
38%, Sp 57%), aura, postictal subclavian steal)
• Stroke/TIA guideline-directed
confusion • Carotid dopplers are of low clinical utility
• Subclavian steal Focal deficits: stroke, TIA management & therapy
(changes management in <2% of patients)
Steal: syncope after arm exercise (JAHA 2014;3:e001063)

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Cardiology Severe Asymp. HTN & Emergency

D E F I N I T I O N S , T R I A G E , A N D M A N A G E M E N T : see Outpatient CV Health for workup (NEJM 2019;381:1843; HTN 2024)
• Severe asymptomatic HTN (HTN urgency): SBP ≥180 or DBP≥120 w/o evidence of end-organ damage (may have mild headache)
o Assess adherence to prior rx before aggressively up-titrating regimen to avoid overcorrection of BPs & hypotension
o Assess causes before tx; commonly due to pain, anxiety, urine retention, meds (e.g. steroids), OSA, nausea, withdrawal, etc.
• Hypertensive emergency: SBP ≥180 or DBP≥120 w/ evidence of end-organ damage
o End-organ damage: Neuro: HTN encephalopathy (severe HA, seizure, AMS), PRES, TIA, CVA (SAH, ICH); Retinopathy:
papilledema, hemorrhage; Resp/CV: flash pulmonary edema, MI, angina, Ao dissection; Heme: MAHA; Renal: AKI, hematuria

Severe Asymp. HTN (JHM 2018;13:860) Hypertensive Emergency

Floor vs outpatient mgmt (with close follow up) (HTN Floor vs ICU (ICU if needs arterial line, antihypertensive
Triage location
2024) gtt, or if severe end-organ damage)
↓BP no more than 25-30% over hrs-days; then to MAP ↓ by 10-20% in 1st hr, further 5-15% over next 23
Correction time goal as outpt. If hospitalized for non-cardiac reason, hrs. Reduce BP by max 25% within first hour, and to no
course worse outcomes w/ intensifying anti-HTN during lower than 160/100 within 2-6h; reduce to normal range
admission (JAMA IM 2021;181:345-352) over 24-48h
Route of medication PO meds; avoid IV or high-dose meds (risk for AKI, Start with short-acting, titratable IV agents; transition to PO
administration stroke, MI d/t hypoperfusion) agents for floor/discharge
Suggested meds PO: start captopril, labetalol >> hydralazine IV: labetalol >> hydralazine (high risk of overcorrection)
(see below for (unpredict., reflex tachy) & convert to long-acting Topical: nitro paste or patch (may be used on the floor)
dosing) before discharge OR start long-acting agents Drips: see below
Disease Process-Specific Recommendations for Hypertensive Emergency
BP Goal Suggested Medications
Nitro (topical, gtt), esmolol > labetalol, nicardipine/clevidipine. No BB if LV
ACS SBP <140 w/in 1h; keep DBP >60 failure w/ pulm edema, HR <60, SBP <100, shock, high-grade HB.
Judicious nitro if RVMI. No nitroprusside (cor steal) or hydral (ischemia).
Acute pulm edema SBP <140 w/in 1h Nitro (topical, gtt), nitroprusside, nicard/clevid; No BBs.
Aortic dissection Fast!-SBP <120 & HR <60 w/in 20min IV BB (labetalol, esmolol), followed by vasodilator (nicardipine/clevidipine)
Ischemic stroke <185/110 if lysis; <220/120 if no lysis or organ damage (permissive HTN)
Hemorrhagic stroke SBP >220, reduce by 25%. If SBP 180-220, target reduction to 140-160 Labetalol, Nicardipine, Clevidipine
PRES Immediate MAP decline 20%–25%
Antihypertensive Dosing – ICU
Agent Dosing Onset Duration Indications
500µg/kg load (given over 1 min) + infusion 25-50µg/kg/min; Ao dissection, CAD, peri-
Esmolol (IV) <1min 10-20min
then adjust by 25µg/kg/min q10-20min up to 300µg/kg/min op HTN, avoid in ADHF
10-20 mg load + 20-80mg bolus q10min or 20 mg load + 0.5- Ao dissection, CVA, avoid
Labetalol (IV) <5min 3-6h
2mg/min infusion, adjust to goal, max dose 300 mg in ADHF/pulm edema
Nitroprusside 0.25-2µg/kg/min (dose limit to avoid cyanide toxicity), AS/LVSD and HF; avoid in
<1min <2min
(IV) temporarily (<10min) can use up to max 10µg/kg/min ACS/CAD or CVA
Nitroglycerin Start 10-30µg/min, titrate by 10-20µg/min q5-10min; max ACS, flash pulm edema
2-5min 5-10min
(IV) 400 µg/min (if no response by 200 µg/min = non-responder) (FPE)
Nicardipine (IV) Start at 5mg/h;  by 2.5mg/h q5-15min; max 15mg/h 5-10min 15min-4h SAH, CVA, Ao diss, FPE
Clevidipine (IV) Start at 1-2mg/h; most respond to 4-6mg/h, max 21mg/h 2-4min 5-15min SAH, CVA, Ao diss, FPE
Antihypertensive Dosing – Floor
Agent Dosing Onset Duration Indications
IV 5-20mg, followed by 10-80mg q10min prn, then use PO 5-10min 3-6h Ao dissection, CVA;
Labetalol
PO Start 100mg q8-q12h (max: 2400mg/d) 20min 8-12h avoid in ADHF / FPE
5-20mg q15-30min until effect seen, then PO, careful of
IV 10-20min 1-4h
Hydralazine unpredictable response (10-40mg IM if no access) Eclampsia
PO Start 10mg q6h, inc by 10-25mg/dose q2-5d 20-30min ~8h
Captopril (PO) 12.5-25mg q8h (NOT TID) 30-90min 6-8h Scleroderma renal crisis
Initial 2.5-5mg qd. Inc 10mg q2w to max 40mg qd. (Can use
Lisinopril (PO) 1h 24h T2DM, proteinuria, HF
ARB if ACEi intolerance)
Initial 2.5-5mg qd. Inc 2.5mg q7d to max 10mg qd. Requires
Amlodipine (PO) 24-48h 24h No specific indications
few days to take effect
10-30mg TID. May cause pronounced
Nifedipine (PO) 20min 6-8h Post-partum HTN
vasodilation/orthostasis
Initial 12.5mg qd (max: 50mg qd, doses >25 mg a/w
HCTZ (PO) 2h 6-12h CKD1-3a/b
electrolyte derangements)
Isosorbide Initial 5-20mg 2-3 times/d (dose TID not q8h for nitrate
1h ~8h Angina, ESRD, HF
dinitrate (PO) holiday). Mononitrate = long-acting

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Cardiology Peripheral Artery Disease

OVERVIEW (2024 GUIDELINE)
• Definition: arterial stenosis or occlusion causing an imbalance of blood flow relative to muscular metabolism (legs > arms)
• Epidemiology: smoking, DM, HTN, HLD, age (20% prevalence >70y) (Lancet 2013;382:1329)

CLINICAL PRESENTATION AND DIAGNOSIS

• Symptoms: (Circ 2006;113:e463)
o Classic claudication (10-35%) - reproducible exertional pain (buttock, thigh, calf, ankle), relieved by rest (differentiate from
pseudo-claudication from spinal stenosis); atypical leg pain (most common, 40-50%); asymptomatic (20-50%).
o Threatened limb (1-2%): pain at rest (improved w/ hanging feet off bed or walking), ulcers at pressure points, dry gangrene
o Rutherford classification: clinical criteria +/- objective data from treadmill test and ankle BP (JVascSurg;1997;26:517)
• Exam: arterial bruit, peripheral pulses (palpation, Doppler), cap refill, pallor on elevation, ulcers, atrophic changes, hair
• Diagnostics:
o ABI: Doppler US. Ratio of DP/PT (higher value) SBP to brachial SBP.
 Abnormal: ≤0.9 (95% Sn and 100% Sp for detecting arteriogram-positive lesions with ≥50% stenosis). ABI ≥1.40
suggests compressibility usually due to calcifications (e.g., elderly, DM, ESRD)
 If ABI ≥1.40, a toe brachial index can be used for diagnosis
o If ABI abnormal: obtain segmental ABI with pulse volume recordings (PVR) to localize disease
o Exercise testing: if high suspicion for PAD & normal resting ABIs
o CTA (with distal run off), MRA, or angiography: if considering endovascular or surgical revascularization
ABI Interpretation Rutherford Rutherford Clinical Description
>1.40 Noncompressible vessel (not interpretable). Grade Stage
Due to extra-luminal vessel calcification 0 0 Asymptomatic
(Monckeberg) 1 Mild claudication
1.00 - 1.40 Normal I 2 Moderate claudication
0.91 - 0.99 Borderline 3 Severe claudication
0.41 - 0.90 Mild to moderate PAD II 4 Rest Pain
0.00 - 0.40 Severe PAD III 5 Minor tissue loss
6 Major tissue loss
TREATMENT
• Optimize CV risk factors (e.g., HTN, DM, HLD, weight loss), high-intensity
statin, smoking cessation
• Formal exercise program
o CLEVER-RCT: supervised exercise therapy is at least as effective
as stenting (JACC 2015;12:2055)
o ERASE-RCT: supervised exercise therapy + revascularization >
exercise alone (JAMA 2015;314:1936)
• Ischemic ulcers: wound care, may also need revascularization for
appropriate healing depending on ABI
• Anti-platelets: For secondary prevention. If symptomatic, ASA 75-162mg qd
or clopidogrel 75mg qd: MI, CVA, vascular death (NEJM 2017;376:32).If
asymptomatic, consider ASA 81mg. Avoid DAPT (NEJM 2006;354:1706)
unless clinically indicated, usually post-revascularization. Review w/ clinical
decision making algorithm (JACC 2018;71:2450).
• Anti-coagulation: rivaroxaban 2.5mg BID + ASA: major adverse cardiac &
limb events vs ASA alone (Lancet 2018;391:219). Caution as major bleeding,
but no fatal bleeding in pts w/ stable PAD in study Source: SVS
• Cilostazol: Start 100mg BID. PDE3 inhibitor w/ vasodilatory and anti-platelet effects. Adjunct for symptom relief refractory to exercise
therapy/smoking cessation. Use in combination with ASA or anti platelet (Chest 2012; 142:1608). Only AHA/ACC recommended med
to exercise capacity (Circ 2017;135:e686). Contraindicated in HF
• Endovascular repair (angioplasty vs stent) if threatened limb and/or severe symptoms refractory to medical management. Assess
benefit of revascularization vs amputation with SVS WIfI score, above (JVS 2014; 59:P220-234)
A C U T E L I M B I S C H E M I A (BMJ 2000;320:764)
• Sudden decrease in limb perfusion threatening viability. Emergency - consult Vascular Surgery and Vascular Medicine STAT
o Viable: no immediate threat of tissue loss; audible arterial Doppler signal, intact motor/sensory
o Threatened: salvage requires prompt intervention; no audible arterial Doppler signal, motor or sensory deficits
• Etiologies: embolic (e.g., AF, endocarditis) > thrombosis (e.g., atherosclerosis, APLAS, HITT), trauma, connective tissue disease
• Precipitating factors: dehydration, HoTN, abnormal posture (i.e. kneeling), malignancy, hyperviscosity, hypercoagulability
• Presentation: (6Ps) Pain, Poikilothermia, Pallor, Pulselessness, Paresthesia (unable to sense light touch), Paralysis
• Diagnosis: pulse (w/ Doppler) + neuro checks; angiography (CTA w/ run-off or arteriography)
• Treatment: anti-coagulation ± IA lytic; endovascular repair vs thrombectomy; continuous prostaglandin infusion
• After treatment, monitor for reperfusion acidosis, hyper-K, myoglobinemia (ATN), & compartment syndrome

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Cardiology Cardio-Oncology
O V E R V I E W (JACC 2017;70:2536; JACC 2017:70:2552)
Chemotherapy cardiovascular toxicity: includes many different presentations including cardiomyopathy, ischemia, vasospasm (5-FU),
atherosclerosis, HTN, myocarditis (ICI), pericardial disease (chemo or XRT), thromboembolism, QT prolongation, and arrhythmias.

Risk factors: pre-existing CV disease or known cardiovascular risk factors (DM, HLD), extremes of age, female sex
Diagnosis: TTE (compared to baseline), ECG, TnT (↑correlates to adverse cardiac events post-chemo), MRI/PET/biopsy if suspect ICI
myocarditis (Lancet Onc 2018;19:e447)
Prevention: consider BB/ACEi if EF <50%, EF drop >10% or abnl TnT (Am J Clin Onc 2018;41:909), ARB>BB protection against EF
decline in early breast Ca with adjuvant tx (EHJ 2016;37:1671); consider pre-emptive vasodilators/serial ECGs in 5-FU + capecitabine
Screening/monitoring:
• TTE surveillance schedule depends on therapy & baseline cardiac risk; ranges from q3-6mo with long-term risk >10y. Additional
imaging modalities should be used in patients with cardiac risk factors (Circulation 2023;48:1271)
• Monitor weekly BP in first cycle, then q2-3 weeks on therapy
• Certain therapies with well-studied CV risk (i.e., anthracyclines, Trastuzumab, radiation) have guidelines to direct CV monitoring,
however, most do not and proper CV monitoring is an ongoing area of investigation. Pragmatic surveillance strategies have been
proposed and may be useful managing a cancer patient with a new cardiac symptom/condition (JAHA 2020;9:e018403))
Treatment: Optimize preventative CV health (e.g., lipids, DM, blood pressure, etc.) and standard HF and ischemic work up/management
(generally, ASA if plt>10k, DAPT if plt>30k). Cessation of chemotherapy often last resort (multi-disciplinary conversation)

Direct effect of anticancer therapy

Indirect effects of Anthracyclines (e.g. Doxorubicin) Potential effects of
anticancer therapies Antimetabolites (e.g. 5-FU) cancer
Vascular toxicities Alkylating agents (e.g. Cyclophosphamide) Inflammation
Arterial HTN Taxanes (e.g. Paclitaxel) Cachexia
Myocardial ischemia HER2 inhibitors (e.g. Trastuzumab) Cancer by-products
Thromboembolism VEGF inhibitors (e.g. Bevacizumab)
Valvular heart disease Proteasome inhibitors (e.g. Bortezomib)
Protein Kinase inhibitors (e.g. Osimertinib)
(Cardio-Oncology: Management of Toxicities in the
Era of Immunotherapy 2022;1:33)

Cardiac Dysfunction
Heart Failure
IMMUNE CHECKPOINT INHIBITORS AND RADIATION
Examples: Ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab

• ICI Cardiac Toxicity (see ICI): Myocarditis (best studied), also been associated with Takotsubo syndrome, ACS, arrhythmias,
pericardial disease, fulminant myocarditis (RF = combo therapy)
o Dx: troponins, EKG, TTE, cMRI (Sn 50%), endomyocardial bx (lymphohistiocytic inflammatory infiltrate, T cells in HPF)
o Tx: stop ICI; pulse-dose steroids (e.g., 1g IV methylprednisolone x 3-5d) → steroid taper; with cardiology/oncology team can
consider further immunosuppressive agents
• Radiation: Can cause CAD (up to 85%), pericardial disease (6-30%), CM (up to 10%), valvular abnormalities, PVD, arrhythmias,
autonomic dysfunction, can occur 10-15 years later, many RF including dosage, metabolic RF
o Screening: Recommend stress testing within 5-10 years after chest radiation

ADDITIONAL COMMON CARDIOTOXIC THERAPIES

• Anthracyclines (Doxorubicin, idarubicin, epirubicin, daunorubicin): Best characterized cardiotoxicity; HF in dose-dependent manner;
LV dysfunction (5-23%), irreversible damage; should perform baseline cardiac imaging (TTE) prior to tx
• Taxanes (paclitaxel, docetaxel): Conduction abnormalities (bradycardia, heart block); potentiate toxicity of anthracyclines
• Alkylating agents:
o Cyclophosphamide: Cardiomyopathy associated with high-dose protocols (not cumulative dose); hemorrhagic myocarditis
o Ifosfamide: Arrhythmias, ST-T changes, HF (dose-related)
o Cisplatin: SVT, bradycardia, ST-T changes, LBBB, ACS, iCM. Peripheral vascular: Raynaud, HTN, CVAs
• 5-FU: Myocardial infarction, vasospastic angina
• Monoclonal Abs:
o Trastuzumab (HER2): 2.1% risk of ↓LV dysfunction, resolves once stopped; TTE q3months
o Bevacizumab (VEGF): HTN, 3-fold increase in arterial thromboembolic events
• Protein kinase inhibitors:
o Osimertinib, mobocertinib (EGFRi): CMP, QTc prolongation
o Sorafenib, sunitinib (multi TKI): HTN, HF, conduction abnormalities
o Ibrutinib, zanubrutinib (Bruton TKI): SVT, VT, HF, HTN
Proteasome inhibitors (carfilzomib, bortezomib): HF, pHTN, MI
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Cardiology Outpatient CV Health

EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE
Overview: Leading cause of death in developed countries; CVD includes: CAD, CVA, PAD, aortic disease
Risk Factors:
● Non-modifiable: Age (each decade confers 2x ↑ risk from prior), Sex (F with ~20%  risk than M, though risk ↑ 3x in F post-
menopause), FHx premature ASCVD (1st degree relative w/ ASCVD before 55y M or 65y F), elevated lipoprotein(a)
● Modifiable: HTN, HLD (↑ Total, LDL-C, ApoB, Non-HDL, Lp(a), or TG;  HDL), DM, CKD, obesity, smoking (esp. current), exercise,
alcohol, diet, psychosocial stress (chronic + acute), chronic inflammation (CRP best biomarker), mediastinal radiation, HIV

ASPIRIN FOR CVD PREVENTION

Primary prevention:
● 2019 ACC/AHA 1° prevention guidelines: No routine rx; might consider low-dose ASA for 1° prevention in select pts 40-70y at
↑ ASCVD risk & not at ↑ bleeding risk; avoid ASA for 1° prevention in pts >70y (Circ 2019;140:e596)
● Key trials: ASCEND (NEJM 2018;379:1529, pts >40y w/ DM), ARRIVE (Lancet 2018;392:1036, pts w/ multiple non-DM CVD RFs), &
ASPREE (NEJM 2018;379:1519, pts >70y [>65y if Black/Hispanic]): low-dose ASA either w/out sig CV benefit or w/ CV benefit
counterbalanced by ↑ risk of major bleeding
● CAC >100 or >75th percentile per MESA calculator (Circ. 2020;141:1541–1553): Consider low-dose ASA (JAMA Cardiol
2021;6(2):179–187). CAC >1000, very high risk for ASCVD, requires aggressive primary prevention including low dose ASA
(Circulation. 2021;143:1571–1583).
Secondary prevention: In pts w/ stable CVD, low-dose ASA  incidence of adverse CV events and all-cause mortality (AmJMed
2008;121;43)

OUTPATIENT BLOOD PRESSURE SCREENING AND MANAGEMENT

2017 ACC/AHA guidelines (HTN 2018;71:1261):
● Definition: HTN = SBP >129 or DBP >79 independent of kidney function or age; US prevalence 46%
● Method: 2 checks >1w apart, sitting 5min with arm at heart level, cuff bladder 80% length & 40% width of arm circumference
o 24h ambulatory SBPs show greater association w/ all-cause mortality than clinic BPs. Patient log here.
● Categories: Normal: <120/(and)<80; Elevated: 120-129/(and)<80; Stage 1 HTN; 130-139/(or)80-89; Stage 2 HTN: >140/(or)>90
Initial Workup: BMP, Ua, Ualb/Cr ratio, CBC, fasting glucose, TSH, lipids, baseline ECG, 10-yr ASCVD risk, consider TTE (eval for LVH)
2° HTN: targeted approach to workup, consider the following indications (HTN 2018;72:e53):
● Resistant HTN (not controlled on 3+ agents [at least one diuretic]) OR Severe HTN (controlled on 4+ agents [at least one diuretic])
● Acute rise in blood pressure in a previously well-controlled patient, esp. DBP
● Age <30y w/o risk factors (e.g. obesity, FHx)
● HTN with suggestive electrolyte disorders (hypoK, metabolic acidosis)
● Malignant OR Accelerated HTN (severe HTN presenting with clinical or laboratory signs of end-organ damage)

Secondary Causes of HTN

Cause Clinical Clues Work-up
NSAIDs, OTC decongestants, OCPs, anti-
Medications/Drugs
depressants, corticosteroids, sudden d/c of Thorough history
(use or withdrawal)
anti-HTN meds (i.e., clonidine)
OSA Obesity, snoring, smoking Sleep study
Renal disease Elevated Cr, protein/blood on UA See AKI and CKD
Plasma aldo:renin activity; measure together in morning
Hypokalemia, hypernatremia, adrenal
Primary aldosteronism (~8AM), after pt awake for >2h, seated for >5 minutes;
incidentaloma, FHx
high rates of underdiagnosis and undertreatment
>50% rise in Cr after ACE/ARB initiation; If intervention likely to be pursued, begin with Duplex
lateralizing abdominal bruit; severe HTN in s/o Doppler US (Sn 85%, Sp 92%)  if stenosis
Renal artery stenosis
atrophic/asymmetric kidneys, or diffuse (ARAS>50%) or ambiguous results, consider angio
atherosclerosis/FMD
Rare: pheochromocytoma, Cushing’s disease, hyper/hypothyroidism, hyperparathyroidism, aortic coarctation, ADPKD

Lifestyle Counseling (HTN 2018;71:1261)

Intervention Approach SBP impact in pts w/ HTN
Exercise Aerobic: 90–150 min/wk at 65-75% HR reserve 5-8mmHg
Exercise Dynamic resistance (see guidelines for program specs) 4mmHg
Exercise Isometric resistance (see guidelines for program specs) 5mmHg
Weight loss Weight reduction in overweight/obese adults 1mmHg for every 1kg of weight lost
Diet (DASH) ↑veg, fruit, whole grain, lean meat; sweets, red meat 11mmHg
Sodium Consume <1.5g/day 5-6mmHg
Potassium Consume 3.5-5g/day 4-5mmHg
Alcohol Limit consumption to <1/2 standard drink/d in F/M 4mmHg

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Cardiology Outpatient CV Health

Medical Management (HTN 2018;71:1261)
When to Treat Stage II HTN or Stage I if: clinical CVD, DM2, CKD, or ASCVD ≥10%
Target BP <130/80
First-line: thiazides (chlorthalidone may not be > HCTZ, SEs (JAMA IM 2020;180:542)), ACEi/ARB, CCB
Choice of Agent
Other: βB, hydralazine, isosorbide, clonidine, α-blockers (e.g. doxazosin), minoxidil (rare)
DM2: ACEi/ARB (if proteinuria) HF: βB, ACEi/ARB, diuretic, spiro CKD: ACEi/ARB
Compelling Indications
CAD: βB, ACEi/ARB Pregnancy: labetalol, CCB
Follow-up eval for BP response/adherence at monthly intervals until BP controlled
Monitoring
Labs: check BMP/Mg if starting ACEi/ARB or diuretic, 2-4w after initiation, then yearly or w/ ∆dose
SPRINT (NEJM 2015;373:2103): SBP goal <120 vs 135-139 CVD events & all-cause mortality in high-risk
Important Trials Re: BP
pts, but non-orthostatic hypotension, syncope, electrolyte abnormalities, & AKI
goals
ACCORD BP (NEJM 2010;362:1575): in pts w/ DM, no CV mortality benefit a/w SBP goal <120 vs <140

OUTPATIENT CHOLESTEROL SCREENING AND MANAGEMENT

2018-9 ACC/AHA guidelines (Circ 2018;139:e1082, Circ 2019;140e596)
● Screening:
o Check a lipid panel in adults ≥20y to establish baseline LDL-C and estimate ASCVD risk
o Measurement of apoB and Lp(a) may confer nuance to risk estimation; approaches are evolving (JAMA Cardiol
2019;4(12):1287; JAMA 2021;326(4);352)
● Methods:
o Fasting: not routinely recommended; consider if non-fasting TG >400 or pt has FHx premature ASCVD or genetic
hyperlipidemia
o Low LDL-C: If LDL-C <70 and precise measurement warranted, measure direct/modified LDL-C (Friedewald formula less
accurate with decreasing LDL-C)
● Familial hypercholesterolemia (FH): Heterogeneous diagnostic criteria, typically combo of suggestive clinical (premature CVD,
tendon xanthomas), lab (LDL-C ↑↑), genetic (LDLR, APOB, PCSK9), and FHx (strong FHx premature CVD) findings
● Common 2° causes of dyslipidemia: Diet (weight gain, anorexia, alcohol, diet rich in trans/sat fats or refined carbs), drugs (orals
estrogens, glucocorticoids, diuretics, anabolic steroids, amiodarone, tamoxifen, raloxifene), diseases (nephrotic syndrome, chronic
renal failure, biliary obstruction), disordered metabolism (hypothyroid, obesity, pregnancy, poorly-controlled DM)
● See indications for/approaches to rx below; statin therapy is the cornerstone of med rx, should be added to maximally tolerated effect
before reaching for secondary meds
● Lipid monitoring:
o Yearly if pt at goal & compliant
o Assess 4-12w after statin initiation or dose change, repeat q3-12mo as needed
Lifestyle Counseling (Circ 2018;139:e1082,Circ 2019;140e596)
Intervention Approach
Emphasize: veg, fruit, whole grain, legume, healthy protein sources (low-fat dairy/poultry, fish, nuts), non-
Diet tropical veg oils, unsat fats
Limit: sweets, refined carbs, processed/red meats, trans/sat fats, sweetened beverages
Weight control Weight loss in overweight/obese pts; reasonable to track risk with BMI, waist circumference measurement
Target: aerobic, 3-4 sessions/wk, ~ 40min/session, moderate-to-vigorous intensity. At least total/week of
Exercise
150min of moderate-intensity or 75min of vigorous-intensity physical activity. Decrease sedentary behavior
Tobacco Screen for use at every visit and assist with quitting/reduction when possible

Indications for Statin Therapy

ASCVD Risk Estimator PREVENT Score
Established pooled cohort 10yr risk calculator for 1° prevention New 10yr and 30yr risk calculator for 1° prevention
Ages 40-79y Ages 30-79y
Currently in guidelines, likely to be replaced by PREVENT Race free. Includes eGFR/UACR, BMI, A1c, and zip code (proxy for SDH)
Clinical ASCVD, <75y (e.g. CHD, TIA/stroke/CAS, PAD, TAA/AAA) Maximally-tolerated statin to reduce LDL-C by ≥50%
LDL-C ≥190, 20-75y Maximally-tolerated statin to reduce LDL-C by ≥50%
Moderate-intensity statin; consider high-intensity statin for ASCVD risk >20%, multiple ASCVD RFs to reduce
Diabetes (age 40-75)
LDL-C by ≥50%
(10 yr ASCVD) Low risk <5%: lifestyle changes
Borderline risk 5-7.5%: consider mod-intensity statin based on risk-enhancers*
Age 40-75 w/o above
Intermediate risk 7.5-20%: statin to LDL-C ≥30-49%, CAC may help decision
High risk >20%: statin to LDL-C ≥50%
*ASCVD risk enhancers: FHx premature ASCVD, LDL-C ≥160, CKD, premature menopause (age <40), hypertensive disorders or
pregnancy (eg pre-eclampsia), metabolic syndrome, inflammatory dz (RA, HIV, SLE, psoriasis), ethnicity (South Asian), TG ≥175, hs-CRP
≥2, Lp(a) ≥50, apoB ≥130, ABI <0.9
*Coronary artery calcium (CAC) score: 0 favors no statin in intermediate risk in absence of DM, active smoking, or early FHx; 1-99 favors
statin therapy; CAC 100+, initiate statin
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Cardiology Outpatient CV Health

Common Medications
Effect on CV
Medication Mechanism Indication %  in LDL-C Adverse effects
outcomes
Myopathy (prevalent
HMG-CoA 1° & 2°prevention, CV
1st-line therapy for 1° & 20-60% LDL-C in RCTs vs “practice”),
Statins* reductase events (ARR 1.1%,
2°prevention reduction LFTs, memory loss &
inhibitors NNT 91, HOPE-3)
confusion
- Statin-intolerant
intestinal Ezetimibe + Ezetimibe + statin CV
Ezetimibe - LDL-C >70 w/ CVD or Mild LFTs (usually w/
cholesterol statin therapy  events (ARR 2%, NNT
(10mg qd) <50% LDL-C w/o CVD statin)
absorption LDL-C by ~23% 50, IMPROVE-IT)
on max-tolerated statin
Evolocumab + statin
Block High risk pts w/ CVD &
PCSK9 38-72% CV events (ARR
degradation of LDL-C >70 on statin + Uncommon; mainly
inhibitors 1.5%, NNT 67 at 48w,
reduction; ~60%
LDL-R on ezetimibe; approved for injection site reactions
(alirocumab, FOURIER); alirocumab +
in pts on statin
hepatocyte use in familial Cost: 150k/QALY
evolocumab) therapy statin CV events
surface hypercholesterolemia
(ARR 1.6%, ODYSSEY)
O3FAs (e.g. Severe hyperTG, hyper EPA + statin CV
Incorporate into TG ≥30% with Interaction (e.g. warfarin),
Vascepa TG despite statin, CVD events (ARR 4.8%,
phospholipids no ∆ in LDL GI sx
[EPA]) prevention NNT 21, REDUCE-IT)
Note: if patient has concomitant severe hypertriglyceridemia (TG >886 mg/dL), then also start fenofibrate (many formulations)

Statin Potency *Statin Properties:

High-intensity atorvastatin 40-80mg Biggest change in LDL: rosuvastatin > atorvastatin > simvastatin
(≥50% LDL-C) rosuvastatin 20-40mg Safest in CKD: atorvastatin, fluvastatin (no renal dose adj. required)
atorvastatin 10-20mg, rosuvastatin 5- Safest in cirrhosis: pravastatin
Mod-intensity 10mg, simvastatin 20-40mg, pravastatin HIV patients: pitavastatin (REPRIEVE)
(30-49% LDL-C) 40-80mg, lovastatin 40-80mg, Lowest rate of myopathy: pravastatin, fluvastatin
pitavastatin 2-4mg Least DDI: pravastatin, rosuvastatin, fluvastatin (no CYP450 metabol.)
Low-intensity simvastatin 10mg, pravastatin 10-20mg, Lower overall side effects: pravastatin, rosuvastatin (hydrophilic)
(<30% LDL-C) lovastatin 20mg ACC Statin Intolerance Tool: to assess for muscle side effects

MANAGEMENT OF CHRONIC CORONARY DISEASE (CCD)

2023 ACC/AHA guidelines (Circulation. 2023;148:e9–e119)
● Definition: a) prior ACS event or revascularization b) impaired LV systolic function from ischemic cardiomyopathy c) medically
managed stable angina +/- positive stress test d) angina from microvascular disease and coronary vasospasm, or e) ASCVD based
on screening test (eg stress test, cCTA) or clinical judgement
● Evaluation: Yearly evaluation by cardiologist is recommended to assess for worsening of symptoms. Anatomic or ischemic evaluation
in the absence of symptoms is not recommended.
● Medication:
o Lipid Lowering: Goal ≥50% LDL reduction and/or LDL ≤ 70mg/dL (for very high risk clinical ASCVD), see above
▪ No evidence for use of fish oil and omega-3 fatty acids/vitamins in reducing cardiovascular events.
o Anti-platelet: ASA 81mg in all patients. See Adjuncts to Revascularization for post-stent anti-platelet therapies
o Beta-blocker: Long term beta-blocker is indicated among individuals with prior MI <1 year, LVEF ≤40% regardless of prior
MI; in patients with LVEF ≤50%, use of metoprolol succinate, carvedilol or bisoprolol is preferred.
▪ Among CCD individuals with prior MI > 1 year and no history of LVEF≤50%, angina, arrhythmias or uncontrolled
HTN, can consider discontinuation of long-term use (>1 year) of beta-blocker
▪ No known benefit for beta-blockade among individuals with CCD without prior MI
o Anti-Hypertension: Goal BP <130/<80; See Outpatient Blood Pressure Screening and Maintenance above
o Special populations:
▪ Patients with diabetes: SGLT2i or GLP-1 receptor agonist reduces risk of MACE
▪ Patients with EF ≤40%: SGLT2i reduces risk of cardiovascular death and HF hospitalization.
▪ Patients with overweight or obesity (BMI ≥27): GLP-1 receptor agonist, semaglutide over liraglutide
o Anti-anginal: Beta blocker or calcium channel blocker as first line agents for symptom management, followed by long-
acting nitrates, use ranolazine as 3rd line
● Lifestyle modification: See Lifestyle Counseling above

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Cardiology Anti-Arrhythmic Medications

Side effects,
Class Name Mechanism Usage Dosing
Contraindications (CI)
VT: 100mg q5min until total 500mg, wait 10min for
HoTN, PVCs, VT,
Na+ channel blockade; VT; AF, especially distribution. Admin to arrhythmia control, HoTN or
QT, drug-induced lupus (long
Procainamide conduction slowing; in accessory QRS inc. by 50%
term use), agranulocytosis, neg.
(IV) action potential; also bypass tracts WPW: 20mg/min until total 17mg/kg (e.g., ~1h, BP
inotropy.
has Class III action (WPW) q5min); then 2-6mg/min (in urgent situations, up to
CI: CHB, AVB, SLE, TdP
IA 50mg/min may be given to total dose ≤17 mg/kg)
VT: if <50kgload 200mg x1, then 100mg q6h; if
HOCM (efficacy
>50kgload 200mg x1, then 150mg q6h Anticholinergic side effects,
Disopyramide Na+
channel blockade; relates to negative
AF conversion: 200mg q4-6h neg. inotropy, HoTN,
(PO) anticholinergic effects inotropic effect),
AF prevention: 400-750mg, divide q6h (w/ BB/CCB) CI: QTc, HFrEF
VT, AF, Aflutter
HOCM: 200mg q12h, CR form is oral
Na+ channel blockade; Bradycardia, junctional
Load: bolus 1.0-1.5mg/kg. May give additional 0.5-
Lidocaine no effect on VT, VT/VF arrest, arrhythmia, HoTN, angina, AMS,
0.75 mg/kg IV push PRN q5-10min; total ≤3 mg/kg
(IV)* conduction; may polymorphic VT tremor, seizure, dysarthria,
IB Maintenance: 1-4mg/min (30-50mcg/kg/min)
action potential paresthesias, nausea, dizziness
Mexiletine PO analogue of Load: 400mg x1 Tremor, nausea, dizziness, GI.
VT
(PO) lidocaine Maintenance: 200mg q8h CI: cardio shock, 2°/3° AVB
pAFib (“pill in the Ventricular arrhythmia (risk if
Pill in the pocket: 200mg (<70kg) or 300mg (>70kg).
Flecainide pocket”), rarely structural heart dz), neg. inotropy,
Na+ channel blockade Max: qd
(PO)* ventricular dizziness. CI: HFrEF, IHD, QTc,
Sinus rhythm maintenance: 50-150mg bid
IC arrhythmia CrCl<50, liver dz
Pill in the pocket: 450mg(<70kg) or 600mg (>70kg). Ventricular arrhythmia (risk if
Propafenone Na+ channel blockade;
Same as above Max: once/24h. Start BB/CCB prior structural heart dz), GI sx, dizzy.
(PO) Some β1 blockade
Sinus rhythm maintenance: 225-425 bid ER q12h CI: IHD, HFrEF, LVH, QTc
Acute HR/BP
Esmolol β1 antagonist. Load: 0.5-1mg/kg x1min
control in Ao Same as other β-blockers
(IV) t 1/2 = 9min Maintenance: 2-21mg/min IV (25-300mcg/kg/min)
dissection, SVT Atenolol is renally cleared (adjust
Atenolol β1 antagonist; 2x as SVT, ACS, post- if AKI)
25-50mg qd (max: 100mg qd)
II (PO)* potent as metoprolol MI, CAD, HTN, HF
Thyroid storm,
Propranolol IV: 0.5-1mg load1-3mg every several hours Crosses BBB, may cause AMS.
AoD, tremor, EV
(IV, PO)* Non-selective βB ppx, pheo, anxiety PO: 120-320mg/d (based on indication) Less HoTN than β1 antagonists

Nadolol (PO)* Variceal ppx 20-80mg qd (max: 240mg) AMS, HoTN

Pulseless VT/VF: 300mg IV push, may repeat 150
HoTN (IV), bradycardia, QT.
K+ channel blockade, mg IV push every 3-5min as needed
Long t1/2 (58d). Systemic SEs w/
slows repol. WCT:
SVT, VT, long-term use (check baseline
Amiodarone Multiple effects incl - IV: 150mg x1 (repeat q10 min prn)1mg/min x6h
pulseless VT/VF, PFTs, LFTs, TFTs). Do NOT use
(IV/PO) class Ia, II, & IV. (360mg)0.5mg/min x18h (540mg)
(off-label) AFib for TdP, pre-excitation.
Class II (i.e. βB) = - PO: total 8-10g over days (200-400mg, BID-TID)
CI: QTc, SSS, 2°/3° AVB, sx
fastest effect - Maintenance: 100-200mg PO QD-BID
bradycardia, cardiogenic shock
AF: PO 8-10g over 2-4w
III IV: 75mg q12h, may dose by 37.5mg q3d (max:
Nonselective QT, typical effects of β-
Sotalol 300mg/d)
β1/β2 antagonist, K+ AFib, VT blockade; CI: CrCl <40, LVH,
(IV, PO)* PO: 80mg q12h, may dose by 40mg q3d (max:
channel blockade HFrEF, QTc, hypoK
320mg/d). Adjust dosing interval in renal impairment
Ibutilide >60kg: 1mg over 10min; can repeat x1 in 10min;
AFib, AFlutter QT, TdP, HA
(IV) K+ channel blockade, <60kg: same except dose is 0.01mg/kg
prolongs action QT; CI: thiazide, dolutegravir,
Dofetilide AFib, AFlutter, Initial dose 500mcg bid max
potential trimethoprim, verapamil, hypoK,
(PO)* SVT Decrease dose by 50% if CrCl<60 or QT prolonged
hypoMg, CrCl<20
Diltiazem IV: 0.25mg/kg (≤25mg) q15min prn; gtt 5-15mg/h
CCBslows AV node ↓ inotropy
(IV, PO) AFib, AFlutter, PO: 120-320mg ER qd or ≤480mg/d IR q6h
conduction & phase II CI: SSS, bradycardia, 2°/3°AVB,
IV SVT, MAT, angina, IV infusion: 5-10mg, repeat q15-30min PRN (≤20-
Verapamil of cardiac VT, AF + WPW, HoTN, pulm
HTN 30mg); gtt 5-20mg/h if needed
(IV, PO) action potential edema, HFrEF (<40%), ADHF
PO : 120-360mg ER qd or ≤480mg/d IR q8h
Na/K ATPase IV (initial): total dose 8-12mcg/kg IBW (≤0.75-1.5mg)
Digoxin tox (>2ng/mL usually),
inhibitionCa influx. 3 divided doses, 50% over 5min as 1st, then 25% for
Digoxin AFib, Aflutter, N/V, visual disturbance, atrial
AV node conduction 2nd & 3rd, q6h. Follow with maintenance. Goal: 0.5-
(IV, PO)* HFrEF, SVT tachycardia with AV block, PVCs,
suppression, vagal 0.8 (HF), <1.2 (AF)
VT, VF. CI: VF
Misc. tone, +inotrope Oral (maintenance): 0.125-0.25mg qd
Treating SVT IV (admin over 1-2sec, PIV): 6mg12mg after 1- Arrhythmia, angina, HA, flushing,
AV node conduction
Adenosine Differentiating re- 2min if ineffective, repeat x1 if needed, flush GI distress, dyspnea.
slowing, coronary
(IV) entry SVT from a- immediately. Half dose if patient using central line, or CI: 2°/3° AVB, SSS, sx brady,
vasodilation
fib/flutter/tach receiving carbamazepine or dipyridamole. lung dz, asthma, s/p OHT
*Renal dosing required

David Iskhakov
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Cardiology Telemetry and Physical Exam

BRIEF PHYSICAL EXAM TIPS (MCGEE 2021)
Pathophysiology Tips for measurement Sens/Spec & Diagnosis
Likelihood Ratios
JVD Jugular vein is a central vein Angle changes measurement (see below); For measured CVP Elevated in HF, tension
that is contiguous with the veins have respiratory variation & rise w/ >8cm: Sn 47-92%, Sp PTX, tamponade, SVC
right atrium and act as a proxy hepatojugular reflex; nonpalpable. Add 5cm to 83-96%, +LR 8.9, -LR syndrome, tricuspid
for right atrial pressure approximate RAP; Reported in cm H2O 0.3. Preop JVD +LR stenosis and large CV
11.3 for postop waves in TR
edema/+LR 9.4 for
postop MI if no addl
mgmt
S3 "Sloshing" of blood as it hits Heard best with bell at apex in left lateral For EF <30%: Sn 68- Associated with HF; can
compliant ventricular wall. decubitus 78%, Sp 80-88%; +LR be physiological in
Occurs after S2; Early to 4.1, -LR 0.3 younger patients
middle diastolic sound
S4 Flow of blood from atrial kick Heard best with bell at apex in L lat decubitus. For elevated L heart A/w LVH, AMI,
into stiff ventricular wall; late Longer interval b/w S4/S1 → poorer filling pressure: Sn 35- cardiomyopathy; can be
diastolic heart sound, right prognosis 71%, Sp 50-70% normal in older adults;
before S1 Cannot have in AF (no
atrial kick)
Peripheral Occurs when capillary +1 = 2mm depression, quick rebound For elevated L heart Volume overload
edema hydrostatic pressure +2 = 3-4 mm depression, quick rebound filling pressure: Sn
overwhelms ability of +3 = 5-6 mm depression, rebound <1min 10% Sp 93-96%,
lymphatics to drain fluid from +4 = 8mm+ of depression, rebound 2-3min nonsignificant LR
the instertitum; the lymphatic Measure in dependent area (i.e. sacrum for
valves fail and the lymphatic bedbound pts) and assess how far up extends
vessels dilate.
RV heave An indiciation of RV (or, Felt best over left parasternal region; if heel of Limited; for pHTN, Sn RV enlargement (incl
rarely, LA) enlargement hand rises with systole, there is heave 42%/Sp84%, nonsig pHTN, RV volume
LR overload), or MR, rarely
LA enlargement
AS Turbulent flow across stenotic Loudest R 2nd intercostal space, radiates to R For mild or worse AS: Aortic stenosis; DDx
murmur AV; as severity increases & carotid 1st as severity increases Sn 79-90%, Sp 85- increased Ao flow without
ejection takes longer, murmur 87%, +LR 10.5, -LR obstruction (anemia,
becomes later & diminishes 0.1. For severe AS Sn fever, pregnancy,
S2 83-98%, Sp 71-76%, nonobstructing
+LR 3.5, -LR 0.1 calcification)
JVP MEASUREMENT PEARLS
EJV is a good proxy for IJV in most patients; good reliability
for discriminating high from low CVP (Arch Intern Med
2006;166:2132, Chest 2011;139:95)
Distance from sternal angle to right atrium is variable
between patients and across positions (JGIM 2002;17:852
median 5 cm at 0°, 8 cm at 30°, 10 cm at 60°); interpret JVP
in clinical context and trend while intervening on volume
status (McGee 2021)
Sonographic JVP when bedside JVP difficult to visualize;
correlates well with right atrial pressure (Ann Intern Med 2022;175:344, JASE 2023;36:278). Lay patient 30° - 45°, scan with vascular
probe in short-axis just above the clavicle to find IJV and CA and slide cranially to find the IJV meniscus, then usual JVP calculation.
Alternatively, if the IJV is distended (> carotid) with minimal pulsation just above the clavicle at 45°, can call JVD (JASE 2023;36:278).
Easy rules: if IJ > carotid in short axis at 90°, rules in elevated RAP. If IJ < carotid in short axis at 30°, rules out elevated RAP
CARDIAC TELEMETRY: RUNNING THE “TELE”
Step 1: Locate the name of the desired patient on the telemetry monitor and select their telemetry strip.
Step 2: Once on patient’s telemetry strip, select “Patient Data.”
Step 3: Click “Event Review” which will show you any abnormal events the patient had since being placed on telemetry. From this list,
click the desired episode of choice.
Step 4: After clicking on the desired event, you will have multiple options to choose from:
o Events: events sorted in reverse chronological order (e.g. runs of NSVT, bradycardia)
o FD Strip: telemetry strip for a specific moment in time
o FD Page: global view useful in identifying abrupt changes that can be zoomed in on using the FD Strip view
o Graphic Trends: graphic view of HR trends over time
o Calipers: interactive calipers used to calculate intervals on telemetry strip

While a patient is on telemetry, review indication daily and discontinue if not using monitoring for clinical decision-making (refer to AHA
Guidelines for appropriate use of hospital telemetry)

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Pulmonary & Critical Care Respiratory Distress

Respiratory distress is a constellation of symptoms that portends impending DYSPNEA DDX
respiratory collapse. It is different from dyspnea, which is the subjective - CV: MI, HF, VHD, arrhythmia, tamponade, PE,
sensation of shortness of breath. Key symptoms of respiratory distress are: PHT
• Tachypnea (go look at the patient and measure yourself. RR ≥20) - AIRWAYS: asthma, COPD, mucus plugging,
• Cyanosis (typically SpO2 <80%) angioedema, anaphylaxis, FOB, vocal cord
• ↑WOB (nose flaring, retractions, grunting, tripod-ing, diaphoresis) dysfxn
• Obstruction (wheezing, stridor) - ALVEOLI: edema, PNA, hemorrhage
- PLEURAL: large effusion, PTX
APPROACH - CNS: CVA, intox (CO, ASA, BZD), met.
1) Confirm code status acidosis (sepsis, DKA, etc), psych/anxiety
2) Low threshold to call Rapid Response for assistance - OTHER: anemia, abd girth, ALS/GBS/MG,
3) Assess airway, breathing, circulation & confirm access Rapid Response x6-3333 for Senior On,
o Place on supplemental O2: NRB to start, can always wean later nursing supervisor, RT, pharmacy
o Red flags (RICU STAT): Inability to protect airway due to AMS, pooling DECISION TO INTUBATE:
secretions, hemoptysis, life-threatening hypoxemia despite RICU: x6-3333, ask for “STAT RICU”
supplemental O2 (SpO2 <80%, PaO2 <55mmHg), severe hypercapnia RICU Communication Guide: have following
despite BiPAP, tiring out (↑WOB, progressive hypercapnia), RR >35 information ready prior to intubation
o Temporize: suction, head-tilt chin lift (preferred if no concern for C- - Code status & urgency/acuity of decline
spine injury) vs jaw-thrust to open airway, bag-mask ventilation - Hemodynamics: LV, RV, valves, volume
(enough volume to see chest rise, no more than 8-10cc/kg or 5-6cc/kg status, access
during CPR; 8-10 breaths/min). If use of bag-mask will not be brief & pt - Aspiration risk: NPO, last meal, risk factors
unresponsive, consider OP airway prior to intubation - Difficult airway (from prior intubation notes)
4) Initial workup: - Allergies
o CXR (order STAT, must call x6-3050): look for new infiltrate Have ready: sedation (propofol, fentanyl,
(aspiration, PNA), pulmonary edema, lobar collapse (mucus plug), midaz), pressor (Neo >> Levo), IVF w/ push
PTX. For read, call x4-1533. If nl, consider ischemia, PE, acidosis line; RICU brings paralytic
o ABG: worrisome if PaCO2 >45mmHg (poor ventilation), PaO2 MICU/CCU: Resource RN will call for RICU;
<60mmHg (poor oxygenation), pH <7.25. MD or RT can obtain. make sure attending/OI, fellow, RT, RN aware
o Labs: VBG (& ABG if possible, correlate to VBG. Widened A-a
gradient >20 = abnormal gas exchange vs nl <20 = global INTUBATION IS NOT AN ACT OF
hypoventilation), hs-Trop, NT-proBNP, lactate, BMP, CBC WEAKNESS Do not delay intubation in
o Additional studies based on clinical suspicion: CT-PE (if stable patients with impending respiratory failure
to travel), TTE (acute valvular dz, RV strain), US (PTX/effusion)

TREATMENT
• Supplemental oxygen therapy (see Oxygen Delivery Therapies for more detail):
o NC: for every liter increase in O2, approx. FiO2 0.03/L (max: 6L = 0.40 FiO2, dependent on Ve/entrainment)
o NRB: can give FiO2 ~0.90, but in tachypneic patient, FiO2 ~0.60 (due to entrainment of room air)
o HFNC: FiO2 0.6 to 1.0 at 10-60 L/min (humidified air); 90d mortality vs NIPPV for pts with hypoxemic respiratory failure
not due to cardiogenic pulmonary edema or obstructive lung disease (NEJM 2015;372:2185)
• NIPPV (BiPAP for COPD; CPAP for CHF): RR >25-30, accessory muscle use, pH <7.35, PaCO2 >45mmHg
• Intubation: see red flags above

DISEASE SPECIFIC TREATMENT

• CHF: CPAP, IV diuresis, nitrates (paste or drip, if BP room)
• Asthma: nebulizers (albuterol 2.5-5mg q20min or stacked DuoNeb), steroids (IV methylpred 125mg q6h), Mg (2g/20 min). Trial
BiPAP ; however, if RR remains >25, VBG w/ nl or rising CO2, AMS, or bradycardia, discuss intubation. Decreasing wheeze
can portend respiratory collapse (sign of worsening air movement/increased bronchoconstriction)
• COPD: BiPAP, stacked DuoNebs, steroids (IV methylpred 60-125mg); abx if 2/3: sputum volume, purulence, dyspnea
• Hemoptysis (massive): place pt in lateral decub, bleeding lung side down; volume resuscitate, reverse coagulopathies, call IP
• Mucus plugging: airway suctioning, percussion/chest PT, guaifenesin, place pt in lateral decubitus, good lung side down
• PE (see VTE Treatment); if high suspicion and no contraindication, start empiric AC (LMWH therapeutic faster vs UFH gtt).
Consult PERT x4-7378
• PTX: if unstable, bedside needle thoracostomy (STAT page Thoracic Surgery, 14G angiocath, 5th ICS at mid-axillary line or
2nd ICS at mid-clavicular line); then chest tube (Thoracic Surgery or IP)
• Pleural effusion: thoracentesis (see Thoracentesis; must be performed by IP or supervised by pulm attending)
• Opioid overdose: Narcan 0.4-2mg IV/IM q2min, observe response, uptitrate to adequate RR. Given short half-life, consider gtt
if responsive to bolus at 2/3 of bolus dose per hour (ex: 0.2–0.6 mg/h)
• Anaphylaxis: MGH Pathway Initial: epi (1:1000) 0.3mL = 0.3mg IM, q5-15min PRN. Other agents may follow:
diphenhydramine 25-50mg IV, nebulized albuterol, methylprednisolone 1-2mg/kg IV, If persistent may require epi gtt.
• ACS (see ACS): ASA 325mg, atorvastatin 80mg, nitrates (SL/nitropaste gtt), heparin, consult Cardiology
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Pulmonary & Critical Care Hypoxemia & Hypercapnia

Respiratory Failure: inability to oxygenate (deliver O2) or ventilate (blow off CO2). Can be hypoxemic (PaO2 <60mmHg),
hypercapnic (PaCO2 >45mmHg), or both. P:F Ratio (P=PaO2/F=FiO2) quick surrogate for A-a gradient (consider ARDS if
P:F <300; see ARDS). A quick algorithm can be used to determine the etiology of hypoxemia based upon ABG results.
Hypoxemia
O2 sat 90% ~ PaO2 = 60
Pulmonary Physiology
Normal
Dead space Shunt
Elevated A-a Gradient?
Normal = Age/4 + 4 VA/Q > 1→ ↑CO2 VA/Q < 1→ ↓O2
Alveolar (A) = FiO2 * (760-47) – PaCO2/0.8
arterial (a) = PaO2

No Yes

PaCO2 > 45 or ↑ from baseline Corrects with 100% O2?

No Yes No Yes
↑ ventilation ↑ perfusion
High Altitude Hypoventilation R to L Shunt V/Q Mismatch
↓FiO2 Diffusion Limitation
↓ perfusion ↓ ventilation
Cardiac,
Vascular,
Alveolar filling or
Note: continuum between these extremes – in
collapse between is V (ventilation)/Q (perfusion) mismatch

**Pulse oximetry may be inaccurate in dark skin tones, delaying detection of hypoxemia. Consider ABG (JAMA 2022;182(7))
HYPOXEMIC RESPIRATORY FAILURE
• Hypoventilation & low FiO2: decreased O2 delivery to lungs
• V/Q mismatch: imbalance in delivery of oxygenated air & blood flow;
note:↑pulmonary vasoconstriction can ↓hypoxemia by ↓Q to poorly
ventilated regions, ↑V/Q matching (ratio closer to 1)
1. FOCAL alveolar infiltrates: pus (PNA), edema, hemorrhage (DAH),
cells (cancer), aspiration
2. Airway: asthma, COPD, bronchiectasis
3. Vascular: pHTN, PE
• Shunt: flow of blood through lung without encountering oxygenated
air, “perfusion without ventilation” (severe V/Q mismatch). Will not
improve with supplemental oxygen (refractory hypoxemia)
1. DIFFUSE alveolar infiltrates: above + ARDS
2. Alveolar collapse: PTX, atelectasis, mucus plug
3. Intra-cardiac/pulm shunts: PFO/ASD/VSD (↑PEEP worsens this by
↑west zones 1&2 = ↑RV afterload), AVM (e.g., hepatopulm.)
• Impaired diffusion (DLCO): hypoxemia worse w/ exertion
ILD (correlates with severity on CT), pHTN, advanced COPD
(JAP 1964;19:713)
HYPERCAPNIC RESPIRATORY FAILURE
• “Won’t breathe” (RR): sedatives, obesity hypoventilation, brainstem stroke/tumor/infection, central sleep apnea,
compensation for metabolic alkalosis (chemoreceptors), hypothyroidism (myxedema coma)
• “Can’t breathe” (VA):
1. Dead space (airspace not participating in gas exchange; “V without Q”)
 Dead space = anatomic (~150cc upper airway air without perfusion)
+ alveolar AKA West Zone 1 (~0 normally; in disease, capillaries get ACID-BASE INTERPRETATION
destroyed or compressed VD) Hypercapnia Resp acidosis (pCO2)
 Parenchyma: emphysema, ILD/fibrosis, HF, PNA, ARDS • Acute: HCO3  by 1 (per pCO2  10)
 Airway: asthma/COPD, CF, bronchiectasis, OSA, tumor, high PEEP • Chronic: HCO3  by 3-4 (per pCO2  10)
 Vascular: severe PE -> wasted V due to blocked Q; most apparent if Hypocapnia Resp alkalosis (pCO2)
unable to augment ventilation eg in ALS (more often see pCO2 • Acute: HCO3  by 2 (per pCO2  10)
secondary to hyperventilation) • Chronic: HCO3  by 5 (per pCO2  10)
2. Chest wall/pleural constraints lung volume: effusion/fibrosis, obesity,
kyphosis/scoliosis, abd distension, PTX
3. Neuromuscular (Neurol Clin 2012;30:161): trend at bedside with single breath test (non-intubated pts), negative
inspiratory force (NIF) (intubated pts). Consider EMG. Ddx: neuropathy (C-spine/phrenic nerve, GBS, ALS, polio),
NMJ disorder (MG, botulism), myopathy (polymyositis/dermatomyositis, hypophosphatemia), critical illness
• CO2 production (VCO2): WOB, fever, seizure, sepsis, steroids, overfeeding, thyrotoxicosis

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Pulmonary & Critical Care Non-Invasive Oxygenation/Ventilation

CONVENTIONAL OXYGEN DELIVERY DEVICES
Recommendations for Supplemental Oxygen Therapy
• Target SpO2 91-96%: Recent trials of O2 targets found no benefit to higher/lower targets in critical illness (ARJCCM 2021, PILOT)
• Lower target (SpO2 88-92%): At risk for hypercapnic respiratory failure (COPD, OHS, OSA, decreased central respiratory drive,
neuromuscular respiratory disease)
• Higher Target (~SpO2 ~100%): CO poisoning, cluster headaches, sickle cell crisis, pneumothorax
Flow
Mask Type FiO2 (%) Notes Aerosol?
(LPM)
FiO2 by 0.04 per L
Nasal Cannula 1-6 24 - 40 N
Allows patient to eat/speak. Consider humidification if >4LPM
Oxymizer 1 - 15 24 - 45 20mL reservoir allows for higher FiO2 compared to NC N
Simple
6 - 10 30 - 60 Flow rates < 6LPM lead to re-breathing of CO2 N
Facemask
Face Tent Less claustrophobic, FiO2 variable (lots of leakage). Use if stable O2 needs
5 - 10 24 - 50 Y, if humidified
(Shovel mask) Offers humidification without a mask
Consider first for acute hypoxemia (easily accessible)
Non-
10 - 15 60 - 100 FiO2 with tachypnea and Vt due to entrainment N
Rebreather
Titrate flow rate to avoid reservoir bag collapse (<1/3) on inspiration
Color-coded adapters determine flow and FiO2 independent of ventilatory
Var. Y, if >15 LPM or
Venturi 24 - 50 demand. Useful for set SpO2 goals (e.g., COPD)
color humidified
NOT for acute respiratory distress
Racial disparities in pulse oximeter measurement: accuracy in Black patients w occult hypoxemia (NEJM 2020, Annals of ATS 2022)

HIGH FLOW NASAL CANNULA (HFNC) & NONINVASIVE POSITIVE PRESSURE VENTILATION (NIPPV)
NEJM 2022;387:1688-98
HFNC NIPPV (CPAP + BiPAP)
Parameters Flow: 10-60 LPM (up to 80 at some institutions) CPAP: constant level of pos. pressure; targets oxygenation
FiO2 (%): 21-100 BLPAP (or BiPAP™): provides positive inspiratory
~0.7-4.2cm H2O of PEEP w/ mouth closed (~0.7cm H2O/ pressure (IPAP) above PEEP with each pt-triggered breath;
10LPM) targets ventilation and oxygenation
Physiologic Effects Oxygenation: delivery of O2, some PEEP Oxygenation: atelectasis, upper airway obstruction,
Ventilation: ventilation (dead space during expiration) WOB (& O2 consumption)
Other: Humidification mucociliary clearance of secretions Ventilation: tidal volume and minute ventilation (via IPAP)
Other: venous return (LV & RV preload), LV afterload
Clinical Scenarios
Acute COPD Strong indication for BiPAP (ERS/ATS: ERJ 2017;50)
exacerbation w BiPAP: off-load respiratory muscles, counter-act dynamic hyperinflation, ventilation  mortality, intubation, &  LOS
resp. acidosis (Cochrane Rev 2017). Asthma can be treated similarly but there is less evidence to support.
Acute cardiogenic NIPPV (BiPAP / CPAP) intubation, in-hospital mortality by  WOB, FRC, LV / RV preload, LV afterload (NEJM
pulmonary edema 2008;359:142; Cochrane Rev 2013)
Acute hypoxemic Mixed evidence for NON-hypercapnic resp. failure NIPPV may mortality & intubation (JAMA 2020;324:57).
respiratory failure May intubation, but no Δ in mortality or LOS vs standard Consider if also significant hypercapnia eg OHS,
(AHRF) O2 tx (Cochrane 2020). Consider 1st if ILD, ARDS physio. neuromuscular failure (e.g. ALS, MG).
May be non-inf to BIPAP in PNA. Can be used as rescue in Caveats: (AJRCCM 2017;195:67-77)
asthma or in pts that can’t tolerate bipap to help w/ dead • P:F < 150:  death vs. up-front intubation
space wash out along w/ ongoing eval. for intub. • TV > 9-9.5 cc/kg IDW: death, intubation
Post-extubation Extub. to NIPPV or HFNC  reintub. and post-extub. resp. failure in risk pts: COPD, obesity (JAMA 2016;316:1565)
Contraindications to NIPPV:
• Risk of delay: emergent indication for intubation, acute life-threatening non-respiratory organ failure
• Risk of aspiration (d/t gastric insufflation): cannot clear secretions, AMS if pt cannot remove mask (exception: AMS due to hypercapnia)
• Risk of injury: PTX (can induce tension physiology), recent esophageal anastomosis or tear, cannot tolerate preload from venous return,
recent facial trauma/surgery
Monitoring for and Preventing Failure
• Risk of failure varies based on cause (15-20% aeCOPD vs 40-60% AHRF) and with severity of respiratory failure
• ROX index: tool for prediction of HFNC failure & monitoring for need for intubation in pts with pneumonia (AJRCCM 2019;199:1468-76)
• HACOR score: tool for prediction of NIPPV failure & need for intubation (ICU Med 2017;43:192-9)
• Sedation: IV precedex, haldol, and zyprexa can be considered to help pts tolerate NIPPV w/o suppressing resp drive (see Sedation)

BiPAP/HFNC on the floor: huddle with nursing and RT (also notify Sr On). Trial BiPAP or HFNC for 2-3 hours and assess
response; consider ABG/VBG to assess oxygenation/ventilation. If no improvement, discuss escalation of care to ICU
REMEMBER: BiPAP/HFNC MUST NOT DELAY AN INDICATED INTUBATION!

Kimberly DeBruler
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Pulmonary & Critical Care Interpretation of Chest Imaging

CHEST X-RAY
Systematic approach to CXR (ABCDEF approach):
1. (A)ssess technical quality and (A)irways:
• Rotation: ensure spinous process bisect btwn medial end of clavicles
• Lung volumes: adequate inspiratory effort is 9-10 posterior ribs
• Penetration: good when vertebral bodies visible behind cardiac silhouette
• Airways: look for narrowing, deviation, foreign bodies. ITP pushes
trachea away (PTX). ITP pulls trachea towards (atelectasis/plugging).
• Always compare previous studies.
2. (B)ones/soft tissue: subcutaneous air, rib fractures, cervical ribs
3. (C)ardiac Silhouette (mediastinum/hilum): AP films  cardiac silhouette. CT
ratio=max cardiac width/max thoracic width, >50% suggests cardiomegaly
(only PA films). Widened mediastinum generally >8cm (watch out for rotation).
4. (D)iaphragm (gastric bubble): left hemidiaphragm usually lower than right.
Flattening of diaphragm sensitive for emphysema.
5. (E)ffusions: blunting of CP angle. Small effusions seen 1st on PA lateral.
Fluid not seen on upright chest until >250ml.  sensitivity when semi
recumbent or supine. Can assess free flowing vs. loculated effusions on lateral decubitus view (free flowing will track equality on horizontal
plane vs. loculated will not).
6. (F)ields (lung fields) & (F)oreign bodies (lines/drains): Look for focal vs. diffuse processes PTX, PNA, pulm edema. Look for silhouette
sign (loss of the normal visible boarder of an intrathoracic structure) that indicates pulmonary density. Look for lines/tubes (see
Interpretation of Common Studies). ETT best 3-5cm from carina, adjust if not.
CT CHEST
• To characterize abnormal CXR w/ cross-section or w/ suspicion for
pathology despite unrevealing CXR
• HRCT (thin-section CT, <2mm): for diagnosing diffuse lung path. Must
be non-con. Includes expiratory, inspiratory, prone and supine images.
Approach to interpretation:
• Review scout imaging: gives anatomic overview.
• Review lines/tubes, extra-thoracic abnormalities.
• Mediastinum/Heart/Vessels: soft tissue window: LV>RV normally.
Diameter of main PA should be < ascending aorta (PAd >/= 29 mm: PPV
97% for pHTN, Pulm HTN radiology). Cor calcium visible on non-con.
• Airways: review in soft tissue and lung windows. Inspiratory HRCT=
round trachea; Expiratory HRCT= “D-shaped” trachea.
Common Findings Definition Associated Etiologies
Consolidations Complete filling of alveoli, dense  attenuation obscuring underlying lung PNA > Malignancy
architecture +/- air bronchograms
GGO’s Partial filling of alveoli +/- interstitium, appears as hazy  lung attenuation Infxn, edema, blood, fibrosis, malig
(light gray) that does NOT obscure underlying architecture
Tree-in-Bud Branching linear opacities & nodules that represent dz’d lobular bronchioles Infxn (incl. tb), CTD, ABPA, carc.
(AJR 2009;193:472) or bronchiolitis & filling with fluid, pus, mucus, or pulmonary tumoral emboli Endarteritis, CF
Emphysema Airspace enlargement > 1-2 cm in diameter. “Bleb”= similar, but < 1-2 cm COPD, congenital, spont
Mosaic Attenuation Patchy low and high atten. areas due to air trapping, decreased perfusion, HP, OLD, CTEPH, Infxn,
GGOs. Air trapping identified as worsening with expiratory films. Edema/hemorrhage
Honeycombing Clustering of cystic airspace disease. Microcystic <4mm, macrocystic >4mm ILD: NSIP <4mm; IPF>4mm
Subpleural Retic Linear opacification of the inter/intralobar septae around 1 cm from pleura. UIP>NSIP, NL w/ aging
Atelectasis, Effusion Atelectasis enhances w/ con, resolves proned. Effusion more homogenous
Consolidations GGOs Tree-in-bud opacities Centrilobular Nodules Emphysema Atelectasis & Eff.

Mosaic Attenuation Honeycombing Supleural Reticulation ILS Thickening Bronchiectasis

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Pulmonary & Critical Care PFTs & Asthma

PULMONARY FUNCTION TESTING (PFTS)

Table adapted from Up To Date

A S T H M A (GINA 2023, NAEPP 2020)

Definition: heterogeneous condition with resp sx (wheeze, SOB, chest tightness, cough) and variable expiratory airflow limitation
Symptoms Resp sx (wheeze, SOB, cough, chest tightness) that vary over time & intensity, worse @ night/early AM
Triggers Exercise, cold air, allergens, irritants (smoke, perfume), viral respiratory infections, drugs (ASA, NSAIDS, β-blockers)
Obstructive (FEV1/FVC < LLN or 0.7), reverses w/ bronchodilator (↑0.12 or >200mL), worsens w/ methacholine (can be nl
Spirometry
before provocation, FEV1 ↓ 0.2)
Endotypes T2-high (atopic triad, ↑Th-2/eosinophil response; steroid-sensitive), T2-low (poorly understood, often steroid-refractory)
New-onset adult cases ddx: systemic disease (ABPA, EGPA, systemic mastocytosis), occupational asthma (10-25%; NEJM 2014;370:640),
ASA-exacerbated resp. disease (7%, esp. if nasal polyps; J Allergy Clin Immunol 2015;135:676)
OUTPATIENT CARE
• Controller + reliever: stepwise based on severity (below); step up if not controlled; step down if well controlled 2-3mo
o Note: GINA guidelines rec ICS-containing controller; no longer rec. tx w/ SABA a/w ↑allergic responses & airway inflammation,
↓response, & overuse a/w ↑severe exacerbations, though NAEPP still recs SABA PRN
o May be some phenotypes w/ low eos. inflamm. (<2% in sputum) in whom ICS ↓effective (NEJM 2019;380:2009)
• Non-pharm interventions: smoking cessation, regular physical activity, vaccines, breathing exercises, weight loss if obese
NEJM 2019;238:2020; NEJM 2018;378:1865; NEJM 2018;378:1877; AJRCCM 2005;171:129; Chest 2006;129:246; Lancet 2011;377:650
Mild intermittent Mild persistent Moderate persistent Severe persistent Severe
Adapted from GINA 2023
STEP 1 STEP 2 STEP 3 STEP 4 STEP 5
Symptom frequency Infrequent 2-7d/week Most days All day All day
Nighttime awakenings <2/month 3-4n/month >1/week Nightly Nightly
Exacerbations 0-1/year >2/year >2/year >2/year >2/year
Baseline FEV1 Normal Normal 60-80% predicted <60% <60%

Med dose ICS-formoterol

and LAMA
Controller
Med dose ICS- Consider: phenotypic
(Preferred) Low dose ICS- formoterol assessment and biologics*
formoterol
None
None
Low-dose ICS whenever Same as above, can
Controller alternative Low dose ICS Low dose ICS-LABA** Med/high dose ICS-LABA
using PRN SABA consider LTRA, azithro
Reliever
PRN low dose ICS-formoterol
(Preferred)
Reliever alternative PRN SABA or ICS-SABA

*Biologics: anti-IL4R-alpha, anti-IgE, anti-IL5, anti-TSLP. **LABA w/o ICS ↑ rates of death (CHEST 2006;129:15; NEJM 2010;362:1169).
ASTHMA EXACERBATIONS
OUTPATIENT: short course pred. 40-50mg x5-7d + controller/reliever regimen, consider 4x controller ICS if mild (NEJM 2018;278:902)
INPATIENT: assess severity of exacerbation (VS, mental status, SpO2, WOB, PEF < 50% severe), consider VBG/ABG, CXR
Severe: ↑resp drive→↑RR→↓pCO2, nl/↓pH suggest resp. failure. If sig hypoxemia, consider resp. failure vs PTX, PNA, PE, plug, etc.
Floor Patient ICU Patient (Thorax 2003;58:81)
- Bronchodilators: albuterol (2.5-5g) ± ipratropium (0.5-1.5mg) q20m x3 - Bronchodilators: albuterol + ipratropium, Methylpred 125mg IV q6h
o DuoNebs in ED a/w admit (Cochrane Rev 2017) - NIV: BIPAP -> BIPAP w/ sedation -> HFNC
o SABA mono-tx unless severe/worsening (GINA 2023, NAEPP 2020) - Rescue therapies: Mg IV 2g, continuous albuterol nebs (CAB). Less
- Steroids: pred 40-60mg total x5-7d (Cochrane Rev 2016) data: IV epi, ketamine, inhaled anesthetic, Heliox. ECMO=last resort
- O2 >92% (93-95% in severe; >95% increases pCO2; Thorax 2011;66:937) - Mechanical ventilation: large ETT (8+), ↑insp flow rate (80-100L/min),
- If impending respiratory failure: stacked DuoNebs (x3/h), methylpred IV ↓VT (6-8cc/kg), ↓RR (10-14), ↓PEEP, paralysis; Goal: max exp. phase,
60-125mg q6h, Mg IV 2g/20min, transfer to ICU minimize hyperinflation, permissive hypercapnia

A S T H M A / C O P D O V E R L A P ( A C O ) (GINA 2023;163; AJRCCM 2017;196:375; NEJM 2015;373:1241)

• Some patients have persistent airflow limitation together with clinical features c/w both asthma & COPD
• ICS-containing treatment is essential; Also need LABA and/or LAMA. Can escalate to triple therapy, biologics

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Pulmonary & Critical Care COPD

DEFINITION: persistent respiratory symptoms (dyspnea, cough, sputum production, recurrent wheezing, exacerbations) d/t abnormalities of airways
(bronchitis, bronchiolitis) and/or alveoli (emphysema) that lead to persistent airflow obstruction (GOLD 2024)
D I A G N O S I S A N D S T A G I N G (GOLD 2024: AJRCCM 2017;195:557)
1. Diagnosis: respiratory sx + fixed obstruction w/FEV1/FVC <0.7 or LLN on spirometry post-bronchodilator
2. GOLD Grade (1-4) is defined by severity of airflow limitation (FEV1 % of predicted), helps establish prognosis
& guide non-medical therapy
3. GOLD Group (“ABE”) is defined by exacerbations &
sx (mMRC, CAT score) guides therapy
4. Other testing: lung volumes, DLCO (<60% a/w sx,
exercise, ↓health), exercise test (6MWT), α1-antitrypsin
DIFFERENTIAL
Pre-COPD: respiratory symptoms with structural lung lesions (emphysema) and/or physiological abnormalities w/o airflow obstruction
Preserved Ratio Impaired Spirometry (PRISm): respiratory sx w/ normal ratio (FEV1/FVC > 0.7) but impaired FEV1 (< 80) after bronchodilation
Chronic bronchitis: overlapping condition; chronic cough + sputum > 3 months / yr for 2+ years. Asthma: see PFTs and Asthma
Bronchiectasis: large vol of purulent sputum, a/w bacterial ifxn, bronchial dilat on CXR/HRCT. Obliterative bronchiolitis: lung/BM txp, HRCT:
hypodense areas on exp. Diffuse panbronchiolitis: Asian pts, chronic sinusitis, CXR/HRCT: diffuse small centrilob nodular opac & hyperinflation
M A N A G E M E N T O F S T A B L E C O P D (GOLD 2024; NEJM 2019;381:1257); Chart w/list of common inhalers: Allergy/Asthma Resp Rx 2024
Pharmacologic interventions:symptoms, risk/severity of exacerbations, health status, survival
GOLD A GOLD B GOLD E
Starting tx: Bronchodil (LABA or LAMA) LABA+LAMA LABA+LAMA. If eos>300 or asthma: LABA+LAMA+ICS
Rescue therapy: Short-acting bronchodilator
Escalate to: Dyspnea: LAMA + LABA Dyspnea: Switch inhaler device or molecules. Nebulizers may be helpful in severe COPD.
Exacerbation: LAMA + LABA Exacerb: Eos >100: LAMA+LABA+ICS (Lancet RM 2018;6:117), consider adding biologics
(i.e. dupilumab (BOREAS Trial)); Eos < 100: Roflumilast (bronchitis) (Lancet 2015;385:857)
vs. Azithro (former smokers) (NEJM 2011;365:689; Lancet RM 2014;2:361; Cochrane Rev 2018)
Notes • Long-acting>short-acting • LABA+LAMA > mono- • Include ICS if features of asthma
unless occ. dyspnea therapy (Chest • LAMA+LABA+ICS > LAMA+LABA to ↓exacerbations,
• Tiotrop may slow decline 2014;145:981; Cochrane but may ↑PNA (TRIBUTE; IMPACT; ETHOS ). Consider
in FEV1 in early COPD Rev 2015) d/c ICS if persist. exacerb, PNA (if eos >300, high risk
(NEJM 2017;377:923) ↑exacerb. w/ d/c)
Non-Rx interventions: Smoking cessation:↓mortality; Annals 2005;142:233, Vax: Flu, COVID, PCV20 (or PCV15PPSV23), Tdap, Zoster, RSV
Lung CA screening: annual low-dose CT (age 50-80 & ≥ 20 pack-years & has smoked in last 15y) (USPSTF 2021)
Pulmonary rehab (GOLD B/E): QoL, exercise capacity (Cochrane Rev 2015), possibly ↓mortality (JAMA 2020;323:1813)
Home O2: if PaO2 ≤55 or SpO2 ≤88% (PaO2 ≤59 or SpO2 ≤89 if pulmonary HTN or Hct >55% or CHF) for goal SpO2 >90%
Nocturnal NIPPV: if daytime pCO2 >53 & nocturnal SpO2 ≤88% (despite 2L O2) or recent exacerb. & persistent PaCO2 >53 (↓risk of readmit &
mortality: JAMA 2017;317:2177) Interventional therapies: bronchoscopic lung reduction (emphysema + hyperinflation), bullectomy, lung txp
(indications: progessive dx despite max rx, non-surgical candidate, BODE index 5+, frequent exacerb, low FEV1 (20-25%), or rapidly  BODE)
C O P D E X A C E R B A T I O N ( A E C O P D ) (ERS/ATS: ERJ 2017;49, GOLD 2024)
• Hx: dyspnea, /Δ sputum, and/or cough < 14d; ask re: URI sx, CHF sx, VTE risk fx, prior exacerbations/steroids/intubations/abx
• W-up: CXR, ABG/VBG ± ECG, trop, NT-proBNP. Flu, COVID, PE (PE in 25% severe exacerb w/o clear trigger: Annals 2006;144:390)
Management: • Antibiotics: controversial; mortality but challenging to identify
• SpO2 88-92%: hyperoxia  vent. via Haldane effect & hypoxic who will benefit (Chest 2008;133:756; Coch Rev 2012)
vasoconst., V/Q mismatch; mortality (BMJ 2010;341:c5462) o Indicated if: all 3 cardinal sx, 2/3 w/sputum purulence, or
• Bronchodilators: albuterol, ipratropium, DuoNebs (combo) require NIPPV/mechanical ventilation
o “Stacked” DuoNebs (x3 in 1h) initially  space to standing  CRP may be useful (NEJM 2019;381:111). PCT may be
DuoNebs q4 w/ albuterol PRN q2  space further as able useful but mortality when used in ICU (Eur Resp Rev
• Steroids: pred 40mg x5d. PO ~ IV (Chest 2007;132:1741) & 5d ~ 14d 2017;26; ICM 2018;44:428)
(REDUCE JAMA 2013;309:2223; Cochrane Rev 2018); some may need o Choice: based on PsA risk, prior SCx, resist. ⊝ PsA RFs:
higher dose/longer course if severe, but PNA risk FQ, CTX; amox/clav, azithro, doxy. ⊕ PsA RFs: FQ, cefe,
o If severe: IV methylpred 60-125mg q6-q12x72h, budesonide neb. pip/tazo Duration: 5-7d inpt; 3-5 outpt (vary by drug)
• NIPPV: if resp acidosis (pH < 7.35 & PaCO2 > 45), severe dyspnea,  Concurrent CAP: treat by CAP guidelines
WOB, pers hypoxemia. mortality, intub., LOS (Cochrane Rev 2004). • Antivirals: oseltamivir if influenza⊕, even if ≥48-72h
• Intubation: NIV failure, s/p arrest, aspiration/vomiting, HDUS • VTE ppx
INHALED THERAPIES FOR ASTHMA & COPD
Class Example Meds
Short-acting β-agonist (SABA) Albuterol, levalbuterol (SE: HR; levalbuterol more selective so less HR effect but $$)
Short-acting muscarinic antagonist (SAMA) Ipratropium (Atrovent) (SE: urinary retention, dry mouth)
Long-acting β-agonist (LABA) Salmeterol, formoterol (NB: in asthma, do not use without ICS)
Long-acting muscarinic antagonist (LAMA) Tiotropium (Spiriva), umeclidinium (Incruse Ellipta)
Fluticasone-salmeterol (Advair), budesonide-formoterol (Symbicort), mometasone-formoterol
Inhaled corticosteroid (ICS) + LABA
(Dulera), fluticasone-vilanterol (Breo Ellipta)
LAMA + LABA Umeclidinium-vilanterol (Anoro Ellipta)
LAMA + LABA + ICS Fluticasone-umeclidinium-vilanterol (Trelegy Ellipta)

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Pulmonary & Critical Care Bronchiectasis & Hemoptysis

B R O N C H I E C T A S I S (permanent airway dilatation from recurrent infxn/inflammation) (AJRCCM 2013;188:647; NEJM 2022;387:533)
Symptoms Chronic productive cough, recurrent bronchitis/pneumonia, wheezing, dyspnea, hemoptysis, recurrent pleurisy
Recurrent insult: infection (PNA, MAC, TB, PsA, childhood infections, ABPA), inhalation, GERD/aspiration
Impaired immunity: mucus clearance (CF, 1° ciliary dyskinesia [PCD]), immunodeficiency (e.g., HIV, CVID, IgG)
Etiology
Obstruction: foreign body, tumor, COPD, tracheomalacia/tracheobronchomegaly, CTD (Marfan’s), radiation
Systemic disease: RA, Sjogren’s, SLE, IBD, A1AT; Idiopathic = ~50%
Dx: 1) productive cough most days/week, 2) exacerbations, and 3) CT w/ ≥1 of: bronchial diameter > adj artery
(signet-ring sign), thickened bronchi w/ lack of tapering (tram track sign), radiographically visible airways in perimeter
Workup Initial: MDCT or DLDCT, PFTs, CBC/diff, Ig levels, sputum Cx (bacterial, mycobacterial, fungal)
As indicated: CF eval (gene/sweat Cl- testing), Aspergillus IgE, ANA, RF/CCP, SSA/SSB, A1AT, HIV, Ig levels;
consider nasal NO (PCD), pneumococcal vaccine titers (often low), bronch w/BAL, colo (IBD), pH/motility testing
Natural Hx Exacerbations,  in FEV1, PsA colonization  worsening disease; prog. w/ Bronchiectasis Severity Index or FACED
Chronic Management Acute Exacerbation
CF: AJRCCM 2013;187:680, AJRCCM 2009;180:802; non-CF: AJRCCM 2013;188:647, ERS: Eur Resp J 2017;50, BTS: Thorax 2019:74
• Airway clearance: nebs (albuterol, 3% NaCl), chest PT (acapella, vest) • Sx: ∆ in ≥3: change in cough/sputum, purulent
o CF: add DNase to neb bundle; not effective in non-CF sputum, worse dyspnea, fatigue, hemoptysis,
• Antimicrobials/anti-inflammatories: clinical judgment (Eur Resp J 2017;49)
o Non-CF: Long-term azithro exacerb. but c/f abx resistance • Obtain resp cx prior to abx, CXR
(Lancet 2012;380:9842; JAMA 2013;309:1251; Coch Rev 2018; Lancet • Micro: PsA, S.aureus > H. flu, Moraxella,
RM 2019;7:845). Ensure no NTM first Burkholderia; treat Stenotrophomonas,
 Intermittent abx (FLQ, β-lactam, tobra) in pts w/ ≥3 exacerb/y Achromobacter as pathogenic; Aspergillus in CF
exacerb but abx resistance (Coch Rev 2022) not always pathogenic
 Trial inhaled abx if PsA colonization & ≥3 exacerb/y, consider • Abx: use previous Cx data; tx 10-14d
eradication of new PsA isolate o No prior cx data: empiric FLQ (for PsA)
o CF: azithro + inhaled tobramycin (for PsA; alt: aztreonam, colistin) o If prior R-PsA: IV abx; 2 agents – β-lactam &
• Disease specific treatment: either FLQ or IV tobra (dosed qd)
o Non-CF: treat underlying cause if found; consider PPI/H2 blocker  No great evidence for double coverage of
o CF: CFTR mut defective Cl-/HCO3- transport on airway surface PsA though is standard of care in CF
 Potentiators open CFTR channel (ivacaftor); correctors bring o If β-lactamase⊕ H flu or Moraxella:
it to surface (lumacaftor, tezacaftor, elexacaftor, VX-659) amox/clav, CTX, doxy, macrolide, or FQ
 Dual/triple tx long-term FEV1 benefits (NEJM 2015;373;220; o Cont home azithro ± tobra (practice varies)
NEJM 2017;377:2013; NEJM 2018;379:1599; NEJM 2019;381:1809) • Steroids only w/ concom. asthma, COPD, ABPA
 Pancreatic enzyme supplementation, vitamins ADEK • Continue chronic treatment (airway clearance)
H E M O P T Y S I S (expectoration of blood from lower respiratory tract) (Am Fam Physician 2022;105:144)
• Airway: bronchitis, bronchiectasis (incl. CF), masses (usually 1* lung CA), trauma (incl. foreign body)
Etiology • Pulmonary parenchyma: infection (PNA, abscess, TB, aspergilloma), vasculitis (ANCA, anti-GBM,
(common & life- immune-complex, drug-induced; see Vasculitis and Autoantibodies), coagulopathy, endometriosis,
threatening) inhalation injury, collagen defect, sarcoid, pulmonary hemosiderosis, trauma
• Pulmonary vascular: PE, CHF (esp if on AC), mitral valve dz, bronchovascular fistula, aneurysm, AVM
1) Consider pseudohemoptysis from other sources (GI or nasopharyngeal)
Work-up 2) CXR (most important), CBC, coags, U/A (vasculitis, anti-GBM), sputum Cx, CTA chest (if stable), bronch
3) Consider NT-proBNP, D-dimer, ESR/CRP, C3/C4, ANA, ANCA, anti-GBM, APLAS, IGRA/AFB, RVP
Non-massive: if minimal (<30mL) & benign (eg. infxn/bronchiectasis): observe. If active, recurrent, >1w: CT  bronch
MASSIVE HEMOPTYSIS (>500mL/d or >100mL/h) = life-threatening emergency with mortality 50-80%. Asphyxiation, NOT
exsanguination, is mechanism of death (maximum pulmonary blood volume ~500mL, CCM 2000;28:1684)
• LIE PATIENT WITH SIDE OF SUSPECTED BLEED DOWN (preserve gas exchange in unaffected lung)
• Ensure hemodynamic stability, active T&S, correct coagulopathy. Inhaled TXA may be beneficial (Chest 2018;154:1379)
• STAT RICU (x6-3333)  control airway if dyspneic, rapid bleed, largest possible ETT (8mm+), suction as blood can fill ETT
• Call IP  bronch to localize; temporize w/ balloon tamponade, bronchial blockade, electrocautery, topical vasoconstriction
Call IR  if stable, can CTA to localize; otherwise, bronchial angiography to embolize site. If refractory, call thoracic surgery
• Can consider pulse dose methylprednisolone if vasculitis suspected

D I F F U S E A L V E O L A R H E M O R R H A G E (disruption of alveolar-capillary basement membrane) (Chest 2010;137:1164)

Presentation: hemoptysis (can be absent in 1/3), cough, fever, dyspnea, diffuse radiographic opacities, abnl gas exchange
Etiology: capillaritis (rheum, drugs, idiopathic), bland hemorrhage (AC, plt, HF), diffuse alveolar damage (ARDS, infxn, PE, drugs)
Workup: CXR, CT (diffuse GGO central > peripheral), BAL (progressively more hemorrhagic serially), labs guided by clinical picture
Management: Primarily supportive. Manage hypoxemia and treat underlying etiology, eg.:
Capillaritis/AI syndromes: Systemic glucocorticoids (pulse dose IV methylpred 500-1000mg/d up to 5 doses w/ taper), cyclophos,
ritux ± plasmapheresis. Excess AC/bleeding disorder: reverse AC. (Int J Mol Sci. 2021;22:793)

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Pulmonary & Critical Care Interstitial Lung Disease

OVERVIEW
Heterogeneous group of lung diseases involving the replacement of normal lung parenchyma with varying degrees of inflammation and
fibrosis (scarring), can involve any part of the lung parenchyma
Presentation: progressive dyspnea, non-prod. cough, hypoxemia (esp. w/exercise); some w/ constitutional sx (AIP, HSP, COP)
History: tempo, hx CTD/IBD/malig/thoracic XRT, rheum dz, meds, exposures (chemicals, dust, humidity, pets, barns), smoking, FHx
Exam: “velcro-like” crackles, inspiratory squeaks, clubbing, e/o CTD (heliotrope rash, Gottron’s papules, mechanic’s hands, synovitis,
foot/wrist drop, sclerodactyly, sicca), vasculitic rash, extrapulmonary manifestations of systemic dz (sarcoid, amyloid, IBD, cancer)
E T I O L O G I E S : known & idiopathic causes (ATS/ERS: AJRCCM 2013;188:733)
Idiopathic Interstitial PNAs (IIPs) Connective Tissue Disease7 Exposure-Related Granulomatous
Idiopathic Pulmonary Fibrosis (IPF) 1 Scleroderma Organic: grain, mold, birds, hay Sarcoidosis9
Idiopathic Non-Specific Interstitial PNA Sjogren’s syndrome (cause HSP)8 Hypersensitivity pneumonitis8
(NSIP)2 MCTD Inorganic: silica, asbestos, coal, Mycobacterial disease
Acute Interstitial PNA (AIP)3 Polymyositis/Dermatomyositis metals (causes pneumoconiosis) Fungal disease
Cryptogenic Organizing PNA (COP)4 Anti-synthetase syndrome Drugs: nitrofurantoin, MTX, Langerhans cell histiocytosis10
Respiratory Bronchiolitis-ILD (RB-ILD) Rheumatoid arthritis
5 amiodarone, pembro/nivo (see:
Desquamative Interstitial PNA (DIP)6 Lupus PneumoTox), radiation
Radiographic Associations: (91% sensitive, 71% specific JAMA 2024)
1 Usual interstitial pneumonia (UIP) pattern: heterogenous subpleural/basal predominant, honeycombing, traction bronchiectasis
2 Non-specific interstitial pneumonia (NISP) pattern: lower lobe predominant, reticulation/GGOs predominantly in periphery, micronodules
3 Diffuse alveolar damage (DAD) pattern: diffuse, bilateral, central>peripheral ground glass or consolidative opacities
4 Organizing PNA (OP) pattern: bilateral peripheral, perilobular consolidations with subpleural sparing
5 Respiratory-bronchiolitis (RB) pattern: centrilobular nodules (usually in upper zones), GGOs, interlobular septal thickening
6 Desquamative interstitial pneumonia pattern: homogenous or patchy GGOs in mid/lower lung zones
7 May be associated with any pattern (UIP, NISP, etc)
8 May be associated with RB pattern (see 5), with progression to traction bronchiectiectasis, honeycombing, centrilobular nodules
9 Peribronchovascular, hilar, subpleural nodules (granulomas) 10 Stellate nodules, thick walled cysts, bullae

UIP NSIP OP RB

DIAGNOSTIC EVALUATION: REQUIRES A MULTIDISCPLINARY DISCUSSION

• Exclude fungal/atypical bact. infxn, esp. in immunocompromised pts; consider sputum bacterial/fungal culture, HIV/hepatitis testing
• General Approach: remove potential environmental causes. If improves no further w/u. If not assess for systemic dz. If unlikely
systemic dz, HRCT (see Radiographic Associations above), consider bronch and/or biopsy based on findings
• Labs: CBC/diff, CMP, UA, CK/aldolase, C3/C4, autoantibodies (ANA, RF/CCP, RNP, Ro/La, Scl-70, ANCA, hypersensitivity panel,
myositis panel, anti-GBM Ab)
• Lung biopsy: If dx unclear (atypical presentation or c/f malignancy) + Δ tx. Bronchoscopic transbronchial cryobiopsy less invasive than
VATS. Not helpful if known CTD. If definite UIP, rec against (high morbidity, exacerbations) (AJRCCM 2018;198:e44).
• Assess Severity: 6 minute walk test and PFTs: Restrictive (TLC, FRC, RV; FEV1/FVC normal to ); DLCO can be early sign
TREATMENT
• IPF: (AJRCCM 2015;192:e3)
o Acute exacerbations: ddx includes infxn, PE, HF; send BNP, trop, procal, d-dimer, blood cultures, S. pneumo & Legionella urinary
antigens, extended RVP. Treat with pred ~1mg/kg/d & broad-spectrum abx (vanc/cefe/azithro) X 7d.
o Chronic therapy: consider pirfenidone (antifibrotic; SE: nausea, fatigue; NEJM 2014;370:2083), or nintedanib (TKi; SE: diarrhea;
NEJM 2014;370:2071). Promising data for new PDE4 inhibitors (NEJM 2022; 386:2178). All FVC decline, may not Δ overall
survival. Consider lung transplant eval. AZA, pred, NAC tx mortality (NEJM 2012;366:1968). GERD tx to benefit lung disease not
recommended (ATS 2022;205:18)
• NSIP: remove inciting exposures, tx underlying condition; can be steroid-responsive (pred 0.5-1mg/kg/d or pulse methylpred if
requiring hospitalization); 2nd agent (AZA, MMF, ritux, CYC) pending response. Nintedanib may benefit non-IPF progressive fibrotic
disease irrespective of underlying ILD diagnosis (NEJM 2019;381:1718; Lancet RM 2020;8:453)
• COP: monitor; if sx persist/progress pred ~0.75-1mg/kg/d (pulse if fulminant)
• AIP: idiopathic ARDS; usually not steroid-responsive, but often trial steroids & abx as in-hospit al mortality is >50%
• Systemic Sclerosis: permutations of Nintedanib, MMF, CYC, Rituximab, and Tocilizumab depending on symptoms (JAMA 2024)
Transplant Referral (JHLT 2022;40:1349): Any ILD: FVC<8% or DLCO<40% predicted; change in FVC ≥10%, DLCO≥15%, or FVC≥5%
over 2 years w/worsening dyspnea or radiographic progression; supplemental O2 at rest or exertion. OR: IPF: Time of dx. Inflam ILD:
progression of dz despite tx. CTD or familial: early referral.

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Pulmonary & Critical Care VTE Diagnostics

CLINICAL MANIFESTATIONS
Signs/Symptoms
Deep Vein Thrombosis (DVT)
• S/Sx: pain, warmth, erythema or cyanosis, edema (esp. asymm.), palpable cord, venous distention, Homan’s sign (sudden
dorsiflexion of ankle w/ knee flexed to 30˚  pain in upper calf); none Sn/Sp (JAMA 1998;279:1094); can be asx
• Types: proximal = iliac, femoral, popliteal veins; distal = calf veins below knee (ant./post. tibial, peroneal, soleal, gastrocnemius)
o Massive iliofemoral DVT: phlegmasia alba dolens (edema, pain)  phlegmasia cerulea dolens (cyanosis, venous gangrene)
o May-Thurner syndrome: anatomic variant  compression of L common iliac vein by R iliac artery  LLE DVT and/or swelling
• Central venous catheters are most common cause of upper extremity DVT (PICC > CIC > Ports) (Hematology ASH 2014;1;306).
• Ddx: superficial thrombophlebitis, cellulitis, arthritis, arterial occlusion, varicose veins, lymphedema, ruptured Baker cyst, chronic
venous insufficiency (Arch IM 1998;158:2315)
Pulmonary Embolism (PE) (EHJ 2020;41:543)
• Sx: dyspnea, pleuritic CP, cough, orthopnea, leg swelling/pain, syncope, hemoptysis, diaphoresis, palpitations, can be asx
• (NEJM 2016;375:1524; JACC 2019;76:744)
• Signs: tachypnea, tachycardia, hypoxemia, hypotension, rales, S4, P2, breath sounds, JVD, fever, wheezing, RV heave, pleural
friction rub, S3
• EKG Δs: sinus tach., atrial arrhythmias (AF, AFL), RAD, RBBB, inf. Q, anterior STΔs/TWIs, S1Q3T3 (ERJ 2005;25:843)
Risk Factors: Virchow’s triad of venous stasis, vascular injury, hypercoagulability (Circulation 2003;107:I9; ERJ; 2020;41;543)
Risk factors tend to be additive
Strong Moderate Weak
- Thrombophilia
- Hospitalization for HF - CHF (JACC 2020;75:148)
- Prior VTE
or AF (w/in 3 mo) - Resp. failure, asthma (ERJ - Bed rest >3d
- Arthroscopic knee surgery -CKD (J Thromb. Haemost
- MI (w/in 3mo) 2014;43:801) - Immobility due to sitting
- CVC (Lancet 2013;382:311) 2014;12:1449)
- Hip/knee - Paralytic stroke (e.g. airplane, car)
- Estrogen-containing meds -Diabetes
replacement - IBD, nephrotic syndrome - Increased age
- Pregnancy (postpartum) - Cirrhosis (Thromb
- Lower limb fracture - Infection/sepsis (Chest - Lap surgery (e.g. CCY)
- IVF Haemost 2017;117:139)
- Major gen. surgery 2015;148:1224) - Obesity (Circ 2008;117:93)
- Malignancy - Varicose Veins
- Major trauma - Autoimmune disease, IBD - Pregnancy (antepartum)
- Some forms of
- Spinal cord injury - ESAs
chemotherapy
D I A G N O S I S / R I S K S T R A T I F I C A T I O N (ASH: Blood Adv 2018;2:3226; AHA: Circ 2011;123:1788; ESC: EHJ 2019;41:543; JAMA 2018;320:1583)
• Pre-test prob: Wells for LE DVT and PE, Constans’ for UE (Thromb Haemost
2008;99:202), Geneva for PE I N T E R P R E T I N G D - D I M E R (nl <500)
o If low (or mod. DVT), can r/o w/ D-dimer (see below) or PERC score for PE; if - If nl and low pretest prob, excludes DVT/PE
D-dimer ⊕ need further eval. If high (or mod. PE)  imaging (NEJM 2003;349:1227; JAMA 2006;295:199;
o Wells score discriminates risk of VTE in outpatient settings; not sufficient to Thromb Haemost 2009; 101:886)
rule out DVT in hospitalized patients (JAMA 2015; 175; 1112) - Adjusted D-dimer:  imaging w/o  in PE
• DVT diagnosis: venous Doppler US of lower or upper extremity (LENI, UENI).  Age-adjusted: if >50, use age x10 as cut
• PE diagnosis: off (JAMA 2014;311:1117)
o CTPA: study of choice; may also detect alternate dx (NEJM 2006;354:2317)  Prob.-adjusted: use of <1000 cutoff w/ low
o V/Q scan: validated (JAMA 1990;263:2753). Performed if c/i to CTPE, Need nl prob. (NEJM 2019;381:2125)
CXR (minimize other causes of V/Q mismatch), cannot be done urgently - Ddx for D-dimer: arterial thrombus (MI,
o LENIs: if suspect PE, unable to CT or V/Q, & ⊕, can treat; if ⊖, however, stroke, AF/intracardiac, acute limb ischemia),
does not exclude PE (clot may have migrated or be from another source) DIC, CA, inflammation/infection, ESLD, CHF,
o Echo: most useful for risk stratification (not dx), though demonstration of clot renal disease, age, aortic dissection,
or new RV strain can provide presumptive diagnosis if needed rapidly trauma, surgery
o ABG: can see hypoxemia (A-a gradient, normal in ~20%), resp. alkalosis
• PE risk scores: PESI (PE Severity Index): prediction of morbidity/mortality in patients w/ newly diagnosed PE, sPESI (simplified
PE Severity Index), and BOVA for PE complications in HDS patients.
Risk Stratification
Risk HDUS: shock, SBP <90, Elevated Cardiac Imaging Evidence of PESI Class III-V
cardiac arrest Biomarkersa RV Dysfunctionb and/or sPESI≥1
High* + + + +c
Intermediate-High - + + +
Intermediate-Low - One of two + +
Low - - - -
*Syncope and Clot in Transit are also considered High Risk
a BiomarkerEvidence: hs-TnT: ≥14 in age <75 & ≥45 in age >75 may NPV (ERJ 2015;45:1323); NT-proBNP (ERJ 2014;43:1669)
b Imaging
Evidence: CT: RV/LV diameter ratio >0.9 (EHJ 2011;32:1657); TTE: RV Overload/Dysfunction - enlarged RV, flattened IVS, .mod/severe TR,
McConnell’s Sign (RV free wall akinesis sparing apex; Circ 2008;118:517), TAPSE (JEM 2020;58:449).
c Hemodynamic instability and confirmed PE on CTPA and/or RV dysfunction on TTE = high-risk. PESI classes/cardiac biomarkers unnecessary.

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Pulmonary & Critical Care VTE Management

M A N A G E M E N T O F V T E (CHEST: Chest 2021;160:545); ESC: EHJ 2020;41:543); ASH: Blood Adv 2020;19;4693)
Proximal DVT (popliteal, femoral, iliac vv.) Distal DVT (calf: ant./post. tibial, peroneal vv.)
Serial imaging vs. anticoagulation
Anti-coagulate (unless contraindications), regardless of sx Serial imaging: if asx, low risk for extension, or high risk for
bleeding
Agent: DOAC > VKA > LMWH; if malig.: DOAC > LMWH > VKA • Repeat US at 1-2w (1/3 will extend; risk in muscular
(for dosing & info on choosing agent, see AC and AC Mgmt sections) veins: soleal, gastrocnemius)
Duration: at least 3mo for all. Individualized decision to extend >3 mo, Anti-coagulate (same AC regimen as proximal DVT) if:
balancing bleeding risk with risk factors of recurrence (eg provoked vs • Severe symptoms
non-provoked, malignancy-related or not, APLS or not) • RFs for extension: ⊕ D-dimer, extensive (>5cm, mult.
veins, >7mm in diam.), close to prox. veins, no
If stop AC, consider ASA 100mg if no contraindications (NEJM reversible provoking factor, active CA, h/o VTE, inpt
2012;367:1979; NEJM 2012;366:1959; Circ 2014;130:1062)
• On serial imaging, extends into proximal veins. AC
also suggested if extends but remains in distal vein
IVC filter: Only if contraindications to AC (e.g. active bleeding,
• Patient prefers treatment over serial imaging
recent/planned high bleeding-risk procedure, major trauma, acute ICH)
• Remove once no longer needed (typical implantation time ~1-2mo; Post-thrombotic syndrome: Long-term sequelae of DVT
JVIR 2011;22:1522). Complications incl. IVC thrombosis, due to poor venous flow. Treatment with compression +/-
acute/recurrent DVT or PE, filter migration/erosion/fracture endovascular/surgical intervention (Cardiovasc Diagn Ther
2016;6;623).
UE DVT (NEJM 2011;364:861): brachial, axillary, subclavian; complications vs. LE DVT. Tx same as LE DVT. If PICC/CVC (catheter-
associated), no need for catheter removal if needed/functional/infected; poor evidence for whether to initiate AC.
Bleeding risk: low = 0 RFs (1.6%/3mo; 0.8%/y after 3mo); mod = 1 (3.2%/3mo; 1.6%/y); high = ≥2 (12.8%/3mo; ≥6.5%/y)
RFs: age >65-75, previous bleeding, CA, renal failure, liver failure, thrombocytopenia, prior CVA, DM, anemia, anti-platelet tx, poor AC
control, functional capacity, recent surgery, frequent falls, AUD, NSAID use
Further diagnostic testing in unprovoked VTE: age-appropriate cancer screening (found in 5% within 1y; Annals 2017;167:410),
hypercoagulability w/u limited during acute episode
*Superficial vein thrombosis: Tx w/reduced-dose DOAC for 45 days in some patients (Chest 2021;160;545), otherwise, heat/elevation
High Risk PE Intermediate Risk PE Low Risk PE
PERT c/s (x47378): for intermediate-high or high risk, consider SHOCK c/s (p11511) for high risk
Resuscitation: Anticoagulation: LMWH preferred > UFH (faster time Anticoagulation:
• Cautious IVF: can trial if CVP low, but RV to therapeutic range) unless impending hemodynamic See above (DVT) and AC, AC
distention RV ischemia + septal collapse, thrombolysis (or CrCl <30 or severe obesity). Mgmt sections
bowingLV SV CO
Discharge: if no other
• Inotropes: if low CO, consider dobutamine Intermediate-high risk: transition to long-term AC agent reasons for hospitalization,
Vasopressors: norepi, epi, or vaso after 48-72h of stability. can d/c; can use Hestia
• O2: HFNC preferred. Mech vent high risk: Intermediate-low risk: transition after 24h. score to stratify for outpatient
HoTN from induction & PPV  venous treatment
return  RV CO, RV failure Thrombolytic therapy (catheter-directed preferred
• Circulatory collapse/arrest: Pulse = tPA over systemic) in select pts: (Circ 2011;123:1788) No Isolated Subsegmental PE
Pulseless = TNK and CPR for 15 minutes to strict guidelines, indications include: developing shock, (w/ no DVT): Rule out
ensure circulation; eval for VA ECMO resp failure, mod/severe RV dysfunction on TTE (RV proximal DVT. If low risk of
• Anticoagulation: LMWH vs UFH (w/ bolus) hypokinesis, RVSP >40) w/  hs-TnT/NT-proBNP recurrent VTE, can consider
Thrombolysis: systemic, though some cases (>900) surveillance with repeat
warrant catheter-directed tPA thrombolysis • Routine tPA in int. risk PE  hemodynamic imaging. If higher risk,
Embolectomy: if thrombolysis contraind/fails; can decomp., no clear long-term Δ in mortality; major anticoagulate (Chest 2021;
be catheter-directed; surgery if all options bleeding & hemorrhagic CVA (NEJM 160:e545)
contraind/fail or if clot in transit in RA/RV, PFO 2014;370:1402; JACC 2017;69:1536)
Thrombolysis:  mortality (Am J Card 2019;123:684; JAMA 2014;311:2414; CDSR 2021;4:CD00437)
Systemic: Patient with pulse = tPA 50-100mg/2h. Cardiac arrest = weight based TNK over 5 seconds (see ellucid thrombolysis
guidelines). Hold AC during infusion (but do not delay if got LMWH), restart heparin when PTT <2x ULN. Follow fibrinogen q6h.
• Absolute contraindications: intracranial neoplasm, CNS surgery/trauma <2-3mo, h/o ICH, active bleeding, non-ICH stroke <3mo
Catheter-directed: infused into pulmonary artery via PA catheter, significantly less lytic agent given than in systemic lysis. May be
preferred if high-risk for bleeding, failed systemic thrombolysis, or otherwise selected pts; can couple w/ US-assisted thrombolysis
(EKOS) to enhance mechanical breakdown of thrombus or suction thrombectomy.  in RVSP, RV/LV ratio, no data for mortality benefit
(Circ 2014;129:479; JACC Card Interv 2015;8:1382; Am J Med 2019;132:240; Am J Card 2019;124:1470)
PERT (x47378): call if large PE w/ abnormal VS (tachycardia, hypotension), evidence of RH strain (TTE, EKG, biomarkers), saddle PE.
SHOCK (p11511): call for consideration of ECMO if worsening refractory hypoxemia or hemodynamic instability
Order: CBC/diff, BMP, LFTs, lactate, D-dimer, ABG, PT/INR, PTT, T&S, NT-proBNP, hs-TnT, EKG, CT-PE, LENIs, TTE
Monitoring: Routine evaluation at 3-6mo; in continued symptomatic patients, consider PH/CTEPH (evaluate w/ V/Q scan, TTE, BNP
and/or CPT).

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Pulmonary & Critical Care Pulmonary Hypertension

Pulmonary Hypertension = mean PA pressure (mPAP) ≥20 mmHg CLINICAL MANIFESTATIONS
PVR = (mPAP - PCWP) / CO; rearranged: mPAP = (PVR x CO) + PCWP S/Sx: nonspecific; 2y delay to dx in 20% (Chest 2011;140:19)
∴  in PVR or PCWP can  pulmonary hypertension (PH) - Early: DOE, lethargy, fatigue (2/2 inadequate CO w/ activity
 Pre-capillary PH: PVR ≥2, PCWP ≤15, DPG & TPG - Late: exertional CP, syncope, edema, anorexia, abdominal
 Post-capillary PH: PVR <2, PCWP >15, nl DPG & TPG distention (secondary to progressive RV failure)
 Mixed PH: PVR ≥2, PCWP >15, DPG & TPG - Rare: cough, hemoptysis, hoarseness (Ortner’s syndrome)
Transpulmonary gradient (TPG) = mPAP – PCWP; nl <12 Exam: loud P2; JVP, edema, ascites, TR murmur, R-sided
Diastolic pulmonary gradient (DPG) = PA diastolic (PAd) – PCWP; nl <7 gallop, parasternal heave (LSB), PA tap (L 2nd ICS), edema,
hepatomegaly, ascites
D I A G N O S I S (ERJ 2019;53:1801904) Imaging: CXR w/ enlarged PA, RA, RV (retrosternal space on
• RHC: gold standard (may not be needed in all circumstances) ± iNO lat.), pruning of peripheral vessels; CT w/ PA/Ao diameter ≥1
vasoreactivity testing (+ response = mPAP ≥10 mmHg to reach ECG: normal vs signs of RV hypertrophy/strain: RAD, R/S >1 in
mPAP ≤40 mmHg w/  or = CO; guides treatment in idiopathic PH) V1, RBBB, P pulmonale in II (RAE)
• Evaluation for etiology: TTE: TR peak velocity ≥2.8 (= RVSP >35mmHg), PA diameter
o TTE: eval for left HF (& whether severity explains PH) >25mm; RVOT acceleration time<105ms, TAPSE <1.7 cm, RV
o RUQUS: Assess for portopulm HTN, portocaval shunt dilation/hypokinesis, RV/LV>1, IVC>21mm
o PFTs, DLD-CT, polysomnography: chronic lung disease, OSA
o CPET: determine etiology of exercise intolerance (cardiac vs pulmonary/PAH vs other)
o V/Q scan: eval for CTEPH
o Labs: NT-proBNP, BMP, LFTs, eval for systemic disorders in groups 1 & 5 (if not already known) – HIV, connective tissue diseases
(ANA, RF/CCP, ANCA, Scl-70, Ro/La), schistosomiasis (if clinically appropriate), urine & serum toxicology
W H O C L A S S I F I C A T I O N (6th World Symposium on PH: ERJ 2019;53:1801913; JACC 2013;62:D34)
Pre-Capillary Post-Capillary
Group 1: Pulmonary Arterial Hypertension Group 3: Lung disease Group 4: Pulmonary artery Group 2: Left heart
(PAH) and/or hypoxemia obstructions disease
- Idiopathic (♀>♂) Obstructive: COPD Chronic thromboembolic HFpEF
- Heritable (e.g. BMPR2) Restrictive: ILD disease (ERJ 2019;53:1801915) HFrEF
- Drug/toxin-induced: cocaine, anorexigens, etc Mixed NB: only ~33-75% had known Valvular disease
- Associated with: CTD (MCTD, SSc, SLE), HIV, obstructive/restrictive prior VTE. Occurs after ~4% of Congenital/acquired
portal HTN, congenital heart disease, schisto Chronic hypoxia w/o lung PEs (NEJM 2004;350:2257) conditions
- PAH long-term responders to CCBs disease: OSA, OHS Other PA obstructions: malig., (ERJ 2019;53:1801897)
- PVOD and/or pulm. capillary hemangiomatosis Developmental lung dz arteritis w/out CTD, parasites,
- Persistent PH of newborn (ERJ 2019;53:1801914) congenital PA stenosis
Group 5: Misc. chronic hemolytic anemia (e.g., sickle cell), MPN, sarcoid, metabolic d/o, complex congenital heart disease
WHO Functional Classes: Class I = asx w/ ordinary activity, II = sx w/ ordinary activity, III = sx w/ minimal activity, IV = sx at rest
MANAGEMENT
Treat underlying etiology: CTD, CHF, hypoxemia, VTE, etc. Advanced therapies (below): guided by WHO functional class (reserved for II-
IV). Most evidence in Group 1. Surgery: pulmonary thromboendarterectomy (CTEPH), atrial septostomy (R L shunt), lung txp in select
pts. General: exercise/pulm rehab, O2, diuresis (in RHF), contraception required in ♀(2 forms vs permanent form), vaccines
Mechanism Medication Indication Side effects
Blocks
Endothelin Bosentan, Group 1: sx, 6MWT (NEJM 2002;346:896; Circ Anemia, PNA, edema, hepatotox.
pulmonary
receptor ambrisentan, 2008;117:3010) Macitentan: also flu, HA, UTI,
vasoconstriction
antagonists macitentan Macitentan: morbid/mortality (NEJM 2013;369:809) bronchitis
& proliferation
PDE5 inhibitors: Increases cGMP Erythema, flushing, indigestion,
Group 1 (sildenafil studied in some etiologies of
sildenafil, tadalafil, → vasodilation, HA, insomnia, epistaxis, rhinitis,
Group 2 and 5): sx, 6MWT (NEJM 2005;353:2148;
vardenafil (not FDA blocks retinal hemorrhage,
(NO)-cGMP NEJM 2009;361:1864)
approved for PAH) proliferation *contraindicated if using nitrates
enhancers
BP, n/v/d/const., GERD,
sGC stimulator: Group 1 & Group 4: sx, 6MWT (NEJM
anemia, dizziness, HA,
riociguat 2013;369:330)
hemorrhage
Increase cAMP Group 1: 6MWT, QOL, mortality w/ epo.;
Analogues: → vasodilation, reserved for sickest patients. (NEJM 1996;334:296) CP, BP, HR, flushing, abd
Prostacylin
epoprostenol, blocks Group 3: 6MWT, NTpro w/ treprost. (NEJM pain, anorexia, n/v/d, MSK & jaw
pathway
treprostinil, iloprost proliferation 2021;384:325) pain, dizziness, HA, hemorrhage
agonists
Group 5: some etiologies
(PPA)
Receptor agonist: Group 1: hospitalization; no Δ mortality (NEJM Diarrhea, nausea, jaw pain, HA,
selexipag 2015;373:2522) anemia
CCB (trial) Nifedipine, diltiazem Vasodilation ⊕ iNO vasoreactivity test,  RV failure BP, LE edema
Initiating Therapy based on ERS/ESC risk stratification guidelines (ERJ 2015;46:903, ERJ 2022): refer to Pulm HTN clinic
Risk stratification criteria: WHO functional class, 6MWT, NT-proBNP, TTE/cMRI, RHC at dx, consider CPET
• Low/intermediate risk: dual oral therapy (target ERA/NO pathways; ambrisentan and tadalafil preferred). Can add CCB if vasoreactive.
• High risk: IV prostacyclin agonist (epoprostenol preferred) + ERA + PDE5i
• Goal of therapy is to attain low risk criteria: NT-proBNP < 300, WHO/NYHA class I or II, 6MWT>440m. May add IV/SQ prostacyclin if
low risk criteria are not met 3-6mo after initiation of oral agents (ERJ 2017;50:1700889; ERJ 2022)
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Pulmonary & Critical Care Mechanical Ventilation

INDICATIONS FOR INTUBATION Call RICU for intubation: x6-3333
• Failure of NIPPV: unable to tolerate, progressive hypoxemia/capnia, high RICU will ask: AMPLE
pressures, ↓mental status, ↑fatigue/WOB A = allergies
• Poor ventilation: PaCO2 >60 with severe acidemia (COPD/asthma, sedation, M = medications (current)
neuromuscular disease, resp. muscle fatigue, trauma) P = past medical hx (incl. h/o LVEF and RV
function, prior intubations or difficult airway)
• Poor oxygenation: worsening P:F ratio (PNA, pulmonary edema, ARDS, PE)
L = last meal/K (succinylcholine can cause hyperK)
• Airway protection: AMS/secretion management, shock, facial/head trauma, E = events (prompting intubation)
n/v/UGIB, severe bronchospasm/anaphylaxis, procedural necessity During intubation, have at bedside:
• Persistent increased work of breathing: severe bronchospasm, airway (1) Good access (2) IVF (3) sedative agent (e.g.
obstruction, inability to compensate for severe acidemia propofol) (4) pressors (neo >> levo)
• Hemodynamic instability: unstable arrhythmia, severe shock
HEMODYNAMIC CONSEQUENCES OF INTUBATION
• PPV  intrathoracic pressure   LV & RV preload,  PVR/RV afterload (variable) &  LV afterload. Can precipitate RV failure in
pHTN and RV dysfx
• In acidosis such as DKA, can be difficult to match RR to physiologic needs
• Vasoplegia and loss of compensatory tachycardia from sedatives  sympathetic tone =  BPs; have appropriate pressors ready
G E N E R A L P R I N C I P L E S : (NEJM 2001;344:1986; Respir Care 2017;62:629)
Five main variables: (1) RR, (2) tidal volume (VT), (3) FiO2, (4) positive end-expiratory pressure (PEEP), (5) mode of ventilation
• Ventilation determines PaCO2: PaCO2 by increasing RR and/or VT (minute ventilation where MV = RR x VT)
1) RR: often adjust this first; avoid >RR 30-35 due to risk of inadequate expiratory time  air trapping/auto-PEEP
2) VT (often set at ≤6cc/kg IBW): when , ensure Pplat ≤30 & driving pressure (ΔP = Pplat – PEEP) ≤15 to minimize lung injury
• Oxygenation: PaO2 by FiO2 and/or PEEP
3) FiO2: avoid FiO2 >0.6 for prolonged periods due to oxygen toxicity
4) PEEP: if recruitable lung present, PEEP will alveolar recruitment, improve V/Q match and compliance  P:F & Pdrive stable/;
if PEEP  no Δ/ P:F, PaCO2, or Pdrive, lung is not recruitable & PEEP = dead space/compliance due to overdistention
V E N T I L A T O R M O D E S : (Respir Care 2007;52:301)
SET MEASURED
MODE PROS/CONS HOW TO READ WHEN TO USE
Indep. Var. Dep. Var.
AC/VC “Pt is on Volume Control w/ VT
VT - Acute resp failure
Assist : control (fixed VT prevents of 400 (4cc/kg), set at a rate of
PEEP - ARDS
Control/Volume PIP & Pplat barotrauma or atelectrauma) 16 breaths/min, PEEP of 8, and
RR - Airflow limitation
Control: delivers a I:E or flow : fixed insp. flow regardless FiO2 0.6; breathing at set rate of
FiO2 (e.g. COPD,
breath until set tidal of effort, dyssynchrony 16 (or over) with VT ~400 for
I:E or flow asthma)
volume is reached MV of 6.4L”
AC/PC : variable flow (& VT) during “Pt is on Pressure Control of 18
Pinsp - Air leak (e.g.
Assist inspiration to satisfy pt (Pinsp) over 5 (PEEP), set at a
PEEP PTX)
Control/Pressure Flow demand, dyssynchrony rate of 16 breaths/min, and FiO2
RR - May trial in
Control: delivers a VT : can cause volutrauma as 0.3; breathing VT ~400, at set
FiO2 situations of vent
breath until set compliance or pt effort rate of 16 (or over) for a MV of
I:E dyssynchrony
pressure is reached changes 6.4L.”
PSV - Intubated for
: better tolerated, less
Pressure Support “Pt is on Pressure Support of 10 non-cardiac or
Pinsp I:E sedation, trial pre-extubation
Ventilation: delivers (Pinsp) over 5 (PEEP) with an lung failure (e.g.
PEEP Flow (e.g. SBT on 0/0 or 5/5)
set pressure FiO2 0.3; breathing VT of ~500 AMS)
FiO2 VT : control over parameters,
triggered by at 20 breaths/min. for a MV of - Weaning vent
RR (backup) RR volutrauma possible, no fixed
patient’s spont 10L.” - Severe met
RR (only backup)
breaths acidosis

MONITORING MECHANICS VENTILATOR MANEUVERS FOR

Parameter Target Evidence MO
ONN II TT O
ORR II N
NGG ME
ECCH
HAAN
N II C
CSS
ARDS: 4-8 ARDS: VT 6cc/kg had mortality and vent- o
o Inspiratory hold: end
Inspiratory hold: end inspiratory
inspiratory pause;
pause; measure Pplat
measure P plat
cc/kg PBW free days vs 12cc/kg (NEJM 2000;342:1301)  calculate ΔP, airway resistance, compliance
 calculate ΔP, airway resistance, compliance
Tidal Volume (VT) Non- Non-ARDS: VT 10cc/kg vs 4cc/kg  no Δ o Exp hold: end expiratory pause; quantifies autoPEEP
o
ARDS: 6-8 mortality or vent-free days (JAMA o 0.1: measures resp drive w/ neg pressure generated
o P0.1:
cc/kg PBW 2018;320:1872) by occluded insp, indep of muscle weakness, C, R
Plateau pressure ARDS: driving pressure a/w survival
<30
(Pplat) (NEJM 2015;372:747)
Driving pressure Non-ARDS: driving pressure not a/w 30d
<15
(ΔP = Pplat-PEEP) mortality (Crit Care 2019;23:424)
Compliance
>50 Maximizing O2 transport and minimizing
(VT/ΔP)
dead-space occurred at the greatest total
Airway Resistance
<10 static compliance (NEJM 1975;292:284)
(PIP-Pplat)

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Pulmonary & Critical Care Mechanical Ventilation

VENTILATOR COMPLICATIONS
• Dynamic hyperinflation (auto-PEEP): measured by end expiratory hold. Auto PEEP = end exp pressure – set PEEP
o Diagnosis: end-expiratory flow >0 due to incomplete alveolar emptying
o RFs: vent strategy causing hyperinflation (high RR, I:E ratio) or
obstructive disease (asthma, COPD, CF) 1Adapted from Medscape
o Consequences: adverse hemodynamic effects (HoTN secondary to
venous return), alveolar over-distention ( volu-/barotrauma); effort to
trigger breath
o Tx: longer exhalation (I:E ratio, RR), set exogenous PEEP to 2/3 auto-
PEEP, bronchodilators for obstruction
o If severe hemodynamic or resp. compromise, transiently disconnect pt
from ventilator and manually bag ventilate to allow deflation
• Ventilator-induced lung injury (VILI): alveolar injury alveolar permeability, interstitial & alveolar edema, alveolar hemorrhage,
hyaline membranes, & alveolar collapse (similar to ARDS) (NEJM 2013;369:2126). Avoid w/ lung protective ventilation (see ARDS).
o Volutrauma: over-distension of alveoli due to high VT; or, if there is heterogenous consolidation or atelectasis, a disproportionate
volume from each breath is delivered to open alveoli
o Atelectrauma: shear forces from cyclic alveolar recruitment and de-recruitment injure adj alveoli/airways
o Biotrauma: cytokine release from lung epithelium  multi-organ dysfunction
o Oxytrauma: FiO2 free radical production, lung injury
o Barotrauma: injury from high Pplat (highest risk >35)  PTX, subcutaneous emphysema, pneumomediastinum
•  Peak inspiratory pressure (PIP) = airway resistance + elastic resistance (Pplat). To troubleshoot, determine Pplat with insp. hold
o If normal Pplat (<30): airway resistance: bronchospasm, secretions/mucus plug, ET malposition/kink/biting, airway edema
o If elevated Pplat (>30): elastic pressure = ↓compliance
 Decreased functional lung size/overdistention: auto-peep, atelectasis, R main stem, ARDS, PNA, DAH, pulm edema
 Increased thoracic pressure: obesity, kyphosis, burns, abdominal compartment/ascites, effusions, PTX, Tberg position
 Parenchymal disease: ILD, post radiation
o Low PIP? leak in the system: bronchopleural fistula, ET cuff rupture/dislodge, tubing damage
• Other complications: VAP, laryngeal edema, tracheal stenosis, PTX
ALGORITHM FOR RESPIRATORY PLAN (REMIX)
R Reason for intubation ARDS, PNA, COPD, pulmonary edema, aspiration, hypoventilation, altered mental status, etc
E Exchange (gas exchange) Recent ABG; plan to improve PaO2 (i.e. diuresis, pulmonary vasodilators) and/or PCO2 (i.e. #RR)
M Mechanics Pplat, PIP, resistance pressure, elastic pressures; chest wall/respiratory muscle strength
I ID/infection Sputum cx data, abx day #, source control, need for bronchoscopy; assess for VAP
X eXtubation barriers Daily SAT/SBT, secretion clearance, mental status, planned procedures
(S) Sedation Current sedation, whether ∆ needed e.g. start dexmedetomidine/quetiapine as bridge peri-extubation

L I B E R A T I O N & E X T U B A T I O N : (ATS/CHEST: AJRCCM 2017;195:115; Chest 2001;120:375S; NEJM 2012;367:2233; ERJ 2007;29:1033)
• Requirements for extubation:
(1) adequately treated underlying disease and hemodynamic stability
(2) adequate oxygenation and ventilation: PaO2/FiO2 ≥150-200, PEEP ≤5-8, FiO2 ≤0.4-0.5, pH >7.25
 Rapid Shallow Breathing Index (RSBI) = RR/VT; RSBI >105 predicts extubation failure (Sn>Sp) (NEJM 1991;324:1445)
(3) ability to cough/manage secretions (ideally alert/following commands, but if protecting airway, AMS does not preclude extubation)
(4) +cuff leak. Absence of cuff leak is concerning for laryngeal edema  consider methylpred 20mg IV q4h 12hrs prior to
extubation or IV methylpred 40mg x1 4hrs prior or IV dexamethasone 5mg q6h (Eur J Anaesthesiol 2010;27:534).
• Liberation protocol: daily Spontaneous Awakening Trial (SAT) + Spontaneous Breathing Trial (SBT)
o SAT:  ventilator time, ICU LOS, & mortality if paired with SBT (NEJM 2000;342:1471; Lancet 2008;371:126)
o SBT: ~30-120min daily trials w min support (PEEP ≤5 on PSV)= vent time (NEJM 1996;335:1864; NEJM 1995;332:345)
Ways to fail: hypoxemia (SaO2 <90%, PaO2<60), hypercarbia (PaCO2  by >10), low VT, respiratory distress (HR, RR, HTN,
accessory muscle use, diaphoresis), arrhythmia, hemodynamic instability, anxiety/agitation, somnolence
Causes of SBT failure: underlying etiology not corrected, volume overload, cardiac dysfunction, neuromuscular weakness,
delirium, anxiety, metabolic abnormalities
• Extubation strategies:
o Extubation to NIPPV or HFNC in patients with hypercarbia / risk factors for reintubation, not done routinely   post-extubation
respiratory failure (Lancet 2009;374:1082; JAMA 2016;316:1565). HFNC w/ intermittent NIV post-extubation   reintubation
compared to HFNC alone (JAMA 2019;322:1465).
o If agitation is limiting ability to extubate, consider dexmedetomidine  may improve odds of extubation (JAMA 2009;301:489)
• Post-extubation respiratory failure: due to poor secretion clearance, CHF, aspiration, bronchospasm, laryngeal edema
o NB: no benefit to NIPPV as rescue therapy during post-extubation respiratory failure and may be associated w/ worse
outcomes (NEJM 2004;350:2454). Not recommended per ERS/ATS guidelines (ERJ 2017;50).
• Tracheostomy: usually performed once intubated for 14-21 days. Early tracheostomy (7 days) if expect intubation >14 days 
comfort, allows  sedation,  risk of tracheal stenosis,  vent-free and  ICU days, though no change in VAP rate (JAMA
2010;303:1483; Crit Care 2015;19:424; Br J Anaesth 2015;114:396)

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Pulmonary & Critical Care ARDS

PATHOPHYSIOLOGY OF ARDS
Direct lung injury: pneumonia, aspiration, inhalational injury, near drowning, pulmonary contusion; indirect lung injury: sepsis, trauma,
pancreatitis, drugs, burns, cardiopulmonary bypass/pump, transfusion-related acute lung injury (TRALI)
Ddx (ARDS Mimics): Eosinophilic PNA (AEP), acute interstitial PNA (AIP), organizing PNA
Pathway: diffuse, immune-mediated lung injury causing pulmonary capillary and alveolar epithelial damage leading to increased vascular
permeability, impaired gas exchange, and decreased lung compliance (NEJM 2017;377:562)

Global Definition for ARDS & Management Summary (AJRCCM 2024;209:37, AJRCCM 2024;209:24)
1) Onset or worsening within 1 week of insult
2) Not primarily due to hydrostatic/cardiogenic pulmonary edema
3) Imaging showing bilateral opacities on CXR/CT or bilateral B lines/consolidations on ultrasound
4) PaO2:FiO2 (P:F) ratio ≤ 300 or SpO2:FiO2 (S:F) ratio ≤ 315
A. Nonintubated: on HFNC ≥ 30L/min or NIV/CPAP ≥5cm H2O
B. Intubated: with PEEP ≥5cm H2O
C. Resource Limited: No minimum flow rate or PEEP required for Dx

Mild ARDS Moderate ARDS Severe ARDS

- P:F 200-300 or S:F 235-315 - P:F 100-200 or S:F 148-235 - P:F ≤100 or S:F ≤148
- Mortality: 27% - Mortality: 32% - Mortality: 45%

Mechanical Ventilation
Is the patient stable, tolerating NO
- VT 4-6cc/kg predicted body weight (PBW), Pplat ≤30, ΔP ≤15
NIV, P:F >200? - Optimal PEEP titration (see below)
- Maintain PaO2 55-80 mmHg or SpO2 88-95% with pH ≥7.25
YES
Continue noninvasive ventilation Is P:F ≤150?
NIPPV = HFNC YES
(Chest 2017;151:764)
1) Prone Consider VV
2) Paralysis if dyssynchrony Is P:F ECMO
3) Consider pulm vasodilator ≤80?

M A N A G E M E N T P R I N C I P L E S I N A R D S : (ATS/ESICM/SCCM: AJRCCM 2017;195:1253)

Strategy (in order of decreasing level of evidence) Effects
• Maintain oxygenation while preventing ventilator-induced lung injury (VILI)
Low Tidal Volume • VT 4-6 cc/kg PBW w/ goal Pplat ≤30, driving pressure (Pplat-PEEP) ≤15 mortality (31% vs
Ventilation (LTVV) o May allow Pplat if ascites, obesity, etc. as may not accurately reflect 39.8%) and vent-free
(NEJM 2007;357:1113) transpulmonary pressure (see “esophageal balloon catheter” on next page) days vs “traditional” VT
(NEJM 2000;342:1301) • Permissive hypercapnia: pH goal ≥7.20-7.25 permits lower VT to minimize VILI (12 cc/kg, Pplat <50)
o Contraind: ICP, RV fail./PH (pulm. vasoconst.), TCA/ASA o/d, pregnant
• Initiate within 36h in pts with P:F<150 on FiO2≥0.6, PEEP≥5cmH2O
Prone Positioning
• V/Q mismatch by compressive atelectasis from heart & diaphragm  more
(PROSEVA NEJM mortality (28d & 90d)
2013;368:2159) homogenous vent.  alveolar recruit.  regional volutrauma & compliance in mod/severe ARDS
(Chest 2023;163:533) • Contraind.: hemodynamic instability, ICP, inability to turn neck (fixed/unstable
C-spine), 2/3rd tri. pregnancy, recent sternotomy
• Minimize pulmonary edema, avoid ⊕ fluid balance after reversal of shock
Conservative Fluid ICU LOS & vent-free
Management • Dynamic assessment of volume responsiveness (i.e. pulse pressure variation,
days, no Δ in 60d
(NEJM 2006;354:2564) passive leg raise) (CCM 2017;45:1538)
mortality or AKI
• FACTT Trial: CVP<4 (conservative) vs. CVP ≤10-14 (liberal)
• Maximize recruitment, minimize trauma from cyclic atelectasis
Positive End-Expiratory
• Higher PEEP distributes VT over more alveoli  less over-distention  No clear mortality benefit.
Pressure (PEEP)
improves oxygenation (via V/Q mismatch and shunt fraction) & compliance Possible benefit for
(NEJM 2004;351:327)
• CV effects of PEEP: preload/SV, RV afterload varies, LV “afterload”, BP PEEP if P:F ≤200
(JAMA 2010;303: 865)
• Harms of PEEP: barotrauma, dead space, hemodynamic effects
Neuromuscular • oxygenation and VILI by vent dyssynchrony and chest wall compliance possible mortality &
Blockade • No survival benefit to routine early paralysis for mod-severe ARDS (P:F <150) as vent free days when
(ROSE NEJM compared to light sedation, possible mortality benefit when used for vent used for synchrony
2019;380:1997) synchrony or in early severe ARDS when deep sedation is otherwise required Risk: ICU-acquired
(AJRCCM 2024;209:24) • Can use as bolus/infusion to maintain vent synchrony in mod-severe ARDS weakness
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Pulmonary & Critical Care ARDS

S U M M A R Y O F R E S C U E T H E R A P I E S F O R H Y P O X E M I A (6 P’s of refractory hypoxemia)
• Pee: consider diuresis to reduce pulmonary edema (see “conservative fluid management” above)
• PEEP: optimize PEEP (see “PEEP” below)
• Prone positioning: should be implemented early (12-24h) if P:F <150 (or 200) despite optimal PEEP titration
o Maintain prone ≥16h. If supinate and P:F remains >150 (or 200) and ΔP ≤15 after 2h, can remain supine
• Pulmonary vasodilators: start with iNO trial (40ppm; up to 80ppm); if effective, use inhaled epoprostenol (Veletri)
o Should see at least 20% PaO2, otherwise do not continue therapy due to cost and risks, including hypotension
o V/Q mismatch by selectively dilating vessels that perfuse well-ventilated lung; also PVR and RV afterload
o No mortality benefit and risk of renal failure, but may improve oxygenation in first 24h and total lung capacity at 6mo (Cochrane
Rev 2016; Crit Care 2012;16:R36). NB: risk of methemoglobinemia w/ iNO, inhaled pulmonary vasodilators exhibit tachyphylaxis
• Paralysis: can be used to maintain vent synchrony (see “neuromuscular blockade” above), esp. when double triggering – permits
maintenance of LTVV. Now also conditionally recommended in early ARDS (<48h) w/ P:F <100 if already under deep sedation. Start
w/ intermittent boluses & transition to infusion if persistent dyssynchrony >3 boluses/2h (cisatracurium 0.1-0.2mg/kg q30min PRN 
0-5mcg/kg/min; rocuronium 0.6-1.2mg/kg q30-60min PRN  0-20mcg/kg/min, start at 8-12mcg/kg/min). Do NOT wean sedation
while under blockade (RASS goal -5 prior to initiation). Monitor depth of sedation with BIS (target 40-60)
• Perfusion (ECMO): for severe, refractory hypoxemia with P:F ≤ 80 +/- hypercarbia w/ pH <7.25 and pCO2 >60; see ECMO
LUNG PROTECTIVE (ARDSNET) VENTILATION
• Initial ventilator set-up: VT = 6 cc/kg PBW, RR to approximate baseline MV (RR <35), moderate PEEP (8-10)
• Adjustments: (also see Mechanical Ventilation)
Mechanical Ventilation Goals in ARDS
o Oxygenation: goal PaO2 55-80 mmHg or SaO2 88-96%
OX-ICU raised concern hyperoxia leads to mortality. However, recent studies Measure Goal
demonstrate equipose without clear beneficial target (ARJCCM 2021, PILOT) PaO 2 55-80mmHg
Oxygenation
 If persistent hypoxemia requiring FiO2 >~0.6, optimize PEEP (see below) SaO2 88-96%
o Mechanics: goal plateau pressure (Pplat) ≤30 & driving pressure (ΔP) ≤15 Plateau pressure (Pplat) ≤30
Mechanics
(obtain with inspiratory hold) Driving pressure (ΔP) ≤15
 If Pplat >30 and/or ΔP >15: VT by 1 cc/kg PBW (minimum VT 4 cc/kg pH 7.20-7.25 to 7.45
PBW); limit on ability to  is MV  pCO2 & pH
 If Pplat <25 and VT <6cc/kg PBW: can VT by 1 cc/kg until Pplat >25 or VT 6 cc/kg PBW
o pH: goal 7.20-7.25 to 7.45 (“permissive hypercapnia” unless contraindicated, lower boundary context dependent)
 pH below goal: RR (up to 35/min) until pH at goal or PaCO2 <25; watch for auto-PEEP development at high RR
 If RR = 30-35/min & pH goals not met: can VT (may cause Pplat >30)

OPTIMAL PEEP FOR ARDS

• ARDSNet FiO2/PEEP scale:
o If P:F <150 w/ PEEP 5cm H2O, assess ability to recruit lung by increasing NIH NHLBI ARDS Clinical Network Mechanical
PEEP from 5  15cm H2O Ventilation Protocol Summary
o If improvement, use ARDSNet high PEEP/low FiO2 scale; if no
improvement, use low PEEP/high FiO2 scale (see right)
• Best PEEP trial: select the PEEP corresponding to best global recruitment with
lowest risk for overdistention based on resp system compliance (CRS = VT /
[Pplat - PEEP])
o Keep VT constant and use decremental titration of PEEP; choose best
PEEP based on balance of highest compliance, lowest driving pressure
(<15), Pplat <30, acceptable oxygenation, and stable hemodynamics
• Driving pressure: ΔP = Pplat - PEEP (goal: ≤15)
o Represents the relationship between tidal volume and lung compliance (ΔP = VT/CRS)
o Lower ΔP associated with survival independent of other variables (VT, PEEP, Pplat) (NEJM 2015;372:747)
• Recruitment maneuvers (if hemodynamically stable):
o Used to open collapsed alveoli to tidal opening and closing (atelectrauma) and participation in gas exchange
o Begin with high PEEP to open up alveoli, then decremental PEEP titration to optimize mechanics (JAMA 2008;299:637)
o Outcomes are mixed w/  (JAMA 2017;318:1335) and mortality (low quality, Cochrane Rev 2016); avoid PIPs (>50)
o Strong recommendation against prolonged lung recruitment maneuvers in moderate-severe ARDS (AJRCCM 2024;209:24)
• Esophageal balloon catheter: estimates intrapleural pressure; used to calculate transpulmonary pressure (Ptp = alveolar pressure
[Pplat] - intrapleural pressure). PEEP then titrated to maintain optimal Ptp (<25 at end-inspiration to prevent VILI, 1-2 at end-expiration
to prevent atelectrauma) (NEJM 2008;359:2095)
o No effect on mortality, ventilator free days, or ICU days, despite improved oxygen and lung compliance, but risk of needing
advanced rescue therapy (JAMA 2019;321:846)
o Consider in cases of high intra-abdominal pressure (e.g., obesity, ascites, abdominal compartment syndrome)
STEROIDS FOR ARDS
• For indication & use in COVID-19, see MGH guidance (directory in Handbook), RECOVERY trial (NEJM 2021;384:693)
• Non-COVID-19 ARDS: suggested in ARDS but optimal regimen unknown (conditional rec, moderate certainty) (AJRCCM
2024;209:24) and there are conflicting data; Dexa-ARDS (Lancet RM 2020;8:267)  ventilator-free-days & mortality in mod-severe
ARDS. Other trials: possible benefit in early mod-severe ARDS, mortality if ARDS ≥14d (Chest 2007;131:954; NEJM 2006;354:1671)

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Pulmonary & Critical Care ECMO

T Y P E S O F E C M O (JACC 2014;63:2769) To call ECMO consult:
1. Venoarterial (VA, replaces heart and lungs): primarily cardiogenic shock - MGH STAT App
o Venous blood is removed, oxygenated, CO2 extracted, and reinfused in arterial system - Directory: type “ECMO
o Venous cannula in com. femoral vein (drainage from IVC or RA); arterial cannula in R fem. artery Consult” or p24252
2. Venovenous (VV, replaces lungs): manages hypoxemic resp. failure; relies on native cardiac output # 857-310-0335
o Venous blood is removed, oxygenated, CO2 extracted, and reinfused in venous system
o Either two venous cannulae (common fem. vein and SVC) or a bicaval dual lumen single cannula via R IJ that allows for mobility
Indications: Contraindications:
• Reversible acute resp failure (VV): e.g. ARDS, bridge to • Absolute (VA or VV): non-recoverable multi-organ
transplant or recovery failure/neurological disease; unwitnessed arrest/CPR >30min w/o
PaO2/FiO2 <80 despite optimization, unable to achieve safe ROSC; active severe bleeding; contraindication to AC, recent
inflation pressures (Pplat <30), CO2 retention (pH<7.25 w/ PCO2 NSGY procedure/active intracranial bleed (<10d)
> 60) with inability to mechanically ventilate. See ELSO. • Absolute VA: BMI>40; AoD; severe AI; ESLD/ESRD
• Reversible cardiogenic shock (VA): e.g. PE, cardiac arrest. • Absolute VV: severe right or left HF
Refractory low cardiac index (<2L/min/m2) & HoTN despite • Relative: age>70; multi-organ failure; severe pHTN; unknown
adequate volume, inotropes, & IABP. ECPR. neuro status; GVHD; active cancer; immunosuppression;
• Bridge to definitive therapy (transplantation, VAD, recovery) ventilated >7d; DIC; survival <30% (via RESP and SAVE scores)
ECMO VARIABLES
Drainage Cannula in large central veins (IVC, SVC, or RA) || Return Cannula in RA or Ao (depending on configuration)
• Sweep (aka gas flow, replaces ventilation (L/min)): sweep  PaCO2 in blood returning to pt therefore sweep requirements =
worsening ventilation vs  CO2 production (fever, infxn, renal failure). Controls O2 delivery if any. When sweep is weaned off or
“capped” in VV-ECMO, ECMO support for ventilation / oxygenation is also off.
• FdO2 (fraction delivered O2 in sweep gas flow): Generally set at 1.0
• RPM: Predominant determinant of blood flow (2-5L/min; >7LPM limited by membrane lung efficiency also affected by cannula size &
native CO). VV ECMO – based on BSA to estimate O2 consumption (BMI may limit candidacy), partially weaned. VA ECMO –
indicates % of CO support from ECMO, main weaning variable.
• Transmembrane Pressure (dP or ΔP = Ppre - Ppost): reflects oxygenator (membrane) function, trended daily
o  ΔP: check membrane for clots and ABG to assess impact on gas exchange. Check RPM (ΔP = BF x R so may reflect  flow).
o  ΔP: check ECMO circuit for kinks either at the inflow or outflow sites
• AC: UFH, follow PTT, Xa, AT-III. Goals: d/w attending/pharmacist
• Mechanical Ventilation: Pt may be placed on PC with low Pinsp to enable “lung rest.” Increasing spontaneous TV reflects
improvement in lung function/ability to wean circuit. Once lung function improved, wean sweep to assess ability to ventilate
endogenously, and from there can attempt to wean off VV-ECMO Surg Clin North Am 2022;102:23
C O M P L I C A T I O N S (Heart Lung Circ 2014;23:10)
• ECMO: clots (oxygenator, pump, tubing, hemofilter; 0.13-22%); cannula displacement (0.8-8%); air embolism, oxygenator
failure, pump failure. For emergencies, STAT page ECMO team.
• Patient: bleeds (access sites, ENT/Pulm/GI/GU, intracranial, hemolysis, DIC; 5.3-79%); neuro (ICH, stroke, seizure,
encephalopathy; 10-33%); limb ischemia (13-25%); infxn (17-49%; to help minimize this risk NO additional access placed after
ECMO placed- all labs drawn off circuit); AKI (30-58%); multi-organ failure (10%); cannular (4.8%)
TROUBLESHOOTING THE CIRCUIT
• Baseline lab goals: Hgb >7.5g/dL; plt >75K; fibrinogen >150; active T&S. Maintain SpO2 > 85% and PaO2 > 55.
• Chatter: shaking/sound caused by ⊝pressure in tubing; can be due to venous collapse, hypovolemia, thrombosis, tamponade,
other cause of CO, straining, kinking. Tx: volume resuscitation (usually albumin),  RPMs, cannula and/or repositioning
• Hypoxemia (as measured on patient ABG or sats):
a) Recirculation: blood travels from the outflow (return) catheter back into the inflow (drainage) catheter, bypassing body. Can be
NL if <25 % recirculation. If >25% or  consider catheter malposition. Dx: unexplained inflow O2 sat, BRB in drainage catheter Tx:
reposition cannula (10 cm apart) or switch to dual lumen cannula, RPM
b) Membrane failure: often due to excessive and/or abnormal clots/fibrin Dx: visual inspection of circuit with worsening hypoxemia
on outflow sat/ABG (PaO2<200 on 100% FdO2) or ΔP by 20 in 4hrs Tx: replace membrane
c) Shunt: occurs if native CO >> ECMO flow or w/ improving native CO (larger % of blood never travels through ECMO circuit and
is poorly oxygenated) Dx: hypoxemia on pt ABG/sats. Tx: RPM to flow. To  CO: fever, inotropes, ßB, CCB, phenylephrine
• Harlequin (North-South) syndrome (VA only): hypoxia of upper extremities R worse than L, heart, brain – can occur only when
fem. artery cannulated. Cardiac recovery, but poor lung fx  native CO (deoxygenated) pushes against oxygenated ECMO blood in
aortic arch leading to hypoxia of UE, brain, heart. Dx: low sats on R arm but normal sats on L (need R radial art line in VA ECMO) Tx:
add a venous return cannula/transition to V-AV ECMO (Heart Lung Ves 2015;7:320)
OUTCOMES
• Acute respiratory failure: 2 major studies show mortality, but unclear if from referral to ECMO center or ECMO itself: CESAR:
(Lancet 2009;374:135) & EOLIA: (NEJM 2018;378:1965) with similar mortality in COVID-19 ARDS Lancet 2020;396:1071)
• Refractory cardiogenic shock: ~40% discharge survival; time CPRECMO = best death predictor (CCM 2008;36:1404; ASAIO
2017;63:60)
ECPR: ECMO as extension of CPR in cardiac arrest. In-hospital cardiac arrest: survival (OR: 0.17) compared to CPR (CCM 2011;39:1);
OHCA; no difference between 30d outcomes with ECLS vs traditional therapy for out-of-hospital cardiac arrest (NEJM 2023;388:299) and
MI related cardiogenic shock (NEJM 2023;389:1286). Consider calling ECMO team if nearing 10 minutes w/o ROSC to discuss VA ECMO

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Pulmonary & Critical Care Sedation

GOAL O F I C U S E D A T I O N : addressing ICU triad of pain, agitation, & delirium (NEJM 2014;370:444)
1. Pain: common, energy expenditure; analgesia alone adequate in some (Lancet 2010;375:475)
2. Agitation: target light sedation in intubated pts; no benefit to non-sedation (NEJM 2020;382:1103)
3. Delirium: 16-89% ICU pts; a/w worse mortality, QOL, cognitive outcomes (NEJM 2014;370:444); risk w/ deep sedation, BZD use
(Intensive Care Med 2007;33:66; JAMA 2007;298:2644) RASS (Richmond Agitation Sedation Scale) (AJRCCM 2002;166:1338)
+4 Combative Overtly combative, violent, immediate danger to staff
+3 Very agitated Pulls or removes tube/catheters; aggressive
+2 Agitated Frequent, non-purposeful mvmt; fights ventilator
+1 Restless Anxious, but mvmt not aggressive or vigorous
0 Alert & calm†
-1 Drowsy† Sustained awakening to voice (≥10sec)
-2 Light sedation Briefly awakens w/ eye contact to voice
-3 Mod. sedation Mvmt or eye opening to voice but no eye contact
-4 Deep sedation Mvmt/opens eyes to physical stimulation but not voice
-5 Unarousable No response to voice or physical stimulation
†Goal for most pts w/o indication for deep sedation

A2F Bundle ↓mortality ↓delirium (Crit Care Med 2019;47:3)

A Assess, Prevent, and Manage Pain
Both Spontaneous Awakening Trials (SAT) and Spontaneous Breathing
B
Trials (SBT)
C Choice of analgesia and sedation
D Delirium: Assess, Prevent, and Manage
E Early Mobility
F Family engagement and empowerment

S E D A T I O N A G E N T S (SCCM: CCM 2018;46:e825)

Sedative-Hypnotics (Non-Benzodiazepine)
Propofol: GABA agonist Dose: 5-50 µg/kg/min (Max 83)
1st line Sedative. Earlier extubation, ICU LOS, & mortality vs BZDs (AJRCCM
2014;189:1383)
Onset/Duration: Fast on (30-60sec) Easily titratable. Often rapid awakening but
has “context-sensitive” T1/2 d/t ↑ lipid solubility. Duration prolonged by 1) long
infusion time, 2) ↑BMI, 3) adv. liver failure (hepatic metab.; still 1st line in ESLD)
Analgesia: None
Respiratory: Powerful resp. depressant  cannot use w/out ETT outside an OR.
CV: Powerful vasodilator & direct cardiac depressant ↓↓BP and ↓HR
• ICP & anti-seizure effects  use in EtOH w/d & status epilepticus.
• Monitor TGs with prolonged use. TG > 500  risk of pancreatitis
• Propofol Infusion Syndrome: Rare. ↑ Risk if >48h of gtt, ↑infusion rate. Rhabdo,
AGMA, ↓HR, LV dysfxn, HSM, Liver/Renal failure
Dexmedetomidine (Precedex): α2-agonist Dose: 0.2-0.7 µg/kg/min (Max 1.5)
Use as Early Adjunct: ↓delirium & earlier extubation (JAMA 2016;315:1460)
(Has EEG pattern most similar to natural sleep). (Anesthesiology 2015;123:937).
Onset/Duration: Slow on (5-10min, peak 15-30min). Slow off (>1-4hr). Therefore, less
versatile & less titratable vs. propofol.
Analgesia: Mild, unclear mechanism (use as adjunct, not primary analgesic).
Respiratory: Less resp. depression vs. other hypnotics  OK for non-intubated
patients in monitored setting (e.g., the ICU).
CV: Strong negative chronotropy, dose-limiting SEs = ↓HR & high-grade AVNB.
Less vasodilation/↓BP vs. propofol; but can see w/d & rebound HTN if abrupt d/c. Strategies for weaning sedation:
Assess daily for improving resp failure (↓FiO2,
• Falsely low BIS (interpret with caution in paralyzed patients)
PEEP, no NMB).
• Precedex Fever: idiosyncratic high-grade fever, resolves w/ drug d/c. MGH criteria for extended taper:
Ketamine: NMDA-antagonist Dose: 5-30 µg/kg/min Sedation > 7 days + P:F > 200 + transition to
Onset/Duration: Fast on (30-60sec). Slow off 2.5hrs; accumulates in renal/liver failure PS in 24-48h
Analgesia: Clinically relevant analgesia via anti-NMDA; synergistic w/ opioids. •↓BZDs ~20-25%/day  phenobarb or
Respiratory: Minimal Resp. depression. Bronchodilatory. ↑Secretions: caution lorazepam
peri-/post-extubation
•↓dexmed. ~20-25% q6h  clonidine q8-
CV: Indirect sympathomimetic: ↑HR + ↑BP in early illness/stable pts.
12h or patch
Direct negative inotrope: ↓BP in extremis/↓cardiac reserve (no longer offset by
endogenous catecholamine release). (Br J Anaesth 2021;127:23) • ↓opioids ~20-25%/day (taper last)  PO
opioid (methadone)
• Dissociation/nightmares if used w/out GABA agent. Higher risk in elderly.
• Falsely high BIS
• Epileptogenic. May p/w non-convulsive status. Avoid if seizure risk.
• DILI: ALT>AST rise first, then ALP. ↑ risk w/ chronic EtOH. Monitor daily LFTs.

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Pulmonary & Critical Care Sedation

S E D A T I O N A G E N T S (continued)
Opioid Analgesics (as a class): μ-opioid agonists
Analgesia: All are strong analgesics. No amnestic effects. Tolerance & w/d w/ prolonged use (~10-14d) and/or abrupt d/c.
Respiratory: All are respiratory depressants and synergistic with most other sedatives.
CV: All are sympatholytic, but most have limited direct cardiovascular effects  less ↓BP & less ↓HR vs. propofol.
• As a class, opioids frequently can cause constipation/Ileus.
Hydromorphone Dosing – gtt: 0.5-5mg/hr, bolus: 0.25-1mg q1-q3hr,
Onset/Duration: Intermediate onset (5 min), Intermediate duration (T1/2 = 3-4h). Fewer renal metabolites vs. morphine/oxy.
• Less adipose accumulation vs. Fentanyl & Morphine  preferred agent for treatment duration > 24h.
• Quick onset + short T1/2 (vs. morphine) = can be useful for procedural sedation, though less titratable than fentanyl.
Fentanyl Dosing – gtt: 50-250mcg/hr, bolus: 25-100mcg q30-60m,
Onset/Duration: Fast on (1 min), Context-sensitive T1/2 (↑ lipid solubility)Bolus T1/2: 1-3h vs. gtt T1/2: 9-16h. No renal metabolite.
• Adipose accumulation  delayed awakening. Avoid gtt if need frequent neuro checks (bolus may be useful)
• Rapid onset + short T1/2 (if context is short treatment duration) = useful for procedural sedation.
Morphine Dosing – gtt: 2-30mg/hr, bolus: 2-4mg q1-q4hr
Cheaper, but generally less preferred agent. Fewer ventilator-free & ICU-free days vs. fentanyl (AJRCCM 2021;204:1286)
Onset/Duration: Slower on (5-10 min) & long-acting (T1/2 = 3-5h). Accumulates in renal failure  avoid if CrCl < 30mL/min.
Respiratory: Histamine release can cause/exacerbate bronchospasm  Avoid in reactive airway disease.
CV: Both longer duration of effect and vasodilatory SEs d/t histamine  prefer Hydromorphone or Fentanyl if HDUS.
• Histamine release  pruritis, urticaria, flushing.
Benzodiazepines (as a class): GABA agonists
Avoid whenever possible: BZDs Mortality, time to light sedation & extubation, & delirium
Analgesia: None. || Respiratory: Resp. depression at higher doses. Synergistic w/ opioids: be cautious w/ co-administration.
CV: Sympatholytic and synergistic w/ opioids. Be cautious in acutely unstable patients unless prepared to intubate.
Midazolam (Versed): Dosing – gtt: 2-8mg/hr, bolus: 0.5-4.0mg (> 2mg more likely to → apnea), 2mg IV = 5mg IM
Onset/Duration: Bolus = Fast on (<1 min) & Fast off (bolus lasts 1-2h). Gtt accumulates in liver/renal failure and in adipose.
• CYP3A4 substrate: many drug-drug interactions (e.g., fluconazole, macrolides, Flagyl, amiodarone)
• Rapid onset + short T1/2 (if context is short treatment duration) = useful for procedural sedation
Lorazepam (Ativan): Dosing – (only) bolus: 0.5-2.0mg, IV=PO, Ativan 1mg ≈ 2mg Midaz ≈ 6mg Diazepam
Onset/Duration: Bolus = Fast on (1-2 min) but longer-acting (6-8h). Not renally cleared.
• Propylene glycol (solvent) toxicity w/ ↑dose (p/w ↑lactate, ↓BP, arrhythmia, AGMA)
• Longer T1/2 = ↑accumulation risk, particularly with shorter bolus intervals
Adjunct Agents: Dopamine Antagonists: Quetiapine (50mg q6-12h, max 400mg/d), Haloperidol (2.5-5mg IV q4-8h), Olanzapine
(2.5-5mg). SEs: ↑QTc  risk of TdP; ↓gastric motility; extrapyramidal effects, NMS (rare, but an emergency) – high fever, “lead pipe”
paralysis, hyporeflexia, Rx = dantrolene (takes a long time to prepare).
Neuroleptics: Valproate (10-15 mg/kg, max 60mg/kg/day). Many serious SEs: DILI (boxed warning); severe pancreatitis (boxed
warning); multiple cytopenias: ↓PLTs, aplastic anemia, neutropenia, acquired vWD; SJS/TEN and DRESS.
Barbiturates: Phenobarbital (consult pharmacy for dose). Highly effective anti-seizure & ↓ICP; CYP450 inducer (many drug-drug
interactions); many serious SEs: CNS depression, respiratory depression, hypotension, bradycardia, SJS/TEN

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Pulmonary & Critical Care Shock

O V E R V I E W (NEJM 2013;369:1726)
• Definition: state of tissue hypoxia due to decreased or dysregulated oxygen delivery or extraction, resulting in end-organ damage
• Clinical manifestations: hypotension (SBP <90mmHg or SBP >40mmHg from baseline); end-organ dysfunction: oliguria (UOP
<0.5cc/kg/h), AMS, metabolic acidosis (± anion gap, lactate, bicarb 2/2 renal failure); cool & clammy vs. warm & flushed
extremities. (Any of these can be normal—including BP—in a patient in shock, so a high index of suspicion is needed)
• Initial workup: focused H&P, ensure access, review meds, ECG/CXR, ABG/VBG, CBC/diff, CMP, TnT, lactate, CVO2, monitor UOP
MAP: determined by CO (cardiac output) & SVR (systemic vascular resistance) Lactic Acidosis (NEJM 2014;371:2309)
MAP = RAP + CO x SVR SVR determined by vessel Type A: tissue Type B: NOT marked tissue
diameter/length and blood viscosity hypoperfusion, typical hypoperfusion. Metformin,
in shock; can be cancer (e.g. Warburg), EtOH,
SV determined by preload,
(2/3) DBP + (1/3) SBP HR x SV profound iso bowel thiamine, albuterol, D-lactate,
afterload, & contractility mitochond dysfunc., liver dz
ischemia, necrosis

ETIOLOGIES OF SHOCK
Signs of CO: SHOCK Signs of CO:
- Widened pulse pressure - Narrow pulse pressure
- Low diastolic BP
CO CO - Cold extremities
- Warm extremities - Slow cap refill
- Normal cap refill

Distributive (66%) Hypovolemic (16%) Cardiogenic (16%) Obstructive (2%)

Pathophys. SVR & altered oxygen extraction cardiac output  inadequate oxygen delivery
Sepsis/SIRS, anaphyl., adrenal insuff., Hemorrhagic, GI losses, MI, HF, myocarditis, severe
Extra-cardiac causes: PE,
Examples liver fail., tox/med, neurogenic (NEJM 3rd spacing (pancreatitis) valve disease,
tension PTX, tamponade
2013; 369:840; NEJM 2001;345:588) (NEJM 2018;378:370) arrhythmias
Extremities Warm and dry Cold and dry Cold and wet Cold and dry
CVP/PCWP (Preload) /normal  (< 5 mmHg) (> 7 mmHg) /normal
/normal   
CO or CVO2 (Can be low pre-resuscitation) (<70%) (<70%) (<70%)
SVR (Afterload)    
Tamponade: pericardial
Normal chamber size, normal/ Small chambers, Large chambers, poor
TTE Findings contractility normal/contractility contractility
effusion
PE/PTX: dilated RV
GENERAL CONSIDERATIONS (ANY ETIOLOGY)
• Vasoactive agents (Vasopressors): titrate MAP >65 mmHg (cardiogenic MAP >60 mmHg); acidosis = vascular response to pressors
• Ventilatory support: intubate if necessary (concomitant respiratory failure, unable to compensate for metabolic acidosis, marked
hemodynamic instability) with pressors available; SpO2 may be unreliable due to peripheral vasoconstriction, use ABG
• PA catheter: no mortality/LOS/cost benefit in unselected ICU or CHF pts (Cochrane Rev 2013; JAMA 2005;294:1625; Lancet 2005;366:472)
• Steroids: known adrenal insufficiency / chronic steroids, stress-dose steroids (hydrocortisone 50mg q6h / 100mg q8h x5-7d)
• Bicarbonate: if pH <7.1 or <7.2 w/ severe AKI, can use bicarb amps or bicarb gtt. No mortality benefit except in AKI (Lancet 2018;392:31)
• Refractory Shock: Consider: dynamic LVOT obstruction (due ↑inotropy), anaphylaxis, abdominal compartment syndrome, abdominal
catastrophe (can be masked by steroids), new obstructive shock (HOCM/PE), and refractory vasodilation
• Rescue therapies: hydroxocobalamin (NO scavenger), methylene blue (reverse NO mediated vasodilation), thiamine, ECMO
DISTRIBUTIVE SHOCK
Septic Shock (see Sepsis); Anaphylactic Shock (see Anaphylaxis); Neurogenic Shock: Suspect if hypotension is in the context of TBI
or SCI. Fluid resuscitate with NS, not LR (slightly hypotonic and will worsen edema in TBI), watch for signs of increased ICP
HYPOVOLEMIC SHOCK
• Access: obtain 3 IVs (16G or less) if possible. Consider Cordis for rapid infusion; TLC, PICC cannot resus. as quickly
• Etiology: poor PO, GI (vomit/stool/fistula), GU (osmotic diuresis/diuretics, hypoaldo, salt wasting), burns, heat stroke, third spacing
(pancreatitis, low albumin, trauma), hemorrhage (trauma, surgery, GIB)
• Fluid resuscitation: Crystalloid boluses (LR>NS) unless hemorrhagic shock, then use minimal necessary to bridge to blood availability
Management of Major Bleeding: obtain STAT coags, CBC, fibrinogen, iCa2+. Ensure access. Hold pressure. Correct coagulopathies and
consider AC reversal (see AC Management). If INR >2, use 4F-PCC (unless ESLD, no INR goal); Plt <50, transfuse plts; fibrinogen <100,
use cryoprecipitate. If iCal < 1.10, give IV Ca.
o If suspect bleed secondary to variceal bleeding, administer octreotide for splanchnic vasoconstriction (see UGIB)
o If surgical/trauma/gyn, consider TXA (1g IV over 10 min → 1g over 8h) or aminocaproic acid (5g IV over 1hr → 1g per hr x 8hr)
• Resus: Transfuse to hemodynamics if bleeding is driving shock. Call for Emergency Blood or Massive Transfusion (see MTP)
• Obtain source control: Call surgery/vascular/GI/IR/ pending location of bleeding. Obtain STAT CTA if stable.
CAR D I OGE N I C SHOCK
• Cardiomyopathic: Ionotropic support with dobutamine, 2-5 mcg/kg/minute, diuresis. In MI, revascularization w/ PCI or CABG.
• Arrhythmogenic: Tachyarrhythmia: synchronized DCCV, vagal maneuver, adenosine, βB. Bradyarrhythmia: atropine, pacing.
• Mechanical: (e.g. due to acute valvular insufficiency). Hemodynamic support, endovascular or surgical intervention.
OBSTRUCTIVE SHOCK
Relief of obstruction is primary management strategy (see Tamponade) (see PE)
• PTX: O2, needle decompression or chest tube placement); Avoid mechanical ventilation or BIPPV
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Pulmonary & Critical Care Sepsis

OVERVIEW
• Definitions: updated in 2016 by Sepsis Definitions Task Force (Sepsis-3) (JAMA 2016;315:801) qSOFA
o Sepsis: life-threatening organ dysfunction (SOFA score ≥2) from dysregulated host response to infection 1. RR>22
o Septic shock: sepsis + (1) pressors to sustain MAP >65 AND (2) lactate >2 w/o hypovolemia 2. AMS
• SIRS may reflect appropriate host response. SIRS + infectious source not sensitive for sepsis (NEJM 3. SBP≤100
2015;372:1629)
Sequential Organ Failure Assessment (SOFA) score: includes PaO2/FiO2, plts, bili, BP, GCS, Cr/UOP
o qSOFA ≥2 can be used to identify pts outside ICU w/ suspected infection likely to have poor outcomes (ICU LOS, mortality)
o Surviving Sepsis Campaign guidelines recommend against qSOFA vs other screening tools as single-screening tool for sepsis
and septic shock (Crit Care Med 2021;49:e1063)

P A T H O P H Y S I O L O G Y / C L I N I C A L M A N I F E S T A T I O N S (NEJM 2013;369:840; BMJ 2016;353:i1585)

• Microbial components bind immune cells  inflammatory mediators, PMN migration; if exceeds boundaries of local environment 
sepsis (generalized inflammatory response)  tissue ischemia (thrombosis in microcirculation 2/2 altered coag., RBC deformability
 O2 extraction), cytopathic injury (mitochondrial dysfunction), impaired endothelial barrier ( edema)  organ dysfunction
Cardiovascular Vasodilation  hypotension; ventricular function may be either hyperdynamic or depressed
Pulmonary Pulmonary edema, ARDS
GI intestinal permeability  bacterial translocation  worsening systemic inflammation
Hepatic Cholestasis (“sepsis-induced cholestasis”), impaired reticuloendothelial function
Renal AKI of multifactorial etiology, including microvascular dysfunction, oxidative stress, global hypoperfusion
Hematologic Early inflammation, late immunosuppression; procoagulant and anticoagulant disequilibrium: DIC, plt
Endocrine Altered glycemic control, adrenal dysfunction, sick euthyroid syndrome
Neurologic Encephalopathy

I N I T I A L M A N A G E M E N T (2021 Surviving Sepsis: Crit Care Med 2021;49:e1063)

Sepsis & septic shock are medical emergencies, so early recognition is critical. Components of initial management include:
1) Antibiotics: administer empiric broad spectrum IV antibiotics ideally within one hour of recognition. Order STAT.
• Delay  mortality by 7.6%/h (CCM 2006;34:1589; CCM 2010;38:1045). More rapid abx  mortality (NEJM 2017;376:2235)
• Abx selection: guided by infection site, prior micro, community resistance patterns, exposures (SNF, lines, hx abx), host immunity
o Consider double coverage of PsA if known/suspected PsA infection w/: severe sepsis/septic shock, bacteremia in neutropenic pt,
burn pt, or otherwise high incidence of resistance to chosen class (10-15%). Usually β-lactam + (FLQ or aminoglycoside)
o For ESBL organisms in non-GU infections, carbapenems are preferred to pip-tazo despite micro sensitivity (JAMA 2018;320:984)
o If there is suspicion of toxic shock syndrome, add clindamycin or linezolid for anti-toxin effect (& more staph/strep coverage)
o If RFs for invasive Candida infection (neutropenia, chemotherapy, transplant, indwelling catheters, TPN, recent major surgery
[esp. abdominal], prolonged admission/abx), consider empiric antifungals (typically micafungin)
• β-lactam Administration: After load, extended or continuous infusion of beta-lactams is recommended (Lancet Infect Dis 2018;18:108)
• De-escalation: once causative organism identified, Δ to narrowest effective agent, w/ duration individualized to pt/etiology/trajectory
o Procalcitonin may be useful in guiding cessation (Lancet 2010;375:463; Lancet ID 2016;16:819; CCM 2018;46:684)
2) Resuscitation: initial resusc. with crystalloid completed w/in 3 hours (~30 mL/kg in most pts,  caution w/heart/renal failure)
• Balanced crystalloids (e.g. LR) with mortality and renal impairment in critically ill adults compared to NS (NEJM 2018;378:829); no
mortality benefit to colloids (NEJM 2004;350:2247; JAMA 2013;310:1809; NEJM 2014;370:1412)
• Targets of resuscitation: lactate clearance (normalization or >20%/2h) (JAMA 2010;303:739); cap. refill (<3s) (JAMA 2019;321:654)
• After the initial resuscitation effort, further fluid administration should be guided by dynamic measures of fluid responsiveness (see
table below). Lack of volume responsiveness  use/increase vasopressors instead
• Mortality similar between restrictive vs liberal fluid strategies (NEJM 2022;386:2459; NEJM 2023;388:499)

A S S E S S I N G F L U I D R E S P O N S I V E N E S S (JAMA 2016;316:1298)
Method Fluid responsive if:
Pulse pressure variation: validated in mechanically
PPV ≥13%
ventilated w/ VT ≥8cc/kg, not spontaneously triggering
If on ascending portion of
ventilator, & in NSR (Crit Care 2014;18:650)
Starling curve, sensitive to Δs
Mech ventilation = pos. pressure during inspiration 
in preload. Volume responsive
venous return & RV preload  LV filling/output
pts will show larger variations in
 PPmax in inspiration, PPmin in expiration
PP or SV during resp cycle
PPV = (PPmax- PPmin)/PPmean
Passive leg raise: raise legs to 45° w/ torso horizontal x1min in any mech.
PP ≥10% (surrogate for SV
ventilated pt  “autotransfusion” of ~250-350cc; assess Δ in hemodynamics
if no invasive measure of CO)

Fluid challenge: bolus 250-500cc fluids; check CVP before & immediately after, if  ≥2, adequate Improved hemodynamics, UOP,
volume challenge lactate; PP ≥10%

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Pulmonary & Critical Care Sepsis

INITIAL MANAGEMENT CONTINUED
3) Vasopressors: target a mean arterial pressure (MAP) of >65mmHg (NEJM 2014;370:1583) (see Vasopressors for full details)
NOTE: permissive hypotension (MAP goal >60) reduces vasopressor use and may be appropriate in select patients (JAMA 2020;323:938).
• Norepinephrine (“levo”): first choice vasopressor
• Vasopressin (“vaso”): add when NE at 5-15mcg/min to kidney function. Not titrated, on or off at 0.04U/min (NEJM 2008;358:877)
• Epinephrine (“epi”): recommended when 2nd or 3rd agent is needed; consider trial when NE escalating >25mcg/min
• Phenylephrine (“neo”): recommended primarily when (a) NE is associated with serious arrhythmias, (b) CO is high & BP persistently
low, (c) NE + vaso have failed to achieve MAP target at >25mcg/min and pt is tachycardic (d) hypotension a/w AFRVR
• Dopamine: reserved for highly selective patient population with bradycardia and low risk of tachyarrhythmia; a/w risk of
arrhythmias/mortality in all-comers (CCM 2012;40:725; NEJM 2010;362:779)
• Methylene blue: used in refractory distributive shock, AE: risk of hemolytic anemia in pt with G6PD deficiency, serotonin syndrome in
pts on serotonergic meds)
• Hydroxycobalamin: used in refractory distributive shock, similar mechanism of action as methylene blue
• Angiotensin II: not currently avail at MGH; ATHOS-3 trial (NEJM 2019;377:419)
4) Source Identification and Control Where to draw blood cultures?
• Cultures: obtain cultures prior to antimicrobials (unless will significantly Drawing cultures from vascular access devices
delay administration) as Sn (Annals 2019;171:547). Get at least 2 sets of BCx can lead to high rates of false positives. Obtain
with at least one drawn percutaneously (see Bloodstream Infections) cultures from vascular access devices only
o Consider 1,3 beta-D-glucan, galactomannan, and/or cryptococcal Ag if if concerned for CRBSI (rigors with infusion,
concerned for fungal infection erythema/induration around line site); otherwise
• Identify conditions that require source control: necrotizing soft tissue infection, obtain only peripheral blood cultures
abscess, cholangitis, cholecystitis, GI perforation/ischemia, pyelo a/w
obstructive renal stone or abscess, empyema, septic arthritis, devices
• Low threshold to obtain cross-sectional imaging to identify infectious source

OTHER ASPECTS OF MANAGEMENT

Corticosteroids
• Rationale: critical illness affects HPA axis, may cause relative “critical illness-related corticosteroid insufficiency” (CIRCI)
• Conflicting evidence regarding mortality benefit of corticosteroids in septic shock: “Annane/French trial” (JAMA 2002;288:862) mortality
w/ IV hydrocort 50mg q6h + fludrocort 50mcg/d x7d in pts w/ septic shock, replicated (NEJM 2018;378:809), others showed no
Δmortality (NEJM 2008;358:111; JAMA 2016;316:1775; NEJM 2018;378:797). Fludrocortisone + hydrocortisone > hydrocortisone alone
(JAMA Intern Med 2023;183:451)
• CAPE COD trial showed mortality benefit for patients hospitalized with severe bacterial CAP (NEJM 2023;388:1931)
• Consider hydrocort 50mg q6h or 100mg q8h (≤400mg/d) + 0.1 mg fludrocort in septic shock with ongoing vasopressor
requirement (e.g., NE >15-25 mcg/min) (Crit Care Med 2021;49:e1063; Crit Care Med 2024)
AKI
• Timing: no mortality benefit to early (<12h) vs delayed (>48h) initiation of RRT in patients with septic shock and severe AKI
without urgent indication (NEJM 2018;379:1431; NEJM 2016;375:122; NEJM 2020;383:240)
• Modality: CVVH and HD are largely equivalent for treating AKI, but CVVH minimizes fluid shifts in hemodynamically unstable patients
Metabolic Acidosis/Lactic Acidosis
• Ultimately, need to correct underlying etiology. Can temporize with bicarbonate if:
o Severe acidemia w/ pH <7.1: used as cutoff as evidence in animal/tissue studies of myocardial depression, catecholamine
efficacy, arrhythmias, though generally not replicated in human studies & pts w/ DKA can have pH <7 w/o these effects
o Less severe acidemia (pH <7.2) w/ AKI: BICAR-ICU  NaHCO3 gtt to keep pH >7.3 (≤1L/24h) mortality (Lancet 2018;392:31)
• Bicarbonate administration: 1 amp = 50mEq/50mL (or 8.4%); or infusion of solution of 150mEq (3 amps) in 1L of D5W
o Caution: HCO3  pCO2 that must be ventilated off, so must have sufficient resp. drive/be intubated. Also  iCa
Transfusions
• Transfusion goal of Hgb 7g/dL unless cardiac ischemia or active hemorrhage (NEJM 2014;371:1381)

INTERVENTIONS WITHOUT CLEAR BENEFIT

Vitamin C
• Rationale: Vitamin C is an antioxidant; may also act synergistically with hydrocortisone and thiamine to inflammation
IV Vitamin C associated w/mortality and organ dysfunction compared to placebo in adults w/sepsis (NEJM 2022;386:2387).
Short-Acting Beta Blockers
• Rationale: β-blockade may attenuate harmful effects of sympathetic adrenergic response in septic shock
• Controversy: single RCT mortality in pts w/ septic shock w/ esmolol to keep HR 80-94 (JAMA 2013;310:1683), but control group
mortality rate (80.5%). Subsequent RCT of landiolol in septic shock did not demonstrate mortality benefit, and point estimate
favored standard care group (37.1% vs 28.6%) (JAMA 2023;330:1641)
• Conclusion: need further validation of findings; short-acting beta blockers not routinely used in septic shock

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Pulmonary & Critical Care Vasopressors

Category
Name α β1 β2 D PVR SVR CO α1: vasoconstriction, duration of heart contraction
Phenylephrine 5+ 0 0 0 2+   α2: sedation/analgesia, vasoconstriction (if
Vasoconstrictors peripheral) vs vasodilation (if central, e.g. clonidine)
Vasopressin V1 ±  -/
Norepinephrine 4+ 2+ (+) 0 1+   β1: inotropy, chronotropy
Dopamine (low) 0 1+ 0 2+ ± -/  β2: vasodilation
Inoconstrictors Dopamine (med) 1+ 2+ 0 2+ ±   D: renal/splanchnic/coronary/cerebral vasodilation
Dopamine (high) 2+ 2+ 0 2+ ±   V1: vasoconstriction (especially splanchnic)
Epinephrine 4+ 3+ 2+ 0 1- -/ 
Dobutamine (+) 3+ 2+ 0 1-   Access: Ideal access is central (CVC, IO)
Inodilators Temporize w/ peripheral levo (<15 mcg/min) or neo
Milrinone PDE inhibitor 2-  
(<150 mcg/min) for <72 hrs. Requires PIVx2, <20G
Chronotrope Isoproterenol 0 3+ 3+ 0 0   w/ blood return in upper extremity AC or more prox.
Pressor Initiation/titration: Start when SBP drops by >30 or MAP <65 WITH Check q2h given risk of extravasation (policy). If
end-organ dysfunction despite optimization of volume status. Monitor MAP, UOP, extravasation, draw back any infusing medication,
mentation to titrate pressor dose. Responsiveness may decrease over time. give phentolamine 5-10mg in 10cc NS directly into
*Subcutaneous medications may ↓effectiveness due to ↑vasoconstriction. area of extravasation, apply dry warm compress.

V A S O P R E S S O R S & I N O T R O P E S (Circulation 2008;118:1047)

Name Mechanism Uses Side effects Dosing
α1 > β1 agonist: Initial: 2-12mcg/min
Norepinephrine (NE) SVR, CO Septic shock (1st) Arrhythmia, ↑LVOT (0.1-0.15mcg/kg/min)
Levophed Reflex brady from Cardiogenic shock (1st) Digital ischemia PIV: <10mcg/min
“Levo” vasodilation can negate Hypovolemic shock (1st) FSBG Max: 35-100mcg/min
HR from chronotropy (0.75mcg/kg/min)
Initial: 50-180mcg/min
Phenylephrine Septic shock if HR from NE Reflex bradycardia (0.5-2mcg/kg/min)
Pure vasopressor
Neosynephrine or CO w/ BP or 3rd agent needed CO, PAP, SVR PIV: <150mcg/min
α1 agonist:  SVR
“Neo” AFRVR, HOCM, AS, RV failure Digital ischemia Max: 360-1000mcg/min
(6mcg/kg/min)
Septic shock (2nd), add when NE 5-15
mcg/min (mortality vs. NE alone) (NEJM Coronary ischemia Usual: 0.04U/min
Vasopressin V1 agonist: SVR Consider when NE 5-15
2008;358:877) Mesenteric ischemia
Pitressin V2 agonist: renal H2O
Anaphylaxis (2nd) (especially high dose)
“Vaso” reabsorption
Pulmonary HTN/RV failure Na Max: 0.08U/min
Hepatorenal syndrome (only as salvage therapy)
Low: β1 > β2 > α1: ACLS (1st) HR, arrhythmias, ↑LVOT
Epinephrine Anaphylaxis (1st) Myocardial ischemia Low: 1-4mcg/min
VASOPRESSORS

CO, neutral SVR

Adrenalin Symptomatic bradycardia (2nd) lactate
“Epi” High: α1 > β1 > β2: Septic shock splanchnic SVR
CO, SVR High: 5-35mcg/min
Bronchospasm FSBG
Low: D1 > β1: Symptomatic bradycardia
CO, UOP Tachyarrhythmia Low: 1-2mcg/kg/min
Septic shock w/ bradycardia
Dopamine Myocardial ischemia
Med: β1 > D1:
Intropin BP (low dose)
CO, SVR mortality vs. NE in septic (CCM Med: 5-10mcg/kg/min
“Dopa” PCWP, pulm shunt
High: α1 > β1 > D1: 2017;45:486) & cardiogenic shock (NEJM
FSBG
SVR 2010;362:779) High: 10-50mcg/kg/min
Refractory vasoplegia in distributive shock Falsely SpO2 Arrhythmias
Post-cardiopulm bypass PVR Initial: 1-2mg/kg
NO and cGMP, smooth Amlodipine overdose Rash, hemolysis, serotonin
Methylene
muscle tone: Metformin overdose syndrome
blue
SVR Methemoglobinemia  in G6PD
Max: 5mg/kg
Early MB decreased vasopressor time in Avoid in severe PH (PA
septic shock (BMC 2023;110) pressure)
Refractory septic shock
Angiotensin II ANG-II agonist: SVR Peripheral ischemia 10-20ng/kg/min; max 40
(NB: not available at MGH)
IV form of Vitamin B12
Tx of vasoplegia refractory to methylene Urine discoloration Initial: 5g over 15 minutes
NO synthase inhibition
Hydroxocobalamin blue treatment (or if methylene blue Interference w/ many labs (Clin Max: 30g in 24 hrs
Modifies H2S (NO and
contraindicated) Biochem 2021;91:31)
smooth muscle activity)
BP, HR Initial: 0.5-1mcg/kg/min
Dobutamine
β1, β2 > α1 agonist: Cardiogenic shock Arrhythmias (2.5 if more severe)
Dobutrex
CO, SVR Sepsis + LV EF (add to NE/vaso) Myocardial ischemia
“Dobuta” Max: 20-40mcg/kg/min
Tachyphylaxis
INODILATORS

PDE inhibitor (cAMP), Hypotension Initial: 0.125mcg/kg/min

Milrinone Cardiogenic shock
inotropy, vasodilation: Arrhythmias
Primacor RV failure (PVR, LVEDV)
CO, PVR/SVR Myocardial ischemia Max: 0.75mcg/kg/min
BP, HR Initial: 2-10mcg/min
Isoproterenol β1 = β2 agonist: Symptomatic bradycardia Arrhythmias (can bolus 2-6mcg first)
Isuprel HR, SVR Mg-refractory torsades de pointes Myocardial ischemia
Max: 30mcg/min
Flushing, anxiety
Cassandra Fiorino
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Pulmonary & Critical Care Toxicology

Tox resident pager 21827 • Poison Control 1-800-222-1222 • MGH Lab Tox Screen Guru: Dr. Jim Flood
Drug/Toxin Presenting Symptoms Diagnostic Workup Management
Anticholinergic Mydriasis, hyperthermia, sweating,
Supportive, cooling for hyperthermia; charcoal
Atropine, Benztropine, (1g/kg, max 50g) if <1h, BZDs for agitation &
flushing, delirium, urinary retention, Hx, EKG, CPK
Scopolamine, seizure, physostigmine if severe (ICU,
ileus, tachycardia, HTN
Diphenhydramine atropine at bedside; not for TCA ODs)
100% O2 (avoid succinylcholine for intubation),
“DUMBBELLS”: Diaphoresis/Diarrhea,
Cholinergics Urination, Miosis/Muscle spasm, ABG, EKG, BMP, CPK,
atropine (2-5mg, redose to effect q3-5min, no
Organophosphates, effect on muscular symptoms); pralidoxime
Bronchoconstriction/Bronchorrhea, lactate. Can monitor RBC
carbamate (30mg/kg over 30min8-20mg/kg/h. Only for
Bradycardia, Emesis, Lacrimation, AChE inhibitor if available
insecticides, nicotine organophosphate toxicity), benzodiazepines
Lethargy, Salivation/Seizure
for seizure
Toxidromes

Sympathomimetics Agitation, mydriasis, hallucinations,

IV BZDs, atypical antipsych, cooling. if
Amphetamines, paranoia, tachycardia, HTN, EKG, BMP, lactate, CPK,
refractory agitation, avoid succinylcholine and
MDMA, cathinones diaphoresis, hyperthermia, piloerection, LFTs, coags
ketamine
“bath salts” seizure, vasospasm, ACS
Neuroleptic Search for causative agent.
AMS, “lead pipe” rigidity, sialorrhea, D/c causative agent (restart dopamine if
Malignant hyperthermia, dysautonomia,
CPK (), CBC (WBC),
DCd), IVF, cooling blanket, nitroprusside for
Syndrome (NMS) LDH, LFTs, BMP, serum Fe
diaphoresis HTN, BZD for agitation. Dantrolene,
Dopamine blockade, (often ); consider brain
Typically no N/V/D or hyperreflexia bromocriptine, amantadine
dopaminergic w/d imaging, LP, EEG
Serotonin BZDs for agitation (avoid antipsychotics);
AMS, hyperreflexia (LE predominant), Search for causative agent.
Syndrome hyperthermia, mydriasis, HR, HTN, CBC, CPK, BMP, coags,
supportive care for altered VS (esmolol,
Antidepressants, nitroprusside for HR & HTN, cooling). If all
diarrhea, diaphoresis, clonus, rigidity LFTs, UA, CXR
Linezolid, Tramadol else fails, consider cyproheptadine
Depressed MS, ataxia, slurred speech, Hx, urine tox can give Supportive; avoid flumazenil as it precipitates
Benzodiazepines hyporeflexia, RR, coma qualitative result withdrawal + seizure
Physiologic depression, miosis, NaHCO3 for QTc prolong.; Mg, isoprot.,
CMP, CBC, CPK, LDH, LFTs,
Antipsychotics anticholinergic effects, extrapyramidal overdrive pacing if torsades. Avoid class IA,
Psychiatric Medications

serum iron, EKG, EEG

reactions/NMS, tachycardia IC, and III antiarrhythmics
CPK, tox screen, EKG:
Prolonged QRS, arrhythmia, QRS duration (>100ms, NaHCO3 (for the Na) if QRS >100ms or
hypotension, anticholinergic toxicity, 26% szr risk; >160, 50% HoTN. BZDs for szr. Salvage: 3% NaCl, lipid
TCAs myoclonus, hyperthermia, AMS, coma, risk), terminal R wave >3mm emulsion, avoid physostigmine. VA-ECMO
szr in aVR. Watch for ventricular for refractory cardiac toxicity and shock.
arrhythmia
N/V/D, tremor, hyperreflexia, clonus, BUN/Cr, Li levels (nl 0.5-
Frequent neuro checks; IVF (NS preferred),
ataxia, AMS, szr, AV block, sinus brady, 1.5mmol/L), EKG. Toxicity
Lithium long QT, hyper/hypothyroid, common w/ AKI from
maintain UOP, HD if encephalopathy, renal
dysfunction
nephrogenic DI if chronic NSAIDs, ACEi, diuretics
Malaise, vomiting, sweating, RUQ pain, See flowcharts in Consensus Statement: JAMA 2023;6(8)e2327739 and See
Acetaminophen DILI/ALF Acute Liver Injury & Failure
Pain Medications

RR & VT, CNS depression, bowel IV or intranasal naloxone (0.4-2mg). See
Opioids EKG, core temp, FSBG, CPK
sounds, miosis Opioid Use Disorder & Withdrawal
ABG (mixed resp Avoid intubation (if required, hyperventilate to
Tinnitus, fever, vertigo, N/V/D, RR, alkalosis/met acidosis), BMP, avoid acidemia), IVF, charcoal (1g/kg),
Salicylates pulmonary edema, AMS (can have CXR, salicylate level (>30- glucose (100mL D50), NaHCO3, alkalinize
neuroglycopenia w/ nl FSBG) 50mg/dL). Trend levels & urine to pH 7.5-8, avoid acetazolamide.
ABG q2h Consider HD
Hx, EKG (HR, long PR),
Calcium, pressors, glucagon, HIGH DOSE-
blood levels (slow, correlate
N/V, HoTN, CHF, HR, AV block, insulin (1U/kg bolus, then 0.5-1U/kg/h gtt,
CCBs stupor, cardiac arrest, FSBG
poorly). Extended release
adjust to cardiac response) + D10, IVF;
more dangerous. High FSBG
consider pacing, atropine, ECMO
Cardiac medication

= poor prognosis
Pressors, calcium, glucagon (5 mg bolus, if no
HoTN, HR, AV block, long QTc Hx, EKG, blood levels (slow, improvement of HR or BP repeat in 10-15
B-Blockers (sotalol), CHF, bronchospasm, FSBG, correlate poorly); propranolol min), high-dose insulin (see CCB), IVF;
stupor, K, szr (propranolol), miosis highest mortality atropine, pacing, ECMO. HD for atenolol,
sotalol
EKG, BMP, UOP, dig level (nl
HR, AV block, N/V/abd pain, K, 0.9-2ng/mL; may not be Digoxin-specific Fab fragments (if K>5.5,
Digoxin AMS, xanthopsia (yellow-green halo), accurate if drawn w/in 6h of severe end-organ dysfxn, or life-threatening
bidirectional VT, “regularization of AF” last dose, as includes bound arrhythmia), Mg, AVOID hypokalemia
Fab fragments)
Serum/urine tox (metabolites
Agitation, psychosis, seizure, HTN, Hyperthermia treatment (cooling, BZDs), treat
detectable for 2-5d), EKG,
Other

Cocaine HR, vasospasm/MI, arrhythmia,

cardiac biomarkers if chest
chest pain with ASA, CCB, nitrates, (no pure
stroke, vasculitis, lung injury, rhabdo βB). Lido/sodium bicarb for WCT.
pain, CPK, UA

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Pulmonary & Critical Care Toxicology

Drug/Toxin Presenting Symptoms Diagnostic Workup Management
Hx (house fire, winter w/
Minor sx: headache, N/V
space heaters), cyanide & 100% O2 (t½ 250-320 mins75-90 min);
Major sx: confusion, LOC, seizure,
Carbon Monoxide coma, cardiac ischemia,
carboxyhemoglobin levels, hyperbaric O2 (t½ 250-320 mins30 min);
co-oximetry (SpO2 invalid), watch for delayed neuropsychiatric sequelae
arrhythmias
AG acidosis, EKG, TnT
Other Exposure

HA, nausea, AMS, seizure, coma,

Lactate, AGMA, cyanide & Hydroxocobalamin (5g over 15min, use amyl
Cyanide shock. Suspect in structural fires,
carboxyhemoglobin levels nitrate if unavailable) & sodium thiosulfate
prolonged nitroprusside infusion
Not detected on routine tox
Agitation, HR, RR, BP, coma screen, need 100mL urine &
Gamma-hydroxy- Supportive; BZDs for withdrawal. Note: OD at
(sudden onset/resolution), co- 10-30mL blood for send-out.
butarate (GHB) intoxicants common EKG, r/o other causes,
low dose if on protease inhibitors
βhCG
Anxiety, paranoia, sedation, memory
Synthetic Not detected on routine tox
impairment, hallucinations, Supportive care. BZDs for agitation and szr.
Cannabinoids
psychosis, szr, tachycardia, HTN,
screen, can send blood &
Antipsychotics for agitation
“Spice” or “K2” urine for send-out
N/V, AKI
(Pharmacotherapy 2015;35:189; Chest 2011;140:795; Crit Care Clin 2012;28:479; Circulation 2023;148:149); see Nephrology for alcohols
DECONTAMINATION THERAPIES
• Activated Charcoal
o Most effective if given when substance is still in stomach (usually considered to be within 1h of ingestion, but data is lacking)
o Not useful for: cyanide, lithium, ethanol/methanol, glycols, mineral acids (e.g. sulfuric acid, nitric acid), alkali metals (potassium,
magnesium, sodium, including sodium hydroxide [Drano]); iron; ammonia
o Other therapies not routinely used: whole bowel irrigation (with polyethylene glycol), gastric lavage, Ipecac
• Dialysis and Acid/Alkaline Diuresis (consult Nephrology):
o Dialyzable toxins: methanol, isopropyl alcohol, glycol, acetone, lithium, salicylates, barbituates, INH, atenolol/sotalol, rarely EtOH
 Acid diuresis (give vitamin C): quinine, PCP; Alkaline diuresis (give NaHCO3): phenobarbital, salicylates, MTX, TCAs

LUNG TRANSPLANT OVERVIEW

• Lung composite allocation score: medical urgency & post-lung transplant (LT) survival: use similar factors (e.g., age, Cr, dx,
functional status, pCO2, mech ventilation) + cardiac index for post-LT survival, candidate biology: blood type/antibodies & height,
patient access (+points for some groups), placement efficacy or proximity/travel (AJT 2022; 22:2971), (OPTN LT policy 2022)
• Procedure choice: bilateral LT (BLT) is most common (~80%) d/t better long-term outcomes, but ongoing controversy regarding
benefit of BLT vs. single LT (SLT) in COPD and IPF; SLT often not recommended in CF and pHTN (JTD 2018;10:4588)
• Outcomes: median survival in adults post-LT 6.7 yrs, some dx have more favorable outcomes (e.g., CF) (JHLT 2019;38:1042)
LUNG TRANSPLANT EVALUATION
As a medicine provider: HCM, tx comorbidities,  substance use, optimize weight, limit blood product, refer for txp early
Pre-op assessments: Medical: cardiac, pulm, ID, GI, renal, HCM; Surgical/anesthesia; Functional: 6MWT, pulm rehab, nutrition;
Psychosocial: SW, psych, financial services, caregiver eval
Contraindications to transplant (JHLT 2021;40(1350))
• Absolute: acute medical instability, significant multiorgan dysfunction (+ untreatable coagulopathy), high risk malignancy, uncontrolled
HIV, active TB, hx of non-adherence to medical therapies, active substance use
• Relative: age >70, BMI > 35, EF<40%, active hepatitis, MDRO colonization/ifxn, hx chest surg, severe esophageal dysmotility
POST-TRANSPLANT COMPLICATIONS
Early: surgical (post-op hemorrhage), airway (stenosis, necrosis, bronchomalacia), ifxn, 1° graft failure (ischemic-reperfusion injury)
Late Complications (JCS 2022;55:338)
• Infectious: typically, donor-derived pathogens in immediate post-op period; bacterial (esp. P. aeruginosa, S. aureus, B.
cepacian, E. faecalis), viral (esp. CMV, HHV), fungal (esp. Aspergillus)
• Malignancy: esp. dermatologic, SCC #1, post-transplant lymphoproliferative disorder (PTLD)
Complication Diagnostics Treatment
Graded on scale of 0-4 histology, degree of Initial therapy: Pulse dose steroids
Acute-Cellular Rejection (AMR)
perivascular, interstitial, & air-space mononuclear Refractory: Repeat steroids, change cyclosporine >
(ATM 2020;8:410)
inflammation tacro, ATG*, sirolimus, ECP*, Cytoxan
Immunologic

Antibody-Mediated Rejection (AMR) Clinical diagnosis, detection of donor-specific abs, Plasmapheresis, IVIG, rituximab, proteasome and
(ATM 2020:8:411) histology, lung bx C4d staining complement inhibitors (usually steroid-resistant)
Chronic Lung Allograft Dysfunction
Diagnose based on PFTs – CLAD staged 0-4 BOS: change tacro > cyclosporine, azithro, TLI*,
(CLAD): Bronchiolitis Obliterans
depending on FEV1 compared to baseline. BOS is fundoplication if +GERD, NO steroids
Syndrome (BOS) & Restrictive Allograft
obstructive; RAS is restrictive. RAS mortality > BOS RAS: experimental -> antifibrotics
Syndrome (RAS) (JHLT 2019;35:493)
*Extracorporeal photopheresis (ECP), total, lymphoid irradiation (TLI), antithymocyte globulin (ATG)

I M M U N O S U P P R E S S I O N (ATM 2020;8:409)
• Induction: basiliximab (anti IL-2R), alemtuzumab (anti CD52), ATG
Maintenance: tacrolimus/cyclosporine (CNIs), mycophenalate/AZA (anti-proliferative), sirolimus/everolimus (mTORi), steroid
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Gastroenterology Upper GI Bleeding

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A C U T E U P P E R G I B L E E D (AJG 2021;116:5; Annals 2019;171:805; NEJM 2016;374:2367)

• Definition: bleeding proximal to ligament of Treitz Etiologies (Dig Dis Sci 2018;63:1286)
• S/Sx: hematemesis, melena (on exam: +LR 25; JAMA PUD (~50%; duodenal>gastric): H. pylori, NSAID, EtOH,
2012;307:1072), hematochezia if brisk, BUN/Cr >30 (+LR 7.5; tobacco, Cameron lesion (in hiatal hernia), Zollinger-Ellison
JAMA 2012;307:1072), especially >35 (100% Sp; J Clin Gastro Esophagitis or gastritis (~30%): GERD, pill, ASA, NSAID,
1990;12:500). Clots in stool make UGIB less likely (+LR 0.05) clopidogrel, EtOH, infectious
• Risk Stratification and Triage: Varices (~5%): EVB (esophageal) > gastric
o High-Risk Features in UGIB: hypotension, tachycardia, Vascular malformation (~5-10%): Dieulafoy’s lesion, AVM,
coagulopathy (INR > 1.5), Hgb <10, AMS, syncope, age > GAVE, HHT, XRT, aorto-enteric fistula
65, liver dx, CHF, Traumatic (~5%): Mallory-Weiss, foreign body, Boerhaave’s
o Risk scores: Glasgow-Blatchford Score and ABC score Neoplastic (~5%): primary > metastatic
recommended over AIMS65. Blatchford 0-1 = low risk of Post-procedural (varies): polypectomy, sphincterotomy
rebleeding, consider outpt management) (Annals 2019;171:805; Biliary: hemobilia, hemosuccus pancreaticus
BMJ 2017;356:6432; Gut 2021;70:707;)
o Triage: May need ICU if BP <90 and HR >100 x2 30min apart; Hct <20/Hgb <7 regardless of vital signs with evidence of
active significant bleed in past 12hrs; require >2L IVF or 2u pRBCs to prevent instability/keep Hct >25.
• Assessment/Management: Stabilize  Intervene
o Initial Workup: CBC (q2-8hr), CMP, coags, type & screen, orthostatics, abdominal exam, rectal exam to assess stool color.
o Stabilization: NPO, intubation if high-risk for aspiration (large volume hematemesis, AMS); ensure ≥2 PIV (18G or larger).
o Resuscitation/Transfusion: IVF (isotonic crystalloid) for hypotension. Do not delay transfusion if active hemorrhage,
otherwise transfuse pRBCs for Hgb >7 (NEJM 2013;368:11; Lancet 2017;2:354) or Hgb >8 if CAD (Annals 2019;171:805).
Note: Hct drop lags 24-72h from onset of bleeding. For severe/ongoing bleeding (generally after 4u pRBCs), activate
massive transfusion protocol (see Transfusion Medicine ). Avoid overtransfusion, EVs (can  portal pressures and
worsen bleeding).
o Correct coagulopathy: Transfuse for plt >50k. For INR >2 consider PCC (preferred over FFP for lower volume, faster
onset). If ESLD, INR inaccurate - avoid FFP (volumeportal HTN). If uremic, consider ddAVP. No utility to TXA.
o Consults: GI for EGD and/or colonoscopy, surgery/IR if hemodynamic instability or if endoscopy not preferred
▫ EGD generally within 24hrs, but no ∆ in outcomes if between 0-6hrs vs. 6-24hrs for non-variceal or non-
HDUS bleeds (NEJM 2020;382:1299).Barium studies are contraindicated d/t interference with EGD/angiography.
NGT placement/lavage is not associated with improved outcomes (ERGH 2017;12:63) and is generally not
recommended for diagnosis of UGIB. May be useful for removal of blood/clot to facilitate EGD.
o Pre-EGD Pharmacotherapy:
o IV PPI: pantoprazole 40mg BID (neutralizing acid stabilizes clots);  high-risk lesions requiring endoscopic therapy
but unclear clinical impact pre-EGD (Cochrane Rev. 2010)
o IV prokinetics: erythromycin 250mg 30m prior to EGD gut motility & visualization (Ann Gastroenterol
2016;29:312) Takes time to come from pharmacy. If unable to obtain, substitute 10mg IV metoclopramide
o For cirrhosis: IV octreotide 50 mcg bolus (may repeat bolus in first hour if bleeding uncontrolled) followed by gtt at
50 mcg/hr for 2-5 days. IV CTX 1g q24hr x7 days for ppx against bacterial infections and mortality benefit (Gastro
2006;131:1049; APT 2011;34:509). Hold β-blockers through day 5.
o Anticoagulation/Antiplatelet Management: (Gastrointest Endosc 2016;83:3; Am J Gastroenterol 2022;117:542)
o Warfarin: Hold during bleed. For reversal, can consider PCC, but FFP or vit K NOT recommended. Resume after
hemostasis (w/ UFH bridge for ~48hrs if indicated; see Hematology section).  risk of thrombosis/death in AF if
resumed within 7d (Am J Cardiol 2014;113:662).
o DOAC: Hold during bleed. Reversal with idarucizumab, andexanet alfa, or PCC NOT recommended. Resume within
72hrs in high thrombotic risk pts, within 7d for low thrombotic risk pts.
o ASA: Continue during bleed if low-moderate risk, hold if high risk (unless recent PCI/ACS – see below). Resume
ASA for 2° prevention after hemostasis endoscopically confirmed (Gastrointest Endosc 2016;83:3)  risk of 30d
mortality if not resumed (Annals 2010;152:1); if PUD, add PPI to  risk of re-bleeding.
o DAPT for PCI/ACS: Discuss with cardiologist. Generally if very recent (<30d PCI, <90d ACS), continue both unless
life-threatening; if more distant, continue ASA but less risk with holding P2Y12i. Resume within 1-5d pending course
o Overall, restarting AC/AP sooner   risk of vascular events, though  risk of bleeding (APT 2019;50:8).
o Post-EGD Pharmacotherapy/Management: Review GI procedure note for specific diet, PPI, etc. recommendations.
o For high-risk PUD: IV pantoprazole 40mg BID x 72hrs (intermittent dose non-inferior to bolus+gtt [JAMA IM
2014;174:1755]) re-bleeds and need for repeat EGD. Switch to PO PPI after 72hrs, d/c with BID dosing x 2-8wks.
Treat H. pylori if positive (see GERD and Peptic Ulcer Disease).
o For variceal bleed: consider octreotide x 2-5d, continue IV CTX 1g q24hr x5 days. Restart βB on day 5.
o For angiodysplasia: consider long-term octreotide (APT 2012;36:587), bevacizumab, or thalidone w/ GI help.
o If re-bleed: consider repeat EGD, angiography, surgical/IR consult. If variceal bleeding, consider balloon tamponade,
TIPS, or BRTO.
• Prognosis:
o PUD rebleeding w/o med management: 90% if active bleed, 50% if visible vessel, 30% if clot, 20% if ooze, else <10%.
o EV bleed: 40-50% resolve spontaneously; 30% mortality  70% if continued bleeding; 60% risk re-bleeding overall.

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Gastroenterology Lower GI Bleeding

A C U T E L O W E R G I B L E E D (NEJM 2017;376:1054; Gut 2019;68:776)
• Definition: distal to ligament of Treitz
• S/Sx: hematochezia (maroon or bright History Etiologies (NEJM 2017;376:1054)
red blood, blood clots; Note: BRBPR can Painless Divertic. (30-65%), angioectasias (5-10%), hemorrhoid (5-20%)
be seen in brisk UGIB); rarely melena Abd. pain IBD (3-5%), ischemic colitis (5-20%), perforation
(requires blood spend 14hr in GI tract); Weight loss Malignancy (2-15% neoplasm or polyp), IBD (3-5%)
BUN/Cr typically <20 w/ normal renal fxn Fever/diarrhea IBD (3-5%), acute mesenteric ischemia, infectious colitis (2-5%)
• Risk stratification: AS/ESRD/LVAD Angioectasias (5-10%); Heyde syndrome
o Risk scores: ABC score predicts 30d Recent colo. Post-polypectomy (2-7%)
mortality (Gut 2021; 70:707); Oakland Constipation Stercoral ulceration (0-5%)
score <8 may predict safe discharge Abd/pelvic XRT Radiation proctopathy/colitis (0-2%)
(JAMA 2020;3:e209630, Lancet NSAIDs NSAID-induced colopathy (0-2%)
2017;2:635) Liver disease Colorectal varices (0-3%)
• Assessment/Management: See Figure AF Acute mesenteric ischemia
1 in AJG 2023;118:208 for flow chart. Prior GI surgery Anastamotic ulcers
o Initial Workup: CBC (q2-12hr AAA repair Aortoenteric fistula
depending on severity of bleed), Recent SCT/DLI Graft-vs-host disease
CMP, coags, type & screen. HDUS(HR,BP) Brisk UGIB (13%)
o Colonoscopy is the diagnostic test of choice for hemodynamically stable LGIB. CT angiography is diagnostic test of
choice for hemodynamically significant LGIB (shock index HR/SBP >1). (AJG 2023;118:208). CTA low yield for
minor or improved bleed. Tagged RBC scan more sensitive than CTA, but rarely used due to poor localization.
o If hemodynamically unstable, consider UGIB. 10-15% of patients with severe hematochezia will have UGIB (AJG
2010;105:2636). Diagnose with EGD. NG lavage has poor sensitivity and is not routinely used for diagnosis of UGIB
(AJG 2023;118:208).
o Resuscitation
o Ensure ≥2 PIV (18G or larger). IVF (isotonic crystalloid) for hypotension. Do not delay transfusion if active
hemorrhage, otherwise transfuse pRBCs for Hgb >7 (NEJM 2013;368:11; Lancet 2017;2:354) or Hgb >8 if CAD (Annals
2019;171:805; JAMA 2021;325:552). Note: Hct drop lags 24-72h from onset of bleeding. For severe/ongoing bleeding
(generally after 4u pRBCs), activate MTP (see Transfusion Medicine). Plt goal >30k or >50k if undergoing procedures.
o Anticoagulation/Antiplatelet Management
• Most data extrapolated from UGIB, see AC/AP Management section in Upper GI Bleeding
• Lower GI bleeding data suggests ASA for 1° prevention should be stopped and generally not resumed. ASA for
2° prevention should not be held; if it is, should be resumed soon after bleed resolves (Gastro 2016;151:271).
o Approach to intervention:
o If hemodynamically UNSTABLE: Consult GI, IR, and consider surgery.
• GI: Exonerate UGIB first with EGD (10-15% of patients with severe hematochezia)
• IR angiography: Employed when patients are too hemodynamically unstable for endoscopy (get CTA
first).Therapeutic if embolization done, but risk of bowel ischemia and vascular injury.
• Surgical consult for subtotal colectomy if cannot locate or control bleed.
o If hemodynamically STABLE: Consult GI for discussion of colonoscopy vs flexible sigmoidoscopy.
o Colonoscopy: Recommended for most patients hospitalized with LGIB, unless bleeding subsided and pt had colo with
diverticulosis in last year (AJG 2023;118:208)
• Timing: Colonoscopy at 24-36hrs may be a safe approach in most stable patients (Gastro 2020;158:1). Remains
controversial, studies show delay has no impact vs ↓ identification of stigmata of hemorrhage, ↓ LOS
(Gastroenterology 2020;158:168; J Clin Gastroenterol 2019;53:591; Am J Gastroenterol 2005;100:2395).
• Bowel preparation: No solid food or red liquids for 8 hours prior, use order set “Gastroenterology Bowel Prep”

U N I D E N T I F I E D S O U R C E A F T E R E G D / C O L O N O S C O P Y (ACG: AJG 2015;110:1265)

• Source: ~75% small bowel, 25% UGIB/LGIB
• Small Bowel Causes: Common: angioectasia (20-30%), IBD (esp. <40), Dieulafoy’s lesion, neoplasm, Meckel’s diverticulum
(esp. <40), polyposis syndrome (esp. <40), NSAID ulcers; Rare: varices, portal hypertensive enteropathy, amyloid, HHT,
Kaposi, inherited connective tissue disorders, congenital vascular abnormalities. Consider Heyde syndrome (triad of AS, GI
bleeding, and acquired Von Willebrand syndrome).
• Assessment/Management: (ASGE 2017;85:22, see Figure 1 for flow chart)
o Video capsule (VCE): 1st line but CI if strictures (retention). Consider post-placement IV erythromycin 250mg IV to promote
passage
o 2nd look EGD ± push enteroscopy: (prox 60cm jejunum) if recurrent UGI sx; 2nd look colo: if recurrent hematochezia
o CT enterography: if ⊖VCE or if risk of strictures (IBD, XRT, prior SB surgery, suspected stenosis); CTE>MRE
o Balloon enteroscopy (single vs double): if strong suspicion of SB lesion and therapy required; often after ⊕VCE
o If brisk bleed: CTA if stable then angio. If unstable, can intervene with embolization, enteroscopy, or surgery
o If no source found: iron repletion; consider octreotide, anti-angiogenic tx; replace aortic valve if Heyde & ongoing bleeding
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Gastroenterology Abdominal Pain

Abdominal Pain History and Physical – Key Elements
History: Location, chronicity, quality, radiation, pain ∆ w/ eating or BMs, ∆ in BMs (caliber, color,
diarrhea, constipation), fever, wt. loss, jaundice, medications (NSAID, abx, steroids), surgeries Initial Tests to Consider
Exam: Tenderness, distention, rigidity, rebound, guarding, fluid wave, shifting dullness, auscultation, BMP, Ca, Mg, CBC w/ diff,
Carnett’s sign (AJG 2017;112:760), Castell’s sign, McBurney’s point, Rovsing's sign, obturator sign, HSM, LFTs, lipase, lactate,
abdominal veins, caput medusa, DRE ESR/CRP, UA, b-hCG,
Special populations: immunosuppressed, sexually active, elderly (Am Fam Physician 2006;74:1537) troponin, coags, T&S
Infectious studies as
RED FLAGS of Acute Abdominal Pain indicated. (Gastro
• HDUS, rigidity, guarding, or rebound • “Pain out of proportion” • “Tinkling” or absent bowel sounds
2020;159:320)
• Gross distention + cannot tolerate PO • Bilious emesis, hematemesis, hematochezia
“Can’t miss” Dx: vascular infarct, perforation, extra-intestinal hemorrhage, obstruction, ectopic preg

Acute Abdominal Pain – Anatomic Approach

Adapted from (Am Fam Physician 2008;77:971)
Right Upper Quadrant Epigastric Left Upper Quadrant
• Liver pathologies (hepatitis, abscess, Budd- • Pancreatitis • Splenic pathologies (splenomegaly,
Chiari, portal vein thrombus, Fitz-Hugh-Curtis) • Gastric pathologies (GERD, PUD, abscess, infarction, rupture, trauma)
• Biliary pathologies (cholelithiasis/biliary colic, gastritis/gastropathy, functional • Gastritis, PUD
cholecystitis, cholangitis, Sphincter of Oddi dyspepsia, gastroparesis) • Sub-diaphragm or abdominal abscess
dysfunction) • Mesenteric ischemia (either side)
• Extra-abdominal: PE, PNA, CHF • Esophagitis
• Extra-abdominal: MI, Aortic Left or Right Lower Quadrants
Right Lower Quadrant dissection • Intestinal pathologies (diverticulitis,
• Appendicitis • Lymphadenitis • Ileal Crohn’s colitis, constipation, IBD, IBS, volvulus,
Periumbilical lymphadenitis)
• Early appendicitis
Diffuse • Renal pathologies (nephrolithiasis,
• PUD pyelonephritis)
Obstruction/SBO/LBO, ischemia, AAA,
• Bowel obstruction (SBO >LBO)
perforation, peritonitis, gastroenteritis, IBD, • Pelvic pathologies (ectopic preg, fibroids,
• Umbilical hernia
dietary, SBP, toxin, meds (iron), cancer, ruptured cyst, endometriosis, torsion, PID,
ketoacidosis, adrenal insufficiency, celiac, Suprapubic abscess, epididymitis)
Familial Mediterranean Fever, hereditary • Cystitis • Prostatitis • Hernia
angioedema, Acute Intermittent Porphyria • Urinary retention • Hematoma
IMAGE NEGATIVE ABDOMINAL PAIN
Imaging/Testing (ACR Appropriateness Metabolic: DKA, Ca, uremia, heavy metals, AI, Acute Intermittent Porphyria
Criteria) Meds/Toxins: EtOH, opioids/opioid withdrawal, cocaine, anticholinergics, lead/heavy
metal
• Acute, nonlocalized with fever: CT AP I+ Functional: IBS, abdominal migraine, functional dyspepsia
• Suspect bowel obstruction: CT AP I+ over Episodic: passed kidney stone, sphincter of Oddi dysfunction
plain film (no need for PO contrast) Other: acute MI, angioedema, VZV, eosinophilic gastroenteritis, gastritis,
• Suspect mesenteric ischemia: CTA AP polyradiculopathy, abdominal epilepsy
• AAA suspected: HDS stable  CTA AP;
Centrally Mediated Pain Syndrome (CAPS) and Narcotic Bowel Syndrome
HDUSSTAT surgery consult (NBS) (Gastro 2016;150:1408) Rome IV Criteria
• Epigastric pain, suspected PUD: H. pylori
stool antigen, EGD CAPS: Type of functional GI disorder with freq/near continuous pain not related to
• Epigastric, suspect pancreatitis: CT AP I+ impaired gut function, structural, or metabolic causes. Instead caused by CNS
• RUQ, suspect biliary: RUQUS followed by sensitization and altered pain signals. Multimodal treatment with therapy/stress
MRCP w/ clinical suspicion reduction/meds. Early psychologic, behavioral, or mindfulness referral (such as
• RLQ, suspect appendicitis: CT AP I+ vs Benson-Henry Institute at MGH). Trial SSRI (least analgesic), SNRI, or TCA for 4-6
ultrasound weeks  dose titration  potentially dual therapy. Psychiatry referral for refractory
• Lower quadrant, suspect diverticulitis: CT patients.
AP I+ NBS: Chronic abd. pain treated with acute high-dose or chronic narcotics. Not
• Lower quadrant/flank, suspect kidney explained by structural causes/other dx, and pain worsens when ↓ narcotics. Tx:
stone: CT AP I- reduce opioid while controlling pain (consider antidepressants and
• Lower quadrant/pelvic, b-hCG+: pelvic nonpharmacologic therapy). Education key, esp. re: hyperalgesia. Consider inpatient
and transvaginal US detox. (AJG 2012;107:1426).
Chronic Abdominal Pain – Etiologies
Adapted from Chronic Abdominal Pain (2015)
Visceral Somatosensory Functional
Anterior cutaneous nerve entrapment (PE:
Chronic pancreatitis, IBD, mesenteric Centrally mediated (functional) pain,
Carnett sign), myofascial pain, slipping rib
ischemia, adhesions, cancer, pelvic functional dyspepsia (see section), IBS,
syndrome, radiculopathies, post-herpetic, diabetic
etiologies narcotic bowel syndrome (NBS)
neuropathy

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Gastroenterology GERD & Peptic Ulcer Disease

G A S T R O E S O P H A G E A L R E F L U X D I S E A S E ( G E R D ) (ACG: AJG 2022;117:1 ; AGA: Gastro 2008;135:4)
Signs & Sx: “heartburn” w/ food (i.e. spicy foods, coffee, soda, chocolate, EtOH) or position (reclining), regurgitation, sour taste after
awakening, sore throat, dysphagia, globus sensation, chronic cough/throat clearing, hoarseness, asthma exacerbation, chest pain
• Alarm symptoms: dysphagia/odynophagia, wt loss, GIB, IDA, persistent vomiting, anorexia, new onset age ≥60
Ddx: infectious esophagitis, pill esophagitis, eosinophilic esophagitis (EoE), motility disorder, reflux hypersens./functional dyspepsia
Evaluation: No alarm sxs  trial of 8-wk normal dose or short (1-2 wk) high-dose PPI BID (metanalysis: Sn 79% / Sp 45%; NEJM 2022;
387:1207). If alarm symptoms or no/incomplete response to PPI  EGD w/ biopsy: look for tissue damage, complications, or malignancy
• If endoscopy ⊝ but persistent symptoms  ambulatory pH monitoring/impedance testing
• If endoscopy ⊝ but persistent symptoms w/ CP and/or dysphagia  assess for motility disorder w/ esophageal manometry
Management (Gastro 2018;154:302):
• Lifestyle Δs: wt loss (goal BMI <25), tobacco cessation, drinking <2 cups of coffee/tea/soda, “prudent” diet (i.e., high intake of fruits,
vegetables and whole grains); ≥30 min exercise daily, no eating 2-3 hours before bed (JAMA IM 2021;e207238)
• PPIs > than antacids/H2RAs for sx relief in empiric tx and optimal for erosive esophagitis (Cochrane Rev 2013)
o Start low-dose PPI (e.g. 20mg omeprazole) 30min before AM meal. Reassess 4-8wk, uptitrate to high-dose (e.g. 40mg
omeprazole), then BID if no relief. Assess at 8w if able to d/c.
o Maintenance PPI: If sx after PPI d/c or if complications (see below). Lowest effective dose. Test for reflux + EGD at 1yr
Discontinuing PPI: if on PPI >6mo., taper by 50% per wk to prevent rebound hypersecretion.
o PPI risks: probable association: ↓Ca, Mg, Fe absorption, AIN, C.diff/other enteric infxns. Insufficient evidence for risk of
osteoporosis, CKD, or dementia (Gastro 2017;152:706), (Gastro 2020;115:671).
• H2RAs (famotidine 10-20mg BID): can also use nightly PRN w/ PPI, tachyphylaxis common after wks
• Others: PRN antacids, sodium alginate (APT 2013;38:1059; APT 2014;39:595), baclofen (as adjunct)
Severe/Refractory Symptoms: If no relief after 8w on high-dose PPI BID, refer for EGD/impedance testing & consider ddx e.g. functional
dyspepsia (symptoms >3mo; Gastro 2020;158:2286), nonerosive reflux disease, reflux hypersensitivity, EoE, rumination, hiatal hernia
o EoE: dysphagia, GERD sx, food impaction; a/w allergic conditions. Dx with >15 Eos per HPF on biopsy. Tx: PPI, topical steroids
(Gastro 2020;158:1776), dupilumab (IL4,13 antibody) (JACI 2022;149:AB312)
o Hiatal hernia: Type I (sliding); Type 2-4 (paraesophageal hernias) – refractory GERD; surgery controversial
o Reflux hypersensitivity: dx w/ pH impedance w/ acid exposure time <4% + reflux symptom association (normal manometry)
• Gastric fundoplication may be superior to medical tx for refractory heartburn (NEJM 2019;381:1513)
Complications:
• Barrett’s Esophagus (BE): squamous epithelium  intestinal metaplasia (IM). AdenoCA risk 0.38% (IM) vs 0.07% (no IM)/yr.
Screen w/ EGD in: chronic GERD sx + ≥3 RFs (>50, white, male, central obesity, tobacco hx, FH of BE or adenoCA)
(AJD2022;117:559). Mgmt: indefinite PPI. Surveillance EGD interval depends on degree of dysplasia on biopsy (AJG 2022;117:559)
• Esophageal stricture: p/w progressive dysphagia to solids. Endoscopy w/ biopsy can differentiate stricture from cancer
P E P T I C U L C E R D I S E A S E ( P U D ) (BMJ 2019;367:I5495; Lancet 2017;390:613)
Signs & Sx: dyspepsia - intermittent gnawing, dull, aching, or “hunger-like” epigastric pain relieved w/ antacids though 70% are asx (often
in elderly and NSAID use); Associated sx: early satiety, bloating, n/v
Etiology: majority caused by H. pylori or NSAIDs (idiopathic becoming more common). Others: meds (bisphosphonates, clopidogrel,
sirolimus), ZES, mastocytosis, HSV, CMV, EBV, fungal infxn, post-surgical, XRT, ischemia (cocaine), Crohn’s, sarcoid, critical illness
Ddx: other causes of dyspepsia: biliary disease, gastric CA, celiac, chronic pancreatitis, drug-induced, functional dyspepsia
Evaluation: H. pylori testing in all w/ dyspepsia; if >60  EGD to exclude CA (AJG 2017;112:988)
• H. pylori testing: stool Ag or urea breath test (not avail. at MGH) preferred to dx Forrest Class - Description Re-bleed
active infection. Testing affected by PPI & abx ( false ⊝) but not affected by Ia - Active arterial bleeding 85%
H2RAs. Serology (IgG) not affected by PPI/abx/bismuth but cannot distinguish Ib - Oozing w/o visible vessel 30 %
active vs. past infection; a ⊝ serology excludes infection if low pre-test IIa - Non-bleeding visible vessel 40%
probability. Bx w/ urease, histology or cx IIb - Adherent clot 25%
• EGD: biopsy malignant-appearing & select benign-appearing ulcers; obtain IIc - Flat spot 10%
samples for H. pylori testing. Rebleed risk per Forrest classification. III - Clean ulcer base 3%
Management: PPI (duration depends on etiology); if need to continue ASA, continue
w/ PPI (NEJM 2005;352:238; Gastro 2010;138:82). F/u EGD after 8-12w if refractory sx (see below) or most gastric ulcers to exclude
malignancy (Gastrointest Endosc 2010;71:663).
Treatment for H. pylori (AJG 2017;112:2)(Gastro 2016;151:51)
• First line = quadruple therapy: PPI BID, bismuth 300mg QID, tetracycline 500mg QID (alternative: doxy 100mg BID), metronidazole
500 QID x 14d. Combo pill (Pylera) available.
• Salvage therapy: Avoid antibiotics used previously. Trial clarithromycin, levofloxacin, or amoxicillin-based regimens (AJG 2017;112:2).
Recently approved combined treatment with rifabutin, amoxicillin, and PPI BID for 14d (as salvage therapy) was shown to have no
difference in eradication rates but ↑ compliance and ↓ AEs compared to bismuth quad. therapy (J Inf Dis 2023;228:511).
• Confirmation of eradication: confirm for all pts w/ stool Ag, urea breath test, or EGD >4 wks after completion of abx and off PPI for 2w.
Refractory PUD: ulcer that does not heal after 8-12wks adequate tx; 5-10% of ulcers are refractory to PPI tx
• Ensure H. pylori eradicated, NSAIDs & other contributing meds discontinued. Test for ZES w/ fasting serum gastrin (if on PPI, recheck
1 week s/p cessation); secretin stimulation test if non-diagnostic. Search for rare causes.
• Continue PPI x additional 12w and then repeat EGD. Surgical tx: rarely required; resection, vagotomy, partial gastrectomy
Complications and Management: ulcer considered complicated if any of the following are present: bleeding: see Upper GI bleeding;
perforation, or gastric outlet obstruction: pyloric channel/duodenal ulceration  inflammation  fibrosis/scarring; May need
endoscopic dilatation or surgical tx if persists despite medical mgmt. If gastric outlet obstruction sxs - exclude malignancy.
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Gastroenterology Functional Dyspepsia

DEFINITION (ROME IV CRITERIA)
• Functional dyspepsia (Must have one of the following and no evidence of structural disease (endoscopy))
o Bothersome post-prandial fullness, early satiety, epigastric pain, epigastric burning
WORKUP (AJG;112:988)
• Should exclude organic causes for dyspepsia including GERD, PUD, biliary type pain, chronic pancreatitis.
• Physical exam may be positive for epigastric tenderness. Assess for Carnett’s sign (worse pain with tensing abdominal
muscles) to exclude abdominal wall pain.
• Alarm features include: Weight loss, difficulty with swallowing, risk factors for cancer, lab abnormalities (including
anemia), which should prompt EGD. In patients >60 years of age, should proceed with endoscopy without alarm signs
• Test for H pylori, and treat if positive prior to considering other management options
MANAGEMENT (AJG;112:988)
• If there are no other causes identified and H Pylori is negative or treated, can trial PPI
• If PPI ineffective in above setting, can trial TCA. The following step could be pro-kinetic therapy but there is low evidence.
• There is also low-quality evidence regarding utilizing psychologic therapies in functional dyspepsia in contrast to IBS

-EGD if alarm signs or

Treat
>60 years of age Trial tricyclic
emperically with
-Rule out H. Pylori and antidepressants
PPI
other organic diseases
PATIENT COMMUNICATION
• Some patients worry that a functional diagnosis is saying that the issue is in their head. However, it is important to frame
that we do not believe that the diagnosis is all in their head. Rather it may be helpful to frame that there are many
neuronal connections between the central nervous system (brain) and enteric nervous system (gut), and that they
experience real discomfort and pain, but it could be a misinterpretation of signaling. Not unlike some forms of tinnitus.
May help with also discussing interventions such as TCA, which works on the connection (neurotransmitters) between
neurons.

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Gastroenterology Nausea & Vomiting

A P P R O A C H T O P A T I E N T W I T H A C U T E ( < 1 M O . ) N A U S E A / V O M I T I N G (Gastro 2001;120:1, AFP 2007;76:1)
1) Initial assessment
a. Rule out life-threatening causes: bowel obstruction, perforation, mesenteric ischemia, pancreatitis, MI, DKA, ↑ ICP
b. History: onset, frequency, & severity, hematemesis, feculent vomit. Last BM, LMP
Triggers: relation to POs, relation to time of day, recent foods/meds, sick contacts, drug use (opioids, marijuana)
Other symptoms: abd pain (see Abdominal Pain), fever, wt loss, diarrhea, melena, heartburn, vertigo, headache, CP, SOB
PMH: head trauma, prior abd surgery, uncontrolled DM, migraines
c. Exam: dehydration, orthostatics, jaundice, abdominal tenderness, masses, lymphadenopathy, CN exam/nystagmus, gait
2) Labs to consider: BMP, LFTs, lipase, B-hCG, UTox, UA, ABG, lactate, cort stim, TSH, Troponin
3) Studies to consider: KUB, EKG, CT abdomen (I+/O+), Barium swallow or EGD, Gastric emptying study, CT head
4) Manage complications: IVF to correct hypovolemia. Address electrolyte abnormalities (hyperchloremic metabolic alkalosis, HypoK)
5) Address underlying cause while treating sxs (see table)
• Chemo PPX: dex ± lorazepam ± ondansetron ± aprepitant ± olanzapine (NEJM 2016;375:134)
• Adhesive SBO (prior GI surg, hernias, neoplasms, Crohn’s disease): conserv. mgmt x 48h (NGT with suction, NPO) 
gastrografin per NGT  surgery by 74% (BJS 2010;97:470)
6) Practical approach to empiric inpatient nausea treatment (see table with meds and doses below):
Normal QTc  Start with ondansetron; add prochlorperazine if persistent. Prolonged QTc  Consider lorazepam. If cannot use
benzos, can try dexamethasone, scopolamine, or diphenhydramine. If persistent, further w/u and targeted treatment.
Non-pharm options: acupuncture, meditation, ginger root, inhaled alcohol (AEM 2018;72:2)
Etiologies (VVOOMMIIITING) Receptor Targeted treatment
Vestibular & Acute/gait instability; labyrinthitis, BPPV, Scopolamine, dimenhydrinate, diphenhydramine,
Ach, H1
Vertigo vestibular neuritis, Meniere’s disease meclizine, Dix-Hallpike  Epley maneuver
NGT, bowel rest, IVF, surgery consult, serial exams
Adhesions, hernia, volvulus, constipation, gastric
Obstruction Multiple Meds: Prochlorperazine, ondansetron, NO
outlet obstruction
metoclopramide (risk of perf)
Post-op n/v (risk factors: F > M, nonsmoker, post-
Ondansetron, aprepitant, dexamethasone (use 2 in
Operative op opioids, hx of condition, type of surgery), 1/3 Multiple
combo as ppx if 3+ RFs), gabapentin
cases
Low fat & insoluble fiber diet, metoclopramide,
Gastroparesis (common in uncontrolled DM),
erythromycin (tachyphylaxis after 4 wks; motilin
Motility autonomic dysfunction, cyclic vomiting syndrome, D2 (periph)
agonist), diphenhydramine, cannabis abstinence,
chronic idiopathic nausea (see Motility Disorders)
TCAs, olanzapine, benzos, SSRI/SNRI
Antibiotics, AEDs, chemo, opioids, cannabis Stop offending med if possible, prochlorperazine,
Meds D2 (central)
hyperemesis, anti-arrhythmics haloperidol
Chemo, XRT, bowel ischemia, gastroenteritis, Ondansetron, prochlorperazine, dexamethasone,
Inflammation/
PUD, hepatitis, pancreatitis, cholecystitis, 5-HT3, NK1 olanzapine & aprepitant (chemo), treat underlying
Infection/ Ischemia
pyelonephritis disorder (antibiotics, surgery, etc.)
Uremia, ketoacidosis, hypercalcemia, food Prochlorperazine, haloperidol, treat underlying
Toxins D2 (central)
poisoning, hypo/hyperglycemia disorder
Elevated ICP, migraine, meningeal irritation, Ach, H1, 5-
Intracranial Dexamethasone (if ICP), treat underlying disorder
acute glaucoma HT3
Lorazepam (anticipatory N/V), dexamethasone, pain
Nerves Anxiety, depression, anticipatory nausea, pain Multiple
control
Gums/mouth Mucositis thrush, oral HSV Multiple Treat cause; magic mouthwash

Recep. Med Dose QTc Other side effects

Ondansetron (Zofran) 4-8 mg PO/IV q8h  constipation, HA
5HT3
Palonosetron (Aloxi) 0.075-0.25mg IV x1 - more potent
EPS (black box), dystonia (peripheral),
Metoclopramide (Reglan) 10-20 mg PO/IV q6-8h 
promotility agent
D2
Prochlorperazine (Compazine) 5-10 mg PO/IV/PR q6h  EPS, sedation
Haloperidol (Haldol) 0.5-4 mg PO/IV q6h  EPS, sedation
Dexamethasone (Decadron) 4-8mg PO q4-6h - psychosis, CHF, appetite
Cortical
Lorazepam (Ativan) 0.5-2 mg PO/IV q6h - delirium, sedation
NK1 Aprepitant (Emend) 125mg day 1, 80mg days 2-3 - CYP3A4 inhib, GI upset
CB1 Dronabinol (Marinol) 2.5-10 mg q4-6h - dysphoria, asthenia, appetite
metabolic (wt gain, lipids);  mortality
5HT2A, D2 Olanzapine (Zyprexa) 5-10mg PO QD 
in dementia (black box)
H1, ACh, D2 Promethazine (Phenergan) 12.5-25 mg PO/IV/PR q4-6h  EPS, sedation, tissue injury (black box)
Scopolamine 0.3-0.6 mg q24h -
delirium, sedation, dry mouth, urinary
ACh, H1 Hyoscyamine 0.125-0.25 mg SL/PO/IV q4h -
retention, ileus, blurry vision
Diphenhydramine (Benadryl) 25-50 mg PO/IV q6h -

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Gastroenterology Nausea & Vomiting

A P P R O A C H T O C H R O N I C ( > 1 M O . ) N A U S E A / V O M I T I N G (Gastro 2001;120:1, AFP 2007;76:1, AJG 2018;113:647, Rome IV)
Pathology Symptoms/Diagnosis Targeted treatment
- Early satiety, bloating, N/V, abdominal pain Small particle/low fat diet, hydration,
Gastroparesis - Can be related to DM, medication, autoimmune, post-surgical, or idiopathic metoclopramide, antiemetics, severe:
- Dx with GES showing >10% retention at 4hr and/or >60% retention at 2hr or decompression and jejunal feeding. TCAs
isotope breath test. and Haldol not recommended.
GERD - Heartburn, epigastric pain, vomiting, regurgitation Acid suppression, weight loss, diet/habit
- Dx clinically or with pH monitor, EGD modification
- Epigastric pain, bloating, early satiety, abd distention, abd pain, weight loss
Supportive care, endoscopic intervention
Gastric Outlet - Can be malignant, inflammatory (related to PUD, pancreatitis, caustic
(eg dilation), txt underlying cause. May
Obstruction ingestion), infiltrative (Crohn’s, TB), or iatrogenic.
need NGT decompression
- Dx with CT, barium swallow, EGD
- Abdominal pain, early satiety, N/V diarrhea, weight loss. Can involve
Eosinophilic
anywhere in GI tract. Likely allergic etiology Elimination diet, PO steroids
Gastroenteritis
- Dx with eosinophilic infiltration of stomach on histology
Rome IV criteria (must include all):
- Stereotypical episodes of vomiting regarding onset (acute) and duration (less Supportive care (IV fluids + mIVF w/
than one week) dextrose, antiemetics), abortive
Cyclic Vomiting
- Three or more discrete episodes in the prior year and two episodes in the (sumatriptan, aprepitant, Zofran,
Syndrome
past six months, occurring at least one week apart antihistamine, BZD), prophylactic (TCA,
- Absence of vomiting between episodes, but other milder symptoms can be anticonvulsant, CoQ10)
present between cycles
Rome IV criteria (must include all):
Cannabinoid - Stereotypical episodic vomiting resembling cyclic vomiting syndrome in Acute: Supportive (IV fluids, antiemetics,
Hyperemesis terms of onset, duration, and frequency dopamine antagonist, capsaicin cream,
Syndrome - Presentation after prolonged excessive cannabis use Long term: Cannabis cessation
- Relief of vomiting episodes by sustained cessation of cannabis use
Rome IV criteria (must include all)
- Persistent of recurrent regurgitation of recently ingested food into the mouth
with subsequent spitting or mastication and swallowing. (NB: regurgitation is
Reassurance, Diaphragmatic breathing
commonly misdiagnosed as vomiting)
Rumination (mainstay of treatment, reduces
- Regurgitation is not preceded by retching
Syndrome intragastric pressure), baclofen for
refractory sx
Dx: Consider pH study/manometry to confirm dx and imaging/EGD to rule out
obstruction. History helps distinguish from GERD. Regurgitation typically lacks
acidic taste, and sx are refractory to PPI/ less likely nocturnal.
Supportive: Frequent, small, cold meals
with high protein content separated from
Pregnancy -Starts at 5-6wks, often peaking at 9wks and subsiding by 20 wks. If n/v starts fluid intake. Ginger and Vitamin B6 +/-
Associated and in latter half of pregnancy, alternative dx should be r/o doxylamine are first line. If not resolved
Hyperemesis -HG: ketonuria, weight loss of >5% or vomiting +x3/day and 3kg weight loss and no hypovolemia, switch to
Gravidarum -Motherisk-PUQE Score and Rhodes Index tools to determine severity diphenhydramine. If hypovolemic, call
MFM, IVF + thiamine and trial
ondansetron if >10wks.
*Also consider non-GI causes such as medications, pregnancy, vestibular, and neurologic disorders

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Gastroenterology Diarrhea
A C U T E D I A R R H E A : ≥3 loose stools/d for <14d (ACG: AJG 2016;111:602; IDSA: CID 2017;65:e45; NEJM 2014;370:1532)
• Evaluation: small bowel (absorbs ~10L) = watery, large vol., Pathogen Details
+cramping/bloating; large bowel (absorbs 1L) = freq., small vol., Viral (most cases)
painful, ± fever, blood, mucus. Most acute diarrhea is Norovirus Outbreaks during winter; n/v prominent
infectious/viral. Rotavirus Daycare-associated
Exposure hx: travel, abx, hospitalization, food, sick contact, daycare Adenovirus A/w conjunctivitis + pharyngitis
“High Risk”: immunocomp/HIV, IBD, age >70, CAD, pregnant Bacterial (most severe cases)
“Severe”: fever > 101.3F, >6 BMs/24hr, hypovolemia, severe pain Toxigenic = traveler’s diarrhea; hemorrhagic,
E. coli O157:H7 = undercooked meats, a/w Shiga
• Workup: BMP (hypovolemia), C.diff (if risk factors/abx, no retest if toxin, HUS
confirmed infxn), stool cx (if high risk, severe sx, bloody diarrhea, sx Undercooked/unpasteurized foods, can be a/w
>1wk), stool O&P (3 samples q24h if high suspicion travel, MSM, Campylobacter
reactive arthritis or GBS
immunocomp). If bloody, check shigatoxin and fecal leukocytes. Salmonella Eggs, poultry, milk, often bacteremic
• Common pathogens: See table. Immunocomp: CMV, C. diff, Shigella Low inoculum, often hematochezia
Cryptospor., Isospor., Microspor., MAC, TB, Histopl., Cryptococcus Vibrio spp. Shellfish/salt water; RF: cirrhosis
• Treatment: volume & electrolyte repletion. Empiric abx: Yersinia Undercooked pork, “pseudoappendicitis”
controversial; consider FQ or azithro if severe sx (see above), high C. diff See C. diff
risk, septic, bloody diarrhea, age ≥70, or serious comorbidities. Parasitic
Avoid abx if suspect STEC as can  risk of HUS. Probiotics not In MA, outdoor streams; watery stool
Giardia
recommended except for post-abx diarrhea. progressing to malabsorptive/greasy
Cryptosporidia Water-related outbreaks
• Anti-diarrheals: If NO fever/blood/c diff consider loperamide 4 mg
Cyclospora Contaminated produce
x1 then 2mg after BM, max 16 mg/d, diphenoxylate, soluble fiber. If Contaminated food/water outside US, a/w liver
fever/bloody stool can try PeptoBismol 30mL q30min (for 8 doses) E. histolytica
abscesses
• Diet: potatoes, noodles, rice, oats, bananas, soup, broiled veggies
C H R O N I C O R P E R S I S T E N T D I A R R H E A : Chronic = ≥3 loose stools/d for >4w; Persistent = between 14-30 days
5 types: secretory, osmotic, functional, malabsorptive, and inflammatory
Evaluation (Gastro 2017;152:515; CGH 2017;15:182; Gut 2018;67:1380
• Hx: freq., stool vol., tenesmus, abd pain, bloating, postprandial sx, steatorrhea, surgical hx, travel, immunocomp., meds, diet.
• Alarm features: onset >50y, bleeding, nocturnal pain/diarrhea, progressive pain, unexplained fever/weight loss
• Labs: CBC, BMP, LFTs TSH; stool lytes (Na, K, pH), fecal calprotectin (marker of neutrophil activity)/lactoferrin (marker for fecal
leukocytes), fecal elastase, fecal fat (24-48h collection), FOBT, Giardia, celiac panel (Gastroenterology 2019;157(3):851)
o Negative fecal calprotectin/lactoferrin rules out IBD; ⊕ FOBT w/ diarrhea suggests chronic infection or IBD (poor sensitivity for
colorectal cancer). Other tests to consider: colonoscopy (especially if alarm features or concern for IBD/microscopic colitis), total
stool bile acid, C. diff (recent antibiotics), Cryptosporidium/Cyclospora (travel; exposure to infants in daycares), Microsporidium
(immunocompromised), KUB (overflow incontinence)
• Stool osmotic gap for watery diarrhea: 290 – 2*(stool [Na] + [K]); normal 50-100mOsm/kg
Watery Fatty
Inflammatory
Secretory Osmotic Functional Malabsorptive/Maldigestive:
Addison’s, neuroendocrine Malabsorption: mesenteric
Lactose IBD, invasive
tumors, hyperthyroid, medullary ischemia, mucosal disease
intolerance, bacteria/parasite (C.
CA of thyroid, mastocytosis, (CD, Whipple’s), short gut
mannitol, IBS, functional diff, E. histolytica,
microscopic colitis syndrome, SIBO
Etiologies sorbitol, diarrhea Yersinia, TB),
(lymphocytic or collagenous), Maldigestion: bile acid
magnesium, (see IBS) ulcerating virus (CMV,
DM autonomic neuropathy, malabsorption (ileal disease)
laxative use, HSV), colon CA,
amyloidosis, bile salt (4-5%), or ↓ synthesis, pancreatic
FODMAPs lymphoma, radiation
lymphoma, villous adenoma exocrine insufficiency
Structural problem, mucosal Inflammation
Secretagogue, rapid transit, Osmotic Multi-
Mechanism disease, panc. or bile acid interferes w/
 surface area substance factorial
insufficiency function/absorption
Osmotic gap <50 >125 50-100 Usually >50 Usually <50
Response to No change
Improves Variable Improves No change
fasting
Exclude infxn. +/- colo with bx Stool pH Sudan stain, 24hr fecal fat
Exclude infxn.
(esp. if immunosupp). As (<6), H2 (>20g likely panc dysfxn, 14-
Further Calprotectin, fecal
appropriate: chromogranin, breath test, None 20g likely small bowel
Testing leukocytes, colo w/
gastrin, somatostatin, calcitonin, laxative cause), stool elastase or
biopsies
5-HIAA, TSH, ACTH stim, SPEP screen chymotrypsin, see Celiac
Bile salt: cholestyr. 4g QD-QID Fiber (psyllium),
Microscopic colitis: budesonide, Viberzi (+pain),
Pancreatic enzyme
cont. loperamide, no NSAID hyoscyamine Abx vs.
D/c offending replacement therapy
VIP: somatostatin (octreotide (antispasmodic), immunosuppression
Treatment agent; dietary (pancrealipase 500-2500
50-250 ug TID SQ) Rifaxamin (induction vs
review units/kg/meal);
Other: loperamide 2-4mg QID, (+bloating), maintenance tx)
If s/p CCY, cholestyramine
diphenoxylate 2.5-5mg QID, probiotics,
tincture of opium TCA/SSRIs
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Gastroenterology Constipation, IBS, & Colonic Disorders

CONSTIPATION
Symptoms: Dissatisfaction with defecation with at least 2 of the following: <3 BM per week, hard stools, straining, sensation of incomplete
evacuation, sensation of anorectal blockage/obstruction, or manual facilitation of BM. See Rome IV for exact criteria.
Etiologies:
• 1º constipation:
o Slow-transit constipation (STC): sitz-marker study shows delay in colonic transit; associated with bloating & pain
o Normal-transit constipation (NTC): normal testing, does not meet criteria for IBS-C, but has constipation sx
o Dyssynergic defecation (e.g. pelvic floor dysfunction): impaired rectal evacuation w/ normal or delayed colonic transit; inadequate
rectal propulsive forces or increased resistance to evacuation (e.g. failure to relax or inappropriate contraction)
o IBS-C: see below; recurrent abd. pain or discomfort a/w hard or infrequent stools or relieved by defecation
• 2º constipation:
o Lifestyle: low fiber, dehydration, sedentary o Metabolic: Ca, hypothyroid, Mg, K, uremia, heavy metal
o Medications: analgesics, opioids, anticholinergics poisoning, pregnancy
(antihistamines, antidepressants, antipsychotics), iron, o Neuro: autonomic neuropathy, DM, Hirschsprung’s, multiple
aluminum (antacids, sucralfate), diuretics, clonidine, sclerosis, anorexia nervosa, spinal cord injury, PD, stroke
amiodarone, CCB, ondansetron, barium o Obstruction: anal stenosis, colon ca, stricture, rectocele,
o CTD: amyloidosis, sarcoidosis compression
Diagnosis/Treatment (AGA: Gastro 2013;144:211; Gastro 2013;144:218; JAMA 2016;315:185; AJG 2023;118:936-954)
• History: duration of sx, frequency & consistency of stools, straining, incomplete evacuation, use of manual maneuvers, alarm sx
(sudden change in BMs in >50 y/o, blood, weight loss, strong FH of CRC or IBD), medications
• Initial workup: DRE (fissures, hemorrhoids, tone), CBC (for anemia); colonoscopy if +FOBT or alarm sx or fevers (or if concern for
IBD/CD); other labs not needed unless otherwise clinically warranted
• Further workup (primarily outpatient): see algorithm from AGA guidelines
o Anorectal manometry (ARM), balloon expulsion test: identifies dyssynergia
o Barium, MR defecography: useful when ARM inconsistent with clinical
impression, can identify anatomic abnormalities
o Colonic transit study: via radio-opaque makers (Sitz markers) or wireless
motility capsule study (less commonly used)
• Management: see medications below
o Secondary constipation: treat underlying cause
o STC/NTC: fiber, laxatives (PEG, stimulant), hydration; add secretory agents if
persists; consider transit study on meds or UGI eval if still no improvement
o Dyssynergic defecation: biofeedback/pelvic floor PT; if persists, eval. for
STC/NTC; surgery if structural abnormality
Hospital Constipation Prophylaxis and Bowel Regimens
• Risk factors: >60 yo, prolonged immobility, decreased fluid intake, preexisting constipation, meds (see above)
• Docusate (Colace) lacks evidence in hospitalized pts (J Pain Symp 2000;2:130) & increases cost & pill burden (JAMA Int Med
2016;178:1216); senna 2 tabs QHS > senna + colace (J Pall Med 2008;11:575)
• General ppx for at-risk patients: senna 2 tabs QHS or BID standing + Miralax 17g daily prn
• High-risk ppx for patients on opioids: senna 2 tabs BID standing + Miralax 17g daily standing
• Stepwise approach: senna + Miralax  Miralax to 34 g  mag citrate/lactulose  bisacodyl PR  enemas  disimpaction
 1-2 L GoLYTELY (Note: disimpaction can cause vasovagal; all rectal procedures are contraindicated in neutropenia)
o Types of enemas (stepwise): tap water  soap suds/mineral oil  milk and molasses (MGH specific)  Fleets
• Avoid Mg and Phos containing products in renal insufficiency (MOM, Mg citrate, Fleets enema)  can cause nephrocalcinosis
I R R I T A B L E B O W E L S Y N D R O M E ( I B S ) (AGA: Gastro 2022;163:118,137)
• Definition (Rome IV Criteria): recurrent abd discomfort ≥ 1x/wk for 3 months a/w
2+ of: (1) related to defecation, (2) ∆ in stool frequency, (3) ∆ in stool form. No
alarm symptoms (sudden change in BMs in >50 y/o, blood, weight loss, FH of
CRC or IBD, nocturnal diarrhea, or calprotect/lactoferrin)
• Epidemiology: 10-15% of US adults; younger age pop, ♀ > ♂. Assoc. with
fibromyalgia, chronic fatigue syndrome, psych disorders, GERD
• Types: IBS-C (constipation-predominant), IBS-D (diarrhea-predominant), IBS-M
(mixed), IBS-U (unclassified), by Bristol Stool Scale
• Initial workup: phys exam as per above; if IBS-D, send calprotec/lactoferrin,
Giardia, celiac serologies
• Treatment: all - exercise, diet Δ (low FODMAP), soluble fiber (psyllium
preferred, particularly for IBS-M as helps normalize stool)
o Mild: IBS-C - osmotic lax (e.g. PEG) +/- antispasmodics (dicyclomine,
hyoscyamine, peppermint oil); IBS-D – loperamide (45 min before
meal, sched), bile acid sequestrant (cholestyramine)
o Moderate/Severe: IBS-C – secretagogues; IBS-D – rifaximin (2 week
trial, can retreat if good resp), TCAs (start at 10mg), alosetron (♀), eluxadoline (risk of pancreatitis, contraind. for patients
w/o gallbladder, biliary hx, or significant alcohol use)

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Gastroenterology Constipation, IBS, & Colonic Disorders

COLONOSCOPY PREP
• Adequate preparation = essential. Place pt on clears at noon the day prior to colonoscopy; the prep should start no later than 6PM.
• To prep: 6oz SUPREP ( tolerability (AJG 2019;144:305)) + 10oz water  32oz water over the following hour  repeat both steps in
the morning. If stool is not clear, give additional 6oz SUPREP. Contact GI team if not completely see-through to reschedule
M E D I C A T I O N S F O R C O N S T I P A T I O N (Gastro 2013;144:218; JAMA 2016;315:185; ACG: AJG 2023;118:936-954)
Type Agent Dose Notes
Fiber: Psyllium (Metamucil), 1 tsp up to TID (for Fiber is first-line agent. In some (esp. STC), can 
Bulk agents
Methylcellulose (Citrucel) psyllium: up to 30g/d) bloating in large amounts. Start low & 
Less effective than other laxatives; may be inferior to
Surfactants Docusate (Colace) 50-360mg QD
psyllium, not recommended (JHM 2019;14:110)
Senna 1-4 tabs QHS or BID  colon secretions, motility. Can cause cramping
Stimulants 5-15 mg up to 3x/w up to
Bisacodyl (Dulcolax)  colon motility, can cause cramping. PO QHS or PR AM
4wk
Polyethylene glycol
Modestly more effective/better tolerated (less bloating)
Miralax (PEG alone) 17 g QD; max 34g/d
than lactulose (Cochrane Rev 2010).
GoLytely/NuLytely (PEG+salts)
Non-
Lactulose, sorbitol 15-30 ml QD or BID  flatulence/bloating. Less effective than PEG
absorbed
Benefit of gastric acid neutralization and water retention
substances Milk of magnesia (MOM) 15-30 mL QD or BID
in stool. Avoid in renal insufficiency
(osmotic)
Exact mechanism unknown. Can be used as a lower-
Magnesium citrate 150-300 mL QD volume alternative to PEG bowel prep (2+ bottles +
Dulcolax PR). Avoid in renal insufficiency
Tap water, soapsuds All work via lubrication. Soapsuds also stimulates
Enemas mineral oil, Fleets (sodium Varies peristalsis. Fleets is hypertonic and also has osmotic
phos.), milk & molasses effect. Avoid Fleets in elderly or renal insuff. (phos).
24μg BID for STC/NTC; Binds Cl- channel & increases secretion,  small bowel &
Lubiprostone (Amitiza)
8μg BID for IBS-C colon transit. Most common side-effect is nausea
Secretagogue
Linaclotide (Linzess) 145-290μg QD Guanylate cyclase-C agonists;  Cl/HCO3 secretion &
Plecanitide (Trulance) 3g QD colonic transit; Most common side effect is diarrhea
Pro-kinetic 5-HT4 selective receptor agonist;  cholinergic and
Prucalopride (Motegrity) 2mg daily
drugs noradrenergic neurotransmission to promote motiltiy
Methylnaltrexone: At MGH, methylnaltrexone approved only if on stable
Peripheral
Methylnaltrexone, Naloxegol 1 dose SQ QOD PRN dose of opioids ≥ 2 weeks x3d w/o BM AND failed
opioid
(pegylated naloxone), - 38-62kg: 8mg multiple other laxatives. Contraindicated in obstruction,
receptor
Alvimopan - 62-114kg: 12 mg small risk of perforation (AGA guidelines for OIC: Gastro
antagonists
- CrCl <30: 1/2 dose 2019;156:218; Gastro 2019;156:229)
COLONIC DISORDERS
Stercoral Colitis
• Definition: inflammation of colonic wall 2/2 pressure from impacted feces   intraluminal pressures  ischemic pressure necrosis
• Epidemiology: nursing home residents; bedridden; hypothyroidism; diabetic enteropathy; opioids; clozapine; other constipating meds
• Treatment: fecal disimpaction if no defects in colonic wall on CT; consider CTX/flagyl if septic. Avoid opiates which ↓ motility.
Diverticulosis
• Definition: herniation of colonic mucosa into muscularis propria, where vasa recta penetrate
• Risk factors: low fiber diet ± chronic constipation, BMI, physical inactivity,  age (present in 50% of patients >60yo; common
incidental finding), smoking, NSAIDs. ♀ = ♂. Nuts, seeds, popcorn, alcohol, red meat, and fat consumption are not associated.
• Location: 90% L-sided (primarily sigmoid) in “Western” populations; 75-85% R-sided in Asia
• Bleeding: painless bleeding of vasa recta within the diverticuli. 75% are self-limited & resolve with bowel rest. Recurrence is common.
Tx if bleeding does not stop: 1) colonoscopy, 2) angio (IR embolization), 3) surgery. See Lower GI Bleed
• Diverticulitis develops in 4% of pts with diverticulosis (Clin GI Hep 2013;12:1609).
Diverticulitis
• Definition: infection of diverticuli: micro-perforation secondary to erosion of the diverticular wall by increased intraluminal pressure
o Uncomplicated (75%): abdominal pain (LLQ), fever, leukocytosis, anorexia, Δ in BMs (diarrhea or constipation)
o Complicated (25%): bowel obstruction, abscess, fistula (potentially with bladder, vagina, skin, or peritoneum), or perforation
• Diagnosis: characteristic s/sx & CT A/P (I+,O+) (findings: diverticula, bowel wall >4mm, inflammation w/ pericolic fat ± abscess/fistula)
• Management (AGA: Gastro 2015;149:1944):
o Uncomplicated (medical): PO abx x7d (cipro/flagyl, bactrim/flagyl, or augmentin), bowel rest. No abx is noninferior to abx if
uncomplicated (Clin GI Hep 2021;19:503; Br J Surg. 2019;106:1542)–use selectively (immunocomp., pregnant, comorbidities, sepsis)
o Complicated: IV abx (GNR + anaerobe coverage), bowel rest, and IR/surgical evaluation (peritonitis typically present; evaluation
for abscess drainage or colonic resection)
• To prevent recurrence: high fiber diet (Gastro 2015;149:1950), less red meat/refined grain. avoid NSAID, exercise, d/c smoking/alcohol
• Follow-up: consider colonoscopy 6-8w after to evaluate for malignancy; advised in patients with complicated diverticulitis, first episode
of diverticulitis, or alarm symptoms; can be deferred if recent colonoscopy (within 1yr) (Gastroenterology 2021; 160(3):906)
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Gastroenterology Esophageal and Upper GI Disorders

OROPHARYNGEAL DYSPHAGIA ESOPHAGEAL DYSPHAGIA
Symptoms Difficulty initiating swallowing; drooling, coughing, aspir. Difficulty seconds after initiation, food stuck in esophagus
1°: achalasia, esophageal motility disorders (e.g. distal
Neuro- Central: tumor, stroke, PD, ALS, MS, polio
esophageal spasm, hypercontractile “Jackhammer” esoph.)
muscular Peripheral: neuropathy, myasthenia gravis
2°: diabetes, scleroderma, CTD, amyloid, Chagas, MG
Etiologies

(solids + liq.) Muscular: polymyositis, muscular dystrophy

(Chicago classification: Neurogastro Motil 2021)
Intrinsic: tumor, stricture, infection, EoE, rings, webs (e.g.,
Structural Intrinsic: tumor, XRT, trauma/surgery/infection, Zenker’s
Plummer-Vinson), pills (NSAIDs, doxy, tetracyc., bisphosph)
(solids > Extrinsic: anterior mediastinal mass, goiter, cervical
Extrinsic: vascular rings (e.g. dysphagia lusoria), Ao. enlarge.,
liquids) spondylosis
LA compression, mediastinal, substernal thyroid, LAD
History: onset & duration, progressive/intermittent, solid/liquid & localization, +/- odynophagia, underlying conditions (e.g.,
CNS, malig., thyroid, DM, scleroderma), offending meds (pill esophagitis), immunocompromise (Candida, CMV, HSV
Work-up esophagitis), infectious (Diphtheria, Botulism, Lyme, Syphilis), XRT. Dysphagia in older adults is not normal aging
PE: appearance (systemic disease or CNS issue), HEENT exam (evidence of LAD, tumor, asymmetry), FOBT
Labs (consider): CBC, TFTs, ANA, α-Scl-70, α-centromere, α-RNP, α-Jo, HgbA1C, iron studies, HIV, AChR-Ab
1) Bedside swallow, SLP consult, VSS, neuro eval, 1) EGD may be most useful, though barium swallow is often a
2) Modified barium swallow; ENT if c/f mass, voice good first test (mucosal pathology or structural abnormality)
Diagnostics
change, airway involvement. 2) If normal  esoph. manometry to diagnose motility d/o
3) Consider chest/neck CT to dx extrinsic compression 3) Consider chest/neck CT to dx extrinsic compression
Zenker’s diverticulum: p/w halitosis, regurgitation of food/aspiration, cough. Tx: endoscopic surgery (rigid vs. flexible)
Strictures & rings: if lumen <13mm, dysphagia common. Tx: PPI, dilation, intralesional steroid injection, stent
Distal esophageal spasm: uncoordinated peristalsis a/w intermittent chest pain & regurgitation; barium swallow:
corkscrew (vs. nml). Hypercontractile esophagus: similar sx; nml barium swall. Tx (both): PPI, nitrates/CCB/PDEi, TCA
Selected Achalasia: progressive dysphagia solids/liquids + regurgitation; barium swallow: bird’s beak distal esophagus;
Conditions manometry: absent distal peristalsis, incomplete LES relaxation; EGD/CT r/o pseudo-achalasia (2/2 CA), Can be a/w
Chagas. Tx: CCB, nitrates, pneumatic dilation, myotomy, POEM, botox, esophagectomy (AGA: AJG 2020; JAMA 2015)
Infectious esophagitis: odynophagia; often immunosuppressed – Candida, HSV, CMV
Eosinophilic esophagitis (EoE): dysphagia, refractory GERD sx. EGD w/ stacked rings, strict. Bx: >15 eos/hpf. Tx: PPI,
diet Δs (dairy, wheat > soy, eggs, nuts, fish), topical steroids (MDI/neb/liq.); consider dilation (AGA: Gastro 2020;158:1776)

G A S T R O P A R E S I S (ACG: AJG 2022;117:1197-1220)

Definition: delayed gastric emptying of solid food w/o mechanical obstruction
Sx: nausea, vomiting of undigested food, early satiety, postprandial fullness, bloating ± abd pain
Etiologies: diabetes (vagus nerve damage 2/2 hyperglycemia), post-viral, post-surgical (e.g. vagus nerve injury post-bariatric surgery),
systemic disease (thyroid, critical illness, Parkinson’s, CTD), meds (opiates, CCB, anti-cholinergics), chronically decreased PO
Dx: Gastric emptying tests (hold motility meds, opiates 48h prior). Diagnose with scintigraphy (most common) or wireless motility
capsule/C13 breath test. EGD to exclude obstruction.
• Gastric scintigraphy: (radiolabeled egg > liquid) positive if >10% retention at 4hr and/or >60% retention at 2hr.
o Indications: post-prandial n/v, abd pain, early satiety; reflux unresponsive to therapy; patients with DM w/ poor glycemic control;
evaluate for rapid gastric emptying; w/u of cyclic vomiting syndrome
o Contraindications: hyperglycemia at time of test > 275 mg/dL, motility agents or opiates within 48-72 hours (JNMT 2008)
Labs: TSH, ANA, A1c, tot protein, alb, CBC/diff
Treatment: Optimize glucose control, small meals w/ low fat & low non-digestible fiber. Prokinetic before meals: (metoclopramide, risk of
TD, restrict use <12 wk), erythromycin (tachyphylaxis, give drug holidays after 2wk), D2 agonists (domperidone). Antiemetics (zofran,
benadryl). Venting G-tube or pyloromyotomy if refractory. J-tube for nutrition if wt loss. Rec against nortriptyline/haldol.

C E L I A C D I S E A S E (ACG: AJG 2023;118: 59-76; Gastro 2019;156:885; NEJM 2012;367:2419; Vaccines 2020)
Pathophysiology: abnormal immune response to gluten  diarrhea, wt loss, abd pain, IDA, vit D def, dermatitis herpetiformis
Who: s/sx or laboratory e/o malabsorption i.e., chronic diarrhea with wt loss, steatorrhea, postprandial abdominal pain, bloating; first
degree relative; unexplained elevated
LFTs; unexplained IDA; diarrhea in T1DM; tTG-IgA (Sn 63-93%, ⊝ Yes
Gluten free? HLA-DQ2/DQ8
dermatitis herpetiformis, atrophic glossitis. Sp >95%) + total IgA
Adults may have more mild initial IgA def No
presentation than children. ⊝
Diagnosis: see flow diagram IgG-deamidated gliadin Dx ⊕
⊕
Biopsy: intraepithelial lymphocytes, crypt peptides (IgG - DGPs)
elongation/hyperplasia, villous atrophy, & tTG-IgG
⊝
Marsh Score AJG 2023;118: 59-76) ⊕
Treatment: strict gluten-free diet; IgA anti- ⊕ Gluten challenge
EGD with biopsies Recheck
TTG titer should normalize over time. x2-8 weeks
serologies
Replete vitamin deficiencies (A, D, E, ⊕
B12), Cu, Zn, carotene, folic acid, Fe +/-
thiamine, vit B6, Mg, and selenium. Give CD ⊝
HBV booster every 10 yrs. Bx, serology discordant

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Gastroenterology Inflammatory Bowel Disease

CLINICAL PRESENTATION
Epidemiology: ~1.3% USA prevalence, onset 15-30y, bimodal w/ 2nd peak 50-80y. Genetic predisposition (↑risk: +FamHx, other
autoimmune dz; female (Crohn’s); ↑incidence in Jewish, white, however increasing dx rate in non-white) + environment (↑risk:
Western diet, abx, NSAIDs, sleep deprivation, OCPs; smoking ↑risk for CD & ↓ risk for UC)
Pathophysiology: Inappropriate immune response leading to chronic inflammation of the GI tract. Multifactorial, likely involving
genetic susceptibility, immune dysregulation, defective mucosal barriers, and the gut microbiome (NEJM 2020;383:2652)
Ulcerative Colitis (Lancet 2017;389:1756) Crohn’s Disease (Lancet 2017;389:1741)
Bloody diarrhea (constipation possible in limited
Abd pain (usually RLQ), diarrhea (+/- bloody) (constipation w/
rectal dz), lower abd pain (usually LLQ/LUQ),
strictures), n/v, wt loss, perianal fistula/abscess
cramps, tenesmus
S/S
Extra-luminal: rheum (seroneg. arthritis, ankylosing spondylitis), cutaneous (erythema nodosum, pyoderma
gangrenosum, apthous ulcers), ophthalmic (uveitis, iritis, episcleritis), heme (DVT, AIHA), GU (Ca-Ox / UA stones),
pulm (bronchiectasis, ILD), hepatic (PSC)
Continuous colonic mucosal inflammation Skip lesions, strictures, fistulae, transmural inflamm.,
Dx spreading proximally from rectum, limited to noncaseating granulomas, cobblestoning, may involve any
mucosa/submucosa, crypt abscesses, pseudopolyps part of GI tract (including upper)
Fulminant colitis, anorectal strictures/dysfxn,
Obstruction (2/2 strictures), abscess, fistula, malabsorption
Complic. perforation
risk CRC: colo after 8y of active disease, q1-3y w/ random 4-quadrant bx q10cm of colon
Montreal Age (<16, 17-40, >40)
Classif. Extent (proctitis, left sided, extensive pancolitis) Location (ileal, colonic, ileocolonic, upper GI)
Criteria (Gut Severity (clinical remission, mild, mod, severe) Behavior (non-stricturing and non-penetrating, stricturing,
2006;55:749) penetrating, perianal involvement)

INPATIENT WORK-UP AND MANAGEMENT

Hx: stool patterns, bloody BM, nocturnal sx, fever, weight loss, rashes, joint pain, ulcers, vision changes
Ddx: infectious colitis, ischemic colitis, celiac disease, lactose intolerance, IBS, diverticular colitis, microscopic colitis, lymphocytic
colitis, collagenous colitis, appendicitis, functional abdominal pain
Labs: CBC, BMP, LFTs (ALP?PSC), ESR/CRP, Mg, fecal calprotectin, C. diff, Stool Cx, O&P, Fe/TIBC/B12 (if anemic). Prior to
medication initiation: Hep serologies and TSpot (immunomodulators), TPMT enzyme (metabolizes AZA toxic metabolites) for AZA.
Ensure up to date on vaccines (no live vaccines after starting biologics or immunomodulators).
Imaging: CT A/P if concern for peritonitis/obstruction/mass (abscess). Consider CT/MRI enterography to eval small intestine.
Consider pelvic MRI to eval perianal dz
Procedures: Colonoscopy with biopsy (+/- EGD) necessary to confirm dx

Severity UC (Truelove Witts, Mayo Clinic Score) CD (CD Activity Index)

Ambulatory, tolerates PO/no dehydration, no
Mild <4 stools (bloody or not), afebrile, nml ESR, Mayo score 3-5
pain/toxicity
Moderate 4-6 BM, bloody BM, low fever, pain, mild anemia, Mayo score 6-10 Failed 1st line tx, low fever, N/V, wt loss, pain, anemia
>6 BMs, Hb <10.5, fever, HR >90, wt loss, ESR >30,
Failed advanced tx, toxic, abscess, obstruction,
Severe Mayo score 11-12; Pred. of aggressive disease course include <40
peritonitis, cachexia
yo, disease severity, and early steroid need (Gastro 2020;158:1450)

IBD Flare Therapy

† Methylpred 20mg q8h IV

Mild/Moderate (outpatient) Severe (inpatient)
‡ risk of DVT/PE in IBD pts
ΔIn pts w/ fistula, abscess,
Aminosalicylates (UC>>CD) IV steroids† ± rectal steroids, IV Fluids/lytes peritonitis, pouchitis,
Budesonide oral/enema High-risk DVT ppx‡, ± Cipro/Flagyl
Δ
perforation, high fever,
(UC/CD)  Tspot, Hep serologies, TPMT enzyme leukocytosis, bandemia
PO prednisone (UC/CD) No NSAIDs/opioids/antidiarrhealsϒ ϒ
risk of tox meg in UC
Antibiotics (CD) NPO for endoscopy (c/s IBD team, inform outpt GI), advance * Bridge to maintenance tx
diet as tolerated σAnti-TNF, anti-integrin, etc.

Refractory disease/toxic
Resolution* Refractory after 3-5 days: Advance therapyσ, surgical consult

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Gastroenterology Inflammatory Bowel Disease

Step-up therapy: No longer the standard of care for IBD treatment. Treatment instead is guided by risk factors and prognosis.
(AGA: Gastro 2021;160:2496).
Poor prognostic factors in CD: Young age at diagnosis, initial extensive bowel involvement, ileal/ileocolonic involvement, perianal/severe
rectal disease, deep ulceration, and patients with penetrating or stenosisng disease phenotype (AJG 2018;113:481).
Poor prognistic factors in UC: Young age at diagnosis, extensive colitis, hospitalization for colitis, severe endoscopic disease.
Indications for Surgery: CD: severe stricture, fistulae, abscess, failing medical tx. UC: refractory dz, perforation, toxic megacolon
Management Guidelines: NEJM: NEJM 2021:385:1302
• CD: ACG: AJG 2018;113:481, AGA: Gastro 2021;160:2496
• UC: ACG: AJG 2019;114:384, AGA: Gastro 2020;158:1450, Post Proctocolectomy Pouchitis: AGA 2024;166:59
IBD T H E R A P E U T I C S
Class Drug Use Notes & Adverse Effects (AE)
PO budesonide 1st-line in mild CD, 2nd-line to ASA for mild
Budesonide (PO/PR), Pred
Steroids Induction UC, but can be 1st-line for mod. AE: osteoporosis, infection,
(PO), Methylpred (IV)
AVN, AI, delirium
Sulfasalazine: pro-drug with more AEs, also systemic effects
Sulfasalazine Induction +
Mesalamine forms differ in gut penetration: Pentasa (ileum,
Aminosalicylates Mesalamine (PO: Pentasa, Maintenance
R>L colon), Ascol (R>L colon), Lialda & Apriso (pancolon),
(UC>>CD) Ascol, Lialda, Apriso. for moderate
Canasa & Rowasa (distal). AE: HA, fever, rash, diarrhea,
PR: Canasa, Rowasa) disease
pancreatitis, sperm count, AKI
Typically as combination therapy for induction; can be
Thiopurines monotherapy for maintenance. Test Thiopurine
Induction +
Azathioprine (pro-drug) methyltransferase (TPMT) prior to use. 6-TGN for monitoring.
Maintenance
6-MP AE: n/v, hepatitis, BM suppression, malignancy (non-melanoma
skin cancer, lymphomas)
For pts unable to tolerate thiopurines. Typically as combination
Immunomodulators Antimetabolites Induction +
therapy. Give with folic acid. AE: n/v, hepatotoxicity, BM
Methotrexate Maintenance
suppression, lung injury
C/i in s/o toxic megacolon. Labs: troughs (q2-3d) Cr, Mg, lipids,
Calceneurin Inhibitors Induction only LFTs
Cyclosporine for severe UC AE: renal injury,K, infxn, neurotox/seizures (esp. if Mg or
cholesterol)
Infliximab for induction in pts naïve to biologics.
Anti-TNF
Contraindicated if toxic megacolon, pyogenic infxns. Typically
Infliximab (Remicade) Induction +
in combination with immunomodulator. Preferred agent with
(IV/SC) Maintenance
concomitant IBD-associated arthritis. If flare during
Adalimumab (Humira) (SQ) for mod-
maintenance: measure trough (24hrs prior to dose) and
Certolizumab (Cimzia)-CD severe
antidrug Ab. If non-responsive despite adequate levels ->
Golimumab (Simponi)- UC
another class. AE: infxn, TB/HBV reactiv., malignancy
Induction in pts naïve to biologics. VARSITY (NEJM
Anti-Integrins 2019;381:1215): in mod-severe UC, achieved clinical remission
Induction +
Vedolizumab (Entyvio) at 52wks vs. Humira, but w/ greater steroid use. AE: infusion
Biologics Maintenance
(IV/SC) (NEJM 2013;369:699; reactions, nasopharyngitis
for mod-
NEJM 2013;369:711) ACG recommends against natalizumab due to risk for JC-virus
severe
Natalizumab (Tysabri) associated PML, can consider if pt adheres to JC virus
monitoring
IL-12/23 Ustekinumab shown to have no differences in outcomes
Uztekinumab (Stelara) compared to adalimumab in Crohn’s patients (Lancet
(NEJM 2019;381:1201) Induction + 2022;399:2200). Sometimes preferred for less frequent
Risankizumab (Skyrizi, IL- Maintenance ~q8week dosing.
23 only) (Lancet AE: infection, HA, nasopharyngitis, nausea, abdominal pain,
2022;399:2031) arthralgias
JAK inhibitors
Tofacitinib (Xeljanz) PO, Consider if previously failed anti-TNFs
Induction +
(NEJM 2017;376:1723) AE: infection, herpes zoster, HA, nasopharyngitis, arthralgias,
Maintenance
Upadacitinib (Lancet CPK elevation, acne
Small Molecules
2022;399:2113)
(Oral)
Sphingosine-1-phosphate Induction +
Prior to initiation: CBC, LFTs, EKG. Vaccinate for shingles.
receptor remission
Ohthalmic exam (uveitis, macular edema). Need sleep study if
Ozanimod moderate to
at risk for OSA. AE: anemia, nasopharyngitis
Etradimod (Velsipity) severe UC
Diet: Medeterranian Diet for all with IBD. UC: red meat. CD: saturated fats, fruits & veg (Clin Gastro Hep 2020;18:1381)
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Gastroenterology Intestinal Disorders

I L E U S A N D S M A L L B O W E L O B S T R U C T I O N (J Trauma Acute Care Surg. 2012;73:S362; J Trauma Acute Care Surg. 2015;79:661)
Ileus Small Bowel Obstruction
Definition Slow gut motility without obstruction Obstruction of intestinal flow, can be partial or complete
Risk Intra-abdominal surgery, peritonitis, sepsis, ischemia, meds Prior surgery (adhesions), hernia, inflammation (e.g. IBD), malignancy,
Factors (opioids, anti-cholinergics); worsened by K radiation, foreign body ingestion, gallstones
N/V, mild diffuse pain, obstipation (BMs and flatus), N/V (may be bilious/feculent), severe cramping pain, obstipation, abd
Signs/
bloating/gassiness, abd distention, tympany to percussion, distention, tympany to percussion, high pitched or absent BS,
Symptoms
BS, no peritoneal signs dehydration, ± peritoneal signs
KUB (less useful): decompressed colon, air-fluid levels
KUB or CT: dilated bowel loops, air in colon, no transition
Studies CT w/ PO + IV contrast: transition point, decompressed colon, ±
point, no peritoneal free air
peritoneal free air, ischemic signs, closed loop obstruction
Initial mgmt.: Bowel rest, decompression via NGT for N/V and
distension, IVF, replete lytes. Broad spectrum abx if c/f
ischemia/necrosis or bowel perf
Bowel rest, decompression via NGT if mod/severe sx, avoid Nonsurgical mgmt.: Gastrografin challenge for adhesive SBO only.
opioids, replete lytes (goal nl), methylnaltrexone if hx opioid Draws fluid into the bowel, decreasing wall edema and stimulating
Treatment
use, parenteral nutrition if extended NPO period, treat peristalsis. Contraindicated in pregnancy, bowel ischemia/necrosis/perf,
underlying etiology abdominal surgery w/i 6 weeks
Indications for surgery: any suspicion of ischemia/necrosis or perf,
closed loop obstruction (volvulus), hernia, intussusception, tumor,
foreign body, gallstone, SBO persists after 3-5 days
Acute colonic pseudo-obstruction (Ogilvie’s): typically elderly, hospitalized pts. A/w severe illness, systemic dz (thyroid, DM, renal or liver failure),
neuro (spinal cord compression/trauma, PD, MS), meds (opiates, CCB, anticholinergics). Dx: CTAP + rectal contrast (C.I. if peritonitis) Tx: conservative
(NPO, IVF, NGT/rectal tube), neostigmine if cecal diam. >12 or if fail conservative tx. Colonic decompression if fails. (ASGE: Gastro Endosc 2020;91:228)

Sigmoid volvulus: associated with long redundant colon, constipation (may cause sigmoid dilation and prolongation), colonic dysmotility. Insidious
abdominal pain, constipation, abdominal distention, nausea. Dx: “Bent inner tube” on KUB, confirmed with CTAP
Tx: Alarm signs (perforation or peritonitis): immediate surgical management (detorsion may cause reperfusion injury). No alarm signs: endoscopic
detorsion followed by semi-urgent surgery (allows for complete bowel prep prior to surgery) (World J Emerg Surg 2023;18:34)
I N T E S T I N A L I S C H E M I A (ACG: AJG 2015;110:18; NEJM 2016;374:959)
Colonic Ischemia Acute Mesenteric Ischemia Chronic Mesenteric Ischemia
- Recurrent, post-prandial pain
- Cramping pain (mostly LLQ) 
- Arterial: sudden, pain out of proportion to exam (“intestinal angina”); dull, crampy,
Chief mild/mod hematochezia
- Venous: often insidious onset, waxing/waning abd starts 10-30m after PO, lasts 1-3h
Concern - Uncommon: gangrenous bowel or
distention, N/V, diarrhea ± occult blood - N/V, early satiety, BM Δs
fulminant colitis
- Wt loss, fear of eating
Non-occlusive (95%): SMA occlusion (~75%): embolic (40-50%):
- Progressive atherosclerotic narrowing
- Watershed areas (splenic flexure, AF/endocarditis/aortic plaque, thrombotic (20-35%):
at origins of vessels
rectosigmoid) most susceptible; 25% R- underlying ASCVD, dissection/inflammation (<5%)
- Risk Factors: tobacco, HTN, DM, HLD
sided Non-occlusive (5-15%): hypoperfusion or vasospasm after
Etiology (ASCVD RFs), >60 yo, female,
- Risk factors: cardiopulmonary bypass, CV event/surgery, cocaine, vasculitis
& Risk dissection, vasculitis, fibromuscular
MI, HD, aortic surgery, dehydration, Mesenteric vein thrombosis (5-15%): trauma, surgery,
Factors dysplasia, radiation
extreme exercise thrombophilia, local inflammation (pancreatitis, diverticulitis,
- Vessels: SMA, IMA, celiac artery
- Vessels: SMA, IMA biliary infxn), stasis due to cirrhosis/portal HTN, malignancy
- If pain is constant, consider acute
- Prognosis: 85% spontaneously resolve Prognosis: mortality 50%, but can be 70-90% if delay in
thrombosis
in 2w, 5% recurrence diagnosis leads to intestinal gangrene
Labs: most abnormalities arise after progression to
Labs: lactate, WBC, LDH, CK, & Imaging:
necrosis. pH, lactate, AGMA (in 50%), WBC >15K (75%),
amylase if advanced. Stool guaiac ⊕ in - CTA: ⊕ if stenosis of ≥ 2/3 major
stool guaiac ⊕ in ~50%
~50%. Stool Cx, O+P, C. diff vessels (celiac, SMA, IMA). 91% with 2
Imaging: KUB: Ileus, colonic dilatation, pneumatosis. CT
Imaging: CT A/P (I+/O+): wall vessels, 55% with all 3 vessels
A/P (ideally CTA; no oral contrast): wall thickening,
Dx thickening, edema, thumbprinting, - Doppler U/S to measure mesenteric
pericolonic fat stranding, pneumatosis, arterial occlusion,
pneumatosis, no vessel occlusion blood flow and r/o median arcuate
portomesenteric venous gas.
Colonoscopy (to assess extent): ligament syndrome
Angiography: if CTA non-diagnostic but high suspicion, or if
petechial blood, pale mucosa, segmental - Gastric tonometry exercise testing
vasculitis affecting small-medium size vessels; potentially
edema/ulceration - Angiography (see left)
therapeutic with stent/tPA
Occlusive disease: NGT/NPO, IVF/blood product - Surgical revascularization: open vs.
- Bowel rest, IVF, d/c vasoconstrictive
- Broad-spectrum abx endovascular or angioplasty +/-
meds
- Anticoagulation (heparin +/- tPA) if not bleeding for stenting, Peri-op mortality 0-16%; no
- GNR/anaerobic abx if ≥ mod sxs (per
occlusive dx role for prophylactic intervention if
society recs)
Tx - If infarction/peritonitis/perforation  surgery asymptomatic
- If suspicion for necrosis, gangrene, or
- Thrombectomy/embolectomy vs. intra-arterial vasodilators - Restenosis common (7% open
perf, call surgery
(IV papaverine) vs. thrombolysis revasc; 34% endovascular)
- If atherosclerosis on imaging, treat with
Non-occlusive: treat underlying cause (statins etc.) - TPN for nutrition support
lipid lowering agent
Mesenteric vein thrombosis: anticoag x3-6m - AC if acute-on-chronic ischemia
Celiac artery compression syndrome: chronic, recurrent abdominal pain related to compression of the celiac artery by the median arcuate ligament.
Abdominal pain, weight loss +/- nausea, diarrhea. Exam often normal but epigastric bruit may be heard
Dx: arteriography, duplex ultrasound, gastric tonometry, ganglion nerve block Tx: celiac artery decompression (MIS or open) (Cardiovasc Diagn Ther
2021;11:1172)

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Gastroenterology Nutrition & Feeding

G E N E R A L A P P R O A C H (ACG: AJG 2016;111:315)
1) Assess nutritional status (Clin Nutr ESPEN 2018;26:13)
o Hx/Exam: dietary intake/tolerance, n/v/d, muscle/fat wasting, weight loss, functional capacity (grip strength, ADLs). Screen for
food insecurity (Hunger Vital Sign)
o Weight loss as indicator of malnutrition: >2% in 1 wk, >5% in 1 month, >7.5% in 3 months, >10% in 6 months, >20% in 1yr
o Labs: INR prolongation may indicate malnutrition. Consider vitamin levels if history/exam is suggestive. Albumin can be a helpful
marker (may be confounded by sepsis). Avoid using pre-albumin, transferrin, retinol binding protein as indicators of nutrition.
o 24-hr calorie count; nutrition consult if c/f malnutrition (screen with NRS-2002 or NUTRIC Score in hospitalized pts)
2) Determine dietary route (oral > enteral [EN] > parenteral [PN]):
o Oral: assess aspiration risk, dysphagia, odynophagia. Consider SLP c/s for dietary modifications (e.g. pureed, thick liquids etc.)
o Enteral (EN): NGT if pt unable to tolerate oral diet safely or meet caloric needs through oral diet alone, may need enteral nutrition.
Measuring gastric residuals not recommended (NEJM 2014;370:1227). In critically ill pts, consider Tylenol absorption test to assess
enteral nutrient/med absorption. Place tube post-pyloric (JG/PEG-J) if gastroparesis, gastric outlet obstruction, severe vomiting, or
high aspiration risk. Consider PEG if head/neck cancer, dysphagia, neurodegenerative disease, prolonged recovery.
o Parenteral: TPN (central access) or PPN (peripheral). Used when GI tract non-functional or no reliable enteral access anticipated.
3) Initiate diet: early EN initiated within 24-48 hours of admission, advance to goal within 48-72 hours (as tolerated, 3-4 days if refeeding
risk). Nutrition/TPN consult for specifics. Watch for refeeding (see below).
ARTIFICIAL NUTRITION
Supplements (order “Adult/Pediatric Nutrition Supplements”): Ensure Plus (standard), Ensure Clear (low fat), Mighty Shake (standard, has
lactose), Magic Cup (pudding, dysphagia), Glucerna Shake (DM), Nepro (CKD), Beneprotein (protein powder), Prosource Protein (liquid)
TUBE FEED FORMULAS
TPN: “Nutrition Support Team” in PPD (p22445)
Indication Formula Consider if ≥7d w/o enteral nutrition. Need central access w/
Normal absorptive capacity Osmolite 1.0 clean dedicated lumen (PICC Preferred). Order by 1PM to
Long-term TF start same day. Page about new orders if close to 1 PM.
Jevity 1.5
Prevent constipation (high fiber) • Monitor for complications of TPN (if applicable):
Wound healing (high protein) o Metabolic effects: hyperglycemia (2x > enteral),
Promote
ICU patients (on propofol) serum electrolyte alterations, refeeding syndrome
IBD, pancreatitis Vital (see below), Wernicke’s encephalopathy, hepatic
post-abdominal surgery (semi-elemental) dysfunction, biliary sludge/gallstones. Small amt of
Respiratory failure/ARDS insulin included but can be adjusted if needed
Osmolite 1.5
Volume overload (high protein) o Monitor BMP, Mg, Phos, LFTs, and TGs
Renal or liver failure (low Na/K/phos) Nepro o Bloodstream infection: increased risk of infection
Beneprotein/ProSource (fungal and bacterial)
Wound healing Liq Protein • If no central access, Clinimix (amino acid solution in
(modular protein) dextrose, no fats) can be given as PPN
TwoCal HN • To stop TPN, coordinate careful transition to EN w/
Max fluid restriction
(normal protein, no fiber) nutrition; stop when EN provides >60% energy needs
Diabetes Glucerna (AJG 2016;111:315)

REFEEDING SYNDROME
Electrolyte/fluid shifts caused by initiation of nutrition in severely malnourished patient (d/t insulin surge and increased Na/K pump activity),
can be fatal; most likely to occur within 72h of starting nutritional therapy (Nutrition 2018;47:13; Front Gastro 2019;11:404)
• Risk factors: minimal/no intake for 5 (minor) to 10 (major) days, significant wt loss, age, excessive alcohol use, malnutrition 2/2
chronic dz/malabsorptive conditions, anorexia nervosa, persistent n/v/d, low initial lytes (J Clin Med 2019;8:2202)
• Characteristics: early: Phos, K, Mg, vitamin deficiency (thiamine); late: cardiac damage (CHF), respiratory failure (volume
overload); other s/s: AMS, n/v, diarrhea, tremors, paresthesia
• Prevention and management: close lab monitoring (at least BID when concerned) w/ aggressive repletion of electrolytes (Phos, K,
Mg, Ca; IV preferred) for first 3 days & administer thiamine before refeeding regardless of level, slow/hypocaloric initial feeding,
consider fluid/sodium restriction, cardiac monitoring in high-risk patients. Stop feeding if electrolyte abnormalities persist.
SPECIAL CONSIDERATIONS
• IBD flares, pancreatitis: early enteral feeding (ideally within 24-72 hrs of admission)
• Critical care: EN should start within 48 hrs of ICU stay (superior to TPN if GI tract functional); contraindications include high dose
pressors/unstable (risk of bowel ischemia, hold off until patient more stable) or significant GI pathology (e.g. GI bleed or obstruction)
for which patient should be NPO (Clin Nutr ESPEN 2019;38:48)
• Dementia: avoid dietary restrictions, use nutritional supplements as needed; guidelines recommend against TFs in advanced
dementia (a/w higher mortality), lack of evidence to support appetite stimulants (Nutr Clin Pract. 2014;29:829; Clin Nutr 2015;34:1052)
TIPS FOR ORDERING INPATIENT DIETS
• Diabetes: Consistent carbohydrate (must add carb gram restriction within order)
• Cardiac: no added salt (4g) vs 2g Na (renal/liver/cardiac). Consider fluid restriction (usually 2L) for HF/SIADH/cirrhosis
• GI: low fat (GI) for gallbladder dz/fat malabsorption/pancreatitis, red dye restricted for pre-EGD/colo
• Renal: low K (2 g), low protein in some CKD (NOT dialysis), low phos for ESRD
• Onc: Neutropenic/BMT (no garnishes), PET scan is carbohydrate restricted
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Gastroenterology Pancreatitis and Pancreatic Mass

E T I O L O G Y (NEJM 2014;317:1983)
• Gallstones/sludge (40-75%): #1 in female sex • Drugs (<5%): Class Ia: ACEi, dapsone, Lasix, Flagyl, pentamidine,
• Alcohol (30%): #1 in male sex statins, sulfa, tetracycline, valproate, mesalamine; Class Ib:
• Hypertriglyceridemia (10%): #3; suspect if TG>1000 amiodarone, azathioprine/6-MP, dexamethasone; Class II: didanosine,
• Anatomic: ampullary diverticula/stenosis, duodenal estrogen, propofol, tamoxifen, HCTZ (CGH 2007;5:648)
stricture, tumor, divisum, parasites, foreign body • Toxins: smoking, organophosphates, methanol, scorpion venom
• Post-ERCP: 4.5% of ECRP; rectal NSAIDs risk • Infections: viral (Coxsackie, EBV, CMV, HIV, Mumps, VZV, HAV, HBV,
(Endoscopy 2020; Endosc Int Open 2019;7:477) HSV), bacterial (Mycoplasma, Legionella, Leptospira, Salmonella),
• Autoimmune: IgG4, +ANA (Am J Gastro fungal (Aspergillus), parasitic (Toxoplasma, Crypto, Ascaris)
2018;113:1301) • Ischemia: vasculitis (SLE, PAN), hypoTN/shock, cholesterol emboli
• Acute hypercalcemia: Ca activates panc enzymes • Trauma: blunt, especially s/p MVA
• Genetic: CFTR, CTRC, PRSS1, SPINK1, A1AT • Idiopathic (10-25%)
D I A G N O S I S (Revised Atlanta Classification: Gut 2013;62:102; Pancreatology 2014;14:324)
• Presentation: LUQ/epigastric abd pain (90%, band-like pain to back in 50%), N/V (90%), ileus, jaundice, flank/umbilical ecchymoses
• History: prior episodes, EtOH/smoking, prior GI procedures (e.g., CCY, ERCP), meds, infxn sx, autoimmune hx, FH
• Diagnosis – need 2/3: 1) consistent clinical presentation, 2) lipase >3x ULN, 3) characteristic imaging (US, CT w/contrast, MRI)
• Labs: lipase (no need to trend; false ⊕ in CKD, DKA), CBC (often Hct), BMP (Ca), LFTs (ALT > 3.5x ULN has 95% PPV for
gallstone pancreatitis: AJG 1994;89:1863), lipid panel (TGs). Recheck HCT/BUN <6-8hrs after presentation.
• Imaging: All: RUQUS for gallstones; If needed for dx: CT (90% sens), also for complications (~48-72h); MRI/MRCP if c/f necrosis,
stricture, or stone w/ neg RUQUS
• Risk Factors for Severe AP: +SIRS, Age >55, BMI >30, BUN >20, HCT >44, pleural effusions/infiltrates, extra-pancreatic collections
• Severity: mild: absence of organ failure and local or systemic complications; moderate: organ failure that resolves within 48 hours or
local/systemic complication; severe: organ failure >48h (22% mortality). Organ failure: can use modified Marshall score
• Prognosis: SIRS mortality. Many scoring systems to identify mild type; BISAP is quick/superior. RANSON, APACHE II less practical.
M A N A G E M E N T (AJG 2024:119(3)e419; WATERFALL trial NEJM 2022; 389:989)
• IV fluids: moderately aggressive in 1st 24hrs: infusion 1.5mL/kg + PRN boluses 10mL/kg over 2h if hypovolemic (UOP < 0.5ml/kg/hr
or SBP <90). Goal is to not allow Hct or BUN to rise, most pt will benefit from 3-4L in 1st 24hrs. LR superior to NS, avoid LR if Ca.
Avoid aggressive resus after 24-48h (risk of abdominal compartment syndrome, intubation). Ok to d/c at 20 hr if tolerating PO >8hr.
• Pain control: IV opioids Abx: No role for prophylactic abx.
• Nutrition: start PO (low fat/residue) within 24-48h as tolerated. At 5-7d, if PO not tolerated start continuous TFs (NG > NJ). Enteral >
TPN: maintains intestinal barrier, prevents gut flora translocation. TPN a/w risk of infections, organ failure/death
• Reverse precipitants: treat Ca or TG, stop culprit meds. For gallstone pancreatitis, urgent ERCP (24hrs) if cholangitis or CBD
obstruction. CCY ideally prior to discharge as biliary complications if CCY is delayed (Lancet 2015;386:1261).
o HyperTG: insulin gtt (0.1-0.3U/kg/hr) + D5, q1h FSBG (initially), q12h TG. Goal TG <500 (may take several days). (MGH ellucid
policy) No good evidence for apheresis. If tolerating PO, fibrates are first line. DC: lifestyle Δs, lipid clinic referral
• If idiopathic: Repeat RUQUS and triglcyerides as an outpt. If second episode of iAP, recommend cholecystectomy +/- genetic testing
C O M P L I C A T I O N S (AGA: Gastro 2020;158:67; NEJM 2016;375:1972)
Local Vascular Systemic
<4 weeks >4 weeks Thromboses: splenic, portal,
Abd. compartment
Acute peripancreatic fluid Pancreatic pseudocyst: fluid collection SMV; AC if portal vein or bowel
Interstitial syndrome: intra-abd
collection: w/o features of w/ well-defined wall. If dx unclear, EUS ischemia
edematous pressure >20 w/ new organ
pseudocyst; resolve w/ FNA (amylase). Drain if sx, rapidly ,
pancreatitis failure. Check bladder
spontaneously w/o drainage infxn (endo vs. perc/surg) Pseudoaneurysm: erosion of
pressure in ICU.
Acute necrotic fluid Walled off necrosis: encapsulated GDA/splenic artery  bleeding
ARDS: via phospholipase
collection: intra- or extra- necrotic collection. Drain at >2-4 wks if sx into pseudocyst. Suspect if
degradation of surfactant
pancreatic or infxn (endo vs. perc) Hgb, expansion of fluid
Necrotizing Metabolic: Ca, Glc, TG
Infected necrosis: 1/3 become infected, suspect ~7-10d. Early enteral collection, unexplained GIB.
pancreatitis GIB: via pseudoaneurysm
feeding ↓risk Dx: discuss CT-FNA, assume infected if +Bcx/gas. Abx: Dx: arterial phase CT
AKI
(cefepime or cipro) + flagyl vs. pip/tazo vs. carbapenem in critically ill. Tx: IR embo. prior to drainage
DIC
Drainage/necrosectomy: urgent if unstable vs delay >4w if stable on abx of fluid collection

C H R O N I C P A N C R E A T I T I S (ACG: AJG 2020;115:322)

Repeat acute attacks (esp. EtOH & smoking)  fibrosis & loss of glandular tissue  chronic abd pain, exocrine insufficiency (steatorrhea,
wt loss, vitamin deficiencies), endocrine insufficiency (brittle DM). Lipase/amylase may be  early but nml/low as more tissue lost. ⊕ Fecal
fat, stool elastase. CT/MRI with calcifications, ductal dilation, parenchymal atrophy. risk of pancreatic CA. Consider genetic testing.
Tx: pancreatic enzyme replacement (Creon), ensure vit ADEK replete, pain control. Refer to MGH Pancreas Center: 617-726-5523
P A N C R E A T I C M A S S E S (Curr Gastro Rep 2013;15:347)
• Solid: adenoCA (85-90%), autoimmune panc, neuroendocrine (1-5%), 1o lymphoma (<1%), mets (melanoma, RCC, etc.)
• Cystic: inflammatory (pseudocyst, paraduodenal wall cyst), neoplastic (malignant potential: main duct IPMN >> side branch IPMN >
mucinous cystic = solid pseudopapillary > serous cystadenoma) (AJG 2018;113:464; Gastro 2015;148:819) Refer to MGH cyst clinic.
• Imaging: CT abd pancreatic mass protocol; EUS with FNA for lesions >2-3cm (87% Sn, 96% Sp); MRI useful in <2 cm lesions or
when vascular involvement needs to be delineated better; consider PET-CT, MRCP for malignancy in IPMN (70% Sn, 92% Sp)
• Labs: CA 19-9 (⊕ in 80% of panc CA, 86% Sn, 87% Sp), CEA (mucinous), ANA, IgG4 (if autoimmune suspected)
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Gastroenterology Weight & Weight Loss

OBESITY
Definition: BMI*: <18.5 underweight; 18.5-24.9 normal weight; 25-29.9 overweight; 30-34.9 class I obesity; 35-39.9 class II obesity; >40
class III (“severe”) obesity. Avoid using stigmatizing terms such as “morbid” or “extreme”
• Increased waist circumference: >40 inches men, >35 inches women
• *Caveat: studies suggest using a lower BMI criterion for people of Asian descent (AADI BMI calculator)
Epidemiology: 30-45% Americans; Midwest, South > NE, West; non-Hispanic Black > Hispanic > non-Hispanic White > Asian; associated
with lower SES, income, education (CDC 2020; NEJM 2019;381:2440).
Associated with: HTN, HLD, T2DM, CAD, stroke, GB disease, OA, sleep apnea, certain cancers, ↑ all-cause mortality
Goal: 5-10% weight loss within 6 months. Benefits at 3-5% weight loss  improved TG,  risk of DM; >5%  BP, improved BG; 10%
decreases fibrosis in MASLD
Treatment:
• Diet: 1200-1500 kcal/d for women; 1500-1800 kcal/d for men; a diet that is 500-750 kcal/day less than usual. Variety of diets – all
achieve calorie deficit: balanced low calorie, higher protein, low carbohydrate, low-fat vegan, vegetarian, macronutrient targeted,
Mediterranean style, intermittent fasting (Circ 2014;129:S102). Patient choice based on highest likelihood to adhere, comorbidities.
• Lifestyle: comprehensive program – dieting, exercise (effective for weight loss but much more important for weight maintenance),
behavioral techniques (Weight Watchers, outpatient programs)
• Meds: see table. Indication: wt loss & mgmt. + diet for adults w/ initial BMI ≥30 or BMI ≥27 + wt-related comorbidities (DM, HTN, HLD)

M E D I C A T I O N S F O R W E I G H T L O S S (APJ 2016:43; JAMA 2016;315:2424; DMJ 2020;44; NEJM 2022; 387:205)

Agent Mechanism of Action Dose Side effects Notes
1st line. Benefit in
Sema: 0.2mg → N/V/D/C, delayed GE,
GLP-1 receptor agonist DM, CAD,
2.4mg weekly pancreatitis, cholecystitis. Incr.
Semaglutide (weekly, Subq) (Tirzepatide GLP-1/GIP MASLD; Potential
Lira: 0.6mg → 3mg risk of thyroid cancer in animal
Liraglutide (daily, Subq) agonist) benefit in HFpEF
daily models. Contraindicated if
Tirzepatide (weekly, Subq) (NEJM 2021;384:989) (NEJM2023;389:1
(JAMA 2021; 325: 1414) Tirz: 2.5mg → 15mg personal/FHx of medullary
(JAMA 2022; 327:138) 069)
weekly thyroid cancer/MEN2.

Inhibit GI lipases that Steatorrhea, fecal incontinence

Reduced BG,
hydrolyze TGs into FFA; (>10%); reduced ADEK
Orlistat (Xenical, Alli OTC) 60-120mg TID AC lipids, BP; not
increases fecal excretion absorption; drug interactions;
first-line
of TG rare liver/ kidney injury
Phentermine = stimulant,
Teratogenic. Interacts with
anorectic, increases 3.75/23mg x14d  Should not be
metformin. Activating/
Phentermine/topiramate satiety by action at the 7.5/46mg x12w; used w/ HTN or
insomnia. Paresthesia,
(Qsymia) hypothalamus can increase to max CAD, caution in
constipation, dry mouth, URI,
Topiramate = mechanism 15/92mg anxiety
dysgeusia
for weight loss unknown
Works at hypothalamus to Nausea, constipation, HA, Not first line due
Naltrexone/bupropion increase satiety + 8/90mg daily vomiting; lower seizure to side effects,
(Contrave) inhibition of mesolimbic 16/180mg BID threshold; increase BP; cannot helpful in patients
dopamine (reward) circuit be taken with opioids w/ AUD
Choice of agent: GLP1/GIP likely most effective. Greater weight loss with tirzepatide (GLP-1/GIP) vs semaglutide (GLP-1) though no
RCTs (NEJM 2022; 387:205). Current data: tirze> sema > lira. If <5% weight loss within 3 months on full dose can try another agent/ med
class. Metformin can produce modest weight loss in overweight patients (<5% weight loss) but not FDA approved for weight loss.
W E I G H T L O S S S U R G E R Y (NEJM 2007;356:2176; Lancet 2022;400:441)
Indications: adults with BMI >40 or BMI >35 with obesity-related conditions & who have not
responded to behavioral tx w/ or w/o pharmacotherapy. Consider MGH Weight Center referral.
Mechanism of weight loss: restriction (reduced stomach capacity) ± malabsorption
(nutrient absorption by shortening the absorption length of the small intestine)
Types: Restrictive: sleeve gastrectomy, gastric banding, intragastric balloon; Malabsorptive:
jejunoileal bypass (JIB) and biliopancreatic diversion (BPD) ± duodenal switch; Restrictive +
malabsorptive: Roux-en-Y gastric bypass (RYGB), single-anastomosis duodenoileal bypass
with sleeve gastrectomy
Benefits: 49% (endo sleeve) excess wt lost at 1y vs 3.2% (control) (Lancet 2022;400:441);
remission of DM, HTN, HLD, OSA; CV & cancer mortality (30-50%), extended life
expectancy by 3 years (NEJM 2020;383:1535; Annals 2020;173:694), improvements in NASH
(JAMA 2021;326:2031)
Complications:
• <30d: anastomotic leak, MI, and PE (total 0-1.55%) (Obes Rev 2018;19:529)
• Long term: food aversions/intolerances, vitamin deficiencies (ADEK, Vit C, thiamine,
B12, folate, iron, zinc, selenium, copper, Ca), psychosocial impairment, dumping
syndrome (rapid transit of hyperosmolar carbs cause fluid shifts, hypotension,
sympathetic surge), osteoporosis, weight re-gain, increased sensitivity to EtOH

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Gastroenterology Liver Chemistry Tests

Upper Limit of Normal (ULN): ALT (IU/L): 33 (males), 25 (females); ALK-P: 115 (males), 100 (females) (ACG: AJG 2017;112:18)

1) Identify pattern of liver test abnormality. R-factor = (ALT / ULN) / (Alk-P / ULN) 2) Identify chronicity
Hepatocellular: R factor >5, ↑↑ ALT Acute: < 6 months
Mixed: R factor 2-5, ↑ ALT, ↑ Alk-P Chronic: > 6 months
Cholestatic: R factor <2, ↑↑ Alk-P, ↑↑ GGT, ↑ ALT

Hepatocellular markers: Released from hepatocytes in response to injury AST/ALT ratio: Usually ALT>AST (AST
ALT: Expressed primarily in liver, more specific has shorter serum half-life, 18h vs 36h).
AST: Expressed in liver. Also cardiac muscle, skeletal muscle, kidney, brain, and RBCs Ratio can vary widely, especially in acute
liver injury
Magnitude of ALT and AST elevation: • Mild AST/ALT elevation with ratio
• Extreme elevation (>15x ULN or >1,000 U/L): Most c/w acute liver injury, ~2:1 suggestive of alcohol related
including ischemic hepatopathy (shock liver), acetaminophen toxicity liver dz
• Moderate elevation (5-15x ULN): Ddx as above AND acute hepatitis A/B/C/E • Typical AST/ALT ratio in
• Borderline to mild elevation (<5x ULN): Broad ddx: meds/toxins (see below), hepatocytes is 2.5:1, so ratio >2.5:1
chronic liver disease (etoh, MASLD, hepatitis B/C, autoimmune, hemochromatosis, think non-hepatic source of AST
Wilson’s, alpha-1-anti-trypsin deficiency), biliary obstruction (mixed markers) (Clin. Bio. Rev.; 2013; 34(3)117)

For more info and work-up, see Acute Liver Injury & Failure, Non-Alcoholic Fatty Liver Disease, Viral Hepatitis, and Alcohol
Related Liver Disease

Cholestatic markers: Released from cells lining bile canaliculi/ducts in response to injury
Alk-P: Expressed in bile duct, liver, kidney, bone, intestinal mucosa, and placenta. Confirm source with GGT as below or fractionated
assay (slow to result). If accompanied by other LFT abnormalities (e.g. elevated bili), do not need to confirm source.
GGT: Expressed in bile duct, liver, pancreas, and kidney. Supports biliary/hepatic source of Alk-P. Non-specific marker of EtOH use.
Magnitude of Alk-P elevation:
• 1-1.5x ULN: Common in adults over age 60 (esp women 2/2 increased bone turnover)
• 1-3x ULN: Any liver disease
• >4x ULN: Cholestatic liver dz, infiltrative liver dz (e.g. cancer and amyloidosis), bone conditions characterized by rapid bone
turnover. In absence of ↑ bili or ALT/AST, suggests early cholestasis or hepatic infiltration by tumor or granulomatous dz

Cholestasis: extrahepatic 2/2 anatomic obstruction to bile flow (e.g. choledocholithiasis, malignancy, PSC, HIV/AIDS cholangiopathy)
vs intrahepatic 2/2 functional impairments of bile formation (e.g. PBC, infiltration (sarcoid, atypical fungal infxn, malignancy))

For more info and work-up, see Biliary Disease

Markers of liver function:

Bilirubin: Heme breakdown product conjugated in the liver and excreted in bile. Decay is related to albumin half-life (3 weeks).
• Conjugated (direct) bilirubinemia: ↑ total and direct bilirubin seen in hepatocellular damage, impaired excretion, or biliary
obstruction. Only conjugated bilirubin excreted in urine, so bilirubinuria also implies liver disease. Consider bile duct
obstruction/stricture, hepatitis (viral, toxic, EtOH, ischemic, autoimmune), PBC, PSC, infiltrative dz, congestive hepatopathy,
TPN, HCC, Rotor syndrome, and Dubin-Johnson syndrome.
• Unconjugated (indirect) bilirubin: ↑ indirect bilirubin caused by ↑ production, ↓ uptake by the liver, or ↓ conjugation.
Consider hemolysis, hematoma resorption, fasting, ineffective erythropoeisis, and Gilbert syndrome (usually < 3mg/dL).
Albumin: ↓ in chronic liver disorders such as cirrhosis. Not specific to hepatic dysfunction; can also occur in systemic inflammation,
nephrotic syndrome, malnutrition, ascites (due to marked increase in plasma volume)
Prothrombin (PT-INR): ↑ PT-INR due to ↓ vitamin K absorption/use 2/2 parenchymal liver disease. PT measures extrinsic coag
pathway and relies on vitamin K dependent coag factors. First, consider consumption of clotting factors (e.g., DIC, GI bleed) and meds.
Vitamin K challenge (10mg IV x3 days): If INR normalizes, likely deficiency (e.g., dietary intake, malabsorption [inadequate
bile salts needed for Vit K uptake], abx altering gut flora). Vit K supplementation does NOT improve INR in liver disease.
Platelet Count: ↓ platelets associated with ↓ synthesis (liver produces thrombopoietin), splenic sequestration in portal hypertension,
and ↑ destruction through multiple pathways.
For more info and work-up, see End Stage Liver Disease

Commonly used drugs that cause hepatocellular injury: acetaminophen, allopurinol, amoxicillin-clavulanate, amiodarone, aspirin,
carbamazepine, clindamycin, fluconazole/ketoconazole, fluoxetine, glyburide, heparin, hydralazine, INH, labetalol, lisinopril, losartan,
methotrexate, niacin, nitrofurantoin, NSAIDs, phenytoin, protease inhibitors, statins, sulfa drugs, trazodone, valproic acid
Supplements: kava-kava, black cohosh, green tea extract, chaparral, ephedra, ji bu huan, germander, weight loss supplements
Illicit drugs: anabolic steroids, cocaine, ecstasy, PCP. Environmental: Amanita mushrooms
See livertox.nih.gov for full list (J Hepatology 2019;70:1222; NEJM 2019;381:264; US Gastro Hep Rev 2010;6:73; AJG 2017;112:18)

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Gastroenterology Biliary Disease

G A L L S T O N E D I S E A S E S (J Hep 2016;65:146)
Cholelithiasis: presence of stones in GB (6% of M, 9% of F) Choledocholithiasis: stones in common bile duct
- Sx: aSx (<20% develop clinical events), larger, multiple, older gallstones
and Female sex events [Gastro 2016;150:156]) vs biliary colic (dull
- Sx: RUQ pain, n/v, jaundice; may be asx
RUQ/epigastric pain, 30m-6h, caused by GB contracting around
- Labs: ALP, bilis ± AST/ALT
sludge/stone, often postprandial & w/ n/v)
- Dx: RUQUS to look for CBD dilation >7mm (poor Sn for
- Dx: RUQUS (Sn 84%, Sp 99%) > CT (Sn 55-80%); EUS if ⊝; labs wnl
visualizing stones themselves); repeat RUQUS, MRCP, or
- Stone types: cholesterol (most common); pigment: Crohn’s/ileal disease,
EUS if equivocal
extravascular hemolysis, TPN
- Tx: ERCP w/ stone removal; interval CCY
- Tx: asymptomatic: observe; CCY only if at risk for GB CA (stone >3cm,
- Complications: ascending cholangitis, acute pancreatitis
porcelain GB, GB adenoma); symptomatic: elective CCY
FYI: can occur s/p CCY if de novo formation in CBD
- Complications: cholecystitis, choledocholithiasis, pancreatitis, GB CA,
gallstone ileus, Mirizzi syndrome (compression of CBD/CHD)
Cholecystitis: stone in cystic duct  inflammation of GB ± infxn Cholangitis: ascending biliary infxn 2/2 obstruction in CBD
- Sx: RUQ pain (w/ radiation to back/shoulder), Murphy’s sign, n/v, fever - Etiologies: stone, stricture (malignancy, PSC, AIDS), liver
- Labs: WBC; +/- ALP, Bili; if ALP/Bili c/f CBD obstruction fluke
- Acalculous cholecystitis: GB stasis/ischemia w/o obstruction. Unexplained - Sx: Charcot’s triad: RUQ pain, fever, jaundice; Reynold’s
fever, WBC. RF: trauma, burns, TPN, severe illness, fasting, sepsis, pentad: + shock and AMS
immunosuppression (CGH 2010;8:15) - Labs: WBC, ALP, Bili, ± AST/ALT (can be )
- Dx: RUQUS (GB wall thickening, pericholecystic fluid, sonographic - Dx: RUQUS (ductal dilation), MRCP/ERCP. Tokyo
Murphy’s)  HIDA scan if ⊝; pre-tx w/ 2mg IV morphine Sn (given by Guidelines for dx & severity (J Hep Panc Sci 2018;25:17)
nuclear rads at MGH) (AJR 2016; 207:865). Tokyo Guidelines for dx & severity - Tx: broad spectrum abx (Zosyn or CTX/flagyl; carbapenem
(based on deg. of organ dysfunction) (J Hep Panc Sci 2018;25:41) if life-threatening) x7d; urgent ERCP w/ decompression
- Tx: abx (Zosyn or CTX/Flagyl). Early (<7d) CCY during hospitalization  (<24-48h) if severe (associated organ dysfunction/shock)
morbidity (Br J Surg 2015;102:1302). If critically ill with biliary sludge and or if fails to improve on abx x 24h. Perc drainage if ERCP
LFTs or high surgical risk & fails to improve after 1-3d abx  not feasible. Interval CCY if due to gallstones
percutaneous cholecystostomy with IR. Stop abx 24h post-CCY unless - Higher risk for cholangitis after palliative CBD stent
septic/perc chole: 4-7d (JAMA Surg 2019;154:873) placement in patients with malignant obstruction
- Complications: gangrenous cholecystitis, emphysematous cholecystitis - Complications Post-ERCP: pancreatitis, bleeding, infxn,
(gas-forming organism), perforation, enteric fistula, gallstone ileus perforation (GIE 2017;85:32)

AUTOIMMUNE BILIARY DISEASES

Primary Biliary Cholangitis (PBC) (AASLD: Hepatology 2019;69:394) Primary Sclerosing Cholangitis (PSC) (AASLD: Hepatology 2022)
Autoimmune destruction of intrahepatic bile ducts Affects intra- + extrahepatic bile ducts
- Clinical manifestations: F>M; asx (50-60%), pruritus, fatigue, sicca - Clinical manifestations: M>F; asx (50%), pruritus and fatigue (most
symptoms, cirrhosis (late) common), cirrhosis (late); cholangitis due to strictures
- Dx: ≥2 of the following: ALP ≥1.5x ULN; Antimitochondrial - Dx: ALP ± bili; may have +auto-Abs but of unclear significance;
Ab>1:40 titer (95% pts); biopsy findings; can have AMA (-) PBC MRCP (segmental strictures), ± biopsy if suspect small duct PSC
- Biomarkers: SPATA31A3 and GARP (Liver Int. 2019;39:2124) (otherwise not required); check AMA/IgG4 to exclude alt. dx
- Associated with: hypothyroidism (20% pts), anemia, metabolic - Associated with: IBD (60-80%; UC>Crohn’s), cholangioCA (10-
bone disease, Sjogren’s, autoimmune hepatitis (overlap) 15% pts), metabolic bone disease, AIH (overlap), HLA-83
- Tx: ursodiol: 1st line, progression & survival (NEJM - Tx: supportive; ursodiol may improve sx, ERCP for stricture, liver
1994;330:1342); obeticholic acid (FXR agonist) 2nd line after transplant definitive tx (MELD exceptions for recurrent
ursodiol, C.I. in decomp ESLD & portalHTN, fibrates: off label cholangitis, intractable pruritus): 20% recurrence 5 years post-LT
altern, C.I. in decomp ESLD; cholestyramine for pruritus; - Hepatobiliary CA surveillance q6-12 month (imaging, CA 19-9,
modafinil for fatigue; liver transplant: 22% recurrence in 5yrs AFP) improves survival (Hepatology 2018;67:2338)
MALIGNANT DISEASE OF THE BILIARY TRACT
Gallbladder carcinoma: risk factors: gallstone disease (34x more likely to develop CA), porcelain GB, GB polyps, PSC, chronic infxn
- Diagnosis: LFTs usually normal, CA19-9/CEA; RUQUS best screening test, then CT/MRI/MRCP
Cholangiocarcinoma: may be extrahepatic (90%) or intrahepatic (10%); risk factors: PSC, liver flukes, intrahepatic gallstones
- Diagnosis: ALP, bili, CA 19-9/CEA ± AST/ALT depending on deg. of obstruction; RUQUS screening test, then ERCP/MRCP/EUS
SPHINCTER OF ODDI DYSFUNCTION
F>M; Often occurs post-CCY, provoked by opioids (due to spasm of sphincter) and associated with idiopathic recurrent pancreatitis, Rome
IV criteria (MD Calc). Diagnosis: ERCP/manometry. Treatment: surgical/endoscopic sphincter ablation (Curr Gastro Rep 2015;17:31)
R A D I O G R A P H I C A S S E S S M E N T O F S U S P E C T E D B I L I A R Y P A T H O L O G Y (Am J Roentgenol 2011;197:551)

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Gastroenterology Acute Liver Injury & Failure

Acute Liver Injury (ALI): acute liver injury <26w with coagulopathy but NOT encephalopathy
Acute Liver Failure (ALF): encephalopathy & coagulopathy (INR >1.5) of <26w in pts without cirrhosis or known liver disease
Presentation: fatigue, lethargy, anorexia, n/v, RUQ pain, pruritis, ± jaundice  ascites, confusion in ALF (and may progress to coma)
Initial diagnostics: CBC w/ diff, CMP, PT/INR, fibrinogen, LDH, T&S, lactate, ABG, arterial ammonia, FSBG, hCG, HIV, APAP, blood/
urine tox screen, PETH, viral/autoimmune serologies (as below), amylase/lipase, CT head if HE, RUQUS w/ Doppler (JHM 2017;12:184)

Type Etiologies Diagnostics

Acetaminophen (dose-depend: >6g/day or 150/mg/kg/day for 24-48h,
Drugs >4g/day or 100 mg/kg/day for >48h): most common cause of ALF in US History: all APAP-containing meds, herbal
(see Toxins: Amanita phalloides mushroom, occupational exposures (CCl4) supplements, new meds/OTCs, EtOH use
LiverTox) Idiosyncratic DILI (dose-indep): abx (*Augmentin), AEDs, anti-TB, etc. Labs: APAP level, EtOH, tox screen
(Alcohol-related hepatitis: considered acute-on-chronic and not ALF)
History: travel, PWID, occupational exposures,
HAV, HBV, HCV (rare w/o HBV co-infection), HDV (risk co-infection > sexual exposures, vesicular rash, blood transfusion,
superinfection or HBV alone), HEV (pregnant or in endemic areas) immunocompromised state
Viral
Others: HSV (may be anicteric, WBC), adenovirus, EBV, HIV, CMV, Labs: HAV IgM, HBsAg & core IgM, HCV Ab &
VZV (if immunocompromised) PCR, HSV Ab; check HDV if +HBV, HEV if preg.,
VZV if immunocompromised, EBV PCR
Systemic hypoTN (sepsis, cardiac dysfunction), vasoconstricting drugs History: HoTN, hypercoag. state, drugs/meds
Ischemic/
(cocaine, meth.), Budd-Chiari (hepatic vein thrombosis), veno-occlusive Imaging: RUQUS w/ Doppler; CT or MRI/MRV are
vascular
disease (post-HSCT); ALT/LDH <1.5 suggestive of ischemic alternatives; consider TTE if no known cause
Autoimm. AIH: F>M; can present as ALF but uncommon Labs: IgG (), ANA, ASMA, anti-LKM-1
Wilson’s: <40, F>M; AST>ALT often >2; nml/ALP & ALP/Tbili <4; a/w History/exam: FH, slit-lamp exam for KF rings
Genetic
DAT-neg. hemolytic anemia, uric acid, rapidly progressive renal failure Labs: ceruloplasmin (though may be nml/ in ALF)
HELLP, acute fatty liver of pregnancy, malignant infiltration (breast CA, Labs: U/A if pregnant
Others
SCLC, lymphoma, myeloma), HLH, heat stroke, hepatectomy Liver bx if dx remains elusive after thorough eval

M A N A G E M E N T O F A C U T E L I V E R F A I L U R E (AASLD: Hep 2012;55:965; AGA: Gastro 2023;118:1128; NEJM 2013;369:2525)

• Consult Hepatology for OLT workup. Urgency based on HE severity (ASAP if grade 3-4) Hepatic Encephalopathy
• Monitoring: freq. coags, CBC, ABG, CMP, NH3; q2 hr neuro checks to monitor for worsening HE or Grade Mental Status Asterixis
ICP (esp. gr. 3-4), e.g., Cushing’s triad (bradycardia, irregular respirations, and wide pulse I Attention deficit ±
pressure) requiring more intensive monitoring. Lethargy
II +
• Hemodynamics: IVF (NS) and/or pressors (norepi ± vaso); goal MAP ≥75 for cerebral perfusion Moderate confusion
• N-Acetylcysteine (NAC): tx APAP toxicity ± non-APAP ALF w/ gr 1-2 HE (Gastro 2009;137:856). III
Somnolence
+
Initial tx: 150mg/kg/h, 1h, max 15g 12.5mg/kg/h, 4h, max 5g 6.25mg/kg/h, 16h, max 10g Marked confusion
• Encephalopathy: intubation for HE gr. ≥3; cerebral edema in HE gr. 3 (25-35%) & 4 (75%) IV Coma +
o Lactulose in ALF controversial: bowel distent. may worsen outcomes Complications of Acute Liver Failure
o CRRT lowers ammonia levels within 3 days and decreases mortality (Hep 2018;67:711) Neuro HE, cerebral edema
o If risk for cerebral edema (gr. 3-4, aNH3 >150, ARF, pressors), prevent w/ 3% NaCl CV Shock, high-output state
for Na 145-155 (Hep 2004;39:464), HOB 30°, stimulation; avoid: overhydration & PEEP Pulm. Pulm. edema, ARDS
o Treat cerebral edema w/ IV mannitol (0.5-1g/kg bolus x1-3); if impending herniation, GI GIB, pancreatitis (esp. APAP)
hyperventilate to PaCO2 ~25-30 (temporary; may worsen edema by  ischemia); Endo. Glc, adrenal insuff.
pentobarbital/thiopental if other measures fail (may cause hoTN which  CPP) Renal dysfxn in >50%; met.
Renal
• Seizures: phenytoin; benzos if refractory. Consider routine EEGs for subclinical seizure acid. (lactate), Na, K, P
Heme Coagulopathy, plt, DIC
• Infection: high risk for bacterial (Staph, Strep, GNRs) & fungal. Check serial BCx, UCx, SCx,
Infection In ~90%; bacterial + fungal
CXR. May not fever, WBC, or have localizing s/s, though worsening HE or AKI may be sign.
Low threshold for empiric abx ± antifungal (esp. if prolonged hosp., abx, steroids, CVVH). Avoid nephrotoxic/hepatotoxic abx
• Coagulopathy/bleeding: can trial vit K, routine FFP not recommended. In ICU, ppx w/ PPI. Viscoelastic tests (e.g., TEG) may be more
accurate assessment of coagulopathy

ETIOLOGY-SPECIFIC MANAGEMENT
• APAP  Ingestion <4h or rising level, give activated charcoal. Ingestion >30g or deranged AST/ALT, give empiric NAC. See Figure 1:
treatment pathway, Figure 2: revised nomogram, Figure 3: NAC guidelines in Consensus Statement: JAMA 2023;6(8)e2327739
• HBV/HCV  OLT; possible role for antivirals in HBV King’s College Criteria (specific but not sensitive)– list for OLT if:
• HAV/HEV  supportive care, possible OLT • Acetaminophen-induced ALF: Arterial pH <7.3 OR all 3 of:
• Amanita poisoning  IV silibinin (20-50 mg/kg/d x2-4d) INR >6.5, Cr >3.4, grade 3-4 HE
• AFLP/HELLP  delivery; follow up for need for OLT • Other causes of ALF: INR >6.5 OR 3/5: age<10 or >40, Tbili
• HSV/VZV  acyclovir (5-10mg/kg q8h); may need OLT ≥17, INR >3.5, time from jaundice to encephalopathy >7d,
• AIH  consider glucocorticoids; OLT if needed unfavorable etiology (seronegative hepatitis, DILI, Wilson’s)
• Wilson’s  OLT; chelation ineffective Prognosis: MELD score >25 = poor prognosis. HBV, Wilson’s, Budd-
• Budd-Chiari  anticoag, TIPS, surg decompression, lysis, OLT Chiari, AIH, DILI also associated with poor prognosis.

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Gastroenterology Viral Hepatitis

H E P A T I T I S A (CDC 2020)
Fecal-oral transmission from personal contact or contam. food/water, international travel. Sx: abrupt n/v, anorexia, malaise, fever, jaundice,
RUQ/abd pain, ALT>AST (often >1000), bilirubin/ALP. 70% of adults have sx, lasts 2-8w (often self-limited), jaundice peaks after 2w.
Dx: ⊕ anti-HAV IgM, persists 3-6mo, or RNA. Anti-HAV IgG forms at 2-3w, confers immunity. Tx: Care is supportive unless ALF
(rare,<1%). Vaccinate if: MSM, PWID, chronic liver dz, HIV, travel, homeless, certain exposures. Havrix and Vaqta = 2 doses. Twinrix = 3
doses, covers HBV. Pre and post-exposure ppx: Single HAV vaccine +/- immune globulin in non-immune pts w/in 2 wks of exposure.
H E P A T I T I S B (AASLD: Hepatology 2018;67:1560; USPSTF: JAMA 2020;324:2452)
HBsAg. Pts from area w/ prev. > 2%, parents from high prev. area >8%, HIV+, PWID, MSM, close contact of HBV+
Screening
person, unexplained elevated LFTs, those requiring immunosuppressive therapy (e.g. done before chemo)
Risk Factors Vertical transmission (SE Asia), sexual contact, PWID, needlestick, unvaccinated (US before 1994), immunosuppress.
Acute: 70% subclinical, 30% w/ jaundice, <1% ALF. S/S: anorexia, nausea, fatigue, RUQ discomfort. ALT>AST in
Clinical Pres.
1000s, +/- Bili. Chronic: ⊕HBsAg >6mo. (often w/ persistent ALT), occurs <5% adults. 40%cirrhosis
Extrahepatic Polyarteritis Nodosa, membranous nephropathy/MPGN, aplastic anemia, arthritis
Diagnosis HBsAg, anti-HBs, anti-HBc total (identifies all infected). Interpretation below
First line: tenofovir or entecavir (Hepatology 2018;67:1560) PegIFN option for young w/o cirrhosis for a finite treatment
Treatment
course. Monitor HBV DNA, LFTs, Cr while on therapy. Goal: suppress HBV DNA, lose HBsAg & HBeAg
HCC Screen. Indications: all HBsAg+ w/ cirrhosis, HBsAg+ & high-risk (Asian/Black M >40; Asian F >50; +HDV; +FH HCC)
HBsAg Anti-HBs Anti-HBc (total) Interpretation Next Steps
Check anti-HBc IgM (acute vs. chronic), HBV DNA, HBeAg, total
⊕ - ⊕ Hepatitis B infected (acute or chronic)
anti-HDV
- ⊕ ⊕ Past infection (resolved) None;  risk of reactivation w/ chemo/immunosuppression
(1) Recovery from remote acute infxn (w/
Differentiate possibilities w/ anti-HBc IgM (acute infxn vs. others),
anti-HBs titers that have waned), (2)
anti-HBe, HBV DNA, repeat anti-HBc (later). “occult HBV” = DNA⊕
- - ⊕ chronic infxn (& low level HBsAg), (3)
w/ HBsAg⊝ +/- HBcAb⊕. Low risk reactivation but  if
acute HBV in window period, (4) false ⊕
chemo/immunosuppression
anti-HBc or false ⊝ HBsAg
- ⊕ - HBV-immune from prior vaccination None
Vaccinate. Engerix-B (3 doses, at 0,1,6mo). NB: If receiving HD,
- - - Uninfected, non-immune
double dose, at 0,1,2,6mo
HBV reactivation: indicated by: (1)  in HBV DNA vs. baseline or (2) reverse seroconversion from HBsAg-/anti-HBc+ to HBsAg+. Check
serologies before high-risk therapies: rituximab, anti-TNF, high dose steroids (>20mg pred/d x4w), HSCT, chemotherapy, anti-rejection
therapy. HBsAg+ is greatest risk, need ppx. HBsAg-/anti-HBc+ is lower risk, ppx vs monitor for reactivation
Management: Acute: unless severe, supportive. Chronic: tx if decompensated cirrhosis or if compensated w/ DNA >2k (& consider if <2k)
regardless of ALT to ↓ risk of decompensation. If no cirrhosis, depends on eAg/ALT/DNA level (see p.1571 Hepatology 2018;67:1560)
H E P A T I T I S C (AASLD/IDSA: CID 2023 https://www.hcvguidelines.org/)
HCV Ab. If positive, order RNA Viral Load (PCR), MGH does not have reflex testing. Everyone: universal one-time
Screening
screening (CDC: MMWR Rec Rep 2020;69:1; USPSTF: JAMA 2020;323:970). IVDU or MSM w/ HIV: annual
IVDU, blood products pre-1992, MSM, HIV, chronic HD, incarceration, immigration from ↑prevalence area, HCV
Risk Factors
infected mother, sex with HCV+ partner
Diagnosis ⊕Ab, ⊕RNA = current infection. ⊕Ab, ⊝RNA = cleared or treated (can still get reinfected)
Acute HCV: 75% subclinical. If sx, develop 2-26w after exposure, last 2-12w. Fulminant rare (<1%)
Natural
Chronic HCV: 80%  chronic; if younger, female sex, genotype 1, IL28B, jaundice, ALT more likely to clear
History
spontaneously 20%  cirrhosis (risk if male sex, EtOH, obesity, HIV, immunosupp.). HCC risk 1-13%/yr
Extrahepatic Mixed cryo., porphyria cutanea tarda, lichen planus, LCV, thyroiditis, Sjogren’s, renal dz (e.g., MPGN), NHL
1) Assess advanced fibrosis with FIB-4 score, U/S Elastography (FibroScan), FibroSure
2) Obtain HIV test (if +, initiate ART 1st), HBsAg (tx if applicable), and Upreg neg. Get CBC, LFTs, GFR baseline
3) Confirm pt eligible for simplified tx. Eligible if: compensated cirrhosis, no prior HCV tx; NOT eligible if cirrhosis AND
eGFR <30, HBsAg (+), pregnant, prior liver transplant, c/f HCC. Consider GI/ID referral if not eligible
Treatment
4) If eligible for simplified tx: If no cirrhosis, start pan-genotypic Rx: Mavyret (Gle/Pib) x8wks or Epclusa (Sof/Vel)
x12wks. If +compensated cirrhosis, genotype guides therapy unless using Gle/Pib which works for all genotypes.
Monitoring: If on warfarin, monitor for subtherapeutic INR. Monitor for hypoglycemia w/ DM meds. Note: patients DO
NOT need to abstain from drugs or EtOH. (AASLD, IDSA 2020).
HCV RNA and LFTs >12 wk after Tx to assess SVR. If cirrhosis, continue HCC surveillance/variceal screening (q6mo
Follow-up
U/S, EGD) EVEN after SVR. If no SVR at 12 wk, ID/GI referral and assess for fibrosis q6m (LFTs/CBC/INR)
H E P A T I T I S D (Gastro 2019;156:461)
Coinfection with HBV similar to HBV but more severe, risk ALF; often biphasic ALT course. Superinfection on HBV most severe, highest
risk ALF & chronic infxn (90%)  cirrhosis in 80% in 5-10y. 3x risk HCC vs. HBV mono-infection. Check total anti-HDV once in all HBV
infected patients (usually appears after 4 weeks). If suspect false negative Ab, confirm with HDV RNA PCR
H E P A T I T I S E (APT 2017;46:126; Gastro 2012;142:1388)
Most common cause of viral hepatitis in endemic areas. Transmission: fecal-oral, vertical, zoonotic (swine organ meats). Most asx, resolve
spontaneously. Extra-hepatic: neuro (e.g., GBS), renal, arthritis, anemia, pancreatitis. risk of ALF/mortality in pregnant women (Annals
2007;147:28). Rarely chronic HEV in transplant recipients. Dx: HEV IgG+ IgM, high false ⊕/⊝. Tx: supportive care (if immunocompetent)
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Gastroenterology Alcohol-Related Liver Disease
A L C O H O L - R E L A T E D L I V E R D I S E A S E ( A L D ) (AASLD: Hepatology 2020;71:308; ACG: AJG 2024;119:30)
Risk factors: sex (F>M), pattern (daily ± binge), obesity, DM2, genetics (e.g. PNPLA3, α-1 antitrypsin, TM6SF2, MBOAT7), smoking,
comorbid HCV/MASLD/etc.; coffee risk. Harmful drinking: Men: ≥3 drinks/d or ≥21/wk. Women: ≥2 drinks/d or ≥14/wk
Pathophysiology: EtOH  fat accumulation; EtOH  gut permeability  innate immune response, liver cell inflammation, injury,
necrosis, fibrosis; may be important role for gut microbiota (Nature 2019;575:505)
Disease spectrum:
• Steatosis: usually asx; may have mild AST>ALT, GGT; develops in 90% w/ >60g/d EtOH after 2w; reversible w/ 4-6w abstinence
o 20-40% develop fibrosis  8-20% to cirrhosis  20-40% decomp/acute-on-chronic liver failure; HCC in 3-10% w/ cirrhosis
• Steatohepatitis: histopathologic correlate of AH; can develop at any stage of ALD; often  to fibrosis (40-50%) & cirrhosis (>75%)
• Alcohol-related hepatitis (AH): an acute inflammatory syndrome that can occur at any stage of ALD
• Cirrhosis due to ALD: pathologic fibrosis distorting liver architecture, resulting in abnormal blood flow
Prognosis: 5-year mortaility due to liver disease is 25.8%. (Lancet;8:1028)
Treatment: Motivational interviewing, CBT, and behavioral intervention (5 “A” model: ask about use, advice to quit/reduce, assess
willingness, assist to quit/reduce, and arrange f/u). Pharmcology: Baclofen, acamprosate or naltrexone, gabapentin or topiramate. Suggest
against disulfram, C.I. in liver disease. (See AUD)
Alcohol Liver Evaluation Team (ALiVE, p26299): eval. inpts w/ ALD or AUD w/o known ALD admitted for non-liver related complaints.
Goal earlier identification of subclinical advanced fibrosis and connection to hepatology team for treatment.
ALCOHOL-RELATED HEPATITIS
Presentation: varies from few sx to liver failure; jaundice, anorexia, fever, abd pain (tender hepatomegaly), malaise, weakness, nausea
• Can lead to portal HTN & its sequelae (EVs, ascites, HE) in the absence of cirrhosis due to hepatic swelling & portal venous obstruct.
Dx: jaundice w/in prior 8w, ongoing heavy EtOH (F >3 std. drinks/d, M >4 std. drinks/d for >6mo). <60d abstinence before onset of
jaundice, AST moderate  (50-400) w/ AST/ALT >1.5, Tbili >3. Often WBC (<20k, PMNs), INR
• Must exclude other etiologies of acute hepatitis/jaundice (viral, meds/herbs, ischemia, AIH, Budd-Chiari, biliary obstruct.),
decompensated cirrhosis; can be superimposed in 10-20% (Alcohol CER 2004;28:31). Check HAV/HBV/HCV, APAP level, US w/
Doppler, ± (ANA, ASMA, IgG levels, AMA). Assess for signs of cirrhosis
• Transjugular Bx: consider if atypical presentation and/or labs (e.g., AST/ALT >400), uncertain alcohol intake hx, jaundice >3 months,
or suspicion for alternative etiology, such as use of hepatotoxic meds, possible ischemic insult (e.g., HoTN, cocaine use), etc.
Exclude infection: May have SIRS/fever due to inflamm., but screen for infxn as at high risk (esp. if severe AH: 12-26% at admission)
Prognostic Tool Use Components Stratification
Maddrey Discriminant PT, PT control (14.5 at MGH), ≥32 = severe  1mo. mortality 30-50%;
Function (MDF) Identify who will benefit from Tbili GI consult re: steroids (Gastro 1978:75:193)
steroid therapy >20 = inpt admission, 3mo. mortality 20%; Consult GI
MELD Tbili, INR, Cr, Na
for steroids (Hepatology 2005;41:353)
≥0.45: Nonresponse  stop steroids
Perform on day 4 & 7 to Day 0: Age, Albumin, PT, Cr
Lille <0.45: Response  continue steroids
assess steroid response Day 0, 4, & 7: Tbili
(Hepatology 2007;45:1348)

TREATMENT OF ALCOHOL-RELATED HEPATITIS MDF ≥ 32 or 20 < MELD < 50

Corticosteroids: see algorithm
• Prednisolone used as not metabolized by liver (methylpred 32mg is IV Contraindications to Steroids*
alternative): 40mg x 28d w/ 2-4w taper. Lille score at 4 or 7 days to assess Uncontrolled diabetes, upper GI bleed, or infection
Severe renal failure (AKI w/ Cre >2.5mg/dl)
steroid response. Multi-organ failure or shock
• No mortality difference at 28d or 90d, infxn (NEJM 2015;372:1619). HBV, HCV, DILI, HCC, acute pancreatitis, HIV, TB
*Consider once controlled
NAC: may benefit, no harm (though is large volume load) x5d
Supportive therapy: hold βB if MDF ≥32 as AKI incidence (Liver Int. 2015;35:8) No Yes
Nutrition: Goal 35 kcal/kg/d with 1.2–1.5 g/kg of protein; supplement w/ MVI, Prednisolone 40mg/day +/- Consider early OLT or
thiamine, folate, B6, B12, and Zn. Low kcal in severe AH a/w infxn (Gastro NAC palliative care (esp. >3 organ
2016;150:903). Nutrition consult. If <21 kcal/kg/day, consider TF w/ NGT. failures or not OLT candidate)

Abstinence: can result in rapid improvement in outcomes w/in 3mo. Combination Day 4 or 7 Lille Score
of psychosocial + pharmacotherapy achieved best outcomes (J Hepatol 2016;65:618). Non- Stop steroids
Age and lack of past alcohol use treatments were independently associated with Responder Responder

complete abstinence (Hepatology 2017;66:1864) Complete 28 days of 40mg/day

then 2-4 week taper
LIVER TRANSPLANTATION:
Definitive therapy for ALD. Traditionally required 6mo abstinence. 6mo survival Other therapies with potential efficacy:
with low risk of alcohol relapse and low impact on donor pool in appropriately • NAC: w/ steroids x5d, may mortality at 1mo, not 3 or
selected pts (NEJM 2011;365:1790, Am J Transplant 2016;16:841) 6mo (NEJM 2011;365:1781, Gastro 2015;149:958)
• MGH offers early LT eval. prior to 6 mo. abstinence for pts w/ 1) 1st alcohol- • Pentoxifylline: Not recommended. Consider if steroids
related decompensating event (i.e., no prior knowledge of alcohol-related liver contraind, no convincing data on mortality, but
disease or alcohol-related legal issues), 2) maddrey discriminant function doesAKI/HRS (Gastro 2000;119:1637, APT 2013;37:845)
(MDF) ≥32, 3) no response to steroids, 4) no grade 3-4 HE (to allow for psych • G-CSF: in clinical trials (Hepatology 2019;70:802, AJG
2014;109:1417)
eval), 5) strong social support, 6) no severe psychiatric co-morbidities, and 7)
• Fecal transplantation: Small RCT,  90d mortality but
no other SUD. Consult hepatology for candidacy. Can discuss if candidate at risk of donor related infx (Hepatol Int 2023;17(1):249)
MELD >10 to give time for education/evaluation.

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Gastroenterology MASLD
D E F I N I T I O N S ( Hepatology 2023;78:1966)
Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): presence of hepatic steatosis (imaging or bx) w/o 2°
cause (includes NASH)
Metabolic dysfunction-associated steatohepatitis (MASH): hepatic steatosis and inflammation with hepatocyte injury ± fibrosis
Metabolic and alcohol related/associated liver disease (MetALD): metabolic dysfunction + 140-350 g/wk or 210-420 g/wk of alc
for female and male respectively.
MASH cirrhosis: cirrhosis with current or previous histological/clinical evidence of steatosis or steatohepatitis
E P I D E M I O L O G Y (Gut 2018;67:963; CLD 2016;8:100; J. Hepatol 2022;77:1237)
• Prevalence: 10-46% in US; >95% in pts w/ obesity undergoing bariatric surg, 33-66% in pts w/ T2DM, and 50% in pts
w/dyslipidemia,  with TC:HDL & TG:HDL (but growing number of lean MASLD)
• Risk factors for progression: insulin resistance, DM, weight gain, HTN, AST/ALT >1 (JAMA 2015;313:2263)
• Progression rates: MASLD  cirrhosis: 3% in 15 yrs, compensated cirrhosis to first decompensation: 33% in 4 yrs.

D I A G N O S I S (NEJM 2017;377:2063; Hepatology 2018;67:328; Hepatology 2011;54:344)

• Presentation: mild AST, ALT (2-4x ULN with AST:ALT ratio <1) or imaging w/ hepatic steatosis (~70% w/ nl LFTs)
o No indication for routine screening in high-risk pts due to limited tx options. However, maintain high index of suspicion in
those with RFs (CLD 2021;17.1:23)
• History & Physical:
o DDx: EtOH use, viral hepatitis, parenteral nutrition, Wilson’s disease, malnutrition, hemochromatosis, autoimmune liver
disease, α-1 AT deficiency, DILI, celiac disease, thyroid disease. Uncommon: hypobetalipoproteinemia, LAL deficiency,
carnitine/choline deficiency
o Screen for significant EtOH consumption (>21 standard drinks/wk in men, >14 in women)
o Evaluate for associated comorbidities (T2DM, obesity, central adiposity, dyslipidemia, hypothyroidism, PCOS, OSA)
o Assess for signs of cirrhosis and insulin resistance (e.g., acanthosis nigricans)
• Labs: LFTs, CBC, PT/INR, HCV Ab, lipid panel, HgbA1c, celiac serologies, TSH
o If elevated LFTs: consider iron studies, α-1AT, ANA, ASMA, SPEP, HBV
 Ferritin may be  in hemochromatosis and MASLD, so if iron sat also elevated, consider HFE testing
• Imaging: ultrasound to confirm hepatic steatosis, rule out other pathology
o Non-invasive evaluation for advanced fibrosis (F3-4); assess q3y – if indeterminate, consider 2nd test including liver biopsy
(J Hepatol 2015;63:237; Hepatology 2019;70:1521; DDS 2016;61:1356; Hepatology 2018;67:260)

Diagnostic Considerations Rule Out Rule In

Use to triage pts 35-65yo w/ risk of advanced fibrosis < -1.455 ≥ 0.676
NAFLD fibrosis score (NFS)
& monitor progression; quick but not liver-specific. (Sn 90%, Sp 60%) (Sn 67%, Sp 97%)
If clinical suspicion for metabolic liver disease, FIB-4
< 1.3 > 2.67
FIB-4 recommended in every 1-2 yrs in pre-DM2/DM2 or 2+
(Sn 82%, Sp 57%) (Sn 36%, Sp 93%)
metabolic RF vs every 2-3yrs if <2 metabolic RF
Most used/validated; high user variability, limited in pts < 9.9 kPa ≥ 11.4 kPa
VCTE (FibroScan)
w/ severe obesity and ascites (Sn 83%, Sp 61%) (Sn 75%, Sp 71%)
Similar to FibroScan, also provides imaging; obtain if < 7.1 kPa > 9.2 kPa
Ultrasound elastography
need for ultrasound (Sn 94%, Sp 52%) (Sn 93%, Sp 81%)
• Referral to Hepatology: persistent/significant transaminase elevation (ALT >30), advanced fibrosis, need for liver bx
• Biopsy: for pts with F3 or > on non-invasive imaging, at high risk of advanced fibrosis/MASH or competing etiologies of liver
disease (CLD 2021;17.1:23)

M A N A G E M E N T (CLD 2020;15:4)
• Lifestyle intervention: weight loss is 1° therapy. ≥5% reduces hepatosteatosis; 7-10% may improve fibrosis (target 
500-1000 kcals/d); Mediterranean diet, low carb, higher protein diet associated w/ improvement in weight loss; reducing
fructose consumption helpful; exercise can significantly improve insulin resistance & outcomes (see weight loss for med.
options). Abstain from excessive alcohol use.
• Pharmacotherapy: pioglitazone improves histology; vitamin E 800IU/d improves histology in pts without DM in bx-proven
MASH (PIVENS trial, NEJM 2010;362:1675); omega-3 FAs improve hyperTG in pts with MetALD (APT 2010;31:679); GLP-1ra:
semaglutide in pts with F2/F3 fibrosis to MASH resolution w/o improved fibrosis (NEJM 2021;384:1113). SGLT-2i reduce
steatosis on imaging.
o Not recommended currently: metformin (give if T2DM for weight loss), UDCA, obeticholic acid, elafibranor
• Surgery: consider bariatric surg in eligible pts with obesity and MASLD or MASH
• Other considerations: Prevent progression of liver disease – vaccinate for HAV/HBV, avoid EtOH consumption. Treat
comorbidities (T2DM, HLD, HTN) Statins are recommended in MASLD for CVD risk reduction.

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Gastroenterology End Stage Liver Disease

DEFINITIONS
• Cirrhosis: irreversible fibrosis and formation of regenerative nodules that distorts hepatic architecture and vasculature
o Compensated: no ascites, encephalopathy, jaundice, or GI bleeding. May have nonbleeding varices. Usually asx
o Decompensated: ascites, HE, jaundice, SBP, Hepatopulmonary syndrome, variceal bleeding or HRS
• End-stage liver disease (ESLD): accompanying pathophysiologic state of impaired liver function
C L I N I C A L M A N I F E S T A T I O N S A N D D I A G N O S I S (JAMA 2012;307:832)
• Symptoms: fatigue/weakness, jaundice, pruritus, nausea, anorexia, abdominal distention, GIB, confusion, muscle cramps
• Exam: BP, splenomegaly, caput medusae, ascites (+LR 7.3), jaundice, spider angiomata (+LR 4.3), gynecomastia, testicular
atrophy, palmar erythema, asterixis, white nails, Dupuytren’s contracture
• Labs: TBili, INR, alb, Na, PLT (<160, +LR 6.3), ± Hgb/Hct, WBC; AST, ALT, alk phos, and GGT may be  or normal
• Diagnostics: viral hepatitis panel, iron studies, ANA, ASMA, AMA, α1AT, ceruloplasmin
• Imaging: RUQUS (with Doppler) to assess echogenicity/morphology of liver, ascites, vascular patency, biliary tree, HCC; US
elastography measures liver stiffness by applying mechanical waves and measuring propagation speed through tissue
• Biopsy: gold standard but performed less often. Main indications are dx uncertainty or indeterminate fibrosis severity (NEJM
2017;377:756). Perc. (cannot do through ascites, massive obesity) or transjugular (allows HVPG measurement; pref. if coagulopathy)
ETIOLOGIES
• Most common: metabolic associated liver disease (metAFLD), alcohol, viral (HCV, HBV). Global epi: metAFLD (54%), HBV (29%),
HCV (9%), ALD (2%) (CLD 2021; 17:365): in the US, ALD a much higher proportion.
• Genetic disorders: hemochromatosis, Wilson’s, α1AT deficiency, CF, inherited disorders of glucose metabolism,
hypobetalipoproteinemia, LAL deficiency
• Immune-related: autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), celiac disease
• Vascular: post-hepatic portal HTN (right heart failure, Budd-Chiari syndrome, veno-occlusive disease)
• Other: infection (i.e., schistosomiasis), meds (e.g., MTX, isoniazid, amiodarone; see LiverTox), cryptogenic/idiopathic, carnitine/choline
deficiencies
N A T U R A L H I S T O R Y A N D R I S K S T R A T I F I C A T I O N (J Hepatol 2006;44:217)
• MELD Na score: predicts 90d mortality, used for transplant allocation using Na, Tbili, INR, Cr,
• New MELD 3.0 added: 1) female sex and albumin to correct transplant disparities for women, 2) interaction btwn Tbili & Na and
albumin &Cr, 3) upper bound of Cr of 3 (Gastro 2021;161:1887)
• Child-Pugh class: assesses cirrhosis severity, predicts 1-2y mortality using Tbili, INR, albumin, presence of ascites encephalopathy
o Compensated: Child-Pugh Class A; median survival 12y, 1y survival >95%. 5-10% risk of decompensation per year
o Decompensated: Child-Pugh Class B/C; median survival 2y, 1y survival 40-80%
COMPLICATIONS OF CIRRHOSIS
• Portal hypertension: esophageal varices, portal hypertensive gastropathy, hypersplenism (cytopenias), ascites, SBP, hepatorenal
syndrome, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary hypertension, cirrhotic cardiomyopathy
o Hepatic venous pressure gradient (HPVG) is gold standard measurement for portal HTN (gradient b/w portal vein and IVC)
o Normal HVPG <5mmHg; Portal HTN ≥6; Clinically-significant portal HTN: ≥10; Risk of EV bleed: ≥12
• Hepatic encephalopathy: see ESLD: HE
• Immune dysfunction: increased risk of infection; bacterial and fungal infections are major causes of morbidity & mortality
• Endocrinopathies: hypoglycemia, thyroid dysfunction, hypogonadism, hyperestrinism (palmar erythema, spider angiomata)
• Coagulopathy: see ESLD: Hematologic Abnormalities
• Portal vein thrombosis: risk due unbalanced hemostasis & slowing of portal flow. Start AC for acute PVT w/ LMWH (unless high
bleeding risk); transition to DOAC or warfarin once stable & continue at least 6mo (AGA: Gastro 2019;157:33)
• Hepatocellular carcinoma: see ESLD: HCC
• Frailty: encompasses sarcopenia, functional decline, deconditioning, malnutrition, impaired cognition. A/w decompensation,
hospitalization, and mortality (Hepatology 2017;66:564; Am J Gastroenterol 2016;111:1759)
VIBES: a systematic approach to the management of cirrhosis
General: etiology of cirrhosis, complications, compensated/decompensated, etiology of decompensation (infection [including
new/reactivation of HBV/HCV], GIB, EtOH, HCC, dehydration, meds, surgery, etc.), Child-Pugh class, MELD3.0 score
Volume (ascites, edema, hepatic hydrothorax, hepatorenal syndrome)
• Current diuretics & response; dietary Na+ restriction (<2 g/d), fluid restriction 1.5L (if Na<125)
• Prior history of LVPs, thoracentesis for hepatic hydrothorax, consideration of TIPS if refractory
Infection
• Prior history of SBP, whether has indication for 1° or 2° ppx
• Current treatment or ppx
Bleeding (esophageal/gastric varices, portal hypertensive gastropathy, coagulopathy) (JOURNAL OF HEP 2022;76:959)
• Prior history/source of bleeding, therapies (e.g., banding, sclerotherapy, TIPS), current prophylaxis (β-blocker, carvedilol preferred)
• Current bleed: severity, IV access, H/H trends, medical therapy (PPI/octreotide), results/plan for EGD, SBP ppx as above
Encephalopathy
• Prior history, precipitant, and treatment
• Current severity, trend, precipitant, medicines, goal #BM (e.g., 4 BM/day, 500cc stool, mental status improvement)
Screening/Surgery (transplant)
• Vaccinations: HAV, HBV, Influenza, Pneumovax, Prevnar, COVID, all other standard vaccines, see Transplant ID
• Maintenance: alcohol abstinence, avoid NSAIDs, HCC screening with q6mo RUQUS ± AFP
• Transplant status: listed or not listed, MELD score, Milan criteria if HCC

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Gastroenterology End Stage Liver Disease

A S C I T E S (AASLD: Hepatology 2021; 74(2):1014))
• Most common cirrhosis complication (50% in 10 years); development of ascites  15% 1y mortality, 44% 5y mortality
• Pathophys: portal hypertension (>12 mmHg) NO, prostaglandins, glucagon  splanchnic arterial vasodilation  intravascular
volume and SVR  RAAS, ADH  Na & water retention. Severity of dilutional hypoNa (from ADH secretion) ∝  survival
• Diagnosis: Ultrasound to visualize. Dx para indicated for ALL patients with cirrhosis and ascites presenting to the hospital. No role for
routine use of ppx FFP or platelets (Hepatology 2021;73:366). EARLY paracentesis (within 24 hours of admission) is associated with
reduced inpatient mortality and 30-day readmissions (AJG 2019; 114:1863)
o Studies: cell count w/ diff, albumin, total protein, GS/Cx ± glucose, LDH, amylase, TG, bilirubin, cytology, AFB Cx/ADA (TB)
o DDx: portal HTN vs. non-portal HTN. SAAG (serum ascites albumin gradient) differentiates 97% of time (Annals 1992;117:215).
SAAG ≥1.1 g/dL: related to portal HTN SAAG <1.1 g/dL: NOT related to portal HTN
Etiology related to portal hypertension Etiology not related to portal hypertension
• Cirrhosis (ascites fluid total protein [AFTP] <2.5) • Infectious (Secondary bacterial peritonitis, Peritoneal TB)
• CHF, constrictive pericarditis (AFTP >2.5) • Peritoneal carcinomatosis (+cytology)
• Acute hepatitis (including EtOH) • Chylous ascites (triglycerides >200)
• Acute liver failure • Hypoalbuminemia (nephrotic syndrome, protein-losing enteropathy,
• HCC, massive liver metastases severe malnutrition; Ascitic fluid total protein <2.5)
Budd-Chiari syndrome (AFTP >2.5) • Serositis (e.g., SLE)
• Portal vein thrombosis • Pancreaticobiliary (i.e., bile leak, disrupted pancreatic duct)
• Management of ascites:
o 1st line: <2g Na, EtOH, NSAIDs, diuretics (see below), avoid ACEi/ARB (renal perfusion), stop anti-hypertensives when
MAP < 82 mmHg, fluid restrict 1L if Na <125
 Initiating therapy: 100mg/d spironolactone + 40mg/d furosemide for starting dose (5:2 ratio). Ideally single, daily AM
dosing. Ratio maintains eukalemia & mobilizes fluid faster. Consider spironolactone alone for mild first ascites if outpt (lasix
is added for normokalemia, never add it alone for managing ascites).
 Ongoing therapy: dose q3-5 days if inadequate diuresis (5:2 ratio, though can increase lasix PRN if hyperK). Max doses:
400mg spironolactone and 160mg furosemide. ∆ to eplerenone ($$) or amiloride if painful gynecomastia w/ spironolactone
 Check UNa/UK ratio if pt gaining weight/requiring LVPs on diuretics; UNa/UK <1 suggests ineffective diuretic dose or
resistance; UNa/UK >1 suggests >2g Na dietary intake
o Weight loss goals: 0.5 kg/d (TBB -500) if no peripheral edema (AKI risk if too fast); if edema, 1 kg/d or -1L. Avoid IV diuretics
(azotemia risk ). Ascites mobilizes fluid slower than other compartments at a rate of 0.5L/day (Gastro 1986;90:1827)
o Therapeutic LVP: indicated for tense or refractory ascites or inability to use diuretics; if >5L removed, give 6-8g albumin for
every 1L ascites removed to reduce risk of post-paracentesis circulatory dysfunction (PPCD); if >8L removed, risk of PPCD 
o Unproven therapies: long-term administration of albumin (40g 1-2x weekly, $$) in pts with cirrhosis and uncomplicated ascites
may offer survival benefit (Lancet 2018;391:2417) but no benefit (and potential harm) in hospitalized pts with acute decompensated
cirrhosis targeting albumin > 3 g/dl (NEJM 2021; 384:808). SGLT2i may also  ascites. (Hepatology 2020; 72(5):1880)
• Refractory ascites (10% of patients; associated with decreased survival):
o Defined as: 1) unresponsive to Na-restriction & high-dose diuretics (or unable to tolerate iso HE, lytes, azotemia) or 2) rapid
reaccumulation after LVP; associated with very advanced cirrhosis and low urinary excretion of Na
o Mgmt: R/o PVT and HCC. D/c diuretics if UNa<30mEq/day, discontinue βBs (mortality in refractory ascites [Hepatology
2010;52:1017]), midodrine TID (J Hepatol 2012;56:348), serial LVPs (<8L ~q2w), TIPS if intolerant of LVPs (poor TIPS candidate if:
MELD>18, Child-Pugh class C cirrhosis, heart failure, severe HE), indwelling peritoneal catheters in certain cases (e.g., EOL)
S P O N T A N E O U S B A C T E R I A L P E R I T O N I T I S ( S B P ) (AASLD: Hepatology 2021; 74(2):1014)
• Must r/o SBP in all inpatients w/ cirrhosis & ascites ASAP w/ dx para and blood Cx; 10-30% hospitalized pts w/ cirrhosis have
SBP. Look for abdominal pain, TTP, ileus, HE, and AKI as presenting sxs, but 1/3 of patients may be asx
• Diagnosis: >250 PMN/L w/ positive GS/Cx (SBP) or negative GS/Cx (CNNA = similar mortality to those w/ +Cx; treat similarly)
o RBC >50,000/mm3, often due to traumatic tap  correct PMN count by subtracting 1 PMN for every 250 RBCs
• Usually monomicrobial; GNR 70% (E. coli, Klebsiella), GPC 25% (S. pneumoniae), anaerobes 5%; if polymicrobial, consider
secondary bacterial peritonitis 2/2 perforation vs. loculated abscesses. Bowel perf. suggested if ≥2 of the following: TP >1, LDH
>ULN, or Glc <50; also CEA >5 & ALP >240 (Runyon’s criteria)
• Treatment:
o 1) Abx: Community acquired: CTX 2g q24h x 5d; IV cipro (400mg q12) if allergy to cephalosporin (unless taking cipro for ppx)
 Tx should be broader if risk of MDRO infxn (recent hospitalization, nosocomial infxn, ICU pts): Pip-Tazo + Daptomycin (if
prior VRE infxn or GI colonization) OR Meropenem if known MDR gram negative organisms or recent Pip-Tazo exposure
o 2) 25% albumin: 1.5g/kg day 1 + 1.0g/kg on day 3, max 100g (given risk of AKI in SBP) (Note: AASLD recommends for all pts
but some groups only recommend for those meeting study pop. criteria: Cr >1, BUN >30, or TBili >4 (NEJM 1999;341:403).
o Hold βBs while hospitalized given increased risk of AKI & HRS once SBP is diagnosed, may attempt reintroduction with GI once
recovered (Gastro 2014;146:1680).
o Repeat diagnostic para 48 hours after starting abx to assess response. A negative response is defined by a ↓ in PMN count
<25% from baseline  broaden abx and investigate secondary peritonitis w/ CTAP+GI consult. Repeat para may be avoided if
an organism is isolated, it is susceptible to the abx used, and pt is improving clinically (not widely in practice yet at MGH)
• Prophylaxis:
o IV CTX 1g q24h x5 days if GIB
o All patients w/ prior SBP should receive 2° PPX (after full tx above) w/ PO cipro 500 qd (at MGH) or PO Bactrim DS qd
o Consider 1° prophylaxis if ascitic TP <1.5 AND impaired renal function (Cr ≥1.2, BUN ≥25 or Na ≤130) or liver failure (Child
score ≥9 and bilirubin ≥3) (Hepatology 2021;74(2):1014)
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Gastroenterology End Stage Liver Disease

H E P A T I C E N C E P H A L O P A T H Y ( H E ) (NEJM 2016;375:1660; AASLD: Hepatology 2014;60:715)
• Pathophysiology: NH3  neurotoxic effects, abnl neurotransmission, GABA- & BDZ-
like neurotransmitters & altered glutaminergic inputs  excitatory transmission. In ALF, Grades of Hepatic Encephalopathy
(West Haven Criteria)
acute NH3  cerebral edema
• Diagnosis: clinical. Serum NH3 should not be used to screen for HE. NH3 does not add Inattention, euphoria/ anxiety,

Covert
diagnostic or prognostic value in CLD (JHM 2017;12:659). Only helpful in ALF (predicts 1 altered sleep pattern, attention
span
mortality). Trend via exam findings (see grades). Exclude other causes of AMS.
• Classification: type of underlying disease, severity grade, time course (episodic, Lethargy, time disorientation,
recurrent, persistent), precipitations (precipitated vs non-precipitated) 2 asterixis, personality Δs,
• Asterixis: “flapping tremor” is negative myoclonus w/ loss of postural tone; elicit with hypoactive DTRs
hyperextension of wrists or squeezing of examiner’s fingers (milk maids sign)

Overt
Somnolence, responsive to stimuli,
• Precipitants: infection, dehydration/overdiuresis, GIB, K or alkalosis (renal NH3), renal 3 time & place disorientation,
failure, constipation, hypoxia, sedatives/BZD/opioids, new HCC, new clot, TIPS hyperactive DTRs
• Treatment: GI NH3 absorption, avoid/correct precipitating factors
4 Coma, unresponsive to pain
o Lactulose: Δs gut microbiome  pH  traps NH4+ in colon; has laxative effect;
30mL q2h until BM  titrate to 3-4 BM/day, often dosed 2-4x a day (PO or enema)
o Lactulose + rifaximin 550mg BID > lactulose alone for HE reversal. Add rifaximin ($$) if refractory or 2nd admission
o If refractory, consider non-standard therapies: oral branched-chain AAs (Cochrane Reviews 2017;5), IV L-ornithine L-aspartate
(Hepatology 2018;67:700), probiotics (Cochrane Rev 2017;2), PEG (JAMA Int Med 2014;174:1727); FMT (Gastro 2019;156:1921)
o Maintain K >4 to improve ammonia clearance via kidneys (Mineral electrolyte metab.1993;19:362)
o Nutrition: calories: 35-40kcal/kg/day, protein 1.2-1.5g/kg/day (in general, don’t restrict protein intake unless HE worsening)
V A R I C E A L B L E E D I N G (AASLD: Hepatology 2024;79:1180)
• Clinically Significant Portal HTN (CSPH): HVGP ≥ 10 OR varices on EGD OR portosystemic collaterals/ascites on imaging OR liver
stiffness (LSM)* by transient elastography ≥25 kPa, LSM 20–24.9 kPa w/ plt <150, or LSM 15–19.9 w/ plt <110.
*Caution: Careful interpretation in obesity, metAFLD, ALT > 3xULN, and PSC. PPV of test drops.
• EGD screening: esophageal varices most common. If alt. evidence of CSPH and on NSβB, sEGD may be deferred. Pursue sEGD if
unclear LSM w/o surrogate of PH on images and C.I. to empiric NSβB, continue q2yr if ongoing liver injury or q3yr if quiescent. If
known varices or decomp cirrhosis and C.I. to NSβB, sEGD q1yr. Avoid sEGD if LSM<20 & plt>150, as high risk varices unlikely
Compensated cirrhosis without CSPH: No 1° PPX indicated. Check LSM every 3-5y if LSM5-9.9kPa or annually if 10-14.9kPa.
Compensated cirrhosis with CSPH or decompensated cirrhosis w/ only ascites: Carvedilol (6.25mg qd x3d   to 6.25mg BID) C.I. in
1° asthma, AV block, SSS, HR <50
PPX Decompensated cirrhosis: Non-selective βB (NSβB, see below) are technically tx of choice, however MGH favors continuing carvedilol if
tolerated. Indications to stop βB outside of acute illness are most often 1) BP is unable to tolerate 2) recurrent AKI (esp. iso necessary diuretics)
If known EV and C.I. to NSβB: Serial endoscopic variceal ligation (EVL) q2-8w until eradication in med/large EV with screening q1-2yrs
Episode of variceal bleeding without - Non-selective βB: nadolol 20-40mg qd or propranolol 20-40mg BID on day 5 s/p bleed (d/c of
2° placement of TIPS  ppx to prevent vasoactives); adjust every 2-3d to goal HR 55-60, SBP>90; max daily dose in pts with|without ascites:
PPX recurrence w/ combination of non- propranolol 160|320mg/d or nadolol 80|160mg/d
selective βB + EVL - Serial EVL: q1-4w until obliteration; repeat EGD 3-6mo after & then q6-12mo
• Acute bleeding: Assess airway and IV access. IV PPI, IV octreotide (50 mcg bolus followed by 50 mcg/hr for 2-5 days), CTX 1g q24h
x 5d, EGD within 12hrs. Resuscitate w/ IVF/pRBCs prior to intubation and give erythromycin for EVL. Balloon tamponade as a bridge
(GI), urgent TIPS (IR) if cannot band. Conservative transfusion: goal Hgb 7 (NEJM 2013;368:11), avoid attempts to correct INR/plts.
Start enteral nutrition w/ control of bleeding and assess for provoking factor (i.e. PVT, HCC, etc). See Upper GI Bleeding
• Indications for TIPS: early “preemptive” TIPS (<72h) in pts with high risk of treatment failure or rebleeding (Hepatology 2024;79e224);
“rescue” TIPS if uncontrolled bleeding or if recurs despite max medical & endoscopic therapy
• Gastric varices: similar mgmt. of acute bleed but difficult to band. Consider TIPS (favored if EV too), BRTO, or endoscopic glue/coil
H E M A T O L O G I C A B N O R M A L I T I E S (AGA: Gastro 2019;157:33; NEJM 2011;365:147; CGH 2013;11:1064; Thromb Haemost 2018;118:1491)
• Cytopenias: thrombocytopenia (splenomegaly, TPO), leukopenia (splenomegaly), anemia (bleeding, hemolysis) may have BM
suppression from EtOH/infection, nutritional deficiencies (e.g. folate), direct effect of HCV/HBV
• Coagulation abnormalities: coagulation factors (except for FVIII), anticoagulant proteins (C, S, ATIII), dysfibrinogenemia,
accelerated fibrinolysis (tPA), +/-  Vit K risk of both clotting and bleeding & patients not auto-anticoagulated; balance tends to
favor thrombosis in early stages vs bleeding in late stages of cirrhosis
o Labs: PT/INR, PTT, /nml fibrinogen (though does not function normally;  if fulminant), /nml D-dimer (vs  in DIC), factor VIII
(vs  in DIC); note PTT and PT/INR do NOT correlate with risk of bleeding or clotting
• Anticoagulation (J Hepatol 2017;66:1313; JACC 2018;71:2162):
o VTE ppx: should not be withheld unless high risk of bleeding or plts<50
o Systemic AC: ok unless Child-Pugh C or bleeding risk. EGD if EVs prior. VKA, LMWH, or DOAC all options. VKA dosing c/b baseline
PT/INR; LMWH c/b ATIII levels; some DOACs safe (apixaban preferred)– can use w/ caution in Child-Pugh B
• Bleeding: consider role of coagulation factor deficiency, dysfibrinogenemia, hyperfibrinolysis, thrombocytopenia
o If suspect vitamin K deficiency, give vitamin K 10mg x3d to correct nutritional component
o pRBCs Hgb <7, platelets <50k, cryo for fibrinogen <100-120. FFP if persistent (though large volume  portal pressures)
o Delayed bleeding or oozing from mucocutaneous sites  Amicar (3g PO QID or 4-5g IV over 1h  1g/h) or TXA (1g IV q6h)
• Procedures:
o Platelets: >50k for surgery, TIPS, liver biopsy, or other procedure w/ high bleeding risk; TPO agonists are not generally recommended
but in specific instances can reduce need for peri-procedural PLT transfusions (but takes ~10d to PLT) (NEJM 2012;367:716; Gastro
2018;155:705). No role for plt transfusion for routine paracentesis (data ok with plt >19k).
o PT/INR: NO benefit to giving FFP pre-procedure to “correct” INR. volume can bleeding risk by portal pressures
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Gastroenterology End Stage Liver Disease

H E P A T O C E L L U L A R C A R C I N O M A ( H C C ) (AASLD: Hepatology 2023;78:1922)
• 2-4% risk per year. May be asx, lead to decompensation, and/or have sx related to mass effect (pain, early satiety, palpable mass)
• 1° prevention: HBV vax in high-risk pts not vaccinated at birth, HBV/HCV antiviral tx, healthy lifestyle, coffee consumption (1+ cup)
• Screening indicated in:
o Cirrhosis due to any etiology, except in Child-Pugh Class C pts not on transplant list (due to low survival time)
o Chronic HBV w/o cirrhosis if: M >40 / F >50 from endemic ctry, African/African-American >30, FHx HCC, or PAGE-B score ≥10
• Screen with: RUQUS ± AFP q6mo; if U/S visualization is limited (e.g., ascites), can use multiphase CT or contrast-enhanced MRI
o If lesion <1cm, repeat US + AFP in 3-6mo
o If lesion ≥1cm, AFP ≥20ng/mL, or rising AFP, obtain multiphase CT or MRI & proceed according to LI-RADS class
• Staging:
o Barcelona (BCLC) system: size, # of nodules, LN & portal vein involvement, mets, Child-Pugh score, performance status
o Recommended discussion at multidisciplinary tumor board; if HCC > BCLC Stage 0, obtain noncontrast CT chest for eval of mets
• Management:
o Curative: surgical resection (1st line if Child-Pugh A & T1-T2 nodule) ± adjuv ICI, OLT (if non-resectable but within Milan criteria)
o Noncurative: ablation, chemoembolization (TACE), radioembolization (TARE), radiation, chemo, immunotherapy
o Within Milan criteria  locoregional tx (LRT) as bridge to OLT. Outside Milan  LRT to downstage to w/in Milan  OLT
o Not OLT candidate (and non-resectable)  LRT and/or systemic chemotherapy
• Prognosis: survival by BCLC stage: 0-A (early): >5y, B (intermediate): >2.5y, C (advanced): >2y, D (terminal): 3mo

H E P A T I C H Y D R O T H O R A X (AASLD: Hepatology 2013;57:1651, Hepatology 2020;72:1851)

• ~5-15% pts w/ cirrhosis. Transudative effusion due to ascites  pleural space (neg. intrathoracic pressure) via small diaphragmatic
defects. Can be seen w/o significant ascites. Unilateral: R- (~75%) > L-sided (~15%) > bilateral (~10%) (Medicine 2014;93:135)
• Diagnosis: exclude other causes of transudative effusion; thora + imaging (chest CT, abd U/S, TTE); radioisotope inj. if dx unclear
• Treatment: first line: diuretics, 2g Na restriction. Therapeutic thora for dyspnea. Serial thoras, TIPS, pleurodesis, surg. repair or OLT
if refractory. Chest tube not recommended due to risk of serious complications +  mortality 2.5% (Chest 2019;155:546)
• Spontaneous bacterial empyema: can become infected (~15%) due to translocation of bacteria from abd. cavity. ~40% occur in
absence of SBP (Hepatology 1996;23:719). Dx: >250 PMNs w/ +Cx or >500 PMNs w/o +Cx. No e/o PNA. Tx: same as for SBP

H E P A T O P U L M O N A R Y S Y N D R O M E ( H P S ) (NEJM 2008;358:2378; EASL: J Hepatol 2018;69:406; ILTS: Transplantation 2016;100:1440)

• V/Q mismatch (shunt) + O2 diffusion limitation via intrapulmonary vascular dilatations; mechanism unclear, possibly  NO
• Presentation: shunting tends to occur at bases  platypnea (dyspnea when upright, relieved when supine) & orthodeoxia (upright
hypoxemia, PaO2  by 4 mmHg or ≥3-5%), clubbing, cyanosis, diffuse telangiectasias, hypoxemia (PaO2 <70-80)
• Diagnosis: If SpO2 <96% A-a gradient ≥15mmHg (or ≥20mmHg if age ≥65) or PaO2 <80mmHg  TTE with late bubbles (3-6
cardiac cycles after RA vs early bubbles in PFO)  PaO2 to grade severity
o 99mTc MAA scan is alternative to TTE but more invasive, less sensitive. May be useful in quantifying shunting if severe
hypoxemia and coexisting intrinsic lung disease
o Pulmonary angiography performed if severe hypoxemia poorly responsive to 100% O2 & areas amenable to embolization
o PFTs can be performed to evaluate for intrinsic lung disease; DLCO in HPS
• Management: no effective medical therapies. Monitoring q6-12mo in mild to moderate HPS. Consider OLT in pts w/ severe/very
severe HPS (PaO2 <60); OLT can significantly improve (and reverse) HPS – MELD exception points given for severe HPS

P O R T O P U L M O N A R Y H Y P E R T E N S I O N (EASL: J Hepatol 2018;69:406; ILTS: Transplantation 2016;100:1440)

• Rare cause of group 1 pulmonary hypertension in setting of portal HTN; 3x risk in F > M; ↑ risk in autoimmune liver disease
• Pathogenesis: blood flow to pulm. arterial bed. Mechanisms unclear but include vasoconstrictors normally cleared by liver (e.g.,
endothelin-1, estradiol) reaching pulmonary circulation, prostacyclin synthase, endothelial proliferation and PLT aggregation
• Diagnosis: screening w/ TTE (PASP >30mmHg; 100% NPV); confirmation is euvolemic RHC w/ PAH (mPAP ≥20mmHg, PCWP <15
mmHg, PVR >3) in pt with portal HTN in absence of other etiology (mild: mPAP 25-35, moderate: mPAP 35-44, severe: mPAP ≥45)
• Management: may benefit from advanced therapies (epoprostenol, bosentan, sildenafil, iloprost); OLT can improve PAH (MELD
exception points given for moderate PPHT); β-blockers and TIPS may be harmful and should be avoided
• Transplant: increased risk of morbidity/mortality with mPAP ≥35; mPAP ≥50 is a contraindication to transplant

C I R R H O T I C C A R D I O M Y O P A T H Y (Hepatology 2020;71:334; EASL: J Hepatol 2018;69:406, JACC 2010;56:539)

• Chronic cardiac dysfunction in cirrhosis pts w/o known cardiac disease; characterized by 1) impaired cardiac contractility in response
to stress, 2) altered diastolic relaxation, 3) electrophysiological abnormalities such as prolonged QTc and chronotropic incompetence
• Pathophysiology: myocardial dysfunction 2/2 systemic inflammation; shear stress from portal hypertension  mechanical force on
myocardial fibers; other possible mechanisms involve collagen configuration, sodium retention, activation of RAAS, ↑ bile acids
(Biochim. Biophys. 2018; 1864:1345)
• Prevalence: up to 50% of pts undergoing liver transplantation have signs of cardiac dysfunction
• Diagnosis & Treatment: echocardiography (CCC Criteria) w/ dynamic stress testing; OLT and HF management as in pts w/o cirrhosis
• Prognosis: largely subclinical; risk with stressors (infection, paracentesis, TIPS, OLT); detailed cardiac assessment before intervention

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Gastroenterology Hepatorenal Syndrome

H E P A T O R E N A L S Y N D R O M E ( H R S ) (Clin Gastro Hep 2018;16:162; BMJ 2020;370:2687, NEJM 2023;388(8)e733, Gastro 2024;166:202)
• Pathophysiology: portal HTN  NO, prostaglandins  splanchnic vasodil.  EABV  RAAS, ADH, SNS  renal vasoconstr.
• Diagnosis: dx of exclusion; need: (1) advanced hepatic failure w/ portal HTN (ascites)
(2) AKI: sCr > 0.3 mg/dl from baseline within 48 hrs OR sCr >1.5x baseline within past 7d OR UOP <0.5 ml/kg/hr x6hrs
(3) absence of and/or optimization of alternative AKI etiology. Examples: shock (GIB, sepsis, pancreatitis), infection (SBP),
dehydration (diuretics/diarrhea), nephrotoxin (ATN: IV contrast, bile cast nephropathy. AIN: Abx, NSAIDs, PPI), obstruction,
glomerular disease (e.g. IgA, MPGN, cryoglobulinemia).
• Type I (HRS-AKI): Cr >2x b/l and >2.5 mg/dL in <2w; Type II (diuretic-resistant ascites): Cr from 1.5-2.5mg/dl, slower progression
• Most Common HRS Precipitants: infection (SBP > other), GI bleed, fluid shifts after LVP, alcohol-related hepatitis
• Prevention: In SBP, albumin day 1 + day 3 has mortality benefit (Clin Gastro Hep 2013;11:123); 1° SBP ppx (Gastro 2007;133:818)
• Management: Obtain history and treat reversible causes. Discontinue diuretics, βB, ACEI/ARB, or other vasodilators or nephrotoxins.
Obtain paracentesis for SBP eval. Obtain urine studies for urine sediment, FeNa, FeUrea, and renal ultrasound. Then see algorithm.

MGH Algorithm for the Diagnosis and Treatment of Hepatorenal Syndrome

Concern for HRS-AKI - Consider plasma volume expansion with 1g/kg/day 25%
- Diagnosis of cirrhosis and ascites albumin (<100g/day in divided doses) for 48hr (also known as
- Diagnosis of AKI (as above) without untreated an Albumin Challenge). Repeat urine studies at 24h to re-
other etiology for AKI assess for ATN
- No macroscopic signs of structural injury: - Lack of response to albumin is the final piece of the
proteinuria <500 mg/day, <50 RBCs per HPF, HRS-AKI definition, however, if clinical concern for
and normal renal US. volume overload and low concern for pre-renal AKI,
Note: Presence of muddy brown/granular casts early vasoconstrictor therapy may be pursued without
does not preclude HRS-AKI. challenge as volume can be prohibitive to terlipressin
- FeNa <0.1% and FeUrea <21% are suggestive - Consult hepatology/renal for guidance
of HRS
No Response to Response to
Challenge or Challenge Challenge or
First line: Terlipressin (CONFIRM) Deferred Confirmation of ATN
- V1a receptor agonist
- Only approved HRS-AKI agent. Increase in MAP 10-
15mmHg and/or 50% increase in UOP are good
Initiate Vasoactive - Response: Improvement of Cr to
indicators of effect.
- Can be used on the floor via PIV with continuous O2 Medications within 0.3mg/dl of baseline OR Cr
monitoring. Requires GI/Renal approval. below 1.5 mg/dl if no baseline
Contraindications: Cr >5mg/dl, SpO2 <90%, pregnancy, HD, available. Monitor and cautiously
decompensated HF/ACS, mesenteric/peripheral ischemia, reintroduce chronic medications w/
actively listed for transplant GI.
- ATN: Supportive care and diuretic
challenge if needed

No Contraindications Contraindications

Second line: Norepinephrine

Starting Dose: 0.85mg IV q6h (at MGH) - Catecholamine with α1, α2, and β2 agonism
Assess volume status daily, can consider 25g albumin per Side
Effects - Requires ICU admission and (likely) central access
day as adjunct. - Starting Dose: 0.5-3mcg/min continuous IV infusion
Side Effects: abdominal pain, nausea, diarrhea, respiratory - Titrate to achieve MAP increase of >10mmHg. Max
failure*, ischemia. *Must stop if SpO2 <90% or if ACLF dose 10mcg/min.
grade 3 (3 severe organ failures) - Assess volume status daily, can consider 25g
albumin per day as adjunct.
Assess Creatinine on
Day 4 No Improvement or Worsening Cr
Improvement
Midodrine and Octreotide are
- ↓Cr by ≥30% from no longer part of the MGH
terlipressin initiation: HRS algorithm
Continue dose Monitor Creatinine Daily for HRS-AKI
- ↓Cr by <30% from Reversal:
initiation: Increase dose to Definition: Two consecutive Cr measurements No Reversal by Day 14 of
1.7mg IV q6h ≥2 hr apart within 0.3mg/dl of baseline OR Cr Vasoconstrictor Therapy
below 1.5 mg/dl if no baseline available

Successful Reversal Discontinue Vasoactive Therapy

Multidisciplinary discussion of options:
Discontinue Vasoactive Therapy Transplant discussion, potential consideration
Discuss possible TIPS with GI
24h after 2nd qualifying creatinine of RRT in select cases, and/or palliative care

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Gastroenterology Liver Transplant

INDICATIONS FOR L I V E R T R A N S P L A N T (AASLD: Hepatology 2014;59:1144)
• Acute liver failure: see Acute Liver Injury & Failure
Milan Criteria:
• Cirrhosis with MELD ≥15 or complication (e.g., ascites, HE, EV bleed, HRS, chronic
One lesion ≤5cm or up to 3
gastropathy bleed). (AJT 2005;5:307) Child B cirrhosis w/ portal HTN and low MELD can lesions all ≤3cm
be considered also. Start/refer for evaluation at MELD >10 (to give time for No extra-hepatic involvement
education/evaluation). No major vessel involvement
• HCC: first-line option within Milan criteria but unsuitable for resection (NEJM 1996;334:693;
Hepatology 2018;69:182) assigned score of 22; can be “down-staged” to within Milan with treatment; composite criteria
(surrogates of tumor biology such as AFP, treatment response, tumor size, number of nodules) may replace conventional
criteria. See ESLD: HCC
• Liver-based metabolic disorders w/ systemic manifestations: A1AT deficiency, familial amyloidosis, Wilson’s disease
(won’t resolve neurologic issues), hemochromatosis, glycogen storage disease, primary oxaluria
• Decompensated biliary disorders: PBC (intractable pruritus), PSC (recurrent cholangitis and sepsis)
• Systemic complications of chronic liver disease: hepatopulmonary syndrome, portopulmonary HTN
• Conditions qualifying for Exception Points (see below under “Prioritization for Liver Transplant”)

CONTRAINDICATIONS TO LIVER TRANSPLANT

• Absolute: severe cardiac or pulmonary disease, AIDS, HCC w/ metastatic spread, ongoing EtOH/illicit substance use
within 6mo (changing for EtOH in select cases; see Alcohol-Related Liver Disease), uncontrolled sepsis, anatomic
abnormality that precludes LT, intrahepatic cholangiocarcinoma, extrahepatic malignancy (other than skin, not meeting
criteria for cure), mPAP >35 or PVR >400, fulminant hepatic failure with sustained ICP >50mmHg or CPP <40mmHg,
hemangiosarcoma, persistent nonadherence to medical care, lack of adequate social support system
• Relative: BMI ≥40, HIV (all center-specific); age >70 is not a contraindication (Mayo Clinic Proceedings 2009; 84)

PRIORITIZATION FOR LIVER TRANSPLANT

• Prioritized based on MELD Score (AJT 2015;15:2552)& stratified by blood type
• Certain conditions result in impaired survival but are not directly accounted for in the MELD score  specific disease-
related criteria for MELD exceptions that upgrade MELD score w/ subsequent automatic upgrade q6mo
• Standard MELD exceptions: HCC (w/in Milan criteria, AFP <1000), hepatopulmonary syndrome (RA PaO2 <60mmHg),
portopulmonary HTN (mPAP <35), familial amyloid polyneuropathy (TTR mutation), primary hyperoxaluria, CF (FEV1
<40%), hilar/early-stage cholangiocarcinoma, hepatic artery thrombosis (w/in 14d of LT but not meeting status 1A
criteria), cystic fibrosis
• Can also petition review board for non-standard exceptions (e.g., refractory complications) esp if MELD score does not
reflect severity of mortality/morbidity related to the liver disease
• Some patients are candidates for double transplantation (e.g. with heart, kidney, lung)

TRANSPLANT EVALUATION PROCESS

• Laboratory testing: order set in EPIC; BMP, Ca, Mg, Phos, LFTs, GGT, CBC w/ diff, PT/PTT, T&S, Fe/TIBC, ferritin,
ceruloplasmin, A1AT level, autoimmune (ANA, ASMA, AMA, SPEP), viral hepatitis (HAV IgG, HBsAg, HBsAb, HBcAb
[total], HBeAb, HBV DNA, HCV Ab & PCR, HDV Ab), HIV, EBV, CMV, VZV, HSV, RPR, toxo, measles/mumps/rubella
titers, IGRA, AFP, PSA, amylase, uric acid, total cholesterol, U/A, UCx
• Additional tests: ABG (on RA), EKG, CXR, U/S w/ Doppler, abdominal CT or MRI (eval for HCC), age-appropriate cancer
screening (colonoscopy annual for PSC w/ IBD, mammogram, pap smear), bone density, cardiopulmonary eval as below
• Immunizations: HAV, HBV, pneumococcus, influenza, Tdap, MMR, varicella, COVID19
• Consults: Hepatology; will subsequently involve transplant surgery, transplant psychiatry, social work (address
psychosocial issues, adequacy of support, financial screening, insurance counseling), nutrition, transplant ID if indicated
• Cardiopulmonary eval: TTE w/ bubble ± PFTs. Dobutamine stress echo may be indicated (typically if >40 or CAD RFs).
Optimal strategy debated – AASLD: stress testing in all candidates; AHA/ACC: if multiple CAD RFs (JACC 2012;60:434);
may consider PCI prior to LT if significant stenosis; if concerned for HPS can get Tc99 shunt scan
• ID eval: eval for LTBI as above and tx pre-LT if able. Coccidiomycosis, strongyloides testing if from endemic area. Dental
extractions pre-LT. HIV not a contraindication if immune function adequate. HBV tx pre-LT. HCV can be tx pre- or post-LT
(timing depends on if LT imminent, access to HCV+ donor, comorbidities). Transplant ID consult
• Combined kidney transplant: eligible if CKD w/ GFR ≤30 or ESRD on HD; sustained AKI w/ dialysis ≥6wk or GFR ≤25 for
≥6wk; or metabolic disease (e.g. hyperoxaluria) (UNOS/OPTN: AJT 2016;16:758)
• Living Donor Transplant (LDLT): recipients should fulfill same minimal listing criteria as for deceased donor. Recipients of
LDLT have reduced wait list mortality compared to potential recipients of deceased donor organs.

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Nephrology Acute Kidney Injury

D E F I N I N G A K I (KDIGO 2012 Guidelines)
Stage Serum Creatinine Urine Output Work-up and management
 ≥0.3 mg/dl w/in 48h or (1) H&P (2) monitor Cr and UOP (3) UA and sediment
1 <0.5 ml/kg/h for ≥6h
1.5-1.9x baseline w/in last 7d (4) urine electrolytes (5) renal U/S and other tests (below)
2 2-2.9x baseline <0.5 ml/kg/h for ≥12h Above measures plus:
(1) renally dose meds (2) eval need for RRT (3) consider
3x baseline, Cr ≥4, <0.3 ml/kg/h for ≥24h ICU for CRRT, pressors for renal perfusion (4) avoid
3
eGFR to <35 (<18 yo), or RRT or anuria ≥12h subclavian CVCs/PICC (to preserve potential fistula sites)
and RIJ CVC in case emergent HD need arises

Diagnostic Tips
• Serum Cr approximates GFR at steady state only (unable to estimate GFR w/ ∆Cr): must assume GFR <10 if ∆Cr > 1 mg/dL/day
• Drugs can impair Cr excretion without ∆GFR (BUN remains stable): trimethoprim (in Bactrim), H2 blockers (cimetidine), dronaderone
• BUN out of proportion to Cr: pre/post-renal, UGIB, steroids. Cr out of proportion to BUN: rhabdo, AIN, TMP-SMX, vanc,  nutrition

STEPWISE WORKUP
1) History/exam: vitals (HTN/HoTN), volume status, exposures (contrast, meds), recent infection (IgA nephropathy 1-2d, post-strep GN in
10-14d), active infection (sepsis can induce ATN independent of BP or RBF (JASN 2011;22:999)), trauma/myalgias/found down
(rhabdomyolysis), rashes (AIN, vasculitis)
2) Urinalysis (UA): see Urinalysis. If AKI and UA demonstrate unexplained heme and protein, need to consider GN and renal c/s.
3) Urine chemistries:
o FENa: FENa <1% c/w pre-renal AKI, >2% c/w ATN. ONLY verified in oliguric AKI, not useful if on diuretics (FEUrea). Interpret
with caution in baseline CKD or chronic prerenal disease (CHF/cirrhosis). Note: GN, rhabdo, & IV contrast can all cause FENa
<1%. Overall limited use, except to rule out HRS with FeNa (J Hosp Med 2016;11:77)
o FEUrea: if on diuretics and high pretest prob. of pre-renal physiology. FEUrea <35% c/w with pre-renal (Kid Int 2002;62:2223)
o Urine Osm: >500 is consistent with a pre-renal etiology (high ADH state)
o Urine protein: if proteinuria on UA, send serum albumin, urine total protein, urine microalbumin, & urine Cr. Urine albumin/protein
ratio (APR) >0.4 suggests glomerular > tubulointerstitial process (Sn 88%, Sp 99%) (Nephro Dial Trans 2012;27:1534). Note: dipstick
detects albumin, will not help identify light chains/paraprotein.
4) Urine sediment: see Urinalysis. Look for casts, RBC morphology.
5) Eosinophilia/eosinophiluria: Not recommended - poor test for AIN. Urine eos >1% has Sn 31%, Sp 68% (J Hosp Med 2017;12:343)
6) Renal U/S: exclude hydronephrosis; often preceded by bedside bladder ultrasound. In absence of a suggestive history, <1% of renal
U/S for AKI showed post-renal etiology; can provide evidence of chronic processes if no known hx (BMC Nephrol 2013;14:188)
7) Monitor Cr, UOP, BP, and electrolytes: assess response to empiric treatment of presumed cause
8) Next if sediment or history suggests glomerular disease, broaden workup with C3/4, ANCA, anti-GBM, ANA, anti-dsDNA,
HBV/HCV/HIV, cryo, SPEP/UPEP/SFLC as per below. Consider biopsy if expected to change treatment.

DIFFERENTIAL DIAGNOSIS OF AKI

PRE-RENAL INTRINSIC POST-RENAL
GLOMERULAR TUBULO-INTERSTITIAL VASCULAR
 Absolute volume Urinary retention
Anti-GBM ATN Microvascular
- Bleeding - BPH, meds,
ANCA + - Ischemia, sepsis, toxic - TTP/HUS
- GI or skin loss neurogenic
- Microscopic - Contrast, rhabdo, - APLAS
- Diuretics - Foley dysfunction
polyangitis aminoglycosides - HELLP/eclampsia
- Osmotic diuresis Urinary obstruction
- Granulomatosis with AIN - Scleroderma
- Cerebral salt wasting (bilateral)
polyangiitis (GPA) 1) Meds (see below) - Meds (calcineurin
 Effective volume - Stones (single
- Eosinophilic GPA 2) Infectious: CMV, inhibitor/CIN,
- CHF/cardiorenal kidney/transplant)
- Drug-induced ANCA leptospirosis, legionella gemcitabine)
- Cirrhosis/hepatorenal - Malignancy
Immune complex 3) Autoimmune/infiltrative: TINU, Macrovascular
- Nephrotic syndrome - Retroperitoneal
Low complement: IgG4 disease, sarcoid, Sjogren - RAS (athero, FMD)
- Sepsis/third-spacing fibrosis (Radiation)
- PSGN, SLE, cryo, Crystals - Dissection
Δ renal dynamics - IgG4 disease w/
MPGN, MGRS - TLS (uric acid), acyclovir, sulfa - Renal artery/vein
- NSAIDs/COX-2s retroperitoneal
Normal complement: abx, MTX, cipro, ethylene glycol, thrombosis
- ACEi/ARBs fibrosis
- IgA nephropathy/HSP oxalate, bile acids - Polyarteritis nodosa
- Abd compart. syndr. - Congenital
- Fibrillary, Proteins
Relative hypotension anomalies
immunotactoid - MM, amyloid, Ig deposition
Common nephrotoxins (not comprehensive): see AAFP (Am Fam Phy 2008;7:743) or StatPearls for list of common nephrotoxins
AIN: NSAIDs, β-lactams, ciprofloxacin, sulfa drugs, rifampin, PPIs (delayed effect), mesalamine, allopurinol, NSAIDs
Direct tubular injury: calcineurin inhibitors, ACEi/ARB, NSAIDs, TMP-SMX, MTX, acyclovir (IV>PO), protease inhibitors, amphotericin,
tenofovir (proximal tubule), vancomycin (esp. with pip-tazo) (CID 2017;64:116), numerous cytotoxic, targeted, & immunotherapy cancer rx

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Nephrology Acute Kidney Injury

MANAGEMENT
“A Euvolemic Kidney is a Happy Kidney; Fluids are NOT always the answer”
1. Optimize hemodynamics, avoid nephrotoxins: correct volume status – IVF and hold diuretics if hypovolemic, diuretics if
hypervolemic. Stop NSAIDs/ACEi/ARBs. Avoid glucose and contrast. No evidence of benefit for empiric diuretics in oliguria (JAMA
2002;288:2547). If large volume resuscitation or critically ill, generally LR > NS (NEJM 2018;378:819; NEJM 2018;378:829)
2. Renally dose meds: use Lexicomp for help dosing by GFR (note: GFR calculation assumes a steady state. Assess trajectory of AKI,
if creatinine is rising, assume clearance is lower than GFR. If anuric, assume GFR is 0). Run MAR w/ pharmacy for additional support
3. Manage complications:
o HyperK: check EKG, monitor on telemetry until improved. Can stabilize with calcium gluconate, shift K+ with insulin/dextrose,
IVF/Lasix  Remove K from body with sodium zirconium cyclosilicate (lokelma), bowel reg, furosemide. Start low K diet.
o HyperPhos: start phosphorus binder such as sevelamer (start >5.5 mg/dl) vs. calcium acetate depending on calcium level. Avoid
IV calcium if Ca/Phos product> 70) as can precipitate. Low phos diet.
o Metabolic acidosis: sodium bicarb PO/IV (see Acid-Base Disorders)
o Bleeding with concern for uremic platelets: DDAVP 0.3 mcg/kg IV, onset 1h, lasts 4-8h
4. Indications for HD (AEIOU): Acidosis (esp. pH <7.0, refractory to bicarb), Electrolytes (refractory hyperK+), Intoxication (lithium,
ethylene glycol, metformin, salicylates, theophylline), refractory Volume Overload, Uremia (encephalopathy, neuropathy, pericarditis)
RENAL EMERGENCIES (WHEN TO PAGE THE RENAL FELLOW OVERNIGHT)
• Acidosis: severe metabolic acidosis (pH <7.1, <7.2 w/ severe AKI) w/o rapidly reversible cause (i.e. DKA). Temporize with bicarb
pushes and isotonic bicarb gtt, intubate and hyperventilate if unable to compensate by breathing off CO2. May need RRT particularly
if other indications. CVVH impact on lactic acid clearance is debated, pH correction is similar in correction rate to bicarbonate infusion.
• Hyperkalemia: hyperK w/ ECG changes/arrhythmia or K >6.5 (>5.5 if rising from ongoing rhabdo/GI bleeding). Temporize with Ca
gluconate, diuretics, insulin/D50, albuterol, etc. Note iHD clears K faster than CVVH so is preferred in stable pts who can tolerate iHD.
• Hyponatremia: call if severely symptomatic (AMS with low GCS, seizures, etc.) requiring bolus hypertonic saline +/- DDAVP clamp.
• Anuria w/ ADHF: place Foley, monitor UOP/MvO2/signs of shock (LFTs, Cr, Lactate, CI). Improving cardiac output (volume
optimization with diuretics or HD, ± inotropes) will raise GFR.
• Ingestions: lithium, ethylene glycol, methanol (elevated osmolar gap -> elevated anion gap), metformin with end organ damage (i.e.
renal failure, vision loss), see “Indications for HD (AEIOU)” above.
• RPGN: when suspected, urgent renal consultation to consider pulse dose steroids ± plasmapheresis. See Glomerular Disease.
• Scleroderma renal crisis: ACEi (captopril) at maximum tolerated dose (starting at 6.25 or 12.5mg, titrating up q4h). Avoid steroids.
SPECIFIC MANAGEMENT BY CAUSE
• Acute interstitial nephritis (AIN): stop offending agent, consider prednisone 40-60mg qd for 1-2w if biopsy-confirmed or high pre-
test probability though not great evidence (CJASN 2018;13:1851)
• Cardiorenal syndrome (type 1): (Nat Rev Neph 2013;9:99; Circ 2019;139:e840)
o Definition: 5 phenotypes that impact the heart and kidneys with various causal relationships. Type 1 is HF resulting in AKI.
o Pathophysiology: decreased renal perfusion from venous congestion ± CO leads to a low trans-renal perfusion pressure.
More of a problem with “under-draining” (congestion) than “under-filling” (perfusion)
o Treatment: relief of renal venous congestion. Trend Cr against TBB and daily weights to test hypothesis, expect a lag effect.
 Loop diuretics are first line for type 1 ± addition of thiazide (metolazone/chlorothiazide), see Advanced Diuresis
 No benefit of low dose dopamine or nesiritide to improve forward flow (JAMA 2013;310:2533)
o Ultrafiltration showed similar outcomes re: weight loss and CHF sx, but worsened renal function compared to pharmacologic
therapy with loop/thiazide diuretics (NEJM 2012;367:2296)
• Contrast-Induced AKI (CI-AKI, formerly “contrast-induced nephropathy”) (Nat Rev Nephrol 2017;13:169)
o Definition: Cr ≥0.5 or 25% within 48-72h of contrast without other causes
o Clinical syndrome: starts 24-48h, peaks 3-5d, resolves 10d; usually non-oliguric. Recent studies: unclear risk of AKI following
contrast, likely lower than previously estimated (Ann Em Med 2017;69:577). In recent regression discontinuity analysis, no
difference in kidney function at 6 months after contrast administration for CTPE in ED setting (JAMA Intern Med 2021;181:767)
o Pathophysiology: vasospasm vs acute tubular injury due to osmotic injury.
o Risk factors: higher contrast load, hyperosmolar contrast, intra-arterial injection (cardiac cath), DM, proteinuria, concomitant AKI
o Prophylaxis: for high-risk pts (GFR <30 or 30-45 + DM) receiving arterial/IV contrast, consider IV NS per MGH protocol (see
Contrast). If treating volume overload, hold diuretics day of contrast with no additional IVF. No added benefit for IV bicarb or NAC
(NEJM 2018;378:603) or pre/post/intra HD for anuric patient (Am J Med 2012;125:66).
o Rule of thumb: balance risk as detailed above with potential harm of delayed diagnosis that guides treatment on individual basis.
• Crystalline nephropathy: discontinue drug; fomepizole/HD if ethylene glycol toxicity; rasburicase/HD if TLS (see Tumor Lysis
Syndrome); IVF and diuresis if Acyclovir toxicity (goal UOP >150 cc/h)
• HRS: see Hepatorenal Syndrome
• Myeloma kidney (Cast Nephropathy):
o Dx: TP/Cr, SPEP/UPEP/SFLC, kidney bx if dx unclear
o Tx: IV hydration to target UOP >3L/d to minimize precipitation (volume overload can be treated with diuretics), chemotherapy to
decrease production of SFLC per oncology. Unclear benefit of plasmapheresis given rebound of light chain production.
• Post-renal: Foley, α-antagonists; 5α-reductase inhibitor (effect not immediate); urology/IR if perc nephrostomy tube needed
• Rhabdomyolysis: AKI unlikely unless CK >2k-5k; aggressive IVF for UOP >250cc/h with NS. Consider isotonic sodium bicarb if
marked acidosis (NEJM 2009;361:62) and no hypocalcemia, but no convincing evidence HCO3 is superior to NS. Monitor for electrolyte
abnx: hyperK, hypoCa. Continue aggressive IVF until CK <5000; if overloaded, continue IVF with close monitoring and diuresis

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Nephrology Glomerular Disease

NEPHROTIC SYNDROME (NS)
Etiology: podocyte integrity or presence -> glomerular proteinuria (predominantly albumin)
Presentation: Constitutional sx (fatigue, anorexia), HLD + premature atherosclerosis, foamy urine, hypercoagulability (10-40% VTE risk
2/2 loss of antithrombin & plasminogen), Vit D deficiency (loss of binding protein), infectious risk (IgG/opsonins), protein malnutrition
Diagnosis: spot urine PCR> 3000mg/g confirmed by 24h UPr >3.5 g/d AND albumin <3.5 (distinguishes from nephrotic range
proteinuria). Note that low and high muscle mass will over and underestimate proteinuria on spot ratios, respectively.
Work up: UA, Hgb a1c, ANA, anti-dsDNA, anti-PLA2R, THSD7A, SPEP/SFLC, HBV, HCV, HIV, syphilis, cryoglobulins, C3/C4, renal bx
Treatment: Edema: diuretics + low Na diet; HLD: statin; VTE risk: consider ppx or therapeutic AC; ACE/ARB (glom pressure). May
consider steroids. See KDIGO 2021 guidelines.
Disease Associations Biopsy Findings
Diabetes T1DM and T2DM, retinopathy/neuropathy; MCC of adult NS Nodular glomerulosclerosis
1°: toxin or circulating permeability factor → podocyte effacement
Mesangial collapse & sclerosis.
2°: viral (HIV, parvo, EBV, CMV), drugs (NSAIDS, pamidronate, INF,
FSGS Collapsing variant (a/w HIV & SLE)
rapamycin, heroin), adaptive (2/2 nephrectomy, CKD, obesity, reflux,
rapidly progresses to ESRD
HTN), chronic hypoxemia (OSA, sickle cell)
1°: Abs to podocyte PLA2R (75%) (NEJM 2009;361:11) or THSD7A Thick BM w/dense subepithelial
Membranous
2 : SLE, HBV, syphilis, drugs (NSAIDs, penicillamine, gold), solid tumors
° deposits & no cellular infiltrates
Minimal Change Idiopathic, a/w NSAIDs, lymphoma (HL most commonly), children>adults Podocyte effacement (EM)
Immune complex mediated: Chronic Infxn (HCV>HBV, endocarditis,
Thick BM, mesangial proliferation,
abscess); Autoimmune: SLE> sjogren’s, RA; Monoclonal
MPGN subendothelial ± subepithelial
gammopathies; Other: Lymphoma, solid tumor cancers. Complement-
deposits
mediated: dense deposit disease or C3/C4-glomerulonephritis
Diffuse amorphous hyaline glomerular
Amyloidosis AL (myeloma) and AA (systemic inflammation, e.g. RA, IBD)
deposits; +Congo red. IF κ/λ, LC if AL
GLOMERULONEPHRITIS (GN)
Etiology: Immune-mediated inflammation of the glomerulus leading to endothelial and podocyte injury  hematuria w/ active sediment
Presentation : AKI, HTN, edema, proteinuria, hematuria, hypercoagulability, rapidly progressive azotemia. If systemic vasculitis, often
fatigue, fever, weight loss, small-vessel involvement of other organ systems (palpable purpura, DAH, mononeuritis multiplex), SLE sx
1) Asx urinary abnormalities: subnephrotic proteinuria +/- microscopic hematuria; no renal impairment, edema, or HTN
2) Rapidly progressive GN (RPGN): GFR >50% in ~3 mo, glomerular crescents on bx, 0.5-2.5 g/d proteinuria, dysmorphic RBC.
3) Chronic GN: persistent proteinuria, +/- hematuria, slow progression
Workup: UA/sed (dysmorphic RBC; specific, less sensitive), RBC casts (rare, very specific), sub-nephrotic proteinuria (<3.5g/d, but 10-
30% >3g/d). Consider serololgic work up as per below. Early renal consult for consideration of biopsy.
Treatment: Tx of etiology (abx, antivirals, removal of offending drug), BP mgmt, diuresis, low Na diet. Sparsentan approved for tx of IgA
nephropathy (Lancet 2023;401:1584). Bx will guide immunosuppression, but if severe RPGN, consider empiric IV methylpred pulse (0.5-1
g x3 days) as you await bx followed by cyclophosphamide (CYC) or rituximab (RTX). RPGN from ANCA vasculitis: induction w/ steroids
+ RTX or CYC (NEJM 2010;363:221); maintenance w/ RTX > AZA (NEJM 2014;371:1771). Induction w/o PLEX and w/ -dose steroids
appears non-inferior and  infx risk (NEJM 2020;382:622).
Disease Associations Labs
Renal-Limited Immune Complex Deposition
Post-strep GN ~1-2w post-pharyngitis, 3-6w post-cellulitis ⊕ASO, C3
Fibrillary GN Idiopathic; cancer; autoimm (Crohn's, SLE, Graves', ITP) Normal C3 (bx IF +DNAJB9)
IgA nephropathy 1°: ~1-2d post-viral URI or GI infx. 2°: liver dx, Celiac, HIV +/- IgA, nl C3
Systemic Immune Complex Deposition
Photosensitivity, malar rash, sicca, pleuritis, cytopenias, ⊕ANA, ⊕anti-dsDNA, ⊕anti-Sm, C3,
SLE (Classes 3, 4)
arthralgias C4
Cryoglobulinemia (Type 2) HCV > HBV, ESLD, MM ⊕Cryos (⊕RF), ⊕HCV, C3, C4
Endocarditis Fever, valve dx, emboli ⊕BCx, C3, ANCA (⊕can be induced)
⊕IgA, nl C3 (IgA does not fix
IgA Vasculitis (HSP) Post-URI, malignancy, nephropathy, purpura, arthritis, GIB
complement)
Pauci-Immune Glomerulonephritis
Granulomatosis with Granulomatous sinusitis/otitis, other ENT sx, pulm sx c-ANCA/anti-PR3 (80%), p-ANCA/anti-
polyangiitis (DAH, granuloma), arthritis, palpable purpura, RPGN MPO (10%)
Eosinophilic granulomatosis Multi-system, new-onset asthma, allergic rhinitis/sinusitis,
p-ANCA/anti-MPO (50%), eos ≥1500
w/ polyangiitis mononeuritis multiplex
Microscopic polyangiitis Multi-system, non-granulomatous Anti-MPO (60-70%)
Hydralazine, PTU, allopurinol, adulterated cocaine -titer p-ANCA (95% drug-ind; MPO,
Drug-induced vasculitis
(levamisole  ear necrosis) HNE); c-ANCA (50%; anti-histone)
GBM Diseases
Anti-GBM/Goodpasture RPGN (crescentic), DAH (Goodpasture) Linear IgG along BM, ⊕anti-GBM IgG
Alport Mutant COL4A (renal, hearing, eye dx), familial EM w/ split GBM, ⊕COL4A3-5 testing
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Nephrology Chronic Kidney Disease

OVERVIEW
● CKD definition: GFR <60mL/min OR kidney damage
(albuminuria ≥30mg/d for ≥3mo (JAMA 2015;313: 837) Percentage of US Population by
● Estimating GFR: 2021 CKD-EPI (NEJM 2021;385:1737) eGFR and Albuminuria Category:
KDIGO 2012 and NHANES 1999-
(race omitted). Race in eGFR calc can lead to 2006. Colors represent risk for
undertreatment and transplant inequity for Black pts (NEJM progression, morbidity, and mortality:
2020;383:874) green (low), yellow (moderate),
orange (high), red (very high). Lancet
● Role for Cystatin C: protein excreted by cells, less affected 2012;379:165
than Cr by gender, age, body size, nutritional status (Expert
Rev Mol Diagn. 2020; 20(10): 1019). Input w/ Cr into
combined 2021 CKD-EPI eGFR calculator.
● Etiology: DM (47%), HTN (28%), GN (7%), cystic kidney
(3%), other (15%) (USRDS 2018)
● Epidemiology: 15% US adults; ESRD prevalence 4-fold
higher in Black pts than White pts (USRDS 2021). 13% of
Black individuals have a high-risk apolipoprotein-1
(ApoL1) genotype, which confers ↑CKD risk
● Disease Monitoring: G1-G3a: risk factor reduction. G3a-
G3b: evaluate & treat complications. G4 (or A3): nephrology
referral, prep for RRT/transplant. G5: RRT (if indicated), transplant eval
MANAGEMENT
● BP control: goal <120/80 (KDIGO 2024 guidelines). Mortality benefit w/ intensive BP mgmt (SBP <120 mmHg) (NEJM 2021;384(20)).
o If proteinuria: ACEi; if edema: loop diuretic if eGFR <30, thiazide if >30 (emerging evidence for considering chlorthalidone in
advanced CKD in select pts) (NEJM 2021;385:2507); if resistant HTN or HFrEF/HFpEF: spironolactone.
● Proteinuria: Albuminuria independently predicts mortality and CKD progression w/ tx goal as <300mg/d. Start w/ RAAS blockade
(ACEi or ARB) uptitrated as tolerated (NEJM 2013;369:1892). If albuminuria >300 mg/d or proteinuria >500 mg/d, add SGLT2-i if
eGFR>20-30 to ↓ CKD progression (NEJM 2022;388:117). If CKD a/w diabetic kidney disease w/ GFR ≥ 25, ACEI/ARB maximized +
SGLT2i started + K ≤ 4.8 + continued albuminuria ≥ 30mg/d, consider finerenone (non-steroidal MRA shown to reduce CV risk
primarily by reduction in HF exacerbations). Watch out for cost and ↑K+ when starting finerenone (KDIGO 2024 guidelines).
● DM: goal HgbA1c <7%. SGLT2i (if eGFR >20-30) indicated in pts with T2DM and DKD (BMJ 2021;372:4573), other agents include
metformin (eGFR >30-45), GLP-1r agonists (eGFR >30). Insulin safe at any eGFR, though may have to be dose adjusted as insulin
clearance ↓ w/ ↓GFR. ↓Rate of CKD progression with SGLT2i (NEJM 2019;380:2295) & GLP-1r agonists (NEJM 2017;377:839).
● CVD: risk 2-4x general population. Statin if >50 y/o and no ESRD/tx (Kidney Int 2014;85:1303). SGLT2 inhibitors ↓CKD
progression/mortality/CVD outcomes. (NEJM 2020;383:1436). No benefit seen in initial invasive vs. conservative strategy in stable
CAD + advanced CKD, and mod/sev ischemia (NEJM 2020;382:1608)
● Nephrotoxins: Avoid NSAIDs, chronic PPI’s, contrast, select and dose meds renally (abx, tacrolimus, statins, opiate pain meds)
● Nutrition: nephrocaps (B-complex / C), Na <2 g/d, ↑ fruit/vegetable intake, ↓protein to 0.8 g/kg for non-nephrotic CKD w/ eGFR <60,
restrict K/Phos prn
● Monitoring: q4-12mo Cr & electrolytes, PTH, CBC, Fe studies. Annual UAlb/Cr & UProt/Cr ratios, 25-OH Vit-D. Renal U/S at dx
● Nephrology referral: GFR ↓ 30, sudden ↓ in GFR, severe proteinuria (Alb:Cr >300), UA w/ +blood/protein with ↓GFR, resistant HTN
● Prognosis: based on 1) cause of CKD, 2) GFR category, 3) albuminuria, 4) other risks Tangri risk score (JAMA 2016;315:164)
COMPLICATIONS
Hyperparathyroidism
Type Ca PO4 PTH VitD Pathophysiology
1º HyperPTH ↑ ↓ ↑ nl Excess PTH production by parathyroid gland
2º HyperPTH (2/2 ↓VitD) ↓ ↓ ↑ ↓ Decreased Ca absorption stimulates PTH secretion
2º HyperPTH (2/2 CKD) nl/↓ ↑ ↑ nl/ ↓ ↓ PO4 excretion increases PTH secretion
3º HyperPTH ↑ ↑ ↑↑ nl/ ↓ Longstanding 2º hyperPTH leads to PTH gland hyperplasia
● Mineral and bone disorder: check Ca, PO4, ALP, 25-OH vit D (1,25-OH vit D level will fluctuate) (Annals 2018;168:422).
o PTH rising or persistently above goal (2-9x ULN, based on CKD stage): restrict dietary phos, non-Ca phos binders (sevelamer
preferred, w/ meals & snacks) (CJASN 2016;11:232), calcium/Vit D supplements not recommended unless on HD
o Severe/refractory PTH > 1000: calcitriol vs calcimimetic vs parathyroidectomy if non-responsive to medical therapy
● Anemia: Hgb < 13 (M), < 12 (F). Screening: annual if eGFR >45, q6m if <45, q3-6m if anemic. Goal Hb 10-11.5 (Kidney Int 2012)
o Iron repletion (PO or IV): Consider 1 gram IV iron empirically if Tsat <20% and/or ferritin <100ng/mL. If TSAT is 20-30% and
ferritin <500, can consider challenging with iron or starting an ESA. Check q3m if on ESA. (Cochrane 2019;2:7857)
o If Fe replete and Hgb <10, consider erythropoiesis stimulating agents (ESA) consider ESA, which ↓ transfusions, Fe overload,
Ab formation. Contraindicated in cancer, SBP>160, HF, stroke. Hb >13 with ESA increases risk of CVA (NEJM 2009;361:2019)
● Metabolic acidosis: NaHCO3 starting at 650 mg 2-3x/day titrating up to 1300 mg up to TID for goal HCO3 in normal range (23-29
mEq/L; avoid >29 mEq/L bc ↑ mortality). Slows progression of CKD, improves bone health (CJASN 2019;14:1011)
● Uremic bleeding: Treat depending on clinical context or if pre-procedure; can use DDAVP 0.3-0.4 mcg/kg x1 with max 40 mcg
● Preparation for HD access: avoid BP measurements and venipuncture in non-dominant arm, avoid subclavian/PICC lines due to risk
of central stenosis (precludes future AVF placement) → prefer IR small bore tunneled IJ. Prefer LIJ CVC in case need for HD

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Nephrology Dialysis & Transplant

O V E R V I E W (NEJM 2022;386(10):964)
Diffusion: concentration gradient drives small molecules (e.g. urea, creatinine) across Emergent Indications for RRT (AEIOU)
selectively permeable membrane Acidosis: metabolic, pH <7.1
Convection: hydrostatic pressure forces medium-weight molecules across membrane Electrolytes: refractory/rapidly rising K
Ultrafiltration (UF): volume removal, removal of plasma water by hydrostatic pressure Ingestions: dialyzable toxins (eg: Li, ASA,
IMPORTANT CONSIDERATIONS methanol, ethylene glycol, metformin)
Timing: controversial, most recent studies suggest no benefit to early RRT Overload: diuretic-refractory volume
• ELAIN (JAMA 2016;315:2190): early RRTduration RRT, LOS/mortality Uremia: encephalopathy, pericarditis,
coagulopathy with uremic bleeding
• IDEAL-ICU (NEJM 2018;379:1431): no ∆mortality w/ early RRT (pt w/ sepsis, AKI)
• STARRT-AKI (NEJM 2020;383:240): early RRT did not reduce 90d mortality vs. standard RRT (clinical indication).
• AKIKI-2 (LANCET 2021;397:1293): delayed RRT in oliguria >72h or BUN >112 until clinical indication showed mortality
ACCESS FOR HEMODIALYSIS
• Dialysis lines can only be accessed by dialysis/ICU RNs (except in codes); contact dialysis unit (x63700).
• PICCs: HD or future HD candidates should not receive PICC unless first cleared by Renal (to preserve options for vascular access)
Types of access for HD Durability Benefits Risks/Downsides
Non-tunneled double lumen Days-weeks Can be placed and used immediately. Infection. Can clot or kink. ONLY to be used for RRT
central line, femoral or R IJ while admitted.
Tunneled central line Weeks-mos, Can be placed by IR within hrs. Can be Infection and clot. ONLY to be used for RRT. Long term
can be yrs used as an outpt. risk of central venous stenosis
AV fistula (pt A-V) Yrs Lowest infection and clot risk. ~3-6 mos to mature, 1° failure in ~40%. Limb edema,
Associated with increased survival aneurysm/stenosis/clot, vascular steal, high output CHF
AV graft (synthetic graft Yrs Useable in days-wks. Lower infection Delayed failure (~25%) 2/2 stenosis/thrombosis. Risk of
connects A-V) and clot risk than central access. aneurysm. Infection requires surgical resection.
I N T E R M I T T E N T H E M O D I A L Y S I S ( I H D ) (NEJM 2010;363:1833); consider in critically ill pts (Lancet 2006;368:379)
• Mechanism: Cr, urea, K+ move from blood to dialysate; Ca2+ and HCO3- move from dialysate to blood (diffuse via concentration
gradients). Volume removal occurs via UF. Blood flow rate ~200-500mL/min. Usually three 4h sessions/wk.
• Intradialytic medications: erythropoietin, iron, vitamin D analogues, antibiotics, heparin (to prevent clotting of HD circuit)
• Complications: HoTN, arrhythmia/cardiac events, cramps, disequilibrium syndrome, dialyzer reaction, HIT, hemolysis, EtOH w/d
PERITONEAL DIALYSIS (PD)(NEJM 2021;385:1786) Daytime: PD RN (617-726-0717)
• Mechanism: infusion of fluid rich in osmotic agent (e.g. dextrose)  use peritoneum as membrane solute removal via diffusion
• Benefits: preserves residual GFR longer than IHD, better middle molecule clearance, can be done at home.
• Modalities: (1) continuous ambulatory PD (CAPD) manual exchanges occurring day and night (2) nocturnal intermittent peritoneal
dialysis (NIPD) w/ dwells only at night (3) automated PD (APD) multiple automated exchanges overnight w/ long daytime dwell
• Complications: Encapsulating peritoneal sclerosis, hernia, pleural effusion, leaking, hypoK (dialysate has no K). Peritonitis (dx 2/3:
1) abd pain/cloudy fluid 2) effluent fluid WBC >100 w/ >50%PMNs (after >1-2 hr dwell) 3) +effluent fluid culture (see ellucid). Treat
after culturing w/ IP vanc/ceftazidime (use IV gram+&- coverage if septic). Remove catheter if no resolution w/in 5d or if fungal infxn.
CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)
• Principles: continuous slow clearance, replacement fluid must be added back to restore volume, A/B balance + electrolytes. Less
effective in toxin removal/volume overload compared w/ IHD. Not ideal for hyperK/toxins. Blood flow rate ~100-200mL/min.
o CVVH: continuous veno-venous HF, removes solute via convection; AVVH: intermediate CVVH circuit setting w flow rates/12h
o CVVHD: continuous veno-venous HD, removes solute by diffusion; CVVHDF: combines convection + diffusion to remove solute
• Indications: (1) HD instability/inability to tolerate iHD (2) persistent acidemia despite iHD (3) risk of cerebral edema w/ iHD.
• Volume management: run negative, even, or slightly positive. Replacement fluid w/ dextrose, bicarb, lactate, acetate or citrate.
• Anticoagulation: used to risk of circuit clotting, use heparin OR citrate, citrate achieves regional AC by Ca chelation  follow iCa
levels (willtotal Ca but iCa), metabolized in liver  if Cat/iCa >2.5,AG with met alk=possible citrate toxicity (avoid in liver failure).
• Complications: HoTN, arrhythmias, hypothermia,iCa/K/PO4, bleeding, thrombocytopenia (mechanical destruction), HIT
• Drug dosing: drugs can bind to circuit resulting in VD  work with pharmacy to re-dose all meds based on flow rate
RENAL TRANSPLANT
• Basics: mortality & QOL benefit, more cost-effective than HD; LDKT > DDKT; racial disparities exist in transplant access
• Listing: refer EARLY (GFR <30), pts can be listed when GFR <20; pt & graft survival are improved if transplant occurs PRIOR to HD
• Contraindications: short life expectancy, active malignancy, SUD, nonadherence. Age/HIV/psych comorbidities NOT contraindications
• Allograft dysfunction: delayed graft function: <1w (prerenal, ATN, thrombus, obstruction), early: 1-12w (prerenal, CNI tox, infxn [BK
virus, CMV], acute rejection), late acute: >3mo (prerenal, CNI tox, noncompliance), late chronic: yrs (HTN, CNI tox, BK virus,
recurrence of original renal pathology, chronic allograft nephropathy)
IMMUNOSUPPRESSION
Class Examples Mechanism of Action Adverse Events
Cyclosporine Inhibits calcineurin-mediated activation of NFAT  Nephrotoxicity (long-term fibrosis), HTN, tremor,
Calcineurin inhibitor (CNI)
Tacrolimus (FK506) blocks T-cell cytokine production insomnia, hirsutism (CsA only)
mTOR inhibitor Sirolimus (Rapamycin) Inhibits mTOR  blocks IL-2 production Pulm edema, poor healing, TG, oral ulcer
Mycophenolate Inhibits de-novo purine synthesis N/V/D, cytopenias
Antimetabolite
Azathioprine Purine analogue BM suppression, N/V/D, hepatitis

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Nephrology Advanced Diuresis

GENERAL PRINCIPLES
• Obtain daily standing weights, Na+ restriction 2g/day + fluid restriction 1.5-2L
• Loop diuretics have a sigmoidal dose-response curve (i.e. diuretic threshold effect),
so double dose until adequate response is achieved
• Transient  in serum Cr are common in diuresis (~20% of cases in DOSE-AHF,
ROSE-AHF), can be tolerated if effective decongestion. No assoc. between renal
function during diuresis and biomarkers of tubular injury; rather, associated with better
outcomes in HF (Circ 2018;137:2016, JCF 2016;22:753).
Loop Diuretics (Loop of Henle) Thiazide Diuretics (DCT)
Chlorthalidone, HCTZ (PO)
Furosemide Torsemide Bumetanide
Metolazone, Chlorothiazide (PO/IV)
Mechanism of Inhibit Na-K-2Cl transporter in asc. limb of loop of Henle to Na Inhibit NaCl channel in DCT to Na reabsorption
Action reabsorption and “break” medullary concentrating gradient and prevent urinary dilution
PO Bioavail. 20-50% 80-90% 80% Variable
Duration of HCTZ: 6-12h; chlorthalidone: 24-48h
~6 hours 6-8 hours 4-6 hours
action metolazone: 24h; chlorothiazide (IV): 2h
1mg Bumetanide IV/PO = 20mg Torsemide PO = Administer metolazone 2.5-10mg PO or
Dosing 20mg Furosemide IV = 40mg Furosemide PO. chlorothiazide 500-1000mg IV 30 min before loop
considerations Consider dosing BID-QID to avoid anti-natriuresis seen in QD diuretic to “disable” Na reabsorption in DCT
dosing (see NEJM 2017;377:1964 Fig. 2C) (sequential nephron blockade (SNB)).
Na (avoid if SIADH), K, Mg, Ca, urate,
Side effects Na, K, Mg, Ca, urate, HCO3, ototox, allergy
glucose, HLD, pancreatitis, MBD
DISEASE-SPECIFIC CONSIDERATIONS
Condition Mechanism Treatment
• GFR  delivery of diuretic to nephron  higher doses • High-dose loop ± thiazide augmentation (prefer
CKD/AKI needed for effective diuresis Furosemide in CKD given renal excretion, longer ½
• Organic acids accumulate and compete with diuretics life)
Chronic • “Braking phenomenon” of compensatory DCT hypertrophy
• Add metolazone or chlorothiazide
Diuretic Use leads to  distal Na reabsorption
• DOSE (NEJM 2011;364:797): in ADHF, no ∆ sx or renal
• In ADHF, GI edema leads to absorption of PO diuretics
CHF fx for pts receiving drip vs bolus dosing
• High sympathetic tone  RAAS, Na reabsorption
• Consider SNB (see Stepwise Approach in CHF)
 Albumin,
• Loop diuretic (needs to bind to albumin) leaks out of • Consider bumetanide (lower albumin-binding need)
nephrotic
vasculature (VD) resulting in delivery to nephron • No evidence for benefit of albumin + loop diuretic
syndrome
• Decreased delivery to nephron in setting of  albumin • Avoid IV diuretics unless respiratory distress or
Cirrhosis • Splanchnic vasodilation  EABV  renal hypoperfusion significant peripheral edema
• SNS and RAAS  Na reabsorption • See ESLD: Ascites
O T H E R D I U R E T I C S A N D S T E P W I S E A P P R O A C H I N H E A R T F A I L U R E (NEJM 2017;377:1964)
1. IV loop diuretic. Starting dose: 2x-2.5x home dose as IV furosemide (CHF) (e.g. if home 80mg PO lasix, give ~80-100mg IV) or
Cr×40 as IV furosemide (e.g. if Cr 3, use lasix 120mg IV)
2. Reassess in 1-2 hrs and double dose Q1-2H until response achieved. Adequate dose causes brisk diuresis (Goal >100-150 cc/hr).
a. Consider loop diuretic gtt (bolus when initiating gtt and re-bolus every time gtt increased), though evidence suggests
not more effective in ADHF (NEJM 2011;364:797).
3. If refractory edema, consider augmentation to achieve SNB. Selection of agents should be tailored to severity of overload, clinical
setting, long term benefits, labs, and ability to replete Mg/K.
a. Chlorothiazide: short term augmentation or diuretic challenge is required inpatient, can help with hypernatremia
b. Metolazone: when a longer duration of augmentation is required inpatient or outpatient, can help with hypernatremia
c. Acetazolamide: PCT blockade. Acetazolamide IV 500 mg daily in addition to a loop diuretic, especially if metabolic
alkalosis limiting diuresis. (HCO3, pH >7.45). ADVOR (NEJM 2022;387:1185) showed better decongestion when
added to loop diuretics in ADHF compared to loop diuretics alone when used daily for 3 days. Caution in COPD,
acidosis, and sulfa allergies.
d. Aldosterone Antagonists: Spironolactone: 12.5-200 mg / eplerenone 25-50 mg QD. Role in CHF/Cirrhosis. Causes
K, gynecomastia (10% pts, only spironolactone). Useful when hypokalemia is limiting diuresis and minor
augmentation needed.
e. SGLT2i: Modest diuretic effect started closer to DC (Circ 2022;146:289). Maintenance diuretic may need to be
variably decreased when starting. Caution in pts w/ frequent UTIs, AUD, and  PO intake.
4. Nephrology consult for consideration of short term UF/RRT as a bridge to renal recovery or advanced therapies
5. If starting maintenance loop diuretic at discharge, no strong evidence to prefer torsemide over PO furosemide (TRANSFORM-HF:
JAMA 2023;329:214), but make sure to adjust the amount of maintenance diuretic if also discharging w/ MRA or SGLT2i.
6. Be conscious of potassium repletion during hospitalizations and discharge with standing K repletion or increased MRA if needed.
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Nephrology Acid-Base Disorders

OVERVIEW
• ABG vs VBG: VBG pH ~0.04 lower, HCO3 ~2mEq lower (BMP more accurate), CO2 ~3-8 mmHg higher. VBG can screen for
hypercapnia w/ pCO2 cutoff ≥45mmHg (100% Sn) but does NOT accurately assess degree of hypercapnia. VBG PCO2 non-
correlative in severe shock. When in doubt, check ABG (AJEM 2012;30:896).
• Severe acidemia (pH <7.2) may precipitate systemic vasodilation, inotropy/MAP, response catechols/pressors, arrhythmia,
K, insulin resist., AMS
• Severe alkalemia (pH >7.6) may precipitate systemic vasoconstriction, coronary/cerebral perfusion, SVT/VT, K/Ca/Mg/Phos,
AMS, seizure, hypoventilation
S T E P - W I S E A P P R O A C H (NEJM 1998;338:26; NEJM 2014;371:1434)
1. Is there acidemia (pH <7.36) or alkalemia (pH >7.44)?
2. Is 1° disorder metabolic (parallels pH ∆) or resp (opposite pH ∆)?
Expected Compensation (JASN 2010;21:920)
3. Is pt compensating? (respiratory takes min-hrs, renal 3-5d) Metabolic acidosis: 2-24h
4. Is there an anion gap? Calculate regardless of pH or HCO3 Winter’s formula: pCO2 = (1.5 x HCO3) + 8 ± 2
AG = Na – (Cl + HCO3) = unmeasured anions – unmeasured cations Metabolic alkalosis: start 30min, complete 24h
Correct AG for albumin: AGc = AG + 2.5(4 – albumin) PaCO2 = 0.7 x (HCO3 -24) + 40 ± 2 = HCO3 + 15
Negative AG: ↑↑Na or other cations (Ca, Mg, Li), lipids (interfere with ∆ HCO3  1  expect ∆ pCO2  0.7
chloride), protein (multiple myeloma), bromide or iodine intox, Respiratory acidosis:
5. If there is ↑AG metabolic acidosis (AGMA), calculate “delta-gap” Acute: ∆ pCO2  10  ∆ HCO3  1 or  pH 0.08
Delta gap = (Albumin corrected AG-12) + HCO3. If <18 additional Chronic: ∆ pCO2  10  ∆ HCO3  4 or  pH 0.03
NAGMA, 18-30 no additional disorder, >30 additional met alk Respiratory alkalosis:
6. Consider Osm gap = [2(Na + K) + Urea/2.8 + glucose/18 + EtOH/4.6 – Acute: ∆ pCO2 10  ∆ HCO3  2 or pH 0.08
serum Osm] to screen for exogenous osmoles (e.g. toxic alcohols), also Chronic: ∆ pCO2 10  ∆ HCO3  4 or pH 0.03
seen in pseudohyponatremia

ALGORITHMIC APPROACH

R- RTA
A- Ammonia/
Acetazolamide/
hyperAlimentation
G- GI losses/
GU conduit
E- Endocrine
S- Saline

UAG “neg-GUT-ive
in GI disorders

AG OG Ingestions Metabolites Manifestations

∆MS, blurry vision, pupil dilation,
Methanol Formic acid
papilledema
∆MS, CN palsy, GU symptoms (flank
Ethylene glycol Oxalic acid pain, hematuria), tetany 2/2Ca, Ca
 
oxalate crystals → AKI
Propylene glycol Lactic acid AKI, liver injury
AKI, n/v, hepatitis, pancreatitis,
Diethylene glycol Diglycolic acid
neuropathy, later ∆MS, lactate
Isopropyl alcohol Acetone ∆MS, fruity breath, pancreatitis,  lactate
(via 5-oxoproline) nl/ 
Ethanol Acetaldehyde Keto/lactic acidosis ± met. alk 2/2 emesis

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Nephrology Acid-Base Disorders

M A N A G E M E N T O F A C I D - B A S E D I S O R D E R S : treat the underlying cause!
• Metabolic acidosis:
o Acute:
 In BICAR-ICU (Lancet 2018;392:31), pts with metabolic acidosis (pH <7.2) tx w/ IV HCO3 for goal pH >7.3 had no ∆ in overall
mortality but RRT initiation. A subset of pts w/ AKIN stages 2-3 had improved mortality at 28d
 For pH <7.1 or HCO3- <6: if HDS, can start isotonic HCO3 gtt. Monitor VBG/ABG q1h + electrolytes (K, iCa) and volume
status. Bolus admin is controversial due to c/f CO2 accumulation  hypercapnia (acidosis), hypernatremia, hypocalcemia,
hypertonicity, hypervolemia, overshoot alkalosis
 For bicarb to have full effect on serum pH, pt must be able to increase minute ventilation to ventilate off CO2
o Special considerations:
 Toxic alcohols: call poison control, NaHCO3, fomepizole, or HD (if vision ∆, AKI, HAGMA, methanol >50mg/dL, ethylene
glycol >300mg/dL)
 Salicylate poisoning: NaHCO3 to goal urine pH >6.5 and serum salicylate level <40 or HD (if level >80mg/dL, coma, AKI,
hypervolemia, AMS), dextrose containing fluids if AMS. Acetazolamide is contraindicated
 NAGMA and uremic acidosis are more responsive to HCO3 than lactic and ketoacidosis
o Chronic: in CKD, replete with PO NaHCO3 for goal HCO3 >22. See CKD
• Metabolic alkalosis: replete volume, K, & Cl
o Treat both (1) underlying cause of metabolic alkalosis and (2) cause of renal retention of HCO3
o If saline responsive: NS w/ KCl until urine pH >7. For pts w/ CHF/cirrhosis & alkalosis 2/2 diuresis, consider Acetazolamide
and/or K+ sparing diuretic. See Advanced Diuresis
o If saline resistant: for mineralocorticoid excess  use K+-sparing diuretic (prefer amiloride, faster than spironolactone) &
consider surgical removal of adenoma
o If pH >7.6 & persistently volume overloaded, give acetazolamide + loop diuretic with close K+ monitoring. May need KCl
• Respiratory acidosis: treat underlying process; adjust vent settings if intubated. NaHCO3 unlikely to be helpful, theoretically harmful
if unable to ventilate subsequent CO2 produced. For every 100mEq HCO3 administered, 2.2L CO2 must be exhaled.
• Respiratory alkalosis: address underlying cause (correct hypoxemia, treat pain/anxiety/fever); adjust vent settings if intubated

R E N A L T U B U L A R A C I D O S I S ( R T A ) (Int J Clin Pract 2011;65:350)

Consider in select pts w/ Hyperchloremic NAGMA or hyperK (Type IV). R/o GI losses & IV NS use before ordering UAG!
Pathophysiology: inappropriate net retention of acid or inadequate reabsorption of bicarb
o In acidemia, kidney should NH4+Cl- excretion and urine pH should be <5.3; this process is defective in RTAs.
o Caveat: CKD of any etiology is associated with NH4+ production & acidosis
Etiologies:
• Proximal RTA (Type II): decreased threshold for proximal tubule HCO3- reabsorption → more HCO3 spills into urine
o Primary (rare): Na-HCO3 cotransporter defect
o Acquired: amyloidosis, MM, post-renal transplant, bladder outlet obstruction, heavy metals, Vit D, Wilson’s disease, PNH
o Meds: acetazolamide, cisplatin, tenofovir, aminoglycosides, topiramate
o Often a/w Fanconi Syndrome: glucosuria (w/ serum gluc <180), hypouricemia, aminoaciduria
• Distal RTA (Type I): inability to secrete H+ in distal tubule. Various subtypes of distal RTA related to affected transporter/tight junction
o Primary: genetic loss of H+ or HCO3 transporters in intercalated cells
o Acquired: autoimmune disease (RA, SLE, SS); hypercalciuria (any cause); obstructive nephropathy; SCD, MM, amyloid,
cryoglobulinemia, tubulointerstitial injury, renal transplant rejection, cirrhosis, glue sniffing (toluene)
o Meds: amphotericin B, Li+, ifosfamide, ibuprofen, codeine
• Type IV: effective hypoaldosteronism: aldo secretion OR tubular resistance  K  NH3 synthesis  NH4+ excretion
o Hyperkalemia inhibits glutaminase enzyme, which generates NH3 (“ammoniagenesis”). Acidosis ensues as unable to fix and
excrete H+ as ammonium.
o Hyporeninemic hypoaldosteronism (most common): diabetic nephropathy, CIN, NSAIDs, calcineurin inhibitor, HIV
o  Aldo production: ACEi/ARB > heparin > adrenal insufficiency, severe illness
o Aldosterone resistance: (ENaC inhibition) K-sparing diuretic, trimethoprim, pentamidine
Workup: clinical history (PMH – autoimmune or malignancy, med review, stones), response to HCO3 supplementation
o VBG, BMP (AG, HCO3, K), UA (pH), urine lytes. Consider urine Ca/Cr to differentiate proximal vs distal RTA
o Estimate of Urine NH4+: UAG = Na + K - Cl (less useful when urine pH >6.5 or UNa < 25, high aldo state)
PROXIMAL RTA (TYPE II) DISTAL RTA (TYPE I) TYPE IV RTA
Defect Proximal HCO3- resorption Distal H+ secretion Distal K and acid secretion
Serum HCO3- 12 – 20 <10 >17
Serum K  or normal  or normal 
Urine pH during acidemia Varies, but >5.5 after HCO3- >5.5 <5.5, but cannot buffer w/ NH4+
Urine AG = Na + K – CL ⊝ ⊕ ⊕
Urine Ca/Cr nml, give bicarbonate
Additional dx testing Urine Ca/Cr elevated Renin, aldosterone, cortisol
and check urine pH
Complications Rickets, osteomalacia CaPO4 urinary stones Hyperkalemia
Tx Challenging. NaHCO3 (10-20 Treat hyperK: loop, low K diet
NaHCO3 (1-4mEq/kg)
(Goal HCO3 22-24) mEq/kg) or KCitrate. If hypoaldo, can give fludrocort

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Nephrology Sodium Disorders

H Y P O N A T R E M I A : free water excess relative to serum sodium (JAMA 2022:328(3):280-291)
S/Sx: often asymptomatic; can present with AMS, HA, N/V, weakness, seizures, signs of increased ICP
Workup: H&P: symptoms, etiology, chronicity, new meds, endocrine ROS, volume status, surg w/ irrigation (prostate/bladder/uterine)
• Studies: Obtain prior to treatment Serum: BMP, Osm. Consider uric acid, TSH, AM cortisol. Urine: UA, Osm, Na, uric acid.
• Determine if ADH is present (UOsm >100**). Can approx UOsm from UA: last 2 digits of SG x 30 (e.g., SG 1.010 ≈ UOsm 300)
• Other diagnostic clues (Eur J Inter Med 2016;29:22; JCEM 2008;93:2991; Ann Intern Med 1980;93:716; Cureus 2020;12:e7762):
o Other solutes: SIADH: often serum uric acid (sUA) <4, BUN <5, fractional excretion of uric acid (FEUA) ≥10-12% (small studies:
100% PPV for SIADH/thiazide hypoNa; FEUA ≤8% = 100% NPV for SIADH). EABV: often sUA >5, BUN, FEUA <4%
o IVF: SIADH: NS initially SNa but then will SNa (Na is excreted while H2O retained). Hypovolemia: NS will SNa
Note: Serum osm may be misleading and not reflective of serum tonicity if ineffective osms are present (BUN or ethanol)

HYPOtonic hypoNa (SOsm <300) ISOtonic hypoNa (SOsm ≈300) HYPERtonic hypoNa (SOsm >300)
AKA “pseudohyponatremia”: AKA “translocational hyponatremia”:
hyperproteinemia (myeloma, IVIG), lipemia hyperglycemia, ↑osmolal gap (mannitol, glycine,
✓ UOsm Consider VBG w/ lytes for more accurate Na sorbitol, IVIG stabilizers)

UOsm <100** UOsm >100** ✓ UNa Figure adapted from

ADH absent ADH present Surrogate for volume status Am J Med 2010;123:652

ADH Absent States UNa <30: RAAS active, Na avid UNa >30: RAAS inactive, Na wasting
ETIOLOGY

Overwhelming kidney’s ability to dilute  EABV, ADH “appropriate” Kidney will not dilute, ADH inappropriate
1° polydipsia: psychogenic, True hypovolemia (TBW and EABV) SIADH: CNS dz, pain/nausea, lung infxn/cancer,
endurance athletes, MDMA use TBW but EABV meds (NEJM 2023;389:1499-1509), idiopathic.
solute intake: tea & toast, beer 3rd spacing (pancreatitis, musc injury) Other: thiazides, ACEi/ARBs, ESRD, cerebral Na
potomania CHF, cirrhosis, nephrotic syndrome wasting, adrenal insuff, severe hypothyroid

1° polydipsia: restrict fluids Hypovolemia: replete volume (at high risk Correct underlying cause.
TREATMENT

solute intake: SLOW introduction of for overcorrection, watch UOP, may need SIADH: Use UOsm to guide management. If
solute, will correct RAPIDLY, at high DDAVP) mild, fluid restrict (1-1.5 L/d); consider NaCl tabs
risk for overcorrection Pancreatitis: replete volume (1g TID), urea (15-60 g/d, KI 2015;87:268), or
CHF, nephrosis: diuresis SGLT2 (JASN 2023;34(2)322); if UOsm >2x
**UOsm cutoff  w/ GFR in severe Cirrhosis: only if Na <120; fluid restrict, SOsm or UNa+UK >SNa → consider NaCl tabs +
AKI/CKD. If GFR <15, kidney cannot correct hypoK, consider vaptans/3% NaCl Lasix (10-20mg BID; cortico-medullary gradient)
dilute urine below UOsm ~200-250 only if severe or OLT or vaptans w/ renal input (NEJM 2006;355:2099)

Treatment: depends on acuity, severity, and etiology (JASN 2017;28:1340). Renal c/s if patient needs 3% NaCl and/or DDAVP clamp
• Rate/goal: Na 4-6 mEq/L per 24h, to short-term goal ≥125; typically Na 4-6 will alleviate sx
• Severe symptomatic (sz, AMS): 3% NaCl via 100mL bolus over 10 min; up to 3x until sx resolve or Na 5 (max 8-10 / 24h)
• Severe asymptomatic (Na <120): 3% NaCl at Na Correction Rate, usually 15-30mL/h, until Na ≥125; Na <120 a/w 6-10% in-hosp
mortality (Clin J Am Soc Nephrol 2018;13:641). Consider proactive DDAVP clamp in high ODS risk (see Risk Factors below)
• Mild/mod (Na 130-134/Na 120-129): etiology-specific treatment (e.g., fluid repletion, fluid restriction, diuresis, hold diuresis)
Overcorrection: Na  >8 in 24h or >18 in 48h. In high ODS risk patients, some guidelines say ∆Na >4-6meq/24h is overcorrection
o Osmotic demyelination syndrome (ODS): delayed onset (2-6d) dysarthria/dysphagia, paresis, behavior∆/AMS, locked-in synd.
 Dx with MRI ~4w after sx onset
 Risk Factors: starting Na ≤110 (ODS unlikely if starting Na >120, Hosp Pract 1995;37:128), malnutrition, EtOH use, cirrhosis, K
o Be aware that rapid correction more likely in hypovolemic hyponatremia and low solute hyponatremia (CJASN 2018;13:984). Monitor
for water diuresis post fluids (presents with rapid increase in UOP (>100ml/h)) and consider DDAVP clamp.
o If Na trajectory predicts overcorrection, consider DDAVP clamp (AM J Kidney Dis 2022;79(6):890)
 DDAVP 2-4mcg IV/SC q6-8h with Na measured q4-6h, until Na ≥125. If needed, add 3% NaCl at Na Correction Rate
o If already overcorrected, urgently Na to within previous goal (i.e., ∆Na < 8 mEq/L/24h or <4-6 mEq/L/24h in high ODS risk):
 D5W 6mL/kg IBW over 2h (Na by 2) and continue with q2h Na measurements until at goal level, PLUS
 DDAVP 2-4mcg IV/SC q6h for 24-48h even after relowering goal initially achieved
• Concurrent hypokalemia: K and Na freely exchanged, giving 1mEq of K = giving 1mEq of Na; can overcorrect w/ K supplementation
H Y P E R N A T R E M I A : free water loss in excess of NaCl loss (Crit Care 2013;17:206, NEJM 2015;372:55)
Etiologies: access to free water or thirst, DI
• Renal losses: UOsm <800; ADH release or kidney response: post-ATN, osmotic, DI, loop diuretic, hyperCa, elderly
• Extrarenal losses: UOsm >800; GI loss from NGT, vomiting, diarrhea, insensible losses, hypodipsia
Treatment: BMP q12-24h, strict I/O. Aim to SNa by 12 mEq/L per 24h (accidental overcorrection unlikely to be dangerous, complications
of more rapid correction (e.g. cerebral edema) are rare in adults, CJASN 2019;14:656)
1. Calculate current free water deficit. Shortcut FWD (L) = (Current Na – Goal Na)/3. Target Na should be 24h goal
2. Account for ongoing losses:
• Insensible losses: 700-900 mL/d typically but  if burns, fever, diarrhea (cannot measure, so  replenishment if inadequate)
• Urine: 24h UOP x (1- (UNa+UK)/SNa)); alternative = (0 x 1st L) + (0.5 x 2nd & 3rd L) + (1 x urine beyond 3L)
3. FW to give today = current FWD + ongoing losses. Give via PO, TF (FWB), or IV (D5W). If DI see Pituitary Disorders for DDAVP

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Nephrology Potassium Disorders

N O R M A L P O T A S S I U M H A N D L I N G / H O M E O S T A S I S (NEJM 2015;373:60)
• Ingested K+ absorbed in intestines  taken up and sequestered by liver/muscle cells via insulin & β2 receptors  Na-K ATPase
• 98% of K+ is intracellular; remaining extracellular levels trigger aldosterone secretion  principal cell K+ secretion excretion in urine
• Excretion also driven by Na+ delivery to distal nephron (macula densa). Na+ delivery  K+ excretion; Na+ delivery  K+ retention
HYPERKALEMIA
• S/S: Muscle cramps, weakness (ascending), paralysis, conduction delay (e.g. CHB, BBB, sinus arrest), arrhythmia (VT/VF, asystole,
idioventricular rhythms) (CCM 2008;36:3246)
• Dx: confirm K+ not d/t hemolyzed sample, plt>500K, WBC>120,
or infusion of K+-containing IVF; consider blood gas K+
• ECG: peaked T waves  QT PR interval ± AVB, flat p 
wide QRS ± BBB  sine wave pattern  PEA/asystole/VF
o ECG does not correlate w/[K+](Clin J Am Soc Neph 2008;3:324)
• Etiologies: Acidosis, Aldosterone; B-blocker, Blood; Cell lysis/turnover; Drugs, DM, Decreased GFR
o Redistribution: cell lysis (hemolysis, rhabdo, TLS), acidosis, insulin, hyperosm, meds (digoxin, β-blockers, minoxidil), hyperK
periodic paralysis, post-hypothermia
 Usually transient unless impaired renal K+ excretion
o  Renal K excretion: required for persistent hyperK+
  Aldo production/action: ACEi/ARBs, NSAIDs, K+-sparing diuretics, calcineurin inhib, pentamidine, TMP, type IV RTA
 Impaired Na delivery to distal nephron: hypovolemia, CHF, cirrhosis
 AKI/CKD (esp. if oliguric): usually GFR<15
 Other: ureterojejunostomy – urine K+ reabsorbed
• Management: acute changes are most dangerous  STAT ECG. Treat if ECG changes, K+>6, rapid rise, or sx
o Elimination is key, other measures are temporizing. Address reversible factors (optimize volume status, low K+ diet, meds). Of
note, hyperK-related sine waves can be misinterpreted as VT. Do NOT use amiodarone if suspected hyperkalemia (deadly)
HYPERKALEMIA TREATMENT
Strategy Treatment Onset Duration Notes
Calcium: calcium gluconate or CaCl2 (central line) 1-2g 1st line if any ECG Δs. Stabilizes
Stabilize 1-3m 30-60m
IV, can repeat q5 min PRN cardiac membrane. Avoid if on dig
Drives K+ into cells. Consider
Bicarb (sodium bicarbonate 1-2 amps IV vs gtt) 5-10m 1-2h
especially if  pH
Redistribute Insulin (5U IV) + D50 25g (if BS<250) 10-30m 4-6h
Drives K+ into cells.
Albuterol (10-20mg neb)
15-30m 15-90m K+ 0.5-1.5mEq/L
(Avoid w/ active ACS or significant tachyarrhythmias)
Furosemide ≥40mg IV; can approx. as 40xCr if K>6 Urinary K+ excretion
30m Variable
(Can give with NS to provide volume to diurese) If  volume can + thiazide
Eliminate Lokelma (10g TID) > Patiromer 8.4 g daily prn
1h; 7h 24h Swaps K+ for Ca++ or Na+ in gut
(avoid GI binders if SBO/constipation/ileus)
HD lowers K immediately N/A 3h Removes K+, may rebound d/t shifts
Note: Kayexalate use has  in favor of Lokelma given issues w/ efficacy and risk for GI complications (JAMA Intern Med 2019; 179:1023)
HYPOKALEMIA
 Signs and symptoms: usually with K+<3  cramps, ileus,
weakness (ascending, can involve respiratory muscles), rhabdo,
paralysis, worsened HE in cirrhosis (Nat Rev Neph 2010;7:75)
• ECG: flat T waves, ST dep, U waves, QT, atrial or ventricular
ectopy  VT, VF (esp if K+<2.5, susceptible pts, or on digoxin)
• Etiologies:
o Lab artifact (pseudo-hypokalemia): WBC >100 absorb K+ if sample sits out (check K+ on blood gas)
o Inadequate intake: unlikely to be 1° cause, usually combined with another etiology
o Redistribution: pH, insulin, refeeding syndrome, β-adrenergic activity (e.g. albuterol, epi), blood cell prod (e.g. s/p G-
CSF), hypothermia, toxins (cesium, barium, chloroquine), antipsychotics, hypokalemic or thyrotoxic periodic paralysis
o Extrarenal losses: diarrhea (esp. if chronic, VIPoma, villous adenoma, laxatives), vomiting/NGT
o Renal losses (w/o HTN): urine flow (1° polydipsia, excess IVF), Mg, meds (ampho B, ifosphamide, cisplatin, gent)
 Acidemia: DKA, RTA (proximal [Type II] and some distal [Type I])
 Alkalemia: diuretics, UGI losses (2° hyperaldo), Bartter’s (~loop diuretic), Gitelman’s (~thiazide)
 Other: urine excretion of anions (β-OH-butyrate in DKA, bicarb [e.g. UGI losses], toluene + PCN metabolites)
o Renal losses (with HTN):
 1° hyperaldo: aldo, renin (e.g. adrenal adenoma); 2°: aldo, renin (e.g. renal artery stenosis, renin-secreting tumor)
 Other: glucocorticoid or EnaC activity (e.g. Cushing’s, Liddle’s syndrome, black licorice)
• Management: 10mEq raises K+ by 0.1mmol/L; caution if Cr or if due to transcellular shifts (e.g. periodic paralysis)
o Oral KCl (ER = pill, IR = powder) preferred for tx as safer, quick acting, and many pts are Cl- depleted
o IV formulation KCl if unable to take PO  max 10mEq/h (floor), 20mEq/h (ICU)
o Always replete Mg, otherwise K+ repletion ineffective due to K+ wasting via ROMK (JASN 2007;18:2649)
o Avoid dextrose-containing solutions  can acutely worsen hypokalemia (dextrose insulin secretion  K+ shifts into cell)
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Nephrology Magnesium & Phosphorus Disorders

H Y P O M A G N E S E M I A (Med Sci (Basel) 2019;7:56)
• S/Sx: lyte disturbances (K, Ca), hypoparathyroidism, weakness, delirium, coma, neuromuscular hyperexcitability (e.g.
hyperreflexia, tetany, seizures),QRS, peaked T waves, later PR, QTc, U waves, VT/TdP, accentuation of digoxin
toxicity
• Etiologies:
o GI: intake, loss (diarrhea, pancreatitis, malabsorption, small bowel resection, PPIs), cellular shift (refeeding
syndrome)
o Renal: Meds (thiazide, loop diuretics, amphoB, aminoglycosides, foscarnet, tacro/cyclosporine, cisplatin, digoxin,
pentamidine), Gitelman syndrome, EtOH
 Use FEMg to distinguish renal vs GI loss (>3% suggests renal wasting)
• Treatment: oral (slow) vs. IV (fast, typically used inpatient), slow repletion better for sustained correction
o IV: MgSO4 1-2g over 2-15min x2 if unstable. If stable, 1-2g over/30min; favor IV if sx, reduce dose if CrCl<30
o PO: MgCl2 4-8 tabs/day, causes less diarrhea than Mg oxide 800-1600mg/day, always use in divided doses
o If hypoMg due to thiazide or loop diuretic, can add K-sparing diuretic to decrease Mg excretion

HYPERMAGNESEMIA
• S/Sx (typically only if Mg > 4): nausea, flushing, HA, neuromuscular depression (hyporeflexia [first sign], lethargy,
weakness, resp failure), cardiovascular (HoTN, bradycardia, conduction defects [PR, QRS, QTc, CHB, arrest]),
hypocalcemia (hyperMg can suppress PTH)
• Etiologies: Mg intake > renal clearance. Rarely pathologic w/o renal insufficiency
o Med overdose (Epsom salts, laxatives, Maalox, Mg enemas)  avoid these agents in ESRD, pre-
eclampsia/eclampsia treatment
o Gastritis/PUD/colitis (increased Mg absorption in these states)
o Misc - DKA, hypercatabolic states (TLS), lithium, adrenal insufficiency, milk-alkali syndrome
• Treatment (symptomatic only): Ca gluconate 1g IV over 10 min vs gtt to counteract resp depression/cardiac toxicity;
IV fluids + loop diuretics to enhance renal excretion. If ESRD, HD for removal

HYPOPHOSPHATEMIA
• S/Sx: (typically if phos <1.0 mg/dL, esp. if acute): intracellular ATP global cellular dysfunctionAMS/encephalopathy,
paresthesias, seizures, CHF, resp depression, proximal myopathy, rhabdo, dysphagia/ileus, hemolysis, mineral ∆ (bone
pain, hypercalciuria, rickets/osteomalacia) (JASN 2007;18:1999)
• Etiologies:
o Redistribution (into cells): insulin (DKA, HHNK, refeeding), acute resp alkalosis (pH  glycolysis), hungry
bone syndrome (deposition of Ca and phos in bone immediately following parathyroidectomy)
o GI absorption: poor PO, chronic diarrhea, vit D, antacids or phos binders (e.g. aluminum, Mg, sevelamer)
o Renal excretion: PTH (1° or 2° hyperPTH), Fanconi syndrome (multiple myeloma, tenofovir), FGF-23
(genetic/paraneoplastic), meds (acetazolamide, metolazone, IV iron) (QJM 2010;103:449), osmotic diuresis
(glycosuria), CVVH (esp at high bicarb dose)
o Use FEPO4 to distinguish GI/redistribution vs renal (>5% suggests renal wasting)
• Treatment:
o Severe (<1 mg/dL or 1-2 mg/dL and at high risk of becoming severe e.g. refeeding) or symptomatic
 IV Na or K phos 30mmol q6h with frequent levels (can give 15, 30, or 45mmol doses at MGH). Change to PO
once >1.5mg/dL. Give ½ dose in CKD/ESRD.
 Aggressive IV tx can cause Ca precipitation, hypotension (often due to hypocalcemia), AKI, arrhythmia
o Asymptomatic (<2 mg/dL and not at high risk): Na or K phos 1mmol/kg/d PO in 3-4 divided doses (max 80mmol/d)
 NeutraPhos: 1 packet = 250mg phos (8mmol); 7.1mEq K, 6.9mEq Na; preferred if need K or want lower Na
 K-Phos Neutral: 1 tab = 250mg phos (8mmol); 1.1mEq K, 13 mEq Na
 If poorly tolerated (can cause diarrhea), can give scheduled skim milk (8oz = 8mmol phos)

A C U T E H Y P E R P H O S P H A T E M I A (for chronic hyperphosphatemia, see CKD)

• S/Sx: results from Ca precipitation  hypocalcemia (muscle cramps, tetany, tingling, perioral numbness)
• Etiologies:
o Acute phos load (TLS, rhabdo, exogenous/phosphate-containing laxatives)
o Acute extracellular shift (DKA, lactic acidosis, severe hyperglycemia)
o Acute kidney injury or CKD due to decreased clearance (including acute phosphate nephropathy)
o Increased tubular reabsorption (vit D toxicity)
o Pseudohyperphosphatemia (hyperglobulinemia, hyperlipidemia, hyperbilirubinemia, hemolysis)
• Treatment: normal saline (though can worsen hypocalcemia), HD. Consider low phos diet, phos binders (sevelamer),
renal consult if refractory/profound
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Nephrology IV Fluids & Electrolyte Repletion

I V F L U I D S (NEJM 2013;369:1243)
• Types: crystalloid (e.g. NS or LR), free water (e.g. D5W), and colloid (e.g. albumin, blood products)
o Fluids can be isotonic (NS more isotonic than LR), hypotonic (D5W, 1/2 NS, 1/4 NS), or hypertonic (3% saline)
• Bolus fluids = volume expansion in distributive/hypovolemic shock, GI losses, burns
o Rate: 1L over 30min-2h. If concerned about volume overload, start w/ smaller volume (250-500cc).
o LR has minor quantities of K & lactate, K & lactate are NOT contraindications to LR (JEM 2018;55:313).
o NS in large volumes can cause hyperchloremic non-AG metabolic acidosis (NAGMA) and need for RRT (NEJM
2018;378:829; NEJM 2018;378:718) however no Δ mortality when compared to LR (JAMA 2021;326:818). NS likely > LR in
ICP (LR is slightly hypotonic and may cerebral edema).
o Colloid is NOT superior to crystalloid for volume resuscitation in shock (JAMA 2013;310:1809)
• Maintenance fluids = goal to replace daily losses (~1.6L/d in adults w/ normal renal function) while preserving electrolyte
balance +/- supplying a sugar source. Always order with time limit.
o Rate 60 – 100 mL/h (guided by comorbidities, insensible losses (intubated/burns/fever), oliguria, or ADH excess).
o D5NS or LR are typical maintenance fluids (NEJM 2015;373:1350). Consider NS in oliguric AKI w/ K (distal Na
delivery and K excretion) (CJASN 2022;17:588). Consider isotonic bicarb in high output GI fistulas/ostomies.
Fluid pH Osm [Na+] [Cl-] [K+] [Ca2+] Dextrose Other/Notes
275-295 135-145 94-111 3.5-5.0 2.2-2.6 60-100
Human plasma 7.35-7.45 1-2 mEq/L lactate
mOsm/L mEq/L mEq/L mEq/L mg/dL mg/dL
Normal Saline (NS) 4.5-7 308 154 154
Lactated Ringers 6-7.5 281 130 109 4 1.35 29 mEq/L lactate
D5-LR 4-6.5 525 130 109 4 1.35 5 g/dL 29 mEq/L lactate
D5-NS 3.2-6.5 560 154 154 5 g/dL
1/2 NS 5 154 77 77
3% NS 5 1026 513 513 See Hyponatremia
D5-1/2 NS 3.5-6.5 406 77 77 5 g/dL
D5-1/2 NS w/ 20-40KCL 3.5-6.5 426-446 77 97-117 20-40 5 g/dL
=3 amps 50mEq
Isotonic NaHCO3 ~8 552 150 5 g/dL
NaHCO3 in 1L D5W
D5W 3.5-6.5 252 5 g/dL use to correct ↑Na
D10W 3.2-6.5 505 10 g/dL use w/ insulin gtt
D20W 3.2-6.5 1010 20 g/dL use w/ insulin gtt
Albumin: MGH Albumin Policy put in place to prevent non-evidence-based overuse (ASA Choosing Wisely)
Albumin 25% = 12.5g albumin in 50mL solution; Albumin 5% = 12.5g albumin in 250mL solution
Indications: use to replace serum oncotic pressure, not typically for volume resuscitation
• SBP: improves renal outcomes. Dosing: 1st dose albumin 25% at 1.5g/kg w/in 6h (max 100g), 2nd dose 1g/kg on Day 3
• Large volume paracentesis in cirrhosis: only if >5L removed. Dosing: Albumin 25% at 6-8g/L ascites removed
• Augmenting diuresis in ARDS: already on high dose loop diuretic AND albumin <2.5 or Total Prot <6
Dosing: Albumin 25% at 25g q8h for 3 doses (requires attending approval; stop once alb >2.5. Max 3 days)
• Hepatorenal syndrome: see Hepatorenal Syndrome
• Other: ECMO chatter, mechanical circulatory support, burns, nephrotic syndrome, acute hemorrhagic shock, intra-dialysis
• NOT helpful in decompensated cirrhosis unless for the above indications (NEJM 2021;384:808)
ELECTROLYTE REPLETION
Potassium Magnesium Phosphorus Calcium
- CAD/arrhythmia: ≥4 - Replete if phos <2 - Replete if sx, long QTc,
- Everyone else: ≥3.5 - CAD/arrhythmia: ≥2 PO preferred Ca <7.5, iCal
Goal and
- Do not replete if on HD - Everyone else ≥1.7 IV if <1 or <1.5 + symptoms <1.15mmol/L
Route
unless <3.0 IV > PO Symptoms: weakness, MKS pain, PO > IV unless iCal
PO > IV SOB/resp failure, CHF, Δ neuro <1.0
- KCl IR (powder): q4-6h - Phos-Nak: 1 packet QID
- KCl ER (pills): giant pills - Mg oxide 400mg (240mg (7 mEq K, 7 mEq Na) - Ca carbonate 1250mg
PO repletion
- If K <3.5, ≥20 mEq KCl IR elemental Mg) TID x1d - K-Phos-Neutral: 1 packet QID PO BID
- see Lexicomp for dosing (1 mEq K, 13 mEq Na)
- Peripheral: 10mEq/h Give 15-45mmol Phos over 6 hr - Ca gluconate 1-2g IV;
IV repletion - Central: 20mEq/h w/ - Mg sulfate 2g IV - K-Phos (1.5mEq K/mmol Phos) - CaCl2 used in codes,
telemetry monitoring - Na-Phos (1.3mEq Na/mmol Phos) 0.5-1g q2-5min
- 10mEq K serum K by 0.1
- Correct for low Alb &
(in normal kidney function) - IV Phosphate can precipitate Ca
- 2g serum Mg by 0.5 hyperphos first
Comments - re-check K every 40mEq  causing hypocalcemia
- Mg can cause K/Ca - 1g Ca gluconate
unless on stable daily dose - Reduce/halve dose in CKD
serum Ca by 0.5
- Correct hypoMg
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Nephrology Urinalysis & Nephrolithiasis

URINALYSIS
URINE DIPSTICK – urine should be analyzed within 2-4h
Can help approximate urine osm: decimal of SG x 30 (e.g. SG 1.020  20 x 30  ~ 600mosms)
Specific
SG <1.010: post-ATN (concentrating defect), diuretics, DI, polydipsia, hypovolemic hypoNa after resuscitation
Gravity
SG 1.010 – 1.025: normal; SG >1.025: prerenal, contrast (esp >1.030), EABV, glycosuria (DM), proteinuria, SIADH
Normal 4.5 - 8, but strongly depends on serum pH and dietary intake
pH If normal urine pH + metabolic acidosis, suspect type I RTA (kidney not secreting H+ ions)
If pH ≥7, suspect urease-producing organisms (Proteus, PsA), strict vegetarians (low protein diet), type I RTA
LE Released from lysed PMNs; FP: pH or SG (lyses WBCs); FN: proteinuria, glycosuria. For UTI, Sn 80%, Sp low
Nitrite Indicates nitrate-reducing GNR (E. coli, Klebsiella, Proteus, PsA – NOT Enterococcus). For UTI, Sn 60%, Sp>90%
WBC UTI; if sterile pyuria, consider AIN, GN, chlamydia, ureaplasma, urethritis, TB, foreign body, exercise, steroids
Detects heme (glomerular, renal, or urologic); FP: hemoglobinuria (hemolysis), myoglobinuria (rhabdo), semen,
Blood
drugs (rifampin, chloroquine, iodine), peroxidase producing bacteria
Only detects albumin, not LMW proteins or light chains. + Protein when excretion >300mg/d.
Protein
Falsely elevated by high SG, heavy hematuria (heme protein), and iodinated contrast (w/in 24h)
Ketones Detects only acetoacetate, NOT β-hydroxybutyrate; yield decreases as collected urine sits
Reflects glomerular overflow (serum glucose >180mg/dL or SGLT-inhibitor/mutation) OR
Glucose
PCT failure (glycosuria w/ normal serum glucose  consider Fanconi’s syndrome 2/2 MM, heavy metal, drugs, etc.)

URINE SEDIMENT (MICROSCOPY) Findings Description

• Urine microscopy room: to the left of Harris room, outside White 10 Glomerular (dysmorphic RBCs “mickey
• Nephrology fellow/attending (day) or Security (night) can let you in mouse ears”) vs non-glomerular (normal).
RBCs
1. Obtain 10cc of fresh urine If present, can require outpt repeat with
2. Centrifuge using a balance @ 3000 RPM x3-5min timing based on #RBCs and risk factors
3. Invert/drain supernatant and resuspend sediment in the few UTI/cystitis (>10/microL expected for true
drops of urine that remain in the tube. Place one drop of sample WBCs infxn), pyelonephritis, AIN, atheroembolic,
on slide and place coverslip. glomerular injury, renal/bladder TB, stones
4. Bright Field Microscopy: keep light source subdued, lower Tubular (ATN), transitional (proximal
condenser to maximize contrast, start at low power (10x) to Epithelial
urethra to renal pelvis), squamous
obtain a general impression. Pay attention to coverslip edge Cells
(contamination by genital secretions)
where casts tend to migrate. Viewed best w phase contrast: Hyaline,
5. Phase contrast microscopy: maximizes contrast and definition, Casts RBC, WBC, Muddy brown, Granular,
allows better visualization of casts and cells. Raise condenser up Waxy, Fatty
high and turn light source to maximum brightness. Objective and Viewed best w phase contrast: Acyclovir
condenser annulus should always match. Crystals (“needles”), Tenofovir, Struvite
(NH4⸱Mg⸱PO4), ethylene glycol (oxalate)
CONDITION UA CELLS CASTS/CRYSTALS COMMENTS
Pre-renal azotemia SG >1.010 Hyaline, granular FENa (if oliguric), FEUrea
Nephrotic syndrome 3+ protein Oval fat bodies, hyaline
Glomerulonephritis + heme, +protein Dysmorphic RBCs RBC casts, WBC, granular
SG ~ 1.010 Hallmarks: renal tubular epithelial cells (RTECs) and muddy casts (CJASN 2008;3:1615)
ATN
(“isosthenuria”) PPV for ATN ~100% if pre-test prob and any RTECs and/or muddy casts present.
Rhabdomyolysis, 3+ heme w/o RBCs Acellular hyaline casts with
NO cells FENa, red/brown urine
hemolysis on sediment red or brown pigmentation
AIN Sterile pyuria WBCs WBC casts, granular Urine eos NOT sens or spec
Renal infarct Sterile pyuria + RBCs, WBCs urine LDH (serum LDH)
Cholesterol emboli Sterile pyuria Cholesterol
Myeloma kidney Bland Bland Proteinuria NOT detected by UA
CKD Waxy ± impaired ability to concentrate
NEPHROLITHIASIS
Composition and prevalence: CaOxylate > CaPhosphate > Urate = Struvite > Cysteine
Risk factors: male, obesity, DM, white, southeastern US, oral antibiotics, CKD, ESRD, family history (2% attributed to inherited disease)
Workup: CT (I-) > US (urological procedures require CT for planning). Can strain urine to type stone. Can also get 24h urine (“Litholink”) at
home both before and after interventions (usually dietary) are made
Precipitating factors: low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, hypomagnesuria, hypercystinuria,
urea splitting bacteria, high sodium intake, acidic urine (urate, cysteine), or basic urine (calcium phosphate, struvite), drug-induced
(guaifenesin, triamterene, sulfa drugs, protease inhibitors), toxic ingestion (ethylene glycol → Ca oxalate stones)
Acute management: IVF, pain management (ketorolac preferred to opioids) alpha blockers (>5 mm); urologic intervention if >10mm,
concern for infected stone, AKI, unremitting pain/n/v, or anuria. See: Ureteral obstruction. See AAFP algorithm (Am Fam Phy 2019;99:490)
Chronic management: fluid intake >2.5L/d, low Na diet, high K diet, low oxalate diet (no nuts, chocolate, green leafy veggies, etc.),
increase Ca intake, avoid excess vitamin D, thiazide diuretics if calcium stones, allopurinol if hyperuricosuria
Citrate supplementation: used for inhibition of Ca and uric acid stone formation. Leads to metabolic alkalosis. new stones, stone size

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Infectious Disease Empiric Antibiotics & Antibiogram

P R I N C I P L E S O F A N T I B I O T I C S E L E C T I O N (IDSA Guidelines, Sanford Guide, Johns Hopkins Abx Guide)
Consider the substrate:
- Is the patient immunocompromised? Think about age, DM, medications (≥ 20 mg prednisone QD x 2 weeks), HIV,
neutropenia, ESLD, ESRD.
- Is the patient at risk for any particular kind of infection? Think about prostheses, lines, altered anatomy, behaviors, and recent
hospitalizations.
Consider the tempo/severity:
- Is the patient unstable? If so, start broad spectrum antibiotics quickly; time to antibiotics correlates with mortality in septic shock.
Consider the syndrome:
- What evidence is there of infection? e.g., fever, localizing symptoms, leukocytosis, hypotension, inflammatory markers
- What is the likely source? e.g., PNA, UTI, SSTI, bone & joint infection, CLABSI, GI
- If a source is evident, what are the most common pathogens?
- Might there be metastatic foci of infection? e.g., blood, CSF, valves, bones, joints
Other considerations:
- If safe, cultures before antibiotics to improve diagnostic yield.
- Review the patient’s prior microbiology to assess for history of resistant bugs
- Broader ≠ better. We routinely overcover for MRSA, Pseudomonas, and anaerobes.
- Longer ≠ better. Emerging studies show shorter duration is noninferior in a number of infections.
- Fever ≠ infection. Don’t forget to consider inflammation, thrombus, medications, etc.
- Narrow and convert to PO when able (if indicated). Use the MGH antibiogram and, eventually, the susceptibility report.
- Inadequate source control is a common cause of treatment failure. Remove the line, drain the abscess, etc.
Antibiotic pharmacokinetic properties:
- High CNS penetration (not exhaustive): PCN, ampicillin, nafcillin, CTX, imipenem, mero, metronidazole, doxy (Lyme only),
linezolid. Vanc is moderate but improves with severe meningeal inflammation. MGH Antibiotic penetration tip-sheet
- High oral bioavailability (i.e., PO=IV) (not exhaustive): metronidazole, linezolid, doxy, FQs, azithro, clindamycin
- High urinary accumulation (not exhaustive): PCN, amoxicillin, cefazolin, cipro, aminoglycosides, vancomycin
Additional resources:
- For up to date MGH Antibiogram & Guidelines for Empiric Therapy for Inpatients: click (VPN or hospital WiFi) & scroll down
- Surviving Sepsis Campaign – 2021 Adult Guidelines

General spectrum of coverage for common IV β-lactams

Gram positives Gram negatives Anaerobes Pseudomonas
penicillin / cefazolin
ampicillin
ceftriaxone / cefotaxime
cefepime
ampicillin-sulbactam
piperacillin-tazobactam / meropenem

Commonly encountered Bugs & Drugs

Microbe Antibiotics Notes
Staphylococcus aureus MSSA: IV nafcillin, cefazolin, oxacillin -Cefadroxil is BID, cephalexin is QID
PO cephalexin, cefadroxil -β-lactam >>>> vancomycin
MRSA: IV vancomycin, daptomycin, ceftaroline -Dapto is inactivated in lung by surfactant
PO doxy, TMP-SMX, LZD, clinda -LZD highly bioavailable if PO and well
Long-acting dalbavancin, oritavancin tolerated for short course (<2wk)
Group A streptococci -penicillins -Add clinda if concern for TSS
Enterococci -ampicillin, vancomycin, daptomycin, linezolid -MGH antibiogram shows good E. faecalis
-fosfomycin, nitrofurantoin (UTI only) susceptibility to ampicillin
-If E faecium, more likely to harbor resistance
Pseudomonas aeruginosa -IV cefepime, ceftazidime, piperacillin-tazobactam, -Ertapenem does not cover PsA
imipenem, meropenem, aminoglycosides -MGH defines resistant PsA as R to ceftaz
-PO ciprofloxacin, levofloxacin and may need ID guidance for abx choice
MDR GNRs (AmpC inducers -IV cefepime, carbapenems, aminoglycosides -AmpC: Enterobacter, Serratia, Providencia,
and ESBL producers) -PO fluoroquinolone, TMP-SMX Proteus (indole+), Morganella, Citrobacter
-Cefepime success highly-dependent on MIC
Cell wall-deficient (“atypicals”) -doxycycline, azithromycin, levofloxacin -Mycoplasma, Chlamydia, Legionella
Anaerobes -IV pip-tazo, amp-sulbactam, carbapenems -Think twice if anerobic coverage needed
-PO metronidazole, clinda, amox-clav -Vanc+cefe does NOT cover anaerobes

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Suspected Process Microbiology Empiric Antimicrobial Therapy Notes
-Generally: S. pneumoniae, HSV, -vancomycin+ CTX 2g Q12 -If S. pneumoniae, add dexamethasone
other viral > N. meningitidis -Listeria: ampicillin (reduces neurologic sequelae)
Meningitis
-If >50 y, immunocompromised, -HSV: acyclovir -Remove hardware if possible (e.g., place
(CID 2004;39:1267; CID
EtOH: Listeria monocytogenes -Healthcare-assoc, hardware, VP shunt, external ventricular catheter in place of
2017;64:e34)
-If hardware or nosocomial: Staph, PWID: vancomycin + cefepime or meropenem shunt)
PsA; C. acnes if VP shunt -See Abx penetration tip sheet
-viral > bacterial -Healthy outpt: amox > azithromycin or doxy -Recommend flu and viral testing
-Legionella, Mycoplasma, -Outpt with comorbidities: -Consider local azithromycin resistance
Chlamydia (“atypical”) Amox-clav+azithro or doxy, -Can substitute doxycycline for azithro
Community Acquired
-S. pneumoniae (classic lobar cefpodoxime+azithro or doxy, or levoflox alone -Levofloxacin preferred for structural lung
Pneumonia (CAP)
PNA), H. influenzae, Moraxella -Most inpatients: CTX+azithro, or levo alone disease outpatient
(AJRCCM 2019;200:e45)
catarrhalis -Prior MRSA/PsA OR IV abx in past 90 d: -If postviral, consider S aureus
-S aureus (usually very sick) vancomycin+cefepime+azithromycin -If empyema, needs drainage
-Klebsiella (EtOH)
Hospital-Acquired and -CAP organisms, S aureus, GNRs -vancomycin+cefepime -Consider local MDRO prevalence
Ventilator-Associated including PsA, Stenotrophomonas
Pneumonia (HAP/VAP)
(CID 2016;63:e61)
-Native: S aureus, strep, -Native: vancomycin+ceftriaxone -Early ID consult improves mortality and
enterococci, few GNRs, HACEK -Prosthetic: vancomycin+gentamicin+rifampin, can help guide empiric therapy early
Endocarditis
-Prosthetic: S aureus, S. but ask ID based on patient characteristics!!
(Circ 2015;132:1435)
epidermidis most likely; others -MSSA: β-lactam >>> vancomycin
above rarely
-E. coli, Klebsiella, enterococci, -CTX+MNZ, cipro+MNZ -Source control: CCY, ERCP, or perc
Cholecystitis/ anaerobes -Nosocomial/severe: cefepime+MNZ, choly
Cholangitis -Often polymicrobial piperacillin-tazobactam, imipenem, -Consider vancomycin if c/f enterococci
(CID 2010;50:133) meropenem -Often polymicrobial → broad abx for 48 h
even if BCx growing only 1 organism
-Abscess: GNRs, anaerobes, -CTX+MNZ, ciprofloxacin+MNZ -Drain if abscess
enterococci, Candida, -Nosocomial/severe: cefepime+MNZ, -Surgical evaluation if peritonitis,
Other Intra-abdominal
polymicrobial piperacillin-tazobactam, imipenem, perforation, fistula, recurrent diverticulitis
(CID 2010;50:133)
-Diverticulitis: GNRs, anaerobes, meropenem
rarely enterococci, polymicrobial
Spontaneous Bacterial -Enteric GNR, streptococci, -ceftriaxone, cefotaxime -Ciprofloxacin reserved for patients w/ β-
Peritonitis (SBP) enterococci; rarely anaerobes lactam allergies and used for ppx
(Hep 2021;74:1014) -Initiate ppx after first episode of SBP
-Uncomplicated: E.coli, Klebsiella, -Uncomplicated: nitrofurantoin, TMP-SMX, -Do not treat asymptomatic bacteruria in
S. saprophyticus, Proteus fosfomycin nonpregnant immunocompetent patients
UTI (non-pregnant)
-Complicated (i.e. systemic infxn, -Complicated: CTX, ciprofloxacin/levofloxacin -Exchange Foley, consider repeat UA/UCx
(CID 2011;52:e103; CID
pyelo): above + enterococci, PsA, -CAUTI: vancomycin+ceftriaxone 48 h later if CAUTI
2010;50:625)
Serratia, Providentia -Cefepime if c/f PsA, carbapenem if c/f ESBL
-CAUTI: above + other GNRs
-Hematogenous source: S aureus -No abx if HDS, no signs c/f cord compression, -Dx: CRP, ESR, MRI, bone biopsy
Osteomyelitis -Direct inoculation/vascular: S and awaiting bone biopsy -Debride (ortho/vasc surg/plastics) w/ bone
(CID 2023;ciad527; CID aureus > strep, PsA, GNR, -Vanc+CTX; cefepime if DM/PAD ulcer or bx+cx
2015;61:e26) enterococci, Eikenella (human direct inoculation -Use amp-sulbactam if originated from bite
bite), Pasteurella (animal bite)
Septic Arthritis -staph, strep, N. gonorrhoeae, -vancomycin+ceftriaxone (consider cefepime if -Dx: fluid aspirate with >50k WBC
(Infect Dis Clin North Am PsA (PWID), Lyme PWID or other risk factor for PsA) -Consult ortho for joint washout asap
2017;31:203) -Definitive rx is a joint wash out -Blood+joint fluid cx prior to abx
-Impetigo: S aureus > strep -Purulent: vancomycin -If abscess, drain
-Cellulitis/Erysipelas: strep > staph -Non-purulent: cefazolin -If nec fasc (rapid spread, crepitus, pain
Skin/Soft Tissue (SSTI) -Nec fasc: strep, C. perfringens, -Bite: ampicillin-sulbactam out of proportion), URGENT SURGICAL
(CID 2014;59:e10) MRSA -Nec fasc: vanc+ [pip-tazo or mero] ±clinda EVAL
-DM/PAD ulcer: vanc + [CTX or cefe] -If nec fasc, clinda meant to inhibit
exotoxin production
Septic shock, no -GNRs, S aureus, streptococci, -vanc+cefe±MNZ, vanc+pip-tazo -Start antibiotics within 1 h of recognition
source PsA, anaerobes -Concern for MDRO: carbapenem -Amikacin generally the aminoglycoside of
(Intensive Care Med -Consider TSS -Critical illness: consider 1 dose choice for critical illness
2021;47:1181) aminoglycoside
-TSS: add clindamycin
-Source not identified ~70% of -cefepime -Start antibiotics within 1 h of fever
time -Suspect CLABSI, SSTI, PNA, mucositis: add -If afebrile x 72 h or ANC > 500, consider
Febrile Neutropenia
-When source is identified, 60% vancomycin de-escalation
(T≥100.4F & ANC<500)
GPCs (CoNS > S aureus, -HDUS, GPCs on BCx: add vancomycin -Oral ppx: consider levo or amox-clav +
(CID 2011;52:e56)
streptococci, enterococci), 40% -Persistent fevers > 4-7 d: consider micafungin cipro for prolonged neutropenia
GNRs (E. coli, Klebsiella > PsA)

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M G H ANTIMICROBIAL SUSCEPTIBILITY (JAN. – DEC. 2023) MGH Handbook

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Infectious Disease Multidrug Resistant Organisms

M D R G N R S (CID 2023;ciad:428)
AmpC β-Lactamase (cephalosporinase)
• Mechanism: Inactivate 3rd gen cephalosporins & pip-tazo. Can be
constitutive or inducible (turned on by accumulation of cell wall
fragments due to β-lactam inhibition of penicillin-binding proteins).
• Pathogens: Inducible AmpC producers include:
MISPACE: Morganella spp., Indole-positive Proteus spp. (non-
mirabilis), Serratia spp., Providencia spp., Acinetobacter spp.,
Citrobacter spp., Enterobacter spp.
HECKYes: Hafnia alvei, Enterobacter cloacae, Citrobacter freundii, Klebsiella aerogenes, Yersinia enterocolitica
o Organisms don’t equally produce AmpC; E. cloacae, K. aerogenes (formerly E. aerogenes), & C. freundii are highest
risk (CID 2021;74:2089).
• Treatment: Do not treat these organisms with 3rd gen ceph (e.g., CTX), even if the micro lab report says “susceptible.”
o If critically ill, treat with cefepime if MIC ≤ 2 μg/mL. Generally, cefepime noninferior to meropenem (CID 2013;57:781).
o If not critically ill, can de-escalate to alternatives (e.g., FQ, TMP-SMX, or nitrofurantoin [only cystitis]) if susceptible.
Extended-Spectrum Beta Lactamases (ESBL)
• Mechanism: Plasmid-mediated, inactivate most β-lactams (penicillins, cephalosporins, aztreonam).
• Pathogens: Klebsiella spp. (#1), E. coli (#2), Proteus mirabilis (#3), other GNR
• Risk Factors: Abx w/in past 6 mo, long hospitalization, nursing home, >65 yo, lines/catheter/tubes/ventilator, TPN, HD
• Laboratory detection: MGH infection control defines potential ESBL as a GNR resistant to ceftriaxone.
• Treatment: Avoid penicillins and cephalosporins (including piperacillin-tazobactam) even if “susceptible” (JAMA 2018;320:984)
o Uncomplicated cystitis = TMP-SMX or nitrofurantoin; alternatives: Fosfomycin (E.Coli), single-dose aminoglycoside.
Cipro/levoflox or carbapenem are last line. Complicated UTI: TMP-SMX or FQ; alternative: Carbapenems
o If non-UTI, empiric treatment with imipenem-cilastatin or meropenem. Avoid ertapenem in critical illness.
Carbapenem Resistant Enterobacteriaceae (CRE)
• Mechanisms: Inactivating carbapenemase, porin loss (limits penem entry), efflux pump extrusion, or combination of factors
• Risk Factors: Cephalosporin or carbapenem use in past 3mo (**penem exposure not required**), medical care in India/Pakistan
• Laboratory detection: Suspicious when MIC > 2 μg/mL for imipenem, meropenem, or ertapenem
• Treatment: Preferred option is usually ceftazidime-avibactam (+aztreonam if care in India/Pakistan); C/s ID
o Meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are also active
o Alternatives may include extended-infusion meropenem (if MIC ≤ 1 μg/mL), aminoglycoside, or tigecycline [not for
UTI/bacteremia].
o If uncomplicated UTI – FQ, TMP-SMX, or single-dose aminoglycoside if susceptible.
Difficult-to-Treat Resistance Pseudomonas aeruginosa (DTR-PsA)
• Definition: Non-susceptible to pip-tazo, ceftaz, cefepime, aztreonam, fluoroquinolone, meropenem, AND imipenem-cilastatin
• Treatment: Ceftolozane-tazobactam usually preferred but other options (e.g. ceftaz-avibactam, cefiderocol, etc.); C/s ID
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)
Community-associated MRSA: no healthcare exposure, SSTI in young & healthy patient
• Risk Factors: HIV, PWID, prior antibiotic use; outbreaks: incarceration, military, sports, sharing needles/razors
Healthcare-associated MRSA: occurs >48h following hospitalization or within 12mo of healthcare exposure
• Risk Factors: recent hospitalization/surgery, HD, LTC facility residence
• Nasal swab: NPV in CAP = 96.5% (CID 2018;18:1) if ⊝ consider d/c MRSA coverage. MGH use Antimicrobial De-escalation
Guidelines in HAP/VAP; emerging evidence that NPV for Staph infection at other sites is also high (CID 2020;71:1142).
Treatment
• Check the vanc MIC: Vanc susceptible if MIC ≤2 μg/mL (though tx failure and mortality when MIC = 2 μg/mL), Vanc-
intermediate (VISA) if 4 μg/mL ≤ MIC ≤ 8 μg/mL, Vanc-resistant (VRSA) if MIC ≥16 μg/mL
• Serious infections (i.e. bacteremia): vancomycin (consider AUC dosing, trough ~15-20) and ID consult (J infect. 2016;72:19). If
persistent bacteremia or MIC ≥ 2 μg/mL, consider switching to daptomycin (not in PNA or meningitis), adding ceftaroline
(Antimicrob Agents Chemother. 2018;62:01554), or both (Open Forum Infect Dis 2019;7:538).
• Mild infections (e.g., SSTI): TMP-SMX, doxycycline >> clindamycin (increased resistance at MGH); linezolid

VANCOMYCIN RESISTANT ENTEROCOCCI (VRE)

• E. faecium: often resistant & generally less virulent. E. faecalis: more virulent but highly AmpS at MGH.
• RFs: prior abx, Foley, indwelling lines; proximity to other VRE pts; long hospitalization/SNF; immunocompromised
• Clinical sites of infection: UTI (often an asymptomatic colonizer); bacteremia (2nd most common CLABSI); intra-abdominal and
pelvic infections; endocarditis (esp. if prosthetic valve); meningitis (immunocompromised or VP shunt)
• Treatment:
o Invasive infection (e.g., bacteremia, endocarditis): daptomycin (+ amp or CTX or ceftaroline), linezolid; ID c/s
o Uncomplicated UTI: fosfomycin x1 (consider repeat dose on days 4 and 7) or nitrofurantoin

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Infectious Disease Community Acquired Pneumonia

C O M M U N I T Y A C Q U I R E D P N E U M O N I A ( C A P ) (AJRCCM 2019;200:45)
● Definition: PNA acquired in the community, including patients from nursing homes, dialysis, or with outpatient clinic exposure
● Diagnosis: new infiltrate on chest imaging AND s/sx (e.g. fever, cough, leukocytosis, ∆ sputum, hypoxemia)
o Elderly at risk of blunted s/sx but also prevalence of atelectasis/aspiration
o Radiographic consolidation NOT specific for bacterial vs viral PNA
o If CXR ⊝ but high suspicion  tx and repeat CXR in 24h (PNA may “blossom”) vs. consider chest CT  if ⊝ consider other dx
● Triage: CURB-65 (Confusion, BUN>19, RR>29, BP<90/60, age>65)  outpatient if score 0-1, inpatient if 2, consider ICU if 3-5.
Pneumonia Severity Index (PSI) more comprehensive  outpatient if <70, inpatient if >90
● Severe CAP (ATS/IDSA Criteria): 1 Major: pressors or mech vent, OR 3 Minor: RR>30, P:F<250, multilobar infiltrates, confusion,
BUN>19, WBC<4K (not due to chemo), plt<100K, T<36C, HoTN requiring aggressive fluid resuscitation
● Micro: S. aureus (common in severe CAP), S. pneumoniae, H. flu, GNRs, Legionella. Most common pathogens are viruses –
rhinovirus, influenza, others (NEJM 2015;358:415; CritCareMed 2022;50(7))
● Work-up (inpatient):
o Sputum cx and Gram stain (ET aspirate if intubated): Obtain if inpatient + severe CAP or resistance risk. Adequate sample if
>25 PMN and <10 SEC/lpf. NOTE: “abundant squamous cells” or more squamous cells than polys suggests the sample is saliva
o Blood cultures: controversial benefit, positive <10-20% of inpt PNA
▪ Obtain Scx and Bcx if: severe CAP, empiric treatment for MRSA/PsA, prev. MRSA/PsA, or hosp. w/ IV abx ≤90d
o Procalcitonin (PCT):  in acute resp. infxn from bacterial causes. No validated threshold to distinguish bacterial vs. viral infxn.
(ATS 2019;200:45). Can help in deciding to dc abx; dc if <0.25 or >80% drop from peak. (JAMA 2009;302:1059)
o Legionella urine Ag (Sn 70%, Sp 99%); detects only serogroup 1 (80-90% in US). Check if severe CAP or recent
exposure/travel. Clinical predictors include hypoNa, fever, diarrhea, and recent travel (CID 2019;68:2026)
o MRSA nasal swab: high NPV (~98%). ⊝ test  consider d/c MRSA coverage (CID 2018;67:1)
o Influenza: test seasonally. Tx: oseltamivir (see URI page for tx indications)
● IDSA/ATS CAP Empiric Treatment (NOTE: additional considerations for travelers, immunocompromised) (ATS 2019; 200:45)
Outpatient Preferred Alternative/Other info
No Comorbidities or Amox 1g TID OR doxy 100mg BID OR macrolide NOTE: U.S. has high rates of macrolide- and doxy-
MRSA/PsA RFs (azithro OR clarithro) (if local resistance <25%) resistant S. pneumo
[Amox-clav BID AND azithro*] OR Cefpodox or cefurox. can replace amox-clav; doxy can
Comorbidities°
levofloxacin 750mg QD monotherapy replace azithro
Inpatient Preferred Alternative/Other info
(β-lactam [CTX] AND macrolide [azithro]) OR Amp/sulb can replace CTX; doxy can replace azithro if
Non-Severe
levofloxacin monotherapy macrolide or fluoroquinolone not tolerated
β-lactam (CTX 1-2g QD) AND In ICU, azithro >> levofloxacin (anti-inflamm. effect);
Severe/ICU
(azithro OR levofloxacin) consider addt’l agents for drug-resistance (see below)
Obtain Cx and nasal MRSA swab to inform de-escalation.
MRSA/PsA RFs Vancomycin AND cefepime
Do not use daptomycin (poor lung penetration)
°Chronic heart, lung, liver, or renal disease; DM; AUD; malignancy; or asplenia.
● Risk factors for drug-resistant pathogens in CAP:
o General: hospitalization & IV abx in past 90d; prior respiratory isolation of MRSA, PsA or other resistant organisms
o PsA: GNR on gram stain, h/o PsA, bronchiectasis, COPD w/ freq exacerbations req abx/steroids. Tx: (for normal renal function)
cefepime 2g q8h, ceftazidime 2g q8h, pip-tazo 4.5g q6h, mero/imipenem; double coverage usually not necessary
o MRSA: GPC clusters on gram stain, recent flu-like illness, necrotizing/cavitation/empyema, ⊕ nasal swab, risk factors for
colonization (ESRD, PWID, prior abx [esp. fluoroquinolones]). Tx: vancomycin or linezolid
● Anaerobic coverage: only if suspicion for empyema or lung abscess, (see HAP/VAP & Aspiration Pneumonia)
● Steroids: Recent RCT showed benefit in severe CAP (NEJM 2023;388:1931). Meta-analysis showed steroids may lower risk of MV,
no sig. impact on mortality (Chest 2023;163:484). IDSA/ATS do not have no rec for steroids. AVOID steroids in INFLUENZA as might
 mortality (Cochrane Rev 2016)
● Duration: usually 5d; 7d in suspected or proven MRSA or PsA CAP, assuming clinical stability (afebrile x48h + ≤1 sign of CAP
instability: HR >100, RR >24, O2<90%, AMS, no PO intake). MRSA should be treated longer if not improving within 72h (e.g. 10-14d
in critically ill, 2-6w with ID consult if c/b bacteremia or necrotizing PNA)
o If have not achieved clinical stability, extend course & eval. for resist. pathogen, complication (empyema, abscess), alt. source
o Convert IV  PO when clinically improving; no need to observe x24h on PO
● Response to therapy: tachycardia resolves by 2-3d; fever resolves by 2-4d; hypoxemia resolves by 3-6d.
o CXR clears by 1mo in 50% (up to 12wks in elderly, lung disease); do not need repeat CXR if clinical improvement
o If no response to therapy after 72h: consider chest CT (± BAL) to evaluate for empyema, abscess, fungal infxn.
● Parapneumonic effusion: exudative, develops adjacent to a pneumonia, 20-57% of PNA hospitalizations (CID 2007;45:1480).
Appropriately sized effusions need diagnostic thora for evaluation esp if concern for infx + need for extension of abx course.
o Definitions: Uncomplicated (~pH >7.2/glucose >60, ⊝ GS/Cx)  complicated (requires drainage, pH <7.2/glucose , still
⊝GS/Cx)  empyema (requires drainage, frank pus, + GS/Cx).
o Management: Uncomp. effusions ok for abx alone if <1/2 hemithorax & free flowing; consider therap. thora if symptoms. Chest
tube after diag. thora if: empyema, loculation, >1/2 hemithorax, thickened parietal pleura, sepsis w/ suspected pleural source
(Chest 2000;118:1158; Ann Thor Surg 2018;105:1589)
o Duration of abx, utility of surgery, timing of repeat imaging: guided by severity and clinical/radiographic progression

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Infectious Disease HAP/VAP & Aspiration Pneumonia

H O S P I T A L - A C Q U I R E D A N D V E N T I L A T O R - A S S O C I A T E D P N E U M O N I A (IDSA/ATS: CID 2016;63:e61)
Definitions:
Hospital-acquired pneumonia (HAP) Pneumonia that develops ≥48h after admission
Ventilator-associated pneumonia (VAP)*** Pneumonia that develops ≥48h after endotracheal intubation
Dx criteria: new/progressive infiltrates on CXR + 2/3 of fever, leukocytosis, purulent tracheal secretions
***Ddx also includes non-infectious ventilator-associated events (VAEs) such as atelectasis, ARDS, pulmonary edema, and pulmonary
embolism (Ann Transl Med. 2018; 6: 425; Infect Control Hosp Epidemiol. 2017; 38:867)
Common microbiology: enteric GNRs (Klebsiella, E. coli), MRSA/MSSA, PsA, Acinetobacter
Workup: CXR, SpCx, BCx, MRSA swab; consider induced sputum, bronch with BAL
MDRO RFs: IV abx use w/in 90 days preceding onset (most important); high local prevalence (>10%) of MDR GNRs &
MRSA; structural lung disease (CF, bronchiectasis); prior hx of MDRO infection
o MDR VAP RFs: septic shock/ICU, ARDS, onset ≥5d in hospital, or RRT preceding onset
Empiric Tx of HAP/VAP w/ MDRO risk: 1 anti-PsA (β-lactam pref.) AND 1 anti-MRSA agent (typically vancomycin)
o Consider double PsA coverage if: septic shock, rapid progression of PNA requiring mech. ventilation, hx of MDR PsA
o Pulmonary toilet (oral hygiene including daily tooth brushing, oral and subglottic suctioning, mucolytics, etc.) (JAMA
2024; 184:131)
o For patients on vent ≥72 hrs, 3 days of inhaled amikacin may decrease rate of VAP (NEJM 2024; 2052-202)
Antipseudomonal β-lactams Antipseudomonal non-β-lactams Anti-MRSA agents*
- Cefepime 2g IV q8h - Levofloxacin 750mg IV qd (*PsA
- Ceftazidime 2g IV q8h susceptibility only 70% at MGH)
- Pip/Tazo 4.5g IV q6h - Ciprofloxacin 400mg IV q8h - Vancomycin IV
- Meropenem 1g IV q8h - Tobramycin 5-7mg/kg IV x1, then dose by - Linezolid 600mg q12h
- Aztreonam 2g IV q8h (only if severe PCN level
allergy: Ellucid) - Polymyxin B (call ID)
*Daptomycin cannot be used for MRSA coverage when lung suspected source
Always adjust dosing for renal function. When in doubt, call Pharmacy!
• Tailoring therapy:
o Improvement after 48h or pathogen ID’d: narrow abx and d/c MRSA+PsA coverage if possible. ⊝ MRSA swab w/
96% NPV for MRSA infection, most evidence comes from swab on admission and not further into course (CID
2018;18:67; CID 2020;71:1142). VAP: ⊝ tracheal aspirate NPV 94%, consider d/c abx after 72h (IJID 2010;14:18)
o No improvement after 48h: broaden to cover MDROs (if not already), consider other sites of infection/abscess, non-
infectious causes of clinical syndrome
o MGH Ellucid Policy: HAP/VAP De-escalation Algorithm
• Duration: 7d. Consider serial procalcitonin  d/c abx when <0.25ng/mL (ERJ 2009;34:1364; Cochrane Rev 2011;10)
A S P I R A T I O N P N E U M O N I A (NEJM 2019;380:651)
• Definition: pneumonia secondary to excessive secretions, particulate matter, or fluid into airways. Micro-aspirations are
common and the definition of aspiration pneumonia as a distinct clinical entity remains unclear. Aspiration
PNA/pneumonitis are often result of larger volume/frank aspiration events
• Predisposing factors: AMS/dementia, esophageal dysmotility, post-bronchial obstruction, post extubation, gum
disease/poor dentition, seizure, tube feeding
• Microbiology: most common organisms are GNRs and standard CAP/HAP organisms (AJRCCM 2003;167:1650). Role
of anaerobes is likely overstated (Chest 1999;115:178)
• Characteristics: indolent, putrid sputum, pulmonary necrosis w/ cavitation/abscess/empyema
• Workup: CXR, SpCx (anaerobic respiratory culture not performed at MGH due to low utility)
• Empiric treatment: same as CAP/HAP empiric treatment (AJRCCM 2019;200:e45; JHM 2020;15:754)
o Anaerobic coverage: only recommended in pts w/ suspected lung abscess or empyema. First line: ampicillin-
sulbactam if not severely ill, pip-tazo if severely ill, amox-clav if outpatient; alternative: (CTX+MNZ) OR clindamycin.
If failure to improve on normal therapy; consider imaging to assess for abscess/empyema; may need source control.
o Duration: 7d unless complicated by cavitation/abscess/empyema
• No clear clinical benefit for abx for ppx for aspiration unless pt symptomatic (CID 2018;67:513)
ASPIRATION PNEUMONITIS
• Definition: aspiration of chemical substances into the airways without bacterial infection
• Clinical manifestations: abrupt onset (2h), low-grade fever, WBC, hypoxemia, CXR consolidation (RML/RLL upright,
RUL supine)  often indistinguishable from pneumonia in the acute setting
• Treatment: no mortality benefit in initiating antibiotics in a patient with aspiration pneumonitis, however since it is clinically
difficult to distinguish from PNA in the acute setting generally initiate empiric abx and reassess q24h  d/c if culture data
remains negative AND if signs/sx/consolidation resolve rapidly
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Infectious Disease Viral Respiratory/Head & Neck Infections

V I R A L R E S P I R A T O R Y I N F E C T I O N S (for COVID-19 [VPN/MGH wifi]; for bacterial pharyngitis see HEENT Concerns)
● Epidemiology
o >200 viral pathogens may cause VRIs, most common include rhinovirus, influenza, coronavirus, parainfluenza
o LRTI (bronchitis, bronchiolitis, PNA): coronavirus, influenza, RSV, parainfluenza, adenovirus (Lancet 2011;377:1264)
o In immunocompromised hosts, consider reactivation of latent viruses (e.g. CMV) if not on antiviral ppx
● Presentation
o Transmission: hand contact, small droplets that become airborne, large droplet, peak viral shedding at 2-3d of illness
o Symptoms: nasal congestion, rhinorrhea, dry/sore throat, cough, fever, conjunctivitis, myalgias w/ sx peaking at 3-5d and
lasting 10-14d (if significant systemic illness consider influenza, COVID-19 >> measles, Hantavirus)
o Complications: bacterial PNA (occurs in 1/800 w/ initial improvement  worsening after ~7d, micro: S. pneumo, S.
aureus), asthma/COPD exacerbation, secondary bacterial sinusitis (occurs 2/100), otitis media, ARDS
● Diagnosis
o Clinical diagnosis that generally does not require microbiological testing except for influenza and COVID-19
o Resp. viral panel: at MGH NP swab PCR for COVID-19, Flu A/B, RSV; can help avoid unnecessary abx; collect within 5d
of sx onset. Consider extended resp viral panel for immunosupp or high clinical suspicion with negative limited viral panel
o Influenza testing: (IDSA: CID 2019;68:895)
▪ RT PCR most sensitive and specific; can differentiate A, B and subtypes
▪ Rapid Ag test 62% Sn, 98% Sp (<15min); during season ⊝ test does not exclude, not sufficient to stop tx
● General Viral URI Treatment
o Sx management with decongestants, nasal sprays, anti-inflammatory agents, humidified air. NO role for ppx abx
o COVID-19 specific treatments: remdesivir (NEJM 2020;383:1813), nirmatrelvir-ritonavir (NEJM 2022;386:1397), etc. in select
patients. If using nirmatrelvir-ritonavir, ensure to check drug-drug interactions before initiating therapy. See Handbook
(VPN or MGH wifi) for most up to date guidance.
● Influenza Treatment and Post-Exposure Prophylaxis
o Treatment: oseltamivir 75mg BID x5d (can extend in severely ill or immunocompromised)
▪ Indications: hospitalized pts and outpts w/ severe or progressive dz regardless of illness duration, risk (age >65,
long-term care facility resident, pregnant, <2 wks post-partum, immunosuppressed, cirrhosis, DM, CHF/CAD, CKD,
COPD, SCD, asthma, BMI >40, neuro dz) also regardless of illness duration
▪ Consider: outpts with sx <48h or those with high-risk household members
o Prophylaxis: oseltamivir 75mg qd x7d if ≤48h post-exposure (x14d ± additional 7d after last case if outbreak at long-term
care facility); switch ppx  treatment dosing if sx develop (IDSA: CID 2019;68:895)
HEAD A N D N E C K I N F E C T I O N S (Principles of Crit Care. Chow AW. 4th edition. McGraw-Hill, NY 2015)
• Epidemiology: often from odontogenic, otogenic, or sinogenic infection with contiguous spread
• Organisms: Streptococci, H flu, oral anaerobes. PsA in otogenic source. MRSA in sinogenic source and PWID
• Diagnostics: blood cultures, CT Neck, MRI (consider to evaluate for osteo), IR or ENT for tissue or abscess culture
• Empiric Treatment: varies based on likely source; odontogenic – amp-sulbactam or CTX+MNZ, otogenic - cefepime+MNZ,
sinogenic - vancomycin+CTX+MNZ. Involve ENT early for drainage and airway monitoring
o Submandibular space (Ludwig angina): sources- periodontal infection, peritonsillar abscess, parotitis; p/w mouth pain,
“double tongue,” drooling, dysphagia can rapidly progress to airway compromise; polymicrobial esp viridans strep
o Internal jugular septic thrombophlebitis (Lemierre syndrome): pharyngitis and septic emboli (esp lungs). Most
commonly Fusobacterium necrophorum or viridans strep. Treat with (pip-tazo OR CTX+MNZ) ± anticoagulation
o Deep neck space: involving retropharyngeal, “danger,” or paravertebral spaces. Presents with neck pain and systemic
toxicity. Can progress to carotid sheath abscess, mediastinitis, vertebral osteo, paravertebral abscess
ORBITAL AND P R E S E P T A L C E L L U L I T I S (Surv Opthalmol 2018;63:505)
Preseptal/Periorbital Orbital
Definition Infection of anterior eyelid (not orbit or ocular Infection of orbit contents (fat, ocular muscles) but not the
structures) globe
Pathogenesis Local trauma Rhinosinusitis, oral abscess, dacryocystitis, local trauma,
direct inoculation, ophthalmic surgery
Organism Staph aureus, Strep spp. Staph aureus, Strep spp; in immunosuppressed pt, consider
Mucor and Aspergillus
Symptoms Eyelid pain, edema, erythema ± chemosis & Preseptal sx + pain with eye movement, proptosis,
fever ophthalmoplegia w/ diplopia, fever & chemosis common
Diagnosis Clinical; CT orbit and sinus to r/o orbital Clinical + CT orbit & sinus, blood cx; LP if c/f CNS extension,
cellulitis MRI if c/f cavernous sinus thrombophlebitis
Empiric Augmentin 875mg q12h ± Bactrim 1-2 DS Vancomycin + CTX; add MNZ if c/f CNS involvement or
Treatment q12h (for MRSA coverage) odontogenic/sinogenic spread, involve ophtho early
Complications Rare: eyelid necrosis, amblyopia Vision loss, orbital/subperiosteal abscess, CNS spread

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Infectious Disease Urinary Tract Infections

ASYMPTOMATIC BACTERIURIA
Definition: bacteriuria (≥105 CFU/mL) w/o sx referable to a UTI, irrespective of pyuria
• Treatment: asymptomatic bacteriuria or pyuria should NOT be treated (exceptions: pregnant woman, s/p renal transplant in
past 1mo (controversial), treatment prior to invasive urologic procedures) (IDSA: CID 2019;68:1611)
UTI
Clinical features: frequency, urgency, dysuria (premenopausal), incontinence, nocturia, suprapubic tenderness in otherwise
healthy nonpregnant women. In men w/ UTI sx, consider a dx of prostatitis, evaluate the prostate w/ DRE.

Complicated UTI? Acute UTI + any of: fever, chills/rigors/sx of systemic illness, CVA tenderness/flank pain, pelvic or perineal
pain in men, pregnant, renal transplant
No Yes
Uncomplicated UTI (Cystitis) (JAMA 2014; 312:1677) Complicated UTI
• Diagnosis: clinical; U/A can be used to confirm; pyuria (>10 • 30% w/ UTI and fever are bacteremic (usually older, flank /
WBC); nitrite and LE both ⊕ on dipstick  Sn 68-88% suprapubic pain, CRP, BP) (JAMA 2018;378:48)
o Women: dysuria + frequency w/o vaginal discharge/irritation • Pyelonephritis is a complicated UTI & may itself be
 >90% likelihood of UTI. Outpatient, U/A unnecessary unless complicated by perinephric or renal abscess
immunocompromised or RFs for complicated UTI o WBC casts on U/A are suggestive of pyelo
o Absence of pyuria strongly argues against cystitis
o Nitrite: ⊕ w/ Enterobacterales (convert nitrate  nitrite)
• Microbiology: same as uncomp. UTI plus Serratia,
o Outpatient, get UCx if: male, atypical sx, persist 48-72h after Morganella, Providencia, Pseudomonas, Citrobacter. Gram-
abx initiated, or recur w/in 3 mo of tx positives rare. If S. aureus, think bacteremia. Increasingly
• Differential diagnosis: vaginitis, urethritis, structural resistant organisms (especially to FQ, TMP/SMX)
abnormality, PID, nephrolithiasis • Dx: UCx in all; imaging if ill, suspect obstruction, persistent sx
• Microbiology: E. coli, Klebs, Proteus, S. Saprophyticus, • Treatment:
Enterococcus rarely causes true infection -Outpt: CPO 500mg BID OR LVO 750mg x5-7d OR T/S DS
• Treatment: NFT 100mg BID x5d OR T/S DS BID x3d OR BID x7-10d. Can give 1x IV CTX prior to oral tx.
fosfomycin 3g x1; alternatives: oral β-lactam (e.g. Augmentin -Inpt: CTX OR CEFE OR P/T; CBPN if c/f ESBL. Narrow to
500mg BID, Cefpodoxime 200mg BID) x7d, single dose oral if improving. Duration for inpt: depends on clinical course
aminoglycoside if c/f MDRO (Antimicrob 2019;63:e02165; MGH & oral agent chosen (5-7d for FQ; 7-10d for T/S; 10-14d for β-
Policy Ellucid) lactam), consult ID and IR for associated abscesses
o Avoid NFT if CrCl <40 o Avoid NFT & fosfomycin (poor for upper GU track)
o Avoid empiric T/S if resistance >20% (E. Coli resistance 27% at o Remove/replace coated urologic devices
MGH)
o Prostatitis: FQN preferred for better penetration (can also
o Avoid T/S and NFT in 1st trimester and term for pregnancy
consider TMP-SMX); tx duration up to 6w
C A T H E T E R - A S S O C I A T E D U T I ( C A U T I ) (IDSA: CID 2010; 50:625)
• Definition: leading healthcare-assoc. infection; requires: (1) s/sx with no other identified source of infection; AND (2) UCx with
one uropathogenic species >103 CFU/ml from single catheterized urine specimen (catheter in place >2d) OR midstream voided
specimen from pt whose catheter was removed w/in previous 48h
o In pts w/ neurogenic bladder and  sensation, other signs of UTI include new onset incontinence, autonomic hyperreflexia,
malaise, lethargy, bladder pain (Urology 2015;6:321)
• Prevention: restrict catheters to pts w/ appropriate indications; remove catheters ASAP; consider short-term straight cath
• Dx: do not screen asx patients; pyuria, turbidity, odor cannot differentiate asymptomatic bacteriuria from CAUTI
o Remove/Replace catheter ASAP, obtain repeat UA/UCx from new catheter PRIOR to abx. Catheters may become coated
with a biofilm that acts as a reservoir for microorganisms and can compromise the action of antibiotics and host defenses
o Purple urine bag syndrome: occurs due to byproducts from bacterial enzymes in urine; benign and ≠ UTI
• Micro: same as complicated UTI, with addition of Candida (see below); can be polymicrobial
• Treatment: same abx as complicated UTI, use Cx to narrow. If recent catheterization/instrumentation, h/o MRSA in urine, add
vanc, then narrow pending culture results. Duration: 7d if improving; 10-14d otherwise
F U N G U R I A (IDSA: CID 2016;62:e1)
• Asymptomatic colonization common; only treat if symptoms present OR neutropenic OR before urologic procedure
• Tx: Fluc 200-400mg (pyelo) PO qd x14d OR for resistant C.glabrata or krusei, Amphotericin 0.3-0.6 mg/kg qd x1-7d
RECURRENT UTI
• Behavior Δs: 2-3L water intake daily, post-coital voiding, avoid spermicide use, wiping front to back for pt. w/ female anatomy
• Abx ppx (usually dose T/S or NFT) may be used in some ♀ w/ recurrent simple cystitis (≥2 UTI/6mo) if behavior Δs
ineffective. Either post-coital or continuous if no temporal relation to sexual activity (Cochrane Rev 2004).
• Other inventions include: Vaginal estrogen for post-menopausal women (Cochrane Rev 2008), possible benefit from D-
mannose 2g daily, methenamine hippurate 1g BID (BMJ 2022, 68229), cranberry products (Cochrane Rev 2023), and
Lactobacillus probiotics.
• Pts w/ recurrent admission for complicated UTI, review prior micro & consider resistant orgs. Consider ID +/- urology
involvement. Abx ppx is not indicated for recurrent complicated UTI with resistant organisms due to risk of  resistance
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Infectious Disease Skin & Soft Tissue Infections

C E L L U L I T I S (IDSA: CID 2014;59:147; JAMA 2016;316:325)
• Clinical features: erythema, warmth, tenderness, edema, induration ± purulence; smooth, often poorly demarcated. May have
lymphangitis, LAD, vesicles/bullae, fever (20-77%), leukocytosis (34-50%)
• Risk Factors: trauma, venous stasis, chronic edema (esp. lymphedema), immunosuppression (DM, HIV), obesity, PWID,
neutropenia, inflammation (eczema, psoriasis, radiation therapy), prior surgery/biopsy, toe web abnormalities
• Diagnosis: CLINICAL. Can use ALT-70 score to avoid abx. Cannot use if prior abx. (data req to calc: location, age, WBC, HR) (J Am
Acad Derm 2017;76:618; JAMA Derm 2018;154:529). Consider US to assess for presence of drainable abscess.
o BCx & wound Cx NOT recommended (low yield, pos in <10%). Obtain if: systemic tox, extensive involvement, immunosuppression,
surgical wounds, special exposures (bites, water), recurrent/persistent cellulitis, extremes of age. 20-30% skin bx return pathogen.
• Differential diagnosis: (if “bilateral cellulitis,” strongly consider alternative diagnosis)
o Non-infectious: inflammatory (contact derm, drug rxn, Sweet syndrome, gout, bursitis, EN, pyoderma gangrenosum, GVHD);
vascular (stasis dermatitis, DVT, superficial thrombophlebitis, calciphylaxis), neoplastic (leukemia cutis, lymphoma)
o Unilateral: contact derm, gout, drug rxn, vasculitis, insect bite, DVT, vaccine site rxn, erythema ab igne
o Bilateral: stasis derm, lipodermatosclerosis (often heavily pigmented, thickened subq tissue), lymphedema
o Infectious: abscess, erysipelas (well demarcated, superficial cellulitis involving upper dermis & superficial lymphatics), nec fasc,
septic joint/bursa, osteomyelitis, herpes zoster, HSV, Orf virus, erythema migrans, toxic shock syndrome, mycotic aneurysm
o If abscess present, ddx includes: folliculitis, cyst, hidradenitis suppurativa (often intertriginous skin), lymphangitis
• Treatment: based on 1) purulence and 2) severity. Elevate affected limb. Duration: 5d; up to 14d if delayed signs of improvement
Severity Purulent (abscess or fluctuance) Non-purulent°
MRSA >> MSSA > Strep Strep >> S. aureus > aerobic GNRs
PO: cefadroxil, cephalexin, diclox. pen VK ,
Mild I&D only
amox-clav
Moderate: systemic signs of infxn OR I&D+Cx. Empiric: TMP-SMX OR doxy IV: cefazolin, CTX, pen G
abscess >2cm MSSA: diclox. OR cephalex. MRSA: TMP-SMX Severe ß-lactam allergy: vanc, telavancin
Severe: systemic signs of infxn AND
I&D+Cx. Empiric: vanc OR LZD OR dapto OR Vanc+(pip-tazo OR cefepime+MNZ). Nec fasc
HoTN, immunocomp., rapid evolution,
ceftaroline. MSSA: nafcillin OR cefazolin or TSS: add clinda for toxin inhibition
deeper infection, or failed PO tx
°Non-purulent w/ MRSA risk factors* (prev. MRSA infx/colonization, hosp./surgery/abx in prev 8wks, PWID, penetrating trauma,
hemodialysis, HIV, athletes, prisoners, military, LTC facility residents): add empiric PO/IV MRSA coverage (TMP-SMX or doxy)
*MRSA incidence increasing and many patients with MRSA infection do not have any risk factors (Med. Clin 2021; 4:723-725)
NB: erythema may worsen initially; should improve w/ 72h of abx. Document daily photos & draw margin lines.
Additional coverage: anaerobes (if necrosis, crepitus, certain diabetic infxns [see below], animal bite); GNRs (cirrhosis w/ severe
o
infection, immunocompromise, certain diabetic infxns [as below]); PsA (neutropenic, trauma, burns, post-op)
o Specific associations: gas gangrene  C. perfringens; dog/cat bite  Capnocytophaga, Pasteurella; animals NOS 
Erysipelothrix; human bite/PWID  Eikenella; freshwater  Aeromonas; saltwater Vibrio vulnificus (esp. cirrhosis)
o Sporotrichoid spread ddx: sporotrichosis, Nocardia, NTM (e.g. M. marinum), Bartonella, tularemia
o PWID: infxn sources (H2O, syringe, cotton filter, skin flora), share safe injection practices/PrEP (resources: CDC 1; CDC 2)
• Prevention: Compression therapy: ↓recurrence of cellulitis (v conservative therapy (education) alone). Patients should be advised to
wear compression stockings daily to shift fluid away from the lower leg (NEJM 2020;383:630)
o PCN ppx effective for reducing recurrent cellulitis over 6 & 12 month periods, but not once ppx stopped (PATCH, NEJM 2013;368)
N E C R O T I Z I N G S O F T T I S S U E I N F E C T I O N S (NEJM 2017;377:2253)
• Micro: Type I: polymicrobial (mixed aerobes/anaerobes); Type II: monomicrobial (usually GAS > Strep, Staph, Vibrio, Aeromonas),
associated with TSS; myonecrosis (i.e., gas gangrene): caused by C. perfringens, p/w tissue gas, severe pain, toxin-mediated shock
• Risk Factors: immunosupp., DM (e.g. Fournier gangrene), cirrhosis, neutropenia, EtOH, trauma, skin/mucosal breach, PAD
• Clinical manifestations: pain out of proportion to exam, bullae, induration (risk of compartment syndrome), tissue anesthesia, rapid
skin changes (purple-red  blue-grey), crepitus (suggestive of myonecrosis); systemic toxicity, CK, lactate, Cr, WBC
• Diagnosis: early suspicion and involvement of a surgeon for surgical exploration and ID is critical
o LRINEC score ≥6 high suspicion for nec fasc (uses CRP, WBC, Hgb, Na, Cr, glucose); 90% Sn, 95% Sp (CCM 2004;32:1535)
• Treatment: urgent surgical debridement + abx: vanc + (mero or cefepime/MNZ or pip-tazo) + clinda (NB: LZD also inhibits toxin
production). Adjunctive clindamycin may improve outcomes (Lancet Infect Dis. 2021;21:697)
D I A B E T I C F O O T I N F E C T I O N S (IWGDF/IDSA: CID 2023;ciad527)
• Severity: mild (≥2 items: swelling, induration, pain, warmth, purulence); moderate (no systemic signs, erythema ≥2cm from wound
margin or deeper than skin involvement); severe (systemic symptoms present)
• Initial evaluation: cleanse, debride, probe, culture. Check pulses/sensation, ABIs (40% have PAD).
• Diagnosis: Tissue specimen for cx > superficial swab. Often polymicrobial w/ GPCs>GNRs, anaerobes. Consider Bcx + ESR/CRP
Consult inpatient wound service for deep culture. If c/f osteomyelitis (see osteo)
• Treatment: definitive tx based on deep Cx obtained PRIOR to abx initiation.
o Mild (rx 1-2wk): oral  target GPCs (cephalexin, cefadroxil, amox-clav, diclox, levoflox); TMP-SMX or doxy for MRSA
o Moderate/severe (rx 2-4wk): IV  target GPCs, GNRs ± anaerobes: (CTX or FQ) + MNZ; or amp-sulb. MRSA coverage w/
vanc, LZD, or dapto if: severe infxn, prior MRSA infxn/colonization, other RFs (see above). PsA coverage w/ cefepime or pip/tazo
if: severe infxn, immunocompromised, neutropenic, water exposure, burn/puncture, nosocomial.
o If improving, may de-escalate IV to highly bioavailable PO regimen to complete course of 1-2wk, up to 4 if slow to improve/PAD

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Infectious Disease Osteomyelitis

CLINICAL MANIFESTATIONS
• Acute: <2wk of sx & absence of necrotic bone or sequestrum. Sx: localized, dull pain & diminished function, evidence of
inflammation (fever/chills/night sweats/erythema). Patients may be afebrile
• Chronic: previously failed tx, >3wk sx, presence of bony sequestrum, persistent drainage or sinus tract. Sx: pain (absent
if neuropathy), erythema, swelling, poorly healing ulcers; hallmark is necrotic bone. Fever may be absent
• Etiologies: hematogenous seeding (usually monomicrobial) from bacteremia (risk if endocarditis or indwelling device) or
contiguous spread (polymicrobial) via direct inoculation after surgery/trauma
o Hip, vertebra, pelvis: often have fewer symptoms, can present as septic arthritis
o Vertebral: point tenderness, unremitting, >50yo (except PWID), ± fever (NEJM 2010;362:1022; IDSA: CID 2015;61:e26)
o Pelvic: a/w bacteremia, sacral pressure ulcers, trauma (esp. athletes), urogyn/pelvic surgery, femoral access site;
many present subacutely, may have localized pain or poorly localized, may not have fever
o Sternoclavicular: anterior chest wall swelling, pain, tenderness; may be mistaken for abscess or atypical cellulitis; can
occur via hematogenous spread or post-CT surgery ± mediastinitis
o Mandibular: usually contiguous spread of oral flora/odontogenic infection; often w/ anaerobes
o Foot: toe osteomyelitis or osteo a/w ulcer common in DM (IWGDF/IDSA: CID 2023;ciad527); PAD also risk factor

D I A G N O S T I C A P P R O A C H (JAMA 2008;299:806)
• Exam: probing to bone sufficient for dx in patients w/ DM for foot OM Risk Factors Likelihood Ratio
(83% Sp, 87% Sn) w/o need for further imaging (CID 2016;63:944) Ulcer area >2cm 7.2 (1.1-49)
• Blood Cx: often ⊕ with hematogenous infxn involving vertebra, clavicle, Probe-to-bone 6.4 (3.6-11)
pelvis (always obtain BCx x2 before starting antibiotics) ESR >70mm/h 11 (1.6-79)
• Labs: ESR/CRP (if high can use for monitoring response) ± leukocytosis Abnormal XR 2.3 (1.6-3.3)
• Imaging: MRI c/w OM 3.8 (2.5-5.8)
o >2wk of sx: obtain plain XR first. If XR non-diagnostic and Normal MRI 0.14 (0.08-0.26)
concerning story, obtain advanced imaging (MRI)
o <2wk of sx, suspected vertebral OM or DM: start w/ advanced imaging (MRI), contrast preferred for vertebral OM
o MRI: study of choice for further assessment after plain films; Sn 90%, Sp 82%, high NPV in foot osteo (Arch Intern Med
2007;167:125); best in DM or if c/f vertebral osteo (CID 2015;61:e26)
o CT: if MRI not available; can demonstrate periosteal reaction & cortical/medullary destruction
o Radionuclide bone scan: very sens, but non-spec (false ⊕ if soft tissue inflamm.); option if hardware precludes MRI
• Bone biopsy: gold standard diagnostic test
o If diabetic foot infection, c/s vascular surgery, otherwise c/s ortho. If they decline, consult IR. Open Bx preferred to
percutaneous (CID 2009;48:888). If perc. Bx ⊝ and suspicion high, repeat vs. obtain open biopsy
o Bone Cx may be ⊕ even on abx; need 2 specimens: GS/Cx (aerobic, anaerobic, mycobacterial, fungal) + histopath
o If evidence of OM on imaging or ⊕ probe to bone, bone biopsy ⊕ up to 86% of cases (CID 2006;42:57). Biopsy not
required if ⊕ blood Cx and clinical/radiographic findings of OM

TREATMENT
• Antibiotics (tx based on culture data, see table) Empiric Tx
o Delay empiric tx until biopsy if pt HD stable, has no Vancomycin + GNR coverage (typically CTX 2g
neurologic compromise or e/o epidural abscess q24h). Include PsA coverage (cefepime) for PWID
o Common organisms: MSSA/MRSA, CoNS, Strep, Organism-Specific Tx
Enterococci, aerobic GNRs > Brucella, mycobacteria, fungi Nafcillin 2g IV q4h; cefazolin 2g IV
o Can consider adding rifampin if Staph + hardware (for MSSA
q8h
biofilm) (Antimicrob Agents Chemother 2019;63;e01746) MRSA or Vanc; dapto; dalbavancin (OFID
o Duration: ~6w, PO may be adequate after sufficient CoNS 2018;6:ofy331)
response to IV but d/w ID (OVIVA, NEJM 2019;380:425). If PCN-S Pen G 4 mill U IV q4h; amp 2g q6h;
PO, FQ+RIF most common (RIF monotherapy not rec’d Strep CTX 2g q24h; vanc
due to low barrier to resistance). Longer durations needed Pen G 4 mill U IV q4h; amp 2g q6h +/-
if prosthetic joint infection (NEJM 2021;384:1991; NEJM Enterococci
CTX 2g q24h; vanc; dapto
2023;388:251) and ID should be involved. Retained CTX 2g q24h; cipro 750mg PO BID;
hardware may require suppressive abx GNR levoflox 750mg PO/IV q24h; cefepime
o No residual infected bone (i.e. amputation): abx 2-5d  up 2g q12h (q8h if PsA)
to 10-14 if associated SSTI
o Consider trending ESR/CRP; if elevated at end of abx, consider further w/u (NB: NO routine repeat MRI, findings
take weeks to months to resolve)
• Surgical debridement: indicated if failure to respond to medical therapies, chronic OM, complications of pyogenic
vertebral OM (e.g., early signs of cord compression, spinal instability, epidural abscess), or infected prosthesis

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Infectious Disease Bloodstream Infections & Endocarditis

BLOODSTREAM INFECTIONS (BSI)
Evaluation (JAMA 2012;308;502)
1. Sources: lines, procedures, meningitis, endocarditis, osteomyelitis (OM), septic arthritis, PNA, UTI, SSTI, abscesses
2. When should I/should I not send blood cultures? (JHM 2017;12:510; JHM 2016;11:336)
Predictive signs/symptoms Predictive clinical scenario Other Considerations
Fever+chills (+LR 1.1-6.1); rigors (+LR 4.7, High risk: septic shock (38-69% ⊕ BCx), meningitis (53%)
Immunocompromised (neutropenia, HIV);
Amer J Med 2005;118:1417); SIRS (-LR 0.09), Medium risk: pyelonephritis (19-25%)
hard-to-isolate source (OM, septic arthritis)
normal food intake (-LR 0.18) Low risk: cellulitis (2%), CAP (7%), other community-onset fever (13%)
3. How should I send blood cultures?
o PRIOR to abx, 2 sets minimum, ideally 3 peripheral venipunctures over 1h; draw from central line only if c/f catheter-related infxn
(criteria: catheter CFUs 3x peripheral blood OR cath. growth 2h before peripheral) (IDSA: CID 2009;49:1)
o Signs of contaminant: only 1 bottle growing, certain organisms (e.g. CoNS, GPRs), no systemic sx, time to positivity >3-5d
4. Further testing:
o Staph aureus and Staph lugdunensis: very sticky and never contaminants. Daily surveillance cultures (not necessary for GNRs)
(CID 2017;65:1776), remove lines/hardware, TTE/TEE to r/o endocarditis, consider back imaging for discitis/OM if having back pain
or imaging for pain at other joints and arthrocentesis for swollen joints
o Consider TTE for high grade Strep spp. No routine TTE for GNRs
o Yeast: TTE, ophthalmology c/s to r/o fungal endophthalmitis, remove lines
Antimicrobial selection:
GS Empiric abx Other considerations
S. aureus: ID c/s mortality. Adding β-lactam (cefazolin/nafcillin) may improve outcomes (CID 2013;57;1760)
GPCs Vanc+CTX
MSSA: β-lactam >>> vanc (CID 2015;61;361)
GPRs Call ID More likely true infection in immunocomp hosts, multiple bottles, hardware, or known GPR infection
GNRs Cefe/ceftaz/Zosyn If MDRO, see IDSA guidelines. Can de-escalate to orals (TMP-SMX/FQN x7d) (JAMA IM 2019:179:3; CID 2019;69:7).
Candida Micafungin ID c/s mortality (Lancet ID 2019;19:1336); ALWAYS treat as true infection in blood
E N D O C A R D I T I S (AHA/IDSA: Circ 2015;132:1435; ESC: EHJ 2015;36:3075) Modified Duke Criteria for Infective Endocarditis
• Etiology: cutaneous (40%), oral (29%), GI (23%) – source often unknown MAJOR CRITERIA
• Clinical manifestations: BSI s/sx; valvular complications  acute HF, AV block; ⊕ BCx (likely org.* in 2 separate Cx, rare causal org. in 3
septic emboli (CVA/CNS, pulm/PE, MI, kidneys, spleen, joints), immune-complex Cx) or ⊕C. burnetii, Bartonella spp, T. whipplei PCR; C.
deposition (arthritis, GN) burnetii, B. henselae, B. quintana IgG titer 1:800
• Exam: new murmur, arthritis, embolic phenom. (petechiae, splinter hemorr) Endocardial involvement on imaging (echo or cardiac CT):
• Diagnosis: Duke criteria  2 major OR 1 major + 3 minor OR 5 minor vegetation, abscess, dehiscence, or new regurgitation; PET/CT
w/ abnormal endocardial activity
o TTE in all; TEE if: ⊝ TTE w/ high susp; PVE; intracardiac device; suspected
MINOR CRITERIA
complications (AHA/ACC: JACC 2014;63:e57); consult ID
RFs: valve dz, IVDU, prior IE, CIED, prosthetic, CHD
o May be role for PET in PVE (less so in NVE) (CID 2020;70;583)
• Monitoring: repeat BCx q24h until sterile x48h & serial ECGs for: new AV block Temperature >38C or 100.4F
(prolonging PR most common); p mitrale; low QRS voltage Vascular phenomena: septic arterial/pulm emboli, mycotic
aneurysm, ICH, conjunctival hemorrhages, Janeway lesions,
• Micro: NV: Strep, Staph, CoNS/Enterococc., HACEK; PV (<12mo): CoNS, Staph, cerebral/splenic abscess
Enterococc./GNR/fungus; PV (>12mo): similar to NVE (w/ more CoNS)
Immunologic phenomena: GN, Osler, Roth spots, ⊕RF
• Indications for surgical consult: emergent: new-onset HF (acute valvulopathy),
Micro (not meeting major criteria, likely org*): ⊕ BCx, ⊕PCR
annular/aortic abscess (new AV block on ECG); other: L-sided S. from non-cardiac sterile body site
aureus/fungus/MDRO, persistent infxn after 5-7d abx, PVE w/ recurrent infxn, large Imaging: PET/CT w/ abnormal metabolic activity w/in 3 mo of
vegetation (>10mm on L, >20mm on R), embolic phenomena despite abx (AATS: prosthetic cardiac implant
JTCS 2017;153:1241); can c/s surgery for all PVE (± streptococcal) *S. aureus, S. lugdenesis, all Strep spp (except S. pneumoniae,
• AC/antiplatelet: ok to continue but no indication to initiate; if CVA/ICH, hold x2w S. pyogenes), Granulicatella spp, Abiotrophia spp, Gemella
• IVDU-assoc IE: refer to MGH Drug Use Endocarditis Team (DUET, Epic phrase: spp, HACEK, community-acquired enterococci in absence of 1º
.MGHDUET). Includes CT surgery, ID, ACT focus
• IV  PO may be non-inferior to IV in carefully selected L-sided IE pts (POET, NEJM 2019;380;415)
• Ppx: if prior IE, prosthetic valve, unrepaired cyanotic CHD, or w/in 6mo of CHD repair, give amox. 2g or clinda. 600mg x1 (if PCN
allergy) w/in 30-60 min pre-dental procedure; not recommended for GI/GU procedures unless ongoing GI/GU infxn (Circ 2007;116:15)
Organism Therapy Notes
Streptococci (VGS [mitis, mutans, etc.]; - PCN OR CTX x4w (some infxns may have 2w options) - Dosing: PCN varies; CTX 2g q24; amp 2g
gallolyticus [a/w colon cancer]; Gemella spp.; - may add gent based on PCN MIC and severity of infection q4; gent 1mg/kg q8, peak 3-4, trough <1
Abiotrophia [treat as MIC]) - PVE: generally requires gent - Vanc inferior to beta-lactams
- MSSA: oxacillin (better for CNS penetration), nafcillin (some
Staphylococci (aureus; lugdunensis - Dosing: ox and naf 2g q4; cefazolin 2g q8;
risk for nephrotoxicity), cefazolin (good for kidneys) x6w
[virulent, treat like SA]; CoNS [often dapto 8-12mg/kg q24; gent as above
- MRSA: vanc OR dapto x6w
methicillin-resistant]) - Vanc inferior to beta lactams for MSSA
- PVE: may add gent for first 2w and rifampin for 6w
- Dosing: as above
- Amp AND CTX x6w, may add gent or streptomycin
Enterococci (faecalis, faecium) - 4w amp+gent sufficient if NVE and <3mo
- Vanc if amp-resistant. VRE: dapto + amp OR linezolid
sx; 6w if >3mo or PVE
Gram ⊝ (HACEKs mostly, PsA, other GNRs - HACEK: CTX OR amp OR cipro x4w (6w for PVE) - Rare etiology, minimal data to firmly direct
possible) - GNRs: β-lactam + (AG or FQ) x6w treatment modalities
- Candida: ampho B 3-5 mg/kg/d (± flucytosine 25mg/kg q6h)
OR Micafungin 150mg q24. C/s surgery (CID 2016;62:4) - RFs: TPN, lines, PPM/ICD, prosthesis,
Fungi (Candida, Aspergillus)
- Aspergillus: vori (6mg/kg q12h x2 dose load then 4mg/kg IVDU
q12h) or ampho B (CID 2016;63:4)
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Infectious Disease Meningitis & Encephalitis

BACTERIAL MENINGITIS
Clinical Features
● History: 95% have ≥2 of: fever, neck stiffness, AMS, HA (NEJM 2004;351:1849). Lethargy, hypothermia may be common in elderly. Abd
pain, peritonitis can be seen w/ VP shunts. Can also cause seizures, stroke (infectious vasculitis), hydrocephalus, CN deficits (esp TB
and fungal) (Continuum 2021;27:836).
● Exam: most findings more Sp than Sn. Nuchal rigidity 30% Sn, 68% Sp. Kernig’s 5% Sn, 95% Sp. Brudzinski’s 5% Sn, 95% Sp (CID
2002;35:46). Jolt sign (worsening HA with horizontal rotation of the head) 64% Sn, 43% Sp (Am J EM 2013;31:1601). May be absent if
>65 yo, immunocompromised, taking analgesics (Continuum 2021;27:836-854). Meningococcemia with petechial rash, palpable purpura
Diagnosis (CID 2004;39:1267)
● Blood cultures STAT – BEFORE antibiotics (positive in 70% patients); DO NOT delay antibiotics for LP or imaging
● Lumbar puncture ASAP
o Head CT prior to LP only indicated if: immunocompromised, known CNS disease (mass lesion, CVA, focal infection), new
seizure, papilledema, level of consciousness, focal neurologic deficit (Clin Neuroradiol 2022;32:857)
o Obtain opening pressure with simple column manometer (nml 200mm H2O; mean 350mm H2O in bacterial meningitis)
o For a list of studies to send and CSF analysis/interpretation, see Procedures: Fluid Analysis
o Repeat LP if: no clinical improvement after 48h of appropriate antibiotics, evidence of antimicrobial resistance of cultured
organisms, or ongoing fevers > 8 days w/treatment
Microbiology (NEJM 2011;364:2016; NEJM 2010;362:146; Cochrane 2015;9:CD004405)
Community Nosocomial (intracranial procedure, >48h in
Adults 18-34 Adults 35-49 Adults >50 hospital, head trauma)
Gram neg bacilli (40%)
S. pneumoniae (50%) S. pneumoniae (75%) S. pneumoniae (76%)
S. aureus (10%)
N. meningitidis (35%) N. meningitidis (10%) GBS (8%), Listeria (7%),
Coag neg Staph, particularly w/presence of
H. influenzae (7%) GBS (7%) H. influenzae (6%)
foreign material (10%)
GBS (6%) H. influenzae (5%) N. meningitidis (5%)
C. acnes (takes 10 days to grow!)
Listeria (2%) Listeria (3%) Aerobic gram neg bacilli

Empiric Treatment (Lancet 2021;398:1171)

Adults < 50 Adults > 50 Immunocompromised Nosocomial SEVERE β-lactam allergy
Vanc + CTX 2g Vanc + [cefepime 2g q8h OR Vanc + [cefepime 2g Vanc + mero 2g q8h OR moxi 400mg qd.
Vanc + CTX q12h + meropenem 2g q8h] + ampicillin 2g q4h q8h OR ceftazidime [if >50 or immunocomp., for Listeria:
2g q12h ampicillin 2g (not needed if on mero) 2g q8h OR Bactrim 5mg/kg IV qd div q6-12h] if not on
q4h (consider fungal & viral) meropenem 2g q8h] mero
Note: vancomycin is added empirically to cover PCN-resistant S. pneumo, not MRSA
● Duration: N. meningitidis/H. flu (7d); S. pneumo (14d); Listeria (2-4w if immunocompetent; 4-8w if immunocompromised)
● Dexamethasone: greatest benefit in suspected/confirmed S. pneumococcal meningitis w/ GCS 8-11 (mortality/hearing loss, & short-
term neuro sequelae in high-income countries) 0.15 mg/kg q6h x 4d; start prior to or with 1st dose of abx, but do not delay abx
● CSF shunts: consult Neurosurgery for assistance with mgmt and/or shunt removal (IDSA: CID 2017;64:701)
● BBB penetration: meningeal inflammation BBB permeability esp when severe. Abx with poor penetration into CSF in cases of mildly-
inflamed meninges include β-lactams (overcome by dosage), aminoglycosides, tetracyclines, daptomycin. See Tip Sheet.
● Prevention: MenACWY/MenB, Hib, pneumococcal vaccines. PPx: All close contacts of patients w/ suspected N. meningitidis or close
contacts (w/ increased risk factors) of patients w/ Hib.
A S E P T I C M E N I N G I T I S : meningeal inflammation with negative bacterial cultures
Clinical Features: similar to bacterial, usually less toxic. LP: lymphocytic pleocytosis, low CSF lactate (J Infect 2011; 62(4):255)
Etiology: Infectious: enteroviruses (most common), HSV2>1 (Neurology 2006;66:75-80), VZV, partially tx’d bacterial meningitis (usually
days-wks), any stage of syphilis, Lyme, leptospira, mumps, Nocardia, TB, HIV (primary infxn), LCMV, fungal (see below),
brain/parameningeal abscess; Non-infectious: autoimmune (Behcet’s, sarcoid, SLE, SJS, Sjogren, GPA), neoplastic (leukemia,
lymphoma), drugs (NSAIDs, antimicrobials, IVIG, immune checkpoint inhibitors), pituitary apoplexy
Additional diagnostics: West Nile IgM (June – Oct), VDRL, Lyme Ab, serum HIV, HSV swabs of any concurrent oral/genital lesions
Treatment: HSV, VZV → acyclovir 10-15 mg/kg IV q8h; tx underlying cause (if possible) & supportive care. If suspect TB, c/s ID
F U N G A L M E N I N G I T I S : see Invasive Fungal Infections
Causes: Primary (immunocompetent): Crypto, Blasto, Histo, Cocci, other dimorphic fungi; Secondary (immunocompromised):
Cryptococcus, Candida, Aspergillus, other molds; healthcare related outbreaks 2/2 epidural anesthesia in Mexico (CDC 2023)
Diagnosis: CSF CRAG, (1,3)-B-D-glucan, fungal wet prep, fungal culture, large volume (40-50mL) for Cx (J Clin Microbiol 2013;51:1285)
Treatment: ID to guide. See Invasive Fungal Infections.
E N C E P H A L I T I S (IDSA: CID 2008;47:303)
Presentation: abnormal brain function (vs. normal cerebral function in meningitis): AMS, focal neuro deficits
Etiology: Infectious: HSV1>>2, VZV, arbo (West Nile, WEE/EEE, St Louis, Japanese), enteroviruses (Coxsackie viruses, echoviruses,
polioviruses), HIV, CMV (extremely rare), JC, adeno, influenza, Powassan virus, Zika; Non-infectious: post-infectious demyelination
(ADEM), autoimmune, paraneoplastic (anti-Hu [SCLC], anti-Ma2 [testicular], anti-CRMP5 [SCLC/thymoma], anti-NMDA receptor [ovarian
teratoma, idiopathic])
Diagnosis: send CSF for HSV, VZV PCR; other viruses less common. If clinical suspicion  (West Nile IgM, JC, CMV/EBV [extremely
rare]); autoimmune-Mayo ab panel; consider MRI (HSVtemporal lobe enhancement, W. Nilebasal ganglia/thalamic foci); EEG
Treatment: HSV, VZV → acyclovir 10 mg/kg IV q8h; otherwise supportive care (Neurol Clinic 2021;39:197). If sx recur s/p tx, consider
viral relapse vs. autoimmune encephalitis – high rates of autoimm. dz wks later (Lancet Neurol 2018;17:760)
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Infectious Disease C. Difficile Infection

O V E R V I E W (IDSA 2021 update: CID 2021;73:1029; CID 2018;66:987)
• Definition: C. difficile infection (CDI): acute-onset sx (usually ≥3 episodes/d of watery diarrhea) + e/o toxin-producing C.
difficile or histopathology c/w pseudomembranous colitis
• RFs: abx w/in 3mo (particularly associated with penicillins, 2nd/3rd/4th gen ceph, FQ, carbapenems, clinda), age (≥65yo),
recent hosp or LOS, severe comorbid illness, IBD, chemo/immunocompromise, GI surgery, tube feeding, PPI/H2RA
• Pathogenesis: fecal-oral via spores, colonized host; most often infection requires both acquisition of C. diff plus loss of gut
microbial abundance/diversity (e.g. due to abx). Symptoms are toxin-mediated: toxin A (enterotoxic) & toxin B (cytotoxic)
• Community-acquired CDI: ~1/3 new cases; p/w diarrhea in pt w/o hospitalization in last 12 wks. Potential sources:
contam. food/H2O, pets, asx colonization in family, babies, outpt visits (AJG 2012;107:89; JAMA IM 2013;173:1359)
CLINICAL MANIFESTATIONS
• Features: watery diarrhea (≥3 loose stools in 24h) +/- mucus/occult blood; ileus, fever, abd pain, nausea,WBC
• Ddx: non-C. diff abx-associated diarrhea, infectious diarrhea, post-infectious IBS, IBD, microscopic colitis, Celiac disease
• Severity: see table below; severe colitis may be c/b hypovolemia, AKI, marked leukocytosis, lactic acidosis, protein-losing
enteropathy; fulminant colitis characterized by hypotension/shock, ileus, toxic megacolon w/ mortality
DIAGNOSIS
• MGH protocol: see algorithm to right.
o Toxin B gene PCR: High Sn but can be ⊕ even in the absence of
active infection (strain may have toxin gene but not produce it)
o GDH Antigen: Enzyme produced constitutively by all C. diff strains;
sensitive but cannot distinguish toxigenic & non-toxigenic strains
o Toxin A/B: Assay detects toxin production, high Sp but poor Sn
• DO NOT retest within 7d w/o significant clinical change
• DO NOT test for “cure” (may remain ⊕ for up to 6w despite resolved sx) *Any positive
• CT A/P: if severe illness or fulminant colitis to assess for complications PCR results in
contact plus
warranting surgical intervention (e.g. toxic megacolon, bowel perf) isolation,
• Flex sig: in rare cases when alt dx suspected and need visualization/bx regardless of
Ag/toxin result

T R E A T M E N T (IDSA 2021 update: CID 2021;73:1029; CID 2018;66:987)

Category Criteria Treatment
Non-severe WBC <15 AND Cr <1.5 - Fidaxomicin* 200mg PO BID x10d OR Vanc 125mg PO q6h x10d
- Alternative: metronidazole 500mg PO q8h 10-14d (if Fidax & Vanc not avail)
- D/c antimotility agents, non-essential abx, cholestyramine (binds vanc)
Severe WBC >15 OR Cr >1.5 - Fidaxomicin* 200mg PO BID x10d OR Vanc 125mg PO q6h x10d
Fulminant Hypotension/shock, - Vanc 500mg PO q6h AND metronidazole 500mg IV q8h
ileus, megacolon - If ileus: can add vanc PR 500mg in 100cc NS as retention enema Q6H
- Surgery c/s; consider FMT if ileus, tx nonresponsive, or recurrent dz
Duration: 10d for non-fulminant; if receiving concurrent abx duration may be extended 7d after completion of other abx
*Fidaxomicin: 1st line,  recurrence vs vanc; currently cost prohibitive at MGH (CID 2021;73:1029; Cochrane Rev 2017)
RECURRENCE
• Recurrent CDI: resolution of sx w/ tx, reappearance of sx w/in 2-8 wks after abx completed. Often due to relapse as
opposed to reinfection vs. refractory disease (no resolution on therapy  consider alt diagnosis and ID or GI c/s)
• 1st recurrence: Fidax* 200mg PO BID x10d OR 200mg PO BID x5d then qod x20d OR Pulse-tapered PO vanc 125mg
x6-8w AND IV Bezlotoxumab 10mg/kg x1 w/ fidax or vanc reg. if w/in 6 mos of prior episode (CID 2021;73:1029)
2nd recurrence: Fidax* regimen (same as 1st recurrence) OR pulse-tapered vanc 125mg x6-8w OR vanc 125mg q6 x10d
followed by rifaximin 400mg TID x20d) AND IV Bezlotoxumab as above. IDSA recommends evaluation for fecal
microbiota transplant (FMT) after 2nd recurrence; more effective than vanc or fidax alone (NEJM 2013;368:407; CID
2019;68:1351; Gastro 2019;156:1324). Consult ID for FMT evaluation.
OTHER CONSIDERATIONS
• Infxn ctrl: Contact precautions, wash hands with soap & water after contact (alcohol-based rubs won’t eliminate spores)
• Prophylaxis: vanc 125mg PO qd for abx duration + additional 7d may recurrence in pts w/ prior CDI receiving systemic
abx (AJG 2016;111:1834; CID 2016;63:651; ICHE 2019;40:662). May also be effective as primary ppx in high-risk
patients (≥60yo, current or recent <30d systemic abx) w/ 125mg daily dosing (CID 2020;71:1133)
• Probiotics: Not recommended for prevention of CDI by society guidelines (CID 2018;66:987). Some evidence supports
use w/ abx to reduce abx-associated diarrhea (JAMA 2012;307:1959).

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Infectious Disease Invasive Fungal Infections

RISK FACTORS
Heme malignancy, HSCT > Solid organ transplant > biologic Tx,
HIV/AIDS, prolonged neutropenia, prolonged glucocorticoids, burn
patients, severe lung disease/prolonged intubation
DIAGNOSTIC TESTING
Fungal markers:
• 1,3-β-D Glucan (BDG) (CID 2011;52:750): cell wall polysaccharide,
detects Candida, Aspergillus, PJP, Fusarium, Trichosporon, Histo,
Cocci with Sn 77%, Sp 86% (cutoff 80). CANNOT dx Mucor, Rhizopus,
Blasto, Crypto
o False ⊕ w/ IVIG, albumin, HD, pip-tazo, unasyn, Strep,
Pseudomonas (J Clin Microbio 2013;51:3478)
o False ⊝ possible w/ candidemia (CID 2020;70:1925)
• Galactomannan (GM) (Cochrane Rev 2015): detects Aspergillus cell
wall component; Sn (serum 65-80%, BAL 90-95%), Sp 88%
o False ⊕ w/ some TPN formulations, IVIG, blood products
• Histo Ag: UAg Sn 90% if disseminated (vs. sAg 80%); Sp limited by
cross-reactivity (esp. with blasto)
• Crypto Ag (CrAg): serum Sn&Sp >90% if disseminated,  w/
Notes: [1] See left/below [2] 87% of MGH C. glabrata is fluc-S [3] Only approved for invasive
pulm dz only, Sn for pulm if HIV Aspergillosis/Mucor [4] In aspergillosis, vori + mica not superior to vori alone [5] Covers most
• Blastomycoses: uAg > sAg; Sn, modest Sp d/t cross- invasive fungi few exceptions, e.g., C. lusitaniae, A. terreus, Lomentospora, Scedosporium. Order
reactivity. Sensitivity of uAg for pulmonary dz is ~80%. amphoB w/ pre hydration AND BMP, Mg BID. Adapted from JA Freed and AJ Hale, IDModules.com
Invasive Opportunistic Fungi **ID consultation is advised for these diagnoses**
Aspergillus, Candida, and Pneumocystis account for >80% of fungal infections diagnosed in hospitalized patients (OFID, 2022)
RFs: neutropenia, immunocompromised (heme malignancy, transplant, HIV/AIDS), TPN, PWID, CVC, prior abd. surgery, ICU
Spectrum of illness: sepsis (25% mortality), macronodular skin lesions (10%), endophthalmitis, endocarditis, osteomyelitis, UTI
Candida Dx: BCx (never contaminant, grows slowly [BMC Infect Dis. 2013;13:486]), c/s ophtho & ID, TTE, repeat Cx daily. Sn if deep
CID 2016;62:e1 tissue/hepatosplenic infxn; ⊕ RCx usually colonization not infxn. Ophtho c/s for dilated eye exam in non-neutropenic patients (if
neutropenic, perform within first week of ANC recovery) (CID 2016;62:e1). Skin bx with cx if suspicious lesion. Candida score
Tx: BSI: echinocandins  azole (amphoB for resistant strains); remove CVCs. Endophthalmitis: may need intravitreal
amphoB/vori. UTI: see UTI. Duration: BSI: 2w after 1st ⊝ Cx w/ no dissemination, deep-seated infxn: longer, see BSI
RFs: immunocompromise (HIV/AIDS, malignancy, xplant), liver disease, can occur in immunocompetent (C. gattii > C. neoformans)
Spectrum: asympt.  meningoencephalitis, (pulmonary [AHRF], skin nodules, liver abscesses); can be subacute, fever in ~50%.
Cryptococcus
YEAST

Lancet ID Dx: serum/CSF CrAg (⊕ serum w/ ⊝ CSF = cryptoccal antigenemia), LP/CSF: OP >200 mmH2O, gluc, TP, lymphs,
2024;9:s1473 cryptococcomas on imaging, umbilicated skin lesions. Brain MRI and chest CT. Screen with serum CrAg if CD4<200  LP if +.
Tx: CM: amphoB + flucytosine (x2w)  fluc (≥8w), serial LPs if OP≥20 or symptoms of ICP, fluc for mild pulm dz/antigenemia
Ppx: fluc for HIV/AIDS (CD4<200) in high-risk, low-resource settings (in US not recommended unless positive serum antigen)
RFs: immunocompromised (HIV/AIDS, heme malignancy, transplant), steroids equiv. to pred 20mg/day x4w
Spectrum of illness: pulm sx onset over days/weeks, PTX, hypoxemia out of proportion to CXR (diffuse GGO on CT)
Pneumocystis Dx: LDH >500 (Sn not Sp), BAL > induced sputum for silver stain/DFA 1,3-BDG (Eur J Clin Micr ID 2014;33:1173)
HIV.gov Tx: T/S (PO/IV8-12mg/kg/d, adjust PRN renal fxn). Consider pred 40mg BID if severe hypoxemia; Alternatives: TMP+dapsone,
clinda + primaquine, atovaquone or pentamidine; Duration: 21d
Ppx: T/S (1 DS qD > SS qD, 1 DS MWF), atovaquone, dapsone (check G6PD), pentamidine
RFs: neutropenia, steroids, transplant, COPD w/ prolonged ICU stay, anti-TNF, cannabis use, COVID19 with ARDS/ICU stay
Spectrum of illness: invasive pulm (IPA), aspergilloma, sinus, tracheobronchitis, CNS, endophthalmitis, disseminated, necrotic skin
Aspergillus
Dx: CT w/ halo sign, BAL/sputum wet prep/fungal cx ± biopsy, serum 1,3-BDG (not Sp), GM (Sp; trend serum in tx, BAL > serum)
CID 2016;63:e1
Tx: voriconazole (monitor trough, drug-drug int), Posaconazole or isavuconazole ; debride if necrotic. Duration: >6-12w for pulm dz
MOLD

Ppx: vori or posa (prolonged neutropenia, GVHD [NEJM 2007;356:348]), vori/itra/inhaled amphoB (lung transplant ± h/o IPA)
RFs: DKA, iron overload, heme malignancy, prolonged neutropenia, immunocompromised (Semin Respir Crit Care Med 2015;36:692)
Mucor
Spectrum of illness: rhino/orbital/cerebral invasion, pulmonary, GI, renal; black eschars over ulcers, rapidly progressive
Lancet 2019;
Dx: biopsy, fungal wet prep/culture (broad non-septate hyphae), inform lab concerned for mucor, CT w/ reverse halo sign
19:e405
Tx: DEBRIDEMENT, amphoB, consider posaconazole or isavuconazole (for salvage therapy or if renal dz)
Endemic Mycoses* (maps)
Endemic areas: Central/eastern US (OH/MS River valleys), Central America, Asia, Africa
Spectrum of illness: PNA, meningitis, mediastinal disease, disseminated disease, pericarditis, arthritis
Histoplasmosis
Dx: urine + serum Ag (improves sensitivity for detecting pulmonary infxn), histology, Cx. Chest imaging similar to sarcoid.
CID 2007;45:807
Tx: itra or fluc or no tx (mild-mod), amphoB  itra (severe); NSAID for extrapulm; Duration: 6-12w
Ppx: for both Histo and Blasto (below), consider itraconazole for HIV (CD4 <150) in hyperendemic areas
Endemic areas: Midwest, south-central, SE US (OH/MS River valleys & Great Lakes), Canada
Blastomycosis Spectrum of illness: fever, PNA (acute or chronic), ARDS, ulcerated skin lesions, osteomyelitis, prostatitis, CNS
CID 2008;46:1801 Dx: wet prep (broad-based, budding yeast), Cx, uAg > sAg, never a colonizer
Tx: itra (mild-mod), amphoB  itra (severe); Duration: 6-12mo
Endemic areas: Desert regions: SW and S US, Mexico, Central & South America
Spectrum of illness: PNA (+/- nodules), fever, rash (erythema nodosum), HA, eosinophilia, meningitis, osteomyelitis
Coccidiomycosis Dx: serologies, Cx (if high concern, alert lab for biohazard), spherules on bx/aspirate, Ag for extrapulm (urine, blood, CSF)
CID 2016;63:e112 Tx: no tx (mild-mod, immunocompetent); fluc or itra, consider amphoB (severe); Duration: 3-12mo
Ppx: fluc for 1° ppx for transplant in endemic areas; fluc ppx for HIV in endemic areas if CD4 <250, newly (+) serology w/o evidence
of active disease; fluc for 2° ppx
*Other endemic mycoses include: Paracoccidioidomycosis, Sporotrichosis, Talaromycosis, Emergomycosis (PLoS Pathog. 2019;15:9), etc.

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Infectious Disease Tuberculosis

EPIDEMIOLOGY AND RISK FACTORS
• World: 1/4 infected; US: incidence 2.4/100,000, w/ ~4% HIV coinfection and ~1% MDR (CDC MMWR TB US 2022)
• Acquisition: travel hx (if high-prevalence area), homelessness, incarceration, PWID, healthcare work, racial/ethnic minority
• Reactivation: risk 5% first 2y, 5-10% lifetime, higher if ≥1 risk factor: HIV, immunosupp, CKD (esp. RRT), DM, transplant, TNFα
inhibitor, silicosis, malnutrition, tobacco, EtOH (NEJM 2011;364:1441); untreated HIV has 7-10% yearly risk
SCREENING FOR LATENT TB
Test based on likelihood of exposure & progression to active disease. IGRA TST at 48-72h Patient Population
preferred (TSPOT at MGH); TST acceptable (NB: use TST/IGRA
HIV, prior TB hx, CXR c/w prior
interpreter if BCG vaccinated). Both IGRA and TST are 80-90% Sn and
≥5mm TB, silicosis,
>95% Sp in immunocompetent, Sn in immunocomprom. Neither rules
immunosuppression
in/out active TB, can be discordant ~30% of the time. If ⊕ test w/ no risk ≥10mm Diabetes, CKD, PWID
factors, repeat either IGRA or TST prior to tx. If ⊕ test in risk pt, proceed to ≥15mm No risk factors
tx (ATS/CDC/IDSA: CID 2017;64:111) Size reflects skin induration, NOT erythema
CLINICAL MANIFESTATIONS
• Primary TB: fever, chest pain, cough, arthralgia. CXR can be normal, have focal infiltrate, or ⊕ hilar LAD
• Reactivation TB: fever, cough, hemoptysis, night sweats, wt loss; CXR often w/ posterior/apical involvement or cavitation (seen
in 1/3 of pts, a/w org. burden  infectious, AFB⊕) (J Clin Microbiol 2007:45:4064); more common than primary TB
• Extrapulmonary TB: meningitis with basilar predominance, Pott disease, GU involvement, intestinal TB, pericarditis, scrofula
D I A G N O S T I C S : A C T I V E P U L M O N A R Y / E X T R A P U L M O N A R Y T B (ATS/CDC/IDSA: CID 2017;64:111; Lancet 2007;369:9578)
Site of Infection Diagnostic Tests
Expectorated or induced, AFB smear/Cx x3 ≥8h apart (with one AM sample), add NAAT/PCR (Xpert) to one
Sputum
Lung

of the specimens; smear may be ⊝ if low burden (~20% if HIV-, ~60% if HIV+)
Bronch AFB smear, NAAT/PCR (Xpert), and Cx; +/- transbronch bx, post-bronch induced sputum yield
Ascites or Adenosine deaminase (ADA) >39 units/L high Sn/Sp; free IFN-γ elevated high Sn/Sp; AFB smear,
pleural fluid NAAT/PCR (Xpert), & Cx (poor sensitivity but diagnostic if positive)
Pericardial fluid AFB, Cx, cell counts (typically exudative, protein, lymphocytes), ADA. No evidence for free IFN-γ
At least 3 large volume (10-15cc) serial LPs if possible (yield). glucose, protein, lymphocyte
CSF
predominance; ADA useful adjunct. AFB smear, Cx, and NAAT/PCR (Xpert)
Wound/Tissue AFB-positive staining and caseating granulomas on pathology
Urine UA w/ “sterile” pyuria; send first AM void (large vol ~50cc) Cx x3d. Urine LAM not available at MGH
Blood Can send mycobacterial cultures (isolators) for AFB
P A T I E N T I S O L A T I O N : clinical decision based on likelihood of active pulmonary TB
• When: cough, dyspnea, or hemoptysis + ≥1 risk factor (HIV+, foreign born, PWID, homelessness, recent incarceration, prior
TB/exposure). First obtain CXR; if CXR normal (and HIV- or CD4>200), TB less likely. If CXR abnormal/equivocal (or HIV+ and
CD4<200), maintain isolation & obtain sputum x3 as above. Consider ID c/s
• Discontinue: if alternate dx OR AFB smear ⊝ x3 w/ very low suspicion OR on TB tx x2w + AFB smear ⊝ x3 + clinical improv
A P P R O A C H T O T R E A T M E N T (ATS/CDC/IDSA: CID 2016;63:e147; NEJM 2015;373:2149)
• Prior to starting treatment:
o Check baseline LFTs/Cr, visual acuity/color discrimination, screen for HIV, Hep A/B/C, DM, EtOH use, pregnancy
o Before treating latent TB: rule out active TB (obtain relevant history and CXR. Sputum AFB if clinical suspicion)
o Before treating active TB: c/s ID, send TB for drug sensitivity testing
• Treatment regimens:
o Active TB: isoniazid (INH) + rifampin (RIF) + pyrazinamide (PZA) + ethambutol (EMB) x2mo, followed by INH+RIF x4mo
 In 2022, CDC added 4mo rifapentine-moxifloxacin based regimen as option for drug-susceptible pulm TB
 Obtain monthly sputum AFB smear/cx until ⊝ x2 consecutive months to assess tx response
o Latent TB: INH+rifapentine (RPT) qw x12 (3HP) OR RIF x4mo (4R) OR INH+RIF x3mo (3HR) OR INH+B6 x6-9mo (6H,
9H, less preferred) (CDC Tx Table; R and R 2020;69:1)
o Quinolones: 1st line w/ MDR-TB, avoid in bacterial PNA if suspicious for active TB (dx yield & risk of resistance)
• Drug-resistant TB: suspect if previously treated, treatment failure, from prevalent area (India, China, Russia, S. Africa), or
known exposure. Treatment regimen depends on drug susceptibility profile; usually 12-24mo course. High mortality
o ATS/CDC/ERS/IDSA 2019 Guidelines for Drug-resistant TB (Am J Respir Crit Care Med 2019;200:e93)
• HIV co-infection: discuss timing of ART initiation w/ ID due to risk for IRIS
• Extrapulmonary TB: highly variable presentation/therapy, duration depends on site of infection & response. For CNS TB: 12mo
tx, glucocorticoids confer 25% short term reduction in mortality (Cochrane Rev 2016)
• Medication side effects: hepatotoxicity (INH, RIF, PZA), optic neuritis (EMB), peripheral neuropathy (INH  add pyridoxine [B6]
with initiation of treatment), orange bodily fluids (RIF), numerous drug-drug interactions (especially RIF)
• RIF/RPT remain widely used despite 2020 FDA announcement of nitrosamine impurities as perceived risk TB > cancer risk
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Infectious Disease HIV/AIDS & Opportunistic Infections

DEFINITION AND CLINICAL MANIFESTATIONS
● Acute HIV: mono-like syndrome w/ rash, LAD, fever, oral ulcers, pharyngitis, myalgias, diarrhea; presents 3-6w after infection
● AIDS: HIV w/ CD4 count <200 or AIDS-defining illness
HIV SCREENING AND DIAGNOSTICS
● Screen all 15-65yrs once, every pregnancy, dx of another STI, PWID annually, commercial sex (CS), MSM >1 partner since last
test, partners of all risk pts. MA: verbal informed consent req. HCP can consent for incapacitated pt (e.g. ICU)
● Preferred: 4th gen HIV 1/2 Ab/p24 Ag assay: mean detection limit 18d (STD 2017;44:739). If +, f/u w/ HIV 1/2 Ab differentiation assay
● HIV RNA PCR (viral load, VL): mean 12d, high Sn/Sp but slow, expensive; used for: 1) concern for acute HIV (Ab/Ag testing are
negative early in disease course); 2) confirmation of HIV diagnosis; 3) treatment efficacy in known HIV
PROPHYLAXIS
● PrEP (Pre-Exp): offer to any pt w/ risk of acquiring HIV: serodiscordant couple, STI last 6mo, inconsistent condom use, PWID,
risk sex (JAMA 2019;321:2203). Transmission risk near zero if HIV+ partner has undetectable VL (JAMA 2016;316:171)
o Prior to initiation: negative HIV test, screen for HBV/HCV, other STIs, Cr, pregnancy test
o Daily* regimen: TDF/FTC (Truvada) qd risk (40-75%, >95% w/ excellent adherence), d/c when risk is no longer present.
TAF/FTC (Descovy) also FDA-approved (except for pts w/ receptive vaginal intercourse)  cost, wt gain, renal/bone issues
*Injectable form (cabotegravir extended-release) also recently FDA approved (q2month) (NEJM 2021;385:595)
o Event-driven PrEP: Truvada “2-1-1”: double dose 2-24h before sex, then 1 dose daily x 2d (not FDA-approved). If discrete
exposure (e.g. vacation), start Truvada qd 1w prior and for 1mo after (MSM only) (Lancet HIV 2019;7:113)
o Monitoring: HIV q3mo, Cr q3-6mo (stop Truvada if eGFR <60, consider Descovy eGFR 30-60), STIs q3mo, pregnancy q3mo
● Non-Occupational Post-Exp: pts ≤72h after ↑risk exposure to HIV; case-by-case decision if HIV status of source unknown; check
HIV Ab/Ag, HBV, HCV, STIs. Tx: 1) Biktarvy, 2)Truvada or Descovy + doluegravir, x28d; if ≥1 nPEP in last year, consider PrEP
BASIC EVALUATION FOR NEWLY DIAGNOSED HIV **ID consultation is advised**
● CD4 count w/ %, quantitative HIV RNA (VL), genotype/resistance, CBC/diff, BMP, UA, lipids, 3-site GC/CT, syphilis Ab, TST/IGRA if
no prior TB hx, Hep A/B/C, MMR w/ vax PRN, VZV if nonimmune, hCG, cervical and/or anal Pap, ± HLA B*5701 (IDSA: CID 2020)
● Initiate ART early through referral at all CD4 levels to mortality (NEJM 2015;373:795); exceptions: crypto meningitis & therapy for
HIV/TB co-infection (NEJM 2014;370:2487). ART can often be initiated prior to genotype, even in risk pts (AIDS 2018;32:17)
● Recheck VL after 2-4w, then q4-8w until suppression achieved  monitor VL q3-4mo
T R E A T M E N T : choose based on individual pt factors, DDIs, resistance, HLA B*5701 (abacavir hypersens.) (JAMA 2023;329:63)
● ART naive: 2 NRTI (typically TAF/FTC or TDF/FTC) + 1 of another class (often integrase inhibitor e.g. dolutegravir or bictegravir)
● Pregnancy: if new dx, 1st line TDF/FTC or abacavir-lamivudine (ABC/3TC) + dolutegravir; if prev well treated, cont existing regimen
HOSPITAL MANAGEMENT OF PEOPLE WITH HIV
● Patient on ART: determine regimen & adherence; typically continue ARVs (interruptions can disease progression)
o If ARVs must be held, hold all ARVs and c/s ID. Beware drug-drug interactions esp ritonavir boosted PIs (check DDI database)
o ARVs historically a/w with lactic acidosis (AZT, ddI, d4T) rarely used nowadays. If pt. has elevated lactate look for other causes.
● Patient not yet on ART: prioritize OI tx, ppx, c/s ID re: early inpt vs outpt initiation of ART
● IRIS: worsening sx of underlying infxn (TB, CM, MAC, CMV, others) 1-3mo post-ART initiation, risk if CD4 count
o Early ART initiation safe after OI dx (PLoS ONE 2009;4:e5575) (except in CNS TB or crypto meningitis, or TB pericarditis)
Opportunistic Infections Prophylaxis Summary Recommendations for HIV in the US (HIV.gov 2020: Full, Tables)
CD4 Opportunistic Infection Prophylaxis Criteria for D/C
Influenza, HAV, HBV, HPV, VZV, S. Vax: Flu; HAV, HBV, HPV, PCV15 or 20, PPSV23 after 8w; no live
All None
pneumo (most common OI), TB vax w/ CD4<200; LTBI: see Tuberculosis
Pneumocystis jirovecii (or hx of thrush) TMP-SMX DS qd (preferred) or 1 SS qd or dapsone 100mg qd or
<200* CD4 >200 x 3mo
*screen for cryptococcus with serum CrAg atovaquone 1500mg qd
Histo (hyperendemic or exposure; not in
<150 Itraconazole 200mg PO qd CD4 >150 x 6mo
MA)
TMP-SMX DS qd or dapsone 50mg qd + pyrimethamine 50mg qw +
<100 Toxoplasma CD4 >200 x 3mo
leucovorin 25 qw
<50 Mycobacterium avium complex (MAC) Azithro 1200mg q1wk if not on ART When ART initiated
Treatment of Specific OIs in Adults with HIV (*review renal dosing for reduced GFR)
Pathogen Diagnosis 1st Line Treatment
See Invasive Fungal Infections for diagnostics and therapeutics for PJP and Cryptococcus, Tuberculosis for TB
Oral/genital: DFA, PCR, viral Cx Orolabial: acycl 400mg PO q8h/valacycl 1g PO q12h x5-10d;
Herpes Simplex Virus (HSV)
CNS: LP + CSF PCR Genital: tx x5-14d; CNS: acycl 10mg/kg IV q8h x3w
Retinitis: ophtho exam; Colitis/esophagitis: bx; PNA:
Gancicl IV  valgan PO w/ improvement. Consider foscarnet
Cytomegalovirus (CMV) bronch w/ cytopath; Neuro: CSF PCR, brain Bx,
for resistant dz
Blood: PCR
CT/MRI: ring-enhancing; most pts IgG+ but not IgM+, Pyrimeth 200mg x1; then by wt + sulfadiazine + leucovorin qd
Toxoplasma gondii
brain Bx if tx fails (to r/o CNS lymphoma) x6w
PML MRI: non-enhancing lesions; LP: JCV PCR Only disease-modifying tx is ART
Mucocutaneous candidiasis Clinical dx: white plaque removed w/ tongue Oral: fluc 100mg PO x7-14d; Eso: fluc 100-400mg PO/IV or
(esophageal/oral) depressor, +KOH; EGD + Bx itra oral soln 200mg PO qd x14-21d
(Clarithro 500mg BID > azithro 600mg qd) + ethambutol
MAC Cx (blood/sputum/bronch/marrow/tissue), AFB stain
15mg/kg qd
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Infectious Disease Transplant ID

G E N E R A L P R I N C I P L E S (AJT 2017;17:856)
• Early infections: donor-derived, nosocomial/reactivation early, followed by OIs as immune suppression peaks
• Late infections: community-acquired infections, fungal infections
• Pre-transplant evaluation: check mumps/measles/rubella/VZV/CMV/EBV/HAV IgG, HBV (sAb, sAg, cAb), HCV, HIV, syphilis,
Toxoplasma, TST/IGRA. Consider: endemic fungi (esp. Coccidioides), T. cruzi, Strongy. Goal: immunize or treat prior to txp
o Serologic tests are helpful to identify latent infection pre-transplantation, but less useful after transplant for acute disease
Infections After Hematopoietic Stem Cell Transplant (HSCT) Infections After Solid Organ Transplant (SOT)
<4wk. 1-12mo. >12mo.
Adeno, BK
EBV, HCV, HBV
Donor- HSV

Virus
derived HHV 6,7 HPV, JC/PML, PTLD
VZV
CMV, community-acquired
Aspergillus Aspergillus

Fungus
Candida Endemic fungi Crypto
Mucor PCP Mucor

Surg.- Listeria, Nocardia

Bact.
related TB, non-TB mycobacteria
Toxo, leishmaniasis

Para.
Adapted from AJT 2017;17:856
Strongy, T. cruzi
H S C T P R O P H Y L A X I S (J NCCN 2016;14:882)
- Candida: fluconazole 400mg daily (d0-365 at MGH)
- HSV/VZV: famciclovir 250mg BID, acyclovir 400mg q8-12h or valacyclovir 500mg BID (d0-365)
- PCP: T/S (1 DS > SS qD, 1 DS MWF); also covers Toxo, Nocardia, Listeria; alternatives: atovaquone, dapsone (d0-180 or 365)
- High-risk HBV reactivation: entecavir or tenofovir
- CMV: pre-emptive monitoring of VL in high-risk pts & initiate tx (valganciclovir or ganciclovir) when  in VL vs. ppx in high-risk pts.
Letermovir (CMV-specific; no activity against HSV) can be considered for ppx in select cases (NEJM 2017;377:2433)
Select Transplant-Associated Infections (ID c/s is advised)
Pathogen Clinical Syndrome Diagnosis/Treatment Additional comments
Dx: serum PCR (may be ⊝ in colitis,
15%) ± bx involved organ (GI, BAL w/ Most common infxn s/p SOT.
cytopath) Highest risk: D+/R- in SOT and D-/R+
Fever, malaise, leukopenia, +/- hepatitis, Tx: PO valganciclovir vs. IV in HSCT. May rejection and
CMV
colitis/esophagitis, pneumonitis ganciclovir. Consider resistance testing susceptibility to OIs. Repeat VL at
if not improving (UL97, UL57). Alt Tx: least 7d apart (t1/2 of CMV), not
foscarnet or maribavir (CID comparable between labs
2021;75:690)
In contrast to HIV, there is limited
PCP Subacute dyspnea, hypoxemia, fever See Invasive Fungal Infections
data to support the use of steroids
Nephritis w/ AKI, ureteral stenosis, Dx: BK PCR +/- bx Mainly in renal txp (nephritis) and
BK Virus
hemorrhagic cystitis Tx: immunosuppression HSCT (hemorrhagic cystitis) pts
Progressive multifocal Dx: MRI brain w contrast, LP w JC Mainly in pts with HIV, but also w
JC Virus leukoencephalopathy (ataxia, PCR heme malignancies, organ tx, and pts
hemiparesis, VF deficits, cognitive ∆) Tx: immunosupp, optimize ART receiving lymphocyte-targeted agents
Hyperinfection syndrome: fever, n/v/d,
Ivermectin 200mcg/kg/d until stool ⊝ Identify at-risk individuals and tx pre-
Strongyloides cough/wheeze, hemoptysis, ⊝ eos; 2°
x2w txp
polymicrob. bacteremia (GNRs)
Symptom-Driven Diagnostics
CXR, CT chest, induced sputum (GS/Cx, consider AFB stain, MB Cx, PCP exam), Legionella urine Ag (Sn 70-90%, Sp
SOB 100%), viral resp panel. If cavitating or nodular lesions: 1,3-β-D-glucan/galactomannan, sCrAg, urine/serum histo Ag,
early bronch w/ BAL. NB: engraftment syndrome, cryptogenic organizing PNA also on DDx
Stool Cx, O+P (consider micro add-on for: Cryptosporidium, Cystoisopora, Cyclospora, Microsporidia), C. diff, CMV PCR. If
Diarrhea
high suspicion for viral colitis (e.g., CMV, adeno), c/s GI re: colo w/ Bx. In HSCT, consider typhlitis (NEC) and GVHD
CT head, LP (OP, GS/Cx, glucose, TP, HSV PCR, CrAg, save for more tests). NB: fludarabine, cytarabine, calcineurin
AMS/HA
inhibitors also a/w encephalopathy
Rash Low threshold for skin biopsy (path + cx). GVHD, medication allergy, HSV, cellulitis, local vs disseminated fungal infection
Leukopenia CMV PCR, EBV PCR, consider tickborne illnesses during the correct season or if frequent blood transfusions
If post-HSCT, consider viral (HAV, HBV, HCV, EBV, CMV, HSV, adenovirus & more rarely enterovirus and HHV6), Candida,
Hepatitis
and non-infectious (GVHD, iron toxicity, DILI, hepatic sinusoidal obstruction syndrome)
AKI UA/UCx, renal U/S, BK PCR if renal tx. Consider med toxicity and check levels (esp tacro, cyclosporine)

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Infectious Disease STIs & Travel Medicine

S E X U A L L Y T R A N S M I T T E D I N F E C T I O N S ; Routine STI testing in asymptomatic adults (CDC 2021)
Lesions Symptoms Diagnosis Treatment
1st: anti-treponemal CMIA (Sn & Sp
1°: painless, firm, round ulcer >98%); generally, remains ⊕ for life Prevention: see DoxyPEP below**
2°: fever, condyloma lata of skin/mucus 1°/2°/early latent: benzathine PCN G 2.4milliU
If CMIA⊕, lab reflexes to RPR. RPR
membranes, rash, LAD, uveitis IM x1
Syphilis* titer gives info on disease staging.
3°: aortitis/aneurysm, disseminated 3°/late latent: benzathine PCN G 2.4milliU IM
(T pallidum) Pregnany & anti-cardiolipin can cause
gummas, CN palsies, tabes dorsalis qw x3
(CDC Pocket false ⊕. CSF VDRL if c/f neurosyphilis
(impaired gait, sensation, reflexes) Neuro: IV PCN G 3-4milliU q4h or infusion x10-
Guide; PCOI) (IJSTD AIDS 2006;17:768)
Latent = by definition, asx (early <1y; late 14d (CDC 2021)
Painless

>1y or unknown). Highly infectious in 1°, If CMIA ⊕,ndRPR⊝: send out test to PCN allergy: try to desensitize
2° Neurosyphilis can occur at any stage state for 2 treponemal test (TPPA) to Serologic cure = RPR falls by factor ≥4
confirm CMIA⊕
1°: transient, painless anogenital lesion
LGV* Chlamydia NAAT detects LGV serovars
2°: 2-6w later, painful inguinal LAD Doxy 100mg BID x21d + aspiration of buboes
(C trachomatis LGV-specific PCR available as sendout
3°: pelvic/abd LAD, inflamm diarrhea, (CDC 2021)
serovars L1-3) test
abscess (“genitoanorectal syndrome”)
GI/Donovanosis Painless progressive beefy red ulcerative Presence of Donovan bodies in Azithro 1g qw/500mg qd x3w until healed (CDC
(K granulomatis) genital lesions phagocytes on bx specimen 2021). Relapses can occur 6-18 mo s/p tx
Acyclovir/valacyclovir. Consider episodic vs.
Genital herpes Prodrome  painful vesicles  ulcers Confirm clinical dx with PCR of vesicular
chronic suppressive tx based on frequency,
(HSV2>1) 1° infection: systemic sx ± LAD fluid from unroofed lesion
Painful

severity, & risk of spread (CDC 2021)

Chancroid* Painful genital/perianal ulcer 5-7d post- Usually clinical with negative Azithro 1g or CTX 250mg IV (CDC 2021) x1;
(H ducreyi) exposure w/ inguinal LAD ± drainage syphilis/HSV; GS/Cx, PCR in some labs often empiric PCN for syph; eval partners
Discharge Symptoms Diagnosis Treatment
Prevention: see DoxyPEP below**
Vaginal/cervical: can self-swab, vaginal
Vaginal/cervical: frequently asx, Gonorrhea: CTX 500mg IM x1, 1g if > 150kg
Gonorrhea* > urine NAAT (Sn >65%, >57%)
mucopurulent cervicitis, urethritis, PID (CDC 2021); Chlamydia: doxy 100mg BID PO
(N gonorrhoeae), Penile: first-catch urine NAAT > urethra
Penile: dysuria, purulent discharge, x7d > azithro 1g PO x1 (CDC 2021)
Chlamydia* Pharyngeal/anal swab based on hx (can
epididymitis Concurrent infxn/empiric tx for both: CTX + doxy
(C trachomatis) self-swab) (BMJ Open 2019;9)
Pharyngitis or anorectal infxn possible (azithro-R gonorrhea) (MMWR 2020;69:1911).
NB: Cx if c/f resistance
Eval partners†
Mycoplasma Vaginal/cervical: cervicitis, PID, often
Vaginal/cervical: vaginal swab PCR If failed tx GC/CT (e.g. with doxycycline):
genitalium (Suspect in asymptomatic
Penile: urine or urethral swab PCR moxifloxacin 400mg qd x7-14d (esp. if
pts who fail tx for Penile: dysuria, purulent discharge
(send out test) macrolide-R) (CID 2015;60:1228)
GC/CT) Anorectal: proctalgia, dyschezia
Vaginal/cervical: purulent malodorous Metronidazole or tinidazole 2g PO ±GC/CT tx;
Trichomoniasis
discharge, pruritus, dysuria, dyspareunia Wet mount  vaginal swab NAAT eval partner
(T vaginalis)
Penile: usually asymptomatic Retest after 3 months
Virus Risk factors Screening Prevention
HIV* Bacterial STI, inconsistent condom use, See HIV/AIDS & OI section PrEP (see HIV); condom use
HIV+ partner, persons who inject drugs
HPV Rectal HPV: receptive anal intercourse Rectal: anal Pap, anoscopy HPV vaccine series per USPSTF
Cervical HPV: vaginal intercourse Cervical: Pap per USPSTF
Hepatitis B MSM, PWID, >1 partner in 6 m, HBV+ HBs Ag (can have false + if recent HBV vaccination series
partner, HCV, HIV, other STIs HBV vaccine), HBs AB, HBc Ab
Hepatitis C MSM, HIV+, group / chem-sex, persons HCV Ab (remain + after tx), HCV VL if Condom use, needle exchange,
who inject drugs, intranasal cocaine, non- Ab+ professional tattoos
professional tattoo parlor
*Reportable to public health department. Requirements for reporting other STIs may differ by state.
**DoxyPEP: Consider for trans women and MSM w/ + test for GC/CT or syphilis w/in 1yr. Doxycycline 200mg PO x1 within 72hrs of unprotected sex (oral,
anal, or vaginal). Can reduce reinfection risk by >50% (NEJM 2023;388:1296). Not yet shown to be effective for other demographic groups (NEJM 2023;389:2331).
†In MA: After making a new chlamydia diagnosis, offer treatment for any partner w/i 60d without exam (instructions). Laws differ by state (CDC 2023).

TRAVEL MEDICINE
Pre-Travel Counseling
• Patient: medical conditions, med supply, dosing schedule changes for travel (e.g. insulin), supplemental O2 needs, allergies (epi pen),
pregnancy, immunization history, prior malaria exposure
• Trip: duration, season, purpose of trip, exposures based on itinerary (urban v rural, cruise ship, animals, cave or water exposure)
• General Counseling: sunscreen (SPF 50+), seatbelt/helmet, safe sex, hand hygiene, animal avoidance, considerations re: tap water & raw
foods, considerations re: travel & evacuation insurance, contingency planning if ill. Provide patient with CDC Travel Tips
• Arthropod bite avoidance: exposed skin, insect repellant (DEET, picaridin, Metofluthrin, IR3535), treated clothing, mosquito nets
Immunizations: Ensure routine vaccinations are UTD, then use “Pre Travel PREP” or CDC site for country-specific recs; common travel vaccines:
Influenza, Yellow Fever, Meningococcal, Typhoid, HAV, HBV, Japanese encephalitis, pre-exposure rabies, cholera
Malaria Prophylaxis (typically S/SE Asia, Africa, Central/S America): CDC tool: Rx options based on resistance. ~1w pre-travel, up to 4w after.
Daily: atovaquone-proguanil (Malarone), doxy, primaquine Weekly: mefloquine (a/w bad dreams; avoid if psych hx), chloroquine
Traveler’s Diarrhea (CDC Yellow Book). Pathogens: ETEC, C. Jejuni, Shigella spp, Salmonella spp, Vibrio spp, norovirus, rotavirus, Giardia, etc.
Tx: mild: loperamide; severe (fever, dysentery, travel interference, age>70): azithro 500mg x3 > FQ or rifaximin, avoid loperamide
Infections in a Returning Traveler: Broad ddx, consider geography, exposure risk, pt vulnerability, incubation periods. Common culprits:
Malaria, dengue, EBV/CMV, tick-borne, typhoid fever, respiratory viruses, TB, STIs, typical infections (CAP/UTI etc) (NEJM 2017;376:548)
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Infectious Disease Tickborne Diseases

T I C K B O R N E D I S E A S E S (CDC Guide)
Approach to tick bites and prevention:
Physical prevention: daily tick check, shower after outdoors, check pets, clothing and gear, walk in center of trails (CDC handout)
Chemical prevention: DEET, picaridin, IR3535, lemon eucalyptus oil, para-menthane-diol, 2-undecanone; 0.5% permethrin for fabrics
Removal: ASAP, pull straight out w/o twisting or jerking w/ clean tweezers, then wash area w/ soap/water or rubbing alcohol
Approach to tickborne illness:
Hx: hiking/outdoor activity, late spring-early autumn. Most (50-80%) will NOT recall tick bite (Tick Borne Dis 2019;10;694)
Sx/signs/labs: fever, myalgias, arthralgias, rash; WBC & PLT, AST & ALT. Coinfection is common
Empiric tx: if high suspicion, send all dx incl. babesia smear (not tx by doxycycline), start empiric doxycycline 100mg PO BID
Other zoonoses to consider: tularemia (rabbits), leptospirosis (rats), brucella/coxiella (cows/sheep), though less common
Tick identity and geography (expanding iso climate change):
Amblyomma americanum (lone star/turkey tick, Ehrlichia): widely found in eastern US, more common in the south
Dermacentor variabilis (American dog/wood tick, RMSF): East of Rocky Mtns. (particularly southeast), limited areas of Pacific Coast
Ixodes scapularis (deer/bear/black-legged tick, all others below): Northeast, Mid-Atlantic, and central Midwest

Disease Presentation Diagnosis Treatment

Avoid serologic testing w/o Early: doxy 100mg PO BID
Early localized (days to 1 month): erythema migrans (3-30
specific objective s/sx and x10d OR Amox 500mg TID
d of bite, red ovoid lesion ± central clearing, 80% of pts), ±
endemic area/exposure x14d OR Cefuroxime 500mg
fever, fatigue, myalgia, arthralgia, HA, neck stiffness,
Early: can dx w/ clinical BID x14d
regional LAD. Asx in 30% cases
Early disseminated (wks-mos): multiple EM lesions, sx suspicion only (seronegative
Lyme Disease early on) Disseminated (neuro,
above ± migratory arthralgias 60%; neuro 15%: CN
(IDSA: CID Early & Late disseminated cardiac involvement,
palsies, meningitis, mononeuritis, radiculopathy; cardiac
2021;72:e1; 1. Screening ELISA IgM/IgG arthritis): CTX 2g q24h x14-
1%: heart block, myopericarditis; LAD; conjunctivitis,
Lancet 2. Western blot (WB) if screen 28d based on severity;
keratitis, retinal vasculitis
2012;379:461; ⊕ or equivocal check IDSA for specific recs
Late disseminated (mos-yrs): arthritis 60% (mono- or
NEJM on regimen
polyarthritis of large joints, esp. knee), neuro (mild
2014;370:1724)
encephalopathy, peripheral neuropathy) IgM⊕ = 2 of 3 bands detected
Ppx: doxy 200mg PO x1 IF
Post-treatment syndrome (yrs): nonspecific sx; fatigue, IgG⊕ = 5 of 10 bands detected
tick was attached &
MSK pain, cognitive dysfunction; NOT a “chronic infection”
engorged ≥36h in endemic
and no evidence of dysregulated immune response so no IgG⊕ at 6-8w; if ELISA/WB area AND ≤72h after tick
role for abx or IVIG (CRAI 2022:62:264) IgM⊕ IgG⊝ at 6-8w: false ⊕ removed
Mild-mod: 7-10 d of
Labs: DAT⊝ hemolytic
Asymptomatic: 20% adults; no tx unless smear ⊕ > 1 mo. atovaquone 750mg q12h +
anemia, PLT, ALT/AST
Mild-to-moderate: 1-4 wks after bite or 1-6 mos. from azithro 500mg x1 -> 250mg
Babesiosis Blood smear: ring forms in
blood transfusion; fever, fatigue, chills, sweats, myalgias, qd
(IDSA: CID RBC (Maltese cross rare);
anorexia, HA, n/v, cough – can be subacute (up to 6mo) Severe: c/s ID; Azithro
2021;72:e49; parasitemia = %infected RBCs;
Severe (usually immunosupp, malignancy, HIV, asplenic, 500mg IV qd + atovaquone
NEJM monitor in immunosupp pts
>50yo): sx above w/ pronounced n/v, diarrhea, 750mg q12h; consider
2012;366:2397) until neg smear
Complications: severe hemolysis, DIC, ARDS, exchange transfusion if
PCR: very Sn & Sp, not widely
multiorgan failure, CHF parasitemia > 10% or severe
available
hemolysis or organ failure
Borrelia Relapsing fever, HA, AMS, photophobia, chills, myalgias;
Mild: Doxy 100mg BID x14d
miyamotoi WBC/PLT, ALT/AST (mimics anaplasmosis); rash PCR > serology
Hospitalized: CTX 2g qd x
(Lancet Microbe usually absent; meningoencephalitis possible in NB: EIA cross-reacts w/ Lyme
14-28d
2022;10:e772) immunocompromised (NEJM 2020;383:1578)
Powassan Serum/CSF serology (send-out
Fever, chills, malaise, somnolence, n/v, encephalopathy Supportive care, no
virus to state lab): IgM ELISA, if +
MRI: T2/FLAIR hyperintensities (esp. basal ganglia) antivirals known to be
(CID then neutralizing antibody
CSF: lymphocytic pleocytosis (can also be neutrophilic) effective
2016;62:707) testing
PCR; morulae in neutrophils on
Anaplasmosis Common: fever, malaise, myalgias, HA, n/v, arthralgias, smear in 20-80% of pts Doxy 100mg BID x 7-10d
cough; rash is less common (<30%)
PCR; morulae in mononuclear
Ehrlichiosis Labs: WBC/PLT, ALT/AST, LDH, ALP, CK IDCNA 2015;29:341
on smear in 1-20% of pts
3-5d prodrome (fever, malaise, myalgias, HA, n/v)  Doxy 100mg BID x5-7d
Rocky Clinical dx: start empiric tx
progressive macular rash  petechial rash (limbs  minimum + ≥3d after afebrile
Mountain Serology: undetectable until 7-
trunk, spares face, end stage on palms and soles (tx for all ages)
Spotted Fever 10d after sx onset; repeat 14-
characteristic)
MMWR 21d after sx onset to confirm
Severe: meningoencephalitis, shock, ARDS, DIC, organ Can consider load 200mg x1
Recomm Rep. PCR: special sendout
failure if critically ill
2016;13:1 Skin biopsy: 70-90% Sn
Labs: WBC variable, PLT, Na, AKI, LFTs, INR

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Infectious Disease Mpox & Ectoparasites

VIROLOGY AND EPIDEMIOLOGY
Caused by monkeypox virus, an orthopoxvirus closely related to smallpox. Three clades: Clade I (Central Africa, ~10% mortality rate);
Clade II (Western Africa, 0.1% mortality rate); Clade III (2022 global outbreak, related to clade II, low mortality). (NEJM 2022;387:1783).
Animal-to-human transmission: bites, infected animal fluids, preparation of bush meat. Rodents are likely reservoir.
Human-to-human transmission: direct contact with infectious lesions; respiratory secretions; transplacental; viral DNA found on fomites
and bodily fluids (semen, feces, urine, saliva), but unknown if these are mechanisms of transmission
2022 global outbreak: 98% cases in MSM and close sexual contacts. 40% pts HIV+ (conflicting data on severity vs HIV- pts, likely more
severe in uncontrolled HIV but confounded by delays in tx), 40% on HIV PrEP. Up to 30% associated with concomitant STIs. (HIV Med
2022;BMJ 2022;378:72410;Lancet 2022;400:661;MMWR Morb Mortal Wkly Rep 2022;71:1412).
CLINICAL MANIFESTATIONS
Incubation period: mean 13 d, range 3-34 d
Prodromal phase: associated with viremia; 1-4 days with high fever, headache, fatigue, lymphadenopathy
Eruptive phase: 14-28 days with mucocutaneous lesions (including palmoplantar), progress from macules  papules/vesicles 
pseudopustules (filled w/ debris rather than pus)  crusting and desquamation, may scar. Lesions well circumscribed, umbilicated a/w
pain/pruritus. Clinical images: National STD Curriculum. 2022 outbreak commonly w/ anogenital lesions (NEJM 2022;387:679).
Complications:
• Proctitis: anorectal pain, bleeding, tenesmus, purulent discharge. Associated with receptive anal sex. Anoscopy not routinely
performed due to severe pain. Risk of bowel obstruction, perforation.
• Pharyngitis/tonsillitis: pain may limit PO intake.
• Ocular: conjunctivitis, blepharitis, keratitis, blindness.
• CNS disease: demyelinating encephalitis/encephalomyelitis/transverse myelitis. LP consistent with viral meningitis but may be
negative for mpox via PCR. (MMWR Morb Mortal Wkly Rep 2022;71:1212).
• Superimposed cellulitis: most common complication, in anogenital region may progress to Fournier’s.
DIAGNOSTICS
Consider testing in patients with consistent rash and epidemiological risk factors  c/s infection control/ID; co-test for STIs, HIV.
Orthopoxvirus PCR: vigorously swab lesions to collect cells (do not attempt to unroof), collect 2 swabs/lesion and can swab multiple
lesions. PCR of throat swabs and blood used for epidemiological, but not clinical testing.
Serologic testing: CDC IgM and IgG test  positive 5 and 8 days after rash onset
Lumbar puncture: if c/f encephalitis/myelitis  cell count, glucose, protein, orthopoxvirus PCR, IgM
Biopsy: may be helpful if multiple concomitant infections present (e.g. in immunocompromised patients). Lesions are positive for
orthopoxvirus and histologically distinct from herpesvirus lesions.
THERAPEUTICS
Most patients have mild disease, supportive care only. Hospitalization for complications and/or severe pain.
Tecovirimat (TPOXX): high preclinical efficacy but limited human data. Indicated for hospitalized pts, high risk pts (immunocompromised,
pregnant, skin disease), or oropharyngeal/anogenital/ocular/CNS involvement. Most common side effects: fatigue, nausea, HA. Tx 14d.
(JAMA 2022;328:134;Open Forum Infect Dis 2022;9:377;NEJM 2022;387:579;NEJM 2022).
• PO: take within 30 mins of fatty meal. 40-119 kg: 600 mg q12h; ≥120 kg: 600 mg q8h
• IV: contraindicated CrCl<30 mL/min. 35-119 kg: 200 mg q12h; ≥120 kg: 300 mg q12h
Cidofovir/brincidofovir: limited data suggests less efficacious than tecovirimat. Renal & hepatic toxicity. (Lancet Infect Dis 2022;22:1153).
Trifluridine/vidarabine eye drops: use w/ tecovirimat for ophthalmic infections, q4h 7-10 d, c/s optho. (Arch Ophthalmol 2003;121:715).
CNS involvement: c/s neurology, high dose corticosteroids for demyelinating encephalitis/myelitis (JAMA Neurol 2022;79:1180)
PROPHYLAXIS
Vaccination: JYNNEOS  attenuated nonreplicating vaccinia virus, also confers smallpox immunity. Safe in immunocompromised
patients. Involves two doses, the second dose given four weeks after the first. Post-exposure prophylaxis: Vaccination within 14 d of
close/sexual contact with infected patient or presumed exposure (MSM who have had sex in areas where mpox is spreading). Pre-
exposure prophylaxis: Offer vaccination for MSM/trans/nonbinary patients who have had at least one STI or >1 sex partners in last 6 mo,
or any patient who has had sex at a commercial/public sex venue in last 6 mo. Limited data suggests breakthrough infections rare and mild
(NEJM 2019;381:1897;NEJM 2022;387:2477).
C O M M O N E C T O P A R A S I T E S (Am Fam Physician 2019;99:635; NEJM 2020;382:2230)
• Scabies: Initial infxn w/o sx then intense pruritis ~6wk after inoculation 2/2 hypersensitivity rxn. Sx classically worsen at night. Exam
w/ excoriated papulovesicles +/- burrows in interdigital spaces, intertriginous skin, wrist, inguinal region
o Rx: 5% permethrin cream applied jawline downwards after bathing w/ removal after 8-14hr (reapply 7d later)
o Clothing/bedding needs hot water (>130°F) + high heat drying OR 1wk isolation in sealed plastic bag
• Lice: Pruritis from saliva of lice. Live lice should be visualized. Nits ≠ infestation. W/o human blood meal, lice die ≤2d
o Rx: head lice - 1% permethrin shampoo (re-apply 7-10d later since not ovicidal); pubic lice - 1% permethrin cream (reapply 9-
10d later if persist + test for STIs + rx partners); body lice - laundry and hygiene +/- permethrin
o Use high-heat (>130°F) laundering/drying exposed items + vacuuming OR 2wk isolation in sealed plastic bag
• Bedbugs: Suspect if recent travel. Crops of bites on exposed skin not covered by sheets or clothing. “Breakfast, lunch, and dinner”
sign. Feces leave black debris on bedding + furniture. W/o blood meal, bedbugs can still live 70d
o Rx: Resistant to insecticides. Use mechanical methods. Clothing/bedding needs washed at high heat (>140°F). Can expose
items to -4°F for 2hr. Physical removal via vacuum. Isolate items in plastic bags for prolonged periods
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Infectious Disease Fever of Unknown Origin

D E F I N I T I O N (NEJM 2022;386:463; CCM 2008;36:1330; Medicine 1961;60:1)
• Classically T>38.3C on multiple occasions for ≥3w, persisting w/o diagnosis despite ≥3d of inpatient investigation or 3 ambulatory
visits (Curr Clin Top Infect Dis 1991;11:35; Br J Hosp Med 1996;56:21); newer recommendations call for T > 38 C (AMJMED 2022)
Special subpopulations: nosocomial (first fever > 24h of hospitalization), immunodeficient, neutropenic (current ANC<500 or expected in 1-
2d), HIV-associated, travel-associated. More often an atypical presentation of a more common disease than very rare disease.
W O R K U P (AJM 2015:128;1138e1)
• Ddx: In US, most commonly rheumatologic > infectious > malignant > Etiologies of FUO
other *bold = common causes (OFID 2020;7:ofaa132)
o 25-50% of cases, no source is identified (Medicine 2007;86:26) Abscess (perianal, brain, dental), HIV, EBV,
• History: fever pattern, B symptoms, PMH (incl. dental hx, CMV, HHV6-8, HBV, HCV, endocarditis
immunocompromise), valvular dz, exposures (travel, birthplace, animal, (fastidious/HACEK, nutritionally variant Strep),
arthropod, food, blood products, sick contacts, sexual contact, drugs, nosocomial infection, hardware/graft infection,
occupation), TB risk factors, meds, vaccine hx, procedures/hospitalization, osteomyelitis, septic arthritis, sinusitis,
family hx complicated UTIs, TB (extrapulmonary), tick-
• Exam: dental caries/thrush, sinus and temporal artery tenderness,

Infectious
borne infections, endemic fungi (e.g.
thyromegaly, murmur, abd tenderness, HSM, eyes, fundi, lymph nodes, joints, cocci/histo/paracocci), malaria (#1 cause in
skin/nails, rectal, urogenital returned traveler, also now thought to be
• Initial: CBC, BMP, LFTs, ESR/CRP, UA/UCx, BCx x3 (diff. sites, min 5 d locally aquired in certain US states, CDC
incubation),CXR, HIV 2023), cat-scratch disease, toxoplasmosis, Q
o ESR: measure of chronic inflammation. Falsely elevated in ESRD, fever, brucellosis, bartonellosis, salmonella,
paraproteinemia, anemia, obesity, advanced age typhus, melioidosis, schistosomiasis, visceral
 Correction for age  ♂: age/2, ♀: (age/2)+10 leishmaniasis, Whipple’s disease,
o CRP: rises more acutely than ESR; may be falsely low in cirrhosis lymphogranuloma venereum
• Other labs to consider: IGRA, syphilis Ab, LDH, TFTs, SPEP/SFLC, ANA, Lymphoma, leukemia, MM, myeloproliferative

Malig.
ANCA, RF/CCP, cryo, CK/aldolase, EBV serologies, CMV PCR, ferritin, blood disorders, RCC, HCC, CRC, melanoma,
smear, HBV/HCV pancreatic, cervical, gastric, Castleman’s
• Imaging (Arch Intern Med 2003;163:545): CT C/A/P (71% Sn, 71% Sp), LENIs, Cryo, PMR, GCA, RA, Adult Still’s,
TTE/TEE, FDG-PET/CT (Sn 86%, Sp 52%, 58% yield, vertex to toes and IV
Rheum.

(JRA)/MAS, SLE, dermato/polymyositis,

contrast recommended J Nucl Med 2016;57:1913, AJR 2023;221), tagged sarcoid, HSP, PAN, Kikuchi’s, Takayasu’s,
WBC scan (Sn 45-60%, Sp 78-86%), maxillofacial CT Behcet’s, GPA/MPA/EGPA
• Tissue diagnosis: LN, liver (14-17% yield), BM (low yield at 0-2%), temporal Drug fever, serotonin syndrome, NMS,
artery (GCA), kidney (RPGN), LP if CNS findings DVT/PE/hematoma, hypothalamic
TREATMENT dysfunction, pheo, hyperthyroidism, alcoholic
Other

• Try to avoid empiric antibiotics and observe (unless hemodynamic hepatitis, cirrhosis, IBD, factitious, HLH,
instability or immunocompromised) familial periodic fever syndromes (FMF, Hyper-
• D/C possible offending meds IgD Syndrome, Schnitzler’s, TRAPS)
• If suspicion for GCA, strongly consider empiric steroids (prior to bx) to prevent vision loss/end-organ damage; must be reasonably
convinced infxn/malig are excluded
• If extensive workup ⊝, prognosis usually good, most cases defervesce (AJM 2015:128;1138e1)
ETIOLOGIES BY PATIENT POPULATION
Patient Population Etiologies
General
Infection 14-59%, rheumatic 2-36%, malignancy 3-28%, miscellaneous 0-18%, undiagnosed 7-51%
(Am J Med Sci 2012;344:307)
Elderly patients
Infx 25% (abscess 4%), rheum 31% (most common GCA/PMR), malignancy 12%
(Am Geriatr Soc 1993;41:1187)
Uncontrolled HIV* Infx 88% (dMAC 31%, PJP 13%, CMV 11%, histo 7%, other viral 7%), malignancy 8% (lymphoma
(CID 1999;28:341) 7%) *Mean CD4 count 58/mm3; Immune reconstitution syndrome
Neutropenic (refractory to abx)
Fungal infx 45%, bacterial infx 10-15% (resistant, biofilms), GVHD 10%, viral infx 5%, misc 25%
(NEJM 2002;346:222)
Returned traveler* Falciparum malaria (77%), tyhpoid fever (12%), paratyphoid fever (6%), leptospirosis (2%),
(AJTMH 2013;88:397) rickettsiosis (2%), dengue (1%)
*Only considers infectious etiologies, returned from Central or South America, Africa, Oceania, tropical and subtropical parts of Asia
SELECT CAUSES OF FUO
• Drug fever: dx of exclusion, broadly refers to any febrile response to medication. Can occur at any time while taking drug, with
resolution post-cessation (resolution can take up to 1w)
o Fevers can be in excess of >102F. Rarely, ⊕ accompanying signs (e.g., morbilliform rash, LFT elevations, eosinophilia)
o Mechanisms include: hypersensitivity rxn (incl. SJS/TEN), dysfunctional thermoregulation, aseptic meningitis, Jarisch-
Herxheimer reaction, NMS/serotonin syndrome, G6PD deficiency
o Medications commonly associated: antimicrobials (β-lactams, sulfa, macrolides), AEDs, dexmedetomidine, chemo
• VTE: DVT, PE, thrombophlebitis may cause fever. Usually low grade (6% w/ fever >101F and 1.4% >102F) (Chest 2000;117:39)
• Central fever: most commonly associated with SAH, intraventricular bleed, brain tumors (JAMA Neurol 2013;70:1499)

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Infectious Disease Rare Diseases at MGH

Epi & Transmission Symptoms Labs Diagnostic Tests Treatment (c/s ID)
Malaria Africa, Latin Am, Asia, Mid 12-35d incub (up to yrs if Anemia, PLT, AKI, BinaxNOW (RDT) + c/s ID; Variable
(Plasmodium spp) East, Eastern Europe P. vivax); fever, HSM, LFTs, glucose, thick/thin blood smear (see travel medicine) Promising
Anopheles spp. AMS, jaundice, petechiae acidemia w/ Giemsa RTS,S vaccine
Mosquito-borne viruses: Dengue, Chikungunya, and Zika are often indistinguishable clinically/epidemiologically; consider testing for all 3 if concerned
Dengue fever India, Asia/Pac, Africa, Lat Fever, retro-orbital HA, Lymphopenia, <7d sx onset = NAAT; Rest, fluid; avoid NSAIDs due
(DENV serotypes 1- Am arthralgia “break bone thrombocytopenia, IgG/IgM (cross-rxn w/ to  hemorrhagic sx
4; Flavivirus) A. aegypti & A. albopictus fever”, petechiae, shock Hct Zika); tourniquet test
Chikungunya fever Africa, Asia/Pac, Caribbean, Fever (>102 in chik), HA, Chik: lymphopenia, Chik: PCR if <7d sxs; Rest, fluid; avoid NSAIDs unless
(Alphavirus) Lat Am, S USA rash, polyarthralgia, thrombocytopenia, serology if ≥7d definitely not dengue. Chik:
conjunctivitis; Guillian- LFTs, AKI Zika: serology/plaque Rheum referral if pain >3 mo.
A aegypti & A albopictus
Zika virus Barré syndrome + fetal reduct.; serum/urine Vaccine for Chik (IXCHIQ) if age
(diurnal feeders); STI (Zika)
(Flavivirus) microcephaly (Zika) Zika: labs freq. nml PCR if <7d of sx, 18+.
serology if ≥7d of sx
West Nile virus Africa/MEast, Europe, Asx; fever, HA, myalgia, CSF pleocytosis Serum + CSF Abs > Rest, fluid
(Flavivirus) Americas 1% meningitis (lymphs) CSF PCR only for
Culex spp. (nocturnal) immunocomp. (c/s ID)
Leishmaniasis, C/S America, S Europe, Mid CL: painless ulcer(s), VL: cytopenias, Clinical dx, skin bx Variable, c/s ID; abx if
cutaneous/visceral East, E Africa, S Asia regional LAD LFTs PCR/smear/cx; rarely superinfected lesions
(Leishmania spp) Lutzomyia/Phlebotomus VL: fever, HSM, wt Ab
Bacterial Zoonoses: Coxiella, Bartonella quintana, and Brucella are important causes of culture-negative endocarditis
Cat scratch Worldwide Fever, LAD 1-3w, neuro, ESR/CRP,LFT Ab 1-2w; histology Variable, c/s ID
disease Cat bite/scratch, fleas ocular
(Bartonella henslae)
Leptospirosis Worldwide; tropics > temp. Fever, HA, myalgia, AKI, ALF, rhabdo, Serology if 3-5d sx Outpt: doxy 100mg BID x7d;
(Leptospira spp.) Water contaminated by jaundice, conjuc. suffusion anemia, hypoNa inpt: PCN G, doxy, or CTX
animal urine/sewage
Q fever Worldwide (except N.Z.) Fever, HA, myalgia, PNA, AST/ALT, Bili, Serology ≥7d Doxy 100mg BID x14d
(Coxiella burnetii) Aerosolized ungulate fluid endocarditis PLT, CK
Brucellosis Worldwide Fever, arthritis (SI/spine), AST/ALT, WBC Serology if 7-10d sx Doxy 100mg BID x6w +
(Brucella spp) Dairy products, ungulate endocarditis w/ relative lymph gent/streptomycin or rifampin
contact, lab exposure
Tularemia N America, Europe > Asia Regional LAD; Nonspecific; Serology if sx ≥2w; Streptomycin or gent 7-10d;
(Francisella 6 syndromes: ESR/CRP; PLT GS, Cx (cysteine + cipro or doxy 10-21d if mild dz
Arthropod bite, animal
tularensis) ulceroglandular, glandular, media)
contact (rabbit), food/water, oculoglandular, pharyngeal,
airborne PNA, & typhoidal
Rickettsia: in general, rickettsial diseases with eschars are scrub typhus, African tick-bite fever, RMSF, Mediterranean spotted fever, and rickettsialpox
Murine typhus SE Asia, N Africa, N America Fever, centrifugal rash, Plt, AST/ALT Serology 2w apart Doxy 100mg BID x7d
(Rickettsia typhi) Feces of infected rat fleas HA, myalgia
Scrub typhus India  E Asia; Pacific, Chile Eschar, fever, Plt, AST/ALT, Serology 2w apart; Doxy 100mg BID x7d;
(Orientia Bites from infected mite lymphadenopathy, Bili, AKI, WBC consider eschar bx azithromycin if tetracycline-R
tsutsugamushi) larvae (AKA chiggers) centrifugal rash, HA usually wnl
Helminths: if concerned about intestinal worms, albendazole is an effective and safe medication to give empirically while awaiting lab results
Schistosomiasis Africa, Brazil, MidEast, Asia Acute (3-8w): fever, urticaria, Eos (30-60%) in Serology 6-12w; Acute: pred 20-40mg x5d +
(Schistosoma spp) HA, swimmer’s itch. Chronic: acute, Plt; LFTs stool/urine microscopy praziquantel
Fresh water with free HSM, portal HTN, GN, usually wnl for speciation Chronic: 40-60 x1 of
cercariae from infected snails hematuria, neuroschisto praziquantel
Trichinellosis Worldwide, esp. Europe Abd pain, n/v, diarrhea  Eos, WBC, CK, Serology 2-8d; muscle Albendazole 400mg BID + pred
(Trichinella spp) Undercooked meat, esp. pork myalgia, weakness, ± LDH biopsy 30-60mg qd x8-14d
fever
Strongyloidiasis Rural tropics/subtropics; Skin rxn, epigastric pain, Eos, WBC; Serology Sn > stool, Ivermectin 200 mcg/kg/day x2d;
(Strongyloides Appalachia, SE USA diarrhea, resp. sx; fever, hyperinfection & but  Sp.  BCx, for 5-7d if disseminated. If from
stercoralis) Skin contact w/ soil w/ human n/v, sepsis/shock if disseminated dz (in may have GN endemic region scr. for loiasis
feces, fecal-oral, hyperinfection immunosupp.) w/ bacteremia (gut prior to tx. If RFs, scr. or tx prior
autoinfection normal eos translocation) to immunosuppression.
Other Infections
Typhoid fever India, SE Asia, Africa Fever, lethargy, abd pain, HR, LFTs, WBC Stool/blood Cx. BMBx Azithro/ciprofloxacin
(Salmonella enterica ‘rose spots’, diarrhea (WBC sign of 90% Sn. Serology Severe: CTX (meropenem if
serotype Typhi) Fecal oral; asymptomatic (>50%), constip. (30%), intest. perf.), anemia, effective in non- Pakistan or Iraq)
carriers HSM abnl coags endemic regions
Melioidosis SE Asia, Aus, US Gulf Coast Fever, PNA, skin abscess, WBC; other Blood Cx on Abscess I&D + IV mero/ceftaz
(Burkholderia Soil; aspiration, inhalation, community-acquired nonspecific values Ashdown’s agar, GS x2w  T/S x3mo
pseudomallei) percutaneous inoculation sepsis, GU c/w organ failure
Hantaviruses SW US, Lat Am, Eur., Asia Hemorrhagic fever, renal PTT, Plt, AKI, Serology via state Supportive care
Aerosolized rodent excreta failure, ARDS proteinuria department of health
Toxoplasmosis Worldwide Mono-like symptoms Atypical lymphs, Serology 1-7d; CSF 2- Tx if CNS, chorioretinitis, or
(Toxoplasma gondii) Cats; cont. meat/water AST/ALT 5d preg (consult MFM)
Multiple: NEJM 2017;376:548, NEJM 2018;379:557, NEJM 2007;357:1018, NEJM 2015;372:954, JAMA 2002;287:2391; Malaria: JAMA 2010;304:2048, J Clin Invest;2022:132, JAMA 2022;328:460; Dengue: NEJM 2012;366:1423; Zika: NEJM 2016;374:1552; Chikungunya: NEJM
2015;372:1231; West Nile: JAMA 2013;310:308; Cat scratch disease: Am Fam Physician, 2011;83; Brucellosis: NEJM 2005;352:2325; Schistosomiasis: NEJM 2002;346:1212; Typhoid: NEJM 2002;347:1770; Melioidosis: NEJM 2012;367:1035; Leishmaniasis: Am J Trop Med
Hyg 2017;96:24; Coxiella: MMWR 2013;62.3:1; Strongyloides: Am J Trop Med Hyg 2017;97:645.

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Infectious Disease Infection Control

Resources: Infection Control websites on Sharepoint and Ellucid for the most up-to-date MGH policies and list of diseases/conditions
requiring isolation. For additional support, work with unit-specific nursing leadership and contact Infection Control (x62036)
Standard Precautions: apply to all patients. Hand hygiene (HH) is the most important action to stop the spread of infection. Please
stay up-to-date re: source control for masking/hospital-approved eyewear.
• Disinfect hands with an alcohol-based hand rub (ABHR)
o Before entering and upon exiting the patient room
o After contact with the patient or items in the patient environment
o When glove use is indicated, HH is performed before donning AND after doffing gloves
o Hands are visibly soiled: wash hands with soap/water, dry hands, then apply ABHR
• Gloves/gowns for contact w/ blood, bodily fluids (e.g., wound), secretions, excretions, mucous membranes, broken skin
• Mask + eye protection for procedures that can splash blood, bodily fluids, or secretions (e.g., ABGs, paracenteses)
• Dispose of materials heavily soiled with blood or bodily fluids into biohazardous waste (red bag)
• Disinfect reusable patient equipment (e.g., personal stethoscope, U/S) with hospital-approved disinfectant wipes according to
instructions on label after patient contact/use
Transmission-Based Precautions (follow links in isolation column for additional details)
Isolation Risk & Transmission Description Examples
o Hand hygiene + nonsterile gloves + isolation gowns
o Do not touch phones, beepers, notes while in room
MRSA
Direct or indirect o Remove gown and gloves together only touching inside of PPE with
VRE
bare hands, dispose of PPE inside or immediately outside the room
Contact contact w/ pt or his/her MDROs
o Dedicate the use of equipment (stethoscope, BP cuff) to avoid sharing
environment CRE
w/ other pts. All equipment w/in the room is presumed contaminated
Disseminated HSV
o Disinfect reusable non-critical equipment (stethoscope) using hospital-
approved disinfectant wipes for pathogen of concern
Spore forming & o Contact precautions + hand wash soap/water + ABHR + private room C. diff
Contact alcohol-resistant orgs o After doffing PPE; wash hands with soap/water x15-20sec, dry, then Norovirus
PLUS transmitted by apply ABHR; use bleach wipes for equipment C. auris
indirect/direct contact o Isolate pt empirically while awaiting results Cutaneous anthrax
Cystic Fibrosis
Enhanced o Contact precautions + private room and limitations on use of shared spaces
(bidirection protection)
N. meningitidis
Influenza
Large respiratory
o Surgical mask + eye protection + private room Rhinovirus
Droplet droplets (coughing,
o Isolate pt empirically while awaiting results Adenovirus
sneezing, talking)
Pertussis
Mumps
o Contact precautions + N95/PAPR + eye protection + private room (may
Enhanced cohort known with known COVID-19)
COVID-19 COVID-19
Respiratory o Airborne Infection Isolation Room (AIIR, “negative pressure”) preferred
when aerosol-generating procedures anticipated
Small droplet nuclei that Tuberculosis
Airborne remain suspended in air o Standard precautions + N95/PAPR + AIIR Varicella
& disperse widely Disseminated VZV
SARS/MERS
Highly pathogenic o Contact precautions + N95/PAPR + eye protection + AIIR. If suspected, Avian Influenza
Strict
organisms isolate, contact Biothreats (Non-COVID) Pager #26876 Variola (smallpox)
Mpox
Immunocompromised Hosts:
• BMT, lung txp, neutropenic patients: standard precautions + positive pressure room + N95 for pt during travel + dietary precautions
• BMT: gloves and surgical mask for healthcare workers
• Lung transplant: gown, gloves, and surgical mask for healthcare workers
• Note: Plants and flowers should not be allowed in immunocompromised host rooms due to risk of fungal infection
How Infection Statuses are Resolved and Transmission-Based Precautions Discontinued:
Use .Resolve (previously CORAL/NEMO) for all COVID-related infxn statuses. For screening for resolution of prior MRSA, VRE, MDRO
status, please review MGH Resolution Policy and use .Resolve. Discuss resolving any other infection status w/ Infection Control
Bloodborne Pathogen Exposure: (needlestick, splash to eyes, mouth, nose, open cut), see Exposures & Needle Sticks
1. Immediately wash affected area
2. Normal business hours: call MGH OHS (6-2217). Outside business hours: page on-call OHS clinician, pager #21272. Can also
page MGH needlestick consultant, pager #36222.
3. Notify supervisor. Floor charge nurse can help with paperwork and expediting any necessary patient labs
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Infectious Disease Antimicrobial Dosing

General guidance: if questions re: dosing should confirm with pharmacist. See MGH/Partners antimicrobial dosing guidelines
Drug (By Class) Usual dosing CrCl 50-25 CrCl 25-10 CrCl<10 HD
PENICILLINS
Ampicillin IV (bacteremia) 2g q6h CrCl 10-50: 2g q8-12h CrCl <10: 2g q12h 2g q8-12h*
Ampicillin IV (endocarditis,
2g q4h CrCl 10-50: 2g q6-8h CrCl <10: 2g q12h 2g q8-12h*
meningitis, Listeria)
Ampicillin-sulbactam IV (SSTI, CrCl 15-30: 3g q8-
3g q6h CrCl <15: 3g q12h 3g q12h*
intra-abd, PID) 12h
Piperacillin-tazobactam IV
3.375g q6h CrCl 20-40: 2.25g q6h CrCl <20: 2.25g q8h 2.25g q8h
(non-Pseudomonas)
Piperacillin-tazobactam IV CrCl 20-40: 3.375g
4.5g q6h CrCl <20: 2.25g q6h 2.25g q8h
(Pseudomonas) q6h
CEPHALOSPORINS
1g q24h* OR
Cefazolin IV 2g q8h CrCl 10-50: 2g q12h CrCl <10: 2g q24h
2-3g post-HD
Ceftriaxone IV (bloodstream, No change with renal function; meningitis/Enterococcal endocarditis dosing is 2g q12h to max
2g q24h
bone, PNA, intra-abd, Lyme) 4g/day; on HD days, give post-HD
Ceftriaxone IV (UTI, SSTI, PNA,
1g q24h No change with renal function; on HD days, give post-HD
intra-abd, SBP ppx)
Ceftazidime IV (most CrCl 5-15: 2g
2g x1  1g q24h* OR
indications; UTI can use lower 2g q8h CrCl 31-50: 2g q12h CrCl 16-30: 2g q24h x11g q24h; CrCl
2g post-HD
doses) <5: 2g x11g q48h
Cefepime IV (febrile 1g q24h* OR
2g q8h CrCl 30-59: 2g q12h CrCl 10-29: 2g q24h CrCl <10: 1g q24h
neutropenia, PNA, CF, CNS) 2g post-HD
CrCl 30-59: 1-2g q12- 1g q24h* OR
Cefepime IV (others) 1-2g q8-12h CrCl 10-29: 1g q24h CrCl <10: 1g q24h
24h 2g post-HD
FLUOROQUINOLONES
Ciprofloxacin IV (for systemic
400mg q8-12h CrCl <30: 400mg q24h 400mg q24h*
Pseudomonas, q8h dosing)
Levofloxacin IV/PO (CAP, CrCl 20-49: 750mg
750mg q24h CrCl <20: 750mg x1  500mg q48h 750mg x1  500mg q48h*
complicated SSTI, MDR TB) q48h
CARBAPENEMS
Meropenem IV (most except
CrCl 10-25: 500mg CrCl <10: 500mg
meningitis, CF, obesity in which 1g q8h CrCl 26-50: 1g q12h 500mg q24h*
q12h q24h
case double dose)
OTHER ANTI-INFECTIVES
Acyclovir IV (higher dose for
CrCl 26-49: 5- CrCl 10-25: CrCl <10: 2.5-
CNS/VZV, adjusted wt if obese; 5-10mg/kg q8h 2.5-5mg/kg q24h*
10mg/kg q12h 5-10mg/kg q24h 5mg/kg q24h
recommend confirming dosing)
Clindamycin IV 600-900mg q8h Usual dose since clindamycin not renally eliminated; max 2,700mg/day
Fluconazole IV/PO (invasive 12mg/kg x1  6mg/kg 6mg/kg x1  3mg/kg q24h* OR
CrCl <50: 6mg/kg x1  3mg/kg q24h OR
candidiasis, weight-based dosing q24h OR 800mg x1  400-800mg x1  200mg q24h*
400mg x1  200mg q24h
if obese) 400mg q24h (or 400mg post-HD)
Metronidazole IV/PO 500mg q12h Most indications except CNS infection, C. difficile, H. pylori, & parasites
*Dialysis dosing: if drug dosed multiple times/day, administer 1 of the doses after HD. If drug dosed qd, administer after HD on HD days
Adapted from MGH/Partners antimicrobial dosing guidelines (contains more info on renal dosing for other antimicrobials, including CVVH dosing). To
access, sign into VPN or Epic Resources Handbook  Entity Resources Guidelines  Infectious Disease  Antimicrobial Renal Dosing Guideline (3a)
VANCOMYCIN DOSING including HD/CVVH/PD dosing:
Typical dosing regimen (if stable renal fxn): 20-25mg/kg LOAD (can choose higher dose for obesity or critical illness, max 2g regardless of wt)  10-
15mg/kg q8-24h (using adjusted body wt if obese) maintenance; adjustments for renal function (page 2 of empiric dosing guideline above). Dose by level for
unstable renal function including AKI.
• Monitoring: Trough versus area under the curve (AUC) depending on indication - see table below. Check trough 1h prior to 4th dose (or 3rd/5th to
avoid overnight levels). AUC monitoring: PK calculation assistance from pharmacist, requires peak 1-2h after completion of (typically) 4th dose (usual
infusion 60min/g) and trough 30-60min prior to next dose
SUMMARY OF THERAPEUTIC VANCOMYCIN GOALS
Confirmed or high suspicion for serious MRSA infection
AUC24h 400-600mg-h/L as determined by peak and trough, followed
(bacteremia, bone & joint, endocarditis/vascular, intra-abdominal,
by patient-specific trough (pharmacist will place note in chart)
pneumonia, necrotizing infxns)
Serious non-MRSA infection or empiric use Trough 10-20mcg/ml
Skin/soft tissue & urinary tract infections Trough 10-15mcg/ml
Central nervous system Trough 15-20mcg/ml
Unstable renal function (dose by level) 10-20mcg/ml
• Subtherapeutic level: first trough ≤1.5mcg from target (e.g. 9.3, w/ goal 10-15): continue same dose; first trough 1.5-5mcg lower than target (e.g.
11 w/ goal 13-18): dose by 250mg (e.g. 1000mg1250mg); first trough >5mcg lower than target: ↓dosing interval (e.g. q12q8h) ± ↑dose
• Supratherapeutic level: ≤5mcg/mL higher than target: hold until level is expected to be within target and consider ↓dose; 5-10mcg/mL higher than
target: hold until level is expected to be within target and consider ↑ dosing interval to next highest (8h  12h); >10 mcg/mL higher than target: hold all
future doses, reinitiate when random level ≤target range, ↑ dosing interval ± ↓dose

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Hematology Pancytopenia & Anemia

PANCYTOPENIA
Etiologies
Infection Viral (HIV, HBV/HCV, CMV/EBV, parvo), bacterial (brucella, TB), fungal (histo), parasitic (leish, malaria, schisto)
BM infiltration Malignant: leukemia, MPN, MDS, MM, metastasis. Non-malignant: MF, infection, storage diseases
Nutrition: B12/folate/Cu/Zn, EtOH, anorexia. Marrow suppression from viral (HIV, hep, EBV, CMV, parvo).
BM failure
Immune destruction/suppression: AA, PNH, drugs, LGLL, SLE/RA, sepsis, HLH. Ineffective hematopoiesis: MDS
Destruction /
Consumption: autoimmune, DIC/TMA. Splenomegaly: portal HTN/cirrhosis, infection, autoimmune (SLE/RA), others
sequestration
Congenital Wiskott-Aldrich, Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, GATA2 deficiency, HLH
Work-up
History Time course, prior treatments/transfusions, autoimmune/onc hx, social, travel, occupational, infection hx; constitutional sx
CBC/diff, retic, special slide, T&S, LFT, TSH, Iron Studies, B12, folate, ESR/CRP, INR/PTT/fibrinogen
Initial labs Also consider: Cu, Zn, Vitamin E, LDH, haptoglobin, SPEP/SFLC, DAT, uric acid, ANA, HIV/HBV/HCV/CMV/EBV/Parvo,
UDS
Review meds NSAIDs, PPIs, sulfas, antihistamine, chemo, anticonvulsants, antiprotozoals, heavy metals, many others
Hematology Consult for: unexplained significant neutropenia/thrombocytopenia, Blasts* on Diff, DIC/TMA, HLH, heme malignancy
Always consider the possibility of multiple independent cytopenias in addition to a unifying diagnosis
*Blasts first show up as ‘Others’ on a diff with a comment from the lab on their morphology until confirmed
A N E M I A (Williams Hematology 2021)
S/Sx: O2 delivery  fatigue, lightheaded, DOE, pallor, angina (if CAD), claudication, cramps, abd pain, N/V; compensatory mechanisms
 RR, CO (HR, palpitations, flow murmur, later: high-output HF), erythropoiesis (bone pain)
Other findings: dark urine/jaundice (hemolysis), glossitis (folate/B12/Fe def), motor/sensory deficits (B12 def), pica/koilonychias/angular
cheilitis/RLS (Fe def), splenomegaly (cirrhosis, infxn, thalassemia, malignancy, chronic hemolysis), constipation/bone pain (myeloma),
melena (GIB), heavy menstrual bleeding, unusual thromboses (PNH), petechiae/purpura (coagulopathy, pancytopenia), family hx (thal/SS)
Initial labs (draw/add on prior to transfusion): CBC/diff (Δs in other cell lines, MCV, RDW), retic, special slide, T&S
• Calculate reticulocyte index (RI) = [% retic x (Hct/nl Hct)] / maturation factor, adjusts for Hct/early release of retics. Determines if
adequate BM response: hypo- (<2%) vs hyper-proliferative (>2%); RI <0.1% indicative of aplastic anemia or red cell aplasia
Additional labs depend on RI and clinical history:
• RI <2%  “Anemia labs”: Fe/TIBC/ferritin, folate/B12 (in last 6mo), BMP, LFTs, TSH, CRP, review prior CBC
o If unrevealing/otherwise indicated by history: ± SPEP/SFLC, Hgb electrophoresis, AM testosterone, Epo, BMBx
• RI >2%  “Hemolysis labs” vs recent bleeding: LDH, bilirubin, haptoglobin, DAT (Coombs), coags, UA
C L A S S I F I C A T I O N O F A N E M I A (NEJM 2014;371:1324; Lancet 2018;391:155; JACC: Heart Failure;2019;7:36; Williams Hematology 2021)
UNDERPRODUCTION (RI <2%)
Microcytic (MCV <80 µm3) Normocytic (MCV 80-99 µm3) Macrocytic (MCV ≥100 µm3)
Iron deficiency anemia (IDA) Megaloblastic: smear shows hyper-seg
• Fe, TIBC, ferritin (<30 high Sp; <15=Fe in Inflammation & variant: PMNs and macro-ovalocytes
BM), Fe/TIBC <16%, <20% with inflammation, • Early IDA or early ACI • Folate: homocysteine, nl MMA
RDW • Mixed IDA & folate/B12 (dimorphic: • B12: homocysteine, MMA
Anemia of inflammation/chronic dz (ACI/ACD) nml MCV w/ RDW) (anti-IF Ab, gastrin if pernicious
• Fe, /nl TIBC, ferritin (<100 if ACI+IDA or Organ-specific: anemia; falsely nml B12 possible)
<200 in ESRD), Fe/TIBC /nl (>18%) • Renal (CKD/ESRD): Epo (should • Copper deficiency
• In CHF (concomitant IDA/ACI), ferritin <100 (or 10x per 10% Hct drop)
• Early myeloproliferative d/o
<300, if Tsat <20) • Endocrine (thyroid, pituitary, adrenal, Non-megaloblastic: MCV usually <110
Thalassemias parathyroid, testosterone; metab
• Cirrhosis, EtOH
• Fe studies nml, MCV  (often <70), Mentzer rateO2 demand) ->Epo secretion
• Reticulocytosis: lysis or bleed
index (MCV/RBC <13; high Sp); Hb • Marrow (red cell aplasia, aplastic
electrophoresis • Hypothyroidism
anemia, MDS, myelofibrosis,
Sideroblastic anemia myelophthisis, PNH, MM): check • MDS (refractory anemia) & MM
• ferritin, Fe/TIBC nml; smear: basophilic stippling SPEP, serum FLC, BMBx Meds: antifolates, pur/pyr analogs, AEDs,
(Pb); BMBx: ringed sideroblasts HAART, AraC, Hydrea, others
DESTRUCTION/LOSS (RI >2%)
Extrinsic (to RBC) Intrinsic (to RBC)
MAHA (-DAT, +schisto): see Thrombocytopenia
• Smear (≥2 schisto/HPF), plt ~25K, LDH, indirect bili, hapto Hereditary:
Immune (+DAT, +spherocytosis): Ab- and/or complement-mediated • Hb disease (SS, HbC, thal): Hb electrophoresis
• Warm autoimmune (CLL, HIV, lymphoma, SLE): +DAT anti-IgG/C3 • Enzyme deficiency (G6PD, PK): G6PD levels often
• Cold autoimmune (EBV, lymphoid malig, mycoplasma): +DAT anti-C3 nml in attack; check 4w later & repeat in 3mo if ⊝
• Drugs (PCN, cephalosporins), alloimmune (hemolytic transfusion rxn) • Membrane defect: spherocytosis, elliptocytosis
Non-immune (-DAT): Acquired (new onset):
• Infection: Babesia, Malaria, Bartonella, C. perfringens, H. flu (type B) • PNH (paroxysmal nocturnal hemoglobinuria): flow
• Toxin: lead, copper (Wilsons), insect/spider/snake bites, hypotonic infusion cytometry ± FLAER for GPI anchor, smear nml, UA
• Hypersplenism: many; massive SM usually heme malig or infection (Hgb/hemosiderin), thrombosis (intra-abd/cerebral)
• Vitamin E Acute blood loss: GI blood loss, hematoma
• Mechanical trauma: mechanical valve, aortic stenosis
Intravascular: LDH, hapto, hemoglobinemia & -uria; Extravascular: indirect bili ± LDH ± hapto (if free Hb escapes spleen)
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Hematology Pancytopenia & Anemia

I R O N D E F I C I E N C Y A N E M I A (NEJM 2015;372:1832; Blood 2019;133:30)
• Etiology: loss due to chronic bleeding (PUD/UGIB [BUN w/o Cr], LGIB/CRC, menses, parasites, intravascular hemolysis),
demand (Epo, pregnancy, blood donation), intake (malnutrition) or absorption (Crohn’s, pH [e.g. PPI], post-gastrectomy, Celiac)
• Evaluation: GI bleed eval, H. pylori; consider Celiac disease (esp. if not responsive to PO iron), menorrhagia hx. Calculate Fe deficit
with Ganzoni equation (can also use .irondeficit in EPIC)
• Treatment: PO 325mg FeSO4QOD (QOD  absorp: Lancet Haematology 2017;4:e524). ~6w to correct anemia, ~3-6mo to replete stores.
absorp. on empty stomach, VitC may , w/ Ca foods, antacids. GI SE: constipation, epigastric pain, N/V
o IV iron if ongoing heavy bleeding, CKD, malabsorption, IBD, intolerant to PO, or chronic CHF (NEJM 2009;361:2436). IV Iron at d/c
following ADHF risk of future HF hospitalizations (Lancet 2020;396:1895). Typical dose: iron sucrose 100 – 300 mg per dose,
repeated until total iron req met. SE: n/v, pruritus, flushing, myalgia/arthralgia, CP;  by 48h. Anaphylaxis rare with modern
products. Pt with inflammatory arthritis may have flare from IV infusion.

A N E M I A O F I N F L A M M A T I O N / C H R O N I C D I S E A S E (NEJM 2019;381:1148; Blood 2019;133:40)

• Etiology: autoimmune, infection, malignancy, CHF, CKD, obesity, DM, aging, critical illness; inflammatory cytokines (IL-1, IL-6 &
TNFα)  hepcidin  ferroportin internalized / degraded  intestinal Fe absorption, Fe & hepatic Fe mobilization
• Time course: usually 1-2mo to develop, but can Hgb 2-3g/dL in 1-2d in acute illness
• Treatment: tx underlying disease. Fe if concomitant Fe deficiency.
o Erythropoiesis stimulating agents (ESA): FDA-approved for anemia a/w CKD & HIV on HAART. Controversial in cancer pts
(JCO 2019;37:1336). Evidence against use in CHF (NEJM 2013;368:1210). Maintain Tsat ≥20%, ferritin ≥100 for EPO therapy

M A C R O C Y T I C / M E G A L O B L A S T I C A N E M I A (MCV ≥100µm3)
• Review meds, if without megaloblastic changes (hyperseg PMN): consider thyroid, liver, nutritional causes, MDS, reticulocytosis
• Folate (“foliage”), 3mo stores; intake (EtOH, elderly), absorption (Celiac, jejunum), demand (pregnancy, hemolysis,
malignancy), meds (MTX, TMP, AEDs). When severe a/w hemolysis & pancytopenia; homocysteine, MMA nml
o Tx: 1-5mg PO qd (can worsen B12 deficiency and associated neurologic complications if not replete)
• B12 (“beef”), 3y stores; intake (EtOH, vegan), pernicious anemia (Ab to intrinsic factor (IF), gastric parietal cells), absorption
(gastrectomy, Celiac, Crohn’s, PPI, chronic pancreatitis), competition (SIBO, tapeworm); when severe a/w pancytopenia & subacute
combined degeneration (dorsal columns, corticospinal tract) w/ dementia, ataxia, paresthesia
o Labs: check homocysteine/MMA if B12 borderline (200-350). Consider anti-IF Ab if homocysteine/MMA  or if B12 <200
o Tx: 1-2mg PO B12 qd vs IM dosing (depending on if symptomatic anemia, neuro sx, malabsorption). Post-tx, neuro sx start to
improve 3mo-1y (NEJM 2013;368:149)

A U T O I M M U N E H E M O L Y T I C A N E M I A ( A I H A ) (NEJM 2019;381:647; Blood 2017;129:2971)

• Warm AIHA:
o Etiology: antibody-mediated, often idiopathic, less common CLL/lymphoma/MM, ALPS, SLE, HIV, EBV, hep C, SARS-CoV-2,
babesia, meds. Extravascular > intravascular hemolysis. Rule out other causes of hemolytic anemia
o Dx: +DAT anti-IgG and/or C3d (typically IgG and panagglutinin). haptoglobin, LDH, indirect bili, reticulocytes.
o Tx: transfusion for symptomatic anemia or Hgb <7, steroids, d/w blood bank. 2nd line: rituximab, splenectomy, mycophenolate
• Cold agglutinin disease:
o Etiology: Often associated with lymphoproliferative process, EBV, mycoplasma, autoimmune. Hemolysis mediated by
complement.
o Dx: +DAT anti-C3d only and cold agglutinin titer
o Tx: Tx underlying process, workup clonal lymphoproliferative disorder. If symptomatic, warm transfusions, plasmapheresis,
rituximab, sutimlimab. Steroids/splenectomy not indicated.
• Drugs: both Ab & non-Ab-mediated; abx (PCN, cephalosporins, sulfa); NSAIDs; rasburicase (G6PD), anti-cancer meds, others
o If +DAT but no hemolysis, think drugs, IgG (IVIG/RhIg/myeloma), CTD (e.g., controlled SLE)
• Other etiologies: paroxysmal nocturnal hemoglobinuria (PNH), paroxysmal cold hemoglobinuria (PCH; anti-C3).

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)

• Excessive inflammation/tissue destruction secondary to abnormal immune activation of macrophages and lymphocytes & cytokine
storm
• Workup: molecular testing or dx with 5/8 of fever, spleen, 2/3 cytopenias, TG /fibrinog, ferritin ≥500 (usually >3k), sIL-2R,
hemophagocytosis in BM, spleen, or LN, low/no NK activity. Also LFTs, hepatomegaly, LDH, D-dimer,  fibrinogen, ESR,
CXCL9. H-score for probability.
• Consider evaluating for associated/underlying illness: infection (pan-culture, viral titer/PCR: EBV, CMV, hepatitis, HSV, VZV, HIV,
HHV-8, HHV-6, parvo, bartonella, leishmaniasis), malignancy, CAR-T, rheum, neuro (brain MRI, LP), genetic
• Tx: Depends on etiology. If acutely ill, consider dexamethasone +/- etoposide. Dexamethasone is steroid of choice as it crosses the
blood brain barrier. Consider etoposide-based regimen or allogeneic HCT (ASH: Blood 2019;133:2465)

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Hematology Sickle Cell Disease

O V E R V I E W (JAMA 2022;328;570)
• Definitions:
o Sickle Cell allele: autosomal recessive βglobin gene A->T (Glu6Val) missense mutation
o Sickle Cell Trait (SCT): heterozygous for HbS w/o aberrancy in partnered βglobin gene
o Sickle Cell Anemia (SCA): homozygous for HbS
o Sickle Cell Disease (SCD): any variant of an inherited hemoglobinopathy with formation of HbS leading to sickle shape of RBCs
o HbSC disease: Equal amounts of HbS & HbC (greater loss of K+ dehydrating RBCs & promoting sickling). Freq dehydration,
relative to SCD retain splenic function & less hemolysis. Smear: target cell, HbC crystals, some sickled cells.
• Epidemiology: ~300K born with SCA per year worldwide. ~100K w/ SCD in U.S, 1.2K families in Boston area. ~7-8mil worldwide
• Pathophysiology: deoxygenated HbS polymerization  sickle shaped RBCs, impacts RBC membrane integrity, adherence to
vascular endothelium  hemolysis-related endothelial dysfunction and vaso-occlusive events (VOE) which can affect any organ
• Diagnostics: baseline Hb electrophoresis and HPLC: tests to separate HbS from other variants (HbA, HbF, HbC)
CLINICAL MANIFESTATIONS
• Acute Pain Episodes (Complement Ther Med 2020; 49:102327):
o Complication for which patients most commonly seek medical attention; frequency peaks between ages 19-39
o Sx: severe pain, swelling, tenderness, HTN, N/V. Frequency peaks age 19-39. risk when Hb >8.5 and HbF.
o Triggers: dehydration, infection, changes in the weather, stress, menses, EtOH. Over 50% w/o clear etiology.
o Dx: no objective signs or lab values, patient report is the criterion standard
• Acute Chest Syndrome: #2 cause of hospitalization. Pulmonary arterial circ O2 tension  risk VOE. Complications including
PNA, thromboses, fat embolism. NB: 50% preceded by or a/w acute pain episodes
o Definition: new imaging infiltrate + pulmonary symptoms in a patient with SCD, freq. with fever, chest pain, cough
o Dx: CXR, WBC, r/o PE & MI
o Tx: O2 goal >95%, antibiotics (CTX+azithro or FQ), adequate analgesia is critical to prevent splinting-sickling cycle, transfusions
(simple vs exchange), bronchodilators
• Other organ systems:
o 1) Splenic sequestration: 20% pts; acute 2g/dL Hb
o 2) Infection: given functional asplenia and hyposplenism, risk of encapsulated org, defects in alternative complement pathway.
If febrile, send BCx and cover empirically w/ CTX (+azithro if c/f acute chest; +vanc if HDUS or c/f meningitis)
o 3) CV: major cause of death, CM (secondary to chronic anemia, hemosiderosis), MI risk (even in absence of atherosclerosis)
o 4) Neurologic: stroke (~1/4 of pts with SCA with experience a stroke by age 45)  neurocog impairment, epilepsy
o 5) Hepatobiliary: acute hepatic ischemia, iron overload from frequent transfusions, pigmented gallstones
o 6) Bone: rate Vit D def & osteoporosis, osteonecrosis
o 7) Heme: chronic compensated anemia (Hg 8-10), aplastic crisis, & hyper-hemolytic episode: rare; pain, fever, Hb w/in 7-15d of
transfusion; Tx: notify blood bank, hydration ± steroids, IVIG, rituximab, eculizumab
o 8) Vascular/cutaneous: priapism, leg ulcers, pulmonary HTN, renal insufficiency, proliferative retinopathy
Severe complications of disease requiring urgent hematology consult to discuss red cell exchange: severe acute chest syndrome,
stroke, multiorgan failure syndrome, myocardial infarction
MANAGEMENT
Sickle Cell Pager (p28439) for every admission, consult inpatient hematology for severe SCD-related complications (as above)
• Workup: CBC/diff, BMP, LFTs, coags, reticulocyte count, BCx, UA/UCx; CXR; special slide (polychromasia., sickle cells, Howell-Jolly)
• All inpatients: VTE ppx, pain control, O2 (SpO2 <92%), often IVF for acute pain episodes. See Acute Care Plan. Utilize Epic
Order Set (“General Adult Sickle Cell Crisis”).
o Pain control: IV opioids within <1hr of ED arrival (see MGH ED protocol) ± fluids at 100-150 mL/hr IV ± NSAIDs (5-7 days;
ketorolac ≤ 5 days; Blood Adv 2020;4:2656). If unknown prior dose, ask patient and consider IV morphine 0.1-0.15mg/kg ≤10mg
or Dilaudid 0.02-0.05mg/kg (max 1.5mg). Once admitted, discuss transition to PCA with patient and pharmacy. Do not hold long
acting PO opioids unless on a PCA with a basal rate. Avoid steroids ( rebound pain). Give aggressive bowel regimen ±
methylnaltrexone. If uncontrolled, contact chronic pain for high dose PCA titration and to consider ketamine (MGH policy).
o Pruritis: chronic (non-sedating antihistamine or 5-HT3RA), inpatient consider continuous infusion dose naloxone gtt (0.25
mcg/kg/hr), compatible for simultaneous admin w/ morphine. Note: Avoid IV Benadryl in favor of PO
• Neutral language: misperceptions interfere with management, biased language a/w poor pain control and ⊝ attitude to pt (JGIM
2018;33:685). Avoid stigmatizing terms, including: “sickler, freq. flyer, pain seeking” which foster bias and bidirectional mistrust (JAMA
2022;328;570).
• Transfusions: Indicate Sickle Cell on Epic transfuse order for more extensive match. Mechanisms of benefit include: dilute HbS, Epo reducing
production of new HbS cells, SpO2. Indicated in stroke, multiorgan failure, acute chest, sequestration, peri-op. symptomatic or
severe anemia (drop of hgb >2 from their baseline). No e/o benefit in acute pain episode (Br J Haematol 2015;171:288). Exchange >
simple (risk of hyperviscosity). Judicious w/ transfusion (risk of clinically sig. iron overload if >15-20 RBC units) (Blood Adv 2020;4:327).
o Iron chelators: deferoxamine (subcutaneous and IV), deferiprone and deferasirox (PO, poorly tolerated, toxic). Initiated ~1-2
years of chronic transfusions or ferritin >1000-1500 ng/mL.
• Outpatient: hydroxyurea (HbF; continue inpatient), folate/MVI, L-glutamine ( RBC oxidative stress; NEJM 2018;379:226), voxelotor
(inhibits HbS polymerization; no improvement in VOEs or mortality; NEJM 2019;381:509), crizanlizumab (P-selectin antag, RBC
adhesion; approved for prevention of VOEs; NEJM 2017;376:429). Vaccines for encapsulated bacteria (Mening, HiB, Pneumo), HBV, flu,
CoV-19. Consider prophylactic transfusions in patients with multiple episodes of acute chest despite maximal therapy. Consider
SNRIs, amitriptyline, and pregabalin for chronic pain (Blood Adv 2020;4:2656).
• Other therapies: allogeneic BMT only curative option. Gene therapy targeting BCL11A (CRISPR use) (NEJM 2021;384:205).

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Hematology Thrombocytopenia
T H R O M B O C Y T O P E N I A (Hematology 2012;2012:191)
Definitions: 100-150k mild, 50-99k mod, <50k severe. Bleed risk: <50k w/ surgery/active bleed, <30k w/ mild trauma, <10k spontaneous
Production Destruction Sequestration/Dilution
- Infection: sepsis, HIV/HCV, VZV/CMV/EBV, parvo, tickborne - Immune: ITP, SLE/APLS, RA, lymphoma, post- - Hypersplenism
- Nutrition: EtOH, B12, folate transfusion - Hemangioma
- Drugs: abx, chemo (ASH Edu 2018;2018:576) - Drugs: heparin, MTX, abx, AEDs, anti-GPIIb/IIIa, quinine - Massive transfusion
- Neoplasm: MDS, BM infiltration, 1° heme - MAHA: DIC, TTP, HUS, mHTN, preeclampsia/HELLP - Hypothermia
- Other: hereditary, cirrhosis, aplastic anemia, some vWD - Mechanical: CVVH, CPB, ECMO, IABP, valves - Gestational
Workup:
• H&P focused on bleeding (GI, GU, epistaxis, HA, mucocutaneous), etiology, timing of plt . If new HA: consider CTH
• R/o alarming causes: HIT, TMA, catastrophic APLS. Identify common causes: infxn, drug, immune, nutrition, hypersplenism, MDS
• Initial labs: CBC, BMP, LFTs, coags, special slide, T+S, HIV, HCV, pregnancy test, citrated plt count (r/o pseudo-thrombocytopenia)
• If asymptomatic, mild (100-150k): history of risk factors (i.e. alcohol use), routine exam, CBC for other cytopenias, special slide,
HIV/HCV testing, B12, folate (common cause of over-testing)
• If c/f MAHA (e.g. schistocytes on slide): add LDH, haptoglobin, DAT, retics, D-dimer, fibrinogen
• If c/f SLE/APLS: add ANA, lupus anticoagulant, anti-cardiolipin, anti-β2GP1
• If c/f BM disease: consult Hematology, consider BM biopsy
I M M U N E T H R O M B O C Y T O P E N I A ( I T P ) (Blood Adv 2019;3:3829; Blood 2017;129:2829; NEJM 2019;381:945)
Pathologic antiplatelet antibodies cause plt clearance and bind to megakaryocytes/progenitors, resulting in apoptosis and near-normal rate
of platelet production. Defined by isolated plt <100k, dx of exclusion – must exonerate other causes of thrombocytopenia
Presentation: Precipitous and sudden decline in platelet. Asx or mucocutaneous bleeding; 10% of ITP has AIHA. Associated w/ H.
pylori, HCV, HIV. Consider thrombopoietin level (may predict responsiveness to TPO receptor agonists (Am J Hematol 2018;93:1501-1508)).
Prognosis: <10% spontaneous resolution, up to 50% recover with 1st line tx. 1.4% risk of ICH, 9.5% risk of severe bleeding
Management: “response” = plt 2X to ≥30k within 3mo
• Plt ≥30k & asx/minor bleed: observe; consider steroids if elderly, comorbidities, on AC/anti-plts, upcoming procedures, & plt near 30k
• Plt 10k-29k: steroids ± IVIG, RhoGAM if RhD+; if not bleeding, DO NOT give plts (destroyed & ↓ Plt further) (Blood 2015;125:1470)
o Steroids (takes 4-14d to work): dexamethasone 40mg/d x4d, methylpred 1g/d x3d, or prednisone 60mg/d x3w w/ taper
• Plt <10k: steroids + IVIG, consider romiplostim, do not give plts unless c/f bleeding
• Severe bleeding: Plt, IVIG, steroids (pulse-dose methylpred & dex), Amicar (0.1g/kg/30mingtt 0.5-1g/h)/TXA, romiplostim
• Refractory/recurrent: ↑ romiplostim dose, ritux, fostamatinib; last resort (>12m after dx) splenectomy (>50% effective, risk of relapse)
H E P A R I N - I N D U C E D T H R O M B O C Y T O P E N I A ( H I T ) (Blood Adv 2018;2:3360; Blood 2017;129:2864; NEJM 2015;373:252)
IgG anti-PF4-heparin complex binds & activates plts, hypercoagulable state. Can occur with any heparin (UFH, LMWH, heparin flushes)
Types: HIT Type 1 (mild platelet drop no lower than 100k 1-2d from heparin exposure, not clinically significant) vs. HIT Type 2 (see below)
Presentation: 5-10d after exposure, plt >50%, nadir 40-80k, thrombosis in 30-50% (skin necrosis, DVT/PE, arterial), GIB (~3%)
• Consider rapid-onset HIT if <24h with prior exposure within 100d; delayed-onset can present up to 3w after last heparin
Diagnosis/Management: Calculate 4Ts Score. (If incomplete information, may be prudent to err on side of higher 4T score. Recalculate for
change in clinical picture). If 0-3: HIT unlikely (NPV 99%), OK to continue heparin. If ≥4:
1) Stop heparin, reverse warfarin (prevent skin necrosis), and start non-heparin AC. No plt transfusion unless severe hemorrhage
2) Send anti-PF4. Send serotonin release assay (SRA) (gold standard). Do not wait for results to do Step 1
o PF4 neg: HIT unlikely; OK to resume heparin. PF4 OD ≥2, or OD ≥1.5 with 4Ts ≥6: HIT likely. Otherwise: decide based on SRA
3) Screen for DVT with upper/lower extremity ultrasound
• Duration of AC: if no thrombosis, until plt >150k (at least 4 weeks); if thrombosis, at least 3mo. Non-heparin AC options:
o Fondaparinux (IV or SQ): for stable non-surgical patients, contraindicated if GFR <30, irreversible
o Argatroban (IV): preferred in renal failure & surgical pts, monitor w/ chromogenic Xa (goal 20-40%)
o Bivalirudin (IV): only approved for HIT undergoing PCI, preferred in liver failure
o PO Options: DOACs for non-urgent AC, warfarin not until plt >150K for 2 consecutive days
• Add heparin to allergies, avoid in future & use other VTE ppx. If strong indication (e.g., bypass) small studies suggest no  risk of HIT
in pts with h/o HIT >100d prior if anti-PF4 now neg (NEJM 2001;344:1286; NEJM 2000;343:515). Resolution of ↓ Plt expected in ~7d
T H R O M B O T I C M I C R O A N G I O P A T H Y ( T M A ) (NEJM 2014;371:654)
Microthrombi  MAHA (Hb, LDH, haptoglobin, +schistos, -DAT), plt (consumption), end-organ injury (vascular occlusion)
• Drug-induced (DITMA): gemcitabine, oxaliplatin, quetiapine, quinine, tacrolimus, cyclosporine, bevacizumab, opioids
• TTP (Plt <30K): inherited/acq. ADAMTS13 def. vWF multimers formation of plt microthrombi. S/Sx: purpura, GI sx, neuro sx;
fever, AKI. Dx: PLASMIC score mod/high, lab testing of ADAMTS13 activity. Tx: plasma exchange/FFP, steroids, ritux. DO NOT
transfuse to correct Plt unless severe bleed, though transfusion not a/w  risk of mortality/CNS comp (Transfusion 2009;49;873).
• HUS (plt >30K)
o Shiga-toxin-mediated O157:H7 E. coli, Shigella (“ST-HUS”). S/Sx: bloody diarrhea, severe AKI; severe neuro sx rare. Dx: stool
⊕ for organism or toxin; Tx: supportive (IVF, HD) (Blood 2017;129:2847)
o Complement-mediated (“atypical HUS”): S/Sx: severe AKI + 20% w/ extra-renal sx (CNS, cardiac, pulm hemorrhage, panc.);
Dx: complement genotyping, anti-complement Ab. Tx: plasma exchange; eculizumab (NEJM 2013;368:2169)
• 2° Etiologies: DIC, infxn, malignancy, SLE/APLS, scleroderma, malignant HTN, HELLP, post-HSCT
• Immediate Management: if DITMA, d/c drug. Special slide (+schistos), c/s Heme if concerned and/or severe anemia/↓ Plt, monitor
UOP (for renal impairment), consider complement (C3/C4) testing. 1st line: therapeutic plasma exchange, transfuse RBCs if
symptomatic anemia, transfuse platelets for <20k or <50k with bleeding/pre-procedure.
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Hematology Eosinophilia
O V E R V I E W (Am J Hematol 2022; 97:129; Hematology 2015;2015:92)
• Eosinophilia: AEC >500. Hypereosinophilia: AEC >1500. Hypereosinophilic syndromes (HES): AEC >1500 + organ dysfunction
o Eosinophils are quickly eliminated by steroids  eosinophilia may be unmasked as pts taper off chronic glucocorticoids
• Primary = due to clonal expansion (HES/leukemia). Secondary (reactive) = due to infection, atopy, meds, rheum dz, etc

Helminthic: strongyloides, toxocariasis, schistosomiasis, ascaris, filariasis, trichinellosis, hookworm, fascioliasis.

Infections
Fungal: aspergillus (ABPA), coccidiomycosis, histoplasmosis. Protozoal: isospora. Viral: HIV, HTLV1/2
Malignancy Primary HES (PDGFRA-assoc.), eosinophilic leukemia, CML, NHL, HL, mastocytosis; less common with solid tumors
Autoimmune EGPA (see Vasculitis), PAN, eosinophilic fasciitis, RA, IBD, EoE, IgG4, sarcoidosis, GVHD, blistering disease
Drugs (i.e. penicillins, cephalosporins, NSAIDs, ranitidine, aspirin, allopurinol, phenytoin, tetracyclines), DRESS,
Allergic
asthma/atopy, ABPA, hyper IgE syndrome, AIN, episodic angioedema (Gleich syndrome)
Misc Adrenal insufficiency, cholesterol emboli syndrome, acute arterial thrombosis, radiation exposure, familial (Chr 5q mut)

W O R K U P (Br J Haematol 2017;176:553; J Allergy Clin Immunol Pract 2018;6:1446; Hematology 2015;2015:92)
• Hx: meds/supplements (<6w), diet, travel, occupational exposures, atopy, infxn, malignancy, rheumatic dz, full ROS, ∆ in sx
• Exam: assess for rashes, cardiac/pulmonary abnormalities, nasal/sinus involvement, LAD, hepatosplenomegaly, neuropathy
• Initial diagnostics: CBC/diff (repeat), special slide, BMP, LFTs, LDH, ESR/CRP
o If AEC 500-1500: check troponin, B12/tryptase, CXR if clinically indicated
o If AEC >1500, assess for HES: check U/A, CK, troponin, EKG, CXR, PFTs, CT C/A/P or PET (for adenopathy, organomegaly,
masses, organ infiltration), tissue biopsy of affected organs; also B12, tryptase, serum Ig levels
• Additional diagnostics (as clinically indicated): Strongyloides serology, stool O&P, other parasitoid/fungal serologies; ANCA if c/f
EGPA; ANA, RF, CCP if c/f rheum dz; ACTH/cort stim if c/f AI; IgE levels, allergy testing if c/f allergy; imaging/bronch; endoscopy if c/f
EoE/EGE; TTE/CMR if c/f cardiac dz; periph. flow ± BMBx if c/f MPD or >1500 & no obvious 2° cause
• When to suspect drug reaction: isolated Eos or w/ systemic illness (e.g. DRESS, hepatitis, AIN). PCN/cephalosporins common
culprits. Suspect DRESS if new drug 2-8w prior, fever, rash, facial edema, LAD, ↑ LFTs, ± organ involvement, atyp. lymphs.

T R E A T M E N T (Hematology 2015;2015:92)
• Urgent Tx: if cardiac, neuro, or thromboembolic complications, AEC >100,000/rapidly rising, or s/sx of leukostasis  1mg/kg to 1g
methylpred (+empiric ivermectin 200mcg/kg if potential Strongyloides exposure); obtain HES diagnostics above prior to initiating
• Non-urgent Tx: symptomatic or evidence of end-organ damage but does not need urgent Tx; see below for Tx by condition
• No Tx: if asymptomatic, no organ involvement, & no identified cause to treat, can monitor for resolution & organ damage

ORGAN-SPECIFIC PATHOLOGY
Cardiac: (Immunol Allergy Clin North Am 2007;27:457; JACC 2017;70:2363)
• Eosinophilic endomyocarditis: necrosis  thrombus formation ( embolic events)  fibrosis  restrictive CM, valve involvement
o May be due to hypersensitivity myocarditis, parasitic infections, malignancy, idiopathic HES
o Dx: TTE (LV/RV apical dysfunction, restriction, intracardiac thrombi), cardiac MRI (+subendocardial LGE), endomycocardial bx
o Tx: high dose steroids & remove culprit med (if hypersensivity), treat underlying disorder (parasite, HES)
• Eosinophilic coronary arteritis: rare complication of EGPA; may mimic ACS
Pulmonary: (Clin Microbiol Rev 2012;25:649; Chest 2014;145:883; J Allergy Clin Practice 2014;2:703)
• Acute eosinophilic PNA: <7d fever, cough, SOB; a/w smoking; periph. Eos often absent; Dx: BAL Eos ≥25%; Tx: steroids
• Chronic eosinophilic PNA: >4w fever, cough, SOB, wt loss; a/w asthma; Dx: BL mid-upper lobe infiltrate; BAL Eos ≥25%; Tx: steroids
• Allergic bronchopulmonary aspergillosis (ABPA): asthma/CF c/b recurrent exacerbations w/ fever, malaise, brown mucus plugs; Dx:
Eos, total IgE, Aspergillus IgE & IgG, imaging w/ central bronchiectasis, UL/ML consolidations; Tx: steroids + itraconazole
• Loeffler syndrome: transient/migratory pulm. opacities, Eos 2/2 helminth larvae; Dx: larvae in resp secretion (stool usually ⊝)
GI: (AGA EoE: Gastro 2020;158:1776; NEJM 2015;373:1640; Clin Rev Allergy Immunol 2016;50:175)
• Eosinophilic esophagitis (EoE): dysphagia, food impaction, GERD-like sx/refractory GERD, assoc w/ allergic conditions; Dx: EGD w/
bx, exclude other causes (GERD, motility d/o, Crohn’s, infxn, CTD, etc.); Tx: dietary Δs, PPI, topical steroids (MDI/neb, PO liquid)
• Eosinophilic gastroenteritis (EGE): stomach/small bowel/colon ± esoph.; Sx: n/v/d, abd. pain, malabsorption (mucosal dz), poor
motility/obstruction/perforation (muscular layer dx), ascities (serosa dz); Tx: dietary Δs, PO steroids

P R I M A R Y H Y P E R E O S I N O P H I L I C S Y N D R O M E S ( H E S ) (Am J Hematol 2022; 97:129; Hematology 2015;2015:92)

• Myeloproliferative HES (~20% of HES in US): acute/chronic eosinophilic leukemia; 80% pts have FIP1L1-PDGFRA fusion gene
o Dx: anemia, thrombocytopenia, tryptase, B12, special slide (dysplastic eosinophils), BM Bx (fibrosis, hypercellularity)
o Tx: if PDGDR+, imatinib ± steroids if cardiac sxs; if JAK2+, JAK2 inhibitor; if FGFR1+, chemo. 2nd line: sorafenib, midostaurin, or
ponatinib.
• Lymphocytic HES: clonal T-cell expansion IL-5  Eos. Often p/w skin/soft tissue involv., polyclonal hyper-IgG, IgE. 5-25%
progress to lymphoma (a/w Chr 6p deletion).
o Dx: flow cytometry for aberrant Th2 type CD4 cells; Tx: steroids; 2nd line: IFN-α, hydroxyurea, anti-IL-5
• Idiopathic HES/Hypereosinophilia of Uncertain Significance (HEus): eosinophilia w/o identified cause +/- organ involvement 
consider ANCA-neg EGPA, suggested all pts get f/u to ensure no end-organ involvement even if asx at dx. Tx: Steroids only if sx.

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Hematology Coagulation Disorders

H Y P E R C O A G U L A B L E S T A T E S (NEJM 2017;377:1177) (ASH 2023 Guidelines)
Do not test at time of event or during anticoagulant therapy. If performed, should be >2 weeks following d/c of anticoagulation
Testing includes: Factor V Leiden, prothrombin gene mutation, protein C/S def, antithrombin deficiency, antiphospholipid Abs*
*[Caveat in someone with compelling history there may be benefit to testing for APLS (serologies only) in the setting of acute clot as it may change management]
Do not test for thrombophilia Test for thrombophilia
- VTE provoked by nonsurgical major transient risk factor (e.g.
- Unprovoked VTE (warrants indefinite AC) admission for PNA) or OCP/pregnancy/PP [controversial]
- VTE provoked by surgery - Cerebral/splanchnic VTE (+ test JAK2, PNH in hepatic/PVT)
Patients with
- VTE provoked by other clear predisposing - VTE in patient < 45y or with 1st deg relative w/ VTE < 45y
established VTE
medical syndrome (nephrotic syndrome, MPN, - Recurrent or multiple thromboses
HIT) - Arterial thrombosis (test for APS)
- Warfarin-induced skin necrosis (test for protein C deficiency)
- Females considering OCP/HRT without FHx - Females considering OCP/HRT or planning pregnancy if +
Patients without
thrombophilia FHx high-risk thrombophilia
VTE – special
- Patients with cancers at high risk of VTE - Patients with cancer at low/intermediate risk of VTE and
situations
(Khorana score)  thromboprophylaxis undergoing tx if +FHx VTE
INHERITED CONDITIONS
Condition Clinical Pearls Testing
- APC resistance assay (reliability iso heparin products
Factor V Leiden - Most common inherited cause of hypercoagulability
depends on assay)  reflex FVL genetic test
PTG mutation - 2nd most common cause; prothrombin (FII) - PCR for PTG G20210A mutation (most common)
- Free protein C/S functional assays
- Activated protein C/S inactivate FVa and FVIIIa; level
Protein C/S -  by acute thrombosis, VKA, liver dz, DIC, chemo,
(more common) or function leads to hypercoagulability
deficiency uremia (Prot C), pregnancy/OCP/nephrotic sx (Prot S)
- A/w warfarin-induced skin necrosis (screen if hx)
-  by DOAC (Prot C/S), HLD and nephrotic sx
- level or function - ATIII functional assay assessing FXa inhibition
Antithrombin III
- Heparin works via ATIII to inactivate FIIa and FXa; if -  by acute thrombosis, UFH/LMWH, liver dz,
deficiency
ATIII defic., will be heparin-resistant & require doses nephrotic;  by DOAC, direct thrombin inhibitors
ACQUIRED CONDITIONS
- Primary or secondary to SLE/other autoimmune dz - Lab criteria: ⊕ LA, anti-cardiolipin, or anti-β2
- S/Sx: Unexplained venous/arterial thrombosis (esp. in glycoprotein >2x ULN, twice 12w apart
Antiphospholipid
young pts), adverse pregnancy outcomes, livedo - LA unreliable on AC (false ⊕) and acute thrombosis
syndrome
reticularis/racemosa, valvular dz,  platelets (false ⊝); anti-CL and β2GP not affected
(APLS)
- Catastrophic APS: ⊕ aPL w/ 3+ organ thromboses in - ⊕ aPL Ab can be seen in infx, rheum, malig, meds
<1w, mortality ~50%. Tx: AC + steroids + TPE or IVIG - False ⊕ VDRL (NEJM 2018;378:2010)
C O A G U L O P A T H Y (NEJM 2014;370:847)
Disorders of 1° hemostasis (platelet # or function, VWD  mucocutaneous bleeding, petechiae, menorrhagia) or 2° hemostasis (factor
deficiency/activity  deep tissue bleeding, joint, organ, brain; prolonged PT/PTT)
• Rule out artifact, anticoagulant use, or systemic disease (cirrhosis, DIC, abx, malnutrition, renal disease, cancer)
o Consider diseases affecting vascular function (e.g. HHT, scurvy, EDS)
• If prolonged PT/PTT and etiology is not clinically apparent, order mixing study w/ normal plasma (JAMA 2016;316:2146)
o If PT/PTT corrects: supports clotting factor deficiency (confirm w/ factor specific assays)
o If no/partial correction: supports presence of inhibitor (confirm w/ inhibitor specific assays)
 Types: drugs (e.g. heparin), acquired factor inhib (VIII, V>>IX, XI; autoimmune d/o, malig), nonspecific inhib (e.g. LAC)
o If work-up is unrevealing, consider VWD testing, platelet function testing, thrombin time (TT), fibrinogen, factor XIII
• Tx: replace missing factor, eliminate inhibitor (immunosuppressants), treat underlying condition
Hemophilia: most common severe bleeding disorder, X-linked. Caused by Factor VIII (Hemophilia A) or Factor IX (Hemophilia B)
deficiency reduced clot formation and stabilization bleeding (joint damage from recurrent bleeds common cause of morbidity)
• Dx: PTT (can be normal in mild def)  1:1 mixing study (if PTT corrects = factor def)factor specific assay to distinguish A and B
• Tx: Concentrates of FVIII/FIX ppx for bleeding events or on-demand w/ bleeds. Emicizumab (bispecific ab which functions like Factor
XIII) approved for prophylaxis in Hemophilia A. Multiple novel gene therapies currently under investigation (Blood 2019;133:389).
Coagulation Defect Normal aPTT Prolonged aPTT
Platelet dysfunction (VWD, other platelet Intrinsic pathway: VIII, IX (hemophilia), XI (Ashkenazi);
Normal PT
disorders), Factor XIII VWD; XII, PK, HMWK (no bleeding); LAC (prothrombotic)
Extrinsic pathway: Factor VII, warfarin, liver Common pathway: liver disease, DIC, Vit K deficiency,
Prolonged PT
disease, Vit K deficiency warfarin. Rarely common pathway deficiency/inhibitor
DIC: massive activation of coag cascade caused by various inflamm. etiologies (sepsis, CA, obstetric complications, trauma, pancreatitis).
Consumption of coag. factors  bleeding, microvascular thrombosis, MAHA, organ dysfunction (kidneys, lungs, CNS, adrenal)
• Dx: PT/PTT, D-dimer, fibrinogen, plts, +schistos, LDH, hapto (often normal coags in chronic DIC). Can differentiate DIC
from liver dz w/ FVIII (FVIII present in endothelium, not liver), DIC score
• Tx: treat underlying cause, transfuse plts if <10k, cryo if fibrinogen <100, FFP if INR >2. Amicar contraindicated generally.
o If severe bleed: plts <30 or 50 and Fibrinogen <150

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Hematology Anticoagulation Agents

O R A L A G E N T S (ASH: Blood Adv 2018;2:3257; CHEST: Chest 2021;160:2247)
Agent Dosing Bridging/Switching/Reversal
Bridging: (see below to bridge from parenteral AC):
- Initiation: 5mg qd x2d; frail, HF, kidney/liver dz: consider
To parenteral AC: start IV w/o bolus when INR <2
2.5mg; BMI >40: consider 7.5mg
Reversal for life-threatening/intracranial bleed: (Ellucid)
- Adjust by INR, which lags 48h behind dose Δ
Warfarin (Coumadin) 1) Vit K 5-10 mg IV over 10-20m
Monitoring: (UW Dosing Nomogram)
- Vitamin K antagonist: 2) 4-factor PCC/Kcentra over 10m if INR >2 (≥1.5 in ICH)
INR < goal: by 5-15% or consider booster dose
inhibits vitamin K- MGH dosing: Kcentra 1500u, follow INR q30m w/ pharm
INR at goal: no change
dependent gamma- Non-MGH dosing: INR 2-4: 25u/kg (max 2500u), INR 4-
INR between 0.1 and 1.0 above goal: by 5-15%,
carboxylation of Fs II, VII, 6: 35u/kg (max 3500u), INR >6: 50u/kg (max 5000u)
consider holding a dose
IX, X, & Protein C+S If Kcentra not available, give 2U FFP by rapid infusion.
INR >1 above goal: hold until INR at goal, restart but 
- t1/2 40h (variable) Reversal without active bleeding:
by 10-20%
INR >10 Vit K PO 2.5-5mg
If overlap with direct thrombin inhibitor: check
INR 4.5-10 Vit K PO 1-2.5mg if ↑risk of bleeding
chromogenic FXa: goal 20-40%
INR <4.5 no reversal, hold warfarin
Bridging/switching: To parenteral AC: start 12h after last
Dabigatran (Pradaxa) - Non-valvular AF: 150mg PO BID if GFR >30, 75mg PO
dose (24h if CrCl <30). From parenteral AC: start <2h
- Direct thrombin (IIa) BID if GFR 15-30 (RE-LY, NEJM 2009;361:1139); some use
before next dose. To warfarin: start 3d before
inhibitor, t1/2 12-17h 100mg PO BID dose if high bleeding risk
dabigatran  if CrCl ≥50; 2d if CrCl 31-50, 1d if GFR
- 80% renal clearance - VTE: 150mg PO BID after 5d UFH/LMWH (RE-COVER,
15-30; bridge PRN. From warfarin: hold warfarin and
- P-gp substrate NEJM 2009;361:2342)
start dabigatran when INR < 2
- S/e: dyspepsia, - PPX: 110mg x1 then 220mg PO QD (RE-NOVATE II,
Reversal if life threat.: can be dialyzed (Ellucid)
?coronary events Thromb Haemost 2011;106:721)
- Idarucizumab 5g (RE-VERSE, NEJM 2017;377:431)
Rivaroxaban (Xarelto) - Non-valvular AF: 20mg PO QD if GFR >50, 15mg ifBridging/switching: (J Thromb Thrombolysis 2016;41:206)
- Direct Xa inhibitor GFR 15-50 (ROCKET AF, NEJM 2011;365:883) - To parenteral AC: start when next DOAC dose due
- t1/2 5-9h; 11-13 in elderly - VTE: 15mg PO BID x21d, then 20mg QD. After 6mo,- From LMWH/fonda: start w/in 0-2h of next dose
- 66% renal clearance consider  to 10mg QD if ongoing risk for VTE (NEJM
- From UFH: start immediately after drip stops (for
- Avoid with CYP3A4 and 2010;363:2499; NEJM 2012;366:1287; NEJM 2017;376:1211)
edoxaban, start 4h after stopping UFH)
P-gp dual inhibitors - PPX: 10mg PO QD (MAGELLAN, NEJM 2013;368:513) - From warfarin:
• Start rivaroxaban when INR <3
- Non-valvular AF: 5mg PO BID, 2.5mg BID if 2/3: Cr
Apixaban (Eliquis) • Start apixaban when INR <2
≥1.5, Wt ≤60kg, age ≥80; some use 2.5mg BID if CrCl
- Direct Xa inhibitor • Start edoxaban when INR ≤2.5
15-29 (ARISTOTLE, NEJM 2011;365:981)
- t1/2 12h - To warfarin: (Note: all INR)
- VTE: 10mg BID x7d, then 5mg BID x6mo; after 6mo,
- lower renal clear. (25%) • Rivaroxaban/apixaban: stop, start warfarin, and use
consider  to 2.5mg BID (NEJM 2013;369:799 & 368:699)
(can use in ESRD) parenteral agent until at therapeutic INR
- PPX: 2.5mg BID (NEJM 2009;361:594)
• Edoxaban: cut edoxaban dose by ½ and begin
Edoxaban (Savaysa) - Non-valvular AF: 60mg PO QD; 30mg if CrCl 15-50 or
warfarin,  edoxaban once INR ≥2
- Direct Xa inhibitor wt ≤60kg; do not use if CrCl>95 (ENGAGE AF, NEJM
- DOAC to DOAC: start when next dose due
- t1/2 10-14h 2013;369:2093)
Reversal if life-threat.: not dialyzed off (Ellucid)
- 50% renal clearance - VTE: 60mg QD after 5d UFH/ LMWH, 30mg QD if CrCl
- Andexanet alfa (recombinant FXa): bolus  2h gtt
- Avoid if CrCl >95 or <15 15-50, ≤60kg, or taking P-gp inhibitor (NEJM
(NEJM 2015;373:2413; NEJM 2019;380:1326)
- P-gp substrate 2013;369:1406)
PARENTERAL AGENTS
Agent Dosing/Monitoring Bridging/Switching Reversal Other
Heparin (UFH) - ACS: 60U/kg  12U/kg/h; PTT 63-83
- To LMWH: give LMWH & - Protamine: 1mg per - Preferred in renal
- Binds & activates - VTE: 80U/kg  18U/kg/h; PTT 70-100
 UFH at same time 100U heparin or 1mg failure (CrCl <30),
ATIII  inactivates - PPX: 5,000U SC q8-12h
- To warfarin:  UFH LMWH (max 50mg). peri-procedure, poor
Xa & IIa - Monitoring: PTT; anti-Xa (goal 0.3-0.7) if
once therapeutic ≥2d 60% reversal for absorption, pregnancy
- t1/2 60-90min baseline PTT or high doses; ACT if )
LMWH, most effective
Enoxaparin (LMWH, - ACS/VTE: 1mg/kg BID; QD if GFR <30 - To UFH:  LMWH & - Acute VTE: LMWH >
if last dose within 8h
Lovenox) - PPX: 40mg SC QD; 30mg BID if risk; start UFH w/o bolus 1-2h UFH (Cochrane Rev
- Do NOT give FFP
- Binds & activates 30% if BMI ≥40; 30mg QD if GFR <30 before LMWH dose due 2017)
(has ATIII, which
ATIIIinact. Xa>>IIa - Monitoring: not routine; can check anti- - To warfarin:  LMWH - Prolonged t1/2 in
potentiates AC effect)
- t1/2 4.5-7h Xa 4h after 4th dose, goal 0.5-1.0 once therapeutic INR ≥2d renal failure
- VTE: <50kg  5mg QD | 50-100kg  - To warfarin:  fonda.
Fondaparinux
7.5mg QD | >100kg  10mg QD once therapeutic INR ≥2d - aPTT at
(Arixtra)
- PPX: 2.5mg SC QD - To UFH: start UFH (no therapeutic doses
- Binds & activates - No reversal agent
- CrCl <30: contraindicated bolus) 1-2h before due - If CrCl 30-50,
ATIIIinact. Xa only
- Monitoring: not routine; can check 4h - From UFH: start 1h after consider Δ agents
- t1/2 17-21h
anti-Xa UFH 
Argatroban - HIT: 1-2mcg/kg/min
- To warfarin:  once
- Direct IIa (thrombin) - Monitoring: PTT, goal 1.5-3x baseline
chromogenic factor Xa 20- - No reversal agent
inhibitor - Caution in critically ill, cardiac
40% (argatroban INR)
- t1/2 45min dysfunction, liver disease
Factor XI/XII inhibitors under investigation (Blood 2022;1:495): antisense oligonucleotides (ASO), antibodies (abelacimab NEJM
2021;385:609, osocimab, small molecules (milvexian, asundexian)
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Hematology Anticoagulation Management

CHOOSING AN ANTICOAGULATION AGENT
Guidelines: CHEST for VTE: Chest 2021;160:2247, ASH for VTE: Blood Adv 2021;5:927, ASCO for VTE in CA: JCO 2020:38;496; ACC/AHA/HRS for AF:
JACC 2019;74:104, CHEST for AF: Chest 2018;154:1121; AHA/ACC for Valvular HD: JACC 2021;77:e25
Obesity Avoid DOAC if BMI ≥45 or wt ≥150kg, use warfarin (Circulation 2024;149). If use, peak/trough (ISTH: JTH 2021;19:1874)
Apixaban (CARAVAGGIO, NEJM 2020;382:1599), edoxaban (NEJM 2018;378:615), rivaroxaban (JCO 2018;36:2017), LMWH >
Active warfarin (CLOT, NEJM 2003;349:146). Prefer apix or LMWH in GI/GU CA w/ intralum. lesions (edox/rivarox bleeding risk).
VTE Malignancy DOAC > LMWH for short-term VTE tx, either for long-term. Apix/rivarox ppx VTE in high-risk outpts, suggest in mod-
risk: consider if Khorana ≥2 (AVERT, NEJM 2019;380:711; CASSINI, NEJM 2019;380:720). LMWH ppx OK in high-risk outpts
Recurrent If on non-LMWH: switch to LMWH. If on LMWH: increase LMWH by 1/4-1/3 of current dose and check Xa level
All Others DOACs > warfarin > LMWH
Non-valvular DOACs > warfarin for stroke risk, mortality, and bleeding risk
Valvular Warfarin if mod/severe MS (regardless of CHADS2VASC)
Dual (P2Y12i+OAC) v triple therapy (+ASA): dual w/ bleeding, likely no events (Annals 2020;172:474; EHJ 2019;40:3757)
Dual therapy: DOAC + clopidogrel x-6-12mo. Rivaroxaban 15mg qd (some use 20mg) (PIONEER AF, NEJM
AF 2016;375:2423) & dabigatran 150mg BID (RE-DUAL PCI, NEJM 2017;377:1513) in guidelines, also data for apixaban (5mg
+ PCI BID unless 2.5mg indicated) (AUGUSTUS, NEJM 2019;380:1509) & edoxaban 60mg QD (*though didn’t bleeding v VKA)
(ENTRUST-AF PCI, Lancet 2019;394:1335). Warfarin + clopi or ticag also option (WOEST, Lancet 2013;381:1107). Ticag may be
used in-hospital or if very high thrombotic risk. After 12mo, can likely Δ to OAC alone (AFIRE, NEJM 2019;381:1103)
If triple therapy chosen (high thrombotic/low bleed risk), typically d/c ASA & transition to P2Y12i+OAC therapy at 1-6 wks
Mechanical Warfarin (+ASA for aortic On-X valve). DOACs not approved. INR goal for AVR = 2.5 (3 if +AF, VTE, etc.); MV/TV = 3
Valve
Bioprosthetic SAVR: Warfarin (INR 2.5) + ASA 3-6moASA. TAVR: ASA/clopi 3-6moASA. If AF/VTE, OAC+clopiOAC (evolving)
APLS Warfarin. Warfarin > rivaroxaban in high-risk APLS (TRAPS Blood 2018;132:1365; AIM 2019; 171:685)
ACS ( PCI) Very low dose rivaroxaban (2.5mg BID) added to ASA/clopidogrelCV mortality but major bleeding (NEJM 2012;366:9)
Very lose dose rivaroxaban (2.5mg BID) + ASA  MACE vs. ASA alone; major bleeding but no Δ in ICH or fatal
2° prevention
CAD bleeding (COMPASS, NEJM 2017;377:1319). Can consider if high risk for events & low bleeding risk
12 mo DAPT, new research w/ 1-3 mo DAPT+12 mo clop non-inf to 12 mo DAPT (STOPDAPT-2, JAMA
s/p PCI
2019;321:2414); can integrate DAPT score into clinical decision making
ANTICOAGULATION BRIDGING
Guidelines: ACC: JACC 2017;69:871; ASH: Blood Adv 2018;2:3257; CHEST: Chest 2022;162:E207
Indication AF VTE Mechanical Valve
Thrombotic
Risk Factors Bridge? Risk Factors Bridge? Risk Factors Bridge?
Risk
- CHA2DS2-VASc ≥7 - Any mechanical MV
- VTE <3 mo
(or CHADS2 5-6) Yes, unless - Caged ball/tilt disc
- Severe thrombophilia: protein
High - CVA/TIA, or systemic major bleed/ICH Yes AVR Yes
C/S or ATIII def, APLAS,
embolism <3mo <3mo - Any mechanical valve
multiple abnormalities
- Rheumatic valvular dz w/ CVA/TIA <6mo
- VTE 3-12mo
- CHA2DS2-VASc 5-6 (or Likely bridge if - Recurrent VTE - Bileaflet AVR w/ ≥1 Consider against
CHADS2 3-4) prior CVA/TIA - Active malignancy CVA risk factor: age risk of procedural
Moderate No
- CVA/TIA or systemic and if no risk of - Non-severe thrombophilia: >75, AF, prior CVA/TIA, bleeding
embolism >3mo bleeding heterozygous factor V Leiden, HTN, DM2, CHF (UpToDate table)
PTG mutation
- CHA2DS2-VASc ≤4 (or
CHADS2 0-2) - VTE >1y & no other risk - Bileaflet AVR w/o AF
Low No No No
- No prior CVA/TIA or factors or CVA risk factor
systemic embolism
• BRIDGE trial (NEJM 2015;373:823) demonstrated no difference in arterial embolism but risk of bleeding w/ bridging in pts with AF
undergoing invasive procedure requiring interruption of VKA (NB: excluded pts w/ mech. valves, stroke/TIA <3mo, major bleeding
<6w, CrCl <30, plt <100k)
• Bridging Vitamin K Antagonist (VKA) w/ UFH or LMWH (prefer LMWH if kidney function allows):
o Stop VKA 5d prior to procedure if therapeutic INR. Start UFH or LMWH when INR <2
o Stop UFH 4-6h prior to surgery and LMWH 12 or 24h prior to surgery (depending on dosing interval)
o Restart UFH/LMWH at 24h postop. if low postprocedural bleeding risk or 48-72h if high risk.  when INR >2
o Resume VKA w/in 24h postop if no bleeding complications (will not early bleeding risk because effect takes 24-72h)
• DOACs: no bridging required; most can be stopped 24-72h prior to surgery, depending on procedural bleeding risk & renal function
Drug High Bleed Risk* Low Bleed Risk*
CrCl >50 CrCl <50 CrCl >50 CrCl <50
*For bleeding risk stratification
Dabigatran ≥48h (4 doses) ≥96h (8 doses) ≥24h (2 doses) ≥48h (4 doses)
use procedural bleeding risk +
Rivaroxaban ≥48h (2 doses) ≥48h (2 doses) ≥24h (1 dose) ≥24h (1 dose)
HAS-BLED score.
Apixaban ≥48h (4 doses) ≥48h (4 doses) ≥24h (2 doses) ≥24h (2 doses)
Edoxaban ≥48h (2 doses) ≥48h (2 doses) ≥24h (1 dose) ≥24h (1 dose)
o If low bleeding risk, can resume 24h after procedure. If high bleeding risk, wait 48-72h. If NPO or more procedures: UFH/LMWH.
**See Peri-Procedural DOAC Management for MGH-specific peri-procedural guidance for cardiac cath. lab & IR procedures**
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Hematology Transfusion Medicine

TRANSFUSION MEDICINE TERMINOLOGY
• ABO typing: front type: A/B antigens (pt's RBC + reagent anti-A or B); back: anti-A or B in plasma (pt’s plasma + reagent RBCs)
• Rh(D) typing: tests for D antigen on RBC (pt’s RBC + reagent anti-D) – NB: anti-D is not a naturally occurring antibody
• Screening (T&S): tests for unexpected antibodies in pt’s plasma (pt’s plasma + screening RBC + Coomb’s reagent), “active” x3d
• Crossmatching (T&C): final confirmation test by mixing pt’s plasma & donor RBC; performed just prior to transfusion
• Direct antiglobulin test (DAT/Coomb’s Test): tests for Ab or complement on RBCs (RBCs + Coomb’s reagents [anti-IgG, anti-C3])
BLOOD PRODUCTS
Product Description Indications Notes
- Hgb <7 (NEJM 2014;371:1381; NEJM 2013;368:11)
1U ~ 330cc - Hb < 7.5 if cardiac surgery (JAMA 2023;1892:1902) - Each unit: Hct ~55%
Processing - Hgb <8 if CAD, ortho surgery (JAMA 2021;325:552) - 1U Hgb ~1
Red Blood - Hgb <10 if acute MI (NEJM 2023;389:2446)
1. Leukocyte reduction - Rate: if active
Cells - Acute hemorrhage (>15% intravascular volume)
2. Irradiation hemorrhage, give over
3. Washing (rarely) - AIHA (no specific Hgb threshold) 60-90min
- Sickle cell disease (see Sickle Cell Disease)
1U = 6pk = 300cc - Response at 30-60m:
Types - <10k: PPX spont bleeding (NEJM 1997;337:1870), 1U PLT ~30K
1. Apheresis platelets antifibrinolytics in refractory thrombocytopenia in CA - No evidence that
derived from 1 donor - <50k: active major bleed, intra- or post-op bleed, ppx prior apheresis > pooled plts
Platelets 2. Pooled platelets from to invasive procedures (<30k bedside procedures) - No evidence that
multiple donors - <100k: post-bypass bleed, ICH/ophthalmic (no data) platelets reverse anti-
Processing - ITP: only if life-threatening CNS/GI/GU bleed (often platelet agents (Lancet
1. Leukocyte reduction preceded by wet purpura, mucus membrane bleeding) 2016;387:2605)
2. Irradiation - CI: TTP/HUS, HIT
- Active bleed d/t deficiency in one or more coag. factors
- Response: 2U coag
1U = 250cc - ALF: consider for plt or INR only if bleed or pre-op
activity ~10%
Typical starting dose 2U - Cirrhosis: cryo preferred, treating INR w/ FFP bleeding
- Max correction: INR
Fresh due to portal pressures, has prothrombotic effect (J Thromb
Non-cellular portion of 1.7
Frozen Haemost 2021;19:664)
blood containing all coag - Effect <6h due to short
Plasma - Warfarin reversal: Vit K>PCC>FFP (Circ 2012;125:2944)
factors; separated and t1/2 of FVII
- Trauma, DIC, congenital TTP (for ADAMSTS13)
frozen after collection - Potentiates effect of
- Ppx prior to bedside invasive procedures for INR >2.0 (low
heparin with ATIII
quality evidence [Cochrane 2019:11:CD012745])
- Fibrinogen <100-150: 50-100mg/dL give 10U; <50 give 20U - 10U cryo should
10U = 150cc - Massive transfusion w/ fibrinogen or abnl ROTEM/TEG fibrinogen ~85mg/dL
Cryo- - Complex cardiac surgery (JAMA 2017;217:738) - Fibrinogen t1/2 3-5d
precipitate Contains factor VIII, factor - Postpartum hemorrhage (Br J Anaesth 2015;114:623) - FVIII or vWF
XIII, VWF, and fibrinogen - DIC, uremia if DDAVP ineffective, FVIII deficiency, VWD replacement: cryo is
- Cirrhosis: fibrinogen <100-120 or c/f dysfibrinogenemia last resort therapy
VIII, IX, rFVIIa, ATIII;
- Blood Transfusion
combo: II+IX+X (Profilnine);
- Coagulation factor deficiency/inhibitor Service approval
Coagulation PCC = II+VII+IX+X
- Von Willebrand’s disease (Humate-P, NovoSeven) required
Factors (Kcentra), FEIBA (anti-
- VKA reversal (IV Vit K first, for severe bleed PCC > FFP) - S/E: allergic rxn,
inhib. complx), vWF/FVIII
thrombosis
(Humate-P)
Contain Lysine derivatives - Amicar: load 4-5g over
- Trauma (Health Tech 2013;17:1)
that bind to plasminogen to 1h  1g/h for 8h or
- Postpartum hemorrhage (Lancet 2017;389:2105)
fibrinolysis and until bleeding controlled
- Cardiac surgery (NEJM 2017;376:136; J Thor C Surg
Antifibrinoly hemostasis - TXA: load 1g over
2019;157:644), ECMO
tics Types (topical, PO, IV): 10min  1g over 8h
- Cirrhosis: when hyperfibrinolysis suspected (see ESLD)
Aminocaproic acid cont. infusion
- Major ortho surgery, plt refractoriness in HLA
(Amicar), Tranexamic acid - S/E: risk of seizures w/
alloimmunization, closed space bleeding, coag factor inhibitor
(TXA) high dose TXA
5% if hypovol/intravasc depl., 25% if fluid/Na restricted
Types - C/I: traumatic brain
- Cirrhosis: HRS, SBP, LVP (see ESLD)
1. 5% (iso-oncotic) injury
- Shock: 4% albumin similar to 0.9% NS for IVF resuscitation
Albumin 2. 25% (hyper-oncotic)
(when alb. >2) (SAFE, NEJM 2004;350:2247) (Also see IV Fluids and
Both contain 12.5g albumin
- ARDS: 25% albumin (25g) q8h x3d + lasix gtt x3d  O2, Electrolyte Repletion)
& 154mEq Na (isotonic)
neg. TBB (when alb. <2) (Crit Care 2005;33:1681)
- Immunodeficiency: hypogammaglobulinemia IgG <400
Types - SE: infusion reactions,
- Immunosuppression in autoimmune disease (e.g. ITP,
Polyclonal IgG and trace aseptic meningitis,
IVIG AIHA, post-transfusion purpura, acquired VWS)
plasma contaminants hyperosm renal tubular
- Neuro: CIDP, myasthenia gravis, GBS
Dose adjust for obesity injury, thrombosis
- ID: toxic shock syndrome, Kawasaki disease
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Hematology Transfusion Medicine

TRANSFUSION MODIFICATIONS
• Leukoreduction (LR): filters leukocytes to (1) HLA sensitization in chronically transfused pts / heme malignancies, bone marrow / kidney /
heart / lung transplant candidates (not liver transplant) (2) CMV risk & (3) febrile non-hemolytic transfusion reaction
• Irradiation: prevents proliferation of donor lymphocytes from attacking the recipient (transfusion-associated-GVHD in 1st degree directed
donors); indications: heme malignancy & BMT to prevent GVHD; not indications: solid tumor, solid organ transplant, HIV
• Saline-washing: removes anti-IgA Ab & plasma proteins; indications: severe anaphylaxis to blood products (w/ or w/o IgA def.)
ADMINISTERING BLOOD PRODUCTS
• Consent: required for administration of all blood products, discuss type of product, indication, benefits/risks, possible alternatives
• Ordering: “Prepare RBC” (or platelets/FFP/cryo)  select number of units to prepare, indication, applicable modifications (see below) and
“Transfuse RBC”  select number of units to administer, and rate of admin (usually over 2-4h)
• Monitoring response: order post-transfusion CBC to be drawn 15-30min after transfusion (if not actively bleeding)
MASSIVE TRANSFUSION AND EMERGENCY BLOOD MGH POLICY
Call Blood Bank (x63623) & physically run down w/ patient sticker and pick-up slip to Gray/Bigelow 2 to pick up cooler(s)
Emergency Release Blood: 4u of uncrossmatched whole O blood (for men & women >50y). For women <50y, 6u group O pRBCs (Rh-neg), 3u
plasma, and one dose of platelets. Only one cooler, sufficient for most bleeding.
Massive Transfusion Protocol: One cooler of 4u whole O blood followed by coolers of 6u O pRBCs, 3u plasma, and 1 dose platelets released
q15min until the blood bank is called to stop. MUST have a blood bank sample sent before 3rd cooler or plasma/platelets will NOT be released.
• Activate MTP when anticipate transfusing 50% TBV (~5U pRBC) in 2h OR 100% TBV (~10U pRBC or 5L plasma) in 24h
• Occurs most commonly in trauma, GI bleeding, cardiac surgery, obstetric complications, rupture of major blood vessel
• Access: Ideal = short and stubby: ≤18g PIV, MAC/Cordis. Take off clave (blue cap) and pressure bag blood vs Belmont.
• No universally accepted ratio: 1:1-2:1 (1u pRBC:1-2u FFP:1u plt) transfusion protocol is most common. FYI: 1 bag /dose plt ~4-6u plts
o Goals: Hb >7-10, INR <2 (unless ESLD), PLT >50k, fibrinogen >100-150
o Cryoprecipitate is ordered separately from MTP guided by fibrinogen or given empirically (1-2 pools Cyro:7-8 pRBC). FYI: 1 pool=5u
o Excessive FFP a/w ARDS in pts not requiring massive transfusion.
• Correct coagulopathy  IV vit K/PCC, AC reversal agents, platelet dysfunction (ASA, plavix, uremia)  DDAVP 0.3mcg/kg
• Consider IV amicar or IV TXA (especially in obstetric, surgical, or trauma. Not helpful in GIB (HALT-IT). Dosing on previous page)
• Complications: hypothermia (cover pt w/ bair hugger, use blood/fluid warmers), hypo-Ca2+ (2/2 citrate, administer CaCl2 to target an iCal of
1-3 mM or consider empiric 1-2g per 6 units pRBC), dilutional coagulopathy esp. w/ IVF, metabolic alkalosis (citrate metabolized to bicarb),
hyper-K+, females of reproductive age may need rhogam post resuscitation.
P L A T E L E T R E F R A C T O R I N E S S : failure to achieve acceptable platelet count following transfusion. Normal t1/2 of 3 days
• Alloimmune: Ab to class I HLA antigens (e.g. +PRA) or PLT-specific antigens. RFs for HLA alloimmunization: multiple pregnancies,
prior transfusions with non-leukoreduced blood products, organ transplants (NEJM 1997;337:1861). Drug-associated ITP (heparin, sulfa,
vanc, linezolid, piperacillin, rifampin, thiazide, anti-GpIIb/IIIa)
• Non-alloimmune: non-HLA Ab-mediated; 2/3 of cases; Ddx: sepsis/DIC, HIT, TTP, CVVH/bypass/IABP, splenomegaly, liver dz,
HSCT, viral infection (HIV/HCV) & drugs (amphotericin)
• Evaluation: check plt post-transfusion on 2 occasions and assess plt recovery (15min-1h later) & plt survival (18-24h later)
o Inadequate plt recovery: corrected count increment <5k on 2 occasions; also usually indicated by plt  <10k x2  alloimmune
refractoriness (JCO 2001;19:1519)
o Normal plt recovery but survival  non-alloimmune refractoriness
• Alloimmune refractoriness workup:
o Consult Blood Transfusion Service p21829. Studies will not be processed without discussing w/ them first
o Send Panel Reactive Antibody: HLA class I Ab screen; test for alloreactivity against HLA antigens. Normal is 0%, range 0-100%
o If platelets required urgently (i.e. actively bleeding), notify Blood Bank and ask for send out to Red Cross
• Management: with each platelet transfusion, must check a post-transfusion CBC w/in 15-60min of completion
o Compatible platelets (specific HLA-antigen negative) or crossmatch compatible
o ABO/HLA-matched apheresis single-donor plts from Red Cross. Takes days to process. Each unit has a shelf life ~3 days
o Consider Amicar if bleeding (contraindicated in thrombotic DIC); correct coagulopathy with DDAVP if e/o uremia
M A N A G E M E N T O F A N E M I A I N J E H O V A H ’ S W I T N E S S E S (Am J Hematol 2017;92:1370)
• Discuss management with patients on a case-by-case basis; consider using a checklist of blood product types
• Acceptable products: hematinics (iron, folate, B12, recombinant human EPO), non-blood volume expanders (NS, LR, hydroxyethyl starches),
hemostatic agents (amicar, TXA, DDAVP, albumin-free clotting factors)
• Acceptable to some: autotransfusion, HD/apheresis/bypass/ECMO, hemostatic products w/ blood fractions (coag. factors, PCC), plasma-derived
products (albumin, cryo, Ig), products potentially containing albumin (rhEPO, vaccines), BM/organ transplantation
• Unacceptable products: whole blood, pRBCs, platelets, FFP, cryo, autologous blood transfusion
• Bleeding, preop: consider IV iron + rhEPO to speed up erythropoiesis  rhEPO onset 2-6 days if Fe/folate/B12 replete
• Critically ill: no expert consensus, consider rhEPO 200-300U/kg IV q24h or 250-500U/kg SQ q48h for goal periop Hb >10-12  can be extrapolated
to hemodynamically unstable/bleeding pts
THERAPEUTIC APHERESIS
• Plasmapheresis (plasma exchange): removes plasma, replaces with saline, albumin or plasma (depending on pt. condition)
Indications: TTP (replace ADAMTS13, NEJM 1991;325:393), hyperviscosity, cryo, Guillain-Barre, CIDP, MG, ANCA, anti-GBM
• Cytapheresis: removes abnormal or excessive # blood cells
Indications: leukapheresis for hyperleukocytosis (goal WBC <100, controversial); RBC exchange for sickle cell patients with acute decompensation
(organ failure, acute chest, etc.), severe babesiosis (high grade parasitemia >10, severe hemolysis, or pulm/liver/renal dz); platelet removal for
thrombocytosis rarely done (goal plts <1000)

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Hematology Transfusion Reactions

I N I T I A L E V A L U A T I O N : Blood Bank (x63623, p21829) (Br J Haematol 2023;201;832)
• S/Sx: f/c/rigors, hives/flushing/pruritis, infusion site pain, shock/oliguria, SOB, Acute Delayed
wheezing, crackles, hypoxia, angioedema, bleeding diathesis, nausea/vomiting AHTR, FNHTR,
DHTR, TA-
1. STOP transfusion, ABCs, VS q15min, notify blood bank Immune- Urticaria/hives,
GVHD, post-tx
2. If only urticarial sx or isolated T ≤39C  treat sx, resume once symptoms resolved mediated Anaphylactic,
purpura
3. Initial workup to consider: CBC, BMP, LFTs TRALI, IgA def
o High suspicion for hemolysis: DAT, Bili, LDH, hapto, crossmatch, UA, smear Non- Cold toxicity,
o High suspicion for sepsis: GS/BCx of both pt & blood product immune citrate toxicity, Viral infection
o High suspicion for TRALI/TACO: JVP, NT-proBNP, ABG, portable CXR mediated sepsis, TACO
Reaction/Per-Unit Risk Presentation/Diagnosis Pathophysiology Treatment/Prevention
ACUTE TRANSFUSION REACTIONS (<24H)
Sx: 15min to 2-4h; fever/chills, - ABO/Kidd incompatibility (preformed Tx: IVF (± diuresis) for goal
Acute Hemolytic nausea, tachycardia, HoTN, Abs)  intravascular hemolysis (IgM), UOP >100cc/hr x24h
(AHTR) back/flank pain, bleeding, DIC cytokine/complement activation - Monitoring: HoTN, AKI, DIC,
1/76,000-137,000 Dx: +Hb (blood/urine), +DAT, - Rh/Kell/Duffy incompatibility  less mortality ∝ volume transfused
+Bili/LDH, +smear (spherocytes) severe extravascular hemolysis PPX: careful crossmatch
- Donor WBCs produce TNFα, IL1,
Sx: 1-4h; low-grade fever,
Febrile Non-Hemolytic IL6
chills/rigors, HA, flushing Tx: APAP ± meperidine
(FNHTR) - RBC: donor WBCs activated by
Dx: hemolysis workup negative, PPX: leukoreduction, little
1/14 (PLT) recipient anti-HLA Abs
also send BCx (results would be evidence for pre-medication
1/200-2,500 (RBC) - PLT: donor WBCs make cytokines
negative)
before transfusion
Sepsis (Bacterial Sx: 15-60min; high fever, rigors, - Bacteria >> viruses in donor blood Tx: antibiotics, quarantine all
Contamination) abd sx, HoTN/shock - RBC: Yersinia, PsA (endotox-GNRs) other similar products
1/75,000 (PLT) Dx: GS/BCx of both pt & bag - PLTs: Staph epi (GPCs) PPX: routine screening
Tx: pause 
Sx: anytime during/after
diphenhydramine  resume if
Urticaria/Hives transfusion; localized or diffuse - IgE-mediated hypersensitivity to
urticaria resolves
1/33-100 hives & redness donor plasma proteins
PPX: washed products, no
Dx: no work-up necessary
evidence for pre-medication
- IgE-mediated hypersensitivity in
Sx: within min; acute HoTN, Tx: ABCs, O2, IVF ±
recipient lacking IgA or haptoglobin
Anaphylactic/ angioedema, urticaria, wheezing, pressors, epi IM Q15min,
- Bradykinin-mediated flushing/HoTN
Anaphylactoid abd pain methylpred 125mg,
in pt taking ACEi or neg charged
1/20,000-50,000 Dx: clinical; consider IgA def., diphenhydr. 25-50mg
filters (e.g. plasma exchange w/
serial mast cell tryptase PPX: washed products
albumin)
Tx: ABCs, O2, contact blood
Transfusion-Related Sx: 1-6h; dyspnea ± fever - Pre-transfusion stress activates lung
bank, intubation
Acute Lung Injury Dx: NT-proBNP nl, bilateral CXR endothelial cells & primes PMNs
PPX: male donor plasma
(TRALI) infiltrates w/o CHF, - Donor anti-HLA Abs/bioactive
(fewer anti-HLA, anti-PMN
1/12,000 (RBC) noncardiogenic pulm edema factors attack primed PMNs of
Abs); defer donors w/ prior
1/38,000 (PLT) (ARDS) recipient
assoc. TRALI
Transfusion-Assoc. Sx: 1-6h; dyspnea - Infusion rate or volume that cannot
Tx: O2, IV diuretics, ±
Circulatory Overload Dx: elevated NT-proBNP, CXR be effectively processed by recipient
nitrates, NiPPV
(TACO) w/ cardiogenic pulm. edema 2/2 - Highest risk in elderly, HF, CKD,
PPX: slower rate (1cc/kg/hr)
1/100 (RBC) vol. overload chronic anemias
- Inflammatory rxn: fever, chills, - Inflammatory rxn: Ab/Ag interaction
IVIG Transfusion Tx: IVF, sx mgmt
flushing, headache, myalgias i/s/o concurrent infxn
Reactions PPX: slow & space out
- Anaphylactoid rxn: urticaria, - Anaphylactoid rxn: unknown,
5-15% of infusions infusions
flushing, chest pain, N/V, HTN potentially kinin-mediated, rare
DELAYED TRANSFUSION REACTIONS (>24H, <28D)
Sx: ~3d; fever, anemia, jaundice, Tx: none
Delayed Hemolytic - Anamnestic IgG against previously
flu-like illness, hemoglobinuria NB: delayed serologic
(DHTR) exposed antigen (Kidd/Duffy/Kell) 
Dx: +DAT, +DBili/LDH, +smear transfusion reaction is the
1/2,000 extravascular hemolysis
w/ spherocytes, low haptoglobin same except w/o hemolysis
- Donor T cells attack non-HLA
TA-GVHD
Sx: 2-30d; fever, rash, mucositis, matched recipient organs in s/o
Rare (typically PPX: irradiation
diarrhea, hepatitis, pancytopenia immunosuppression or 1st degree
immunosuppressed)
relative donor
Post-Transfusion Sx: 3-14d; purpura,
- HPA-1A (common in donor PLTs) Tx: 1st line: IVIG | 2nd: PLEX
Purpura (PTP) mucocutaneous bleed
HPA-1A neg women develop Abs to PPX: HPA-1A negative PLTs
Rare (women>>>men) Dx: PLT <10,000, anti-HPA-1A

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Hematology Peripheral Smear Interpretation

G E N E R A L A P P R O A C H (NEJM 2005;353:498; MGH Slide Rounds)
• Special slide: 5th floor Bigelow building, first left off elevators, then another left, proceed down the hall past the Core lab, then second
door on your left is the heme lab. Inside heme lab, second enclave on the right has the microscope and special slides next to it.
• Low power (20x): scan slide for WBC distribution. Identify the “thick” edge and the “feathered” or thin edge where RBCs are just apart
• Med power (40x): examine feathered edge for rouleaux, parasites, abnormal WBC, platelet aggregation/microsatellites
• Oil Immersion (100x): assess the size, shape, and morphology of major cell lineages:
o RBC: examine where RBCs are close but not touching. Assess size (compare to a lymphocyte nucleus for scale), morphology
(membrane irregularities, fragmentation), color (pallor, reticulocytes)
o WBC: examine at edges and thin end of film. Assess distribution of normal WBC, size, shape, cytoplasm (including granules and
vacuolation), and inclusions (such as Dohle bodies). Evaluate neutrophils for nucleus segmenting (average is 3).
o Platelet: assess for appropriate number (1 plt per HPF [high-powered field] = 20K platelets in CBC), giant platelets, granulation
C O M M O N Q U E S T I O N S A N S W E R A B L E B Y P E R I P H E R A L S M E A R (NEJM 2005;353:498; Harrison’s 18th Ed.)
RBC Lineage

Question Findings Example Clinical Significance Next Steps

Schistocytes - Correlate with CBC, haptoglobin, LDH

Intravascular >1% schistocytes in HPF + absent
(helmet cells, - Assess for clinical causes of TMA, valve
hemolysis alt diagnoses suggests TMA (Int J
fragments, micro- hemolysis. Consider calculating
occurring? Lab Hematol 2012;34:107)
spherocytes) PLASMIC score if concern for TTP
Intra- Ring forms in 84% Sn for babesiosis (Ann Rev Pub - Thick and thin smears for
erythrocytic RBCs; less often, Health 1998;19:237); 65-74% Sn for confirmation/parasite burden
forms present? tetrad (Babesia) malaria (Malar J. 2008;7:22) - Babesia, Lyme, Anaplasma testing

>5% hypochromic cells gold - Iron studies if not yet sent

Evidence of Hypochromic,
standard for functional IDA, incl in (supplementation if no contraindication)
iron microcytic cells;
pts with active inflammation (Clin - Consider thalassemia and sickle cell
deficiency? “pencil” cells
Chem 2002;48:1066) anemia if clinically indicated

Associated with Inflammatory,

Linear - Correlate for causes of elevated
infectious and malignant conditions.
aggregations of Ig/decreased albumin, incl. infection,
Are there Sn but not Sp for MM (Arch Int Med
RBCs throughout inflammation, cirrhosis
rouleaux? 2002;162:1305). Reflects presence of
smear (may be - Consider quant Ig, SPEP/UPEP.
⊕ charged proteins, incl. Ig &
artifact at edges) Correlate for CRAB criteria
fibrinogen (Blood 2006;107:4205)

Functional Howell-Jolly
Sn only for severe splenic hypo- - Assess for causes of hyposplenia;
function; inversely prop to functional consider vaccination & antibiotic
asplenia? bodies
splenic volume (AJH 2012;87:484) adjustment accordingly

WBC Lineage
Question Findings Example Clinical Significance Next Steps

Are PMNs hyper/

Hyper: any 6-lobed Hyper: 98% Sn megaloblastic anemia, 77% Sp - Check folate/B12, consider
or >3% w/ 5 lobes. B12 def (Acta Haematol 1989;81:186). Hypo: 92% supplementation (hyper);
hyposegmented?
Hypo: 2 lobes Sn MDS (Br J Haematol 1986;63:665) MDS workup (hypo)

Are lymphocytes
Large lymphocytes, ≥10% atypical lymphs ⊕LR for infectious - Apply to RegiSCAR;
extra cytoplasm, mononucleosis (JAMA 2016;35:1502); part of consider EBV/CMV, HIV,
atypical?
prominent nucleoli RegiSCAR score for DRESS Toxoplasma infection

Platelet Lineage

Question Findings Clinical Significance Next Steps

Are giant Large Suggests marrow response to destruction; incr. plt - Consider peripheral causes of thrombocytopenia
platelets platelets ≥ turnover (ITP); or proliferation (myelo-proliferative incl drug-induced, hemolysis, sequestration
present? size of RBC dz); clumps suggest pseudo-thrombocytopenia - Consider MYH9 and other hereditary plt disorders
O T H E R C O M M O N F I N D I N G S A N D I M P L I C A T I O N S (Harrison’s 18th Ed.)
Target Cells Acanthocytes (Spur Cells) Echinocytes (Burr Cells)

Membrane redundancy due to Irregular, dense membrane Small, uniform membrane

liver disease, thalassemia, projections present in severe projections present in uremia
HbC disease liver disease and MAHA
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Oncology Acute Leukemia

GENERAL ADMISSION APPROACH
• History: sibling status (for donor search), family history (for inherited syndromes), and if pre/peri menopausal, obtain date of LMP
• Peripheral smear: anemia, thrombocytopenia, variable WBC, circulating blasts (“other cells”), Auer rods (indicates myeloid origin)
• Peripheral flow cytometry: Collect in yellow top. In Epic, order “Flow cytometry labs (blood)”  fill in Clinical hx; select “Leukemia
Panel.” To RUSH case (e.g. for new dx) send page to Group 549 - Leukemia Pathology Team (if not on your directory, call MGH
operator and ask for access). Sample is sent to BWH and interpreted by MGH Hemepath. FYI Routine (non-rush) are sent to Mayo
• Screening: LFTs, lipase, B12, folate, HBV/HCV/HIV serology, CMV IgG, T&S, G6PD, urinalysis, quantitative bHCG (if applicable)
• Monitoring (initially q8h): TLS: BMP (if WBC, use blood gas K), LDH, uric acid, iCal, Phos, Mg. Cairo-Bishop requires 2 lab (uric
acid, K, phos, Ca) + 1 clinical (AKI, arrhythmia, seizure); see Oncologic Emergencies | DIC: PT/INR, PTT, fibrinogen, D-dimer
• BMBx: aspirate+core, flow, cytogenetics (+/- FISH), molecular diagnostics (e.g. BWH Rapid Heme Panel, MGH Heme Fusion Assay)
• Imaging: CXR, TTE (prior to induction due to cardiotoxic chemotherapies), CT head (if CNS sx)
• Access: Coordinate with attending: double-lumen Hickman vs. triple-lumen PICC if induction anticipated, not needed for venetoclax
• LP ± intrathecal chemo: indications for LP  all ALL, AML w/ CNS or ocular symptoms, APL with systemic relapse
o CT or MRI before LP: AMS, focal neurologic signs, papilledema, seizure within the last week
• HLA typing: Initiate allo-HCT work-up if ≤80 yo. In Epic, order “HLA Lab”  select “Specimen Type: Blood,” “Patient: Recipient,”
“Test: Bone Marrow/HSC, Allotransplant – Initial workup.” Coordinate w/ RN, as it is difficult to tell if HLA typing is pending in Epic.
• Use Leukemia Admission Order Set: Neutropenic precautions | TLS ppx: allopurinol 300mg qd (HLA-B*5801 ↑prevalence in
Southeast Asian, black populations, ↑risk of SJS/TEN, consider testing (ACR guidelines) | GI ppx: omeprazole 20mg qd | HSV/VZV
ppx: acyclovir 400mg bid or famciclovir 500mg qd | Hibiclens daily | Peridex mouthwash | No VTE ppx (thrombocytopenia)
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
• Epi: Bimodal. Peak incidence in children, but another peak in >45yo (68% 5y survival)
• S/Sx: pancytopenia sx (pallor, petechiae/bruises, infections), bone pain, B symptoms,
masses (LAD, HSM; anterior mediastinum in T-ALL), CNS sx (CN palsy, n/v, HA), TLS, DIC
• Smear: lymphoblasts with scant cytoplasm, large nuclei containing nucleoli
• Subtypes: B-cell lymphoblastic leukemia/lymphoma (B-ALL/LBL) & T-cell ALL/LBL
o LBL = lymphoblastic lymphoma  pts w/ extramedullary mass(es) w/ <20% BM blasts
• Risk stratification for AYA and Adults (Lancet 2020;395:1146; Blood 2021;138;948):
o B-ALL/LBL (subtyped by clinical/molecular features):
 Favorable: WBC<30k, <35yrs, hyperdiploidy (>50 chromosomes), ETV6-RUNX1, TCF3–PBX1, ERG del, DUX4-rearrange
 Unfavorable: ↑WBC, older, CNS/testicular involvement, hypodiploidy (<44 chromosomes), KMT2A rearrangement, BCR-
ABL1 (Ph+), BCR-ABL1-like (Ph-like, e.g. JAK-STAT pathway abnormalities), TCF3–HLF, MEF2D rearrangement, ZNF384
rearrangement, iAMP21, IKZF1 alterations, complex karyotype (≥5 chromosome abnormalities)
o T-ALL/LBL: Favorable: NOTCH1/FBXW7 mut. Unfavorable: WBC >100k, CNS disease, complex karyotype, RAS/PTEN mut.
o Measurable residual disease (MRD): search for leukemic cells using flow cytometry, NGS or RT-PCR of gene fusions. MRD-
positivity correlates w/ risk of relapse. MRD evaluation → dynamic risk assessment, therapy decisions (e.g. allo-HCT)
• Treatment (NEJM 2006;354:166; JCO 2011;29:532):
o General: no single best regimen, many (e.g. CALGB 10403, R-Hyper-CVAD, BFM). Incorporate (1) induction (2) consolidation
(3) intensification [if needed] (4) CNS therapy [if needed] (5) maintenance (6) allo-HCT [for relapse or unfavorable-risk disease]
 If pt is AYA (age 15-39), pediatric-inspired regimen often used (usually incorporating asparaginase + ↑corticosteroids)
• Asparaginase toxicities: hypersensitivity, pancreatitis, hepatotoxicity, thrombosis (Blood 2020;135:987)
 If BCR-ABL1-positive, TKI is used in conjunction w/ chemo (e.g. R-HyperCVAD plus dasatinib) (Blood 2019;133:130)
 If elderly, low-intensity or chemotherapy-free regimens often used (e.g. dasatinib + blinatumomab, NEJM 2020;383:1613)
o CNS ppx: intrathecal MTX/cytarabine vs. systemic high-dose MTX w/ leucovorin rescue
o Maintenance: weekly MTX/6-MP + monthly Vinc/Pred x2-3y (POMP); TKI maintenance if BCR-ABL1-positive
o Relapsed/refractory B-ALL: blinatumomab (CD19 BiTE), inotuzumab ozogamicin (CD22 ADC), CAR T-cells, allo-HCT
ACUTE PROMYELOCYTIC LEUKEMIA (APL)
• Subtype of AML with distinct biology and excellent prognosis (>80% 5y survival) (NEJM 2013;369:111)
• S/Sx: pancytopenia sx (fatigue, anemia, ecchymoses, infection); very high risk for DIC and bleeding
• Smear: atypical promyelocytes (large, “dirty” granular, bilobed nuclei), +Auer rods (see image to right)
• Cytogenetics: t(15;17)  PML-RARα (>97%), rarely t(11;17), t(5;17)
• Treatment (JCO 2017;35:583):
o Immediately start ATRA (all-trans retinoic acid) if any suspicion for APL given early mortality from
coagulopathy and low toxicity. Dose: 45 mg/m2 in 2 divided doses daily. Target plts >50, fibrinogen >150
• Induction: if low-risk (WBC ≤10K): ATRA + arsenic trioxide (ATO)*. If high-risk (WBC >10K): ATRA/ATO + anthracycline or
gemtuzumab ozagamicin (CD33 ADC). e. Consolidation: ATRA/ATO or gemutzumab ozagamacin. *Monitor qtc
• Complications of ATRA:
o Differentiation syndrome: fever, rising WBC, hypoxemia (pulmonary infilitrates, effusions), peripheral edema, weight gain, AKI
 high-dose steroids (dexamethasone 10mg q12h), supportive care, temporary cessation of ATRA if severe.
 Start primary ppx w/ steroids in highest risk patients (e.g. WBC >10K) (Blood 2014;123:2777).
o Hyperleukocytosis: see Oncologic Emergencies
o Idiopathic intracranial hypertension: HA, vision loss, papilledema  hold ATRA, pain control ± steroids/acetazolamide

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Oncology Acute Leukemia

ACUTE MYELOID LEUKEMIA (AML)
• Pathophysiology: clonal disorder of hematopoietic Risk
progenitor cells w/ infiltration of BM, blood, & other Category Genetic Abnormality (NCCN 2024 AML Guidelines)
tissues. Significant heterogeneity in underlying (5y OS)
molecular abnormalities (see Risk Category table) t(8;21)(q22;q22.1); RUNX1-RUNX1T1
• Epi: most common leukemia in adults (80%). Favorable inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Median age 68 at dx. 5-10% w/ familial syndrome. (55-65%) Biallelic mutated CEBPA
• S/Sx: pancytopenia (fatigue, petechiae, Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow
ecchymoses, infections), myeloid sarcoma, Mutated NPM1 and FLT3-ITDhigh
leukemia cutis (non-tender red/brown Intermediate Wild-type NPM1 without FLT3-ITD or with FLjkmT3-ITDlow
(24-41%) t(9;11)(p21.3;q23.3); MLLT3-KMT2A
papules/nodules), neutrophilic dermatosis (i.e.
Any other cytogenetic abnormalities not favorable or adverse
Sweet syndrome: tender red/violet t(6;9)(p23;q34.1); DEK-NUP214
papules/plaques), gingival hypertrophy (due to leuk. t(v;11q23.3); KMT2A rearranged
infiltration), joint pain/swelling (leuk. infiltration, t(9;22)(q34.1;q11.2); BCR-ABL1
gout), leukostasis (AML > ALL; typically WBC >50- t(8;16)(p11.2;p13.3)/KAT6A::CREBBP
100K; SOB, HA, blurry vision, stroke), spurious K inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2-EVI1
Poor/
(check blood gas K); falsely low PaO2 (check pulse -5 or del(5q); -7; -17/abn(17p)
Adverse
Ox) (see Oncologic Emergencies) t(3q26.2;v)/MECOM(EVI1)-rearranged
(5-14%)
• Dx: ≥20% blasts in BM or characteristic Complex karyotype, monosomal karyotype
Wild-type NPM1 and FLT3-ITDhigh
translocation (e.g. t(8;21)(q22;q22.1)) or myeloid
Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2,
sarcoma (extramedullary tumor of AML cells). U2AF1, and/or ZRSR2
Recent schism in classification (ICC vs. WHO 5th). Mutated TP53
• Complications (see Onc Emergencies): (1) DIC 
keep fibrinogen >150, INR <1.5, plt >30-50, add ATRA if any c/f APL [see APL] (2) febrile neutropenia (3) TLS  allopurinol, IVF,
rasburicase if uric acid >10 (4) leukostasis  hydroxyurea, IVF, leukapheresis, avoid transfusions (can ↑viscosity, worsen). Single
dose cytarabine may also be considered if uncontrolled w/ hydroxyurea.
• Subtypes: t-AML (therapy-related from prior chemo, RT), s-AML (secondary from preceding heme disorder, e.g. MDS, MPN, PNH)
• Risk stratification: based on cytogenetics, mutations, performance status (Karnofsky/ECOG), gero assessment (Blood 2013;121:4287)
• Tx: intensive (see below, NEJM 2009;361:1249) vs. non-intensive (HMA±venetoclax [BCL2 inhibitor], NEJM 2020;383:617)
o Many factors influencing choice: cytogenetics, mutational profiling, performance status (Am J Hematol 2021;96:493)

1) Induction: standard regimen for “medically fit” pts: “7+3” cytarabine (aka “ara-C”) continuous infusion days 1-7 +
ida/daunorubicin (bolus/short infusion) on days 1-3.
Additional/alternative agents for pts with certain subtypes of AML:
• Midostaurin (TKI) added to 7+3 in AML with FLT3 mutations (NEJM 2017;377:454)
• Liposomal cytarabine/daunorubicin (Vyxeos): survival in t-AML & s-AML, but longer neutropenia (JCO 2018;36:2684)
• Gemtuzumab ozogamicin added in CD33-positive core-binding factor AML (RUNX1 or CBFB translocations, (Blood 2017;130:2373)
• Venetoclax + HMA (azacitidine or decitabine) instead of 7+3 if older and/or adverse risk (e.g. TP53). (NEJM 2016;375:2023)

3a) Residual Leukemia: if 3b) No Residual Leukemia: if BM is

2) Day 14 BM Biopsy: residual leukemia cells, “ablated” (i.e. sufficiently acellular w/o
check for residual leukemia re-induction chemo (e.g. 5+2) evidence of leukemia), check again for
may be given complete remission (CR) at day 28

5) Day 28 BM Biopsy: check for CR (<5% blasts in 4) Day 21-25 Count Recovery: await count recovery
BM, nl CBC); 70-80% if <60 yo; 50-60% if >60 yo (may be delayed w/ addition of experimental therapies)

6) Consolidation: initiated soon after firstCR. Goal to eradicate residual disease for 7) Surveillance: CBC q1-
sustainedCR. Options include chemo and/or allo-HCT. In general, allo-HCT preferred in poor- 3mo for 2y, then q3-6mo up
risk disease if patient is candidate and has suitable donor. Chemo alone is used in lower-risk to 5y
disease or if not allo-HCT candidate.
Risk stratification determines management (see table above) (Blood 2017;129:424):
• Favorable risk: HiDAC (high dose ara-C) x3-4 cycles
• Intermediate risk: chemo (HiDAC) vs. allo-HCT 8) Survivorship: cardiac,
• Poor/adverse risk: allo-HCT vs. clinical trial psychosocial, vaccines, etc.

Salvage : If residual disease on surveillance (relapsed) or persistent disease after induction (refractory), initiate salvage therapy with
goal of inducing complete remission and bridging to allo-HCT or clinical trial (Blood 2024;143:11).. IDH1 mutated  Ivosidenib
(NEJM 386(16):1519) or Olutasidenib (Blood Adv 2023;7:3117) | IDH2 mutated  Enasidenib (Blood 2017;130(6):722) | FLT3
mutated  Gilteritinib (NEJM 2019; 381:1728) | Chemotherapy  7+3 (esp. if earlier durable response), HiDAC, mitoxantrone +
etoposide + araC (MEC), fludarabine + araC + G-CSF + idarubicin (FLAG-Ida), others | HMA ± venetoclax

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Oncology Lymphadenopathy & Lymphoma

E V A L U A T I O N O F L Y M P H A D E N O P A T H Y (AFP 2016;94:896)
• Generalized LAD: HIV, EBV/CMV/toxo, mycobacteria, SLE, meds (e.g. phenytoin), sarcoid, lymphoma, Castleman’s, Kikuchi dz, IgG4
• Localized LAD: cervical (EBV/CMV/toxo, mycobacteria, lymphoma), supraclav. (malignancy), axillary (infection, breast), inguinal (STI)
• Hx: chronicity, exposures, travel, meds, B symptoms (fever, night sweats, >10% unintentional wt loss in 6mo), infxn/malignancy ROS
• Exam: localization (think about area of nodal drainage), size (abnormal >1cm), consistency, fixation, tenderness (inflammation)
• Labs: CBC/diff, LDH, HIV (PCR if acute), HBV, HCV. Depending on pre-test probability: T-spot, RPR, ANA, EBV/CMV/toxo serologies
• Imaging: CT C/A/P w/ contrast, PET/CT can define node size, distribution, monitoring of response/progression (w/ Deauville scoring)
• Biopsy: consider if large (>2cm), persistent 4-6w, or increased size, w/ immunophenotyping & cytogenetics. Empiric steroids may
decrease yield of biopsy. Excisional (cells & nodal architecture) > core needle (tissue for molecular studies) > FNA (high false neg.)
LYMPHOMA GENERAL PRINCIPLES
Lymphoma Staging: if Hodgkin lymphoma (HL), add “B” if B Sx. PET Deauville score (1-5): 1 = no FDG uptake; 5 = markedly FDG-avid
Stage I: 1 LN region, or single extralymphatic organ Stage III: LN groups above and below diaphragm
Stage II: ≥2 LN groups on same side of diaphragm Stage IV: disseminated ≥1 extralymphatic organs
LN region: cervical (R/L), axillary (R/L), subpectoral (R/L), mediastinal, hilar (R/L), celiac, paraaortic, mesenteric, iliac (R/L), inguinal (R/L)
Workup: PET/CT, HBV/HCV/HIV serology, G6PD, quantitative bHCG (if applicable), PFTs (+DLCO), TTE (prior to anticipated chemo)
Fertility Preservation: sperm/oocyte/ovarian tissue cryopreservation prior to tx. Menstrual suppression: GnRH agonists if ↓plt expected
H O D G K I N L Y M P H O M A (NCCN; 2024)
Bimodal age distribution (Lancet 2012;380:836). Reed-Sternberg cells (CD15+ CD30+ CD20- CD45- PAX5+ PD-L1+) in inflammatory milieu
S/Sx: neck LAD, mediastinal mass, pruritis, constitutional sx, ↑Eos. Rare: burning pain w/
alcohol, nephrotic syndrome (i.e. minimal change disease), liver dysfunction, skin lesions HL International Prognostic Score (IPS)
WHO classification: nodular sclerosis (70%), mixed cellularity (25%), lymphocyte rich 1 point/factor (JCO 2012;30:3383)
Age >45 Points 5y PFS
(5%), lymphocyte depleted (<1%). Nodular lymphocyte-predominant HL is distinct entity.
Male 0 88%
Treatment: note long-term risk of cardio- and pulm-toxicity, 2° malignancy (t-AML) Stage IV 1 84%
o Stage I-II: ABVD ± XRT. Stage III-IV: ABVD vs. BV-AVD (NEJM 2018;378:331) Albumin <4 2 80%
vs. BEACOPP ± XRT. Interim PET/CT for escalating vs. de-escalating tx Hb <10.5 3 74%
o Relapsed/refractory: salvage chemo (ICE vs GVD) + auto-HCT; brentuximab WBC ≥15,000 4 67%
vedotin (BV); PD1 inhibition (pembro or nivo), bendamustine, allo-HCT Lymphocytes <600 <8% ≥5 62%

NON-HODGKIN LYMPHOMA
Most common blood cancer, a/w immunosupp., autoimmunity, infection (EBV, H. pylori, HCV, HIV, HHV8, HTLV1) (Lancet 2012;380:848)
Indolent (e.g. FL): incurable, but better prognosis (monitor for transformation) vs. Aggressive (e.g. DLBCL): curable, but worse prognosis
Diagnosis % of NHL Clinical Features Treatment
Aggressive, rapid growth, nodal/extranodal - Stage I-II: R-CHOP + RT; Stage III-IV: R-CHOP; if DHL, consider
Diffuse BCL2, BCL6, or MYC translocations common more aggressive Tx (i.e. R-EPOCH); if old/frail, R-mini-CHOP
Large Prognosis: IPI, cell-of-origin (GCB > ABC) - IT MTX CNS ppx for high CNS-IPI controversial (JCO 2023;41:35)
~35%
B-cell Double-hit lymphoma (DHL): more - Relapsed/refractory: CD19 CAR T-cells preferred (Lancet
(DLBCL) aggressive subtype w/ MYC + either BCL2 or 2022;399:2294, NEJM 2022;386:640) vs. chemo + auto-HCT vs Ab-
BCL6 translocations. Triple-hit = ultra-HR. drug conjugates (using polatuzumab) (NEJM 2022;386:351)
- Stage I/contiguous II: Observe; RT preferred; Stage II-IV:
Generally indolent; occasionally aggressive
Follicular observation, anti-CD20 ± bendamustine (BR), lenalidomide (LR),
~25% t(14:18) BCL2+. High grade = more
(FL) CHOP, or CVP; R/R: CAR-T, PI3K inhibitors (JNCCN 2023;21-11)
centroblasts. FLIPI score prognostic
- Monitor for transformation (rapid LN growth, ↑LDH, B symptoms)
Diverse varieties. Peripheral T-cell (PTCL) NOS most common. Cutaneous T-cell (CTCL) i.e. Mycosis fungoides,
T-cell lymphoma ~15% Sezary syndrome (disseminated). Anaplastic large cell (ALCL) a/w ALK, breast implants. Adult T-cell leukemia/
lymphoma (ATL) a/w HTLV-1, geography (e.g. Caribbean). Enteropathy-associated T-cell (EATL) a/w celiac disease
Extranodal MZL (MALT): a/w sites with - Gastric MALT: if H. Pylori+, quad Tx can cure; if H. Pylori-, RT
chronic inflammation, e.g. stomach w/ H. - Nongastric extranodal localized: RT, observation
Marginal Zone pylori+ t(11;18), salivary glands (Sjogren’s), - Advanced nodal: observe, rituximab + chlorambucil/bendamustine
~10%
(MZL) thyroid (Hashimoto’s), small intestine, etc. - Splenic MZL: if HCV+, HCV Tx can lead to regression. If HCV-,
Splenic MZL: often HCV+, cryoglobulinemia Rituxumab (preferred) or splenectomy (definitive for diagnosis to
Nodal MZL: generally indolent, similar to FL differentiate from splenic diffuse red pulp small B-cell lymphoma)
Often indolent, painless LAD, IgM M-protein - Only treat when “active” (Blood 2018;131:2745), i.e. cytopenia, bulky
Small or chronic No risk of leukostasis unless WBC >400k disease, progressive lymphocytosis w/ increase >50% over 2mo,
lymphocytic ~5% Prognosis: Rai/Binet, IGHV unmutated (HR), autoimmune dz (AIHA, ITP), significant constitutional symptoms
(SLL/CLL) ZAP70+ (HR), CD38+ (HR), FISH (del17p = - Evolving combinations with BTKi (zanubrutinib, acalabrutinib,
HR), genetics (TP53 mut. = HR) ibrutinib), anti-CD20 (obinituzumab, rituximab), and venetoclax
Wide clinical spectrum, can involve spleen, - Stage I/non-bulk II: BR, VR-CAP, R-CHOP, or LR + R maintenance
Mantle Cell
~5% GI, BM. Leukemic (SOX11-) often indolent - Stage II-IV: RDHAP ± R-CHOP, NORDIC, or R-B ± R-HiDAc +
(MCL)
t(11;14), cyclin D1+. MIPI score prognostic BTKi vs auto-HCT w/ R maint (Blood 2022;140:1). R/R: BTKi, CAR T
Burkitt Aggressive, extranodal sites (jaw if African). - More aggressive than DLBCL treatment: R-EPOCH, R-CODOX-
~1%
(BL) ↑spont. TLS. t(8:14), cMYC+, EBV/HIV M/IVAC, R-HyperCVAD. Relapsed: chemo + auto- or allo-HCT
ABVD = Doxorubicin, Bleomycin, Vinblastine, Dacarbazine DHAP= Rituximab, Dex, Cytarabine and Carbo-, -Cis- or Oxali-platin
BEACOPP = Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, EPOCH = Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin
Prednisone HyperCVAD = Hyper-fractionated Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone,
CHOP = Cyclophosphamide, Doxorubicin, Vincristine, Prednisone alternated w/ methotrexate & cytarabine, followed by maintenance POMP
CODOX-M/IVAC = Cyclophosphamide, Vincristine, Doxorubicin, Methotrexate, Ifosfamide, R-B ± R-HiDAc = Rituxmiab/Bendamustine x3 + Rituximab/High-Dose Cytarabine x3
Etoposide, Cytarabine VR-CAP = Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone
CVP = Cyclophosphamide, Vincristine, Prednisolone

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Oncology Plasma Cell Disorders

E V A L U A T I O N O F P L A S M A C E L L D I S O R D E R S (Leukemia 2009;23:215)
Evaluation Utility When to Send
If suspecting a 1° (e.g. B cell deficiency) or 2°
Quantify immunoglobulin (Ig) levels in blood (IgG, IgM, IgA, IgD,
Ig Levels humoral immunodeficiency
IgE). Will not discern monoclonal vs. polyclonal
Consider repleting w/ IVIg if IgG < 400 mg/dL
Detect/quantify M-protein (monoclonal protein = M-spike = If suspecting a monoclonal B-cell or plasma cell
SPEP
paraprotein), Ig from an abnormally expanded B/plasma cell disorder, send SPEP & FLC. FLC sensitivity.
Identify the type of M-protein (intact Ig [G, M, A, D, E], light chain “SPEP panel” order contains quantitative
Serum IF
only [LC: κ or λ], or heavy chain only)* IgG/A/M, total protein, SPEP & reflex IF. Serum
Identify light chain abundance (outside normal κ/λ ratio 0.26-1.65) FLC is separate order. At MGH lab, cannot
Serum FLC
Normal ratio w/ LC = immunosuppression force SIFE if no M-spike on SPEP (FLC assay
Assay
Normal ratio w/ LC = infection/inflammation or renal clearance** should be sufficient in most of these cases)
Detect/quantify Bence Jones Protein (BJP, i.e. urine monoclonal Not needed unless high suspicion (+M-prot/abnl
UPEP
protein, which is typically κ or λ LC). UA/dipstick will miss BJP FLC). If UPEP+, can use 24h UProt to quantify
Urine IF Identify the type of BJP (κ or λ) If UPEP+ for BJP (reflex)
*Some therapeutic antibodies may show up in above assays as false positives (e.g. daratumumab)
** LC clearance in CKD: eGFR ≥60, κ/λ 0.26-1.65 | eGFR 45-59, κ/λ 0.46–2.62 | eGFR 30-44, κ/λ 0.48–3.38 | eGFR <30, κ/λ 0.54–3.30 (BCJ 2022;12:133)

C L A S S I F Y I N G P L A S M A C E L L D I S O R D E R S (Lancet Oncol 2014;15:e358)

CRAB criteria: Ca++ (>11mg/dL), Renal dz (Cr >2), Anemia (Hgb <10), Bone lesions (≥1 focal lytic lesion on whole body-CT, MRI or PET)
All those with M-protein ≥1.5g/dL, Non-IgG M-protein of any size, abnormal FLC assay, or CRAB should have BM biopsy to work-up
MGUS Smoldering MM Multiple Myeloma (MM) Waldenström (WM) AL Amyloid
BM Involvement (%) <10 10-60 ≥10 (or plasmacytoma) ≥10 <10
Serum M-protein (g/dL) <3 ≥3 Present Present (IgM) <3
Clinical Signs Absent Absent CRAB, unless SLiM* Hyperviscosity, etc. (see below) Present
• Approach to abnormal asymptomatic SPEP (IMWG):
o If M prot > 3g/dL, classified as SMM:. If 1-2/3, Intermediate-Risk MGUS; If 0/3, Low-Risk MGUS
 Risk Factors: (1) ≥1.5 g/dL (2) non-IgG (3) +/- abnl. FLC ratio
o If SMM: Refer to Medical Oncology
o If Intermediate-Risk MGUS: Refer to Onc. If SPEP/SFLC stable in 6mo, repeat annually, consider stopping if functional status.
o If Low-Risk MGUS: Repeat SPEP/SFLC in 6mo, if stable Q2-3Y or if CRAB crit develop, consider stopping if functional status.
• Smoldering MM (SMM): prog. to MM 10%/yr for 5yr, then . “20-2-20” risk strat (BCJ 2018;8:59). Tx: controversial (JCO 2020;38:112)
• MM: ≥10% BM clonal PC & CRAB symptoms. *If ≥60% BM PC or involved/uninvolved FLC ratio ≥100 or >1 bone lesion on MRI (w/
<10% BM PC) → MM dx w/o CRAB (“SLiM”). Rarer MM types: ~20% LC-only; ~5-10% oligo-secretory (low M-protein); ~3% non-sec.
• Solitary Plasmacytoma: single biopsy-proven tumor w/ clonal PC, imaging w/o other lytic lesions, no CRAB. Tx: RT, monitor for MM
• WM: lymphoplasmacytic lymphoma in BM/LN + IgM M-protein. S/Sx: LAD/HSM, anemia, hyperviscosity (HA, vertigo, dizzy, Δ vision,
AMS), bleeding (acq VWD), cryoglobulins, cold agglutinins. Measure viscosity. Tx: bendamustine+α-CD-20, BTKi, plasmapheresis
• AL amyloid: S/Sx: cardiomyopathy, purpura, nephrotic sx, polyneuropathy, orthostasis, HSM, macroglossia. Congo-red stain (apple-
green birefringence) on affected organ or fat-pad. Send for mass spec. Tx: Daratumumab-CyBorD, early auto-HCT if candidate
• Monoclonal Gammopathy of Renal Significance (MGRS): collection of disorders leading to kidney disease, including light chain &
heavy chain deposition disease, proliferative GN w/ monoclonal immunoglobulin deposits, C3 glomerulopathy (NEJM 2021;384:1931)
• POEMS syndrome: (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes),VEGF, sclerotic bone lesions, &
Castleman disease. ~λ only. Polyneuropathy & MGUS required for dx. Endocrinopathy: hypo-gonad, -thyroid, -adrenal, etc. Tx: ~MM
• Other: Cryoglobulinemia, CANOMAD, DADS-M, Scleromyxedema, Schnitzler’s, Clarkson’s (cap. leak), TEMPI (ASH 2020:2020;380)
M U L T I P L E M Y E L O M A W O R K U P A N D M A N A G E M E N T (Nat Rev Dis Primers 2017;3:17046; NCCN 2024 MM Guidelines)
• Lab findings/workup: AG ratio, globulin, ESR, peripheral smear (rouleaux), LDH, β2M, SPEP/IFE/FLC, whole body low-dose
CT ± PET or MRI. BMBx (IHC, flow, cytogenetics/FISH, rapid heme panel). 10% w/ concurrent amyloid. 10-30% w/ extramedullary dz
• Risk stratification: by age, performance status, comorbidities, R-ISS staging (incorporates cytogenetics/FISH, LDH, β2M, albumin).
High-risk features: t(4;14), t(14;16), t(14;20), amp1q, del17p, extramedullary dz, circulating PC. ≥2 HR FISH = “double-hit” (ultra-HR)
• Treatment agents: most common induction regimens combine a proteasome inhibitor, immunomodulator, & steroids/chemo:
 Proteasome inhibitors: bortezomib (Velcade – V, Bor), carfilzomib (K), ixazomib (Ix)
 Immunomodulatory agents (IMiDs): lenalidomide (Revlimid – R), pomalidomide (Pom), thalidomide (T), iberdomide
 Steroids/chemo: dexamethasone (low dose = d), prednisone (P), melphalan (M), cyclophosphamide (Cy), doxorubicin (dox)
 Monoclonal Abs: anti-CD38 daratumumab (D, Dara; NEJM 2019;380:2104) & isatuximab (Isa); anti-SLAMF7 elotuzumab (Elo)
• Induction & consolidation: NOT curative. Standard risk median OS approaching 10y. High risk median OS ~3y
 Induction: triple w/ VRd most common; CyBorD if renal failure at diagnosis; DaraRd if frail; quad (DaraVRd) use, esp. if HR
 If candidate for autoHCT, usually performed early, but can delay until relapse w/o detriment in OS (NEJM 2017;376:1311)
 Maintenance (e.g. R +/- V) following auto-HCT, or after induction if no HCT. A/w OS (JCO 2017;35:3279), but 2° cancers
• Response criteria: depth a/w better outcomes: partial resp. (M-protein 50-90%); very good partial resp. (M-protein >90%);
complete response (no M-protein, <5% BM PC); measurable residual disease-negative (<1 PC in 105 cells on flow/VDJ sequencing)
• Relapsed/refractory MM: CAR-T (BCMA, GPRC5D), BiTE (teclistamab, elranatamab, talquetamab), venetoclax if t(11;14), chemo
• Other Tx: aimed at reducing skeletal lesions/fractures (bisphosphonates, denosumab, XRT), hyperCa++, renal damage, hyperviscosity,
infections (PCP, HSV, fungal, VZV; depending on Tx), VTE (aspirin vs. AC for IMiD-induced thrombotic risk), anemia (EPO-analog)

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Oncology MDS & MPN

MYELODYSPLASTIC NEOPLASMS/SYNDROMES (MPN/MDS)
● Pathophys: clonal mutation  ineffective/dysmorphic hematopoiesis  cytopenias, risk of transf. to AML, and reduced survival
● Presentation: median age 65-75; s/sx include fatigue (55%), fever/infection (15%), and bleeding (8%)
● RF: old age, male, exposures (benzene, tobacco, chemotherapy, XRT), autoimmune disorders (rheumatic heart dz, RA), PNH
● Diagnosis: 1+ cytopenia, BMBx with dysplasia >10% of cells in at least one lineage and <20% blasts, cytogenetics
o Initial eval: CBC/diff, blood smear, BMBx w/ aspirate, EPO, broad work-up to rule out other causes of bone marrow failure and
peripheral cytopenias (nutritional, infectious, autoimmune, endocrine, drug-related)
o Classification systems (WHO vs ICC) categorize MDS subtypes according to genetic changes, degree of dysplasia & BM blast %
● Prognosis: IPSS-M > IPSS-R predicts progression to AML and survival, which ranges from < 1yr in “very high” risk to 8-10 yrs in “very
low” risk. TP53 multi-hit (not monoallelic), FLT3, KMT2A partial tandem duplication, and other mutations confer risk.
● Treatment: based on IPSS-R, performance status & age
o Low risk: No intervention shown to improve survival (JAMA 2022;328:872). Supportive care if asx or mild cytopenias. ESA for
anemia, TPO-RA for thrombocytopenia. Hypomethylating agents (azacitidine/decitabine) or ATG if multiple cytopenias. alloHCT
in select, younger pts. Targeted tx: lenalidomide for del(5q), luspatercept for ringed sideroblastic (NEJM 2020;382:140).
o High risk: If alloHCT candidate, transplant +/- induction or hypomethylating prior (alloHCT improves outcomes even up to age 75,
per JCO 2021;39:3328). If not alloHCT, azacitidine or decitabine. Ongoing trials with venetoclax plus azacitidine.
Clonal hematopoiesis (CH) is increasingly identified in patients without frank myeloid malignancy; categories of CH include:
● Clonal Hematopoiesis of Undetermined Potential (CHIP): risk factor for MDS/AML and cardiovascular disease, variant allele
frequency (VAF) ≥2% of leukemia-associated gene, no cytopenias, <5% BM blasts, rate of progression to AML 0.5-1%/yr
● Clonal Cytopenia of Unknown Significance (CCUS): unexplained cytopenia + CHIP
● Idiopathic Cytopenia of Unknown Significance (ICUS): unexplained cytopenia, but not CHIP (either VAF <2% or no mutation)
M Y E L O P R O L I F E R A T I V E N E O P L A S M S ( M P N ) : clonal expansion, 1+ myeloid lineages, often involve activation of JAK-STAT
Sequelae vary; PV/ET can progress to 2° MF (~10-20%) or straight to AML (<5%). MF progression to AML is more common (10-20%).
Tx goals: improve quality of life (e.g. constitutional symptoms, splenomegaly w/ JAKi), prevent thrombosis (aspirin), prevent progression to
AML (alloHCT)
Polycythemia vera Essential Primary myelofibrosis Chronic myeloid leukemia
(Hgb +/-WBC Plt) thrombocythemia (Hgb orWBC orPlt) (Hgb WBC Plt)
(Plt)
VTE, aquagenic pruritus, Thrombosis, bleeding Fatigue, night sweats, weight Fatigue, weight loss, night
erythromelalgia, (acquired vWF, consider loss, bone pain, massive sweats, bleeding,
Sx splenomegaly, ruddy if plt >1 mil), vasomotor hepatosplenomegaly, splenomegaly, abdominal pain
complexion, GI (epigastric sx (HA, syncope, Δ abdominal pain, early satiety, (LUQ), L shoulder pain (Kehr’s
pain, ulcers), HA, dizziness, Δ vision, CP, paresthesia thrombotic/hemorrhagic sign), gout flare. 20-50% are
vision, gout flare erythromelalgia, livido) events asymptomatic at diagnosis
Major WHO criteria: Major WHO criteria: Major WHO criteria: Mutation: BCR-ABL1 fusion
- Hgb >16.5 (♂), Hgb >16 (♀) - Plt >450k - BMBx w/ “dry” tap showing (by FISH, RT-PCR),
- BMBx showing trilineage - BMBx w/ enlarged reticulin or collagen fibrosis CBC with  granulocytes
proliferation megakaryocytes with - Mutations: JAK2 65%, CALR (myelo, metamyelo, bands),
- Mutations: JAK2 V617F (95- hyperlobulated nuclei 25%, MPL 5%, others basophilia, eos. Phases:
Dx
97%) or JAK2 exon 12 mut. Mutations: JAK2 60- Minor WHO criteria: chronic, accelerated (10-20%
Minor WHO criteria: 65%, CALR 20-25%, - Leukoerythroblastic smear blasts), or blast (>20% blasts).
- Low Epo (below reference) MPL 5% (left-shift, nucleated and Blast phase can be consistent
Minor WHO criteria: teardrop RBCs), LDH, with AML (80%) or ALL (20%)
- Other clonal markers anemia, splenomegaly
All: phlebotomy (goal HCT < All: ASA81 (unless vWF AlloHCT (only cure), Chronic phase:
45), ASA81 (if no bleeding), syndrome). If age>60 or transfusion, hydroxyurea, TKI: imatinib, dasatinib,
allopurinol, antihistamine risk thrombosis: HU > ruxolitinib (JAK2 inhibitor, nilotinib. 2nd gen TKI (ponatinib
Tx If >60, risk thrombosis: interferon-α > anagrelide primary benefit is symptom > asciminib) if T315I mutation.
Hydroxyurea (HU) or IFN-α, (PDE inhib, blocks plt reduction, splenomegaly) Consider alloHCT if TKI
2nd line: ruxolitinib (JAK2- production) (NEJM (NEJM 2012;366:787). intolerant, resistance.
inhib, NEJM 2015;372:426) 2005;353:33) Momelotibin/fedratinib for Blast phase: Tx as AML/ALL
relapsed/refractory. w/ induction + TKI, alloHCT
Epo: hypoxia-induced Infection, inflammation, AML, CML, ET, PV, Leukemoid rxn (LAP), drugs
(heart/lung dz, carboxy-Hb, iron deficiency, MDS/MPN overlap (steroids, GCSF, ATRA),
DDx smoking) vs. Epo-producing splenectomy, bleeding, syndromes, MDS, hairy cell infection (C. diff, mono),
tumor (rare). Epo: activating other MPN (PMF), MDS leukemia, other malignancies bleeding, splenectomy, DKA,
epo receptor mutation (rare) (e.g. 5q-), solid cancers (e.g. w/ bone metastases) organ necrosis, other MPN
O T H E R M Y E L O I D D I S O R D E R S : WHO 2022 classification. Variety of conditions ranging from aggressive to indolent
● MDS/MPN syndromes: Chronic myelomonocytic leukemia (CMML; see below); MDS/MPN with SF3B1 mutation/ring sideroblasts &
thrombocytosis; MDS/MPN with neutrophilia (“atypical CML”)
o CMML: characterized by peripheral blood monocytosis (≥1x109/L or ≥10%) and MDS/MPN features. Proliferative (WBC
≥13k) vs. dysplastic (<13k). Prognosis: Mayo Molecular. Prog. to AML. Tx: supportive, HU, alloHCT
● Blastic plasmacytoid dendritic cell neoplasm (BPDCN): skin lesions, w/ or w/o marrow involvement and leukemic dissemination
● Mastocytosis: includes cutaneous and systemic mastocytosis. Associated w/ KIT D816V. +Darier’s sign. Recurrent anaphylaxis
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Oncology Hematopoietic Stem Cell Transplantation

TYPES OF TRANSPLANT
Allogeneic Transplant Autologous Transplant
Definition Transplant of non-self (donor) hematopoietic cells Transplant of self (patient) hematopoietic cells
Reconstitute hematopoiesis after conditioning chemo Reconstitute hematopoiesis after high-dose
and graft-versus-tumor (GVT) effect to kill malignant chemotherapy. Intent generally curative except
Goals
cells. Also used for bone marrow failure syndromes. in plasma cell disorders, where goal is to prolong
Always curative intent. remission
risk AML (40-60% 5YS), ALL (40-50% 5YS), MDS 1st relapsed lymphomas (40-50% 5YS), MM
(45% 5YS), risk myelofibrosis, TKI-resistant CML, (35% 5YS); relapsed Waldenström, AL
Indications relapsed lymphoma, aplastic anemia, thalassemia, amyloidosis, select solid tumors (germ cell,
sickle cell disease, primary immunodeficiency (SCID), neuroblastoma, Ewing sarcoma), autoimmune
inborn errors of metabolism disease (MS, SS, Crohns, SLE)
Mostly peripheral blood, but some centers use more
Usually peripheral blood given less invasive
Source of cells bone marrow given lower risk of chronic GVH.
harvest, more rapid engraftment
Umbilical cord blood is occasionally used
Time to engraftment 14-28 days (time for CB > BM > PBSC) 10-14 days
Yes, skin, liver, GI most commonly affected
Graft-versus-host No, but rare “GVHD-like” syndrome occurs in
Acute (within 100 days)
disease (GVHD) ~0.5% of auto-transplants (BMT 2020;55:1879)
Chronic (>100d, morbidity/mortality mo/yrs later)
Graft-versus-tumor Yes, major therapeutic goal is for donor T cells to Likely no, but mechanism via CD8+ T cells under
(GVT) engraft and attack host tumor cells investigation (JCI 2019;129:48)
Pharmacologic Yes (usually 3-6 months; sometimes for 1-2y if GVHD
No
Immunosupression develops)

A L L O G E N E I C H E M A T O P O I E T I C C E L L T R A N S P L A N T (NEJM 2006;354:1813)

• Donor types: matched to pt by HLA typing to minimize GVHD; matching at alleles A, B, C, DR, DQ
o Matched-related donor (MRD): compatible siblings, matched at 10/10 HLA alleles
o Matched-unrelated donor (MUD): NMDP database, matched at 8-9/10 HLA alleles
o Haploidentical: any parent/sib/child (~universal), match at 5/10 HLA alleles, GVT via NK cells (Front Immun 2020;11:191)

Cell Source Collection Engraft GVHD Risk Notes

Less often used despite lower cGVHD risk, due
Bone marrow (BM) Aspirated from iliac crest 18-21d (Reference)
to slower/less effective engraftment
Peripheral blood Mobilization and Generally preferred source due to faster
12-15d Higher risk
(PBSC) peripheral apheresis engraftment (Cochrane Rev 2014)
Cord blood (CB) Immature cells from 28d txp-mortality compared to MUD (similar
Lower risk
(Blood 2013;122:491) umbilical cord at delivery (variable) DFS/OS); allows for more HLA disparity
• Conditioning regimens (Blood 2014;124:344): determined by underlying condition, disease status, and performance status
o Myeloablative conditioning: complete disease eradication & ablation of host BM/immune cells
 Used for young healthy patients, in remission or with measurable residual disease (MRD) (JCO 2020;38:1273)
toxicity, immunosuppr, txp-mortality, relapse
o Reduced intensity conditioning (RIC): tumor debulking & allows for engraftment
 Permits transplant in elderly w/ co-morbidities; toxicity, txp-mortality, relapse (JCO 2017;35:1154)
o Conditioning agents: chemo (ex. alkylating agents – fludarabine, busulfan, cyclophos., melphalan) ± total body irradiation

TERMINOLOGY
• One-liners include: underlying diagnosis; autologous vs allogeneic transplant; day since transplant (transplant = d0, day before =
d-1, day after = d+1); conditioning regimen (myeloablative vs RIC/non-myeloablative); donor type (MRD, MUD, haploidentical), cell
source (BM, PB, CB), GVHD prophylaxis regimen (tac vs. cyclosporine, methotrexate, etc.)
• Example one-liner: 35M w/ AML (FLT3-mutated) who is now day +4 from his myeloablative (Bu/Cy) matched related donor (MRD)
peripheral blood hematopoietic-cell transplant (PBHCT) with tacrolimus/methotrexate GVHD prophylaxis (day 0 = 1/1/21).

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Oncology Hematopoietic Stem Cell Transplantation

I N F E C T I O U S C O M P L I C A T I O N S : 2/2 chemo-related pancytopenia & immunosuppression (ASBMT/IDSA: BBMT 2009;15:1143)
Day 0-30 Day 30-100 Day 100+
MGH Ellucid
Pre-Engraftment Early Post-Engraftment Late Post-Engraftment
Neutropenic, mucositis, lines, Poor cellular immunity, Poor cellular and humoral immunity,
Immune Defect
acute GVHD acute GVHD chronic GVHD
GPCs & GNRs (F&N) Encapsulated bacteria (SHiN)
Bacterial GPCs & GNRs
Neutropenic enterocolitis (typhlitis) Nocardia
Resp/enteral (adeno, flu, RSV, Resp/enteral (adeno, flu, RSV,
Resp/enteral (adeno, flu, RSV,
Viral paraflu), EBV (risk of PTLD), CMV, paraflu), EBV (PTLD), VZV, BK
paraflu), HSV
HHV6 (screen for in CB tx) (hemorrhagic cystitis), JC (PML)
Fungal Aspergillus, candida Aspergillus, candida, PJP Aspergillus, PJP
Parasitic - Toxo Toxo (can mimic PJP PNA)
• Neutropenic enterocolitis (typhlitis): polymicrobial infxn leading to necrotizing enterocolitis, most often involving cecum
o S/Sx: fever, ANC <500, abdominal pain (often RLQ), n/v, watery/bloody diarrhea
o Micro: polymicrobial (GPC/GNR/anaerobes/fungal), clostridium septicum a/w fulminant course & high mortality rate
o Dx: CT (I+/O+) w/ bowel wall thickening, mesenteric stranding, bowel dilatation, mucosal enhancement, pneumatosis
o Tx: pip/tazo vs -penem vs cefepime/MNZ + surgery c/s + add fungal coverage if persistently febrile >72h
• Infectious PPX: items with asterisks (*) have well-established benefit and are employed at all institutions
o Bacterial: cipro 500mg BID or levofloxacin 500mg qd (day -1 to ANC >500)
o Viral (HSV/VZV)*: acyclovir 400mg BID or famciclovir 500mg BID (day -1 to +365 [auto]; 1y min & until off IS [allo])
o CMV: letermovir 480mg qd (dose-reduced w/ cyclosporine) used in CMV-seropositive recipients (day +7 to +100)
 Alternative: monitor weekly CMV VL (from day -1 to +100), with pre-emptive therapy for CMV viremia with IV ganciclovir or
PO valganciclovir
o Fungal*: fluconazole 400mg qd, vori 200mg BID, posaconazole 200mg TID (day -1 to ANC>500 [auto] or 3-6mo [allo])
 Anti-mold (vori-, posa-, isavu-conazole) prophlyaxis is considered in patients with AML, lengthy neutropenia
o PCP/Toxo*: Bactrim SS qd (start after engraftment as outpatient for 6mo [auto], >1y or off IS [allo])
GRAFT-VERSUS-HOST DISEASE MGH Ellucid
• Acute GVHD: D0 to +100. ~40% in MRD, ~60% in MUD (cellular immune response, TH1 cell-mediated) (NEJM 2017;377:2167)
o Risk factors: HLA mismatch, age, female donor/male recipient, donor parity, TBI-myeloablation, PBSC > BM > CB
o Cause: (1) Short-lived donor T cells react immediately; (2) Post-engraft, chronic infl  DAMPs/PAMPs  organ damage
o S/Sx: skin (rash, graded by biopsy findings, % body surface, desquamation), liver (cholestatic injury, graded by bilirubin), GI
(diarrhea, graded by volume of diarrhea/day). Grading here.
o DDx: skin (viral, drug, engraftment), liver (viral, drug, SOS, TPN), GI (C. diff, CMV, adeno, GNR, typhlitis, drug)
o Tx: Grade I topical, II-IV IV methylpred 1-2mg/kg; if severe or steroid-refractory: vedolizumab, MMF, ruxolitinib (NEJM
2020;382:1800), antithymocyte globulin (ATG). Trial enrollment for cell therapies (MSCs, Tregs) (Blood 2020;136:410)
• Chronic GVHD: 30-70% of patients s/p allo-HSCT (humoral immune response, TH2 cell-mediated) (NEJM 2017;377:2565)
o Cause: Pro-inflammatory environment iso graft-vs-tumor response, infx  iatrogenic thymic dysfx in training new T cells + Treg
depletion  chronic inflammation w/ T/B cells  aberrant tissue repair after multiple injurious cycles  fibrosis
o Risk factors: prior acute GVHD, HLA mismatch, age, PBSC > BM
o S/Sx: resembles scleroderma (sicca, dysphagia, arthritis, skin tightening, malar rash), lung (bronchiolitis obliterans), liver
(cholestasis), cytopenias/immunodeficiency; any organ system (see NIH consensus scoring sheet in BBMT 2015;21:389)
o Tx: steroid ± broad immunosuppression, photopheresis for skin; novel therapies including ruxolitinib, ibrutinib & belumosudil
(ROCK2 inhibitor) have shown responses in steroid-resistant disease; cell therapies (BBMT 2020;26:835)
• GVHD PPX: day -3 to indefinite (tapered over months to years), goal to prevent graft rejection & acute/chronic GVHD
o Immunosuppression regimens: combined tacrolimus/methotrexate or tacrolimus/sirolimus most common; obinutuzumab
o T cell depletion regimens: (ATG, decreased T-cell dose) no longer favored; chronic GVHD but no effect on OS
o Post-transplant cyclophosphamide: combined with tacro/MMF, used more widely for haplo and MMUD, a/cGVHD

Immunosuppressant Mechanism Dosing Toxicities

Tacrolimus Calcineurin inhibitor Trough goal: 5-10ug/L AKI, K, Mg, LFTs, n/v, TMA, tremor, DM risk
Sirolimus AKI, sinusoidal obstruction syndrome (SOS),
mTOR inhibitor Trough goal: 3-12ug/L
(Rapamycin) leukopenia, TMA, HLD, cytopenias
Methotrexate Anti-metabolite Given on day +1,3,6,11 w/
Mucositis, myelosuppression, hepatitis, AKI
(MTX) (inhibits thymidine) tacrolimus
Mycophenolate Anti-metabolite
N/A Myelosuppression, n/v/d
(MMF/Cellcept) (inhibits purines)
Post-transplant Expands Treg, limits Given days +3 and +4,
cyclophosphamide allo-reactivity (JCI particularly for Hemorrhagic cystitis, mucositis, cardiac toxicity
(PTCy) 2019;129:2357) haploidentical

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Oncology Hematopoietic Stem Cell Transplantation

N O N - I N F E C T I O U S C O M P L I C A T I O N S : immune-mediated organ damage, toxic effects of chemo, or immunosuppression
QUICK REFERENCE: MGH ELLUCID
(day -8 conditioning to day +30 engraftment)
Monitor S/Sx DDx fever DDx abdominal pain DDx dyspnea/hypoxemia
• Chemo toxicity: • Infection (bacterial, viral,
• Existing disease: CHF, COPD, asthma
mucositis, N/V/D, S/Sx fungal, parasitic)
• PNA: bacterial, fungal, aspiration
of infection • Drug reaction
• Neutropenic enterocolitis • Volume (often on mIVF, transfusions)
• GVHD: rash, jaundice, • Engraftment syndrome
• Colitis: C. difficile, CMV • Drug: chemo-induced lung injury or
diarrhea (24h volume) (day 7-9 for auto, day 14-
• SOS cardiotoxicity
• SOS: RUQ pain, 21 for allo)
• GVHD • Engraftment (pulmonary edema from
jaundice, ascites, • Tumor (initial lysis &
• Obstruction, ileus, capillary leak)
edema cytokine release)
constipation • Pneumonitis
• Engraftment • Immobility (aspiration,
• Alveolar hemorrhage
syndrome: fever, DVT/PE)
dyspnea, edema • PE, TRALI, GVHD
• GVHD

• Pre-Engraftment (day 0-30): common to have mucositis, nausea/vomiting, alopecia, rash, diarrhea
o Mucositis: most HSCT patients get some degree of mucositis; duration & severity are worse in allogeneic HSCT. Treatment is
focused on pain & caloric intake. WHO grade: (1) erythema (2) ulcer, solid+liquid PO (3) liquid PO (4) NPO
 Pain: topical/IV opiates; low threshold for PCA
 Nutrition: TPN initiated if PO intake impaired by mucositis & expected to continue for ≥1w
 Palifermin (recombinant keratinocyte growth factor): might reduce duration & severity with select ablative regimens
o Engraftment syndrome: sudden PMN recovery causing cytokine storm and vascular leak
 S/Sx: fever, rash, weight gain, bone pain; if severe – pulmonary edema, LFTs, AKI, seizures
 Dx: diagnosis of exclusion (DDx: infection, drug reaction, acute GVHD)
 Tx: high-dose IV steroids (discuss with attending prior to initiation of steroids)
o GI – nausea/vomiting: optimal management varies based on timing relative to chemo initiation
 Immediate (day 0-1): 5-HT3 blockade (Zofran, Aloxi), neurokinin-1 antagonists (Emend), steroid (decadron)
 Delayed (day 2-5 post chemo): dopamine (D2) blockade (Compazine, Reglan, Haldol)
 Late (5+ days post chemo): lorazepam, steroids, dronabinol (more helpful in younger pts, marijuana users)
o Pulm – idiopathic interstitial pneumonitis/diffuse alveolar hemorrhage (DAH):
 Cause: direct cytotoxic injury to alveoli
 S/Sx: fever, hypoxemia, diffuse lung infiltrates (ARDS)
 Dx: bronchoscopy w/ serial lavage (r/o infection, blood) – progressively bloodier on serial lavage c/w DAH
 Tx: high-dose steroids; + for DAH: FFP for INR<1.5, maintain plt >50k; limited data for recombinant FVIIa
o Liver – sinusoidal obstruction syndrome (SOS) (previously called veno-occlusive disease [VOD]):
 Cause: direct cytotoxic injury to hepatic venules leading to hypercoaguable state and microthrombi
 S/Sx: RUQ pain, jaundice, ascites/edema; ALT/AST/TBili, INR/Cr (if acute liver failure or HRS)
 Dx: Doppler US c/w reversal of portal vein flow, liver bx; Dx criteria: Tbili >2mg/dL (<21d post-HCT), hepatomegaly/RUQ
pain, sudden weight gain (fluid) >2-5% baseline body weight (see criteria and grading: Br J Haematol 2021;190;822)
 PPX: ursodiol 300mg TID (admit to day +30); Tx: defibrotide
o Renal – AKI (DDx: ATN, hepatic SOS, aGVHD, thrombotic microangiopathy (TMA), TLS, ABO-mismatched transplant)
 Nephrotoxins: calcineurin inhibitors, acyclovir, amphotericin, aminoglycosides
 TMA: subacute onset ~ day 20, caused by endothelial damage 2/2 calcineurin inhibitors, conditioning, & GVHD
 TLS: considered in pts with significant disease burden at time of transplant; PPX: allopurinol 300mg qd
o Heme – graft failure, cytopenias, bleeding:
 Primary graft failure: persistent neutropenia without engraftment
 Secondary graft failure: delayed pancytopenia after initial engraftment (immune or infectious)
 Rx: graft failure may require re-transplantation (CD34 boost); transfusions with irradiated & leukoreduced products
• Post-Engraftment (day +30):
o PTLD (post-transplant lymphoproliferative disease): ~1% in allo-SCT; median day +70-90 (NEJM 2018;378:549)
 Cause: IS leads to EBV reactivation (dormant in B cells) & clonal B cell proliferation (usually donor-derived)
 Risk factors: T cell depleted donor graft, treatment with ATG, HLA-mismatch, CB transplant
 Dx: rising plasma EBV DNA level, biopsy with immunophenotyping for definitive diagnosis
 Tx: reduce IS, anti-viral, rituximab-based chemo (if systemic) vs surgery/RT (if localized), DLI, EBV-targeted T cells
o Pulm – bronchiolitis obliterans (cGVHD), pulmonary veno-occlusive disease
o Liver – cGVHD, drug-induced liver injury, viral hepatitis reactivation, iron overload (secondary hemochromatosis)
o Renal – TMA (chronic onset ~ day 100), drug toxicity (calcineurin inhibitors), nephrotic syndrome

D I S E A S E R E L A P S E : #1 cause of death post-HCT. Mechanisms: immune escape, resistant clones that survive conditioning
• Treatment: donor lymphocyte infusion (DLI), salvage chemo, then second allo-HCT, clinical trials for novel therapies, hospice

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Oncology CAR T cell Therapy

M E C H A N I S M O F A C T I O N (NEJM 2018;379:64)
• Chimeric antigen receptor T cells autologous cell therapy whereby T cells are collected from
patient, genetically modified with construct encoding a chimeric antigen receptor (CAR) that directs T
cells against a tumor antigen. CAR T cells are infused into patient, where they persist in vivo
• CAR: transmembrane engineered protein consisting of extracellular immunoglobulin (antibody)-
derived domains (ScFv), which binds a tumor antigen (e.g. CD19). The ScFv is fused to signaling
(CD3z) and costimulatory domains (CD28 or 4-1BB) that cause T cell activation and proliferation
FDA-APPROVED CAR T CELL THERAPIES
• Yescarta (axicabtagene ciloleucel - “axi-cel”; anti-CD19, CD28 co-stim domain)
o Relpased/refractory large B-cell lymphoma: ZUMA-1/7 → 82% ORR (54% CR) (NEJM 2017;377:2531, NEJM 2022;386:640)
o Relapsed/refractory follicular lymphoma: ZUMA-5 → 92% ORR (74% CR) (Lancet Oncol 2022;23:91).
• Kymriah (tisagenlecleucel - “tisa-cel”; anti-CD19, 4-1BB co-stim domain)
o Relapsed/refractory B-ALL age <25y: ELIANA → 81% CR (NEJM 2018;378:439). Adult phase 2: NEJM 2018;378:449
o Relapsed/refractory large B-cell lymphoma: JULIET → 52% ORR (40% CR), 65% w/o relapse at 1y (NEJM 2019;380:45)
• Tecartus (brexucabtagene autoleucel - “brexu-cel”; anti-CD19, CD28 co-stim domain)
o Relapsed/refractory mantle cell lymphoma: ZUMA-2, Phase 2, 93% ORR (67% CR) (NEJM 2020;382:1331)
o Relapsed/refractory adult B-ALL: ZUMA-3 → 71% CR (Lancet 2021;398:491)
• Breyanzi (lisocabtagene maraleucel - “liso-cel”; anti-CD19, 4-1BB co-stim domain, 1:1 ratio of CD8+:CD4+ CAR T cells)
Relapsed/refractory large B-cell lymphoma: TRANSCEND NHL 001 → ORR 73% (CR 53%) (Lancet 2020;19;396:839)
• Abecma (idecabtagene vicleucel - “ide-cel”; anti-BCMA, 4-1BB co-stim domain)
o Relapsed/refractory multiple myeloma: KarMMa → 73% ORR (33% CR) (NEJM 2021;384:705, NEJM 2023;388:1002)
• Carvykti (ciltacabtagene autoleucel - “cilte-cel”; anti-BCMA, 4-1BB co-stim domain, 2 anti-BCMA camelid nanobody domains)
o Relapsed/refractory multiple myeloma: CARTITUDE-1 → 98% ORR (83% CR), 27-month PFS 55% (Lancet 2023;41:1265)
• Under investigation: combo w/ PD1-axis blockade (Cancer Cell 2019;36:471) & other cell types, e.g. CAR-NK cells (NEJM 2020;382:545)
T O X I C I T I E S (JNCCN 2024; BBMT 2019;25:625) MGH Ellucid
• Cytokine-release syndrome (CRS)
ASTCT CRS Grade Treatment**
o At least Grade 1 occurs in majority of patients, <10% Grade 3.
Typically 1-3d (up to 10-15d) post-infusion, lasts ~7d. Caused by Tylenol, supportive. If
1 Fever (≥38C)
cytokine release (IL‐2, sIL2R, IFNγ, IL‐6, GM‐CSF) triggered by >3d, consider tocilizumab
CAR T cell engagement of antigen and in vivo expansion. risk: Tocilizumab q8h PRN up
Fever & HoTN not
bulky disease, baseline platelets, CRP. Axi-cel > Tisa-cel to x4, add steroids as
2 requiring pressors or
o Signs/Sx: fever, BP, HR, SpO2, malaise, rigors, anorexia, below if still BP after 1-2
hypoxemia on NC
myalgia. Can affect any organ (CV, lung, GI/liver, renal, CNS), doses, IV fluids
arrhythmias, capillary leak syndrome, HLH Fever + BP
Tocilizumab as above,
o Dx: monitor for 7d post infusion for FDA-approved therapies (inpt requiring pressor or
3 dexamethasone 10mg IV
or possibly close outpt); VS, basic labs, ferritin, coags, CRP, TLS SpO2 requiring
q6h (or equivalent)
labs. When suspicious, make sure to rule-out infection HFNC, NRB
o Tx: See table. Tocilizumab (anti-IL6R) 8mg/kg over 1h (≤800mg); Fever + BP Tocilizumab + dex as
siltuximab (anti‐IL6) and/or anakinra (anti-IL1R); 2nd line: requiring multiple above. If refractory,
4
steroids. if plan to treat CRS with steroids or anti-IL6, **first get pressors or SpO 2 consider methylpred
clear approval by the treating attending (even if overnight). requiring BIPAP, MV 1g/d IV x3d w/ taper
o Broad-spectrum antibiotics (cefepime) if fever + neutropenia
Immune Effector Cell-Associated Encephalopathy
• Immune effector cell-associated neurotoxicity syndrome (ICANS) (ICE) Assessment Tool
o Etiology: unclear; cytokine diffusion into brain (IL-1, IL-6, IL-15
a/w neurotoxicity), BBB disruption, CAR T cell trafficking to CNS Max A&Ox3 [+ hosp] (4 pts), naming [clock, pen,
o Timing: typical onset 4-10d post-infusion, duration variable (14- score: button] (3 pts), follows commands (1 pt), writes
17d). Can occur w/ or after CRS, but CRS is not req. for ICANS. 9 sentence (1 pt), serial 10s from 100 (1 pt)
o S/Sx: aphasia, impaired fine motor skills, seizure, motor
weakness, toxic encephalopathy (see ICE & ICANS grade), rare ASTCT ICANS Grade Treatment**
parkinsonism w/ BCMA CAR T cells (Nat Med 2021;27:2099) Grade ICE = 7-9, awakens
Supportive
o Dx: neuro c/s, ICE score, ICANS grade. If grade ≥3: MRI brain 1 spontaneously
w/ w/o contrast, EEG, LP (r/o infection, e.g. HHV6), fundoscopy Grade ICE = 3-6, awakens to
Dex 10mg IV x1
o Tx: See table. Seizure prophylaxis starting on day of infusion 2 voice
(levetiracetam 500-750 mg q12h for 30d). Generally, ICE = 0-2, awakens to
Dex 10mg IV q6h
dexamethasone +/- anakinra, treat CRS if present (i.e. toci), but Grade tactile stimulus, or focal
or methylpred
**first get clear approval by the attending (even if overnight) 3 edema on neuroimaging,
1mg/kg IV q12h
o Prognosis: generally reversible, rare fatal cases or brief seizure
• Persistent Hematologic Toxicity ICE = 0, unarousable, Methylprednisolone
o Can cause grade ≥3 anemia, neutropenia, thrombocytopenia, seizure >5min or w/o IV 1g/d x3d or
Grade
and B-cell aplasia that persists months-years return to b/l, or deep focal equivalent w/ taper.
4
o Mechanism unclear, a/w with decreased baseline hematopoietic motor deficit, or diffuse Can add anakinra if
reserve and inflammation (Blood 2021;138: 2499) cerebral edema, or ICP no response
• Hemophagocytic Lymphohistiocytosis Like Syndrome (IEC-HS): Rare, 1% develop (see Anemia) (TCT 2023 HLH guidelines)

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Oncology Solid Organ Malignancies

Organ Risk factors/screening Diagnostics Treatment
Early stage (I, IIA, IIB through T2N1):
 Breast Conserving Surgery ± RT (NEJM 2023;388:585)
vs. mastectomy ± RT, HR tx, HER2 tx, chemo if high risk
Risk factors:
Breast Locally advanced (Stage IIB T3N0, IIA-IIIC):
Age, genetics (BRCA1/2, H&P
 Infiltr. ductal  Surgery + RT w/ (neo)adj. chemo & HR/HER2 tx
CHEK2, ATM, PALB2), Dx bilateral
(70-80%) (Neo)adjuvant therapy:
FHx, obesity after mammogram
 Invas. lobular  ER/PR+, HER2-: tamoxifen or aromatase inhibitors (AI)
menopause, menopause (Bi-RADS), US,
(5-10%) (anastrozole, letrozole, exemestane); no AI if
>55, chest RT, 1st birth FNA or core Bx
 Mixed premenopausal; ± ovarian suppression if high risk.
>30, nulliparity, HRT, (> excis. Bx),
ductal/lobular Chemo: AC-T (doxo, cyclophos [CYC], paclitax.) or TC
menarche <13y, EtOH, breast MRI if
(7%)  HER2+: TCH(P) (trastuzumab, carboplatin, docetaxel, ±
benign breast disease, young or to
pertuzumab) or ACTH(P) (doxorubicin, CYC, paclitaxel,
 Mucinous (2%) tobacco, DES exposure assess extent
 Tubular (1.5%) trastuzumab ± pertuzumab) + ER/PR tx if HR+
Screening: (good Sn, but
 Medullary (1%)  Triple Neg (NEJM 2017:372;2147): capecitabine
 USPTF: q2y mammo Sp 72%)
 Papillary (1%) Metastatic/recurrent (Stage IV):
40-74 Path review
 ER+: as above ± fulvestrant (ER antagonist); ± CDK4/6
 NCCN: q1y mammo (include Ki-67)
inhibitor or everolimus (mTOR inhibitor)
NCCN Guidelines >40 or 10y before Genetic testing
 HER2+: THP (1st line) or T-DM1 (trastuzumab-drug
Breast Cancer 2024 earliest FHx if >30 or and counselling
conjugate), trastuzumab+lapatinib
10y after RT if >30
 BRCA mutation (NEJM 2017;377:523; NEJM 2018;379:753):
olaparib or talazoparib
 Triple neg: systemic tx
Risk factors:
 FHx, genetic (FAP,  Colonoscopy w/ Colon:
HNPCC, PJS), IBD polyp, bx for I-IIA: surgery + observation, or capecitabine or 5-
(UC>CD), obesity, path FU/leucovorin (IIA)
tobacco, red/processed  CT C/A/P, CEA IIB-IV: surg, RT, systemic tx: FOLFOX (oxaliplatin,
Colon and
meat, EtOH,  MRI for liver leucovorin, 5-FU), CAPEOX (capecitabine, oxaliplatin),
rectum
adenomat. polyps, age mets FOLFIRI (irinotecan, leucovorin, 5-FU), FOLFOXIRI
 AdenoCa (98%)
 Neuroendocrine  death w/ R-sided  Pelvic MRI or (irinotecan, oxaliplatin, leucovorin, fluorouracil), ±
 Lymphoma (JAMA Oncol endorectal US bevacizumab; nivo ± ipi or pembro
2018;4:e173695) for rectal CA  BRAF V600E: encorafenib + EGFR inhib. (cetuximab,
Protective factors: ASA  Genetic panitumumab)
NCCN Guidelines for 50-59yo and ≥10%  MSI-H/dMMR: immuno tx (pembro, nivo, ipi)
testing:
Colon Cancer 2024 CVD risk (Annals  HER-amp +RAS/BRAF WT: trastuzumab +
MSI/MMR
2016;164:814) status in all, pertuzumab/lapatinib
Screening (45-75yo): K/N-RAS,  Rectal: low anterior (LAR) v abdominoperineal resection
colo, flex sig, CT colo, BRAF, HER2 (APR) ± neo v adj chemoRT. Chemo as in colon cancer
FIT, FOBT for 50-75yo
NSCLC: IA: surgery ± RT; IB-IIIA: surgery if able ± adjuv
Risk factors (Nat Rev Ca chemoRT ± osimertinib or atezolizumab. IIB/IIIA
2007;10:778): unresectable, IIIB: definitive chemoRT + adjuvant
 Age, male, tobacco,  CT C/A/P, FDG- durvalumab (NEJM 2018;379:2342). IV: systemic tx as below:
asbestos, occup. PET/CT, brain  ChemoRT: cisplatin + docetaxel/etoposide/ pemetrexed;
exposures, lung MRI carboplatin + pemetrexed/paclitaxel/
Lung
fibrosis or COPD, prior  PFTs gemcitabine/docetaxel
 NSCLC (84%):
cancer history,  Evaluate  Targeted inhibitors: EGFR (osimertinib 1st line, erlotinib,
adeno,
exposure to infectious pathologic LNs afatinib, gefitinib, dacomitinib); ALK/ROS1 (alectinib,
large>SCC
agents (TB, fungal) with biopsy crizotinib, ceritinib, brigatinib, lorlatinib); BRAF/MEK
 SCLC (13%)
 25% lung cancer  Molecular (dabrafenib/trametinib); TRK (larotrectinib, entrectinib)
worldwide not due to testing for  Immunotherapy (PD-L1+) (Lancet 2016;387:1540; NEJM
NCCN Guidelines
smoking  more likely NSCLC (EGFR, 2018;378:2078): pembro ± chemo. ipi/nivo, atezolizumab+
NSCLC 2024
to have single mutation ALK, ROS1, platinum+ taxane + bevacizumab (anti-VEGF)
Screening (Annals NTRK1/2/3, SCLC:
NCCN Guidelines
2014;160:330): MET exon14  Limited: surgery + chemo ± mediastinal RT
SCLC 2024
 Annual low dose CT skipping, RET,  Extensive (NEJM 2018;379;2220): chemo & atezolizumab v
chest for 50-80 yo PD-L1) before durvalumab ± RT for lobar obstruction, SVC syndrome,
current smokers with systemic tx bone/brain mets
≥20 pack-year hx OR  Chemo: platinum agents, etoposide, irinotecan
quit within last 15 yrs

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Oncology Solid Organ Malignancies

Organ Risk factors/screening Diagnostics Treatment
Melanoma Localized disease: wide excision of primary tumor
Risk factors:
 Superficial ± sentinel lymph node biopsy. Topical imiquimod or
 Sun exposure (UVB >  Biopsy of primary
spreading (75%) RT if surgery contraindicated or as adjuvant tx.
UVA), atypical nevi, high tumor (Breslow
 Nodular (15-30%) Metastatic disease: Systemic therapy ± excision (if
nevi count, FHx or depth prognostic),
 Lentigo maligna feasible) ± RT (for sympt. localized disease, e.g.
personal hx, LN sampling, CT
(10-15%) brain mets) ± talimogene laherparepvec (T-VEC,
immunosuppression C/A/P, brain MRI, &
 Acral lentiginous intralesion injection of HSV  tumor cell lysis &
 Familial melanoma with serum LDH for
(<5%) GM-CSF expression) (JCO 2015;33:2780).
germline CDKN2A, active surveillance
 Amelanotic (2- Systemic therapy:
CKD4, POT1 mutations and treatment
10%)  Immunotherapy (NEJM 2015;373:23; NEJM
Most common somatic response
 Ocular (5%) 2015;372:2521): anti-PD-1 (pembro/nivo); anti-
mutations:  Liver MRI for
 Mucosal (~1%) CTLA4 (ipilimumab), ipi+nivo (NEJM
 BRAF (V600E, V600K) ocular/uveal
2019;381:1535)
50%, NRAS 15-20%, KIT melanoma – liver
NCCN Guidelines  Targeted tx (NEJM 2014;371:1867): If BRAF/MEK
10-15% (acral). Genetic most common
Cutaneous Mel 2024 mutated, combo inhibitors(dabrafenib+trametinib,
testing for stage II-IV metastatic site
NCCN Guidelines vemurafenib+cobimetinib,
disease
Uveal Mel 2024 encorafenib+binimetinib). If KIT mutant, imatinib.
Risk factors:
 Tobacco, EtOH, obesity,  CT C/A/P pancreas  Resectable/Borderline: surgery ± systemic tx: 1st
DM, chronic pancreatitis, protocol, EUS+Bx, line FOLFIRINOX (leucovorin, 5-FU, irinotecan,
age, male, FHx, HNPCC, MRCP ± ERCP, oxaliplatin), gemcitabine+nab-paclitaxel,
Pancreas chemical/heavy metal MRI for gem+capecitabine, ± chemoRT
 Exocr./adeno exposure, germline mut. indeterminate  Locally advanced: systemic tx as above or
(~95%) (BRCA1/2, TP53, STK11, lesions, PET/CT in stereotactic body radiation (SBRT)
 Endocrine (<5%) MLH1, MSH2/6, PMS2, high risk patients  Metastatic: systemic tx ±:
CDKN2A).  CA19-9, LFT
• BRCA1/2: olaparib (NEJM 2019;381:317);
NCCN Guidelines Genetic mutations:  Germline testing
• NTRK fusions: larotrectinib, entrectinib
Pancreatic 2024  KRAS, TP53, SMAD4, +molecular profiling
TGFbR1/2, CDKN2A, of tumor tissue • MSI-H/dMMR/TMB-H: pembrolizumab
MLL2/3, KDM6A, ATM,  Bx metastatic site if (NEJM 2015;372:2509)
NTRK, ALK, ROS1, metastatic disease • BRAF V600E: dabrafenib + trametinib
BRAF, HER2, PALB2
Low risk: surveillance (PSA, DRE ± Bx) vs external
Prostate Diagnosis: Bx
beam radiation therapy (EBRT) ± brachytherapy
 Adenocarcinoma Risk factors: After diagnosis:
(BT) vs radical prostatectomy
(95%)  Age, black race, genetic  TRUS, MRI,
Intermediate/high risk: combination of EBRT, BT
 Transitional, basal factors (BRCA1/2 and biomarkers, CT
± prostatectomy w/ lymph node dissection, and
cell, intraductal family history), smoking C/A/P, bone scan
androgen deprivation therapy (ADT):
carcinomas;
Orchiectomy, Androgen R blocker: enzalut-, apalut-,
neuroendocrine, Screening with PSA: Germline testing:
darolut-, flutamide. Androgen synthesis inhib:
carcinosarcoma,  55-69: individualized risk-  High/very high
abiraterone. GnRH agonist: leuprolide, gose-, hist-,
lymphoma, benefit discussion NCCN risk
triptorelin, GnRH antagonist: degarelix, relugolix
stromal sarcoma  70 and above: no testing  Any risk level if ⊕
Metastatic/recurrent: ADT, if fail, ADT+doxetaxel.
NCCN Guidelines (JAMA 2018;319:1901) FHx or intraductal
Bone mets: radium-223 or denosumab/zoledronic
Prostate Cancer 2024 histology
acid, palliative RT. MSI-H/dMMR: pembro
Cancer of Pathologic Diagnosis: Workup: Adenocarcinoma: paclitaxel + carboplatin ±
Unknown Primary  Core needle biopsy  Complete H&P etoposide; gemcitabine + cisplatin or docetaxel;
 Adenocarcinoma (preferred) and/or FNA (breast, GU, pelvic, capecitabine + oxaliplatin (CapeOx); fluorouracil +
or carcinoma not from most accessible site rectal, skin exams) leucovorin + oxaliplatin (FOLFOX) or irinotecan
otherwise  MSI/MMR testing  Routine labs (CBC, (FOLFIRI); docetaxel + carboplatin or cisplatin
specified (85%) electrolytes, LFT, Squamous cell carcinoma: Paclitaxel +
 Squamous cell Initial Evaluation: Cr) carboplatin or cisplatin; gemcitabine + cisplatin;
carcinoma (5%)  Immunohistochemistry  Occult blood stool docetaxel + carboplatin or cisplatin; cisplatin +
 Undifferentiated  Gene expression profiling testing fluorouracil; docetaxel + cisplatin+ fluorouracil
carcinoma (5%)  Tumor serum markers: β-  CT C/A/P with IV (DCF)
 Neuroendocrine hCG (testicular), AFP contrast +/- PET Adenocarcinoma and SCC: capecitabine,
tumors (5%) (testicular, hepatocellular  Endoscopy, UA, fluorouracil, pembrolizumab, selpercatinib
NCCN Occult carcinoma), CEA (CRC), LDH (if indicated) Neuroendocrine tumors: paclitaxel + carboplatin +
Primary Guidelines CA-125 (ovarian) etoposide; cisplatin + etoposide; temozolomide ±
2024 thalidomide.

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Oncology Immune Checkpoint Inhibitors

IMMUNE CHECKPOINT INHIBITORS (ICI)
• Mechanism of Action: Block receptors that down-regulate T cell activation  CTLA-4, PD-1 (on T-cell) or its ligand PD-L1 (on
cancer cell)  antitumor immune response (Nat Rev Clin Oncol 2016;13:473; NEJM 2018; 378:158; NEJM 2016;375:1767)
• Indications: >20 cancers. PD-1i FDA-approved for any microsatellite instability-high (MSI-H) or mismatch-repair deficient
tumors (dMMR). Pre-existing autoimmunity not absolute contraindication, but can flare (JCO 2018;36:1905; Ann Oncol 2017;28:368)
I M M U N E R E L A T E D A D V E R S E E V E N T S ( I R A E S ) (NEJM 2018;378:158; Ann Oncol 2017;28:iv119; J Immunother Cancer 2017;5:95)
• Definition: Systemic autoimmune/inflammatory event 2/2 immune activation by ICI Timing of irAE after ipilimumab
• Grading: 1-4 (mild to life threatening), guides treatment regimen (adapted from Ann Oncol 2017;28:iv119)
• Risk factors: Combination (anti-CTLA-4 + anti-PD-1) a/w earlier onset, incidence and
severity; anti-CTLA-4 > anti-PD-1
• Timing: Highly variable, can present weeks-years after use
• Tx: Based on expert consensus (ASCO J Oncol Pract 2018;14:247). 1st line corticosteroids.
If refractory: infliximab, MMF, tacrolimus, MTX, ATG, tocilizumab. IVIg/plasmapheresis
in autoAb-mediated/neurologic irAEs
• Impact: IRAEs associated with improved OS in ICI therapy, even in context of hospitalization for toxic effects (JAMA 2024;7(1))
S E L E C T E D I R A E D I A G N O S I S , G R A D I N G , A N D M A N A G E M E N T (ASCO: JCO 2021;39:4073; NCCN Guidelines 2024)
Consult SIC (Severe Immunotherapy Complications) Service for inpatient questions regarding concern for IRAEs
Skin toxicity: Common, 30-40% of pts (CTLA-4 > PD-1/L1 blockade). Rash, pruritis, bullous derm, lichen planus, psoriasis, rarely
SJS/TEN/DRESS. Vitiligo seen in melanoma, rarely in other cancers, a/w response to immunotherapy (JAMA Dermatol 2016;152:45)
• Timing: Early, within the first few weeks after tx initiation
• S/Sx: Four types (1) Inflammatory: psoriasiform or lichenoid reactions; (2) Immunobullous: dermatitis herpetiformis or bullous
pemphigoid; (3) Keratinocyte alteration: acantholytic dyskeratosis; (4) Immune reaction mediated by alteration of melanocytes
• Dx: exam; r/o other etiologies (infection, DRESS, SJS/TEN); grading based on BSA (<10% Gr 1, 10-30% Gr 2, >30% Gr 3)
• Tx: topical steroids, oral antihistamines for inflammatory/pruritic reaction. If severe, consider systemic steroids + derm c/s
Colitis: More common w/ anti-CTLA-4; grade 3/4 colitis is higher with ipilimumab (<10%) than with anti-PD-1 agents (1-2%).
• Timing: 6-8w after initiation of therapy
• S/Sx: Diarrhea, weight loss, abdominal pain/urgency/rectal bleeding if severe
• Dx: Lactoferrin/calprotectin; r/o other etiologies (C diff., stool Cx, CMV PCR). CT A/P can show mild diffuse bowel thickening or
segmental colitis. EGD/flex sig/colo for Grade ≥2 sx, path w/ active acute colitis.
• Tx: Antidiarrheal agents, budesonide 9mg PO or prednisone PO vs. high dose steroids w/ taper, infliximab in refractory cases
Pneumonitis: More common w/ anti-PD-1, serious toxicity rare. Higher risk w/ combination or targeted therapy (Chest 2017;152:271)
• Timing: Highly variable, can be later
• S/Sx: Dyspnea, cough, fever, AIP/ARDS; 1/3
asymptomatic (JCO 2017;35:709; Clin Cancer Res
2016;22:6051)
• Dx: Rule out other etiologies, consider BAL,
PCP, CT often non-specific though can show
GGOs and/or nodular infiltrates
• Tx: Oxygen, glucocorticoids w/ prolonged taper,
diuresis, infliximab, mycophenolate mofetil or
IVIg if severe or refractory
Hypophysitis (JAMA Oncol 2018;4:173): Primarily w/ anti-CTLA-4 (3%), rarely w/ anti-PD-1/PD-L1 (0.5%). Mechanistically distinct
from other irAEs; possibly by direct binding of ipilimumab to CTLA-4 on normal cells of anterior pituitary (Sci Transl Med 2014;6:230).
• Timing: Median onset ~8w
• S/Sx: HA (common, can be severe), fatigue, n/v, dizziness, weight changes, hot flashes, cold intolerance, hyponatremia
(anterior hypopituitarism), vision changes; usually without central diabetes insipidus (posterior pituitary spared)
• Dx: MRI brain/pituitary shows diffuse pituitary enlargement (generally resolves by 2mo); test hormonal axes: 8AM serum
cortisol + ACTH and/or cort stim; TSH w/ FT4/total T4/T3; PRL; LH/FSH, serum testosterone/SHBG (in men); IGF-1
• Tx: Hormone substitution: Hypocortisolism: glucocorticoid replacement (prednisone 3-5mg daily) (Cancer 2018;124:3706;
Oncologist 2016;21:804). Central hypothyroidism: levothyroxine. Hypogonadism: consider testosterone replacement.
GH deficiency: GH theoretically contraindicated due to active malignancy, although little clinical evidence
Myocarditis (JACC 2018;71:1755): Rare but serious AE a/w high mortality (46% in severe myocarditis); risk higher w/combo tx
• Timing: Generally within 3mo (Oncologist 2018;23:874; Lancet 2018;391:933)
• S/Sx: Heart failure, arrhythmia (high grade AV block, ventricular tachycardia)
• Dx: CK, EKG, troponin, NT-proBNP, TTE, MRI and EMG ± endomyocardial Bx
• Tx: Discontinuation of ICI; high dose or pulse-dose steroids (1g IV, then PO pred 1mg/kg) (J Am Heart Assoc 2020;9:2); 2nd-line
consider ATG/IVIg or infliximab/MMF/tacro (Oncologist 2018;23:879). GDMT for HFrEF. PPM for new conduction delay.
Other irAEs (JCO 2019;36:1714): Inflammatory arthritis/myositis, PMR/GCA, nephritis, pancreatitis/DKA, adrenal insufficiency,
hepatitis/cholestasis, myasthenia gravis, GBS, peripheral/autonomic neuropathy, aseptic meningitis, encephalitis/ADEM, optic
neuritis, traverse myelitis, AIHA, ITP, TTP/HUS, aplastic anemia, acq. hemophilia, pericarditis, uveitis/iritis, episcleritis, blepharitis
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Oncology Oncologic Emergencies

T U M O R L Y S I S S Y N D R O M E (NEJM 2011;364:1844; JCO 2008;26:2767)
• Pathophys: TLS 2/2 tx initiation or spontaneous in cancers w/ high turnover  release of intracellular metabolites (i.e. uric acid, K+,
phos)  AKI (uric acid causes renal vasoconstriction, precipitates in tubules), seizure, CaPhos crystal deposition (phos  Ca)
• Presentation: UOP, weakness/cramps/tetany/perioral numbness, seizure, arrhythmia
• Risk factors: high risk: ALL/AML (WBC ≥100k), CLL (on venetoclax & uric acid), stage 3/4 Burkitt/lymphoblastic NHL, bulky DLBCL;
intermediate risk: ALL (WBC <100k), AML (WBC 25-100k or <25k & LDH), Burkitt, DLBCL, CLL (chemo-specific & WBC), rare
chemo-sens bulky solid tumor; low risk: HL, indolent NHL, CML, CLL (on alkylating tx & WBC <50k), MM
o High risk substrate: WBC >50k, LDH >2x ULN, bulky tumor (>10cm), hypovolemia, uric acid >7.5, renal failure
• Labs/workup: BMP (electrolytes, Cr, iCal), Mg, phos (calculate Ca-phos product), uric acid, LDH, CBC/diff, ECG
• Diagnosis (Cairo-Bishop criteria):
o Laboratory diagnosis: ≥2 criteria within 3d before or 7d after cytoxic therapy: uric acid ≥8mg/dL, K ≥6mEq/L, phos ≥4.5mg/dL, or
Ca ≤7mg/dL. Criteria also satisfied if 25% change from baseline.
o Clinical diagnosis: laboratory dx & ≥1 clinical criteria: Cr 1.5x ULN, arrhythmia, or seizure
• Prophylaxis and treatment: while treating, labs q2-4h & telemetry (electrolyte abnormalities)
o Hydration: 2-3L/m2 per day. D5-1/2NS or NS if hyponatremic/hypovolemic. Maintain UOP ≥100cc/hr for excretion of uric acid
and phos; diuretics PRN (prefer loops to K) to maintain UOP and treat hypervolemia
o Urinary alkalinization: w/ NaHCO3, only indicated if metabolic acidosis when not using rasburicase, contraindicated in
hyperphos (CaPhos precip). Not common practice at MGH.
o Treat abnl electrolytes: hyperK tx (e.g. lokelma, lasix, insulin, RRT), phos binders, delay tx of hypoCa until phos normalizes or
hypoCa/hyperK is severe (tetany/arrhythmia) to avoid CaPhos precip
o Allopurinol (uric acid formation): 300-600mg/day (adjust dose if renal dysfunction). Can also utilize febuxostat in renal dysfunx.
  clearance of other meds (cyclophosphamide, MTX, 6-MP, azathioprine, ampicillin)
 HLA-B*5801 ↑prev. in Southeast Asian, black pts, ↑risk of SJS/TEN, consider testing (ACR guidelines) + alternative tx
o Rasburicase (uric acid clearance; discuss w/ attending): 0.2mg/kg IV (but 3-6mg IV usually effective), administer if high risk,
baseline renal failure, baseline or rising uric acid >7.5 or Cr despite allopurinol/saline, or cannot hydrate (volume overload)
 Risk of anaphylaxis, methemoglobinemia. Contraindicated in G6PD deficient (can cause hemolysis); check G6PD early
o Renal replacement therapy: indicated if Ca-phos product ≥70mg2/dL2 (albumin-corrected Ca × phos)
H Y P E R V I S C O S I T Y S Y N D R O M E / L E U K O S T A S I S (Blood 2012;119:2205; Blood 2018;132:1379)
• Etiology: (1) hyperproteinemia from monoclonal gammopathies (Waldenström’s macroglobulinemia [IgM] > MM [IgA>IgG]) or
polyclonal (cryoglobulins, HIV, Sjögren’s, RF, IgG4, IVIg or rituximab) (2) hyperleukocytosis/leukostasis seen in AML/ALL with
blasts >50k (leukostasis rare in CLL unless very high counts >400k WBC) (3) other: polycythemia vera, sickle cell, spherocytosis
• S/Sx: pulm (SOB, infiltrates) & CNS (blurry vision 2/2 retinal vein engorgement, HA, dizziness, ataxia, confusion, coma), fever,
epistaxis  page Heme/Onc fellow & Clin Path resident for emergency viscosity study, notify attending to discuss pheresis
• Diagnosis: serum viscosity (Ostwald tube), SPEP, SFLC, WBC (often >100k, but can be lower if AML/ALL blast crisis)
o Lab artifacts from hyperleukocytosis: spurious K (use blood gas K), falsely low arterial pO2 (use pulse oximeter)
• Treatment: always start with plasma volume expansion with IV NS
o Hyperproteinemia: plasmapheresis (aiming for resolution of symptoms); reduces viscosity by 20-30% per session
o Leukostasis: leukapheresis; cytoreduce (hydroxyurea); induction chemo; avoid RBC & plt transfusion (viscosity)

M E T A S T A T I C E P I D U R A L S P I N A L C O R D C O M P R E S S I O N (Seminars in Neurology 2010;30:245; Lancet Neurology 2008;7:459)

• Primary CA: lung, prostate, breast > non-Hodgkin's lymphoma, renal cell, multiple myeloma, Hodgkin’s lymphoma
• Location: T (60%) > L (25%) > C (15%); multiple sites in 30%; ESCC score for spinal level (JNCCN 2016;14:70)
• S/Sx: back pain (usually 1st sx; radicular, localized, worse at night/recumbent/valsalva)  weakness, gait instability  sensory
deficits (ascending numbness, saddle anesthesia in cauda equina), bowel/bladder dysfunction (urinary retention, incontinence)
• Exam: pain precedes other sx by ~7w, weakness/ataxia, paresthesia, reflexes, ⊕ Babinski, anal sphincter tone
• Diagnosis: STAT total spine MRI with cord compression/metastasis protocol, CT myelography if MRI not possible
• Treatment: call Spine Surgery & Radiation Oncology ASAP  more effective than chemo (except for heme, germ cell malignancies)
o Neuro deficits/pain: dexamethasone 10mg x1 IV, then 16mg PO daily (divided), taper once definitive tx
B R A I N M E T A S T A S E S W I T H I N C R E A S E D I N T R A C R A N I A L P R E S S U R E (Ann Palliat Med 2015;4:225; JCO 2015;33:3475)
• Intracranial tumors present in ~10-30% of patients with metastatic disease; call Neurosurgery & Radiation Oncology
• Primary CA: lung > breast > melanoma > RCC, osteosarcoma, head and neck, thyroid, colorectal
• S/Sx: HA (40-50%; “tension”, bifrontal, worse w/ Valsalva and forward bending, n/v), focal neuro deficits (20-40%, hemiparesis most
common), cognitive dysfunction (30-35%), new onset seizures (10-20%), stroke (5-10%)
• Diagnosis: MRI w/ contrast > non-enhanced MRI or CT with contrast.
• Treatment: control vasogenic edema (dexamethasone 10mg IV x1, then 4-8mg IV/PO BID), consider AED (usually not for 1° ppx);
avoid AC if concern for active hemorrhage; definitive treatment will local recurrence: for multiple mets, stereotactic radiosurgery >
whole-brain XRT (neurocognitive impairment can be mitigated w/ hippocampal avoidance/memantine) > surgery
S U P E R I O R V E N A C A V A ( S V C ) S Y N D R O M E (NEJM 2007;356:1862; Mayo CP 2017;92:609)
• Etiology: external compression of SVC from mediastinal mass (commonly lung CA or NHL) causing upper body venous pressure
• Symptoms: cerebral edema (HA, confusion, herniation), narrowing of larynx/pharynx (dyspnea, stridor, cough, dysphagia,
hoarseness), head/neck swelling (visually striking, often not clinically significant), hemodynamic instability (venous return)
• Diagnosis: CT venography (SVC syndrome protocol), obtain/ensure tissue diagnosis ASAP to guide definitive tx
• Treatment: secure airway, RT/chemo, intravascular stent (emergent/refractory), steroids (stridor/resp distress only, d/w attending)
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Oncology Febrile Neutropenia

D E F I N I T I O N S A N D E T I O L O G Y (J Oncol Pract 2019;15:19; NCCN Prevention and Treatment Guidelines)
• Definition: T ≥100.4 (≥1hr or oral >100.9) with ANC <500cells/mL or expected to decrease to <500 over the next 48h
o Functional neutropenia: defective PMNs, common in leukemia (neutrophil function despite ANC>500)
• Microbiology: ~40-50% have infectious source identified; others attributed to translocation of intestinal bacteria
o When organisms identified: 40% GNRs (E. coli, Klebs > PsA); 60% GPCs (CoNS > MSSA/MRSA, strep, enterococcus/VRE) esp
w/ indwelling lines or mucositis; fungal (Candida, Aspergillus) more likely w/ prolonged ANC, broad-spectrum abx use, or TPN

EVALUATION
• H&P: prior micro data, time since last chemo, recent antibiotic therapy/ppx, major comorbid illness, use of devices
• Exam: mouth (mucositis), skin, perineum/rectal (visual inspection, avoid DRE), indwelling lines/port (erythema/tenderness)
• Studies: BCx x2+ sites (≥1 periph, 1 per CVC lumen), UA/UCx, CXR, SCx/GS, resp viral panel/COVID-19 PCR, CMV PCR (SCT)
o Fungal markers: LDH, β-D-glucan; galactomannan if high risk for Aspergillus (SCT, GVHD, neutropenia >10-14d)
• Further site-specific studies to consider:
o GI symptoms: CT A/P (evaluate for neutropenic colitis/typhlitis); stool culture, O&P, C. diff if diarrhea
o Pulmonary symptoms: CT chest ± bronch/BAL (especially if prolonged F&N)
o Headache/sinus pain: CT face/sinus
• Risk stratification: (J Oncol Pract 2019;15:19; NCCN Prevention and Treatment Guidelines)
o MASCC Risk Index (JCO 2000;18:3038) and CISNE (JCO 2015;33:465) can measure risk of F&N-related complications
o High risk: anticipated ANC ≤100 for ≥7d, inpt status, co-morbidities/infections (renal/hepatic impairment, PNA, central line
infxn), allogeneic HCT, mucositis grade 3-4, alemtuzumab use or CAR-T within past 2mo  inpatient management
o Low risk (JCO 2018;36:1443): anticipated ANC ≤100 for <7d, no co-morbidities, good performance status (ECOG 0-1), strong
home social support  treated with PO antibiotics after brief inpatient stay versus strictly outpatient

TREATMENT/PROPHYLAXIS
• MGH Guideline; Alternate guidelines: (NCCN guidelines, Clin Infec Dis 2011;52:e56, J Oncol Pract 2018;14:250)
• Empiric abx: within 1h; up to 70% mortality if delayed abx (Antimicrob Agents Chemother 2014;58:3799)
o Gram-negatives (PsA dosing): broad Gram-negative coverage (including PsA) within 60min of presentation
 Cefepime 2g q8h (or ceftazidime 2g q8h), pip/tazo 4.5g q6h, or meropenem 1g q8h
 PCN allergy: confirm allergy; use Penicillin Hypersensitivity Pathway and test-dose cefepime or meropenem; consider
allergy consult. If true allergy, use aztreonam (avoid in ceftazidime allergy) + levofloxacin
 High-risk ESBL: meropenem 1g q8h (2g q8h if meningitis)
 Low risk: IV -> PO regimen (discuss w/ attending); cipro/levoflox + amox-clav vs clinda (if PCN allergy); avoid if prior FQ ppx
o Gram-positives: NOT part of FN empiric regimen (JAC 2005;55:436; Clin Infect Dis 2011;52:56)
 Indications: HoTN/severe sepsis, GPC bacteremia, catheter-related infxn (rigors with infusion, erythema on exam), SSTI,
PNA on imaging, MRSA colonization (esp in HCT), severe mucositis + prior FQ ppx + GNR coverage with ceftaz
 First line: vanc; if there is concern for VRE then daptomycin (unless pulmonary process, inactivated by surfactant) or
linezolid
o Anaerobes:
 Indications: intra-abd source, C. diff, oral ulcer/periodontal infxn, post-obstructive PNA, necrotizing ulceration
o Fungi:
 Indications: F&N >4-7d despite abx, ⊕ fungal biomarkers, ⊕ CT chest (circumscribed, air crescent, cavity), ⊕ BAL Cx
 Micafungin 100mg q24h or Amphotericin 5mg/kg q24h (admin after 500cc NS)
• Modification/duration: Note recommended duration of empiric therapy varies between guidelines (Ther Adv Infect Dis 2022;9)
o Resolution of fever:
 Documented infxn: narrow abx and tx for recommended course, then switch to FQ ppx until ANC >500
 Culture negative: continue empiric treatment until afebrile & ANC >500 vs narrow to FQ ppx if afebrile x4-5d
o Fever continues >4-7d:
 Clinically stable: do not broaden abx or add vanc, consider other causes (e.g. engraftment, differentiation, GVHD, TLS, drug
fever, thrombophlebitis, hematoma, hepatosplenic candidiasis), discuss w/ ID
 Clinically worsening: broaden abx ± fungal coverage, consider CT chest ± bronch to evaluate for fungal infxn
o Catheter-associated infection: also see Bloodstream Infections & Endocarditis
 Coag-negative staph, non-VRE Enterococcus: can keep line if IV abx + abx lock x2w
 Staph aureus, PsA, fungi: must remove line. For gram negative, d/w ID/attending, consider line removal vs. lock therapy
 Complicated infxn: (endocarditis, septic thrombosis, bacteremia/fungemia >72h post removal), remove line, abx x4-6w
• Prophylaxis:
o Anti-microbial ppx: refer to NCCN guidelines for more specific indications, also see Hematopoietic Cell Transplantation
 Antibacterial (FQs): high-risk pts (heme malignancy) and attending discretion for intermediate-risk pts
 Antifungal (azole vs echinocandin): select heme malignancies during neutropenia and early post-HCT
 PJP (TMP-SMX, atovaquone): if ≥20mg prednisone daily for ≥1mo, purine analog, CD4<200, or post-HCT/CAR-T
 HSV/VZV (acyclovir vs famciclovir): heme malignancy on therapy, post-CAR T, or post-HCT (1-2 years)
o G-CSF: ppx reduces incidence and duration of FN when risk >20% but does NOT decrease mortality (JCO 2015;33;3199);
consider adding if critically ill, anticipated prolonged neutropenia, PTLD, or HIV. Caution if leukemia (d/w attending)

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Oncology Inpatient Leukemia & Lymphoma Regimens

Regimen* Protocol Supportive Care
Leukemia
7+3 Induction for AML Premedication: Assess EF prior given
Idarubicin 12 mg/m2 daily x3days cardiotoxicity risk. Vesicant.
7d of cytarabine and Daunorubicin 60-90 mg/m2 daily x3 days Emetic Risk: High
3d of anthracycline Cytarabine 100-200 mg/m2 continuously, days 1- 7 Neutropenia Risk: High
(Idarubicin or Growth Factor: Filgrastim or Pegfilgrastim
Daunorubicin)
Decitabine MDS/AML: 20 mg/m2 IV over 60 min daily on Days 1-5 Premedication: PPx or tx symptoms with
(5-aza-2'- bowel regimen, antidiarrheals, IVF and/or
deoxycytidine, AML with unfavorable cytogenetic and/or TP53 electrolyte replacement
Dacogen) mutation: 20 mg/m2 IV over 60 min daily on Days 1-10 Emetic Risk: Minimal-to-low; PRN for
breakthrough
28-day or 42-day cycle Neutropenia Risk: Moderate
until disease Growth Factor: Filgrastim or Pegfilgrastim
progression or toxicity
5-Azacytidine AML: 300mg PO qday on D1-14 Premedication: During first 2 PO cycles,
(5-Aza, Azactidine, administer an antiemetic 30 min prior to each
Vidaza, Azadine, MDS: Cycle 1: 75mg/m2/day for D1-7; Subsequent Cycles: dose; antiemetic ppx may be omitted after 2
Onureg) 75 mg/m2/day q4weeks (Dose may be increased to 100 cycles if no n/v
mg/m2/day if no benefit after 2 cycles) Emetic Risk: Moderate, Cycle 1-2
28-day cycle until Neutropenia Risk: Moderate
disease progression or Growth Factor: Filgrastim or Pegfilgrastim
toxicity
HiDAC Consolidation: Premedication: Corticosteroid eye drops
(High-Dose ara-C) HiDAC: 1.5-3 g/m2 over 3h q12h on Day 1, 3, 5 -OR- Day 1, throughout consolidation
2, 3 for 3-4 cycles Emetic Risk: Moderate
(ara-C, Cytarabine) Neutropenia Risk: Moderate
Growth Factor: Filgrastim or Pegfilgrastim
Hyper-CVAD Hyperfractionated Cyclophosphamide (CP): 300 mg/m2 Premedication: NS 100mL/hr prior to
IV over 3h q12h for 6 doses on days 1-3, given with Mesna chemotherapy. Continue through
Dose-intensive phase: 600 mg/m2 as continuous infusion ending 6h after last dose cyclophosphamide
8 cycles of Hyper- Vincristine: 2 mg IV Days 4 and 11 Emetic Risk: Day 1-5, high
CVAD alternating with Doxorubicin: 50 mg/m2 IV on Day 4 Neutropenia Risk: High; Median times to
High-Dose Dexamethasone: 40 mg daily on Days 1-4; 11-14 granulocyte and platelet recovery were 18 and
Methotrexate and 21 days, respectively
Cytarabine (HD MTX- HD MTX-ara-C: Growth Factor: Filgrastim or Pegfilgrastim on
ara-C) MTX: 200 mg/m2 IV over 2h followed by 800 mg/m2 IV over Day 5 (24h after chemotherapy)
+ intrathecal (IT) PPx 24h on Day 1; Leucovorin rescue starting 24h after
each cycle for 16 IT completion MTX; dose according to MTX level
treatments. ara-C: 3 g/m2 over 2h q12h x 4 on Days 2-3
Methylprednisolone: 50 mg IV twice daily Days 1-3
Maintenance phase:
Dependent upon CNS PPx:
clinical response Risk-stratified CNS ppx with alternating intrathecal (IT) high-
dose methotrexate (MTX) and cytarabine (Ara-C)
MTX: 12 mg IT on Day 2
ara-C: 100 mg IT on Day 8
ATRA/ATO Induction: Premedication: none
Induction: ATRA All-Trans Retinoic Acid (ATRA): 45 mg/m2 in divided Emetic Risk: Moderate
should be continued doses daily, starting Day 1. Start ATRA upon first suspicion Neutropenia Risk: High
until CR is achieved. of APL Differentiation Syndrome: maintain a high
Restage with BM Arsenic trioxide (ATO): 0.15 mg/kg IV daily, starting after index of suspicion (fever; WBC >10k; SOB;
aspirate and biopsy on cytogenetics confirmation hypoxemia; pleural or pericardial effusions).
Day 28 Discuss steroid use with attending, supportive
Consolidation: Growth Factor: Myeloid growth factors
ATRA: 45 mg/m2/d for 2 weeks q4weeks for a total of 7 should not be used during induction. May be
cycles considered during consolidation for life-
ATO: 0.15 mg/kg IV 5d/wk for 4 weeks q8weeks for a total threatening infection, sepsis, etc.
of 4 cycles
Hydroxyurea HU: Starting dose 500 mg BID or 1000 mg QD; dose Premedication: none
(Hydrea; HU) adjusted to ANC 500-1000; cytoreduction and WBC count Emetic Risk: Minimal-to-low
goal based on disease and therapy regimen Neutropenia Risk: Moderate
Growth Factor: count recovery within days of
stopping agent
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Oncology Inpatient Leukemia & Lymphoma Regimens

Lymphoma
R-CHOP Rituximab: 375 mg/m2 IV Day 1 Premedication: Diphenhydramine and
Cyclophosphamide: 750 mg/m2 IV over 30 min Day 1, acetaminophen prior to rituximab
14-day cycle, restage combined oral and IV hydration 2-3L on day of chemo Emetic Risk: Day 1, high
after 2-4 cycles, total Doxorubicin: 50 mg/m2 IV Day 1 Neutropenia Risk: High
3-6 cycles +/- radiation Vincristine: 1.4 mg/m2 (max 2 mg) IV over 15-20 min Day 1 Growth Factor: Filgrastim or Pegfilgrastim on
Prednisone: 100 mg PO Days 1-5 Day 6 or 3-4 days after completion of
chemotherapy until count recovery
CNS PPx: 4-8 doses of IT MTX and/or cytarabine or high-
dose MTX during the course of treatment
Dose-Adjusted Rituximab: 375 mg/m2 IV Day 1 Premedication: Diphenhydramine and
R-EPOCH Etoposide: 50 mg/m2 infusion over 24h daily on Days 1-4 acetaminophen prior to rituximab
Doxorubicin: 10 mg/m2 continuous infusion over 24h daily Emetic Risk: Days 1-5, high
21-day cycle, 6 cycles on Days 1-4 Neutropenia Risk: High
(dose adjustments Vincristine: 0.4 mg/m2 continuous infusion over 24h daily Growth Factor: Filgrastim or Pegfilgrastim
based on ANC counts on Days 1-4 after completion of chemotherapy until count
from BID CBC during Cyclophosphamide: 750 mg/m2 IV over 30 min Day 5, recovery
previous cycle) combined oral and IV hydration 2-3L on day of chemo
Prednisone: 60 mg PO BID Days 1-5

CNS PPx: 4-8 doses of IT MTX and/or cytarabine or high-

dose MTX during the course of treatment
R-ICE Rituximab: 375 mg/m2 IV Day 1 Premedication: Diphenhydramine and
Ifosfamide: 5,000 mg/m2 IV continuous infusion over 24h acetaminophen prior to rituximab
14-day cycle, 3 cycles on Day 2 with NS at 1.5-3 ml/kg/hr beginning 2h prior and Emetic Risk: Day 1, 3 – Low; Day 2 High
ending 2-4h after infusion Neutropenia Risk: High
Mesna: 5,000 mg/m2 IV infusion over 24h on Day 2 Growth Factor: Filgrastim or Pegfilgrastim on
Carboplatin: Dose ~ AUC 5 mg/mL IV over 30 min on Day Day 4 or 3-4 days after completion of
2 chemotherapy until count recovery
Etoposide: 100 mg/m2 daily on Days 1-3
ICE See R-ICE above, hold rituximab
R-DHAOx Rituximab: 375 mg/m2 IV Day 1 Premedication: Diphenhydramine and
Dexamethasone: 40 mg PO daily on Days 1-4 acetaminophen prior to rituximab
21-day cycle Cytarabine: 2,000 mg/m2 IV Day 2 (2 doses) Emetic Risk: Moderate
Oxaliplatin: 130 mg/m2 IV over 2h on Day 1 Neutropenia Risk: High
Growth Factor: Filgrastim or Pegfilgrastim on
Day 5 or 3-4 days after completion of
chemotherapy until count recovery
R-Bendamustine Rituximab: 375 mg/m2 IV Day 1 Premedication: Diphenhydramine and
Bendamustine: 90 mg/m2 IV over 10 min or IV over 30 min acetaminophen prior to rituximab
28-day cycle, 6 cycles daily on Days 1-2, CVC recommended for administration Emetic Risk: Moderate, Day 1-2
Neutropenia Risk: High
High-dose CNS PPx: Hydration: Alkaline hydration with 5%
Methotrexate (MTX) MTX: 3,000-3,500 mg/m2 over 4h on Day 1 on alternate Dextrose in sodium bicarbonate 100 mEq/L at
days of chemotherapy regimen 150 cc/hr 4h prior until 72h after completion of
Dependent on Leucovorin: 25 mg IV over 15 min or PO on Day 2 starting MTX infusion
chemotherapy 24h from initiation of MTX and q6h until MTX < 0.05 uM Emetic Risk: Days of MTX, moderate
regimen and count- Neutropenia Risk: High
recovery for 1-8 cycles Growth Factor: Filgrastim or Pegfilgrastim on
Day 4 or 3-4 days after completion of
chemotherapy until count recovery
Solid
FOLFOX, FOLFIRI, Folinic Acid: 200 mg/m² IV Day 1 Toxicities: If acute cholinergic syndrome
FOLFOXIRI, Oxaliplatin: 85 mg/m² IV Day 1 appears use atropine. Can also have
FOLFIRINOX Irinotecan 180mg/m² IV Day 1 laryngospasm and rarely, coronary artery
Fluorouracil: 400 mg/m² IV bolus followed by 2400 mg/m² vasospasm spasm.
(FOL) Folinic Acid 1d for 2 days Emetic Risk: High
(F) 5-Fluorouracil 1-2d Neutropenia Risk: High
(IRI) Irinotecan Growth Factor: Filgrastim or Pegfilgrastim on
(OX) Oxaliplatin 1d Day 6 or 3-4 days after completion of
chemotherapy until count recovery
*Chemo regimens may be modified based on genetics, risk stratification level, cardiac history, QTc prolongation. For further details on
stratification and protocol details see NCCN.org

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Geriatrics & Palliative Care Pain Management

G E N E R A L A P P R O A C H T O P A I N M A N A G E M E N T (NEJM 2015;373:2549; Lancet 2011;377:2236; Fast Facts app for pearls)
• A comprehensive pain hx is essential to guiding therapy. Goal is to maximize level of functioning and quality of life.
• Step-wise approach to pain management: (WHO Guidelines; CDC guidelines; DFCI Pink Book)
o Mild to moderate pain: non-opioids and adjuvants
 Acetaminophen: max dose 4g daily, 2-3g safe in liver disease (Br J Clin Pharmacol. 2016;81:210)
 NSAIDs: celecoxib best if GIB risk, ketorolac if severe pain [10 –15 mg recommended, no added analgesia with higher
doses (Am Fam Phys 2017;96:262)], use with caution in CAD, renal disease, IBD
o Moderate to severe pain: schedule non-opioid options, try topicals, then consider short-acting opioids PRN
o Severe pain: requiring round-the-clock opioids. Discuss w/ attending, consider adding extended release (ER) meds
 Avoid ER opioids if pain source is expected to resolve (e.g., bone fracture, hematoma, abscess, post-procedural)
• “Basal-bolus” strategy: Obtain basal level of pain control throughout the day with scheduled oral doses + PRNs for breakthrough pain
PAIN ARCHETYPES AND USEFUL ADJUVANT ANALGESICS
• Somatic/musculoskeletal: easily localized, sharp, aching, gnawing *Considerations with
o Bony pain: high dose NSAIDs or steroids*. Consider palliative XRT (if cancer-related) or surgery steroids: in cancer patients,
o Muscle spasm: topical lidocaine, capsaicin, methyl salicylate-menthol ointment; muscle may interfere with treatment
relaxants (cyclobenzaprine, baclofen, tizanidine; watch for sedation & delirium) (e.g immunotherapy) and/or
• Visceral: deep tissues and internal organs, vague, referred or difficult to localize diagnostics. If prolonged
o Visceral distension (e.g., hepatic capsular stretch from liver mets, malignant bowel obstruction): course, will need GI and
depends on etiology but steroids* can be helpful. Can consider plexus block with Chronic Pain PJP ppx; determine who will
manage taper plan at
• Inflammatory: associated with other signs of inflammation (swelling, erythema, warmth)
discharge
o NSAIDs (systemic or topical), steroids*
• Neuropathic: burning, stinging, allodynia, hyperalgesia
o Topical: capsaicin, camphor/menthol, lidocaine, diclofenac gel. POs in chart below (start low & go slow in older adults)
• Non-pharmacologics: PT/exercise/activity, heat or ice, CBT, treating comorbid psych dx, massage, acupuncture, other integrative
therapies (note: for inpatient, massage and acupuncture currently only available for heme/onc patients)
N E U R O P A T H I C P A I N A N D O P I O I D - S P A R I N G A N A L G E S I A (*R – dose adjustment needed for renal function)
Drug Initial Dose Titration Dose range Notes
Gabapentin 100 mg po TID *R Inc 100 mg tid q3 days 300 – 3600mg/day Dose adjust for renal function; may take a
few weeks to see effect
Pregabalin 75 mg BID or 50 Can inc by 50-150mg/day 300 mg / day in 2-3
mg TID *R within 1 wk if tolerating divided doses
Duloxetine 20 mg daily *R Inc by 20-30 mg per week 20-60 mg / day Common side effect sweating (6%); avoid
if CrCl<30ml/min
Venlafaxine 37.5-75mg daily *R Inc by 75 mg q 4 days 75 – 225 mg /day Allow 4-6 wks for effect; Risk of withdrawal
syndrome when stopped (need taper)
Amitriptyline 25 mg at bedtime, Titrate dose every few 25-100 mg at Allow 2-4 wks for effect;
Nortriptyline 10 mg in days bedtime Less side effects with nortriptyline
frail/elderly
K E T A M I N E ( General Guidelines on Ketamine for Acute Pain, MGH Ketamine Use Policy)
Initiation of ketamine, and adjustment of dose requires consultation with either Palliative Care or Chronic Pain Service
• Consider in: 1) Expected severe post-operative pain (abdominal/thoracic surgery, orthopedic surgeries) 2) Opioid tolerant pts
presenting for surgery or acute pain exacerbations. 3) Pts at increased risk of opioid-related respiratory depression (OSA)
o Adverse effects: rare at sub-anesthetic dosing (HTN, tachycardia, arrythmia, hallucinations, increased ICP, increased bronchial
secretions, N/V). Psychomimetic effects may be treated w/ 0.5-1 mg IV haloperidol or 1-2 mg IV lorazepam.
o Avoid in: poorly controlled cardiac disease, pregnancy, active psychosis/hospitalization hx (<3 yrs), severe liver dz, elevated ICP/IOP
O P I O I D S ( CDC app for guidelines & MME calculator)
• Opioid-tolerant defined as total daily dose (TDD) x7d: morphine 60mg/oxycodone 30mg/hydromorphone 8mg/fentanyl 25mcg/h
• Patients on buprenorphine/methadone for OUD, or active non-Rx OUD  treat pain w/ full agonists if needed, See OUD &
Withdrawal for strategies for each scenario. Can consult ACT if needed for assistance.
• Avoid using combo pills (limits titration flexibility). See Opioid Pharmacokinetics Chart for sample initial dosing.
OPIOID PHARMACOKINETICS CHART
* For opioid naïve patients in moderate or severe pain. If opioid tolerant, consider home PO breakthrough dose or 10-20% of ER dose
**If concern for hepatic or renal metabolism, would use wider dosing intervals and be more cautious with uptitration
Sample Initial PRN Peak Duration
Onset
Route Doses* (dose reduce Effect of Effect Clearance/Metabolites**
(min)
~50% for elderly) (min) (hr)
IV 2-4mg q3-4h prn 5-10 10-30 3-5
Morphine AVOID in renal disease
PO 7.5-15mg q3-4h prn 15-60 90-120 4
IV 0.2-0.4mg q3-4h prn 5-20 15-30 3-4
HYDROmorphone Safer in renal and liver disease
PO 2-4mg q3-4h prn 15-30 90-120 4-6
OxyCODONE PO 5-10mg q3-4h prn 15-30 30-60 4-6 2nd line for renal disease

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Geriatrics & Palliative Care Pain Management

45m to 2+ Safer in renal and liver disease
FentaNYL IV 25-50mcg q15-30m prn <1 5-7
hr
IV Consult pain and/or pall 10-20 60-120 4-6
Methadone Safer in renal and liver disease
PO care 30-60 90-120 4-12
Methadone:* Beneficial in neuropathic pain (TID dosing for pain) o Safety concerns: if febrile, dose reduce or remove patch
o Cannot be converted linearly from other opioids (cutaneous vasodilation  faster transdermal absorption)
o Safety concerns: bimodal short and long half-life (up to o Less effective in cachexia (less subq fat for absorption)
150 hours), QTc prolongation (monitor K, Mg) o Requires 18-24h to reach therapeutic level
o Takes days to reach steady state. Titrate q4-5 days
Fentanyl Patch:* Safer in both liver and renal dysfunction
*Initiate with Chronic Pain/Palliative Care consult. Must ensure that there is an outpatient prescriber at discharge (PCP or subspecialist).
OPIOID UPTITRATION/ROTATION
• If pain only moderately controlled with scheduled doses (not in pain crisis, no side effects),  total daily dose by 30-50%
• If taking ER opioid and needing >3-4 rescue doses daily,  ER dose by 50-100% of total rescue dose used in past 24h
• Rotate opioids if side effects, dose reduce by 25-50% when rotating. See example/table below.
• If pain persists, repeat pain hx, consider total pain, and involve an interdisciplinary team (eg, palliative care, chronic pain, etc)
Ex: Pt takes morphine ER 60mg PO q12h +/- morphine IR 15mg PO BID Opioid Equianalgesic Doses
Step 1) Calculate total daily opioid requirement
Drug PO (mg) IV (mg)
TDD = (60mg x 2 doses) + (15mg x 2 doses) = 150mg morphine
Morphine 30 10
Step 2) Convert TDD to equivalent dose of new opioid
30mg morphine 150mg morphine OxyCODONE 20 n/a
= x = 100mg oxycodone HYDROcodone 20 n/a
20mg oxycodone x
Step 3) Reduce dose by 25-50% to account for incomplete cross-tolerance  HYDROmorphone 7.5 1.5
~60mg oxycodone total daily dose FentaNYL* n/a 0.1 (100 mcg)
Step 4) Divide TDD by number of doses per day Fentanyl patch (mcg/hr) Morphine PO (mg/day)
- If initiating or converting to long-acting opioid, divide TDD into ER doses and 25 50
add breakthrough dose (10-20% of TDD of ER opioid) *Caution w/ conversion to fentanyl (short duration of
Final dose: oxycodone ER 30 mg q12h with 10 mg oxycodone q4h prn action)
PAIN CRISIS MANAGEMENT
Severe worsening of pain; while treating, pursue reasonable diagnostic workup for etiology (e.g., bowel perforation/peritonitis, procedural
complication, bleeding). Goal is reduction in pain score by at least 50%. In sickle cell VOE, follow patient’s guidance/Acute Care Plan
1) Opioid-naïve: give morphine IV 2-5mg or hydromorphone IV 0.2-0.4mg bolus dose
Opioid-tolerant: convert usual breakthrough PO dose or 10-20% of total daily ER dose to IV and administer
2) Assess for response after 15min:
o No pain relief and no side effects  increase dose by 50-100%
o Minimal relief and no side effects (<50% reduction in pain score)  repeat the same dose
o Pain reduced >50% and no side effects  reassess in 2-3h, use this dose as new breakthrough dose
o Side effects with no pain relief  rotate to different IV opioid (no dose reduction if uncontrolled pain).
PATIENT-CONTROLLED ANALGESIA (PCA)
• Appropriate for patients who are alert & oriented and able to General Opioid-Naïve PCA Dosing
use equipment. Families may NOT use PCA by proxy
Morphine Hydromorphone
• Requires daily delirium assessment (ie, CAM/4AT).
Unrecognized delirium can obscure pain hx/medication use. Patient Administered Dose 1.5mg 0.2mg
• Enables frequent administration of pain meds (vs max q1-2hr) Lockout Interval (per min) 10-15min 10-15min
• Order “General PCA” (opioid-naïve pts) or “High Risk PCA” One-Hour Dose Limit 6mg 1.4mg
(BMI >40, hx OSA, RASS -2 to -5, age >65). If pt is opioid- RN/Clinician Bolus (for 2mg q30min 0.3mg q20min
tolerant, requires basal rate, consult Palliative Care/ Pain breakthrough) PRN PRN
• Increases in basal rate takes ~12 hrs to reach steady state: Continuous Infusion Rate 0mg/hr 0mg/hr
adjust basal rate q24hrs. If nighttime awakening w/ pain, can increase in basal rate at night
ADVERSE EFFECTS OF OPIOIDS AND MANAGEMENT
• Respiratory depression: Follows sedative effects. Hold opioid, consider low dose naloxone but CAUTION if on high dose ER opioids
o Dilute 0.4mg naloxone (1ml) in 9ml saline, give 1-2ml q2min until RR or mental status improves. Naloxone half-life is 30-
120min, watch for recurrence of resp depression and consider naloxone gtt. All patients d/c’d on opioids need a naloxone script
• Constipation: ALWAYS start standing senna and/or Miralax when initiating opioids; use other laxatives if needed;
methylnaltrexone QOD if failed laxative therapy (but can cause severe nausea/cramping; avoid if concern for GI obstruction)
• Opioid-induced hyperalgesia: generally seen w/ high doses (or lower doses in CKD), consider rotating opioids and involving pall care
• Myoclonus: reduce dose or rotate opioid, increase hydration; can give low dose BZD, baclofen, or gabapentin. If persists, c/s pall care
• Nausea/vomiting: start prochlorperazine, metoclopramide, haloperidol, or low dose naloxone gtt; avoid ondansetron (constipating)
• Pruritus: mediated by mu receptor (not histamine – Benadryl ineffective unless rash/allergic reaction); consider opioid rotation,
ondansetron, nalbuphine 5mg IV q6h, or low dose naloxone gtt
• Sedation: occurs prior to resp depression. Consider CNS stimulant (dextroamphetamine, methylphenidate although rarely prescribed)
• Delirium: reduce dose or rotate opioid; IV Haldol 1-2.5mg BID-QID or IV/PO Zyprexa 2.5-5mg PO QD-BID
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Geriatrics & Palliative Care Adv Care Planning & Code Status
SERIOUS ILLNESS CONVERSATIONS MGH CONTINUUM PROJECT
When? Conversations can be planned or may happen spontaneously in any setting (NEJM 2014;370:2506). Should discuss early in disease
course as outpatient, or:
• New, progressive (eg, increasing hospitalizations/ED visits, intolerance of guideline-directed therapies), or life-altering serious medical
illness such as advanced cancer, ESRD, ESLD, HF, COPD
• Prognosis trigger: “Would I be surprised if this patient died in the next year?” (J Palliat Med 2010;13:837). Life expectancy <6mo (UCSF
calculator, J Palliat Med 2012;15:175)
• Age >80 and hospitalized if no previous documentation; see Geriatric Assessment & Frailty
Why? Longitudinal SICs help explore illness understanding, hopes/worries, and what matters most. Involves pt-centered recommendation
regarding a care plan that aligns with pt goals. Can be used for the purposes of Advanced Care Planning, discussion of transition to
hospice/CMO, or referral to palliative care (more than just code status)
How?
Preparation for planned meetings:
• Consider a palliative care consult prior to the formal meeting if complex decisions/psychosocial issues/family conflict.
• Identify time and location to accommodate the patient and their loved ones, RN, SW, primary team, and consultants as applicable.
• Pre-meet with team, including consultants, to discuss: goals, unified assessment of clinical scenario, if a clinical decision needs
to be made urgently, and if so, what are treatment options and team recommendations (in alignment w/ pt stated goals)
MGB Serious Illness Conversation (SIC Guide, Videos):
Step Suggested Prompts
Open the conversation “I’d like to talk about what is ahead with your health. Would that be ok?”
“What is your understanding of your health?”
Assess prognostic awareness “Looking to the future, what are your hopes about your health? What else?” “What are your worries?
Tell me more.”
“Would it be ok if we talked more about what may lie ahead?”
“I hear you’re hoping for ____ and I worry the decline we’ve seen will continue” or “I worry something
Share worry
serious may happen in the next few wk/mth/yrs.”
“It can be difficult to predict what will happen with your health.”
Align “I wish we didn’t have to worry about this”
“What gives you strength as you think about the future of your health?”
Explore what’s important “If your health worsens, what is most important to you?
“How much do your family or friends know about your priorities and wishes?”
“It sounds like ____ is very important to you.”
Make a recommendation
“Given what’s important to you, I would recommend______”

Document Serious Illness Conversation: (Refer to Advanced Care Planning Module in Epic)
● Patient ID banner (top left of storyboard): click “Code: ___”  “Advance Care Planning Activity”  “Serious Illness Conversation” in
left tab; fill out SIC form " “Close”
● Open a note with type “Advance Care Planning” and use the dot phrase to insert the SIC  type .seriousillnesslast
● Consider filling out ACP forms if not already filled out (see Advanced Care Planning Forms)

ADVANCE CARE PLANNING FORMS

● Health Care Proxy (HCP)/medical power of attorney: an advance directive document that designates a healthcare agent to make
future medical decisions if patient loses capacity. Expressly authorized in MA by statute. Filling out this form is a priority for all patients
but more urgently for older adults, those with emerging cognitive impairment, and those with multimorbidity and/or complex life-limiting
illnesses.
o If no HCP: see Section 3, bullet 6 of MA: An Act Improving Medical Decision Making
● Living Will: an advance directive document in which a competent person specifies future medical treatments in the event of
incapacity (usually at end-of-life or if in a persistent vegetative state). Can be used as evidence of a person’s wishes, but not
considered to have legal authority (no MA statute that expressly authorizes)
● MOLST (MA Medical Orders for Life-Sustaining Treatment; pink form available on all medical units): medical orders for patients with
multimorbidity or serious illness that documents preferences for CPR, intubation, hospital transfer, artificial nutrition, dialysis, and
more
o Transferrable to outside facilities; must complete MOLST prior to discharge to rehab/SNF if patient DNR/DNI
o Remember that you do not have to fill out or discuss everything on the back page (clinical discretion)
o Remember that these decisions can be changed (fill out a new MOLST if decisions change)
● Links to existing MOLST/HCP forms are found in Advance Care Planning Activity tab or scanned into the Media tab
o If filling out a new form, provide patients with a copy and scan into Epic for future documentation

CODE STATUS DISCUSSIONS

General Considerations
● Confirm directly with the patient/HCP, MOLST, and/or prior documentation by outpatient providers
● Readdress if a patient’s clinical status changes, or if code status appears discordant with the clinical setting, Do not need to routinely
readdress on admission if has been recently addressed by outpatient providers

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Geriatrics & Palliative Care Adv Care Planning & Code Status
● Code status ≠ ACP. Code status is a medical procedure for which harms/benefits should be weighed iso clinical context.
● Many procedural teams (i.e. cards, surgery) require temporary reversal of DNR/DNI periop, often 30d (JAGS 2022;70:3378-3389):
o If changing code status pre-op (i.e. TAVR), ensure your discharge documentation includes changing status back/date of
conditional code status end
o If changing code status during early post-procedure or during chemotherapy, notify procedural team/primary oncologist
Survival Outcomes (Circulation 2019;139:e56)
● Out-of-hospital cardiac arrest: survival to hospital discharge 10.4%; survival with good neurologic function 9.9%
● In-hospital cardiac arrest: survival to discharge 25.6%; survival with good neurologic function 22%
o Favorable prognostic factors: ACS, drug overdose, drug reaction (up to 40% survival)
o Unfavorable factors: age >80 (<10% survival), multi-organ failure, sepsis, advanced cancer, ESRD, ESLD, dementia
o Post-arrest complications: hypoxic-ischemic brain injury, rib fractures, pulmonary contusion, prolonged ICU care, acceleration of
physical and cognitive frailty/disability

Code status options:

Full Code The patient would want all resuscitative measures to be used
DNR/Ok to Intubate The patient would not want cardiac resuscitation but would want to be intubated in the event of
impending respiratory failure
DNR/DNI In the event of a pulseless cardiac arrest or respiratory failure, the patient would not want cardiac
resuscitation or intubation
DNR/DNI/LLST Comfort The patient would want their care team to orient care around comfort only, and care not oriented
Measures around comfort may be withdrawn while still treating the patient’s symptoms
Do not offer “Full Code Except Do Not Intubate.” Cardiopulmonary arrest requiring CPR nearly always necessitates intubation, and
thus this is not an appropriate code status.

Conducting Code Status Discussions (JAMA 2012;307:917)

• Suggested framing: “Resuscitation is a medical procedure we would perform if your heart were to stop and you died. What have you
heard about resuscitation?”
• Many people would prefer a natural death. If you prefer a natural death then we would protect you from these procedures and ensure
your comfort.” Approaches to discussion of code status based on scenario (Indication and goal based on NEJM 2020;382:2450)
• Suggested opener: “Have you ever discussed CPR and intubation with your medical team? I want to make sure that I understand
whatever decisions you’ve made regarding those two interventions.”
Scenario/Indication Approach/Goal Example
The patient has a stable Make sure the patient “Right now, if your heart were to stop, you would receive CPR. Is this
condition and is likely to does not strongly consistent with your goals?”
benefit from CPR/Intubation prefer to avoid these
medical interventions
The patient already has a Confirm an already “Your records show that you made an emergency plan with your outpatient
preference to limit CPR and established preference doctor to focus on comfort and allow for a natural death. This means that we
intubation that needs would not use chest compressions to start your heart or a use a breathing
confirmation machine. Based on my medical assessment, I think we should continue this
plan now. Does that sound right to you? We will do everything else we can to
help you get through this.”
The patient has an Shared decision- “If an emergency were to occur and your heart were to stop, it is difficult to
advancing illness, and it is making predict what would happen if you received CPR or a breathing tube.
unclear whether the benefits Recognizing this uncertainty, if your heart were to stop and you were to stop
of CPR and intubation would breathing, what would you want your medical team to know about what is
outweigh the burdens (the important to you?”
decision depends heavily on “Given what’s important to you, I would recommend______”
the patient’s values and
goals)
The patient is at risk for Informed Consent Introduce/assess: If urgent: “I wish we were meeting under different
decompensation/death, circumstances.”
unlikely to benefit from CPR Share information: “Given all that’s happened, I worry that your health has
and intubation worsened. What are your thoughts about how things have been going?”
(Discuss medical situation, share concerns using hopes/concerns)
Explore goals: “Given where we are, what is most important to you?”
Make a recommendation:
-“I recommend we make a plan to help you meet your goals and avoid
treatments that are unlikely to help.”
-“I recommend that if your heart and lungs were to stop working, we focus on
your comfort. This means having treatments such as oxygen and medication.
This also means we would not use CPR or a breathing machine. Does that
sound right to you?”

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Geriatrics & Palliative Care End of Life & Pronouncement

ANTICIPATED INPATIENT DEATH
• Involve family, chaplaincy (available 24/7), social work services, longitudinal providers (e.g. PCP, subspecialists) in/during EOL care
• Ask about religious/cultural traditions, final wishes, and/or any specific preferences/experiences to keep in mind
• When passing off a patient who may pass away, prep “Post-Mortem” section under “Discharge as Deceased” Epic Tab (see below)
o Consider asking families about autopsies in advance if/when appropriate
• Assess whether you will need to notify the medical examiner’s office. Common reasons:
o Any death associated with acute or chronic use of alcohol or drugs (including alcohol-related cirrhosis);
o Death associated with diagnostic or therapeutic procedures;
o Death by accidental/unintentional injury (including falls, fires), violence, suicide, or uncertain circumstances
ORGAN DONATION
• Eligibility: IF family & medical team elect to discontinue medical support in any ventilated patient with a non-recoverable
injury/condition, team should then complete a New England Donor Services e-referral form (see below) prior to any of the following:
o Initiating therapeutic hypothermia, initiating brain death testing, transitioning from FULL to either DNR, DNE, or CMO status
• DO NOT broach topic of potential donation with family; NEDs is specifically trained for this and will coordinate consent & donation
process which can take up to 24hrs
• Care prior to donation: maintaining organ viability during severe autonomic/inflammatory responses following severe neurologic injury.
Key goals: MAP 60-110, normothermia, UOP 0.5-1.0cc/kg/hr, LTVV (CCM 2015;43:1291; NEJM 2004;351:2730; JAMA Surg 2014;149:969)
• OR Prep: Death paperwork must be done by declaring MD (prep in advance). After vent withdrawal (usually extubation in OR),
MD/RN coordinate sx management until time of death, declare death based on irreversible cessation of circulatory/respiratory function
W I T H D R A W I N G V E N T I L A T O R Y S U P P O R T (palliative extubation, discontinuation of NIPPV)
• Prior to extubation, refer to MGH MICU Policy & ATS Guidelines (AJRCCM 2008;177:912). Review plan with the following people:
o Family: ask if they want time privately w/ pt prior to extubation. Review expected signs of dying process (agonal breathing/‘rattle’
of pooled secretions, mottled extremities), expected timeline (usually min to hrs [Chest 2010;138:289]), and plan for sx control
o RN: ensure adequate PRNs for air hunger/pain (IV opioids), anxiety (IV Haldol or benzos), and secretions (glycopyrrolate) are at
bedside (see Comfort Focused Care); may need continuous infusions depending on requirements; can use CMO order set. Stop
paralytics though can continue any prior sedative and/or opiate infusion(s) utilized for comfort while mechanically ventilated
o RT: determine plan for immediate withdrawal vs down-titration of vent support
• Do not withhold appropriate sx management because of concern for hastening death or concern for increased sedation
o “The Rule of Double Effect” (NEJM 1998;338:1389): focus on managing sx. If in doubt, ask for help
o The goal is adequate pain, dyspnea, and anxiety relief; dose based on ongoing symptoms and prior dose effectiveness
DEATH PRONOUNCEMENT
• PRONOUNCEMENT: Introduce yourself to the family, express condolences, and explain what you are doing
o FEEL for pulse, LISTEN for heart/breath sounds (>60 sec), SHINE light to assess for absence of pupillary reflex, and NOTE time
at the end of your exam which becomes official time of death (do NOT need to say out loud)
• QUESTIONS FOR NEXT OF KIN: (Not HCP; Order: Spouse > Children > Other Fam). In MA, HCP does not remain in effect after
death, and legal NOK assumes responsibility for post-mortem decisions.
o Would they like to be connected with MGH Decedent Affairs Office (new service;
provide support re: final arrangements; connecting family with spiritual care, social Autopsies are free & do not delay
services, bereavement groups, and even financial resources for burial) funerals (can still have open casket).
o Would they want an autopsy? (consent NOK in MA, NOT HCP) They help determine cause of death &
o If yes, ask about organ disposition (i.e. do they want MGH to retain organs for further can be instrumental in advancing
testing, education, research?) research.
o Are there any other family members whom they would like you to inform?
o Is anyone else coming to view body prior to transport to morgue? (have 4hrs; can’t see body at morgue but can at funeral home)
o What you can tell family: body is kept at MGH morgue until the funeral home they select calls MGH and arranges for pickup.
Family should select and contact funeral home directly (Decedent Affairs office can assist with this)
• ONCE YOU LEAVE THE ROOM:
o Notify ATTENDING and PCP (Email acceptable if death was expected)
o Electronic Documentation: No longer paper form,* now section under Epic Discharge Tab called Discharge as Deceased,
similar to standard floor discharge navigator layout – NOTE: items CAN be prepped & saved ahead of time;
• In “Cause of Death” section: don’t write “cardiac arrest” or “respiratory arrest”; Fill out as many underlying causes as
applicable - do not need to fill in ALL the lines but be as specific as possible. See CDC guide for examples.
• Call Medical Examiner if necessary (see above “Prior to Death”); document first name of said staff member.
• Click on New England Donor Services referral link: replaces initial screening phone call
o Opens separate online tab within Epic with patient’s demographic info prepopulated/filled in; will need to answer
several additional questions (cause of death, vent hx, whether + for HIV/HBV/HCV, if active cancer & what type if so);
o Will still need to subsequently call NEDS coordinator (800-446-6362) to confirm above referral outcome
• Call Admitting Office (x6-3393) to inform them of death. Will ask cause/time of death, Med Examiner, NEDS info;
o Document a brief “note of patient death”: SmartPhrase “.MGHDOMDEATHNOTE”
o Complete short discharge summary within the Discharge as Deceased Navigator tab discussed above
o Debrief process and death with team or Night Teach
*NWH requires paper documentation

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Geriatrics & Palliative Care End of Life Care & Hospice

END OF LIFE CARE GENERAL PRINCIPLES
• The focus of EOL care is to enhance patient’s comfort, optimize symptom management, and ensure alignment with what matters most
to patient. Code status change to DNR/DNI or CMO (Comfort Measures Only) is not a requirement.
o Note that EOL is a medical state while code status reflects patient goals/values. If code status appears discordant with medical
state, close communication among team members is essential for clear understanding of GOC.
o EOL care should involve all members of the interdisciplinary team (clinicians, SW, chaplains) so that a patient's physical,
emotional, social, and spiritual domains of care are adequately assessed and comfort maximized. Additionally, allowing time with
family and respecting cultural and/or religious rituals if feasible is important.
o Communicate expected signs of dying and time course to loved ones. Any clinical provider (MD, NP, RN, SW, chaplain) can
request an EOL visitation policy exception with RN leadership irrespective of code status if passing is expected.
• Prepare paperwork and logistical planning as feasible prior to death (see End of Life and Pronouncement)

BEST SUPPORTIVE CARE: MANAGEMENT CONSIDERATIONS IN CMO

• Comfort-focused Care (also called Comfort Measures Only or CMO): Approach to care with the goal to maximize comfort. Does not
mean all treatments are stopped (e.g., pts may benefit from thoracenteses, paracentesis, or venting G tube if within pt’s goals)
• Lines/tubes: Maintain PIV access as possible, d/c central line if feasible.
• Supplemental O2: Not shown to have benefit if not hypoxemic. Instead, offer fan therapy, HOB elevation, IV/PO opioids (Am J Hosp
Palliat Care 2020;37:294)
• Foley: Can maintain for comfort; discuss w/ RN.
• Stop labs/routine VS unless it is helpful in managing comfort. Reassure loved ones that we can use RR, temp, & appearance as guide
• Medications: Continue meds contributing to patient comfort, those that will prevent uncomfortable events (e.g., rate control, diuretics,
inhalers, nitrates, anticoagulation for stroke ppx, AEDs for seizure control), or that have a withdrawal syndrome (e.g., SSRIs).
• Tube feeds, TPN/PPN, IVF: Generally avoid; may cause volume overload without meaningful benefit (JCO 2013;31:111). Instead,
encourage good mouth care and food/drink for comfort as able. Reassure loved ones that appetite/thirst declines at EOL (Fast Facts).
• Supportive Care Unit: 10 bed unit on Phillips 20 & 21 for patients with serious illness who have acute symptom management or goals
of care needs. Care teams include palliative care attending, NP/MDs, SW, spiritual care, and specialized CM. Transfer to SCU may
be appropriate if pt symptoms are not well controlled despite aggressive management on the gen med floor, though beds
are limited.
Example PRN Orders: if questions or concerns, consult Palliative Care for support
*Always treat acute symptoms with boluses rather than changing drip rate. Drips effectively act as long-acting meds
**If uncontrolled acute symptoms despite IV bolus, can repeat after 20-30min at same dose or doubled dose and change PRN dose
IV access PO only (No IV access)
Analgesia/Dyspnea Opioids: see Pain Management. Can dose more frequently (uptitrate dose q30 min PRN for uncontrolled air
hunger/pain) at EOL when goal is for aggressive symptom management (discuss w/ RN).
Dyspnea: Start with 2-5mg IV morphine equivalents for the opioid naive
Secretions Glycopyrrolate 0.2-0.4mg IV/SC Glycopyrrolate 1mg PO q4-6hrs PRN or atropine 1-2 drops SL q6hrs
*Stop TF, lay on side, pharm q4-6hrs PRN PRN (of note, atropine crosses BBB & may contribute to delirium)
trial, reassure fam
Delirium, Anxiolysis Haloperidol 0.5-1mg IV q4-6hrs Haloperidol 0.5 mg PO q4-6 hrs PRN or Olanzapine 2.5-5mg SL q6h
PRN PRN
Anxiolysis associated Lorazepam 0.5-1mg IV q4-6hrs Lorazepam 0.5-1 mg PO q4-6hrs PRN (increase as needed)
with dyspnea PRN (increase as needed)
Resources: Palliative Care Network of Wisconsin Fast Facts and app; DFCI resources: Pink Book for pain, Green Book for N/V
HOSPICE OVERVIEW
• Hospice: multidisciplinary care for patients with advanced illness and life expectancy <6mo with goal of providing best supportive care
when disease modifying therapy is no longer effective. Paid through Hospice Insurance Benefit (most often through Medicare)
• Can be provided in multiple locations, including home (most common), SNF, hospice house, or acute care hospital depending on
patient’s care needs and caregiver support
• Services include intermittent nursing care (~1-2 visits/week with 24/7 on-call emergency support), social work, chaplaincy, all
medications and supplies related to terminal illness or comfort, equipment (bed, commode, wheelchair etc.), home health aide,
bereavement support, short-term respite care (provides relief for caregivers), and short-term inpatient care for symptoms that cannot
be managed at home. Caregiving most often provided by family and friends
• DOES NOT cover room/board at facilities or 24/7 nursing care. More complex palliative or comfort interventions such as XRT, TPN, or
advanced IV pain therapies (ketamine, lidocaine), are covered by hospices on a case by case basis.
GENERAL INPATIENT HOSPICE (GIP)
• GIP Hospice: hospice level of care for pts who have short-term symptom mgt needs that cannot be provided adequately in any other
setting (e.g., high flow O2, uncontrolled sx requiring IV medications, high RN needs for wound care/suctioning). Most appropriately
offered at hospice house & this DC plan should be prioritized if pt can be transported.
• Consider GIP at MGH for pts who are actively or imminently dying and/or cannot safely transport. If admitted to GIP at MGH, pt will be
“Discharged to Hospice” and Pall Care becomes primary team.
• Discuss w/ floor CM team (for insurance benefit screen and coordinate w/ hospice liaison), hospice agency (ie, Good Shepard, Care
Dimensions, Norwell Home Health & Hospice), and Pall Care if pt is appropriate for GIP Hospice and, if so, which location
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Geriatrics & Palliative Care Geriatric Assessment & Frailty

GENERAL APPROACH TO THE COMPREHENSIVE GERIATRIC ASSESSMENT
• Overview: The comprehensive geriatric assessment (CGA) systematically identifies medical and psychosocial factors that lead to
functional limitations for older adults and should be approached by an interprofessional team. One widely accepted framework is the
“Geriatric 5Ms” (mind, mobility, medications, matters most, multicomplexity) (JAGS 2017;9:2115).
• Outcomes: CGA associated with increased likelihood that inpatients will be alive and in their own homes 3-12 months following
discharge (Cochrane 2017;9:CD006211) & predicts operative/procedural risk (JAGS 2020;68(6):1235; EJSO 2016;42:1890-7).
Outpatient, serial CGA provides opportunity to tailor care to the evolving needs of patients (JAH 2021;33:469).
Topic Examples Tools
Mind Vision, hearing, mood, sleep, memory PHQ-2 or Geriatric Depression Scale (English,
Spanish)
Cognitive Tests (suggested stepwise approach):
1. Mini-Cog (English, non-English languages)
2. RUDAS (minimizes effects of educational level,
cultural learning, and language in assessing cog fxn)
3. MOCA (English, Spanish)
Mobility Pain, feet, falls/fear of falling Timed up and go test (<12s)
Gait speed test (4m/5sec = 0.8m/sec)
30 sec Chair-to-Stand test (>8 in 30 sec)
Medications High risk meds, polypharmacy, immunizations See Frailty & Polypharmacy
Matters most Social history, HCP, code status Massachusetts HCP
Resources for patients: Prepare for your care (5-step
program for patients), The Conversation Project
See ACP & Code Status for further info
Functionality Appetitie/nutrition/weight Mini-Nutritional Assessment (English, Spanish)
Dentition/swallowing Home Safety Assessment
Constipation/incontinence
Sexual history
Substance use
ADLs: bathing, dressing, toileting, transferring, feeding, etc
iADLs: cleaning, finances, engaging w/ technology, etc
Effective interventions to reduce falls:
• Home safety assessments: referral to PT/OT should explicitly request fall reduction program as well as home safety evaluation
• Repair of single cataract decreased risk of hip fracture in the year following repair (refer pts for of ophthalmologic exams)
• Discourage use of progressive lenses (older adults often less able to adjust to changes in depth perception with these lenses)
• Assess for orthostatic hypotension and completing comprehensive medication review. See Polypharmacy
• Multicomponent exercise programs (strength/resistance training, aerobic, & balance) done in groups superior to programs done alone
• Sit-to-stand repetitions both while hospitalized and at home
FRAILTY
Frailty is an identifiable clinical state in which an individual is more vulnerable to stressors due to reduced physiologic reserves. This
increased vulnerability leads to increased risk of falls, hospitalization, loss of independence, iatrogenic harm and death from otherwise
minor illnesses or low burden interventions (JAMDA 2013;14:392). Reframe “failure to thrive” as frailty.
• Frailty is a geriatric syndrome. Though older age is risk factor but is not necessary/sufficient for the dx
• Frailty is dynamic: individuals can move between different states of frailty over time.
• Frailty is potentially reversible: modifying RFs can improve QoL and reduce morbidity and mortality (JAGS 2007;55:11)
o Frailty Tools (In Epic: Rarely Used Additional ToolsGeriatricsFrailty Index) are most commonly based on:
o Fried Frailty Phenotype Model: physical manifestations of reduced physical reserves (self-reported exhaustion, unintended
weight loss, low grip strength/weakness, slow walking speed, physical inactivity) (J Geront 2001;56:M146; BMC Geriatr 2013;13:64).
o Rockwood Deficit Accumulation Model: a concept in which 30 or more factors from the 5M domains and/or variables known to
diminish over time is used to construct a Frailty Index (J Geront 2007;67:722).
o Refer to Comprehensive Geriatric Assessment-Frailty Index or FRAIL screen (J Nutr Health Aging 2012;16:601)
Interventions for frailty (Age Ageing 2017;46:383)
• Screen for and treat high-risk comorbidities (e.g. urinary incontinence, osteoporosis, vision/hearing impairment, driving risk)
• Establish patient- and family-centered goals to guide treatment plan
• Exercise: PT; exercise programs (e.g. Tai Chi) can reduce fall risk (JAMA 2018;319:1705; BMC Geriatr 2020;20;108)
• Consults: for complex patients, refer for nutrition assessment for weight loss and/or concern for micronutrient deficiencies; out-patient
Geriatric Clinic for follow-up CGA and longitudinal consultative geriatric care; MGB Home-Based Palliative Care for severe frailty and
limited life expectancy.
• Cognition: inpatient: cognition screening,delirium precautions (limiting overnight VS/interventions, labs, lines/tethers,
physical/chemical restraints); outpatient: OTand/or SLP consult (cognitive training, info processing, problem-solving, driving eval)
• Environment Modifications: consider SW consult, PT/OT consult, iCMP referral, Home Health (includes PT, OT, Speech, & SW)
• Address advanced directives/HCP/Code Status

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Geriatrics & Palliative Care Polypharmacy & Elder Abuse

POLYPHARMACY: PRESCRIBING AND DEPRESCRIBING MEDICATIONS
Medication Reconciliation: confirm meds w/ pt & family; ask about medication administration system (eg, blister packs, pill boxes)
• Review prior notes, d/c summaries, & paperwork from SNFs for med changes
• Look up pharmacy dispenses in Epic: Chart Review  Misc Reports  Medication Dispense History; or
• Call 24/7 pharmacies: CVS 781-391-2668 (dial 1, 2, “staff”); Walgreens 781-321-1765 (dial 2, #, “other question”)
• Ask about OTC meds, herbal/dietary supplements (including CBD/THC), which can be easily missed culprits of drug-drug interactions
• Coordinate discharge Rx planning and education with patient, pharmacy, PCP.lower risk of readmission with intensive pharmacist
intervention (med rec and education) and coordination with PCP (JAMA IM 2018;178:375), MGH Home Health
Deprescribing Medications:
• Use tools like Medication Appropriateness Index; MedStopper; deprescribing.org (include taper plans & info for patients/families)
• Confirm eGFR with cystatin C: Creatinine-derived eGFR can often overestimate CrCl in older adults due to sarcopenia
o Renal adjustment of medications important for mitigating side-effects/complications (enoxaparin, apixaban, rivaroxaban,
dabigatran, antibiotics, antiepileptics)
• Classes to AVOID in geriatric patients: See Beer’s list (J Am Geri Soc 2019;67:674) and STOPP-START for further details
o Anticholinergics: delirium, falls, blurred vision, urinary retention, tachycardia. Avoid antihistamines, TCAs, MAOIs,
antimuscarinics (oxybutynin), muscle relaxants (cyclobenzaprine), prochlorperazine. Long term use linked to increased risk for
dementia (JAMA IM 2015;175:401)
 Anticholinergic Risk Scale: additive effect of multiple meds w/ minor anticholinergic effects can be significant.
o Benzodiazepines: delirium, falls, cognitive impairment, etc. (also risk w/ non-BZD hypnotics e.g. zolpidem)
o Antipsychotics: #mortality with antipsychotics in the elderly with underlying cognitive impairment (JAMA Psych 2015;72:438)
o Peripheral alpha blockers and central alpha-agonists: -zosins and clonidine " risk of orthostasis and falls
o Long-acting sulfonylureas and rapid/short acting insulin: hypoglycemia (do NOT use nighttime SSI in older adults)
o PPIs: C. diff, bone loss/fracture (taper off or switch to H2 blockers unless clear indication for PPI)
o NSAIDs: CVD, GI bleed, AKI (especially in elderly patients with decreased CrCl)
o Aspirin for primary CVD prevention: bleeding (use with caution and reevaluate at age >70) (NEJM 2018;379:1509)
o Tramadol: multiple drug interactions and receptor activity
o Serotonergic medications: serotonin syndrome can present as anxiety or agitation w/ initiation or titration of meds in older adults
o Parkinson’s disease: ondansetron is antiemetic of choice. Avoid antipsychotics, metoclopramide, prochlorperazine

COMMON SIGNS OF ELDER ABUSE

• Generally includes persons 60 years or older (although this definition is state-dependent).
• Definition (CDC): “An intentional act or failure to act by a caregiver or another person in a relationship involving an expectation of trust
that causes or creates a risk of harm to an older adult.”
• Includes physical, emotional, sexual, neglect, abandonment, and/or financial abuse. Can present as:
o Withdrawn affect, deferring to others to answer
o Unwashed hair, dirty clothes, appearing unkempt (don’t forget to look at feet and nails!)
o Unclean or unsafe living conditions, mismatch in level of social supports/services vs needs based on physical or cognitive
disability, tension w/ family around financial planning to help with care needs
o Worsening of pressure ulcers, skin tears, weight loss
o Lack of necessary medical aids (walkers/canes, adult-pull ups)
o Unpaid bills, eviction notices, inability to hire more services/help or transition to a new level of care etc. despite adequate
financial resources
• Risk Factors (NCEA): advanced age, female sex, non-white race, disability, cognitive impairment
• Screening
o AMA recommends regular screening but USPSTF did not identify sufficient evidence (Screening tools validated in various settings
are available for use, consider using comprehensive geriatric assessment above)
o Concerns should prompt cognitive testing, functional assessment, and obtaining collateral to screen for unrecognized dementia
as an underlying cause of these signs and symptoms (See “Dementia”)
• Guardianship (Gerontology 2007;47:591-603): legal process that gives a guardian permission to take care of and make decisions for an
incapacitated adult who does not have a pre-designated HCP. Consider guardianship in situations where the patient does not have
capacity regarding high-risk decisions and no HCP identified. Pt may be determined to lack competence (legal status) by a court.
o If concern for abuse/neglect from HCP, obtain collateral from longitudinal providers and consider OCC consult before
proceeding with guardianship process.
REPORTING LOGISTICS General, Caretaker, Facility
• Making a report through the Massachusetts Executive Office of Elder Affairs (can be made by any member of the healthcare team)
• Report can be made online or via phone: (800) 922-2275.
o If you make a report via phone, must submit a mandated reporter form to the local Protective Services agency within 48h
o To report abuse of a patient by nursing home or hospital staff, reach out to the other providers/institutions first to discuss and
obtain collateral and understand greater clinical/social context. If continued concern, can contact the Massachusetts Department
of Public Health: (800) 462-5540
• Similar to DCF reports, this is an ask to an objective, multi-disciplinary team to investigate concerns rather than a condemnation
• Documentation: No template currently available in Epic. Document findings as part of a progress note or in a separate encounter.
Remember to be detailed but not inflammatory/derogatory in describing subjective & objective findings suggestive of abuse or neglect.

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Rheumatology Approach to Rheumatologic Disease

O V E R V I E W : rheumatologic diseases may be roughly separated into 4 categories

Category Inflammatory Connective Tissue

Vasculitis Other
Arthritis Disease

Small (GPA, MPA,

Major RA, spondyloarthritis, SLE, Sjӧgren’s, Autoinflammatory
EGPA, cryo, IgA), med
scleroderma, MCTD, diseases, sarcoid,
Diseases crystalline arthritis, (PAN), large (GCA,
reactive arthritis UCTD, myositis (DM, PM) Takayasu), or variable IgG4-related
vessel (Behcet’s) disease, VEXAS

ANA first. Then: C3/C4, Sarcoid: Ca, vit D,

Small: ANCA, cryo
RF, anti-CCP, ANA, anti-Sm, anti-dsDNA, anti- limited role for
Initial Scl70, anti-histone, anti-
(sent warm), C3/C4, UA
work-up XRay Large: imaging, ±optho ACE. IgG4: IgG
U1RNP, anti-Ro/La, subclasses, C3/C4
cs, TA bx (GCA)
antiphospholipid Abs

Treatment Glucocorticoids (aim to minimize steroid exposure)

Hydroxychloroquine DMARD = disease-modifying

antirheumatic drug
DMARDS (MTX, SSZ) DMARDS (MTX, AZA, MMF) MTX = methotrexate
SSZ = sulfasalazine
Severity

AZA = azathioprine
RTX, belimumab, RTX, TCZ, anti-C5a
Most Biologics, JAK MMF = mycophenolate mofetil
voclosporin, antifrolumab
inhibitor Biologics = Ab/protein-based Rx
(anti-TNF, anti-IL17, anti-IL12/23,
Cyclophosphamide (CYC) CTLA4-Ig, anti-IL1, RTX, TCZ, etc.)
RTX = rituximab (anti-CD20)
**Nuances of treatment not encapsulated by this figure – see following pages TCZ = tocilizumab (anti-IL6)

RHEUMATOLOGIC ROS
Fevers, arthritis, rashes/photosensitivity, alopecia, nail/nailfold Δ, sicca symptoms, conjunctivitis, uveitis, episcleritis/scleritis,
Raynaud's, acrocyanosis, oral/genital ulcers, polychondritis, enthesitis, serositis sx, thromboses, neuropathy, pregnancy loss

LABS
CBC/diff, BMP, LFTs, UA, ESR/CRP, TSH. Target serological testing to positive items on rheum ROS

DDX
Consider malignancy (including paraneoplastic phenomenon) and infection as alternative diagnoses

COMMON INPATIENT RHEUM CONSULT QUESTIONS

1. Inpatient inflammatory arthritis: should this patient have a joint aspiration/injection?
2. Guidance on interpretation/further work-up of positive rheumatologic serologies (i.e., positive ANA (>1:80), +RF, etc.)
3. Work-up/management of fever of unknown origin
4. Patient with history of established rheumatological disease and c/f exacerbation or complication
5. Concern for new onset vasculitis, myositis, or connective tissue disease
6. Work-up/management of new interstitial lung disease (in conjunction with pulmonology)
7. Work-up/management of inflammatory eye disease
8. Guidance on immunosuppressive meds for pt w/ established rheumatologic dz & c/f new infection or malignancy

HEALTHCARE MAINTENANCE FOR RHEUM PATIENTS

If prolonged steroids: Ca++/vitD (for bone health), pneumocystis ppx (if ≥20mg prednisone for ≥4 weeks; see ID: Opportunistic
Infections), PPI (GI ulcer ppx), risk stratification for bone density screening, and A1c (see Endocrine:Steroid Pearls).
Consider reproductive planning (many meds teratogenic), immunizations, skin exam/sun protection if anti-TNF or MTX (↑skin
cancer), increased pap frequency (J Low Genit Tract Dis 2019 Apr;23(2):87-101), and optimizing CV risk w/ primary prev
(↑risk w/ chronic inflammation (Lancet Rheumatol 2021;3:e58). Safety labs q3-6 months for most DMARDs (CBCd, CMP).
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Rheumatology Arthritis
APPROACH TO THE PATIENT WITH ARTHRITIS

ACUTE ARTHRITIS SYNDROMES

Arthritis Joint pattern Presentation Diagnosis Treatment
Acute: colchicine (1.2mg x1, 0.6mg 1h later,
Gold std: Arthrocentesis: 0.6mg 1-2x daily until 2-3d after resolved) or pred
neg birefringent (40mg QD until resolved then taper) or NSAIDs
needle-shaped (naproxen 500mg BID, indomethacin 50mg TID for
- Triggers: ~5-7d), or intra-art steroids (if 1-2 joints). Choice
crystals, WBC 10k-
diuretics, meat, driven by pt and side effect profile (UTD algorithm
- Mono > poly 100k/uL
seafood, EtOH, to help choose initial therapy). Anti-IL1 if above
- 1st MTP joint - ACR-EULAR Criteria for
HTN, DM2, CKD contraindicated. If already on allopurinol, should
(also called Gout can help establish
- Acute flares  continue in acute attack. In AKI renally dose.
Podagra; 1st sx likelihood of dx in
Gout chronic Chronic: urate lowering tx indicated if ≥2
in 50% pts) absence of joint
arthropathy (tophi) attacks/yr, disabling attacks, tophi, or erosions.
-hindfoot, aspiration
- Urate Check b/l uric acid outside of flare as it can be
fingers, ankle, - At first dx should obtain
nephrolithiasis, falsely low during flare. Start ~2 wks after flare or
knee, wrists plain films to evaluate for
chronic w/ colchicine ppx 3-6 mo to ↓ flare risk
erosions/tophi as this
nephropathy Allopurinol 1st-line; start low to ↓ hypersens risk,
changes management
- US or dual energy CT if ✓HLA-B*5801 if Korean, Han Chinese, Thai,
dx remains uncertain African descent before starting allopurinol (Clin
Pharm Ther. 2013;93:153)
- Acute: if ≤2 joints  intra-art steroids (1st line).
- Mono > poly - Arthrocentesis: small 2nd line same as gout (colchicine w/in 24h sx
- Can be
CPPD - Knee > wrist, pos birefringent onset)
asymptomatic
(pseudo- shoulder, ankle rhomboid crystals, - Chronic: NSAIDs, colchicine, HCQ, low-dose
- Can coexist with
gout) - Neck “crowned WBC 10k-100k/uL pred, MTX. Anti-IL1 if refractory
gout, OA
dens syndrome” - Chondrocalcinosis - Screen for 2˚ causes: hyperPTH, hypoMg,
hemochromatosis, ?low phos
- Hematogenous - Arthrocentesis: WBC
- Mono (50% spread most 50-150k/uL, ↑PMNs,
- Antibiotics for 3-4w (CTX x7-14 d for
knee), >1 joint common GS/Cx; blood cx
Bacterial gonococcal)
(20%) - risk in RA - staph>strep>GNR
septic - Joint drainage/urgent washout (ortho c/s)
- Gonococcal: - Gonococcal: - Gonococcal: GU NAAT,
arthritis - Often requires hardware explant and longer
mono or oligo fever ± often ↓ synovial WBC +
antibx if prosthetic joint
tenosynovitis & neg cx
skin lesions - XR ± CT/MRI
- IgM/IgG/PCR per ddx:
- Varied, but
parvo, HBV, HCV, HIV,
often symmetric - Often a/w fever & - NSAIDs
Viral rubella virus or vaccine,
poly small joint fatigue - Antivirals if able
arthritis chikungunya, dengue,
(e.g. parvo) ± - Many etiologies self-limited
enterovirus, mumps,
large joint
Herpesviridae

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Rheumatology Arthritis
CHRONIC ARTHRITIS SYNDROMES
Arthritis Joint pattern Presentation Diagnosis Treatment
- PT, braces, weight loss, Tai Chi
- Clinical dx
- Topical NSAIDs, acetaminophen,
- Poly - Bony swelling, joint
- Age >45 PRN NSAIDs, duloxetine
- Knees, hips, deformity, limited ROM
- AM stiff <30min, slow - Intra-articular steroids
Osteoarthritis MTP, CMC, PIP, - XR joint space
progression, no warmth, - If severe, refer to ortho, PM&R
DIP, C-spine, L- narrowing,
muscular wasting - Not recommended: glucosamine,
spine osteophytosis,
bisphosphonates, PRP (ACR
subchondral sclerosis
Guideline 2019)
- Late Lyme - Arthrocentesis, Lyme - Lyme: 4w of doxy or amox
- Mono (Lyme:
- immunocx or RFs: fungal, TB serology, T spot, - TB, endemic or other fungal: see
knee, TB: hip),
Infectious (indolent monoarthritis) fungal cx, ID pages
oligo/poly (T.
- T. whipplei: arthralgias > cx/BDG/GM/Ags, SI - T. whipplei: 2w CTX + 1y
whipplei)
arthritis, diarrhea, ↓weight biopsy (T. whipplei) TMP/sulfa
- Mono in early - Synovitis on exam - Acute: prednisone or NSAIDs,
stage, then poly - F>M, age 35-65 - RF, anti-CCP (neg initiate DMARD if not on already
Rheumatoid - Small peripheral - AM stiff >30min at pres 50%) - Chronic: DMARD (MTX > HCQ,
Arthritis (MCP, PIP, - Joint deformity - Joint XR for erosions SSZ, leflunomide); 2nd line combo
wrists, MTP) - RA nodules - ESR/CRP can be or biologic (infliximab, abatacept,
- Symmetric normal TCZ)
Spondylo- AS: mostly axial
- AM stiff >30min - Clinical dx - NSAIDs (1st line)
arthritis (SpA): (spine, SI)
- Extra-articular: tenosynovitis, - ESR/CRP (not Sn) AS:TNFα inhibitor (2nd line), anti-
PsA: can be
-Ankylosing enthesitis, dactylitis, uveitis, - HLA-B27 IL17, JAKi
distal [DIPs],
spondylitis pyoderma gangrenosum AS: spine mobility, PsA: If mod, MTX > SSZ or
asymm oligo,
(AS) AS: Pain in low back, buttock bamboo spine + leflunomide, apremilast (PDEi).
symm poly,
PsA: nail pits/onycholysis, sacroiliitis (XR or - If severe/erosive, TNFα inhibitor.
-Psoriatic arthritis mutilans,
70% with psoriasis MRI) If non-response, anti-IL17 or anti-
arthritis (PsA) axial
IBDa: oligo varies with IBD PsA: CASPAR criteria IL12/23. Anti-IL17 can worsen IBD
IBDa: distal oligo
activity, poly or axial has (91% Sn, 99% Sp), IBDa: SSZ > MTX or AZA, TNFα
-IBD-assoc. or poly arthritis >
(IBDa) independent course pencil-in-cup DIPs inhibitor, anti-IL-12/23
axial

- 1-4w post-infxn*: - Preceding infection* - If GU infxn, treat. If GI infxn, may

- Oligo > mono >
- Conjunctivitis, urethritis, - Arthrocentesis: not need to treat
Reactive poly (small joints)
cervicitis, oral ulcers, circinate GS/Cx - Acute: NSAIDs > intra-articular
arthritis - Asymmetric
balanitis, keratoderma - Stool cx (if diarrhea) steroids > prednisone
- LE > UE
blennorrhagica, SpA sx -Gonorrhea/Chlamydia - Chronic: if >6mo, MTX or SSZ

* Causes: Enteric: Salmonella, Shigella, Yersinia, Campylobacter, C. diff; GU: Chlamydia, E. coli, Ureaplasma, Mycoplasma

SYNOVIAL FLUID ANALYSIS

Normal Non-Inflammatory Inflammatory Septic Hemorrhagic
Clarity Clear Clear Clear-opaque Opaque Bloody
Color Pale yellow Yellow Yellow to opalescent Yellow to green Red to brown
Viscosity High High Low Variable Variable
WBC (per
<200 0-2,000 2,000-100K 50-150K 200-2,000
mm3)
PMNs (%) <25 <25 ≥50 ≥75 50-75
Many: inflammatory and Septic arthritis; Trauma,
OA, trauma, AVN,
infectious arthritides, occasionally, coagulopathy,
Major Ddx mechanical
rheumatic diseases, noninfectious: gout, iatrogenic, tumors,
dysfunction
gout/CPPD reactive arthritis, RA scurvy

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Rheumatology Connective Tissue Diseases

Disease Clinical Presentation Work-up Treatment Complication
- F>M, 15-40yo, Afr./Latino-a/Asian - All (incl. pregn): HCQ
⊕ANA (>95%; Sn not Sp) - CVD (Semin
descent > White (flares, clots, death)
Arthritis Rheum
- Constitutional sx (fever, wt loss, ⊕ anti-dsDNA (~70%; active dz - Lifestyle: sun
2013;43:77); ↑
fatigue, myalgia), malar rash (spares & lupus nephritis) ⊕ anti-Sm protection, tobacco
NL fold), discoid lesions, risk VTE/ATE
(30%, Sp, remains ⊕ in - steroids (goal to taper
photosensitivity, oral/nasal ulcers (APLS)
remission); ⊕ anti-RNP (30- and d/c if possible).
(often painless), cytopenias, - Lupus nephritis: 2024 - Preg.
SLE 50%); ⊕anti-SS-A/Ro, anti-SS- (neonatal death,
serositis, nephritis, B/La (35%, 15%) KDIGO Guidelines
pneumonitis/DAH/ILD, - If flare/active dz: add pre-eclampsia,
⊕ antiphospholipid Abs (40%) prem delivery)
seizure/CVA/neuropsych, vasculitis - CBC/diff, BMP, +DAT, C3/4, immunosuppressive rx
- Arthritis/arthralgia: migratory, -ESRD
ESR/CRP, UA/UPCR; consider (MTX, MMF, CYC, RTX,
polyarticular (knees, carpal joints, belimumab, antifrolumab), -Osteonecrosis
RF, CCP if sig. arthritis, (2019 (2/2 SLE and
PIPs > other), symmetric, EULAR/ACR Criteria) (Ann Rheum Dis 2024)
steroids)
nondeforming. ⊕Morning stiffness. - Trials of CD19 CAR-T

- Fever, arthralgias/arthritis, myalgias, *Serologies/clinical features Treat sxs, not antibodies

rash, serositis. Nephritis uncommon. often unique to the offending - Generally
- Withdraw offending
~1/3 of isolated cutaneous lupus drug- good prognosis;
drug. ⊕ ANA (almost all cases) agent: resolution may
induced (Br J Dermatol 2012;167:296) life threatening
Drug-induced ⊕Anti-histone (Sn but not Sp take weeks-months
- Months-years exposure (Ann NY disease is rare
lupus for DIL, also in up to 80% - Occasionally NSAIDs,
Acad Sci 2007;1108:166) and should
(DIL) idiopathic SLE) ⊖ anti-dsDNA HCQ, steroids for sx
- High risk: procainamide (15-20% prompt workup
(exc. TNFi, IFN) ⊕ anti-SS- - Avoid common DIL
per y), hydralazine (5-10% / y). Mod: for SLE or other
A/Ro (not Sp) Others: ANCA, drugs in patients with
quinidine. Low: TNFi, penicillamine, CTD
anti-RNP known dx SLE
carbamazepine, methyldopa, others
- 5-10% lifetime
- F>M, 40-60y. Sicca (dry mouth/ - Sicca only: sx mgmt.;
⊕ ANA ⊕ anti-SS-A/Ro risk of NHL,
eyes), caries, parotid enlargement, regular eye, dental care
⊕ anti-SS-B/La MALT
vag. dryness. Extraglandular: fatigue, - Extraglandular:
Sjogren’s - Schirmer test, parotid US, lymphoma
myalgia, vasculitis, nephropathy, immunosuppression rx
salivary gland bx, (2016 - head/neck
neuropathy, cytopenias, pulm, depends on
EULAR/ACR Criteria) cancers (Head
RA/SLE w/ 2° Sjogren’s symptom/organ involved
Neck 2023;45)
Inflammatory CK/aldolase, myositis panel
myopathies - F:M (2:1), 40-50yo. Symm
Often thigh MRI muscle bx - Malignancy in
(polymyositis, proximal>distal weakness. dysphagia, - Induction: prednisone
⊕ ANA (50%), lookup Ab DM (25% w/
dermatomyositis constitutional sx, arthralgias, ILD - Maintenance: AZA, MTX
phenotypes: anti-Jo1 (anti- new cancer dx
(DM), immune - DM skin findings: heliotrope rash, - Resistant/severe: pulse
synthetase), anti-Mi2, anti- w/in 3 years of
mediated poikiloderma (chest: V-sign; back: steroids, AZA, MTX,
necrotizing MDA5, anti-SRP, anti-HMGCR. myositis onset,
shawl; thigh: Holster), scalp rash, MMF, IVIG, RTX, CYC
myopathy, statin LDH and AST/ALT (can be - ILD in 10%
Gottron’s papules, mechanic’s hands
induced) normal in amyopathic type DM)

- 80% Female - SLE fts.: steroids, RTX.

⊕ ANA (often speckled) - Main cause of
Mixed CTD - Overlap of SLE, SSc, polymyositis; - If scleroderma sxs, ↓
⊕anti-U1 RNP (100%, not Sp) death is PAH
Raynaud’s; non-erosive arthritis responsive to steroids

F:M 4:1, 30-50yo. +Raynaud’s (almost

all), skin thickening, telangiectasias, - ILD: MMF, CYC (AZA or
sclerodactyly, calcinosis cutis ⊕ ANA (95%) TCZ) induc.  MMF, ⬆cancer risk
esophageal dysmotility, arthralgia ⊕ anti-centromere* (a/w AZA, TCZ maint. If Renal crisis
Other systemic sx: renal crisis, ILD limited) progressive: anti-fibrotic, (<20%): avoid
Systemic (>70%), PAH (10-40%), digit ischemia ⊕ anti-Scl-70* (a/w diffuse) RTX. (2023 Guidelines) steroids if at
Sclerosis Subtypes: ⊕ anti-RNA pol I,II, or III* (a/w - PAH: CCB, riociguat, risk (can
(scleroderma, Limited cutaneous (acral skin diffuse, is risk factor for ERA, PDEi, prostacyclin trigger). AKI,
SSc) involvement, freq. PAH) scleroderma renal crisis) ag abrupt HTN; a/w
Diffuse cutaneous (diffuse skin - HRCT, PFT, TTE (ILD, pHTN) - MSK: HCQ, MTX anti-RNA-pol III;
thickening, freq ILD). *Ab are >99% specific - Raynaud’s: CCBs tx w ACEi
Systemic sclerosis sine (Arthritis Rheum 2013;11:2737) - Skin: MMF, MTX (captopril)
scleroderma – no skin involvement, - GI: PPI & promotility
+ multiorgan involvement

UCTD & Dx of exclusion; not meeting

- Early Raynaud’s, incomplete SLE Per 1° features Per 1° features
Overlap Synd criteria for dx of specific ds

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Rheumatology Vasculitis
DIAGNOSTIC OVERVIEW (Arthritis Rheum 2013;65:1, image also credited from this source)
● Classified by size and type of blood vessel
involved. Large vessels (aorta + branches) vs.
medium-sized vessels (named visceral arteries) vs.
small vessels (vessels w/o names)
STEP 1 – SUSPECT VASCULITIS
● No “typical” presentation, consider in
constitutionally ill pt w/ multisystem organ
involvement & evidence of inflammation
● LARGE vessel: aorta/branches, e.g. ext. carotid,
temporal, ophthalmic  limb claudication, bruits,
asymmetric BP, absent pulses, HA, vision loss
● MEDIUM vessel: renal/hepatic/mesenteric arteries,
etc.  cutaneous nodules, “punched out” ulcers,
livedo reticularis, digital gangrene, mononeuritis Behcet’s disease
multiplex (e.g. foot/wrist drop), renovascular HTN,
mesenteric ischemia
● SMALL vessel: vessels of skin, small airways,
glomerulipetechiae, palpable purpura, glomerulonephritis, alveolar hemorrhage/ hemoptysis, mononeuritis multiplex, scleritis
General work-up:
● Inflammation?  CBC/diff (anemia of chronic disease, thrombocytosis, neutrophilia, eosinophilia), ESR, CRP
● Organ involvement?  BMP, LFTs, UA + sediment, CXR, brain MRI/MRA (if neurologic symptoms)
● Suspected large vessel? if c/f GCA (HA, jaw claud.,vision Δ), see below. If other sx (GI, limb claud.), consider CTA/MRA C/A/P
● Suspected medium vessel?  consider CTA/MRA c/a/p, deep biopsy of cutaneous findings (derm c/s)
● Suspected small vessel?  ANCA (will reflex to MPO/PR3 ELISA if ⊕), immune complex w/u (C3/C4, RF, cryo), rash biopsy (derm
c/s) (NB: ANA/RF not ⊕ in 1° vasculitis; ⊕RF may suggest cryoglobulinemia/endocarditis; C3/C4 in cryo, SLE, 25% of PAN)
STEP 2 – RULE OUT MIMICS and assess for SECONDARY CAUSES: based on presentation (Int J Rheumatol. 2020:8392542)
● Infections: (endocarditis, Neisseria, chronic osteomyelitis  immune complex deposition; HBV  PAN; HIV, HBV, & HCV 
cryoglobulinemia, EBV-associated vasculitis; syphilis & TB  aortitis). Inflammatory ds: sarcoidosis, amyloidosis, Susac Syndrome
● Malignancies/lymphoproliferative: lymphoma, myeloma, MGUS, IgG4-Related Disease (see Misc Rheum page)
● Coagulopathy/vasculopathy: APLAS, TTP. If skin necrosis of lower ext., consider cholesterol emboli, calciphylaxis, pyoderma
gangrenosum. If renal/internal carotid/vertebral art. involvement/dissections, consider fibromuscular dysplasia.
● Meds/drugs: esp. hydralazine, PCN, sulfa, PTU, levamisole in cocaine, immunotherapy, post radiation (see ANCAs in Autoantibodies
and Drug-Induced Lupus in Connective Tissue Diseases)
● W/u: BCx, HBV (med-v), HCV/HIV (small-v), syphilis/Tspot (large-v), SPEP/SFLC, tox screen. Consider IgG4, TTE, APLAS panel
STEP 3 – CONFIRM DIAGNOSIS
Tissue biopsy: may be required to secure diagnosis. Sites: skin, sural nerve, and muscle (PAN, ANCA), temporal artery (GCA), kidney
(ANCA, IgA), lung (ANCA). Less common: testicle (PAN), rectum/gut, liver, heart, brain (1° CNS vasculitis), sinus (GPA)
Additional imaging: may help support med/large vessel involvement if CTA/MRA non-dx and/or tissue bx infeasible. Generally PET (GCA,
Takayasu) or catheter-based angiogram (of celiac/SMA, renal (PAN), chest (Takayasu, GCA), limbs (Buerger’s), brain (1° CNS vasculitis))

LARGE-VESSEL VASCULITIS (NEJM 2003 ;349 :160, Arth Rheum 2021 ;1349-1365, Ann Rheum Dis. 2020 ;19-30)
GIANT CELL ARTERITIS: inflammation of aorta & extracranial branches (i.e., spares ICA), often temporal artery (TA). Most common
primary systemic vasculitis. Age >50, 3:1 F:M. If <50 yo, rare  consider alternative dx
● Sx: constitutional (low grade fevers, fatigue, wt loss, anorexia), new/different HA (incl. scalp tenderness), abrupt visual disturbance
(amaurosis fugax, blindness, diplopia), jaw claudication (most specific; fatigue with chewing, NOT PAIN), h/o PMR, ischemic stroke
● Exam: asymm BP/pulse; tender/thickened/pulseless TA; bruits; limb/jaw/tongue claud.; formal eye exam; neuro exam
● Dx: suspicion should prompt temporal art US & Rheum c/s. ↑ESR (<50 in 10%), ↑CRP. Gold standard = temporal artery biopsy w/
granuloma (c/s surg). Unilateral false ⊝ in 30-45% (skip lesions, bx length, laterality, lack of TA involvement, steroids), consider
bilateral (↑yield 5%). If c/f large-vessel GCA or bx neg: vessel imaging (PET, CTA/MRA, US w/ similar sens/spec)
● Rx: 1st line: High-dose steroids (PO pred 40-60mg qd; if c/f vision Δ, higher dose/IV immediately if ↑suspicion; NEVER delay for Bx.
Steroid-sparing: TCZ > MTX=LEF=TNFi > abatacept (Arthritis Care Res 2021;73:1349) ↑ sust. remission w/ TCZ (NEJM 2017;377:317).
● Polymyalgia rheumatica (PMR) seen in 50% of GCA pts; 10% pts with PMR develop GCA
TAKAYASU ARTERITIS: “pulseless disease,” granulomatous inflamm. of thoracoabd. aorta & branches. Age <40, 8:1 F:M, Asian descent
● Sx: constitutional (fever, arthralgias/myalgias, wt loss, night sweats), vessel inflammation (carotidynia, limb claudication), vascular dz
(TIA/stroke/sz/dizziness/syncope, MI/angina, HF, mesenteric ischemia). Exam: ↑BP, unequal pulses/BPs (LE>UE), ↓pulses, bruits
● Dx: MRA or CTA; arteriography w/ occlusion, stenosis, aneurysms; consider carotid US/Doppler studies, PET-CT
● Rx: prednisone 1mg/kg/d; 50% of patients will need 2nd agent for chronic sx (MTX, AZA, TNFi > tocilizumab)

MEDIUM-VESSEL VASCULITIS
POLYARTERITIS NODOSA: systemic necrotizing vasculitis that primarily affects the kidneys, skin, muscles, nerves, GI, joints, but almost
always spares lungs. Age 40-60, a/w HBV (Arthritis Care Res. 2021;73(8):1061-1070)

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Rheumatology Vasculitis
● Sx: constitutional symptoms (fever, fatigue, weight loss); mononeuritis multiplex (~70% of pts); GI distress (mesenteric ischemia),
myalgias; AKI (though GN suggests alternate etiology); gonadal pain (>10%), seizures
● Exam: HTN, skin lesions (erythematous nodules, purpura, livedo reticularis, ulcers, bullous eruption, palpable purpura), neuropathy
● Dx: gold standard = biopsy (⊝ granulomas; inflammatory infiltrates of vessel wall and fibrinoid necrosis); HBV/HCV, C3/C4,
CTA/MRA w/ focal stenosis or microaneurysm (renal/mesenteric)
● Rx: prednisone 1mg/kg/d ± MTX or AZA (IV steroids and CYC if severe); antivirals if HBV-related
THROMBOANGIITIS OBLITERANS (BUERGER’S DISEASE): segmental inflammatory nonatherosclerotic occlusive intravascular thrombi
of small-med arteries and veins of extremities. Age ≤50, 70-90% ♂, strongly a/w tobacco use. (Cochrane Syst Rev. 2016(3): CD011033)
● Sx: claudication (arch of foot, calf); Raynaud’s (40%), ulcers and digital gangrene; livedo reticularis (hands, feet, & digits); typically
ischemic symptoms start in distal vessels and progress more proximally.
● Dx: biopsy (rarely) or dx criteria: age, tobacco, distal ischemia (+ABI, thrombophlebitis), ⊕ angiogram/CTA/MRA (segmental dz,
abrupt cutoffs, corkscrew collaterals), r/o mimics (PAD, systemic sclerosis, APLAS, thromboembolism)
● Rx: smoking cessation. Immunotherapy ineffective. Iloprost (PG analog, ↓amputation rates), PCBs for pain, CCB for Raynaud’s
ANCA-ASSOCIATED SMALL-VESSEL VASCULITIS (AAV)
PR3-ANCA+ = cytoplasmic staining (proteinase 3 [PR3]; c-ANCA), MPO-ANCA+= perinuclear staining (myeloperoxidase [MPO]; p-ANCA)
GRANULOMATOSIS WITH POLYANGIITIS (GPA) (Formerly Wegner’s Granulomatosis): necrotizing granulomatous vasculitis commonly
affecting the upper respiratory tract (upper and lower airways [90%]), and kidneys (80%), ± cutaneous leukocytoclastic vasculitis (LCV).
● Sx: upper respiratory: (sinusitis/crusting rhinitis, subglottic stenosis, saddle nose, otitis media, mastoiditis, hearing loss); lower
respiratory: (alveolar hemorrhage, large pulmonary nodules); kidney involvement (crescentic necrotizing glomerulonephritis)
● Dx: sinus CT (± bone erosions), Bx w/ granulomatous inflammation of vessel walls, PR3-ANCA+ 90%. R/o anti-GBM
● Rx: limited disease: MTX + prednisone; severe disease: induction w/ steroids + RTX > CYC (NEJM 2010;363:221; Arthritis Care Res
2021;73(8):1088). Adding avacopan allows ↓ steroids (NEJM 2021;384:599). Maintenance w/ RTX > AZA.
MICROSCOPIC POLYANGIITIS (MPA): necrotizing vasculitis of small vessels without granulomas. All ages (mean 50-60). Similar sx to
GPA w/o ENT/upper airway dz; most common cause of pulmonary-renal syndrome (NEJM 2012;367:214)
● Dx: MPO-ANCA+ 70%, PR3-ANCA+ rare; BAL; gold standard = skin/renal bx; r/o HIV, cryo, anti-GBM, HBV, HCV. Rx: as for GPA
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) (formerly Churg-Strauss Syndrome): necrotizing granulomatous
inflammation of vessels in lungs, skin, nerves, heart (major cause of mortality); ↑asthma/allergic rhinitis (asthma precedes vasculitis)
● Dx: ≥4 of: asthma, >10% periph. eos, neuropathy, migratory lung infiltrates, paranasal sinus dz, consistent Bx. 50% ⊕ MPO-ANCA
● Rx: steroids ± CYC or RTX (if severe disease) or mepolizumab (anti-IL5, if not severe, NEJM 2017;376:1921). Do not delay Rx if c/f
mononeuritis (risk of nerve infarction). Screening TTE for all new dx (Arthritis Care Res 2021;73(8):1088)
RELAPSING DISEASE: 5-50% on maintenance therapy; 80-90% w/o maintenance. Dx: often presents as recrudescence of presenting sx;
new organ involvement/sx possible but uncommon. Rx: steroids, adjustment of maintenance regimen
IMMUNE COMPLEX-ASSOCIATED SMALL-VESSEL VASCULITIS (Arth Rheum. 2019:1904-1912, N Engl J Med. 2021:1038-1052)
IgA VASCULITIS (HENOCH-SCHÖNLEIN PURPURA): 90% in children; ♂>♀; preceding URI (~10d prior); in adults, ↑severity (↑
nephropathy) and ↑ a/w meds or malignancy
● Sx: classic tetrad of 1) palpable purpura (100%, LEs/buttocks = dependent areas), 2) colicky abdominal pain (50-65%, adults w/ ↓
intussusception), 3) arthritis (75%), 4) renal involvement (50%, proteinuria, microscopic hematuria, RPGN) (AFP 2020;102 (4):229)
● Dx: clinical dx in children; in adults, confirmation w/ biopsy (leukocytoclastic vasculitis w/ vessel wall IgA dep.) preferred
● Rx: children: usually self-limited; adults: may require immunosuppression (orchitis, cerebral vasculitis, pulmonary hemorrhage, severe
abd pain/ bleeding) w/ 1-2 mg/kg/day of prednisone or dapsone. (Rheumatology (Oxford). 2019 Sep 1;58(9):1607-1616)
CRYOGLOBULINEMIA: 2/2 immunoglob. that precip. at ↓temp & redissolve w/ rewarming. Most common extrahepatic HCV manifestation.
● Type 1: monoclonal (usually IgM or IgG), a/w MGUS, Waldenstrom’s, MM. S/Sx:↑ hyperviscosity (↑ in cold) → acrocyanosis, digital
ischemia, livedo reticularis, HA, transient CN sx; peripheral neuropathy, GN. Consider sending serum viscosity.
● Type 2: “mixed” monoclonal IgM against polyclonal IgG (IgM w/ RF activity), a/w infx (HCV/HIV/HBV/EBV, endocarditis), autoimmune
dz, malign.
● Type 3: “mixed” polyclonal Ig (IgM or IgG) against polyclonal Ig (IgM or IgG), a/w autoimmunity (CTDs, RA, PAN), HCV.
S/Sx (type 2 +3): immune complex dep. → Metzler triad (palpable purpura, arthralgias, weakness), mononeuritis multiplex, GN.
● Labs/Dx: Send C3, C4, RF, HCV, HBV, CBC w/ diff ± infx/rheum labs per sx above. Note: blood samples for serum cryoglobulins
need to be received warm by lab, wrapped w/ hot pack, w/i 30 min of collection.
● Rx: avoid cold in type 1. Tx underlying cause (e.g. HCV, malign.); prednisone ± RTX/CYC; consider plasma exchange in Type 1
VARIABLE-VESSEL VASCULITIS
BEHCET’S DISEASE: vasculitis affecting vessels of all sizes, both venous and arterial; characterized by recurrent oral and genital ulcers
and skin/GI/neuro/joint/ocular sx. Age 20-40, more common in Turkey, Middle East, and Asia, a/w HLA-B51
● Dx: clinical dx - recurrent painful oral ulcers and ≥2 of: painful genital ulcers (specific), ocular dz (uveitis, retinitis), skin lesions
(pustules, folliculitis, papules, erythema nodosum), ⊕ pathergy test (small needle prick elicits red pustule). May have: GI sx (similar
to IBD), neurologic sx (migraine, CN abnl, venous sinus thrombosis), vascular dz (ATE/VTE, aneurysms), arthritis
(nonerosive/asymmetric). R/o HSV as cause of ulcers.
● Rx: (Ann Rheum Dis. 2018;77:808) Mild (arthritis, ulcers): colchicine, topical steroid, low dose pred. Apremilast for ulcers (NEJM
2019;381:1918); Severe: pred 1mg/kg/d, ±: AZA, TNFi, IFN, CYC, MTX; organ failure (esp ophth.): IV pulse steroids

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Rheumatology Miscellaneous Rheumatologic Diseases

POLYMYALGIA RHEUMATICA
• Inflammatory condition characterized by proximal muscle aches and AM stiffness. Exclusively in pts >50yrs, peak 70-80yrs, 2:1 F:M.
• Sx: abrupt onset symmetrical aching and AM stiffness in shoulders, hip girdle, neck, & torso. Stiffness with inactivity is severe. Can
also have fever, malaise, weight loss. Often have limitation of active shoulder abduction.
• Dx: Nearly all pts have ↑CRP±ESR. Autoantibodies are negative. EULAR/ACR classification criteria (Ann Rheum Dis2012;71:492).
• Tx: prednisone 12.5-20 mg/d w/ slow taper, consider addition of MTX or TCZ if refractory (Ann Rheum Dis. 2022;838-844). Sarilumab (IL-
6R) sustained remission in relapsing dz and reduced glucocorticoids (NEJM 2023:389:1263).
• 10% of patients with PMR will be diagnosed w/ GCA at some point. Screen at initial dx and routinely at f/u visits. See GCA
I G G 4 - R E L A T E D D I S E A S E (Ann Rheum Dis. 2015;74:14; Arth Rheum 2020;72:7)
• Fibro-inflammatory condition, involving pancreas, biliary tree, salivary/lacrimal glands, RP, thyroid, & orbits. Mean age ~60. M>F
• Sx: pancreatitis (w/ otherwise unclear etiol); sclerosing cholangitis; sialadenitis; lacrimal gland hypertrophy; retroperitoneal
fibrosis; orbital pseudotumor; mass-like enlargement of pancreas, lungs, kidneys, or any of above organs. Often insidious.
• Dx: tissue biopsy (storiform [“strawlike”] fibrosis, lymphoplasmacytic infiltrate (↑IgG4+ plasma cells), obliterative phlebitis, tissue
eosinophilia); serum IgG4 levels (90% Sn, 60% Sp, NPV 96%, can track with disease activity). May have ↑ serum IgE and ↓ C3/C4
• Tx: if sx and/or progressive imaging, steroids ± biologics (RTX) to induce remission. RTX often for maintenance as well
S A R C O I D O S I S (Int Emerg Med 2018;13:325; Lung 2016:194:91; Am J Resp Crit Care Med 2020;201:e26)
• Systemic inflamm d/o characterized by granulomatous inflammation of virtually any tissue, most commonly hilar LN, pulmonary
parenchyma, skin, liver, eyes. F>M, young adults.  in Northern pop,  in Black patients
• Sx: fever, arthralgias, ↓ wt, fatigue; dyspnea, cough; rash; HSM, LAD; uveitis; cytopenias (BM involvement); pHTN; restrictive CM
(sudden death); arrhythmias (AVB; ventricular>atrial); nephrolithiasis; neurosarcoid (CNopathy, periph. neuropathy, meningitis,
seizures, hypothalamic dysfn); Lofgren syndr (↑ Sp) = hilar adenopathy, arthritis, erythema nodosum
• Dx: definitive dx usually requires non-caseating granulomas on bx (skin, LN, EBUS), compatible clinical findings, r/o of mimics.
Obtain CXR (CT if atypical). No need to bx isolated asx incidental hilar LAD or if classic syndr w/ ↑ pretest prob of sarcoid (e.g.,
Lofgren). serum ACE 41% Sn, 90% Sp. Mimics: TB/NTM, fungal, lymphoma, GPA, IgG4, CVID, Berylliosis/Silicosis. Check Cr, alk
phos, Ca2+ ± 1,25-/25-vitD (granulomas can produce 1,25-vitD), CBC, baseline eye exam & EKG if new dx.
• Tx: many do not need tx and can be monitored for resolution/stability. If sx, oral steroids ± MTX, TNFi, other DMARDs
A D U L T O N S E T S T I L L ’ S D I S E A S E ( A O S D ) (J Rheumatol 1992;19:424; Rheumatol 2023;00:1)
• Rare systemic inflamm d/o w/ fevers, arthritis, rash. Monophasic, intermittent, or chronic. F=M, bimodal (15-25, 36-46 yo)
• Sx: fever (often spikes 1-2x daily); arthralgias; evanescent salmon-colored maculopapular rash coinciding w/ fever, often truncal,
trauma may precipitate (Koebner phenom.); pericarditis; pleuritis; HLH/macrophage activation syndrome
• Dx: Yamaguchi criteria require ≥5 features, including ≥2 major criteria
o Major: fever ≥39ºC for ≥1w; arthralgias/arthritis ≥2w; salmon-colored rash; WBC (≥80% PMN)
o Minor: sore throat; LAD; HSM; AST/ALT, LDH; negative ANA/RF
o Other labs (non-criteria): ESR/CRP; ferritin >3000 (if >10,000, consider HLH/MAS, see Hematology); plt; Hgb
• Tx: Mild: NSAIDs 1st line, then glucocorticoids/DMARDs. Severe: anakinra, pred 0.5-1mg/kg/d +/- MTX, TNFi, anti-IL6
R E L A P S I N G P O L Y C H O N D R I T I S (Rheumatol 2018;57:1532; Clin Exp Rheumatol 2022;40:81)
• Rare immune-mediated d/o a/w inflammation of cartilaginous structures (ears, nose, trachea, joints) & other tissue (eyes), a/w VEXAS
• Sx: bilateral auricular chondritis (sparing lobe), nasal chondritis (saddle-nose), arthritis, laryngeal/tracheal chondritis, valvulopathy;
eye inflamm; cochlear/vestib dysfunction. Dx: ↑ESR/CRP; eval resp/card (CXR/CT ± bronch, PFTs, ECG/TTE)
• Tx: steroids first-line; NSAIDs for arthritis; MTX, AZA, biologics for steroid-sparing; CYC if organ-threatening
V E X A S S Y N D R O M E (NEJM 2020;383:2628)
• Vacuolated myeloid/erythroid cells; E1 enzyme loss of fnx; X-linked (M>F); Autoinflammatory; Somatic mutations in UBA1
• Sx: recurrent fever (92%); alveolitis; auricular/nasal chondritis; neutrophilic dermatosis; small to medium vessel vasculitis; cytopenias,
macrocytic anemia; thromboses. 60% meet criteria for relapsing polychondritis. Strong a/w myelodysplastic syndrome and MM.
• Dx: Genetic testing, consider BMBx. Tx: High-dose steroids. Emerging data, often tocilizumab or JAKi. Poor prognosis.
F A M I L I A L M E D I T E R R A N E A N F E V E R (Am J Med 1967;43:227)
• Autoinflammatory disorder of recurrent fever & serositis. ↑ in Mediterranean descent, onset <10 yo (65%), <20 yo (90%)
• Sx: recurrent acute attacks (1-3d, resolve spontaneously) of fever a/w peritonitis (often mistaken for surgical abdomen); unilateral
pleuritis; arthritis (monoarticular); skin lesions (erysipelas-like); exertional myalgia; pericarditis; testicular pain; aseptic meningitis.
• Dx: During acute attack:  WBC,  ESR/CRP. Check UA for secondary amyloidosis (proteinuria). Genetic testing for confirmation.
o Diagnostic criteria: requires 1 major or 2 minor criteria (Arthritis Rheum 1997;40:1879)
• Tx: colchicine (to prevent acute attacks and secondary amyloidosis). 2nd line: anti-IL1 (Ann Rheum Dis. 2016;4:644)
F I B R O M Y A L G I A (JAMA Intern Med. 2021; 181(1):104-112)
• Central pain processing disorder manifesting as chronic widespread MSK pain, often w/ fatigue, sleep disturbance, and multiple
somatic sx. F>M, 20-55 yo. Can coexist with other inflammatory dz like SLE, RA. Often psych. comorbidities.
• Sx: widespread MSK pain; fatigue; cognitive disturbance; psych. sx; HA; paresthesia; IBS. “Pan-positive” ROS not uncommon
• Dx: clinical: >3 mo of sxs; multiple tender points. Newer criteria (J Pain 2019;6:611). Labs: normal (ESR, CRP, TSH, CBC, BMP)
• Tx: Initial: patient education; CBT for pain; graduated exercise program; sleep hygiene. Pharmacologic: 1st line amitriptyline,
duloxetine, milnacipran; may consider cyclobenzaprine, gabapentin, pregabalin (monotherapy > combo). Avoid opioids

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Rheumatology Autoantibodies
Antigen Disease Comments
Antibody
(ANA Pattern if ⊕) (See Approach to Rheum Disorders for when to order)
Inflammatory polyarthritis
RA (50-75%), - Not Sp despite name: RA, CTD, cryoglobulinemia, chronic infxn (e.g. HCV, SBE)
Sjogren’s (60+%), - ⊕ in 10% of healthy patients
RF (IgM) Fc gamma
Cryoglobulinemia - RA: “seropositive”, a/w erosive & extraarticular manifestations (nodules, scleritis,
(90%), others ILD, pleuritis, rare rheumatoid vasculitis)
- Most Sp test for RA, ⊕ in 50-75% (“seropositive RA”), a/w erosive dz &
CCP Citrullinated peptides RA (50-75%)
extraarticular manifestations. Used for dx only, NOT marker of dz activity
Connective tissue diseases (SLE, Sjogren’s, SSc, MCTD, UCTD, DM/PM)
When to order: clinical suspicion for SLE or other ANA-⊕disease (not a screening test given high prevalence of false ⊕; not
to track disease activity). In populations with low prevalence of SLE (e.g. elderly), PPV low given high false ⊕ rates
- ANA = antinuclear antibodies (ENAs (“extractable nuclear antigens”) specify Ag and are a subset of ANAs). Low titer ANA
ANA ≤1:160 often false ⊕. If ANA ⊕, order specific autoantibodies guided by clinical presentation; 5% healthy people test ⊕
- ⊕ ANA: MCTD (100%), SLE (98%), scleroderma (90%), drug-induced lupus (DIL, 90%), Sjogren’s (60%), PM/DM (50%)
- Ddx for ⊕ ANA: Autoimmune: autoimmune hepatitis, PBC, IBD, myasthenia gravis, Graves’, Hashimoto’s; ID: malaria,
SBE, syphilis, HIV, HSV, EBV, HCV, parvo-B19; systemic inflammation: lymphoproliferative d/o, IPF, asbestosis; Medications
ds/mtDNA
dsDNA SLE (40-60%) - Sp for SLE, a/w SLE activity (follow titers) & lupus nephritis, consider DIL
(homogenous)
SLE, drug-induced - Sn but not Sp for DIL
Histones
Histone lupus (90%), - Common meds: procainamide, hydralazine, minocycline, phenytoin, lithium,
(homogenous)
Felty’s INH, quinidine, terbinafine, TNFi
snRNP (speckled;
Smith SLE (30%) - Sp for SLE, not indicative of dz activity
ENA)
U1-snRNP (speckled; MCTD (100%),
RNP - MCTD: high-titer anti-U1 RNP. Also seen in systemic sclerosis (20%)
ENA) SLE (30%)
Ro52, Ro60 Sjogren’s (75%), - Can be seen with myositis, PBC, SSc, MCTD. A/w neonatal lupus syndrome,
SS-A/Ro
(speckled; ENA) SLE (40%) cutaneous lupus. 2% SLE pts have ⊝ ANA but ⊕ anti-Ro
Sjogren’s (40%),
SS-B/La La (speckled; ENA) - Sp for Sjogren’s, SLE. Usually seen w/ ⊕ anti-Ro. A/w neonatal lupus syndrome
SLE (10-15%)
CENP A-F
ACA lcSSc (15-40%) - A/w limited systemic sclerosis, risk of PAH, risk of ILD, esophageal disease
(centromere)
Scl-70 Topo-I (speckled) dcSSc (10-40%) - A/w diffuse systemic sclerosis; risk of ILD, scleroderma renal crisis
RNA pol. III
RNA pol III dcSSc (4-25%) - A/w scleroderma renal crisis, rapidly progressive skin disease, cancer
(nucleolar)
Fibrillarin U3-RNP (nucleolar) dcSSc (<5%) - A/w PAH, pulmonary fibrosis, & myositis, esp. in African-Americans
PM-Scl Exosome (nucleolar) SSc (5-10%) - A/w limited systemic sclerosis, risk of pulm. & renal dz, risk inflamm. myositis
Phospholipids (on - Lupus anticoagulant (affected by current AC), ELISA for anticardiolipin, anti-B2-
APL SLE (10-44%)
plasma membranes) glyoprotein. APLAS classification criteria
Myositis
PM/DM (30%),
tRNA synthetase (His) - Antisynthetase syndrome: myositis (DM/PM), ILD (70%), polyarthritis,
Jo-1*^ anti-synthetase
(cytoplasmic) mechanic’s hands, Raynaud’s, fever
syndrome (~20%)
Mi-2 HDAC factor
Mi-2* DM (15-20%) - More likely in acute DM, good prognosis, a/w disease activity
(homog., speckled)
MDA-5*^ MDA-5 dsRNA binder DM - Clinically amyopathic dermatomyositis, rapidly-progressive ILD
TIF1g* TIF1γ (fine speckled) Juvenile DM - A/w malignancy in adult DM
Signal recog. particle - Immune-mediated necrotizing myopathy (degenerating, regenerating, and
SRP* PM
(cytoplasmic) necrotic cells on bx), rapidly progressive disease course
- Immune-mediated necrotizing myopathy, 70% with statin exposure (at any time
HMGCR HMG CoA reductase myositis in past), ≠ statin myopathy (does not respond to discontinuation of statin), very
high CPK, often steroid-refractory, good response to IVIG
Vasculitis
PR3 (c- - Poor correlation of titer with disease flare/remission
Proteinase 3 GPA (90%)
ANCA) - Antibody frequency lower in GPA without renal involvement
MPA (70%), - Poor correlation of titer with disease flare/remission
MPO (p- EGPA (50%), - Drug-induced vasculitis (DIV): high-titer ⊕ MPO (hydral, PTU, minocycline)
Myeloperoxidase
ANCA) Renal-Limited, (Arthritis Rheum 2022;74:134)
DIV (95%) - Levamisole vasculitis secondary to cocaine use: MPO or PR3/MPO
Cryo- Cryoglobulinemic - HCV > HBV, HIV, CTDs, lymphoproliferative disease, endocarditis
Fc gamma
globulins vasculitis - A/w low C4, glomerulonephritis, +RF
* ordered as part of “myositis panel 3”; panel also includes other less common myositis antibodies
^ order separately for faster results if desired
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Rheumatology Rheumatologic Medications

DRUGS INDICATIONS COMMON TOXICITIES/NOTES
Ibuprofen, indomethacin (short act.) OA, SpA, RA, gout, Gastropathy (↑ w/ age; ↓ w/ PPI/misoprostol ppx, celecoxib),
naproxen (long acting) CPPD, SSc, SLE kidney injury (AKI, AIN, papillary necrosis), CV mortality
celecoxib (COX-2 selective inhibitor) (naproxen may ↓ risk, celecoxib noninferior, NEJM 2016;375;2519)
diclofenac (Voltaren, topical)
Colchicine; microtubule inhibitor Gout/CPPD, FMF, Diarrhea, myopathy, myelosuppression, neutropenia, med
Behcet’s interactions (↓ dose if ↓ GFR)
NON-BIOLOGIC DMARDS
Hydroxychloroquine (HCQ, SLE, RA, Sjogren’s, N/V, retinopathy (baseline & q1y retinal exam), dizziness, rash,
Plaquenil) APLAS alopecia, myelosuppr., ↑QTc
Methotrexate* (MTX, Rheumatrex); RA (first line), PsA Myelosupp. (add folate), LFTs, pneumonitis (baseline CXR),
DHFR inhibitor (antifolate) GI, stomatitis, rash, teratogen. Monitor: CBC + LFTs q12w
Azathioprine* (AZA, Imuran); DM/PM, SLE GI, ↑LFTs; myelosuppression, lymphoproliferative d/o, bruising.
purine synthesis inhibitor nephritis, vasculitis Check TPMT deficiency and avoid XOi (allopurinol) as can
(maintenance), RA toxicity (↑ 6-MP)
Mycophenolate* (MMF, CellCept); AAV, DM/PM, PsA, Cytopenias, ↑LFTS, nausea, diarrhea, HA, insomnia, rash,
purine synthesis inhibitor Scleroderma, SLE teratogen, lymphoma/skin cancer
Leflunomide* (Arava); pyrimidine PsA, RA N/V, alopecia, rash, diarrhea, HTN, hepatotoxicity, URI,
synthesis inhibitor dizziness/HA, teratogen
Sulfasalazine* (5-ASA, SSZ, AS, IBD, JRA, Sore throat, stomatitis, rash, HA, N/V, myelosuppression; check
Azulfidine) Psoriasis, RA G6PD
Cyclosporine* (CsA); SLE nephritis HTN, AKI, HA (both); N/V, GI, gum hyperplasia, hirsutism, edema,
Voclosporin* (Lupkynis); calcineurin (voclosporin); RA tremor (CsA); ↓ HTN & AKI and no level monitoring w/ voclosporin
inhibitor (CNI)
Cyclophosphamide* (CYC, Severe organ- Myelosuppression, lymphoma, hemorrhagic cystitis (MESNA
Cytoxan); DNA alkylation threatening dz (SLE ppx), infertility (cumulative dose, leuprolide ppx), teratogen, <1%
nephritis, ANCA) pneumonitis
Apremilast (Otezla); PDE4 inhibitor PsA/sev Ps, Behcet N/D, URI, HA, depression, wt loss
Tofacitinib*(Xeljanz); JAK1&3 inh. RA, AS, psoriasis Malignancy and CV events (NEJM 2022; 386:316). Infection,
Upadacitinib* (Rinvoq); JAK1 inh. ↑LFTs, diarrhea, VTE, death (black box warning)
Baricitinib* (Olumiant): JAK1&2 inh.
BIOLOGICS
Adalimumab* (Humira); anti-TNF AS, IBD, Ps/PsA, RA CHF (contraindicated in HF), HA, nausea, rash, infection, drug-
Infliximab* (Remicade); anti-TNF induced lupus, skin cancer. Can develop anti-therapeutic Ab ->
Golimumab* (Simponi); anti-TNF loss of clinical response. Monitor: CBC, LFTs q3-6 mo
Certolizumab (Cimzia); anti-TNF NB: safe w/ HCV (Expert Opin Biol Ther 2012;12:193)
Etanercept (Enbrel); sol. TNF-R
Rituximab* (RTX, Rituxan); anti- APLAS, ANCA, Infection, HTN, infusion reaction (use premeds), PML, fever,
CD20 IgG4, Scl-ILD, SLE rash/pruritus, LE edema
Obinutuzumab* (Gazyva); anti-CD20
Belimumab* (Benlysta); anti-BAFF SLE Depression, HA, infusion reaction, PML, GI
Abatacept* (Orencia); soluble CTLA4 PsA, RA Infection, HA, nausea, dizziness, HTN, dyspepsia
Tocilizumab* (Actemra); anti-IL6R GCA (toci), RA, PMR Infection, hepatotoxicity, HLD, GI perforation (h/o diverticulitis ->
Sarilumab* (Kevzara); anti-IL6R contraindicated), neutropenia, thrombocytopenia
Anakinra* (Kineret), anti-IL-1R; Gout/CPPD, Myelosupp./neutropenia (anakinra), rash/injection site rxn/pain,
Canakinumab* (Ilaris); anti-IL1β AOSD/MAS HA, arthralgia, fever, N/D (canakinumab)
Secukinumab* (Cosentyx); AS, Ps/PsA Infection, IBD flare, diarrhea; neutropenia (ixekizumab)
Ixekizumab* (Taltz); anti-IL17A
Ustekinumab* (Stelara); anti-IL- Ps/PsA, IBD Infection; RPLS, seizures (ustekinumab); HA, diarrhea
12/23
Guselkumab*(Tremfya); anti-IL23
Risankizumab* (Skyrizi); anti-IL23a
Anifrolumab*; anti Type I IFN-R SLE Infection, bronchitis/URI, heme malignancies, hypersensitivity
Mepolizumab* (Nucala); anti-IL5 EGPA Injection site rxn, HA
Avacopan* (Tavneos); anti-C5aR ANCA (GPA, MPA) HA, N/V/D, HTN, rash, ↑LFTs
Intravenous immunoglobulin APLAS, DM/PM, Transfusion reactions/anaphylaxis, aseptic meningitis,
IMNM, Kawasaki’s thromboembolism, HA
*Can ↑ HBV/TB reactivation and chronic infection risks (check HBV/HCV serologies, HIV, and IGRA or PPD prior to starting)
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Endocrinology Outpatient Type 2 Diabetes Mellitus

S C R E E N I N G (Diab Care 2024:47;S26)
• ADA recs: Begin at age ≥35 years, repeat q3y if normal. Repeat q1y if pre-DM. All adults at higher risk = 1) BMI ≥25 (≥23 in Asian-
Americans) + RF (1st degree relative with T2DM, nonwhite, history of CVD, HTN, HDL<35, triglycerides >250, PCOS, sedentary
lifestyle, acanthosis nigricans) or 2) History of gestational DM or pancreatitis or 3) HIV prior to starting/switching ART. (ADA 2024).
P R E - D I A B E T E S (Diab Care 2024:47;S20)
• Diagnosis: A1c 5.7-6.4%; fasting plasma glucose (FPG) 100-125; or 75g OGTT w/ 2h glucose 140-199
• Monitoring: A1c at least q1y; if A1c 6-6.4%, screen q6mo; at initiation of second-gen antipsychotics & repeat 12-16 weeks after.
• Treatment: lifestyle ∆ most effective; metformin also effective, esp. if BMI ≥35, age <60, or GDM hx (Cochrane Rev 2019)
D I A B E T E S (Diab Care 2024:47;S22) (Diab Care 2023:46;S97)
• Diagnosis: A1c ≥6.5%; FPG ≥126; 75g OGTT with 2h glucose ≥200; or random BG ≥200 & symptoms. Unless diagnosis is made by
symptoms & random glucose >200, confirm with repeat or additional test at the same time or promptly after.
o For T1DM, check TSH at dx and q1y. Screen for celiac at dx, and again if signs/sx develop. (Diab Care 2024;47;S56)
o Use plasma blood glucose criteria and not A1C if high RBC turnover: sickle cell disease, 2nd/3rd trimester of pregnancy,
G6PD, HD, HIV, recent blood loss/transfusion, EPO tx.
o A1c less reliable post-partum, with certain HIV drugs, thalassemia and sickle cell (high cell turnover), and anemia (UTD list)
• Tx: goal A1c <7%; can liberalize to <8-8.5% if life expectancy ≤10 years or high risk for hypoglycemia
Healthcare Maintenance for Diabetic Patients (Diab Care 2024:47;S56) (Diab Care 2024:47;S116,S182)
• Review blood sugar log: goal AM FPG 80-130, postprandial (1-2h) <180; screen for hypoglycemia awareness
• Review medication regimen and medication-taking behavior. Screen for tobacco, EtOH, and substance use. Counsel.
Every
• Blood pressure: goal <130/80 (if it can be safely attained). ACEi/ARB first line.
visit
• Weight, BMI: weight center referral if BMI ≥40 or ≥35 with poor control; nutrition referral for all (Obesity Meds)
• Foot exam (inspect skin, joints, pulses, sensation) esp. if known neuropathy or PVD; ABIs/vascular referral if PVD
Q3-6mo • A1c q6mo if controlled; q3-6mo if A1c above target
• Lipids: Age 20-39 consider statin if additional risk factors (RF). Age 40-75: moderate-intensity statin for all DM pts
regardless of lipid panel. If >1 ASCVD RF, then high intensity statin w/ target LDL-C<70. Pts with clinical ASCVD
(ACS, TIA), target LDL-C<55 with statins + other agents
• Urine mAlb/Cr, Cr/eGFR; ACEi/ARB if hypertensive w/ proteinuria or GFR <60; refer to renal if GFR <30
Annually
• Neuropathy exam: 10g monofilament (+ if no sensation at 4/10 sites, see PCOI); pinprick, vibration, or reflexes
• Retinopathy screen w/ dilated eye exam or retinal photography; can consider q2-3y if normal exam(s)
• LFTs: consider elastography and/or hepatology referral if elevated to evaluate for MASH
• Other: B12 for those on metformin. T1DM – yearly TSH.
Vaccines • Influenza annually, Hepatitis B series if age <60 and not immune, Zoster, TDAP, Pneumococcus (CDC)
Basal Insulin Management (Diab Care 2024:47;S158)
Criteria • Consider if A1c ≥9%, random BG ≥300, fasting BG ≥250, or symptomatic; suspicion for T1DM or LADA; <65yo on
for two agents with A1c >8% (or ≥65yo and A1c >8.5%) on two occasions >3mo apart; or A1c rising quickly.
initiation • Able to perform self-monitoring with glucometer; consider referral to DM educator
• Starting dose: 0.1-0.2U/kg/d or 10U/d (if weight >80kg, may consider starting at 20U/d)
Initial
• Choice of agent: choose long-acting (glargine qd) or intermediate-acting (NPH BID  cheaper)
dose
• Route: pen (easier to use, more expensive) vs needle/syringe
• Increase by 2-4U or 10-15% q3d until AM fasting BS is 80-130 without hypoglycemia; savvy patients can self-titrate.
Titration
• If hypoglycemia occurs or FPG <80 without clear reason, decrease dose by 10-20% or 4U, whichever is greater.
Prandial Insulin Management
Criteria • Consider if A1c still not at goal with basal insulin >0.5U/kg/d and fasting glucose within target range (80-130).
• Strategy 1: add 1 rapid-acting insulin before largest meal  start w/ 4U or 0.1U/kg or 10% basal dose
Initial
dose • Strategy 2: change to mixed insulin (e.g. fixed 70/30, NPH + regular) BID (before breakfast and dinner). Divide
current basal dose into 2/3 AM, 1/3 PM or 1/2 AM, 1/2 PM. Confirm w/ pt they eat 3 meals regularly if choosing this.
• Increase dose by 1-2U or 10-15% q3d until target glucose reached (pre-prandial: 80-130; 1-2h post-prandial <180)
Titration • If A1c still not controlled: add rapid-acting insulin to another meal and titrate as above
• If hypoglycemia occurs or FPG <80 without clear reason, decrease dose by 10-20% or 4U, whichever is greater
INSULIN SUPPLIES
• Needles: Pen needles for pts on insulin pen or 2)needle+ syringe 32G
4mm is less painful (higher gauge = thinner and shorter needle), but Use this barrel size… With this dose range…
larger patients and high insulin doses often require longer/wider needle. 3/10 mL 30U or less
• Syringes: boxes of 100. Choose smallest syringe that will hold the dose 1/2 mL 31-50U
(smaller barrel  clearer scale markings) 1 mL 51-100U
• Alcohol swabs (or patients can wash hands/skin with soap and water)
• Glucometer & test strips: Many choices, each with own strip brand. Most test strips come in boxes of 50-100. Some glucometers can
read BG aloud (helpful for visually impaired). Tip: MassHealth only covers FreeStyle. Otherwise OneTouch Verio usually covered.
• ** All durable medical equipment including test strips and glucometers requires an ICD-10code on the script itself**
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Endocrinology Outpatient Type 2 Diabetes Mellitus

A L G O R I T H M F O R O R A L A N T I - D I A B E T I C T H E R A P Y (Diab Care 2021;44:S111) (PCOI)

NON-INSULIN AGENTS (DUAL COMBINATION THERAPY WHEN A1C >1.5% ABOVE GOAL)
%
Drug/Dose Range Indications/Benefits Contraindications Side Effects/Considerations
A1c
Metformin: 1st line anti-diabetic medication; many effects, primary mechanism is decreasing hepatic glucose production
GFR cutoffs: Nausea, bloating, diarrhea
First line therapy
Metformin (Glucophage) <45mL/min don’t initiate B12 deficiency
1-2 Minimal weight loss
500-1000mg BID <30mL/min discontinue Lactic acidosis in severe liver/renal
Improvement in lipids
Metabolic acidosis disease or hypoperfusion state
Metformin pearls: discuss GI sx (decrease over time). Minimize by advising slow titration (250-500mg/wk), taking WITH food, or switching
to XR formulation. Benefits/side-effects are dose-dependent – maintain highest dose tolerated.
SGLT-2 Inhibitors: block renal glucose reabsorption, increase glucosuria
CV events, ASCVD UTI & GU fungal infections
Canagliflozin (Invokana) mortality, CHF Small risk of euglycemic DKA (hold
hospitalization, CKD GFR cutoffs: in pts 3-4 days prior to surgery &
100-300mg qd
progression (NEJM Start if eGFR ≥20 mL/min post-op until take PO)
Empagliflozin (Jardiance) 0.8-
2019;380:2295) <20 mL/min discontinue Risk of dehydration/HoTN
10-25mg qd 0.9
Dapagliflozin (Farxiga) Weight loss Risk of fracture (canagliflozin)
History of DKA
5-10mg qd risk of hypoglycemia May LDL cholesterol
BP 3-5mmHg ? ↑ risk amputation w/ canagliflozin
SGLT2i pearls: Discuss diuretic effect, replace water loss to avoid euglycemic DKA. Initiate 1 mo low dose, then titrate to effective dose.
For potency, empagliflozin > canagliflozin > dapagliflozin. HF benefit is probably not a function of A1c lowering.
GLP-1 Receptor Agonists: stimulate glucose-dependent insulin release from beta cells. Slow gastric emptying, promote satiety and w/l
Liraglutide (Victoza)
FDA Black Box Warning: GI: n/v, diarrhea
0.6-1.8mg qd CV events, ASCVD
↑risk medullary thyroid ca. in Injection site reactions
Dulaglutide (Trulicity) 0.5- Weight loss
rodents, not yet demonstrated Delayed gastric emptying
0.75-4.5mg qwk 2 * First line injectable therapy
Semaglutide (Ozempic) (before basal insulin) in humans. Avoid if hx risk of pancreatitis
0.25-2.4mg qwk MTC/MEN2 Low starting dose is to avoid GI side
risk of hypoglycemia
Tirzepatide (Mounjaro) fx. Up titrate for effective wt loss/
2.6 doseefficacy (wt/A1C) GFR 30-45: avoid exenatide A1C lowering
GLP1/GIP 2.5-15 mg qwk
GLP-1 RA pearls: for weight loss, semaglutide > dulaglutide > liraglutide > others. Up-titrate to effective dose in 1mo intervals.
DPP-4 Inhibitors: inhibit degradation of endogenous GLP1, glucose-dependent insulin secretion and glucagon secretion.
Sitagliptin (Januvia) Linagliptin preferred if
CKD/ESRD Saxagliptin, alogliptin: hosp for
25mg-100mg qd 0.5- No contraindications, but very
Linagliptin (Tradjenta) 0.8 risk of hypoglycemia weak CHF
5mg qd Joint pain
Weight neutral
Insulin Secretagogues: stimulate release of insulin from pancreatic beta cells, thus only effective in pts who still have beta cell function
Sulfonylureas: T1DM, DKA Weight gain
Glipizide 2.5-20mg qd 1-2 Affordable Low cross-reactivity in pts Hypoglycemia (esp. glyburide)
Glimepiride 1-8mg qd with sulfa allergy Possible CV mortality
Use like bolus insulin Weight gain
(short-acting) Severe liver disease Hypoglycemia
Meglitinides: Repaglinide 0.5-
Concurrent gemfibrozil
(Prandin) 0.5-4mg qAC 0.7 CKD serum conc. w/ clopidogrel
therapy
nocturnal hypoglycemia TID dosing
Thiazolidinediones: increase insulin sensitivity by acting on adipose, muscle, and liver to glucose uptake, ectopic lipid deposition
Hx of bladder cancer, renal FDA Black Box Warning: risk of
Pioglitazone (Actos) 1- risk of hypoglycemia impairment CHF (2/2  fluid retention)
15-30mg qd 1.6 Possible benefit in NASH
NYHA Class III/IV HF Weight gain; risk of fracture

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Endocrinology Inpatient Diabetes Mellitus Management

INSULIN NOMENCLATURE
Type
(Onset)
Formulation Peak Duration Basal insulin: standing (NOT PRN) fixed intermediate/long-acting for basic
lispro (Humalog) metabolic requirements
Rapid 30-60 Prandial insulin: standing (NOT PRN) rapid/short-acting to cover meals
aspart (Novolog) ~4h
(10min) min
glulisine (Apidra) Correctional insulin: sliding scale (can be standing or PRN depending on
Short Regular insulin
2.5-5h ~6h
pt) rapid/short-acting to correct hyperglycemia from prior meal
(30min) (Humulin R, Novolin R) Pre-Mix (avoid in hospital, but consider for transition to outpatient regimen):
Intermediate Insulin NPH
4-12h ~12h combine basal and prandial insulin into one injection
(1-2h) (Humulin N, Novolin N) Insulin gtt: use in ICU if BG >180 x2 and anticipated ICU LOS >3 days;
glargine (Lantus) qD reference MICU Insulin Protocol in Partners Handbook. Always overlap with SC
Long
detemir (Levemir) qD none 24h
(3-4h)
degludec (Tresiba) qD insulin by 2-3h before stopping insulin gtt
I N P A T I E N T M A N A G E M E N T (Diabetes Care 2021;44:S211)
• Glycemic targets: Floor: fasting 100-140mg/dL, random <180 mg/dL. ICU: 140-215mg/dL (NOT stricter) (NEJM 2023(13):1180)
• Check BG in: (1) diabetics (2) non-diabetics with gluc >140mg/dL (3) pt w/ therapies a/w hyperglycemia (glucocorticoids, octreotide)
• How to check: FSBG qAC (at least for 24-48h) initially OR FSBG q6h if NPO or on continuous TF or TPN. FSBGs less accurate in
hypotension (esp. on pressors), hypothermia, edema, anemia, and Raynaud’s/altered blood flow to skin. Confirm with BMP.
Admission Orders (NEJM 2006;355:1903)
1. Hold home oral antihyperglycemic agents when patients are acutely ill (NEVER hold basal insulin for T1DM)
2. Check A1c in all patients with DM/hyperglycemia if not done in last 3 months
3. If on insulin at home: 25-50% reduction given expected change in diet while hospitalized and initiate ISS for correction and then
adjust basal-bolus dosing over the hospitalization (Diabetes Conversion Guidelines) (goal 50:50 basal:bolus)
4. If not on home insulin:
a. Well-controlled: start with lispro ISS and change to basal-bolus once TDD established. Prolonged use of ISS as only anti-
hyperglycemic tx is discouraged (SSI-only reg. suboptimal unless pt well-controlled on orals) (J Hosp Med 2019;2;114)
b. Not well-controlled (BG >180mg/dL): start w/ basal (0.25U/kg/day), use 0.15U/kg in pts with ESRD, elderly, and low BMI. Then
add prandial insulin (0.05-0.1U/kg) qAC PLUS correctional insulin qAC.
5. If NPO: 50% dose reduction or 0.1U/kg/day for basal. Hold prandial & change correctional ISS and FSBG from TID qAC to q6h
6. Correctional insulin sliding scale: use low-dose if insulin-sensitive/ESRD/ESLD/frail, always do TID qAC and MAKE SURE no HS
Adjusting Insulin Dosing: in general, adjust insulin requirement by no more than 20%. insulin if fasting <100 (hypoglycemia risk).
Fasting/AM BG  (or ) from qHS glucose   (or ) basal insulin dose* *Avoid titrating basal insulin
Fasting BG high + qHS BG high but are the same   dinner prandial insulin dose (no ∆ basal) more than q2-3d (d/t long
BG rises with each meal over the course of the day   prandial insulin dose at each meal half life, requires time to
Pre-lunch or dinner BG high (w/ other BGs in range)   prandial insulin dose of preceding meal reach steady state) to avoid
“stacking” and hypoglycemia
1. Glucocorticoids: NPH 0.1U/kg/d for every 10mg pred (or equivalent), up to 0.4U/kg/d (dose BID); if
dexamethasone or continuous glucocorticoid use, use glargine qD
2. Tube feeds: if not on insulin, start with regular ISS q6h. Convert to NPH BID based on needs. If on insulin, use ½ basal (NPH BID)
+ ½ bolus (regular insulin q6h) + ISS. If TF stopped, give D5W at TF rate until next NPH dose would have been due, and NPH dose
by 50% or more based on pre-TF insulin requirements. TPN: regular insulin can be added to TPN (discuss w/ nutrition)
3. Insulin pumps: consists of basal rate (units/kg/h) which replaces glargine, bolus dose based on carb ratio (units insulin:gram carbs) ,
and correctional insulin based on the sensitivity factor (units insulin:mg/dL above target glucose). Complications: site infection, pump
failure, interrupting infusion. Endocrine consult required to develop contingency plan in case of pump failure. IF CONCERN FOR
AMS, TRANSITION TO SUBQ BASAL/BOLUS REGIMEN (the pump is run completely by the patient).
4. Patient’s Home CGM: Can be used to titrate insulin while inpatient but note that often the BG reading is 20-30 minutes delayed and
should be cross-checked with FSBG initially. Should not be used in ICU. Can consult endocrine for help with this.
Discharge: If oral meds are held inpatient, resume 1-2 days before d/c (ADA, 2023). If poorly controlled DM on insulin PTA: increase
home regimen. If new home insulin: nutrition c/s + floor RN teaching and outpatient f/u. Discharge order set: rx for glucometer, test strips,
lancets, syringes/vials or pens/needles to MGH outpatient pharmacy and bring up to floor for RN teaching (MGH video link).
INPATIENT HYPOGLYCEMIA
Risk: T1DM, brittle DM, malnutrition, emesis, body weight, PO intake, steroid dose, AKI (insulin clearance), CKD (esp. dialysis)
Beware of hypoglycemia unawareness in T1DM and longstanding T2DM
Manifestations: BG<70: Adrenergic component: shakiness, anxiety, diaphoresis, acute hyperphagia. Neuroglycopenic component:
AMS, malaise. <55 with risk of seizure, coma Insulin Pro-Insulin C-Peptide Ddx
Treatment: PO (15g gel, tabs, juice) > IV (12.5-25g D50) > IM/SQ (1mg   
Insulinoma, oral
glucagon); recheck in 15min, chase with PO if due to insulin OD hypoglycemic, autoimmune
If sulfonylurea OD: 50-75mcg octreotide SQ. Review and adjust insulin    Exogenous insulin admin
Ddx: If ill/medicated: drugs (insulin [secretagogues], EtOH), sepsis, Non-islet cell tumor, e.g.
nl nl nl
ESLD, ESRD, HF, adrenal insufficiency, non-islet cell tumor IGF-2-secreting tumor
If well-appearing: post-gastric bypass (post-prandial, or “reactive”, hypoglycemia), insulin or insulin receptor antibodies, insulin
(secretagogues), insulinoma (particularly if fasting hypoglycemia)
Workup: must meet Whipple’s Triad to merit eval! Triad of 1) sx c/w BG, 2) reliably BG whene sx present,3) sx relief once euglycemic
1. Mixed-meal with postprandial eval (q30min labs for 5h post-meal, or fasting eval with admission for 72h fast)
2. Check: serum glucose, insulin level, C-peptide, βOHB, proinsulin, sulfonylurea/meglitinide screen at time 0
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Endocrinology DKA/HHS
DIABETIC KETOACIDOSIS (DKA)
Pathophysiology: think about each element of Diabetic Keto-Acidosis
• Diabetes: insulin & opposing hormones (glucagon, catechols, cortisol)  hyperglycemia  osmotic diuresis  hypovolemia
• Ketones: insulin  lipolysis  free fatty acids  ketones (acetoacetate, β-hydroxybutyrate, acetone)
• Acidosis: β-hydroxybutyrate and acetoacetate, and contraction alkalosis with total body HCO3 deficit (NEJM 2015;372:546)
Precipitants (the “I’s”): infection (30-40% of cases, commonly PNA or UTI), initial presentation of DM (20-25% of cases), insulin non-
adherence, inflammation (pancreatitis – but can see amylase/lipase in DKA even w/o this), infarction (MI, CVA, gut), intoxication (EtOH,
cocaine), iatrogenesis (e.g., SGLT2 inhibitors, steroids, thiazides, dobutamine/terbutaline, atypical anti-psychotics), infant (pregnancy)
Presentation: dehydration, polyuria/polydipsia, weight loss, n/v/abd pain, AMS, Kussmaul’s respirations, fruity breath (acetone)
Dx: BG 250-800, pH <7.3, HCO3 < 18, AG >10, ketonemia. Consider euglycemic DKA in pt on SGLT2i, EtOH liver dz, pregnancy
• Check BMP, CBC/diff, UA, SOsm, serum β-hydroxybutyrate, ABG/VBG (if serum bicarb reduced or hypoxemic). Consider hs-trop,
EKG, BCx/UCx, CXR, lipase/amylase
o UA ketone does not test for β-hydroxybutyrate, which is the predominant ketone in DKA (must measure from serum)
• Na correction  use absolute sodium value when calculating anion gap. Use corrected value to assess for underlying hypotonic
hypoNa: Corrected Sodium = Measured sodium + 0.02 * (Serum glucose - 100).
Management: prioritize ABCs, volume status, identifying precipitant  THEN electrolytes (especially K+)  THEN glucose
Labs: BMP q2h until AG closes, then q4h until normal K+; VBG, β-hydroxybutyrate q2-4h; FSBG q1h while on insulin gtt
Step 1: volume resuscitation (typically 5-8L deficit) (QJM 2012;105:334; JAMA Netw Open 2020;3:e2024596)
o Bolus LR 15-20cc/kg/h for initial resuscitation in first 1-2h (unless CHF, ESLD, ESRD, hypoxemia)
o Corrected Na  if low, start NS/LR±K+ at 250-500cc/h; if normal/high or hyperCl acidosis, start ½NS/LR±K+ at 250-500cc/h
o Add D5 to IVF at 150-200cc/h once BG<200 (DKA) or <300 (HHS)
Step 2: potassium repletion and management

Potassium Action K+ may be normal/elevated at presentation, but total body K+ is

K <3.3 Give 20-40mEq KCl IV per hour + hold insulin! low. Multifactorial causes: solute drag of K+ into extracellular
space, osmotic diuresis, insulin not driving K+ into cells.
3.3≤K≤5.3 Add 20mEq K to IVF
Aggressive K+ repletion is critical: HYPOkalemia will limit your
K >5.3 Continue to monitor q2h ability to administer the necessary insulin!

Step 3: insulin therapy, see flow chart (Diabetes Metab Syndr Obes. 2014;7:255)
The #1 goal of insulin therapy in DKA is to stop ketogenesis and close the AG
o Don’t start insulin until you have control of K (>3.3meq/L)
o Don’t stop the insulin gtt unless true hypoglycemia (<65 mg/dL) or hypokalemia (<3.3 mEq) occurs
o Initial: bolus 0.1U/kg regular insulin, then start 0.1U/kg/h IV regular insulin gtt; OR no bolus and start 0.14U/kg/h IV gtt
 Goal is to BG by 50-75mg/dL each hour
 For mild DKA, subcutaneous insulin regimens may be used instead of IV (Cochrane Rev 2016)
o Titrating insulin drip: MICU insulin gtt protocol is NOT for DKA
 If BG does not  by 10% in 1st hr, re-bolus (DKA) or double the gtt (HHS), no evidence for hourly titration afterwards
 If BG >250 and falling: increase gtt by 25% if drop is <40, no change if drop is 40-80, decrease by 50% if drop >80
 Once BG <200 (DKA) or <300 (HHS), gtt to 0.02- For BG <150 ∆ Insulin gtt and glucose source
0.05U/kg/h and add D5 to fluids
BG 91-149 gtt by 25% + D5 gtt by 50cc/hr
 Goal BG is 150-200 (DKA) or 250-300 (HHS)
BG 66-90 gtt by 50% + ½ amp D50 + continue D5 gtt
Other electrolytes:
BG ≤65 hold insulin + 1 amp D50 + continue D5 gtt
• HCO3: no proven benefit w/ pH > 6.9. If pH <6.9, give 2 amps
HCO3 dissolved in 400mL sterile water w/ 20mEq KCl over 2h
• Phos: total body deficit but serum phos may be /nml; will  w/ insulin; only replete if <1.0 to prevent cardiac dysfunction
Transitioning to SQ insulin: start if BG <200 and pt is able to eat and two of the following are met: AG <12, HCO3 ≥15, pH >7.3
• Basal regimen w/ either: home glargine dose OR glargine at 0.25-0.4 U/kg/d OR glargine at (# units on IV gtt over past 6h x 4 x 0.7).
Consider NPH 0.25-0.4U/kg/d in pts presenting with newly diagnosed DM for easier titration (split dose as 2/3 AM dose, 1/3 PM
dose).
• Bolus regimen w/ either: 0.25-0.4U/kg/d divided (if T1DM or unknown) OR ISS only (if T2DM). Overlap IV gtt/SQ insulin by 2-4h.
Ketosis-prone diabetes: characterized by DKA w/ hx T2DM or atypical substrate for T1DM (older age, overweight). Patients should be
discharged on insulin and see an endocrinologist for antibody (GAD65, IA2) and β-cell function (C-peptide levels) testing to determine
diabetes subtype (antibody, β-cell function). Patients may not require long-term insulin therapy.

HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)

Pathophysiology: hyperglycemia  osmotic diuresis  volume depletion; ketogenesis suppressed by low (but present) insulin levels
Precipitants: same as DKA (note: pts w/ T2DM and burnt-out pancreas can also present with DKA)
Presentation: AMS (25-50%), obtundation, seizure, focal neuro def, volume depletion, evolves over days-weeks (vs hours-days in DKA)
Dx: glucose >600mg/dL (frequently >1000), osmolality >320mOsm/kg, pH >7.3, absent or minimal ketones
Management: as above for DKA w/ modifications: more aggressive IVF (~8-10L deficit); goal glucose 250-300mg/dL (in DKA, 150-200);
transition to SQ insulin when BG <300 and mental status improved, and patient is able to eat. Mortality >> DKA (Diab Care 2014;37:3124)

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Endocrinology Adrenal Insufficiency

E T I O L O G Y (Lancet 2014;383:2152; NEJM 2009;360:2328)
Primary AI (Addison’s disease): all adrenal hormones  ACTH. Lesion localizes to bilateral adrenal glands
• Causes: autoimmune (80-90% cases in developed countries; anti-21-hydroxylase Ab+ in 86%, autoimmune polyglandular
syndromes) >> infection (TB, HIV, CMV, meningococcus, histo > all fungi except Candida; most common cause worldwide), bilateral
adrenal hemorrhage (infection, DIC, APLAS), infiltration (hemochromatosis, primary amyloidosis), malignancy (mets), genetic
Secondary AI: ACTH  adrenal hormone (glucocorticoids only). Lesion localizes to pituitary gland or hypothalamus
• Causes: Abrupt cessation of chronic supraphysiologic glucocorticoids, meds, pituitary/hypothalamic lesions (see Pituitary Disorders)
C L I N I C A L M A N I F E S T A T I O N S (Lancet 2003;361:1881)
Primary AND Secondary:
• Signs/symptoms: weakness, fatigue, anorexia, nausea, vomiting, abdominal pain, psychiatric sx, orthostasis, ↓wt, amenorrhea
• Lab abnormalities: hyponatremia, hypoglycemia, hypercalcemia, non-AG acidosis, anemia, eosinophilia, lymphocytosis
Primary only (serum aldo): hyperK (only 65%), salt craving, hyperpigmentation (MSH), n/v, abdominal pain, ↓BP, ↑HR, shock
Secondary only (RAAS intact): ± hypopituitarism, hypoglycemia (more common than in primary AI)
DIAGNOSIS
• Preferred test: cosyntropin stimulation test (aka “cort stim”) (JCEM 2016;101:364). Can be performed any time of day
o Check serum cortisol and ACTH  give cosyntropin (ACTH) high-dose 250 μg IV  repeat serum cortisol 30 and 60min later
o Normal response: serum cortisol >15µg/dL (note: this rules out all cases of 1° AI + chronic cases of 2° AI)
 In acute 2° AI, adrenal glands have not had time to atrophy, so cort stim test will be normal
o If abnormal cort stim, consult endocrine
• Second line: If cort stim is not possible, check AM cortisol and ACTH as a preliminary test to suggest AI
• 6-8 AM cortisol: highly suggestive of AI if ≤3µg/dL (<5µg/dL suggestive); AI ruled out if ≥15 µg/dL (18 µg/dL on older assays).
 Falsely low: albumin (cirrhosis, nephrotic syndrome, critical illness; bound and total cortisol, but free cortisol may be
nml); PM testing (cortisol level is highest in morning)
 Falsely high: pregnancy, estrogen tx (cortisol binding globulin, bound/total cortisol, free cortisol may normal)
• Testing for primary AI: ACTH >2x ULN; aldo, plasma renin, 21-OHase Ab; TB test, VLCFA. Consider CT A/P
• Testing for secondary, tertiary AI:  or normal ACTH, normal aldo
ADRENAL CRISIS
• Acute-onset AI with distributive shock in s/o major stressor (infxn, trauma, major surgery, critical illness). Consult endocrine.
• No known AI: draw ACTH/cortisol but don’t delay empiric treatment; defer cort-stim until stable
• Known AI or taking chronic steroids: start treatment; diagnosis can be presumed by history; no role for cort stim test
T R E A T M E N T (JCEM 2016;101:364; NEJM 2019:381:852)
• Adrenal crisis  stress dose steroids (hydrocort 100mg IV x1) & >2-3L NS or D5NS (if hypoglycemic). BMP, cortisol & ACTH.
Follow w/ hydrocort 50mg IV q6-8h. Start fludrocortisone 0.1mg QD when off IV fluid (in primary AI & hydrocort dose <50mg in 24h).
o Consider in any patient taking glucocorticoids (>5 mg pred eq/day for ≥4 wk or >40 mg pred eq/day for ≥1 wk)
o May taper once patient’s clinical status improves and underlying precipitant is adequately addressed
• AI  glucocorticoid: hydrocortisone 15-25mg/day PO (2/3 AM, 1/3 early PM) > prednisone 3-5mg/day (QD or BID) >>
dexamethasone (significant Cushingoid side effects) 1º AI: add fludrocortisone 0.05-0.1 mg PO QD (n.b. hydrocortisone has
mineralocorticoid activity; dose adjust appropriately); Dose monitoring: hypoK, HTN, edema  reduce dose; New dx: use plasma
renin activity (PRA), goal upper normal range; Liberal salt intake, esp. with exercise or exposure to temps >85 ºF (>29 ºC). Consider
↑fludrocortisone dose in summer; Consider DHEA replacement for 3-6 month trial in women with impaired mood 2º AI: assess other
pituitary hormone deficiencies (treat AI before hypothyroidism to ↓risk adrenal crisis)
o If minor illness (e.g., URI) or minor surgery  sick dose: “3x3 rule” = 3x daily glucocorticoid dose for 3 days
o If severe illness  stress dose: emergency hydrocortisone injection (as below)
o Supply patients with medical alert bracelet + card and glucocorticoid injection kit (100 mg hydrocortisone) for emergency use
o Consider screening for AI diseases (unknown optimal frequency) including DM, thyroid dz, premature ovarian failure, celiac dz
STEROID PEARLS
• Taper: not necessary if steroid use <3w (independent of dose)  low risk of HPA suppression. Usually the patient’s specialist
prescribing the steroid a slow taper if underlying disease might flare with an abrupt decrease in steroid dose. Otherwise can drop
steroid dose to 5mg pred equivalent and perform a cort stim. If AI present, continue pred 5 mg for 6-8 weeks then repeat cort stim
• Ppx: PJP: if taking pred ≥20mg for ≥4w + 2nd reason for immunocompromise; PUD: if taking aspirin/NSAIDs; osteoporosis: calcium
1200mg/d + vitamin D 800IU/d if on any dose >3mo (consider bisphosphonates for pts at intermediate/high risk of fracture); DM2:
monitor glucose/A1C, consider insulin dosing (cover with NPH 0.1 U/kg per 10 mg prednisone equivalents up to 40 mg)
Equivalent Relative Relative Na Duration
Steroid
Anti-inflammatory Dose (mg) Anti-inflammatory Activity Retention Activity (hrs)
Hydrocortisone 20 1 2 8-12
Predniso(lo)ne 5 4 0.8 12-36
Methylprednisolone 4 5 0.5 12-36
Dexamethasone 0.75 30 0 36-72
Fludrocortisone n/a 10 125 12-36

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Endocrinology Pituitary Disorders

HYPOPITUITARISM
Definition: pituitary hormone production/release resulting from diseases of pituitary (1°) or hypothalamus/stalk (2°)
Causes: surgery, radiation, infection (TB, fungal, meningitis), infiltration (sarcoid, hemochromatosis, Langerhans cell histiocytosis,
lymphocytosis), TBI, genetic, tumors (1°: pituitary tumors, mets; 2°: external stalk compression [e.g., craniopharyngioma, meningioma,
mets])
• 1° only: Sheehan’s (infarction), apoplexy (hemorrhage), meds (immune checkpoint inhibitors)
Clinical Manifestations & Diagnosis:
Hormone Deficiency Signs/Symptoms Laboratory Tests
Prolactin (rarely isolated) Reduced lactation PRL
ACTH (2° adrenal insufficiency) Weight loss, anorexia, nausea, dizziness AM cortisol, cort stim test, ACTH
Low energy, central obesity, ↓bone mineral density,
GH IGF-1, insulin tolerance test
↓exercise performance, psych (depression, immaturity)
TSH (2° hypothyroidism) Weight gain, bradycardia, hair loss, dry skin, hyporeflexia TSH, free T4
LH/FSH amenorrhea/oligomenorrhea, decreased libido, ED, infertility LH, FSH, estradiol, AM testosterone
Treatment: replace deficient hormone (JCEM 2016;101:3888) and endocrine consult. Most sensitive issue is cortisol/thyroid hormone
replacement: if concurrent deficiencies treat AI before hypothyroidism as can otherwise precipitate adrenal crisis.
HYPERPITUITARISM
Definition: excess of any of the hormones secreted by the anterior pituitary gland (PRL, ACTH, GH, TSH, LH/FSH)
Causes: (1) hyperfxn pituitary adenoma (2) elevated prolactin 2/2 disruption of pituitary stalk, med (e.g. dopamine antagonists)
Clinical Manifestations & Diagnosis: if pituitary adenoma  headaches, visual field deficits (bitemporal hemianopia)
• Imaging: MRI brain w/ and w/o contrast (ask rads for pituitary protocol)
Hormone Excess Signs/Symptoms Laboratory Tests
Prolactin (Prolactinoma) Infertility, amenorrhea, galactorrhea (F>M), erectile dysfunction PRL
Weight gain, depression, insomnia, easy bruising, poor wound Overnight 1 mg dex suppression test,
ACTH (Cushing’s disease) healing, central obesity, acne, hirsutism, wide violaceous striae, late-night salivary cortisol, or 24h
prox muscle weakness, HTN, osteoporosis, DM urinary free cortisol excretion
Arthralgias, paresthesias (carpal tunnel syndrome),
IGF-1, confirm with GH level after
GH (Acromegaly) hyperhidrosis, OSA, CHF, enlarged jaw/hands/feet, coarse
glucose tolerance test
facial features, deepening of voice, skin tags, hirsutism, HTN
Tremor, palpitation, heat intolerance, weight loss, increased
TSH (2° hyperthyroidism) TSH, free T4, total T3
bowel movements, dyspnea
Treatment:
• Prolactinoma: if >1cm or symptomatic, first-line treatment is dopamine agonist (cabergoline > bromocriptine [preferred in
pregnancy]). If <1cm and asymptomatic, can monitor closely with MRI and prolactin levels (JCEM 2011;96:273)
o Use lowest dose possible to restore prolactin to normal (men and post-menopausal women: <20 ng/mL, pre-menopausal
women: <30 ng/mL); TTE not required prior to initiation (JCEM 2016;101:4189)
• For all other hypersecreting pituitary adenomas, treatment is transsphenoidal pituitary surgery ± radiation therapy
• For GH secreting adenomas in pts who are poor surgical candidates or w/ persistent dz, can tx with somatostatin analog (octreotide)
DIABETES INSIPIDUS (DI)
Definition: polyuria (>50mL/kg/day in DI) in setting of insufficient amount of (central) or response to (nephrogenic) ADH
Causes: Central: trauma, surgery, hemorrhage, infarction, neoplasm, infiltrative (sarcoidosis, histiocytosis), infection, autoimmune, drugs
(EtOH, phenytoin) || Nephrogenic: drugs (lithium, cisplatin), hypoK/hyperCa, infiltrative (sarcoidosis, amyloidosis, MM), sickle cell
Diagnosis: confirm polyuria (24 h urine volume >3 L) prior to referral/evaluation
• Water deprivation test: normal physiology: water restriction  SOsm  ADH  UOsm (JCEM 2012;97:3426)
o Check Na, SOsm, UOsm, UVol q2hr. Urine dipstick for glucose should be negative.
o If UOsm > 700 mEq/kg, stop test due to appropriate vasopressin response (dx: primary polydipsia)
o Once (1) SOsm > 295 mEq/kg, (2) Na ≥145 mEq/L (adequate ADH stimulus)  administer desmopressin 4 mcg IV, then
check UOsm, UVol q30min x 2hr. judge reponse:
 UOsm  to <300 mEq/kg   by <15% complete nephro DI ||  by 15-45%  partial nephro DI
 UOsm  to >300 mEq/kg   by >100% complete central DI ||  by 15-100%  partial central DI
Treatment: correct hypernatremia (see Sodium Disorders). Allow patient to drink to thirst. PO preferred to avoid rapid ∆ in serum Na.
• Central: desmopressin (exogenous ADH) given intranasal (5mcg qhs + 5mcg qd to tid) or PO/SC, can augment with adjunctive
meds. If impaired thirst or no access to water, high risk of hypernatremia.
• Nephrogenic: if partial, may try desmopressin; if complete, use adjunctive meds
• Salt/protein restriction: low solute intake reduces thirst, thereby reducing free water intake
• Adjunctive meds: HCTZ (volume depletion  increases proximal Na/water reabsorption, decreasing distal Na delivery where ADH
acts), amiloride (mechanism similar to HCTZ, beneficial in Li-induced nephrogenic DI by blocking entry of Li across ENaC), NSAIDs
(enhance renal response to ADH), chlorpropamide (enhances renal response to ADH)

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Endocrinology Calcium Disorders

HYPERCALCEMIA
If unsure of validity of total Ca measurement due to hypoalbuminemia or major acid-base disturbances, obtain an iCa. Correction
algorithms for albumin are no longer supported (Things We Do for No Reason)
Definition: mild (Ca 10.5-12; iCa 5.6-8); moderate (Ca 12-14; iCa 8-10); severe (Ca >14; iCa >10)
Clinical signs/symptoms: MSK (“bones”)  osteitis fibrosa cystica (1° hyperPTH), arthralgia, osteoporosis/fractures, weakness; Renal
(“stones”)  polydipsia, polyuria, nephrolithiasis, Type 1 RTA, AKI/CKD; GI (“groans”)  n/v, anorexia, constipation, ileus, pancreatitis,
peptic ulcers; Neuropsych (“overtones”)  fatigue, depression, anxiety, confusion, stupor, coma; CV  bradycardia, short QTc, AV
block, valve/vessel calcification, HTN

Diagnostic approach: PTH  (think malignancy) Abnormal Multiple

Nl / 
myeloma
PTHrP
Urine Ca  1,25(OH)D SPEP, UPEP,
Nl /   Nl /  (active form) SFLC
Nl /  Nl /  WNL
1° HyperPTH: (#1 Familial Ectopic production
outpt) (adenoma Hypocalciuric  Other: (rare)
(#1 inpt): (lung 25(OH)D
> hyperplasia > Hypercalcemia SCC, breast, RCC) (storage form) - T4
carcinoma); a/w (FHH): - Adrenal insufficiency
MEN Autosomal Dom.,  - Meds (HCTZ, lithium,
3° HyperPTH: 24h urine - Granulomatous Vit A, milk-alkali
longstanding CKD calcium/Cr ratio disease (sarcoid, TB) Vitamin D syndrome)
<0.01 - Lymphoma toxicity - Immobilization

Management: (BMJ 2015;305:h2723; NEJM 2005;352:373)

In mild-moderate hyperCa: avoid contributory meds; oral hydration; oral PO4 repletion to 2.5-3.0 (IV could lead to hypoCa)
In symptomatic or severe hyperCa (>14): should be admitted for treatment and have an endocrine +/- renal consult to assess HD needs
• 1st line treatment: IVF and subQ calcitonin (faster but transient) + IV zoledronic acid (for delayed but sustained effect after 2-4d)
o Volume resuscitation: pts are typically very dehydrated; bolus NS then gtt @ 200-300cc/h with goal UOP 100-150cc/h.
o Calcitonin: 4-8U/kg subQ BID x 48 hrs (substantial Ca reduction within 12-24h). Possible tachyphylaxis within 48-72h.
o Bisphosphonates: zoledronate >> pamidronate (except in MM). Takes 2-4d for effect. SE: hypoCa (check vit D, replete
prior), hypoPhos, flu-like illness, impaired renal fxn. Reduce rate or dose if CKD (Cr>4.5). Avoid if CrCl <30.
• Other treatments:
o Denosumab: monoclonal Ab against RANKL  blocks pre-osteoclast maturation. Good option in patients with CKD. May be
favored over IV bisphosphonates in hypercalcemia of malignancy, but both can be used if refactory. Requires careful
monitoring as hypocalcemia risk >> than with bisphosphonates esp at low GFRs. Check 25(OH)D + replete prior to admin.
o Loop diuretics: ONLY if concurrent HF, CKD (once volume replete), elderly; otherwise avoid 2/2 worsen dehydration
o Glucocorticoids: for calcitriol mediated etiologies [i.e. granulomatous diseases], takes 2-5 days to take effect.
o HD: if life-threatening or Ca >18 at onset AND neuro sx.
Special considerations for 1° hyperPTH: surgery is curative. Indicated if (1) symptomatic OR (2) asymptomatic with Ca >11.5,
osteoporosis/vertebral fracture, CrCl <60, nephrolithiasis, 24-hr urinary Ca > 400mg/day, or age <50. If poor surgical candidate, consider
cinacalcet, bisphosphonate, HCTZ, raloxifene (JAMA Surg 2017;152:878; JCEM 2014;99:3607)
HYPOCALCEMIA
Clinical signs/symptoms: neuromuscular (paresthesias, muscle cramps/spasms, tetany, Trousseau sign [carpal spasm w/ BP cuff
inflation 94% Sn, 99% Sp], Chvostek sign [circumoral muscle twitch w/ facial nerve tapping poor Sn, 85% Sp]); seizures; QTc, AMS,
laryngospasm, bronchospasm, abdominal pain, dysphagia (BMJ 2008;336:1298)

Diagnostic approach:
Low/Nl
PTH High

- Hypoparathyroidism (surgical,  PO4  PO4

autoimmune, infiltrative dz, radiation) - Vitamin D deficiency CKD (2° HyperPTH); Tumor lysis; Rhabdo
- Hypomagnesemia (causes PTH - Pancreatitis (early); Osteoblastic mets (breast, prostate ca);
suppression/resistance) - Drugs (bisphosphonate, Pseudohypoparathyroidism (PTH resistance);
phenytoin, cinacalcet) Critical illness; Transfusions (citrate); Post-op
Management:
Replete Mg (hypoCa can be hard to correct w/o first correcting hypoMg (<0.8 mEq/L)  causes PTH resistance and  secretion)
IV Ca repletion: if severe (Ca <7.5, iCa <1) or no PO access. Not indicated for asymptomatic hypoCa in CKD.
• 1-2g IV Ca gluconate (preferred) or CaCl2 (in codes: via central line, risk of skin necrosis if extravasates) over 10-20 min (slowly to
mitigate cardiac risk)-> can repeat in 10-60 min if no effect; Trend iCa q4-6h (more reliable given frequent changes in pH in ICU)
• IV therapy serum levels for only 2-3h, chase with gtt or PO; can do sliding scale repletion in ICU
PO Ca repletion: if Ca >7.5 (iCa>3) or asx: 1-2g elemental Ca QD in divided doses (Ca citrate better absorbed vs CaCO3 esp. if pt on PPI)
Vitamin D repletion: See Vitamin D; often need to give calcitriol for primary hypoparathyroidism.
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Endocrinology Osteoporosis & Vitamin D

OSTEOPOROSIS
Definitions: fragility fracture or BMD T-score ≤-2.5 on DXA. Osteopenia: T-score -2.4 to -1.1. BMD threshold based on fracture risk in
postmenopausal white females, applicable to postmenopausal women and men ≥50 yo (ISCD 2019).
• T-score: SD compared to mean for young, healthy adults of same sex and race
• Z-score: SD compared to mean for age, sex, ethnicity-matched population (preferred younger patients)
• Fragility fracture: occurring spontaneously or from minor trauma (e.g. fall from standing height); fractures of hands, feet, ankles,
cervical spine, face, skull typically do not count.
Etiology: (Osteoporos Int 2022;33:2049)
• 1° osteoporosis most common. RFs: age (women ≥65, men ≥70), low body weight (<57.6 kg), FHx of hip fracture, smoking, early
menopause, excessive EtOH use
• Many 2°causes, including: kidney and liver dz, hyperthyroidism, hyperPTH, ↓vit D, hypogonadism, hypercalciuria, myeloma,
malabsorption, RA, SLE, COPD, drugs (e.g. glucocorticoids, PPI, AED, heparin, aromatase inhib, MTX, GnRH agonists)
Diagnosis:
• FRAX score estimates 10-year fracture risk with or without BMD data. In the US, clinical dx of osteoporosis when FRAX 10-year risk
of major osteoporotic fracture ≥20% or hip fracture ≥3%. (Osteoporos Int. 2014;25:1439)
• Indications for DXA Scan (spine and hip +/- forearm): all women age ≥65 (USPSTF) and men ≥70; younger if RFs; fracture and age
≥50; hx condition or meds assc. with ↓bone mass or bone loss (Osteoporos Int 2022;33:2049)
• Initial labs for 2° causes: CBC, BMP/Ca/Mg/Phos, LFTs, 25(OH)-vitD, PTH, testosterone (men), 24h urinary Ca and Cr
• Consider TSH, SPEP+sFLC, tTG-IgA, iron/ferritin, homocysteine, prolactin; Urine (UPEP, free cortisol, histamine)
Management: (JCEM 2012;97:1802; JCEM 2019;104:1592; Osteoporos Int 2022;33:2049)
• Lifestyle measures: all patients with ↓BMD: weight-bearing exercise 3-4x/wk, smoking cessation, ↓EtOH intake, calcium 1200mg qd
(diet+supplement, divided doses ≤500 mg/dose). Replete Vit D to goal 30-50 ng/ml (usually 800-1000 IU/day).
• Pharmacologic therapy: initiate in postmenopausal women with hip/vertebral fracture; those with osteoporosis; or those with
osteopenia and FRAX 10y risk ≥20% for any fracture, ≥3% for hip; or males >50 yrs with above features & males w/ prostate cancer
receiving androgen-deprivation therapy who are high risk of fracture.
o Bisphosphonates: normal Ca, Vit D >20 prior to initiation. Reasses fracture risk and consider drug holiday after 3 years of IV
and 5 years of oral bisphosphonates in patients with improved T-score > -2.5 & no new fractures. (JCEM 2019;104:1592)
 PO alendronate 70mg or PO risedronate 35mg weekly. Avoid if GFR <30, esophageal dysmotility or h/o bariatric surgery.
Strict instructions: sit upright and take on empty stomach w/ full glass of water 30 min prior to other meds/food.
 IV zoledronic acid 5mg annually if esophagitis/GERD with PO treatment, hx bariatric procedures (Roux-en-Y) or otherwise
unable to tolerate PO. Can experience flu-like symptoms after infusion.
o SERMs (tamoxifen/raloxifene): less effective compared to bisphosphonates and reserved for use if unable to tolerate
bisphosphonate/denosumab or in postmenopausal women with increased risk of breast cancer. Side effects: ↑risk endometrial
ca (tamoxifen only), ↑risk DVT/PE, edema, hot flashes, muscle cramps
o Referral to Endocrine for advanced therapies, refractory disease, severe osteoprosis (T score ≤-3.0 or ≤-2.5 with fragility
fracture) or age< 50: denosumab (RANKL mAb; if discontinued should be started on antiresorptive, preferably a
bisphosphonate) (NEJM 2009;361:756; JCEM 2020;106:264), teriparatide and abaloparatide (recombinant PTH and PTHrP analog,
respectively) (Lancet 2018;391:230), romosozumab (sclerostin inhibitor)
• Inpatient following fragility fracture: assess need for surgical treatment and consult Fracture Liaison Service (p25656).
Bisphosphonates decrease rate of new clinical fracture and mortality post-hip fx (NEJM 2007;357:1799)
Monitoring: variable recommendations; can repeat follow-up DXA hip/spine after 2 years; if stable, can space out scans

VITAMIN D
Definitions: Measured by 25[OH]D (calcidiol) in serum (JCEM 2019;104:234). No consensus cutoff but most groups use: Vit D Sufficiency:
>20ng/mL; Insufficiency: 12-20ng/mL; Deficiency: <12ng/mL; Risk of toxicity >100ng/mL +↑Ca intake
Diagnosis:
• Population screening not recommended, only screen high-risk patients (Choosing Wisely; JCEM 2011;96:1911): Rickets, osteomalacia,
osteoporosis, hyperPTH, inadequate PO, ↓ cutaneous synthesis (↓sunlight i.e., institutionalized or northern latitudes, sun
pigmentation, aging), malabsorption (gastrectomy, IBD, CF, celiac, pancreatobiliary disease), ↓synthesis (ESLD, CKD), change in
catabolism (AEDs, steroids, HAART, immunosuppressants)
• If deficient, obtain PTH, BMP/Phos, ALP, TTG. Consider if insufficient AND concern for secondary cause e.g., IBD
Management (NEJM 2007;357:3; J Am Geriatr Soc 2014;62:147):
• Supplement with D3 or D2 (D3 slightly more preferred but D2 more readily available); recheck levels in 3-4 months
o <12ng/mL: 50,000IU weekly x6-8w followed by 800-1000IU qd; 12-20ng/mL: 800-1000 IU qd
o Calcium citrate may be preferred if patient has constipation, is at risk of renal stones or is taking a PPI or H2 blocker.
• For patients ≥65y at high fall/fracture risk: Vit D ≥1000IU + calcium 1000mg qd with goal of serum 25(OH)D >30ng/mL
• For patients with malabsorption: up to 10,000 to 50,000IU qd and/or UVB irradiation
• For patients with ESRD, ESLD, or vitamin D-dependent rickets (poor conversion of 25(OH)D): calcitriol 0.25-1.0 μg qd
• Intermittent, high dosing of Vit D associated with increased falls in older adults and is generally avoided (JAMA 2010;303:18)

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Endocrinology Thyroid Disorders & Male Hypogonadism

INPATIENT TFTS
Testing: If thyroidal illness suspected, TSH alone is inadequate; should also test for FT4 & T3. TSH reflects changes within 4-6 wks.
Routine screening on admission not indicated. Only send if related to CC or suspect thyroid disease (J Hosp Med 2020;15:560)
• Undetectable TSH (<0.01) suggests true hyperthyroidism, and TSH >20 + low T4 suggests true hypothyroidism
Nonthyroidal illness “euthyroid sick": alterations in thyroid fxn due to illness, not 1° endocrine disorder; may be adaptive (anti-
catabolic); no indication to treat; most likely cause of abnormal TFTs among inpatients (Lancet Diab Endo 2015;3:816)
• Typical pattern: (1) acute illness: T3, T4, /nl FT4, /nl TSH. (2) recovery phase: TSH  recovery of T4, T3
• Sequential FT4 should  in recovering sick euthyroid but remains low in 1° hypothyroid. rT3 can differentiate central hypothyroidism
() from sick euthyroid (), but rarely needed. FT3 only helpful to dx hyperthyroidism w/ altered TBG.
HYPOTHYROIDISM
Definition: elevated TSH with low T4 (primary) or inappropriately low/normal TSH with low T4 (2°/central)
Signs/symptoms: general (fatigue, cold intolerance, constipation, dry skin, myalgias, weight gain), neuro (depression, cognitive
dysfunction, carpal tunnel), CV (bradycardia [severe], diastolic HTN), irregular menses
• Exam: delayed relaxation phase of DTRs, non-pitting edema, lateral eyebrow thinning, macroglossia
Labs: LDL, triglycerides, macrocytic anemia, Na
TSH FT4
• Check other pituitary axes if concern for central hypothyroidism
Primary  
Workup: TSH with reflex, anti-TPO ab. No role for thyroglobulin or anti-thyroglobulin ab
(only useful for monitoring thyroid Ca) Central /Normal 
Causes: Subclinical  Normal
• 1°: Hashimoto’s (most common, ⊕TPO Ab), infiltrative dz (hemochromatosis, sarcoid), transient thyroiditis (Hashimoto’s,
granulomatous, postpartum), drugs (lithium, amio, TKIs, contrast), iatrogenic (thyroidectomy, radiation), iodine deficiency
• 2°: see Pituitary Disorders
•  T4 requirement: pregnancy, estrogen (THBG), weight gain, malabsorptive (e.g., celiac disease), nephrotic syndrome (
excretion), rifampin, phenytoin, carbamazepine, phenobarbital
Tx: levothyroxine (T4) starting dose ~1.4mcg/kg/d PO (use 25-50mcg QD for elderly or comorbidities); IV = 50-75% PO
• Take on an empty stomach 1h before food/meds; several hrs apart from calcium, aluminum hydroxide, iron, cholestyramine
• Check TSH q4-6 weeks and adjust by 12-25mcg until normal TSH. If pituitary insufficiency/2° hypothyroidism, track FT4s as TSH is
not an accurate reflection of thyroid function. Once on stable dose, check TSH q6-12 months
Subclinical hypothyroidism: elevated TSH with normal FT4 (biochemical dx)
• Dx: can check anti-TPO Ab (if ⊕, monitor TFTs because at ↑ risk for Hashimoto’s) TSH Age<65 Age>65
• Treatment: tx all patients with TSH ≥10. If TSH>7 and age<65 OR if age>65 and 5-6.9 Consider RFs No tx
symptomatic, tx. If TSH 5-6.9, consider risk factors (e.g., CV disease, HLD) to guide tx to guide tx
• Elderly patients often have higher TSH levels, can be nl, tx if symptomatic. 7-9.9 Tx Tx only if sx
MYXEDEMA COMA ≥10 Tx Tx
Definition: Manifestation of severe hypothyroidism, STAT endo consult; mortality >30%, commonly 2/2 hypercarbic resp failure
Precipitants: infection, MI, cold exposure, surgery, sedative drugs (esp. opioids) in a poorly controlled hypothyroid patient. Most common
in older women with hypothyroidism
Signs/symptoms: AMS (lethargy/obtundation, +/- coma), hypothermia, hypotension, bradycardia, ventricular arrhythmias, hypercarbic
resp failure, seizure. Exam: puffy hands and face, swollen lips, enlarged tongue. Labs: Na (be careful with IVF), Glu, T4, TSH
Treatment: do not wait for lab confirmation to start tx!
• Test and empirically treat adrenal insufficiency: hydrocortisone 100mg q8h until AI ruled out. Give steroids BEFORE T4 (if
concomitant AI, replacing thyroid first will catabolize residual cortisol and cause HoTN/death). Draw serum cortisol prior to rx.
• Levothyroxine (T4) Loading dose 200-400 mcg IV followed by 50-100 mcg IV QD until able to take T4 orally. Favor low end of range
if elderly or at risk of cardiac complications (MI, arrhythmia).
• Liothyronine (T3) Loading dose 5-20 mcg followed by 2.5-10 mcg q8h, watch for rebound hypermetabolism.
• Monitor FT4 and T3 Q1-2 days, avoiding very high T3 levels.
• Patients are hypometabolic: use lower drug doses at lower frequency, avoid mental status-altering meds.
AMIODARONE-INDUCED THYROID DISEASE
Check TSH prior to treatment, q4-6 mo while on amio, and for 1 yr after amio discontinued
• Typical response to amio acutely: TSH (2-3x nl), T4 and FT4, T3, rT3  levels return to normal in 3-6 months
Amiodarone-induced hypothyroidism: due to Wolff-Chaikoff or thyroiditis
Amiodarone-induced hyperthyroidism
 Type 1: synthesis of T4 and T3 due to iodine, usually will see in pts with latent Graves’ or goiter. Seen early during amiodarone Rx
Tx: methimazole
 Type 2: direct toxicity of drug causing thyroiditis, stored hormone release w/o synthesis. Seen late during or after amiodarone Rx. Tx:
40-60 mg/day prednisone x 1-3mo followed by taper
 If unknown: tx with methimazole and prednisone. Rapid response  Type 2, taper methimazole. Poor response  Type 1, taper
steroid
 Okay to continue amiodarone, esp. if Type 1 (amiodarone prevents T4  T3 conversion)

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Endocrinology Thyroid Disorders & Male Hypogonadism

H Y P E R T H Y R O I D I S M (Thyroid 2016; 26:1343)
Definition: low TSH with high T3/T4 (primary) or high/normal TSH with high T3/T4 (secondary/central)
Signs/symptoms: general (weight, appetite, heat intolerance, tremor, weakness), CV (palpitations, afib, systolic HTN), hyper-
defecation, dyspnea, sweating, anxiety, emotional lability, urinary frequency, abnormal menses, osteoporosis
• Exam: goiter +/- thyroid bruit, lid lag, exophthalmos and pretibial myxedema (Graves’ only), hyperreflexia and tremor
• Apathetic thyrotoxicosis: depression, weakness seen in elderly TSH FT4 Total T3
Labs: HDL, LDL, normocytic anemia, Ca, AlkP, Glu Primary   
Workup: 1) TSI and TBII (⊕ in Graves’), 2) RAIU (not for amio-induced or if Central /nl  
recent IV contrast), 3) thyroid US w/ Doppler
Subclinical  nl nl
Causes:
• 1°: Graves’ disease (most common, positive TSI or TBI establishes diagnosis), toxic adenoma (TA), toxic multinodular goiter
(TMG), transient thyroiditis (lymphocytic, granulomatous, postpartum, viral), drugs (amio, iodine, lithium), iatrogenic (radiation,
palpation), exogenous T3 or T4 ingestion (low thyroglobulin), HCG-mediated, struma ovarii.
• 2°: see Pituitary Disorders
Treatment: β-blocker for adrenergic symptoms (e.g., metoprolol, propranolol)
• Graves’ disease: thionamides (methimazole > PTU due to hepatotoxicity, though PTU preferred in 1st trimester of pregnancy),
radioiodine (risk of ophthalmopathy), thyroidectomy (watch for hypoparathyroidism). Monitor total T3 and fT4 q6wks.
• If using thionamides: obtain baseline CBC w/ diff (10% of patients have neutropenia that resolves with tx (Clin Endo 2021;94:473));
risk of agranulocytosis: routine ANC monitoring not recommended but CBC w/ diff recommended at earliest sign of febrile illness +
discontinue drug until result available
• Toxic adenoma or multinodular goiter: radioiodine, surgery, less commonly thionamides
T H Y R O I D S T O R M (Thyroid 2016; 26:1343)
Definition: Manifestation of severe thyrotoxicosis, STAT endocrine consult. Mortality rate 10-30%, 2/2 cardiovascular collapse
Precipitants: surgery (any), trauma, infection, iodine load (incl. amiodarone), irregular use/cessation of antithyroid drugs
Signs/symptoms: AMS (agitation, delirium, psychosis, coma), hyperpyrexia, tachycardia, atrial arrhythmias, CHF
• Exam: goiter, tremor, warm/moist skin, exophthalmos (Graves’)
Labs/dx: T4/T3, TSH, Burch-Wartofsky Point Scale (BWPS) ≥ 45 highly suggestive
Treatment: Patients are hypermetabolic and will clear drugs quickly
• Βeta blocker: e.g., propranolol 60-80 mg PO Q4-6H (only propranolol decreases T4T3 conversion), doses up to 2g/d. Titrate to
sx and HR (i.e., <80). Can also use esmolol gtt for rapid titration (esp. pts who may not tolerate propranolol, e.g., HF)
• Anti-thyroid meds: only stop formation of new hormone, not release of stored hormone
o Methimazole (20mg q4h-q6h) is preferred unless pt is critically ill. PTU (200mg q4h-q6h) decreases T4T3 but higher rates of
fulminant hepatic necrosis.
• Iodine (100-250mg q6h-q8h) blocks release of thyroid hormone, must be given at least 1h after thionamide to prevent use as
substrate for new hormone synthesis in TA/TMG; can cause Jod-Basedow (iodine-induced hyperthyroid) in toxic adenoma and Wolff-
Chaikoff (iodine-induced hypothyroid) in Graves
• Hydrocortisone (100mg q8h) to reduce T4→T3 conversion
• Cholestyramine (4 g PO qid) to reduce enterohepatic recycling of thyroid hormone
• Plasmapheresis for those unable to take thionamides and urgently being prepared for thyroidectomy
M A L E H Y P O G O N A D I S M (J Clin Endocrinol Metab 2018;103:1715)
Definitions: Clinical syndrome that results from a failure of the testes to produce physiologic levels of testosterone and/or normal number
of spermatozoa due to pathology at the testicular level (1°), hypothalamus/pituitary (2°), or both
o 1° causes (Low T, High FSH/LH): Klinefelter, cryptorchidism, testicular radiation, orchitis, myotonic dystrophy, HIV
o 2° causes (Low T, Low FSH/LH): hyperprolactinemia, obesity, Fe overload, opioids, glucocorticoids, androgens (e.g.
supplementation), progestins, GnRH agonists
o 3° causes (rare): impaired GnRH signaling due to tumors, radiation to the brain, Kallmann, severe malnutrition.
Signs/Symptoms: loss of axillary/pubic body hair, reduced libido, erectile dysfunction, gynecomastia, low sperm count, decreased energy,
depressive mood, normocytic anemia, reduced muscle bulk, increased body fat, osteoporosis
Diagnosis:
o Measure 8am-10am fasting total testosterone x2 (nl total T range ~ 300-800)
 Measure free testosterone only if c/f ∆ in SHBG (obesity, nephrotic syndrome, steroids, HIV, cirrhosis, thyroid dz)
o If testosterone level is low on both measurements, measure LH/FSH to determine 1° vs 2° etiology
 If 2° measure Fe studies, other pituitary hormones, & consider imaging (see Pituitary Disorders); for 1° consider karyotype.
Management:
o Testosterone therapy is the mainstay of treatment to induce/maintain 2° sex characteristics and address symptoms
 Formulations: intramuscular (weekly, q2w, and monthly), transdermal gel, patches, tablets
 SE: site reactions, acne, oiliness of skin, no large RCT to study cardiovascular risk/MACE or VTE
 Contraindications: prostate ca, breast ca, erythrocytosis, severe BPH, untreated OSA, severe LUTS, planning fertility
Monitoring:
o Evaluate around 3-6mo after initiation to assess response to treatment and measure concentrations, then annually
 Goal level is mid-normal physiologic range (300-800)
o Check baseline Hct and 3-6mo after tx, if Hct >54% stop therapy, re-initiate at reduced dose once Hct reaches safe level
o If patient chooses to monitor for prostate ca, perform DRE and measure PSA before treatment and 3-12mo after starting (NEJM 2023)
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Allergy & Immunology Drug & Contrast Allergy

A D V E R S E D R U G R E A C T I O N S ( A D R S ) (Allergy 2019; 74: 1457)
KEY History: Drug, date, dose, route, doses/days into course, co-administered meds, coinciding infections, sx, severity
(home/office/ED/hospital/ICU), treatment given, exposures since
Document appropriately in EPIC allergy section. Include rxn, date, intolerance vs reaction, other meds tolerated

ADRs defined by WHO as any noxious/unintended/undesired drug effect that occurs at doses used for prevention, diagnosis, or treatment.
• Type A = predictable (85-90%): dose-dependent reactions related to a drug’s known pharmacological action which occur in
otherwise healthy patients if given sufficient dose and exposure (e.g., gastritis after NSAIDs)
• Type B = unpredictable (10-15%): dose-independent, unrelated to pharm action, occurs only in susceptible pts
o Drug intolerance: undesirable effect that occurs at low and sometimes subtherapeutic doses w/o abnormalities of
metabolism/excretion/bioavailability (e.g., tinnitus after aspirin)
o Drug idiosyncrasy: abnormal effect caused by underlying abnormalities of metabolism/excretion/bioavailability (e.g., hemolysis
after antioxidant drug in G6PD deficiency)
o Pseudo-allergic reaction (formerly known as anaphylactoid): direct release of mediators from mast cells and basophils rather
than IgE antibodies (e.g., flushing during vancomycin infusion, exacerbation of asthma/rhinitis w/ aspirin in AERD, opiate pruritis)
o Drug allergy (5-10% of all ADRs): immunologically-mediated hypersensitivity reactions, including IgE mediated

H Y P E R S E N S I T I V I T Y R E A C T I O N S (Gell and Coombs Classification) (Clin All 1998;18:515)

Type Reaction Mechanism Presentations Timing
Ig-E mediated degranulation of mast cells due to antigen Anaphylaxis, allergic rhinitis, Min-hrs
I IgE-mediated, binding and cross-linking of IgE (usually
allergic asthma, urticaria,
Immediate
Anaphylaxis Pathway angioedema, hypotension 1 hour)
II Antibody IgM/IgG antigen interactions on target cell surfaces Drug-induced cytopenia Varies
Immune- Immune complex formation & deposition in tissues → Serum sickness, vasculitis, 1-3 wks
III
complex complement activation → local/systemic inflammation drug induced lupus
Ag activates T cells → Ag later binds to activated T cells → Days to
Cell-mediated, Contact dermatitis, SJS/TEN,
IV cytokine release → macrophage & cytotoxic T cell weeks
delayed DRESS, AGEP
accumulation

C L I N I C A L M A N I F E S T A T I O N S O F D R U G A L L E R G Y (AACI 2018;14:60)
Organ Manifestation Clinical Features Timing Causative Drugs
Urticaria, angioedema,
Skin drug exanthem, For information on skin manifestations of drug allergy, see Dermatology: Drug Eruptions
SJS/TEN, AGEP
Varies, but in general:
PCN, sulfa drugs, AEDs,
-Hemolytic anemia: acute
Blood Hemolytic anemia, thrombocytopenia, leukopenia cephalosporins, quinine, heparin,
-Drug-induced TMA: acute
thiazides
or subacute
Sulfonamides, phenothiazines, anti-
Varies, can be acute or
Liver Hepatitis, cholestatic jaundice TB drugs, carbamazepine,
chronic
erythromycin, allopurinol
PCNs, sulfonamides, allopurinol,
Kidney Interstitial nephritis, glomerulonephritis Varies, days to months
PPIs, ACEi, NSAIDs
Urticaria, angioedema, Abx, NM blockers, anesthetics,
Immediate (usually within
Anaphylaxis bronchospasm, GI, contrast, recombinant proteins (e.g.,
1 hr)
hypotension omalizumab)
Rash, fever, eos, hepatic AEDs, sulfa drugs, minocycline,
DRESS 2-8 weeks
dysfunction, LAD allopurinol, mAB (monoclonal Ab)
Multi- Hydralazine, procainamide, INH,
Drug induced lupus Arthralgias, myalgias,
organ Months to years quinidine, minocycline, abx, anti-
erythematosus fever, malaise
TNF
1-2 weeks Heterologous Ab, infliximab, mAbs,
Serum sickness Arthralgias, urticaria, fever
allopurinol, thiazides, abx, bupropion
Cutaneous or visceral Sulfa abx and diuretics, mAbs,
Vasculitis
vasculitis hydralazine, levamisole, PTU

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Allergy & Immunology Drug & Contrast Allergy

D I A G N O S I S (Drug Allergy Practice Parameter 2010)
• Labs (sometimes helpful): CBC w/ diff (eos), LFTs, Cr, tryptase (if anaphylaxis), auto-Abs (e.g., anti-histone in drug induced lupus)
• Skin testing: evaluates for drug-specific IgE antibodies for a limited # of meds. NPV of penicillin skin testing = 95%.
• Deliberate rechallenge = graded challenge = test dose procedure
o Used when there is a low suspicion for true allergic reaction to a medication. Does NOT assess cross-reactivity of
structurally-related drugs. Contraindication = severe non-IgE mediated HSR (ex: DRESS, SJS, etc.)
o How to order: Antibiotic Test Dose in Epic order sets (can also type “penicillin” “allergy” “test dose”)
 Automatically orders the rescue medications, nursing communication orders, and fills in doses of desired med (FYI test
dose = 1/10 of rx dose for IV meds and ¼ of rx dose for oral meds)
o If no reaction: patient is not allergic to that agent and can safely receive it, please update allergy list
 If agent was a related agent (e.g., CTX administered in PCN-allergic pt): update “comments”
 If agent was same agent as recorded allergy (e.g., PCN administered in PCN-allergic pt): remove allergy
o If ⊕ reaction: Anaphylaxis pathway: Epi 1:1000 IM (0.3 mg), Benadryl 50mg IV/PO, page allergy fellow, & complete a
Medication Safety Report.

D R U G D E S E N S I T I Z A T I O N (JACI 2010;125:S126) | Ellucid-Drug Desensitization and Test Dose Administration

• Indications: ⊕skin test, ⊕test dose, or h/o severe type I HSR AND no alt. tx. ONLY for Type I (IgE-mediated) rxns
• Method: administer drug with increasing doses over hours such that it induces state of TEMPORARY tolerance
• At MGH, consult Allergy. Generally, desensitization needs to be done in the ICU but there are exceptions (e.g., chemo, aspirin)
• If patient discontinues medication: procedure must be performed again if pt stops medication for >2-3 half-lives
P E N I C I L L I N & C E P H A L O S P O R I N A L L E R G Y | Ellucid -Penicillin and Cephalosporin Hypersensitivity Pathway
• 10% of pts report a PCN allergy, but 90% of patients with a h/o PCN allergy can tolerate PCN (JACI 2010;125:S126)
• 80% of pts with IgE-mediated allergy to penicillin will lose their penicillin sensitivity over 10-year period (AAAI 2019; 321:188)
• Patients with PCN allergy have a <1% cross reactivity to carbapenems (CID 2014;59:1113); and <2% of patients w/ skin test-
proven sensitivity to PCN will react to cephalosporins (Annals 2004;141:16)
• Allergic determinants of cephalosporins can be derived from the beta-lactam structure, but in later (3rd/4th gen) cephalosporins,
they are most commonly derived from the R-group.
• Refer for outpt PCN skin testing if (Allergy Referal) if: unclear reaction and likely requirement for that drug in the future
• See Penicillin Cephalosporin Hypersensitivity Pathway for guidance on inpatient test dose procedure in pts reporting PCN allergy

OTHER COMMON DRUG ALLERGIES

• Taxanes/platinum-based Chemotherapy: differentiate infusion reaction (SIRS response) from anaphylaxis (type I HSR). Platinum
agents assoc with IgE HSR. Taxanes generally non-IgE mediated, premed usually effective (AAAAI 2009;102:179)
• Allopurinol hypersensitivity syndrome: rash, fever, hepatitis, AKI usually within 4-8 wks. Testing for HLA-B5801 in pts at elev risk
(patients of Southeast Asian descent and African American) recommended prior to starting (ACR Guideline 2020)
• Aspirin/NSAIDs (JACI 2021; 148:283): wide spectrum of drug-induced allergic reactions, including exacerbation of underlying
respiratory disease, urticaria, angioedema, anaphylaxis, and rarely pneumonitis and meningitis
o Management: avoid NSAIDs (COX-1 inhibitors). If NSAIDs are necessary (ie aspirin for ACS), consult Allergy.
o Aspirin-Exacerbated Respiratory Disease (AERD) (aka Samter’s Triad): triad of asthma, rhinosinusitis w/ nasal polyps, and
ASA/NSAID sensitivity (nasal congestion, bronchospasm). Tx: Avoidance of NSAIDs, desensitization and daily uninterrupted
therapy, leukotriene-modifying drugs, or biologics (omalizumab, mepolizumab, dupilumab) (JACI 2021; 148:283)
I V C O N T R A S T M E D I A (ACR Guidelines 2021) | Ellucid -Allergy Premedication | See Contrast for details on contrast reactions
Type/Path Epidemiology Presentation Clinical pearls Pre-Treatment (MGH protocol)
Elective (13h protocol)
Immediate pruritus,
Seafood allergy is NOT a Prednisone 50mg PO at 13, 7, & 1h prior AND
urticaria,
Pseudoallergic Mild rxn: contraindication. Benadryl 50mg PO 1h prior
angioedema, airway
Direct 0.6% pts Oral contrast is NOT Urgent (4-5h)
obstruction, HoTN,
stimulation of contraindicated in a patient Methylprednisolone 40mg IV now & q4h until scan
abd pain. Called
mast cells / Severe rxn: with IV contrast allergy, very AND Benadryl 50mg IV 1h prior
pseudoallergic bc
basophils 0.04% pts rare pseudo-allergic Emergent (no data) (1h)
not immune rxn -can
reactions. Methylpred 40mg IV AND Benadryl 50mg IV @ 1h
still cause danger.
prior
>1h - 1 wk. Usually
Delayed 0.5-14% of Unknown efficacy to steroid/antihistamine ppx. Not
mild, skin eruption. Tx: Supportive care
T cell-mediated patients specifically advocated
Can be more severe

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Allergy & Immunology Angioedema & Anaphylaxis

A N G I O E D E M A (Allergy 2018;73:1393) | (Int J EM 2017)
• Definition: localized non-pitting swelling of skin or mucosal tissue due to interstitial edema; Usually affects areas of loose connective
tissue including face, throat, lips, extremities, genitals, bowels. Often asymmetric. Occurs in min-hrs after exposure and resolves
within 1-3d. Common triggers: food, insect bites, drugs, temp, delayed pressure, solar, vibratory, cholinergic, contact, and aquagenic
Type Symptoms Triggers
Localized swelling Common allergens, ASA, NSAIDs, CCB, opioids, contrast dye, tPA, platinum-based
Histamine Urticaria/pruritis chemo, β-lactams, metoprolol, sirolimus/everolimus, risperidone,
(mast-cell idiopathic/spontaneous
Bronchospasm
mediated)
+/- hypotension
ACEi: 0.1-0.7% pts; may occur any time during treatment and recur 4-6 wks after
Localized swelling w/in 24- cessation. Consider also in ARBs, DPP-4 inhibitors.
36h exposure C1 inhibitor deficiency: Either due to AD inheritance (present at early age) or
Abd cramping/pain acquired (usually lymphoproliferative disorder). Screen: ↓C4, normal C3.
Bradykinin
NO urticaria Hereditary Angioedema: begins in childhood, worsens in puberty. Prodromal sxs
Usually longer w/ worse include erythema marginatum
symptoms TPA mediated angioedema: tPA activates complement system and leads to ↑
histamine release and ↑ bradykinin levels.
• Work up: CBC w diff, BMP, LFTs, CRP, ESR, C4 level, C1 inhibitor level, C1 inhibitor function, & tryptase (see below)
• Treatment: in ALL patients ABCs, secure airway; involve ENT for awake nasotracheal intubation
o If urticaria, multisystem involvement, or underlying illness/infection: remove exposure → treat like anaphylaxis (see below)
o If no urticaria/pruritis: 1 gram TXA (bradykinin-mediated angioedema does not respond to epinephrine or steroids):
 On ACEi: stop ACEi → supportive care (if severe, consider treating similar to Hereditary Angioedema [mixed evidence]),
add ACEi to allergy list
 Known hereditary or acquired angioedema: page Allergy for C1-inhibitor (ecallantide, icatibant). FFP 2nd line.
 Not on ACE; no known disorder: H1 antihistamines + methylpred → PO pred (5-7 d taper) + H1 antihistamine
• Follow-up: Place Allergy/Immunology referral on discharge
A N A P H Y L A X I S (JACI 2020,145:4) | (AAAI 132:124-176) | Anaphylaxis Treatment Protocol
Type Mechanism Triggers
Food (e.g., nuts, shellfish, milk, eggs), insect venom, meds (e.g., NSAIDs, β-
IgE mediated
Immunologic lactams, biologics), latex, occupational allergens, aeroallergens
Non-IgE mediated NSAIDs, HMW dextrans, biologics, contrast
Direct mast cell
Nonimmunologic Physical factors (exercise, heat, cold, UV light, XRT), EtOH, meds (opioids)
activation
Idiopathic No apparent trigger Mastocytosis/clonal mast cell disorder, previously unrecognized allergen
• S/Sx: (1) Cutaneous = angioedema, urticaria, flushing, pruritis; (2) Respiratory = dyspnea, wheeze, upper airway angioedema, rhinitis;
(3) GI = nausea, vomiting, diarrhea; (4) Cardiovascular = hypotension. Can have biphasic reaction: resolution w/ return of symptoms
1-72h (usually <12) after initial symptom resolution despite no further exposure to trigger (4-20% pts)
• Diagnostic criteria: 1 of 3 must be met
1) Acute onset (min-hr) of skin ± mucosal involvement AND either respiratory sx OR hypotension (age appropriate)
2) Two or more of the following after exposure to LIKELY allergen: skin/mucosa swelling, respiratory sx, HoTN, persistent GI sx
3) Low BP (SBP<90 or >30% drop from baseline) after exposure to KNOWN allergen for patient
• Labs: tryptase (within 15min-3h of symptom onset & 24h after sx resolve to establish baseline). Values ≥1.2x baseline + 2ng/dL =
mast cell activation. Normal levels do not rule out anaphylaxis (normal in 37%). Consider plasma histamine (peaks in 5-15 min).
• Treatment: Establish and maintain airway, administer oxygen/IVF (1-2L) and lie pt flat/Tberg for hypotension, remove trigger
o Epinephrine: 1st line. ONLY medication that reverses airflow obstruction & prevents cardiovascular collapse. Dosing:
epinephrine (conc 1mg/mL) 0.3-0.5mg IM in mid-outer thigh. May repeat q5-15min; if >3 doses required, consider continuous
epi gtt (1-10mcg/min). If on beta blockers AND resistant to epinephrine, glucagon (1-5mg bolus → gtt @ 5-15mcg/min)
o Adjunctive agents: Albuterol (stacked nebs x 3) PRN wheezing/cough/SOB
 H1 antihistamines: PRN for pruritis/urticaria. Does NOT treat airway obstruction or hypotension! Benadryl 25-50mg
 H2 antihistamines: famotidine 20mg IV or PO
 Methylprednisolone IV or IM: 40mg if weight <120kg, 80mg if weight >= 120 kg. No evidence to prevent biphasic rxn.
May be beneficial if (1) severe sx requiring hospitalization (2) known asthma (3) significant and persistent bronchospasm
o Make sure to discharge home with EpiPen & refer to Allergy
o If h/o anaphylaxis to stinging insect, refer for skin testing. If +, consider SQ venom immunotherapy, which decreases risk of
subsequent anaphylaxis from 50-60% to 2-3% (NNT = 2) (NEJM 2014;370:1432)
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Allergy & Immunology Mast Cell Disorders

M A S T C E L L B A S I C S (NEJM 2015:373;163)
• When activated, mast cells degranulate and release vasoactive & pro-inflammatory mediators such as histamine, heparin,
serotonin, leukotrienes, prostaglandins, proteases (including tryptase), cytokines (including TNF), etc.
• Signs and symptoms associated with mast cell activation are similar to those of allergic & anaphylactic reaction. However,
angioedema, hives and wheezing are uncommon in mastocytosis.
o Cutaneous: flushing, pruritis, urticaria, angioedema
o GI: heartburn & nausea (histamine  hypersecretion of acid from parietal cells), diarrhea, abdominal cramps
o Cardiovascular: tachycardia, hypotension, presyncope, and syncope
o Neuro: fatigue, lethargy, memory and concentration problems, headache
o Respiratory: wheezing (bronchospastic cough), nasal congestion
• Triggers for mast cell activation: temp changes (e.g., hot showers), exercise, alcohol/spicy food ingestion, mechanical irritation,
stress, insect stings, certain medications (opioids, NSAIDs, muscle relaxants). Can also be spontaneous.
M A S T O C Y T O S I S (JCCN2018;16:1500)
• Heterogenous group of rare disorders (~1:10,000) characterized by excess mast cell proliferation and accumulation.
• Symptoms are primarily related to episodic release of mast cell mediators (lasts 30 min – few hours)
Mastocytosis
Primarily presents as systemic mastocytosis (SM)
Epidemiology
Rare presentations of cutaneous mastocytosis (primarily in infants and young children)
Multifocal infiltration of mast cells in various internal organs
Organ systems Bone marrow is involved in virtually all patients
Skin more common with indolent systemic mastocytosis.
1. Indolent SM (most common): no end-organ dysfunction
2. Smoldering SM
3. SM associated with non-mast cell hematologic neoplasm
Variants
4. Aggressive systemic mastocytosis: + end-organ dysfunction
5. Malignancy: mast cell leukemia, mast cell sarcoma
6. Cutaneous only: urticaria pigmentosa (UP), mastocytoma of skin, diffuse cutaneous mastocytosis
Due to mediator release = flushing, pruritis, urticaria
Cutaneous
Due to mast cell infiltration = maculopapular cutaneous mastocytosis (most common; fixed, salmon/tan lesions;
manifestations
predominate on trunk/limbs), bullous eruptions, mastocytomas, telangiectasis
• GI (50%): n/v/bloating, chronic diarrhea, chronic abdominal pain, steatorrhea, GERD, gastroduodenal ulcers,
hepatomegaly. Liver infiltration: ↑alk phos, AST, ALT, GGT, portal HTN, ascites if advanced SM.
• MSK: fibromyalgia-like pain, osteoporosis (due to prolonged TNF/IL-6), sclerotic/lytic lesions
Systemic
• CV: episodes of tachycardia, hypotension, vasodilation
manifestations
• Heme (50%): anemia (most common), thrombocytopenia, eosinophilia, LAD, splenomegaly
• Neuro: anxiety, mood disorder, insomnia, depression, headache, hypersomnolence, irritability
• Systemic: fatigue, cachexia
• Recurrent symptoms of mast cell degranulation
*Darier’s Sign: If UP detected, rub
• Urticaria pigmentosa (UP) +/- Darier’s sign* affected skin. Erythema/urticaria around
Characteristic
• Hypotensive anaphylaxis, especially with stinging insects lesion within 5 mins suggestive of mast
clinical
• Unexplained osteoporosis and pathologic bone fractures cells within lesion.
presentations
• Sclerotic or lytic bone lesions prompting malignancy eval
• Suspected hematologic disease (heme abnormalities, splenomegaly, fatigue, weight loss)
Lab findings Elevated baseline serum tryptase (>20ng/mL) in non-symptomatic state strongly suggestive of SM.
Diagnosis BMBx/aspirate. Mast cell collections in affected organ. A/w KIT gain of function mutation. See WHO dx criteria).
M A S T C E L L A C T I V A T I O N S Y N D R O M E ( M C A S ) (JACI 2022;10:1941-50)
Recurrent episodes of symptoms of anaphylaxis (hives, swelling, HoTN,
diarrhea, SOB) w/o consistent trigger and w/o clonal population of mast cells.
• Dx criteria: 1) episodic, objective s/s of mast cell release involving
>2 organ systems AND 2) corresponding elevations in mast cell
mediators (preferred: tryptase 120% bl + 2ng/mL) AND 3) respond to
medications that stabilize MC/inhibit MC mediators/block mediator
release (e.g., anti-histamines, cromolyn, anti-leukotrienes). Less-
preferred for #2: urine histamine/PGD2 metabolites >200% individual’s
baseline, less specific
• Tx: anaphylaxis tx as indicated, otherwise H1/H2 blockers, ASA, anti-
leukotrienes, omalizumab (blocks IgE). BWH Mastocytosis center
• For those w/o clear dx, provisional dx “Other MCAD” while search for
other causes of sx (see diagram, JACI 2022;10:1941-50)
• DDx “other MCAD”: other urticaria, angioedema, food
intolerance/aversion & GI d/o, rheum/joint d/o, acute/chronic infx,
endocrine/neuro d/o, intoxication/poisoning/med effects, psych d/o.
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Allergy & Immunology Primary Immunodeficiency

P R I M A R Y I M M U N O D E F I C I E N C Y D I S O R D E R S (JACI 2016 1109-1110,)
Definition: inherited deficits of immune system → increased
incidence/severity/frequency of infections
• Prevalence: 1/1200-2000 pts
• Warning signs in adults: ≥4 infection requiring antibiotics/year (ear
infxn, sinusitis, bronchitis, PNA, otitis media), infection not
responsive to antibiotics, ≥2 severe infections (osteo, septic
arthritis, meningitis, sepsis), ≥2 PNA within 3 years, chronic
diarrhea, recurrent deep abscesses, persistent fungal infection,
persistent thrush, infection w/ benign mycobacteria, relevant FH
• H&P: developmental hx, FH, age at onset, frequency & type of
infections, syndromic features, autoimmune dz,
o Most severe forms are on MA newborn screen; mild
forms go undetected into adulthood (e.g. antibody def)
• Need to r/o 2º causes of immunodeficiency (HIV, immunosuppressants (rituximab and other mAbs, chronic glucocorticoid use),
malignancy, radiation, cirrhosis, diabetes, nephrotic syndrome, SLE, RA, asplenia)
• General principles of management: vaccination, abx ppx, ↑risk of malignancy, immunoglobulin replacement, HSCT
Disorder Presentation Infectious Organisms Testing (JACI 2018 38: 129-143)
Any age
- Sinusitis, PNA, meningitis
(recurrent nisserial infections) → Complement levels:
think late complement def (C5-C8) C1q, C1s, C2, C4, Factor H, Factor I,
Complement - Lupus-like syndrome → early Bacteria: encapsulated esp. Neisseria,
Thrombomodulin, CD46, C1 inhibitor,
(5%) gonococcal infections
complement def C1/C1s/C2/C4a/b CD59, CD55
- Rheumatoid disorders CH50+AH50 (alt pathway)
INNATE

- Atypical AUS
- Protein losing enteropathy
ANC (↓SCN, ↑LAD), ELANE gene in SCN,
Infancy/childhood
Bacteria: S aureus, PsA, Serratia, Oxidative burst via DHR/NBT test for CGD,
Phagocyte - Oral, lymphadenitis, skin and soft
Klebsiella, non-TB mycobacteria, Other tests to order for: SCN gene
abnormalities tissue, liver, lung, bone, anorectal
nocardia abnormalities, WAS, CSF3R, MKL1,
(10%) - Unusually severe infections
Fungi: Candida, Aspergillus G6PD, GATA2, CYBB, NCF1,
- Granulomas, poor wound healing
*On outpt Invitae genetic panel
Infancy
Flow cytometry
- Oral thrush
Bacteria: Mycobacteria Anergy/proliferation tests
T cell subset - Diarrhea (enteropathy)
Viruses: CMV, adenovirus STAT1, AIRE if chronic mucocutaneous
defects (5%) - Respiratory Infections
Fungi: Candida, PJP candidiasis or APECED, FOXP3 (IPEX),
- ILD
IL2RA, CTLA4
- pancytopenia
>6 mos, can present in adulthood
SPEP (IgG, IgA, IgM), IgG subclasses, flow
- Recurrent sinusitis, otitis media,
cytometry
PNA, bronchiectasis Bacteria: H flu, Strep, Staph, Moraxella
Vaccine response
ADAPTIVE

B cell / - Chronic GI malabsorption, cat, PsA, mycoplasma pneumoniae

Polysaccharide PPSV23 titers:
Antibody diarrhea Virus: Enterovirus (esp. with IgA
≥70% of serotypes ≥1.3 = adequate. If not,
(65%) - Autoimmune disease (29% in deficiency)
give PPSV23 & repeat titers in 4-6 wks
CVID) (Blood 2012;119:1650) Parasites: Giardia
Protein: tetanus, diphtheria IgG
- Anaphylaxis to blood products
Conjugated: Hib IgG
(IgA deficiency)
<6 mos old, FTT Bacteria: Salmonella, Listeria, non-TB
- Oral thrush, viral infections mycobacteria B Cell Enumeration (CMF)
Combined B - Chronic diarrhea Viruses: CMV, EBV, VZV As above for B & T cell deficiencies
& T cell (15%) - Absent thymus Fungi: Candida, Aspergillus, Adenosine deaminase deficiency
- Active disease to live vaccines cryptococcus, histoplasmosis Avoid live vaccines
- Autoimmune cytopenias Parasites: PJP, toxo, Cryptosporidium
I M M U N O G L O B U L I N R E P L A C E M E N T (JACI 2017;139:S1)
• Manufactured using donor pools of donated human plasma & contains IgG antibodies, administered as IVIG or SQ Ig
• Replaces antibodies and is anti-inflammatory by inducing autophagy in cells associated w/ Th1 inflammation.
• Starting doses: 400-800 mg/kg q3-4 wks for trough level >500-600 mg/dL (higher in pregnancy & bronchiectasis)
• Consider HBV serologies prior to IVIG: can’t check for 3-4mo after IVIG. If patient already got IVIG, consider HBV PCR
• IVIG in infection depends on host & infection. If CVID w/ infection, can check IgG levels. Beneficial in CMV pneumonitis in solid
organ tx recipients, rotaviral enterocolitis & bacterial infections in lymphoproliferative dz (e.g., CLL)
T H E R A P E U T I C U S E O F V A C C I N E S I N P A T I E N T S W I T H P I D (JACI 2018;141:474)
• ALL patients with PID can receive INACTIVATED vaccines according to routine schedule. Prioritize flu, HPV, PNA. For LIVE
ATTENUATED vaccine safety/benefit, see UpToDate Table
• Pts on IVIG have adequate titers to measles, mumps, varicella, rubella, pneumococci, Hib, and meningococcus (variable). If exposed
to an infection requiring “hyperimmune” Ig (rabies, HBV, tetanus), should still receive pathogen-specific Ig.
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Neurology Altered Mental Status

CAUSES OF AMS
• AMS is any change in patient’s baseline mental status and can include obtundation/non-responsiveness, agitation, lethargy,
disorientation, hypoactivity, hyperactivity, etc.
• Major categories include 1) Metabolic, 2) Infectious, 3) Drugs/Toxins/Medications, 4) Primary CNS, 5) Delirium
• Duration: flow diagram (below)
AEIOU TIPS: Alcohol (intox, HE, withdrawal/DTs, Wernicke’s)/Arrythmia, Electrolyte (high or low Na/iCa/Mg/Phos)/Endocrine (glucose,
pituitary, thyroid, parathyroid, adrenal), Infection (sepsis vs 1° CNS: encephalitis, meningitis, abscess), Oxygen (hypoxia,
hypercarbia)/Overdose (opiate), Uremia/Urine retention, Trauma/Tumor/TTP/Temp, Iatrogenic (see MAR below), Psych/Poison, Seizure
(+post-ictal)/Stroke/Syncope

APPROACH TO ACUTE AMS

• ABCs & vitals: call Rapid Response (+/- RICU if concern for airway, +/- Code Stroke if focal or high risk for head bleed/clot)
• Hx: baseline functional status, last known well, time course, previous AMS, recent clinical events, past medical history (i.e.
neurodengerative disease/dementia, hx CVA, seizure disorder, cranial mets)
o MAR: (stopped/started, withdrawal/overdose) insulin, benzo, opioid, steroid, anticholinergic, antihistamine, antiHTN, AED,
anti/dopaminergic, digoxin, Li, ASA, OTCs, MSK relaxers, abx (cefepime/cephalosporins, PCNs, FQs) (Neurology 2016;86:963)
o Consider catatonia, NMS, serotonin syndrome and see Catatonia, NMS, & Serotonin Syndrome
• Neuro Exam:
o Arousable (GCS): commands, attention, cranial nerve or focal weakness, abnormal movements/nystagmus/ataxia, meningismus
o Not arousable: coma exam: pupils, nystagmus, doll’s eyes, corneal, grimace, cough/gag, w/d to pain, posturing (JNNP 2001;71:i13)
o Other helpful findings: trauma (c-spine, hip frx, fat embolus), asterixis/myoclonus (toxic, metabolic), volume status, cherry red
discoloration (CO), findings c/f toxidromes, incontinence/tongue laceration (seizure)
• Dx:
o FSBG, CBC/diff, BMP, LFTs, TFTs, INR, lactate, VBG, UA, EKG, CXR, bladder scan
o Consider based on initial assessment: cultures, toxicology, drug levels, cortisol, B12, CK, CTH ± CTA head/neck, EEG, etc.
NEUROLOGIC EXAMINATION
Arousal/Mentation Brainstem Functions Motor Sensory
Arousal level: Pupils (CN 2/3):
Muscle strength: Observe
“AVPU scale” - Absent light reflex (upper brainstem injury, excessive sedation)
spont. movements (e.g.,
1) Alert - Bilateral fixed, dilated (upper brainstem injury/compression)
symmetric? Antigravity?); if
2) Verbal stimuli - Unilateral fixed, dilated (herniation w/ CN III compression)
mental status allows,
3) Painful stimuli - Pinpoint (opioids, pontine injury)
perform confrontational
4) Unresponsive Blink to threat or visual field testing if able (CN 2)
testing
Corneal reflexes (CN 5/7): absent (upper brainstem injury, deep
Orientation sedation), normal, or forceful closure
Sensory: compare
Extraocular eye movements (CN 3/4/6):
sensation to light touch
Attention (days of week - Conjugate lateral deviation (destructive or irritative lesions)
backwards) - Vertical disconjugate (“skew deviation”; structural)
Response to noxious
- Roving eyes (esp. if conjugate suggests metabolic cause)
stimuli in each extremity:
Language: more detailed Facial symmetry (CN 7): test at rest and on activation (smile)
(localizing > withdrawal >
exam: comprehension, Oculocephalic reflexes (CN 8): doll’s eye movement
extension)
fluency, repetition, naming Cough/gag (CN 9/10): if intubated, suction

A P P R O A C H T O S U B A C U T E A M S : consider Neurology consult prior to further extensive work-up

• Hx/Exam as above. DDx also includes: infection (HIV, Lyme, syphilis), autoimmune (paraneoplastic/anti-NMDA, sarcoid, CAPS/SLE,
Sjogren’s, ADEM, ALE, vasculitis), metabolic (thyroid, B1, B3, B12, Wilson’s), medications, toxidromes, HTN encephalopathy, hepatic
encephalopathy, PRES (tacro/cyclosporine), adrenal insufficiency/Cushings, porphyria (urine PBG)
• Dx:
o rEEG: for non-convulsive status epilepticus (NCSE); LTM: for intermittent seizures
o MRI with contrast: for stroke, malignancy, infxn/inflammatory process, Wernicke’s
o LP (CTH to r/o herniation first): see Lumbar Puncture, discuss advanced testing with Neurology
T R E A T M E N T O F A M S : diagnose and treat underlying cause; see disease-specific pages
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Neurology Dementia
I N I T I A L E V A L U A T I O N : should almost always be in the outpatient setting, can assess over time without acute illness or delirium
• Obtain collateral, determine symptom onset, ADLs/IADLs, assess safety, screen for depression
• Review medications for those with cognitive SEs (e.g., analgesics, anticholinergics, psychotropic medications, sedative-hypnotics)
• Assess cognitive impairment (MOCA >> MMSE), track score at subsequent visits
• Labs: CBC, TSH, BMP, B12; consider: tox screen, syphilis, Lyme, HIV, UA, metals, ESR, LFT, folate, B1 (AFP 2005;71:1745)
• Imaging: NCHCT or MRI brain (preferred) to r/o structural lesion (tumor), assess atrophy pattern and vascular dementia
• Inpatient eval considered for 1) any rapidly progressing dementia syndrome (c/s Neuro to discuss LP  RT-QuIC 14-3-3 in CSF
(CJD), ACE (sarcoid), autoimmune encephalitis, or 2) new dementia diagnosis in pts <55yo or with new focal deficit (eval stroke)
• Outpt Neurology referral to Memory/Cognitive clinic and formal neuropsychological testing
D E M E N T I A S Y N D R O M E S (Prog Neurol Psych 2012;16:11; BMJ Neurol Neurosurg Psych 2005;76:v15)
**Clinical phenotypes often overlap and may require years to differentiate**
Syndrome Presentation Exam Imaging Treatment
Gradually Progressive
Alzheimer Hippocampal (± global) • AChE-inhibitors
• Short term memory • Nml neuro exam (excluding
Dementia atrophy; ventriculomegaly,(mild-severe dz)
loss early; language & mental status)
(60-80%, mild ?microhemorrhages • NMDA-inhibitors
visuospatial deficits • Neuropsych: amnesia w/ short (cerebral amyloid
cognitive impairment (mod-severe dz)
(MCI) as precursor) • Apraxia in later stages memory span, alexia, agraphia angiopathy (CAA)) • Anti-amyloid abs
• Parkinsonism: resting tremor • AChE-inhibitors
• Fluctuations in
(can be absent), cogwheel (esp. rivastigmine)
attention/alertness
rigidity, bradykinesia, for memory sx
• Visual hallucinations
Lewy Body and stooped/shuffling gait • Carbidopa/levodopa
(LBD)
Parkinson’s • Parkinson’s dementia if motor Global volume loss trial for motor sx
• REM behavior d/o
Dementia sx >1y before dementia • Sx management of
• Falls/syncope
• Neuropsych: fluctuations w/ autonomic dysfxn
• Neuroleptic intolerance
intrusions and confabulation, • Avoid typical
• Memory problems late visuospatial impairment antipsychotics
Behavioral type • Management of
• May have frontal release
• Personality ∆ (disinhib., behavioral sx
signs (non-specific)
apathy, poor insight) Atrophy predominantly (consult psych)
Frontotemporal • 15-20% get motor neuron dz
• Stereotyped behaviors in frontal and temporal • AChE-inhibitors not
Dementia • Neuropsych testing: poor
1° prog aphasia type lobes helpful
impulse control, difficulty in
• Dysnomia, dysfluency, • Avoid NMDA-
organization
poor comprehension inhibitors
Stepwise Progressive
• Abrupt focal sx, • Focal deficits (depends on Cortical or subcortical • 2° stroke prevention
Vascular stepwise progression stroke location), can include: punctate lesions, and RF modification
Dementia • Depression common weakness, dysarthria, ataxia, white matter disease, • AChE-inhibitor for
• Hx: CVA, HTN, HLD, AF gait changes and volume-loss memory deficits
Rapidly Progressive (Ann Neurol 2008;64:97)
• Rapidly progressive sx • Myoclonus, exaggerated MRI: cortical
Prion Diseases in memory, startle response ribboning on DWI, • No tx
(Sporadic, Variant concentration, judgment • EPS (bradykinesia, nystagmus, subcortical • Death w/in 1y
Creutzfeldt-Jacob • Mean onset age ~60 for ataxia), UMN (hyperreflexia, hyperintensity on FLAIR (median disease
Disease) sporadic, 28 for variant babinski, spasticity) EEG: 1-Hz periodic duration 6mo)
• Younger→ ↑psych sx • LP: RT-QuIC>>14-3-3 epileptiform discharges
• Sx evolve days-weeks • Prominent psych features MRI: FLAIR
(more indolent possible) • Dyskinesias, rigidity • Immunotherapy:
Limbic hyperintensity or
steroids, IVIG,
Encephalitis • Short-term memory sx • Autonomic instability contrast enhancement
PLEX, rituximab,
(Autoimmune, • Psych sx: agitation, • LP: lymphocytic pleocytosis, (esp. in temporal lobe)
cyclophosphamide
Paraneoplastic) delusions, hallucinations oligoclonal bands, EEG: extreme delta
brush very specific • Tumor resection
• Focal seizures autoantibodies (CSF + serum)
T R E A T M E N T : can treat symptoms, but treatment does not slow the progression of disease (Lancet Neurology 2023;23:13-15)
• Inpatient Considerations:
o For patients with Parkinson’s, do NOT stop/change home medications (NGT if needed). Stopping sinemet can cause NMS.
o If patient has or may have LBD, avoid antipsychotics. If necessary, atypicals (olanzapine, quetiapine) or trazadone preferred
• AChE (acetylcholinesterase) inhibitors: donepezil (first line), rivastigmine (patch), galantamine. Small effect on decreasing rate of
cognitive decline, ADLs. Major side effects: GI (n/v/d); less common bradycardia and heart block (increased vagal tone)
• NMDA inhibitors: memantine. Can precipitate agitation and exacerbate neuropsychiatric sx (caution in pts with significant behavioral sx)
• Anti-amyloid Abs: In pts w/ MCI or mild dementia + amyloid (confirmed by LP or PET), aducanumab clears amyloid w/ uncertain clinical
sig (Nature 2016: 537; 50-56). Lecanemab inhibits formation of AB plaques, slows decline. (NEJM 2023: 388; 9-21). Amyloid-Related
Imaging Abnormalities (ARIA) (edema or hemorrhage) seen in ~20%. CMS reimburses for FDA-approved anti-amyloid abs.
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Neurology Headache & Vertigo

H E A D A C H E S (Lancet Neurology 2023;23(1),17-19)
Approach: distinguish primary HA (tension, migraine, etc.) from secondary HA (tumor, ICH/SAH, ICP, etc.)
Red Flags (consider neuro c/s or neuroimaging): new onset HA (in pt with c/f trigeminal autonomic cephalgia, hx of SCD, or >50 yo);
positional or sudden+severe onset HA; headache with maximal intensity at onset, PMH immunocompromised, TB, cancer, or VPS; abn
neuro exam, fever/nuchal rigidity
Tension HA: ~40% population, ♀>♂, band-like, forehead radiating to occiput, mild-mod severity, duration 30min to 7d (NRDP 2021;7,24)
Migraine HA: >3/5 “POUND” criteria (Pulsating, 4-72h hOurs, Unilateral, Nausea, Disabling) (JAMA 2006;296:1274)
• Migraine with aura: 1 unilateral/reversible sx [visual/retinal (scintillating scotoma, visual field deficit), sensory (tingling, numbness),
speech/lang (aphasia), motor (wkness), brainstem (dysarthria, vertigo, ataxia, diplopia)] lasting minutes, usually followed by HA
ED/Inpt Management: for migraine/tension HA w/o red flags
Step 1 Step 2 Step 3
1) 1L IVF (adjust volume per 1) Chlorpromazine 25mg 1) VPA 500mg IV (after
60 min 60 min
comorbidities); 2) 2g Mg; 3) 1g APAP OR prochlorperazine 10mg negative pregnancy test); 2)
OR NSAIDs (15mg ketorolac, 500mg OR metoclopramide 10mg; Consider droperidol 2.5-5mg
If not If not
naproxen, 400mg ibuprofen, 25mg 2) Consider adding IV/IM OR haloperidol 5mg
improved improved
indomethacin); 4) 6mg sumatriptan diphenhydramine 25mg IM (after EKG)

Outpatient Management:
Migraine HA
Preventatives (if >4d/mo, long duration, or disability) Rescue (max 2d/w, treat early)
BB/CCB: propranolol 20mg BID up to 160mg/d; metoprolol 25mg BID up to NSAIDs/APAP
200mg/d; verapamil 80mg TID,  gradually Triptans: sumatriptan [5-20mg q2h (max 40mg/d) intranasal,
Antidepressants: amitriptyline/nortriptyline 10mg qhs,  to 150mg; venlafaxine 4-6mg q1h (max 12mg/d) SC, 25-100mg q2h (max 200mg/d)
37.5mg qd,  to 75-150mg PO]; zolmitriptan [5mg q2h (max 10mg/d) intranasal, 1.25-
Anticonvulsants: topiramate 25mg qd,  gradually to 100mg BID; VPA 500- 2.5mg q2h (max 10mg/d) PO]; C/I: CAD/PAD, liver dz,
1500mg qd (avoid both in young ♀) basilar migraine, MAOIs w/in 2w; risk of serotonin syndrome
CGRP antagonists: erenumab 140mg monthly sc, oral atogepant (Lancet CGRP antagonists: ubrogepant 50-100mg q2h (max
2023;402: 775-785) 200mg/d) PO
Supplements: Mg 400mg qd, riboflavin 400mg qd, melatonin, feverfew
Botox: referral to HA clinic
• Tension HA: prevention - smoking cessation, treat OSA, TCA, SSRI; rescue - NSAIDs OR APAP +/- antiemetic, max 2 d/w
• Menstrual migraine: before/during menstruation  NSAIDs or sumatriptan (Neurology 2008;70:1555). Consider preventive tx
perimenstrually w/ slow triptan (frovatriptan) 2.5mg QD/BID (begin 2d premenstrually, for total 6d/month)
• In pregnancy: NO gadolidium contrast, NSAIDs, VPA. C/s OB/Neuro if ? re: med safety/efficacy (Continuum 2022: 28: 72-92)
VERTIGO
Definition: illusion of motion of self or world secondary to vestib dysfunction; a/w n/v, postural/gait instability
Approach: distinguish central vs peripheral (AFP 2017;95:154)
• Hx/Exam: duration of sx, episodic/persistent, triggers (position Δ), prior sx, assoc sx (5D’s for brainstem: dysarthria, diplopia,
dysphagia, dysphonia, dysmetria). Obtain orthostatics. Perform Dix-Hallpike. HINTS exam video.
• HINTS exam: each test must be c/w peripheral to be reassuring. In acute, ongoing vertigo, Sn 97%, Sp 85% for stroke (>MRI)
Head Impulse (pt looks at your nose, passively rotate head ~20°. No saccade = ambiguous. Catchup saccade = peripheral)
Nystagmus (unidirectional e.g., always left-beating = peripheral; direction changing = central, any vertical = central)
Test of Skew (cover one eye, then other, any vertical skew/correction = central) (Acad Em Med 2013;20:986)
Tx (peripheral): metoclopramide, prochlorperazine, meclizine (≤2w, vestib suppression), lorazepam, or diazepam, AND vestibular PT
Symptoms Ddx Imaging
Severe nausea, mild Benign positional paroxysmal vertigo (BPPV), infxn (labyrinthitis,
Peripheral imbalance, hearing vestibular neuritis, herpes zoster oticus), Meniere’s, vestibular If exam reassuring, none
loss/tinnitus migraine, otosclerosis, trauma (perilymphatic fistula)
Mild nausea, severe Vertebrobasilar ischemia/TIA, ICH, toxic, cerebellopontine mass MRI brain w/ contrast
Central imbalance, rare hearing (vestib schwannoma, ependymoma, brainstem glioma, (coronal DWI reformats),
sx medulloblastoma), NF, MS, vestibular migraine MRA head & neck
MGH ED Approach to Acute Dizziness

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Neurology Stroke & TIA

A C U T E S T R O K E A C T I V A T I O N (In-House Stroke Pathway) tPA/TNK Criteria
1) If sudden-onset focal neuro symptoms within past 24h, activate the stroke team pager by Inclusion:
calling the operator at 6-3333. This will notify the stroke resident and nursing supervisors. 1. Severe or disabling neuro deficit
2) BE AT BEDSIDE. This a code equivalent. Obtain 18g PIV in R AC. Place on travel monitor 2. Age ≥18
3) ABC/VS, check EKG, telemetry, glucose. NPO & HOB >30°. Do not treat HTN unless 3. LSW <4.5h or ‘wake-up’ sx
BP >220/120, ACS, or ICH (see below). Confirm weight/MRI contraindications. Exclusion:
4) Be ready to provide the following information: History: stroke/head trauma <3mo;
a) Last seen well (LSW) time. This is NOT when symptoms were noticed but when pt head/spine surg <3mo; prior ICH;
was last witnessed to be normal intracranial malignancy, AVM,
b) AC or antiplatelets, CrCl, allergies, code status aneurysm; incompressible arterial
c) Contraindications to tPA/TNK (if present, patient may be thrombectomy candidate) puncture <7d; GI onc or GIB <21d
d) Physical exam findings: most predictive findings incl. facial paresis, arm drift/weakness, Clinical: BP ≥185/≥110 (treat!);
and abnormal speech (JAMA 2005;293:239) BG <50; active internal bleeding,
e) Premorbid disability (e.g., walks w/ assistance, bedridden) bleeding diathesis
5) Order STAT CTA Head/Neck (only need to order CTA; includes NCHCT). If unable to Heme: plt <100K, PTT > 40s, PT >
receive contrast, stroke team may consider STAT MRI ± MRA 15s; current AC (warfarin w/
6) Obtain STAT Labs: FSBG, CMP, CBC, PT/PTT/INR, type and screen, VBG, trop, UA/UCx, INR >1.7; therapeutic heparin use
tox screen, & AED levels (if appropriate), b-HCG (<50 years) w/in 48h w/ PTT; DOAC w/in 48h)
7) Neurology will perform NIHSS at bedside and may activate stroke group pager (pharmacy, Head CT: hemorrhage; large,
radiology, NSGY, IR, ICU RN) established infarct (e.g., 1/3 MCA
territory, ASPECTS <6)
ACUTE STROKE INITIAL MANAGEMENT (MGB GUIDELINES) Intra-arterial Therapy
1. ISCHEMIC STROKE Inclusion:
IV thrombolysis: tPA or TNK: 0.25mg/kg (max 25mg); tPA given as infusion, TNK given as 1. Clinical: NIHSS ≥6, LSW ≤24h,
bolus. TNK is now preferred thrombolytic at MGB. TNK can be given by any physician. age 18-90, baseline mRS ≤2, life
• LSW 0-3h: goal to start IV tPA/TNK w/in 60min of ED arrival (AHA/ASA: Stroke 2018;49:e46) expectancy >12mo
• LSW 3-4.5h: IV tPA/TNK recommended but w/ relative exclusion criteria including age >80, 2. Radiological: ICA or MCA M1/2
AC (regardless of INR), NIHSS score >25, h/o both stroke & DM2 (ECASS III NEJM occlusion, basilar/vert occlusion,
2008;359:1317) small infarct core volume
• Wake-up or Unknown Onset: consider IV tPA if DWI lesion <70mL w/o FLAIR changes Note: Proven benefit w/ these
(WAKE-UP NEJM 2018;379:611) inclusion crit; probable benefit w/
Intra-arterial therapy (thrombectomy, thrombolysis): NIHSS ≥4, mRS ≤3, prox occlusion
• Patients with disabling deficit & large vessel occlusion with LSW <6h (MR CLEAN NEJM w/ ASPECTS ≥ 5. Discuss all cases
2015;372:11). May extend time to LSW 6-24h based on imaging criteria (DAWN NEJM w/ Neuro, may opt for IAT
2018;378:11; DEFUSE 3 NEJM 2018;378:708) Exclusion:
BP control: low SBP (<150) a/w poor outcome (Arch Intern Med 2003;163:211) Anaphylaxis to contrast, acute ICH
o If tPA/TNK candidate: goal BP ≤185/110 prior to thrombolysis (treat STAT if higher!
1st line: IV labetalol/nicardipine); goal BP ≤180/105 after TNK/tPA for 24h Stroke Mimics: “MINT": Metabolic
o If no tPA/TNK: goal BP ≤220/120 (allow auto-regulation) for 1d; gradually reduce BP (Gluc, Na, uremia, TME, thyroid
goal subsequently disorders, MELAS, hypoxia,
o If anticoagulated: goal SBP ≤180 hypercarbia), Infection (Bell’s Palsy,
meningitis, encephalitis, vestibular
o If active cardiovascular disease (ACS) & requires tighter BP control, discuss w/ neuro neuronitis), Neurological (migraines,
o Monitor neuro exam: sx worse at low BP c/f ongoing ischemia  lay bed flat, give Todd’s paralysis/post-ictal, FND, MS,
IVF bolus, STAT page neuro MOG, NMO), Toxins/Trauma.
2. HEMORRHAGIC STROKE (see CNS Emergencies)
INPATIENT POST STROKE CARE
• Frequent neuro checks q1-2h x 24h if unstable/ICU; q4h if stable/floor pt, STAT head CT if change in exam
• Consult PT, OT, SLP (NPO until bedside swallow eval). Keep euthermic (antipyretics), euglycemic (FSG<180)
• Post tPA/TNK: NCHCT 24h post-tPA  if no e/o hemorrhagic transformation and etiology cryptogenic, start antiplatelet + DVT ppx
• If did not receive tPA/TNK: ASA 325mg x1, followed by long-term antiplatelet or AC (may delay antiplatelet and/or AC for large
ischemic strokes). Start DVT ppx if ischemic stroke (unless large volume hemorrhagic conversion)
Work up: (see below):
• Labs: Acute Code Stroke labs, plus lipids, A1c, TSH, ESR, CRP, if cryptogenic stroke: consider RPR, HIV +/- bloodstream or CNS
infectious w/u +/- hypercoagulability (d/w Neuro). (STROKE 2021;52:364)
• Imaging: MRI brain w/o contrast; head and neck CTA or MRA (TOF if low GFR); carotid U/S PRN
• Cardiac: EKG, TTE (w/ bubble if <60yo), tele then 30d MCOT vs LINQ (STROKE-AF JAMA 2021;325:2169) if tele neg for AF
CARDIOEMBOLIC STROKE
SUSPECT WHEN: DIAGNOSTIC WORKUP:
• ACA/MCA/PCA occlusion w/o sig vascular dz • TTE (w/ bubble if <60yo): if PFO, r/o venous thrombus (LENIs/
• Infarcts in multiple vasc territories or cerebellar stroke MRV pelvis), consider closure (RESPECT NEJM 2017;377:1022)
• Known risk factors (LA/LV thrombus, AF, LVEF<35%, • If no hx of AF: tele followed by 30d MCOT vs. LINQ at d/c
aortic arch athero, LA dilation, R→L shunt) ACUTE MANAGEMENT CONCERNS:
• Hypercoagulability/hyperviscosity (malignancy, HbSS, • Unless c/f hemorrhagic transformation, trans to long-term AC in 2d-
cryo, clotting d/o) 14d. If concerned, delay 2-4w (d/w Neuro).
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Neurology Stroke & TIA

SYMPTOMATIC CAROTID STENOSIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Carotid stenosis present on ipsilateral side • If stroke/TIA and either stenosis >50% or high-risk plaque
• H/o amaurosis fugax features, consider revascularization (stent/angioplasty/CEA)
DIAGNOSTIC WORKUP: ideally w/in 2w of sx (NASCET II NEJM 1998;339:1415)
• CTA vs. MRA head & neck, carotid US typically • Consider temporary anticoagulation (d/w neurology)
needed prior to carotid endarterectomy (CEA) • Consider induced HTN if symptoms fluctuate with BP
INFECTIVE ENDOCARDITIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Unexplained fever w/ stroke or pt with valvular dz • Immediate antibiotics; tPA contraindicated
DIAGNOSTIC WORKUP: • Early cardiac surgery if small non-hemorrhagic stroke; delayed
• Blood cultures, TTE followed by TEE if neg cardiac surgery (2-4w) if large or hemorrhagic stroke
• CTA head +/- conventional angio to identify mycotic • Avoid anticoagulation or antiplatelet w/o a separate indication
aneurysms (bleeding risk) (high risk for hemorrhagic conversion and increased mortality).
CAROTID AND VERTEBRAL DISSECTIONS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• <60yo or posterior circulation stroke in pt w/o RFs • Goal of tx is to prevent stroke: highest risk in first few days
• Neck pain, HA, or Horner’s syndrome • Anticoagulation vs antiplatelet (TREAT-CAD Lancet Neurol
• Trauma (vertebral fx), chiropractor, coughing spells 2021;20:341). Prefer antiplatelet if: sx onset >3d ago, dissection
DIAGNOSTIC WORKUP: extends intradurally (no AC 2/2 risk of SAH), large infarct (risk of
• CTA vs. MRA with T1 fat saturation hemorrhage)
• Consider connective tissue disease (Marfans/FMD) • High rate of recanalization  tx 3mo then re-image vessel
CEREBRAL VENOUS SINUS THROMBOSIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Positional HA, vomiting, papilledema, vision ∆ • Immediate anticoagulation (heparin or LMWH) even in presence
• P/w seizure (common, may be difficult to control) of hemorrhage
DIAGNOSTIC WORKUP: • AEDs if seizures (not indicated for ppx)
• NCHCT: hyperdensity in torcula (dense delta sign) • IV fluids, avoid dehydration, modify risk factors (smoking, OCPs)
• CTV vs. MRV to assess intracranial venous system • Long term anticoagulation (warfarin or DOAC) for 3-6 months,
• Consider hypercoagulable workup then reimage (RE-SPECT CVT JAMA Neurol 2019;76:1457)
2° PREVENTION PLAN: Discuss w/ Neuro (depends on suspected etiology, size of infarct, NIHSS, ABCD2, etc.). Typically, no need for
both antiplatelet & anticoagulation for 2° stroke prevention without other indications that necessitate both
• Start atorvastatin 80mg with LDL goal <70 (TST NEJM 2020;382:9)
• Antiplatelet long-term 2° prevention
o ASA 81mg qd (50-325mg/d effective; ≤200mg/d lower risk of major bleed) (Am J Cardiol 2005;95:1218)
o Clopidogrel 75mg qd (may be superior to ASA for atherosclerotic vascular dz) (CAPRIE Lancet 1996;348:1329)
o DAPT (ASA + clopidogrel OR ticagrelor)
 High-risk TIA (ABCD2 >3) or minor stroke (NIHSS <4): ASA 81mg + clopidogrel 300mg load → 75mg for 3w followed by
clopidogrel or ASA alone (CHANCE NEJM 2013;369:11). May replace clopidogrel with ticagrelor (NEJM 2020; 383:207)
 Symptomatic intracranial stenosis: consider ASA 325mg /clopidogrel 75mg for 3mo → ASA 325 qD (SAMMPRIS NEJM
2011;365:993)
 Recurrent stroke on ASA or clopidogrel alone + significant athero: consider DAPT long-term; however, no clear
evidence & higher bleed risk (CHARISMA NEJM 2006;354:1706; MATCH Lancet 2004;364:331)
• Anticoagulation long-term 2° prevention (embolic infarcts from AFib, paradoxical embolus, LV thrombus, VST, or hypercoag state)
o Warfarin or DOAC for pts w/ AF (start immediately for TIA, wait 2-14d for small infarct, generally 2-4w if c/f large hemispheric
stroke or hemorrhagic transformation)
TRANSIENT ISCHEMIC ATTACK (TIA)
• Definition: transient neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia w/o acute infarction
• Causes: atherothrombotic stenosis (ICA, vertebral, basilar, small vessel), embolic (arterial, aortic, cardiac, paradoxical), dissection
(ICA, vertebral) – identification will guide tx (antiplatelet therapy vs. search for underlying arrhythmia ± anticoagulation)
• Imaging: MRI within 24h of sx onset and vessel imaging of head and neck for large vessel occlusive disease (e.g. MRA head and
neck w/ contrast [w/o contrast TOF if low GFR] vs. CTA head and neck vs. carotid ultrasound)
• Cardiac w/u: TTE (w/ bubble if age <60) to excl thrombus & PFO, MCOT vs. LINQ monitoring to exclude AF if suspected embolic TIA
• ABCD2 score (Age, BP, Clinical features, Sx Duration, Diabetes): used to identify pts w/ high risk of ischemic stroke w/in 1w of TIA
• Management: immediate intervention reduces the risk of recurrent stroke (1.5-3.5% risk w/in 48h), see 2° Prevention above
POST-DISCHARGE STROKE/TIA CARE
Work up: f/u pending labs (e.g. hypercoag panel), repeat APLAS labs after 12w if pos, f/u MCOT/LINQ, order repeat imaging as noted
Management: d/c short term meds as appropriate (e.g. d/c ASA or Clopidogrel after 21d if treating per CHANCE trial); start AC per neuro
(e.g. 2w after large ischemic stroke due to AF); ask about depression (Br J Psychiatry 2013;202:14), consider treating w/ fluoxetine for
enhanced motor recovery (FLAME Lancet Neurol 2011;10:123); remind pts that deficits may continue to improve for >1yr, behavioral
modifications (smoking cessation, diet and exercise, weight reduction), and consider sleep study if concern for OSA

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Neurology CNS Emergencies

I N T R A C R A N I A L H E M O R R H A G E ( I C H ) : epidural (EDH), subdural (SDH), subarachnoid (SAH), intraparenchymal (IPH)
• Causes: trauma (all), ruptured aneurysm/AVM (SAH, IPH), IPH also caused by HTN, cerebral amyloid, tumor (most common w/ met
breast CA, lung CA, melanoma, RCC, choroid, thyroid CAs), cortical vein/venous sinus thrombosis, hemorrhagic transformation of
ischemic stroke
• Presentation: acute focal neuro deficit ± progressive consciousness, n/v. SAH: thunderclap HA, N/V, meningismus; EDH/SDH: s/p
trauma, lucid interval with EDH; IPH: focal neuro symptoms (may mimic ischemic stroke clinically); often with HA
• Tests: STAT imaging (NCHCT for all; +CTA head if SAH/IPH), coags/PLTs; repeat CT head after 6h to assess progression
• STAT management: MGH ICH Guideline
o STAT Neurosurg (p21111) if SAH/SDH/EDH; otherwise, Neuro (inpatient: p20202; ED: p20000)
o Elevate HOB to 30-45° to reduce ICP and prevent aspiration. Obtain labs: PT/INR, CBC, CMP, fibrinogen, type and screen
o BP control: strict SBP <140 with arterial line monitoring (studied in SAH or ICH due to ruptured aneurysm/AVM, to prevent re-
bleeding), use IV labetalol, nicardipine, clevidipine, or esmolol (Lancet Neurol 2008;7:391); consider less restrictive BP goal for pts
presenting with SBP 180-220 (ie. target SBP <160) or 25% reduction if SBP >220 (NEJM 2016;375:1033). For aneurysmal SAH,
PO nimodipine. (Stroke. 2022;53(6):1993-2005)
o Correct coags: warfarin/INR>1.5 (vitamin K 10mg IV x1 AND 4-factor PCC/KCentra); plt (transfuse, goal >50); uremia/
antiplatelet use (consider DDAVP 0.3mcg/kg IV); heparin/LMWH (protamine sulfate); s/p tPA (check fibrinogen, give cryo, ± amicar
4-5g → 1g/hr); rivaroxaban/apixaban (andexanet alfa). Discuss w/ neurosurg and pharm prior to reversal, consider heme consult.
o Venous sinus thrombosis (VST): AC w/ LMWH/UFH despite ICH (Lancet 1991;338:597). Manage seizures (see Seizures) & ICP.
o Prognosis depends on age, GCS, pre-ICH cognitive impairment, and ICH volume/location (FUNC Score; Stroke 2008;39:2304)
o Typically, acceptable to restart DVT ppx in smaller hemorrhages 48h after last stable NCHCT, confirm w/ Neurology
o Start prophylactic levetiracetam 500mg BID x7d for traumatic SDH or SAH (Neurocrit Care 2010;12:165)
E L E V A T E D I N T R A C R A N I A L P R E S S U R E ( I C P ) / H E R N I A T I O N : ICP > 20mmHg
• Etiologies: mass (tumor, abscess, hemorrhage), cerebral edema (infarction, inflammation, hyperammonemia, DKA), hydrocephalus
(tumor, intraventricular hemorrhage, leptomeningeal disease, meningitis), PRES, VST. High ICP may cause compression/ischemia.
Severe local swelling or CSF drainage with large space-occupying lesions causes herniation (displacement & compression of brain).
• Signs of ICP: nausea, vomiting, headache, diplopia somnolence/confusion, or limited upgaze; flexor/extensor posturing; ipsilateral
hemiparesis (uncal herniation); fixed/dilated/asymmetric pupil, Cushing’s triad (bradycardia, SBP, irreg. breathing)
• Tests: STAT head CT, blood gas, BMP, CBC
• Management: MGH ICP Guideline
o STAT Neurosurgery for ICP monitor/EVD placement/decompressive hemicraniectomy, Neurology to discuss need for Neuro ICU
o Secure ABCs, elevate HOB to 30-45˚, keep head midline (to secure venous drainage), treat pain/agitation, maintain BP to avoid
CPP <50mmHg (CPP=MAP-ICP).
o If c/f herniation, hyperventilate to PaCO2 ~ 30-35 mmHg (transiently reduces ICP)
o Hyperosmolar therapy: Check BMP, Sosm q6h. Start with 23% saline boluses, then use mannitol, or both staggered 3h apart
(discuss with Neuro) (Emerg Med J 2014;31(8):679-83)
▫ 23% saline 30cc q6h (requires central line → better option for patients with AKI/CKD, use with caution in HF)
• Hold if Na >160
▫ IV mannitol therapy 1g/kg q6h (max 100g, use with caution in pts on HD). Hold if osm gap >10, Na >160, serum osm >340
o If edema 2° to malignancy or bacterial infection, give 10mg IV dexamethasone x1, then 4-8mg BID
o Complications during LP: if sx of herniation or opening pressures >40cm H2O with space occupying lesion, consider STAT
head CT. Immediately replace stylet into needle, only drain CSF from manometer, STAT Neurosurgery consult.
o Do not use hypotonic solutions for resuscitation (i.e. LR) as this can worsen edema. Use 0.9% NaCl (NS) instead. J Neurosurg
1995;83(6):949-62).
H Y P E R T E N S I V E E N C E P H A L O P A T H Y : PRES (posterior reversible encephalopathy syndrome)
• Dx of exclusion w/ (sub)acute onsed, varied neuro sx, vasogenic edema, & severely elevated BP. (J Neurol 2017; 264(8): 1608–16).
• Typically associated with: severe HTN, but also relative HTN in setting of eclampsia/pre-eclampsia, cytotoxic/immunosuppr meds
(cyclosporine, tacro, cisplatin, bevacizumab), acute/chronic renal failure, uremia, sepsis, vasculitides, TTP  due to impaired cerebral
autoregulation and endothelial dysfunction, hypoMg (NEJM 1996;334:494)
• Symptoms: thunderclap HA, confusion, decreased consciousness, visual disturbances, seizures, ICH and ICP
• Tests: MRI brain w/ contrast: FLAIR w vasogenic edema w/in white matter in the posterior cerebral hemispheres; DWI/ADC typically
nl (though can have strokes); additional regions can be affected incl. brainstem, cerebellum, basal ganglia, frontal lobes
• Management: ICU if severe, strict BP control (goal SBP <140, reduce by 210-15% 1st hour then 5% daily, if severe use nicardipine or
labetalol drip), treat seizures, Mg2+ (esp. in eclampsia), remove inciting factor (i.e stop medication, dialyze if needed, treat infx)
• Prognosis: often fully reversible; complications include progressive cerebral edema, ICH, stroke, death
C O R D C O M P R E S S I O N : high level of suspicion in cancer or injection drug use patients with back pain, urinary sx or LE weakness
• Etiologies: subacute (tumor/mets, abscesses) vs acute (disc herniation, trauma, hemorrhage)
• Symptoms: back pain (worse at night/Valsalva), motor weakness, hyperreflexia below lesion if chronic (hyporeflexic if acute, cauda
equina), ⊕Babinski, loss of sensation (“sensory level”), bowel/bladder incontinence OR retention, loss rectal tone, saddle anesthesia
• Imaging: STAT MRI C/T/L w/ contrast (cord compression protocol), call ED (x63050) or inpt MRI (x64226) to prioritize
• STAT page NSGY/Ortho spine for decompression ± Rad Onc for possible XRT if tumor related (see Oncologic Emergencies)
• Dexamethasone: 10mg IV x1 then 4mg IV Q6H, esp in malignancy (Cochrane Database Syst Rev. 2015 Sep 4;2015(9):CD006716)
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Neurology Seizures
D E F I N I T I O N S Epilepsia 2017;58:522 Continuum 2019;25:306 Continuum 2022;28:230 Lancet Neurology 2023;23:19
• Classification of seizure (sz): describe onset and semiology
o Focal onset: unilateral, occurring in one hemisphere, ± impaired awareness, may evolve to bilateral tonic-clonic
o Generalized onset: occurring in & rapidly engaging bilateral distributed networks, impaired awareness
o Motor: limb stiffening (tonic), limb jerking (clonic), brief muscle contraction (myotonic), loss of tone (atonic), or automatisms
o Non-motor: autonomic changes, staring/behavioral changes, cognitive changes, sensory phenomena
• Epilepsy: ≥2 unprovoked sz >24h apart or 1 unprovoked sz + recurrence risk ≥60% over the next 10y or dx of an epilepsy syndrome
• Status epilepticus: ≥ 5min of continuous sz or 2+ sz w/ incomplete recovery of consciousness in between (Epilepsia 2015;56:1515)
• Non-convulsive status epilepticus: electrographic sz ≥10s or EEG & clinical improvement w/ tx (Epilepsy Behav 2015;49:158)
• Psychogenic non-epileptic sz (PNES): most prevalent phenotype of fxnl neuro disorder (FND). Long & fluctuating course,
asynchronous/side-to-side mvmts, closed eyes, preserved awareness, memory of spell. No pathology. changes in brain physiology.
E T I O L O G Y : provoked vs unprovoked?
• Causes/RFs: primary epilepsy, vascular (ischemia/hemorrhage), withdrawal (EtOH/BZD), masses (tumor, abscess), trauma,
metabolic (BG, CO2, O2, Ca, /Na), meds, infxn (systemic, CNS), HTN/HoTN, high fever, eclampsia, PRES
• Ddx: syncope, TIA, migraine, PNES (~30% have epilepsy, Brain Behav 2022;12), myoclonus, dystonia, cataplexy, tremor, catatonia
• H&P: sz history, prodrome (headache, confusion, anxiety, irritability), med list (sz threshold, e.g. penicillins, opioids, antipsychotics),
triggers (exertion, pain, fatigue, stress, cough, urination/defecation, infxn), tongue biting (lateral), incontinence, lateralizing signs,
EtOH/BZD. GET COLLATERAL.
• Labs: FSBG, Utox & Stox, UA, CXR, AED lvls, BMP/Na, Mg/Phos, CBC, LFT, VBG, CK, INR, lactate, b-hCG. Prolactin less helpful.
• Monitoring: tele (risk for ictal bradycardia/aystole), pulse O2 (NEJM 2013;368:2304-12)
• Neuroimaging: epilepsy protocol MRI w/ contrast for unprovoked 1st sz (Continuum 2022;28(2 Epilepsy):230-260), focal seizure,
focal neuro exam, h/o trauma, malignancy, or HIV. 10% found to have relevant structural lesion (Neuro 2007;69:1996).
• LP/BCx: if febrile, HIV/immunocompromised, 2° autoimmune encephalitis (anti-NMDA) (Epilepsia 2020;61:1341)
• EEG: within 24-48h if not seizing, emergent if seizing. DO NOT wait for EEG to manage. If emergent, contact EEG fellow (p16834).
S E I Z U R E P P X Neuro 2015;84:1705 Neuro 2006;67:s45 Cochrane 2008;CD004424 Neurosurg Focus 2008;25:E3 Stroke 2016;47:2666
• No AED in 1st sz unless prior TBI, abnml EEG, or abnml imaging. Early AED ↓short term recurrence (<2y), not remission (3+y).
• ETOH seizure: ppx not indicated for intox/withdrawal, ICH: only if clinical sz or traumatic etiology, levetiracetam 500mg BID x7d
• Brain tumor: no ppx. If sz, levetiracetam > lacosamide (fewer chemo interactions), Severe TBI: levetiracetam 500-750mg BID x7d
• PNES: Outpatient, CBT & Psychiatry. Inpatient, educate about functional neurological sx, c/s social work.
• In MA, no driving (for LOC event) until 6mo event free. Counsel pt, include in d/c summary. Restrictions vary by state.
TREATMENT
• Seizures that are NOT status epilepticus: tx if a) GTC > 2-3min or b) patient has several focal seizures within 24h (“clustering”)
o Lorazepam 1-2mg IV (1mg if elderly or low weight), can repeat x1 if needed. Then discuss possible ASM load with Neurology.
• Treatment of status epilepticus (MGH Status Epilepticus Protocol)
o Lorazepam 4mg IV q5min x1-2 and order 2nd line agent  persists >5min call Neurology, give 2nd line agent:
levetiracetam 60mg/kg x1 (max 4500mg/dose) vs. valproate 40mg/kg x1 (max 3000mg/dose) vs. fosphenytoin 20 PE/kg (over
10 min)  persists >20min  intubation w/ propofol/midazolam/(3rd-line) ketamine. Avoid etomidate. (NEJM 2019;381:2103).
o If no IV access, midaz 10mg IM/nasal/buccal or diazepam 20mg PR. 2nd line medications require PIV.
• Suspected preeclamptic seizure: 4mg IV Mg x1, consider mag sulfate infusion (2g/h), and call OBGYN
AED Loading Dosing Goal Level Side Effects
Levetiracetam 40-60mg/kg No goal, level to
1:1 PO:IV Psych (aggression, anxiety/depression, psychosis)
(Keppra)* Max 4.5g check adherence
Valproic acid 20-40mg/kg 50-100mcg/mL weight, hepatitis, N/V, tremor, alopecia, encephalopathy
1:1 PO:IV
(Depakote)† Max 3g (>1h post load) (NH3), ↓platelets. Good w co-morbid mood disorder.
10-20mcg/mL, HoTN/arrhythmia (if run >50mg/min; fosphen. has
Phenytoin (Dilantin)†, 20 mg/kg
1:1 PO:IV correct for alb, ↓cardiotox), gingival hypertrophy, nystagmus/ataxia/slurred
Fosphenytoin† Max 1.5g
(2h post load) speech, blood dyscrasia, DRESS, rash (TEN/SJS)
HA, diplopia, dizziness, ataxia, nausea. Get EKG before &
Lacosamide (Vimpat) 200-400mg 1:1 PO:IV 10-20mcg/mL
after load (PR prolongation, flutter/fib).
Rash (TEN/SJS), DRESS, nausea, drowsiness, ↓PMNs,
Lamotrigine (Lamictal)* No Load Only PO 3-15mcg/mL
HLH, aseptic mening. Good w co-morbid mood disorder.
↓weight, drowsiness, glaucoma, NAGMA→nephrolith.,
Topiramate (Topamax)† No Load Only PO N/A
cognitive dysfxn, aggression, anxiety/depression
SIADH, N/V blood dyscrasia, ataxia, blurred vision, DRESS.
Carbamazepine
No Load Only PO 4-12mcg/mL Screen for HLA-B*1502 if Asian descent for risk of
(Tegretol)
TEN/SJS (Epilepsia 2019;60:1472).
1:1
Clobazam (ONFI) No Load N/A Drowsiness, resp. depression (BZD), ataxia, URI, fever
PO:SUSP
Perampanel (Fycompa) No Load 1:1 PO:IV N/A Aggression/irritability, dizziness, drowsiness, weight gain
Others: Brivaracetam, Cenobamate (effective in highly active & ultra-refractory focal epilepsy; Epilepsia 2023;64:1225-35), Ethosuximide
(absence), Phenobarbital (historical), Vigabatrin, Zonsiamide. Aerosolised alprazolam as rescue medication (Epilepsia 2023;64:374-85).
*Preferred in pregnancy, †Teratogenic

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Neurology Weakness & Neuromuscular Disease

CHARACTERIZATION OF A PERIPHERAL PROCESS
• Weakness: ask about function (rising from a chair, stairs, brushing hair, tripping while walking, opening jars, zippers/buttons) and onset/
tempo. Clarify vs. generalized fatigue or systemic symptoms (i.e. of anemia, infection, electrolyte abnormalities, thyroid/adrenal issues)
• UMN signs: spasticity, increased tone, hyperreflexia, ⊕ Babinski; LMN signs: fasciculations, atrophy, decreased tone, hyporeflexia
• Patterns: UMN (UE extensors, LE flexors), LMN (length dpdnt, myotomal), myopathy (proximal), bulbar (dysphagia, dyspnea, dysarth.)
• Sensory sx: negative ( temp/pin (small fibers), vibration/proprio (large fibers), imbalance) or positive (tingling, allodynia, hyperalgesia)
• Autonomic sx: orthostasis, constipation, urinary retention, sexual dysfxn, changes in sweating, post-prandial nausea or early satiety
• Exam: 0/5 - no mvmt, 1/5 - flicker, 2/5 - mvmt if no gravity, 3/5 - mvmt vs. gravity only, 4/5 - dec. power vs. resistance, 5/5 - nml
• EMG/NCS: localization (radicular, nerve, junction, muscle), motor vs. sensory, axonal vs. demyel (guides tx), severity (guides
prognosis). Higher yield if sx for ≥2-3w (do as outpatient).
Localization Associated Signs/Sx Diagnostics Important/Common Causes
Cortical (lang., visual field, MRI Brain (with contrast if c/f cancer, Vascular (hemorrhage, ischemia), tumor,
Brain
neglect), cerebellar, UMN infection, demyelinating dz) trauma, demyelinating dz
Transverse myelitis (MS, NMO,
Truncal sensory level, MRI Spine (level from exam, contrast
sarc/Sjo/SLE), infxn (viral myelitis, abscess, TB,
Spinal Cord bowel/bladder dysfxn, if c/f cancer, infxn, demyelinating dz);
AIDS, HTLV, syph.), paraneop, neoplasm,
UMN (if chronic) CSF if c/f inflammatory or infxn
B12/Cu, vascular, trauma, toxic, myelopathy
Anterior LMN; if motor neuron dz, NCS/EMG
ALS, SMA, poliomyelitis, acute flaccid myelitis
Horn Cell UMN & LMN ± MRI brain and spine
MRI Spine (nerve root from exam) Nerve root compression 2/2 disc hernation,
Motor/sensory
LP if polyradiculopathy spondylosis; polyradiculopathy→DM (thoracic,
Radicular corresponding to nerve
NCS/EMG can aid in localization if sx lumbosacral), AIDP/CIDP, infxn (Lyme, HIV,
root. Radiating pain.
>3w CMV), malignancy (leptomeningeal, chemo)
Symmetric, length dependent: toxic/
Labs: A1c, B12/MMA, S/UPEP
metabolic/nutritional (DM, chemo, EtOH, B12,
Consider: Lyme, syphilis, HIV, B1, B6,
Motor/sensory; autonomic critical illness), hereditary (CMT), AIDP/CIDP,
Peripheral vit E, B3, Cu, ANCA, ANA, ESR, CRP,
dysfxn. Often symmetric/ paraprotein-related
Neuropathy RF, TSH, C3/C4, celiac w/u
length dependent. Mononeuropathy: compression/trauma Multiple
NCS/EMG: localization & pattern (not
mononeuropathy: vasculitis, DM, amyloid,
for eval of small fiber dz)
RA/SLE/sarcoid/Sjogren, leprosy
Ice pack test Myasthenia gravis, Lambert-Eaton, botulism,
Motor only; weakness
NM Labs: MG panel (below) tick paralysis, meds (imm checkpt inhib,
fluctuates with use; a/w
Junction NCS/EMG: repetitive stim, single fiber penicillamine, aminoglycosides), snake/spider
ptosis, diplopia.
EMG. CT chest if above c/w MG venom
Initial labs: CK/aldolase, LDH, LFTs,
Proximal weakness most Critical illness, meds (steroids, statins,
TSH/fT4, PTH, ESR/CRP
Myopathy common. Pain colchicine, cyclosporine, NRTI), inflammatory
EMG: e/o muscle irritability, chronicity
uncommon. (inclusion body, dermatomyositis, polymyositis)
May need muscle biopsy
Sx tx: Pain: gabapentin, pregab, TCA, SNRI; Dysautonomia: compress. hose, abd binder, fludrocort, midodrine, droxidopa, pyridostigmine
ACUTE INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY (GUILLAIN-BARRÉ SX)
• Symmetric, progressive numbness & weakness, hypo/areflexia, ±bulbar weakness, autonomic dysfxn, acute resp failure (10-30%)
• Causes: recent infxn (Campylobacter, HIV, COVID, CMV, EBV, Zika), vaccine (rare), meds (TNF-alpha antag, tacro, imm checkpt inhib)
• Dx: LP w/ albuminocytologic dissociation (protein, nml WBC), NCS/EMG (2-4 wks after symptom onset), RT consult for mechanics
• Tx: IVIG or plasmapheresis; monitor resp with NIF/VC (RT); glucocorticoids not effective
• Elective intubation 20-30-40 Rule: VC <20mL/kg, NIF weaker than -30cm H2O, MEF <40cm H2O, or ≥20% decline in ~24h
• Mimics: CIPD, myelopathy, trans. myelitis, ALS, polio, myositis, tick paralysis, vasculitis, paraneop, toxin/vit def, hexacarbon expos., AIP
• AIDP less likely: persistent asymmetric weakness, bowel/bladder dysfxn at onset, >50 CSF PMN, sensory lvl, severe pulm dysfxn w/o
limb weakness at onset, fever at onset, nadir of weakness in <24h or >4w, purely sensory
MYASTHENIA GRAVIS/LAMBERT EATON (MG/LEMS)
• Weakness of voluntary muscles. MG: worse w exertion, repetitive mvmts, & in the evening. LEMS: transient improvement w activity.
• Typically involves ocular (ptosis, diplopia), bulbar, respiratory, neck, proximal>distal limb muscles
• Cause: auto-Ab against postsynaptic ACh-R in skeletal muscle (MG) or voltage-gated calcium channels (LEMS); ICI therapy.
• Exam: ptosis w up-gaze after 1min. Ice pack test: after observing ptosis, place ice on eyes for 1min, ptosis will improve. Fatiguable
diplopia. (Historical: tensilon test, requires atropine at the bedside. Only improves MG not LEMS).
• Monitor for respiratory failure: track number counting in single breath, worry if <20, assess cough/swallow. Trend mechanics with RT:
NIFs/VC as above (20-30-40 Rule). Aggressive pulm toilet. HOLD pyridostigmine if bulbar sx and/or intubated (2/2 secretions)
• Dx: Ach-R Ab (80-90% seropositive in generalized dz, 40% in ocular dz, ~100% sp); if ⊝, check anti-MuSK. EMG/NCS w repetitive
stim: decremental response (MG) or potentiation (LEMS). Chest CT: r/o thymoma. Find underlying malignancy in LEMS.
• Tx: sx (pyridostigmine); immune: rapid (IVIG, plasmapheresis), chronic (steroids ±AZA/MMF); thymectomy (thymomatous MG or <65yo)
• Myasthenic crisis: exacerbation requiring intubation or noninvasive vent. Triggers include surg, infxn, pregnancy, meds (abx incl FQs,
macrolides, AGs; AEDs; antipsychotics, BBs, CCBs, Mg, iodinated contrast rarely). AVOID succinylcholine.

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Neurology Neuroprognostication
Neurological prognostication refers to the recovery from a consciousness disorder after severe brain injury; Neuroprognostication is
critical, complex and uncertain (Semin Neurol 2017;37:40). The introduction of targeted temperature management (TTM: see Cardiac Arrest &
TTM) can alter the timeframe for neurological recovery and the interpretation of prognostic markers. It is important to use the following as a
framework to conceptualize neuroprognositication in conjunction with active GOC conversations and close interactions with Neurology.

CEREBRAL PERFORMANCE CATEGORY (CPC)

• Original CPC scale (NEJM 1986;314(7):397-403) is commonly used, though does not always reflect patient/family values (Resusc
2016;100:6-10)
• Good Outcome:
o CPC 1. Able to work. May have mild neurologic/psychologic deficits.
o CPC 2. Moderate deficits. Capable of independent activities of daily life. Able to work in sheltered environment
• Poor Outcome:
o CPC 3. Severe deficits. Conscious but dependent on others. Ranges from ambulatory to severe dementia/paralysis
o CPC 4. Coma (no wakefulness) or vegetative state (wakefulness but unawareness)
o CPC 5. Brain death: apnea, areflexia, EEG silence, etc.
POST-CARDIAC ARREST DIAGNOSTICS
• Critical Caveat: each of the below tests has a FPR > 0 (i.e. will be “positive” for prediction of poor outcome in some patients who
would have a good outcome); FPRs are likely underestimated due to “self-fulfilling prophecy” bias; use of prognostic indicators in
combination may reduce FPRs and withdrawal of life sustaining treatment in patients who otherwise would have had a good outcome
(MGH Neuroprognostication Guidelines)
• Clinical exam
o Poor prognosis: status myoclonus (spontaneous, repetitive, unrelenting, generalized multifocal myoclonus involving the face,
limbs, axial musculature ± EEG correlate) < 48h post arrest or rewarming. Absent brainstem reflexes (esp. bilateral
pupillary/corneal) 3-7d post arrest or rewarming.
• Electroencephalography (EEG): started immediately post arrest, continued for 24h post rewarming
o Poor prognosis: absence of EEG reactivity, seizures/status, discharges, voltage attenuation, alpha or delta coma patterns, burst
suppression (Neurology 2013;80:339)
• Neuron specific enolase (NSE): check serially at 24, 48, 72h post arrest
o Non-specific marker of neuronal injury (also found in RBC and platelets)
o Poor prognosis: >70mcg/L at 24-48h, >59mcg/L at 48-72h (Neurology 2022;98:e62)
• Somatosensory evoked potentials (SSEP): 48h post cardiac arrest or rewarming
o Measurement of brain activity in response to somatosensory stimulation
o Poor prognosis: bilateral absence of N20, which reflects the integrity of thalamocortical projections
• CT head: 48h post cardiac arrest or rewarming
o Poor prognosis: widespread hypodensity in combination with poor clinical exam
• Brain MRI: 2-6d post cardiac arrest or rewarming (not useful < 48h post arrest/rewarming)
o Poor prognosis: extensive restriction of diffusion in combination with other poor prognostic signs
BRAIN DEATH
• Variability exists in prerequisites, clinical evaluation, apnea/ancillary testing to evaluate for brain death across hospitals.
• Prerequisites: irreversible CNS catastrophe; absence of severe acid-base, electrolyte, or endocrine abnormality; neg tox screen,
clearance of CNS depressants (i.e., 5 half-lives since last dose or subtherapeutic level), absence of neuromusc blockade, eucapnia,
euvolemia
• In principle, brain death = coma + absence of brainstem reflexes + apnea with irreversible etiology (NEJM 2021;385:2554-61)
• Death by neuro criteria confirmed when all prerequisites met PLUS
o Consistent coma and brainstem reflex exams and positive apnea test OR
o Incomplete brainstem reflex exams due to patient factors, positive apnea test, and one supporting ancillary test OR
o Consistent coma and brainstem reflex exam, inconclusive/aborted apnea test, and one supporting ancillary test
• Clinical exam (by Neuro/NSGY attending or Neurocrit care fellow): coma exam (i.e. absence of response to nox stim in extremities &
head (incl. absence of decorticate/decerebrate posturing), absent brainstem reflexes (pupils, oculocephalic [doll’s eyes], VORs [cold
calorics], corneals, cough, gag)

Apnea testing (Separate Protocol for ECMO)

Set PEEP 5 Send ABG

10 min 5 min 5 min
Disconnect vent Send ABG Send ABG
Set FiO2 100%
Start O2 (6L/min) via catheter
Always perform in presence of RT AND Neurology/Neurosurgery Attending OR Neurocritical care fellow
Stop test and draw ABG for spontaneous respiration, ectopy, SpO2 <90% x30 sec, SBP <100
Test pos if resp movements absent at PaCO2 >60 (or >20 inc from baseline if chronic retainer)
• Ancillary tests (only if clinical exam/apnea test inconclusive): conventional angio, nuclear flow study, SPECT, EEG, TCDs
o For EEG, order evoked potentials and ensure electrodes are tested (touched) at beginning of epoch (ask techs)

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Psychiatry Consent & Capacity

T H R E E E L E M E N T S O F V A L I D I N F O R M E D C O N S E N T (Psychosomatics 1997;38:119; NEJM 2007;357:1834)
1. Relevant clinical information: at minimum: diagnosis, proposed intervention, its purpose, its basic risks/benefits, alternatives, and
risks/benefits of alternatives (including no intervention)
2. Voluntary decision: decision is voluntary and w/o coercion from hospital staff or family/friends (advice/discussion are NOT coercion)
3. Capacity: confirm patient is able to make a decision about the specific question being addressed at the time it is being asked
EXCEPTIONS TO INFORMED CONSENT
1. Emergency in incapacitated patient: imminent risk of death or serious harm without medical intervention. All attempts should be made
to find HCP/other surrogate decision-maker. Always discuss with team attending. Document emergent situation, lack of capacity, lack
of available surrogate, need for emergent intervention. Consider 2nd opinion/consulting MGH lawyer-on-call (p26831) if time allows. If
not, need to make a team-based clinical judgment of emergency.
2. Lack of capacity or competency: turn to the appropriate HCP/surrogate decision-maker; note only a court-appointed surrogate can
override an incapacitated patient’s verbal refusal or physical resistance in a non-emergency situation
CAPACITY ASSESSMENT
• Capacity: person’s ability to make an informed decision about a specific question. It can change over time
• Competence: legal designation made by a judge. When deemed lacking, the judge may make a global determination or define time
and domain-based parameters within which a legally appointed surrogate can make decisions on the patient’s behalf.
• Any physician can make a determination of capacity. Psychiatry should be consulted only for complex cases (i.e neuropsychiatric
illness impairing decision-making, disagreement between patient/family/medical team.) Be ready to tell consult: Specific decision the
pt is asked to make, the decision pt offers, risk/benefit of intervention. Be prepared to accompany consultant during evaluation if
needed to provide info to pt re: proposed dx test/tx/intervention
• The strictness of the capacity test varies as the risk/benefit ratio of a decision changes: the more favorable the risk/benefit
ratio, the lower the standard for capacity to consent and higher the standard to refuse, and vice versa
C R I T E R I A F O R D E T E R M I N I N G C A P A C I T Y (ALL must be met for pt to have capacity) (NEJM 2007;357:1834; NEJM 1988;319:1635)
Criterion Approach in Physician’s Assessment
Communicate a clear Ask pt to indicate a choice. Inability to express one or to participate in assessment is equivalent to incapacity in
and consistent choice a sufficiently high stakes situation. Frequent reversals of choice may also indicate lack of capacity.
Ask pt to describe understanding of the information given by the physician (dx, proposed intervention, purpose,
Understand relevant
risks/benefits, risks/benefits of alternatives including no intervention). Some cueing is OK here. Do not
information
overestimate what is reasonable to expect from a lay person.
Appreciate the situation Ask pt to describe views of diagnosis, interventions, and likely outcomes. Is patient aware of their illness? Its
and its consequences seriousness? Consequences? What are the patient’s non-medical priorities that factor into their decision?
Able to manipulate info Ask patient to compare treatment options, consequences, and reasons for choice. Does the patient weigh the
in a rational fashion risks and benefits logically? A rational choice may not be the same as a “good” one.
SURROGATE DECISION-MAKERS
• Encourage each pt to sign legal HCP form specifying surrogate. “Confirmed” (by court procedure) when pt lacks capacity and retains
ability to refuse/resist medical activities. Confirmation of HCP is not needed if pt is incapable but agreeing, assenting, or unconscious.
• Surrogate’s job is, ideally, to make the decision pt would have made for themself if able — not what the surrogate wants. If a pt’s
wishes cannot be known, the surrogate should make the decision in the “best interests” of the patient
• HCP may be unconfirmed (most common) or confirmed. Court-confirmed HCP is required when pt’s surrogate is activated & pt
actively objects to surrogate’s decision. If HCP confirmation required, contact MGH Guardianship team
• Guardianship: legal process where MA Probate Court grants a guardian the authority to make decisions on behalf of someone who a
judge has ruled is not competent. Required when there is no HCP identified & pt is unable to designate a HCP. Note: a patient
may not have capacity to make a certain medical decision and still have capacity to designate a HCP. For help: ‘Guardianship Team’
• Emergency guardianship is not required to provide lifesaving treatment & should not delay care (see above).
T E M P O R A R Y I N V O L U N T A R Y ( P S Y C H I A T R I C ) H O L D (Section 12 in MA - MGL ch.123 §12): consult Psychiatry for all on 12a
• Section 12a (the front of the “pink paper”): MD, NP, psych RN, psychologist, SW, or police officer uses to apply for involuntary psych
eval and possible hospitalization of pt who, based on MD’s exam & opinion, requires hospitalization to avoid likelihood of serious harm
by reason of primary mental illness. Authorizes transport to psych facility and, if necessary, restraint of the pt to maintain safety
• Issued when likelihood of serious harm to self and/or others is imminent (within 24-72h) AND:
1. Is the result of a “serious mental illness”: must be supported in writing with specific evidence. Symptoms caused solely by
intoxication, withdrawl, delirium, dementia, or intellectual disability do not constitute a serious mental illness
2. Meets ≥1 of the following 3 criteria: (1) substantial risk of physical self-harm; (2) substantial risk of physical harm to others;
(3) very substantial risk of physical self-impairment or injury as manifested by evidence that the person’s judgment is so
affected (i.e., by serious mental illness) that they unable to protect themself in the community.
• Section 12b (reverse side of the “pink paper,”): completed by evaluating psychiatrist, authorizing involuntary psych hospitalization
SAFETY (MEDICAL) HOLD (PATIENTS LEAVING AMA POLICY)
• Order that can be placed that empowers staff to prevent pt from leave AMA when the following criteria are met: (1) Patient lacks
capacity to leave the hospital and is attempting to do so (2) There is imminent risk of harm to self and/or others from leaving AMA (3)
Pt does not meet S12 criteria (4) Physical restraint or chemical tranquilization would be excessive
• Staff may prevent a pt under a safety hold from leaving AMA using non-physical methods (e.g. verbal redirection, standing in a
doorway or exit, preventing an elevator door from closing) but should not place themselves at risk or physically hold a patient.
• If the pt should escalate or become physically aggressive, then providers should follow restraint/seclusion protocols

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Psychiatry Agitation
AGITATION MANAGEMENT 101
• Goals: 1) Safety of pt & staff, 2) Help pt manage distress (promote calm, not put pt to sleep or punish) 3) Avoid restraints as able
• General Considerations:
o Take notice early of anger/fear, yelling, pacing/restlessness, sweating, aggressive body language. LISTEN to RN and PCA
concerns
o Address any easily/quickly reversible issues: hunger, thirst, pain, communication breakdowns. Consider urinary retention, &
constipation as sources of discomfort, particularly in patients who are nonverbal, have ASD, or neurocognitive disorders. Work
up/treat any other contributors (delirium, psych d/o, substance intox/withdrawal).
o Offer PO medications early in escalation process. Think about standing medication if recurrent concerns.
o If pt requires restraints, should always receive med to help ease/lessen time in restraints. Monitor for ongoing need and
discontinue restraints ASAP. Restrained pts are at risk of aspiration, rhabdomyolysis, MSK injury, delirium.
Restraints/seclusion may be traumatizing, are associated with morbidity/mortality, and are the result of treatment
failures. Any restraint episode warrants reassessment of treatment approach.
A P P R O A C H T O V E R B A L D E - E S C A L A T I O N : D E F U S E ( NUEMBLOG)
Decide if pt is appropriate for verbal de-escalation. Clues include a patient who is responsive, engageable, not an active threat to safety.
Ensure safety. Ensure adequate backup. Clear area of potential weapons (loose objects, supplies). Respect personal space (two arm's
length between you and patient)
Form relationship. Introduce yourself by name and title. Ask what they like to be called. If they are responsive in conversation, consider
asking, “Will you allow us to help?”. Use short sentences and simple vocabulary.
Utilize interests. Identify patient’s wants and feelings. Agree as much as possible, either in truth, principle, odds, or to disagree. Reinforce
that you will let no harm come to patient.
Set limits. Speak matter-of-factly about consequences for bad behavior. Offer choices for behavior, even if it’s between oral or IV meds.
Use repetition as needed until you are heard by patient.
Enforce/Evaluate. If aggression escalates and violence seems imminent, withdraw and mobilize help. Once situation defused, by either
verbal de-escalation or medication, debrief staff and/or patient.
CHOOSING MEDICATIONS – CHART REVIEW:
• Consider current standing medications. Can any of these be used for acute agitation?
• Allergies/adverse reactions
• Major medical comorbidities (heart conditions, h/o arrhythmia, OSA, COPD, Parkinson disease, fall risk)
• MAR: previous medications for agitation, medication burden (is patient near max daily dose for an agitation medication?)
• QTc: if high overall load of QTc-prolonging medications or underlying heart disease, consider options with less QTc-prolonging
potential. If no recent EKG, do not defer giving meds to obtain one– you can plan to obtain when next able.
M E D I C A T I O N O P T I O N S A N D S P E C I A L P O P U L A T I O N S : always offer PO option first if pt able to safely take PO
• General principle: Treat exacerbations of the underlying condition with the agent intended for it, within medical reason:
o GABA withdrawal, catatonia, stimulant intoxication  benzodiazepines
o Psychosis  antipsychotics
o Mania  antipsychotics/mood stabilizers/benzodiazepines
o AVOID antipsychotics in patients with catatonia and NMS
• Medication options: (MDD = Max Daily Dose, ODT = Oral Disintegrating Tablet)
o Consider consulting psychiatry for pts requiring IM meds
o Quetiapine (PO) 12.5-100mg. Can lead to orthostatic hypotension.
o Trazodone (PO) 12.5-100mg. Good for elderly; no cardiac or delirium risks.
o Olanzapine (PO, ODT, IM, IV) 2.5-10mg. MDD 20mg. NOTE: do not co-administer parenteral benzos with parenteral
olanzapine within 4 hours (risk of lethal respiratory depression)
o Haloperidol (PO, IM, IV) 2.5-10mg. MDD 30mg. IM haloperidol has greatest risk for EPS side effects. IV haloperidol has
greatest QTc-prolonging potential (check if QTc >550).
o Diphenhydramine (PO, IM, IV) 12.5-50mg Sedating, often not used alone but as an adjunct w/ IM Haldol to decrease EPS
risk. Used with haloperidol and lorazepam with caution in cases of very severe agitation/physical aggression (“5-2-50”)
o Hydroxyzine (PO) 25-50mg antihistamine with anxiolytic effects, rapid onset. Delirium risk.
o Risperidone (PO, ODT) 0.5-2mg. MDD 8mg. NOTE: highest risk of EPS among second generation antipsychotics.
o Chlorpromazine (PO, IM, IV) 25-100mg. Can lead to hypotension (use cautiously in patients with borderline/low blood
pressure). Can also lower seizure threshold. Avoid in pregnancy. IM formulation associated w/ sterile abscess formation.
o Lorazepam (PO, IM, IV) 0.5-2mg. Use cautiously in elderly and patients with COPD/OSA due to risk for delirium and
respiratory depression, respectively. NOTE: do not co-administer parenteral benzos with parenteral olanzapine within 4
hours (risk of lethal respiratory depression).
• Special populations
o Geriatric: PO, consider trazodone 12.5-25mg, quetiapine 12.5-25mg. If cannot take PO, consider olanzapine 2.5-5mg IM/IV
o <18 years of age: If <35kg, can do clonidine 0.05mg PO. If >35kg, can do clonidine 0.1mg PO. If severe and unable to take
PO, can do olanzapine (<25kg: 1.25mg olanzapine IM, 25-70kg: olanzapine 2.5mg IM, >70kg: olanzapine 5mg IM).
o Parkinson’s/Lewy Body Dementia: quetiapine 12.5-50mg PO, or lorazepam 1-2mg IM or 0.5-1mg IV.

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Psychiatry Delirium
D E L I R I U M : definition per DSM-V-TR
1) disturbance of consciousness (i.e. a reduced ability to focus, sustain or shift attention)
2) additional disturbance in cognition (memory, disorientation, language, visuospatial ability, or perception);
2) change from baseline, develops over a short period of time (usually hours to days), tends to fluctuate
4) not better explained by another preexisting neurocognitive disorder and does not occur in the context of a severely reduced
arousal/coma
Complications: a/w mortality (JAMA 2010;304:433), institutionalization (Lancet 2014;383:911), cognition (NEJM 2012;367:30)
RECIPE FOR DELIRIUM= VULNERABLE BRAIN + ACUTE INSULT
• Vulnerable brain: older age, history of: stroke, dementia, TBI, vascular disease/ HTN, SUD, visual/hearing impairment, pre-existing
psychiatric disease, HIV
• Acute insult: Life-threatening etiologies (WHHHHIMPS): Wernicke’s, Hypoxia, Hypoglycemia, Hypertensive encephalopathy,
Hyper/hypothermia, Intracerebral hemorrhage, Meningitis/encephalitis, Poisoning (incl. iatrogenic), Status epilepticus
o Other considerations: states of inflammation such as infection (↑ permeability of the blood brain barrier), disturbances or big
swings in HR/BP (esp. in pts with vascular disease, ↓ cerebral perfusion, common after surgery), intoxication (including
iatrogenic), withdrawal, metabolic disturbance, endocrinopathy, vitamin deficiencies, toxins
DELIRIUM EXAM
• 4AT tool (available in MDcalc)- Sp/Sn 88% (AAG 2021; 50:733)
• Tests level of consciousness, attention, orientation and acuity
AVOID DELIRIUM BY PREVENTING IT IN VULNERABLE PATIENTS
• Minimize deliriogenic meds: anticholinergics, antihistamines, benzodiazepines, opioids
• Ensure: no urinary retention, regular bowel movements, and adequate pain management
• Precautions: frequent reorientation, mobilize with PT/OT, OOB to chair, glasses/hearing aids, minimize lines/telemetry/catheters,
early volume repletion if c/f dehydration. Avoid room changes or physical restraints (JAMA 2017;318:1161)
• Anticipate circadian dysfunction: standing melatonin 3mg q6PM, lights on during day and off at night, schedule meds for earlier in
evening, avoid late diuresis, reduce noise

DELIRIUM MANAGEMENT
Most important step: identify UNDERLYING CAUSE w/ special attention to life-threatening conditions (see Recipe for Delirium,
above):
• Maintain IV access if possible
• Behavioral management: implement delirium precautions, modified deliriogenic medications, treat circadian dysfunction
• Monitor QTc daily (goal <550ms); daily repletion of K>4 & Mg>2 (in anticipation of pharmacotherapies)
• Reserve pharmacologic agents for dangerous behavior ONLY i.e. if danger to self or others; no evidence for altering duration
of delirium (NEJM 2018;379:2506), severity, hospital or ICU LOS (JAGS 2016;64:705) with increased potential for adverse effects
(e.g. QTc prolongation and drug interactions)
Behavioral/environmental management >> 1:1 sitter (re-orients) >> meds >> restraints (deliriogenic)
Medical Management (NEJM 2017; 377:1456)
• For HYPERactive delirium/AGITATION  start low + PRN, escalate to scheduled (see Agitation)
o Haloperidol- least sedating, IV>PO as reduces EPS risk 0.25-0.5mg IV q30-60m PRN vs 0.5-1mg PO q4h PRN vs. IM q1h
PRN
o Olanzapine- most sedating, lowest EPS risk - 2.5-5mg SL/PO/IM qd-q4h PRN
o Quetiapine- PO only, 12.5-25mg PO q1h PRN
• If continued severe agitation or requiring > 2 doses antipsychotic  consider Psychiatry consult:
o Haloperidol PRN: double PRN dose q20 min until effective, ~5-20mg IV
o Quetiapine PRN: standing 25-50 mg TID, extra dose HS
o Olanzapine PRN: standing 2.5-10 mg BID, extra dose HS
• QTc severity: haloperidol > quetiapine > olanzapine; ∆ tx if QTc  by 25-50%, QTc>500, ⊕U-wave/T-wave flattening
• Discontinue when able. Prolonged antipsychotic use in elderly can increase mortality
• Avoid benzos as may worsen delirium, though warrants risk/benefit as in some cases risk of withdrawal > risk of continuing
• For patients with prolonged QTc or refractory symptoms to medications, discuss with psychiatry

WHEN TO CONSIDER PSYCHIATRY WHEN TO CONSIDER NEUROLOGY

CONSULTATION CONSULTATION
• Escalating/persistent delirium, underlying neurodegen, • New focal finding suggesting stroke: Stroke Neuro p20202
d/o (esp. PD), hx TBI, psych d/o, SUD • Other concerning findings (convulsions, meningismus, e/o
• Significant co-morbidities (CV disease/critical illness) elevated ICP, abnl spot EEG/LP): General Neuro p20702
• Know the following prior to calling: workup done thus • Know the following prior to calling: last seen well,
far to identify underlying cause and past/current baseline deficits, anticoagulation
medication list

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Psychiatry Psychosis
M E N T A L S T A T U S : document daily if new AMS or worsening psychiatric sx (AFP 2009;80:809)
APPEARANCE/BEHAVIOR: grooming/hygiene, eye contact, attitude/cooperation, abnormal mvmt (fidgeting, tics, TD)
SPEECH/LANGUAGE: mechanics: rate, volume, prosody, articulation, and fluency. Watch for speech latency, paucity of speech,
mutism, echolalia (copying provider’s speech), verbigeration (repeating meaningless phrase like a “broken record”)
THOUGHT PROCESS: linear, logical, goal-directed vs. disordered. Types of thought disorder: circumstantial (non-linear; initially veers
off but still goal-directed) > tangential (nonlinear, not goal-directed; ultimately loses topic entirely) > flight of ideas (rapid jumps
between somewhat-connected thoughts) > word salad (incomprehensible speech). Disorganization: deficiencies in logical organizing
of thoughts needed to achieve goal. Thought blocking: interruptions in thought causing inability to respond).
MOOD/AFFECT: Mood: subjective description of emotional state. Affect: physical expression of emotional state
THOUGHT CONTENT/PERCEPTIONS: SI/HI, delusions vs overvalued ideas, hallucinations, obsessions, poverty of content
COGNITION: level of consciousness, orientation, Luria sequence, MOCA
INSIGHT/JUDGMENT: insight: pt recognizes sx as pathological/accepts dx). Judgment (pt’s action based on insight)

PSYCHOSIS WORKUP AND DIFFERENTIAL DIAGNOSIS

• Characteristics: delusions, thought/behavior disorganization, auditory > visual hallucinations (visual = often neuro/medical, esp.
delirium, dementia, alcohol withdrawal)
• Ddx:
o Psychotic/mood disorder: schizophrenia (no clinically significant mood episodes), schizoaffective (primarily psychotic disorder w/
some mood episodes), mood disorder w/ psychotic fx (primarily mood disorder w/ some psychotic symptoms)
o Neurocognitive disorder: intellectual disability, autism spectrum, dementia and neurodegenerative disorders
o Medical mimics: delirium (visual hallucinations), migraine, steroid-induced, lupus encephalitis, porphyria, Wilson’s, epilepsy,
autoimmune/paraneoplastic encephalitis, Charles Bonnet syndrome
o Substance induced: Can exclude if hx of psychosis during sobriety. GABAergic (i.e. EtOH, benzo) withdrawal (VH, formication;
24hrs - 5d); cocaine/amphetamine intoxication (persecutory delusions, formication); cannabis intox (paranoia, persecutory
delusions); hallucinogen intox (VH, paranoia). Note: isolated opioid intoxication/withdrawal does not typically include psychosis.
o New-onset primary psychotic disorder in >50yo is rare. Medical causes (delirium, dementia, CNS pathology) more likely
o Refer to psych: outpatient = always, inpatient = if decompensated ± safety concerns
• Labs: CBC, BMP, TSH, CRP, UA, tox screens (should include separate order for urine cannabinoids as these are no longer
routinely tested for but critical for dx), med levels, delirium w/u (see Delirium). Consider RPR, HIV, B12, ANA, pregnancy. Imaging not
routinely indicated unless atypical presentation or neuro/medical etiology suspected.
TREATMENT BASICS
• General principles:
o Confirm home antipsychotics/mood stabilizers early in admission & continue only if pt reliably taking; otherwise, dose
reduce/hold pending psych consult. Ask if pt on long-acting injectable meds/date of last injection and which PRNs work well. Get
collateral from DMH case manager, family, shelter, or Freedom Trail Clinic (if on clozapine). Hold if catatonia on ddx.
o If on >1 standing antipsychotic, confirm before ordering (otherwise avoid). If on valproate, Li, clozapine, check level ASAP.
o Continue home benztropine, benadryl, propranolol, clonidine (if prescribed) to reduce EPS. Note: lamotrigine has SJS risk, if not
taking for >2-3 days re-start at 25mg QD, uptitrate q2w (contact pharmacy/psych for questions).
• Clozapine: Uniquely effective, but many SE. Continue inpatient (withdrawal catatonia if stopped suddenly).
o Neutropenia agranulocytosis in <1% of pts (84% w/in first 3mo); weekly CBC for first 6mo, biweekly for next 6mo, then monthly.
May need to DC if ANC <1.5k. Requires REMS training/monitoring, consult psych/pharmacy w/ questions.
o Risk for myocarditis, withdrawal catatonia, constipation/bowel obstruction. Infx can ↓ metabolism and ↑ levels.
o On admission: continue med to avoid w/d catatonia, ensure bowel reg ordered/effective, check levels if infection or smoker
• Extrapyramidal symptoms (EPS):
o Dystonia: muscle spasm incl. oculogyric crisis (risk of rapid airway obstruction), torticollis, trismus, opisthotonos,
laryngospasm. Tx: anticholinergics (benztropine, diphenhydramine)
o Pseudoparkinsonism: reversible; bradykinesia, tremor, rigidity, masked facies, shuffling gait. Tx: anticholinergics
o Akathisia: subjective feeling of inner restlessness, inability to stay still. Tx: low dose BB (e.g. propranolol)
o Tardive dyskinesia (TD): Involuntary, repetitive, arrhythmic movements: lip smacking, chewing, puckering, writhing. Occurs w/
long-term antipsychotic use, often irreversible. May use VMAT2 inhibitors to treat.
A N T I P S Y C H O T I C S & S I D E E F F E C T S (AFP 2010;81:617)
Anti- Prolong Prolactin Postural Wt Sexual
EPS NMS Sedation HLD DM2
cholinergic QTc ↑ hypoTN gain dysfxn
haloperidol + + ++ ++ +++ + + + + + ++
chlorpromazine +++ ++ + + ++ +++ +++ ++ ++ + +++
aripiprazole 0 + + + 0 + + 0 0 + +
olanzapine + + + + + + ++ +++ +++ ++ +
quetiapine + + 0 + 0 ++ ++ ++ ++ + +
risperidone 0 + ++ + +++ ++ + + ++ + ++
ziprasidone 0 ++ + + + + + 0 0 + +
clozapine +++ + 0 + 0 +++ +++ +++ +++ ++ +

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Psychiatry Catatonia, NMS, & Serotonin Syndrome

CATATONIA
• Behavioral syndrome due to underlying condition that can occur in the context of many psychiatric, neuro, or medical dx; marked by
inability to move or communicate despite full physical capacity; waxes/wanes; pathophysiology incompletely understood
• Subtypes: stuporous: immobility, mutism, withdrawal; excited: hyperkinesis, stereotypy, disorientation; malignant (medical
emergency): sx accompanied by hyperthermia, autonomic instability, rigidity (Arch Gen Psych 2009;66:1173)
Etiology: (Schizophr Bull 2010;36:239; Behav Brain Sci 2002;25:555)
• Psychiatric: mood disorders (e.g. bipolar d/o) > thought disorders (e.g. schizophrenia, autism) > dissociative disorders
• Neuro/medical: seizures/NCSE, PRES, CNS lesion, infection, TBI, delirium, anti-NMDAR encephalitis, PLE, SLE
• Drug: dopamine-blockers, dopamine withdrawal, sedative/hypnotic withdrawal, hallucinogens, synthetic MJ, opiates
Diagnosis: (Psych Scand 1996;93:129,; DSM-5 TR 2022;6:135; Arch Gen Psych 2009;66:1173):
• Bush-Francis Catatonia Rating Scale (BFCRS)– 14-item screening (positive when ≥ 2 items) and 23-item rating scales (Positive when
≥ 4 items) OR the presence of 2-4 of the below signs for several hours:
Observed Signs Elicited Signs
-Immobility: Hypo-akinetic, not influenced by external stimuli -Ambitendency: Stuck on hesitant movement when the
-Stupor: Decreased alertness, diminished response to voice/painful stimuli examiner verbally contradicts own nonverbal signal
-Excitement: Impulsive, stereotypic behavior (extend hand and say “do not shake my hand”)
-Mutism: Verbally unresponsive while awake -Waxy flexibility: rigid tone that is gradually overcome
-Speech mannerisms: Robotic speech, foreign accent, palilalia -Automatic obedience: “Stick out your tongue. I want to
-Behavioral mannerism: Odd, purposeful movements write on it with a pen.” (pt will stick out tongue)
-Posturing: Voluntarily maintaining a posture for a long time -Negativism: Opposite/no response to instruction.
-Echophenomena: Echolalia/echopraxia (mimic sound/movement) -Stimulus-bound behavior: Behavior tied to certain stimuli
-Stereotypy: Awkward non-goal-directed repetitive movements.
-Staring: Fixed gaze
• Lab findings: Leukocytosis (15,000 - 25,000), CK ≥ 1000, and ↓ serum iron in malignant catatonia.
• Lorazepam Challenge: 2mg IV x1 (0.5-1mg in frail/elderly). Partial relief of signs after 5 -10 minutes after is consistent with a
diagnosis of catatonia (Arch Gen Psych 2009;66:1173). Negative challenge test does NOT rule out catatonia.
• Differential dx: delirium, dementia, stroke, PD, stiff person & locked-in syndromes, NCSE, akinetic & elective mutism, anti-NMDAR
encephalitis; If malignant: NMS, malignant hyperthermia, SS, DT, CNS infection/vasculitis, anticholinergic toxicity
Treatment: (Gen HospPsychiatry 2017;48-1)
• Always consult psych. NO antipsychotics/other D2 blocking meds. Trend CK, BMP; q4h VS; supportive care.
• Treatment: 2mg IV lorazepam q6-8h, uptitrate as tolerated. Hold for respiratory depression only, NOT sedation (catatonia sx can
mimic sedation). If no response → ECT, amantadine/memantine, anticonvulsants
N E U R O L E P T I C M A L I G N A N T S Y N D R O M E ( N M S ) (Am J Psych 2007;164:870)
• Overview: abrupt onset of 1) ∆ in mental status 2) rigidity 3) fever 4) autonomic dysfunction (tachy, HTN, diaphoresis), associated
with medication change that causes decreased dopaminergic tone (med list: Neurohospitalist 2011;1:41)
• Risk factors: initiation/increase of dopamine-blocking med or withdrawal of pro-dopamine med (typically occurs within hours/days,
but can be idiosyncratic), withdrawal from EtOH/sedatives, hx of NMS/catatonia, basal ganglia d/o, exhaustion, dehydration, agitation
• Labs: WBC and CK>1000 (correlates w/severity) most common, ↓ serum iron, mild  LDH/alk phos/AST/ALT, ↑↓ electrolytes
• Ddx: serotonin syndrome, malignant hyperthermia, malignant catatonia (significant overlap), CNS infection, spinal cord injury, seizure,
heat stroke, acute dystonia, CNS vasculitis, thyrotoxicosis, drug intoxication/toxicity, withdrawal states
Stage Clinical Presentation Intervention/Treatment
Mild rigidity, confusion, • Stop offending agent & contributors (serotonergics, Li, anticholinergics)
Early
T<100.4F, HR <100 • Aggressive fluids/supportive care ± lorazepam 0.5-2mg IV q4-6h
Moderate Moderate rigidity, T100.4- • Cooling measures ± ICU
(may require ECT) 104F, HR 100-120 • Bromocriptine 2.5mg PO q8h or amantadine 100mg PO q12h
Severe Severe rigidity, ± coma, • ICU level of care (if intubation required, midaz > propofol for sedation)
(may require ECT) T >104F, HR >120 • Dantrolene 1-2.5mg/kg IV q6h x48h

SEROTONIN SYNDROME (SS) (NEJM 2005;352:1112)

• Overview: Exposure to serotonergic agent(s) leading to 1) ∆ mental status 2) neuromuscular hyperreactivity (tremor, clonus,
hyperreflexia) 3) autonomic instability (tachycardia, tachypnea, diaphoresis, mydriasis, hyperthermia, shivering, sialorrhea,
hyperactive bowel sounds, diarrhea). Watch for rhabdo/AKI. Note: n/v/d common in SS prodrome but rarely seen in NMS
• Causative agents: amphetamines, bupropion, buspirone, carbamazepine, carbidopa-levodopa, cocaine, cyclobenzaprine,
diphenhydramine, ergotamines, fentanyl, linezolid, lithium, LSD, MAOIs, MDMA, meperidine, methadone, methylene blue,
metoclopramide, mirtazapine, ondansetron, SNRIs, SSRIs, St. John’s wort, TCAs, tramadol, trazodone, triptans, tryptophan, VPA
• Diagnosis: Hunter's Criteria 84% sensitive 97% specific (QJM 2003;96:635)
• Treatment: 1) hold offending agent (generally will resolve within 24h), 2) use BZDs if agitation present (lorazepam 1-2mg IV, repeat
PRN to effect), 3) if unsuccessful, can use cyproheptadine 12mg x1 then 2mg q2h until clinical response seen. Very severe cases
with hyperthermia may require ICU level of care with cooling, intubation, sedation, and paralysis.

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Psychiatry Depression
MAJOR DEPRESSIVE DISORDER (MDD)
• Epidemiology: common in general population. U.S. lifetime prevalence ~20%, F>M (JAMA Psych 2018;75:336)
• Screening: USPSTF recommends universal screening of adult primary care patients including pregnant and postpartum
women (Grade B): Use PHQ-2: to begin screening (AFP 2012;85:139); PHQ-9 to complete screening (AFP 2012;85:139)
• DSM-5-TR criteria: (mnemonic SIGECAPS): must have depressed mood and/or loss of Interest/pleasure + ≥4 of following sx: change
in Sleep, worthlessness/Guilt, fatigue/decreased Energy, poor Concentration, change in weight/Appetite, Psychomotor
agitation/slowing, thoughts of death (not just fear of death) or SI.
o Sx must be present over same 2w period & cause significant impairment/distress
o Ddx: other psych (e.g. bipolar, adjustment disorder, persistent depressive disorder, primary thought disorder, borderline
personality disorder, prolonged grief), drugs/meds, OSA, hypothyroidism, stroke, TBI, delirium, vit def, dementia, MS, HIV
• Tx: psychotherapy ± medication as determined through shared decision making; combination > either alone (pharmacology >
therapy) (APA 2019; J Clin Psychiatry 2008;69(11):1675-85)
o SSRIs are 1st line: All second-generation antidepressants are roughly equivalent (consider starting with sertraline or
escitalopram as they have best combination of efficacy and acceptability (Lancet 2009;373:746)).
o Response time for SSRIs may vary between 1-2 weeks up until 8-12 weeks, with an average of 6-7 weeks (Am J Psychiatry
2006 163(1):28-40)
o Other common options: bupropion, mirtazapine, & SNRIs. Bupropion lowers seizure threshold and is contraindicated in pts with
risk of seizure (seizure disorder, eating disorder, etc.), may aid in smoking cessation; caution in pts with renal/hepatic impairment
(↑ concentration) or with cardiovascular disease (↑ BP). SNRIs may also ↑ BP.
o Consider mirtazapine in elderly pts with frailty (sedative and ↑ appetite).
o Use Mayo Clinic Depression Medication Decision Aid to choose meds based on side effect profile
o Risk of death in TCA overdose, advising caution when Rxing TCAs to patients with history of suicidality or serious attempts
o Other common uses of antidepressants:
• Anxiety disorders: SSRIs, SNRIs
• Neuropathic pain: SNRIs, TCAs
• Insomnia: trazodone, mirtazapine
• Functional GI disorders: amitriptyline for IBS-D & dyspepsia, nortriptyline/fluoxetine for constipation (WJG 2009;15:1548-53)
• Pregnant pts. In mild/moderate MDD, consider psychotherapy as first line tx. In severe, or if psychotherapy is not available/preferred,
consider medication. If prior successful tx trial, consider using that same antidepressant,
Side Effect Profiles of Commonly Prescribed Antidepressants (Can J Psychiatry 2016;61:540; NEJM 2005;353:1819)
Class Drug Anti- Drowsiness Insomnia/ Nausea/ Wt SexualD Orthostatic ↑ Usual Daily Dose
Choline Activation Vomiting/Di Gain ysfn HoTN QTc (mg)
rgic arrhea
Citalopram - - + + + +++ + ++ 10-40
Escitalopram - - + + + +++ + + 5-20
SSRI Fluoxetine - - ++ + + +++ + + 20-80
Paroxetine + + + + ++ ++++ ++ - 20-50
Sertraline - - ++ ++ + +++ + + 50-200
Duloxetine - - + ++ - + - - 30-60
SNRI
Venlafaxine - + + ++ - +++ - + 37.5-225
Bupropion - - ++ + - - - + 150-450
Atypical
Mirtazapine + ++++ - - ++++ + - + 15-45*
Trazodone - ++++ - ++ - $ ++ ++ 100-400*
SerotoninMo Vilazodone - - ++ +++ - + - - 10-40
dulator Vortioxetine - - + + + + - - 10-20

Amitriptyline ++++ ++++ - + ++++ ++++ +++ + 25-300*

TCA
Nortriptyline ++ ++ - - + +++ + + 25-150*

$ Risk of priapism

Dosing of Antidepressants
• Start at low dose, titrate q1-2 weeks. Adequate trial is 6-12 weeks at full dose; if poor tolerance/response after 4-6 weeks, augment
with psychotherapy or other medications; consider switching SSRIs
• Advise pts of initial side effects that they will develop tolerance to (GI upset, headache, sedation/activation, dizziness). Advise pts that
physical sx of depression (sleep disturbance, appetite changes) usually resolve first, within days-weeks. Mood sx may take weeks to
resolve. Sexual side effects (ED, anorgasmia, delayed ejaculation) may persist.
• Continue antidepressants for at least 6 months after symptom remission to prevent relapse
• Stopping any antidepressant requires tapering off over 2-4 wks to prevent discontinuation syndrome (affective sx, flu-like sx, sleep
disturbance, GI upset, dizziness/balance/sensory sx, electrical sensation or ‘brain zaps’). MAOIs reduction may cause psychosis.
o Paroxetine (short half-life, most likely to cause discontinuation sx): taper down 5-10 mg weekly over 4+ weeks
o Fluoxetine (long half-life): taper may not be needed for doses < 40 mg daily; if ≥ 40 mg daily, taper over 2 wks
o If pt develops discontinuation sx, restart antidepressant or increase dose, then taper more gradually over 6-12 weeks
When to Refer to Psychiatry: concern for bipolar disorder (any history of mania/hypomania), failure of ≥2 adequate rx trials, severe MDD
with SI/HI, psychosis, or catatonia.

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Psychiatry Anxiety Disorders

GENERALIZED ANXIETY DISORDER (GAD)
• Epi: US lifetime prevalence 8%, 2-3x more prevalent among F vs M. (AFP 2022;106:157).90% will meet criteria for at least 1 co-
morbid psych condition in their lifetime (MDD, dysthymia, AUD, simple phobia, social anxiety) (Arch Gen Psych 1994;51:355)
• Excessive worry associated w/ poor CV health, CAD, CV mortality (Nat Rev 2012;9:360)
• Screening: USPSTF recommends screening of adult primary care patients (Grade B). GAD-7: score ≥5 indicates mild GAD (97% Sn,
57% Sp, LR 2.2); score ≥10 indicates moderate GAD (89% Sn, 82% Sp, LR 5.1) (Arch Intern Med 2006;166:1092).
• DSM-5-TR criteria:
o A) excessive anxiety/worry occurring most days for ≥6mo re: multiple life domains, that is
o B) difficult to control, and
o C) associated w/ ≥3 sx: restlessness, fatigue, poor concentration, irritability, muscle tension, sleep disturbance. Must also cause
o D) significant distress/impairment; and
o E/F) not better explained by drugs/meds/other psych disorders
• Tx: 1st line therapy = SSRIs/SNRIs and/or CBT, based on availability/pt preference; no head-to-head trials (meta-analyses have found
effect sizes ≈ equivalent). No individual SSRI/SNRI shown more effective; SSRIs have lower risk of insomnia/activation over SNRIs.
Escitalopram, citalopram, and sertraline generally preferred due to fewer side effects.
o Advise pts that symptoms may take 4-6 weeks to resolve. For first few days, anxiety and activation may worsen as SSRI takes
effect. See Depression for dosing guidelines.
• Adjunctive therapy: Consider buspirone 10 mg, increase by 10mg/day q1-2weeks (note: little efficacy as an acute anxiolytic);
gabapentin 300- 800 mg TID; hydroxyzine 25-50 mg QID; lorazepam or clonazepam 0.5-1 mg PO BID PRN for 4-6 wks while SSRI
takes effect. If refractory, psychiatry may start risperidone/quetiapine. Counsel pt on dependence of BZD, and consider non-BZD
options first if history of substance use.
Refer to Psych: need for CBT, failure of 2 adequate SSRI/SNRI trials, severe GAD w/ recurrent panic, SI
PANIC DISORDER
• Epi: US lifetime prevalence ♀7.0% & ♂3.3% (AFP 2015;91:617)
• DSM-5-TR criteria: A) Recurrent unexpected panic attacks; B) >1 month of persistent worry about panic attacks or their
consequences, or >1 month of significant maladaptive change in behavior related to attacks; C/D) sx not better explained by
drugs/meds/other psych disorders (e.g. social anxiety disorder, specific phobia, OCD, PTSD)
• Workup for panic attacks: vitals, ECG, BMP, CBC, thyroid panel, HCG, tox screen. Consider testing for pheochromocytoma, seizures,
OSA, asthma/COPD if any clinical suspicion
• Treatment: 1st line = CBT and/or SSRI (equally effective). See GAD above for adjunctive therapies during SSRI initiation
Refer to Psych: need for CBT, severe symptoms, failure of 2 SSRI trials, SI
POST-TRAUMATIC STRESS DISORDER (PTSD)
• Epi: US lifetime prevalence 6%: ♂4.1%, ♀8%; higher in combat/severe disaster survivors (AFP 2023;107:273)
• Screening: Primary Care PTSD Screen (PC-PTSD-5): screens for trauma exposure then for sxs based on DSM criteria; score >4 with
Sn 100%, Sp 85.2% (J. Clin. Psychol 2022;78:2299), though cutoff of 3 may be more accurate for female pts due to higher false
negative rates (JAMANTW 2021;4)
• DSM-5-TR criteria:
o A) exposure to trauma
o B) intrusive sx (recurrent, involuntary trauma memories/dreams, dissociative flashbacks, psych distress, marked physiological
reactions to trauma reminders)
o C) avoidance sx (of trauma reminders)
o D) neg cognition & mood (incl amnesia of trauma, neg beliefs about self/others/world, inappropriate self-blame, neg emotional
state)
o E) hyperarousal (irritability/anger, reckless/self-destructive behavior, hypervigilance, exaggerated startle, sleep disturbance);
lasting >1mo & causing significant distress
• Treatment: trauma-focused therapy + SSRIs/SNRIs; tx of psych/SUDs comorbidities; clonidine, atypical antipsychotics; prazosin 1mg
nightly, increasing 3-15mg over few months for sleep disturbance. Counsel pt on risks of orthostasis and rebound HTN for
prazosin/clonidine if discontinued abruptly. All care/conversations should be trauma-informed, recognizing that not all patients
are ready to discuss trauma (and avoid probing patients on their trauma if so).
Refer to Psych: all should be referred for psychotherapy ± pharmacotherapy (depending on complexity of needs)
OBSESSIVE-COMPULSIVE DISORDER (OCD)
• Epi: US lifetime prevalence 2.3%. Mean age of onset ~19-20, rarely develops after early 30s (AFP 2015;92:896)
• DSM-5-TR criteria: A) presence of obsessions (recurrent and persistent thoughts/urges/images that are intrusive and unwanted, and
that pt tries to suppress) and/or compulsions (excessive or unconnected repetitive behaviors/mental acts that pt feels compelled to
perform in response to obsessions or rigid rules to reduce or prevent anxiety/distress); B) obsessions/compulsions are time-
consuming or cause significant distress/impairment; C/D) sx not better explained by drugs/meds/other psych disorders
• Treatment: 1st line = ERP and/or SSRI depending on pt preference, severity of OCD, and presence of depressive sx. Combination tx
is most effective (Curr Neuropharmacol 2019;17:710). Adequate trial of SSRI is maximum tolerated dose for 12 weeks. OCD pts
typically require higher doses than for other indications. If good response to SSRI, duration of treatment should be at least 1-2 years
with taper off over several months (AFP 2015;92:896). 2nd line = clomipramine, venlafaxine, or atypical antipsychotics
Refer to Psych: need for CBT, severe symptoms, failure to respond to 2 high-dose SSRI trials, SI

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Psychiatry Alcohol Use Disorder & Withdrawal

SUBSTANCE USE - GENERAL PRINCIPLES
Screening: Ask all primary care pts & inpatients about current and lifetime
substance use. USPSTF recs screening for unhealthy use. DSM-5-TR Criteria for SUDs
• EtOH: AUDIT-C screens for unhealthy use, CAGE detects dependence 1. Substance taken in larger amounts and/or over a
longer period than intended
• Other substances: “How many times in the past year have you used a
2. Unsuccessful efforts to cut down or control use
recreational drug or used a prescription medication for nonmedical
3. A great deal of time is spent to acquire, use the
reasons?” (Arch Int Med 2010)
substance, or recover from effects
History
4. Craving or strong desire or urge to use the substance
• Most recent use, quantity, frequency, route of ingestion, triggers for use
5. Recurrent use resulting in a failure to fulfill major
• Benefits vs. harms of use; medical, psychiatric, and behavioral role obligations at work, school, or home
complications of use; harm reduction practices
6. Continued use despite persistent/recurrent social
• Age of first use, family hx of use disorders, periods of abstinence or interpersonal problems
• Treatment hx: Medications, structured treatment settings, mutual 7. Important social, occupational or recreational
support groups. Current goals (↓ amt or freq of use vs. abstain) “What activities given up or reduced because of use
would you like to see next for yourself?” 8. Recurrent use in physically hazardous situations
Diagnosis 9. Use continued despite persistent or recurrent
• Use ≠ disorder. Assess for use disorder of all substances reported by physical or psychological problem that is likely
number of DSM-5-TR criteria met (impaired control, social impairment, caused or exacerbated by the substance
risky use, and pharmacological criteria): 2-3 = mild, 4-6 = moderate, ≥6 10. Tolerance, defined as amount of substance to
= severe. Once criteria for use disorder is no longer met, can classify
achieve desired effect; or ↓ effect w/ same amount
as early remission (<1y) or sustained remission (>1y).
11. Withdrawal, defined as characteristic withdrawal
• Ask about 1° vs. 2° substances used. “Of the substances you use, is
syndrome for the substance; or pt is taking substance to
there one you identify as the biggest problem?”
relieve or avoid w/d sx
• Avoid using Polysubstance use disorder ≠ DSM diagnosis =
stigmatizing while being diagnostically/therapeutically meaningless.
• Tox screens alone should not be used to diagnose SUDs. False positives and negatives are possible. It is not recommended to alter
prescribing patterns for meds based on tox screens. Use tox to check for concomitant substance use, monitor opioid use, and initiate
conversations around use with patients.
Approach: Person-first language and trauma-informed care. People w/ SUD experience bias and discrimination from healthcare providers.
Address drivers of self-directed d/c: pain, agitation, discomfort, treating w/d, and allowing pts to leave the floor (MGH policy) (Subst Abus
2020;41:519). Involve ACT (“Substance use team”) early. Consider risks of escalation before directly involving security (ex: may have
security in hall on standby).
Treatment: Medications: many can be prescribed by PCP, except for methadone. Counseling: MI, CBT; Peer support: recovery coach,
mutual help meetings (AA/SMART recovery). See Boston Area and MGH SUD Resources.
SUD Levels of Care
Levels of care usually progress from hospitalization/”detox” " CSS " TSS " long-term residential tx " sober living
Inpatient Outpatient
Acute Treatment Clinical
Services (ATS): Stabilization Long-Term
Service Partial
Medically Residential Intensive Outpatient
Dual Diagnosis Units Hospitalization
Supervised (CSS)/Transitional Treatment (“Halfway Program (IOP)
Program (PHP)
Withdrawal/ Support Service Houses”)
“Detox” (TSS)
-Medical mgmt of -Inpt programs to -Inpt locked psych -Covered by -Highly structured -Outpt., less
acute w/d in a transition from unit, address insurance outpt treatment, 6- intensive than PHP;
standalone detox ATS/hospital to comorbid SUD + 1° -Offer groups, 8h/d for 5d/w. usually ~3h/d for
center. longer treatment; psych disorders. counseling and -Intensive group 3d/w
-Not best for pts very structured -Often reserved for attendance at outside therapy; tx for both -Provides
with risk of severe with counseling. pts w/ severe mutual support SUD and MH psychoeduc./therapy.
alcohol withdrawal. -Usually go from comorbid sx +/- acute -Few offer meds esp concerns. -D/c coord: ACT SW
-LOS: 4-7d CSS to TSS. safety concern. (i.e in OUD (JAMA -D/c coord: Psych -LOS: 1-3mo
-Patients cannot go -D/c coord: ACT mania, psychosis, SI) 2020;324:804). -LOS: 1-3w
to ATS once SW -D/c coord: Psych c/s -D/c coord: ACT SW
admitted to the -LOS: 14d (CSS), -LOS: 3-5d -LOS: 6-12mo
hospital 30d (TSS)
ALCOHOL USE DISORDER (AUD)
Diagnosis and Health Effects
• Diagnose AUD w/ DSM criteria. Quantify use to counsel re: risks. 1 standard drink = 14g ethanol (5oz wine, 12 oz beer, 1.5 oz spirits)
• Risky use ↑ risk for health consequences (not part of SUD criteria). Includes drinking while pregnant; binge drinking: ≥5
drinks/occasion for men, ≥4 for women; heavy drinking: ≥15 drinks/wk for men & ≥8 drinks/wk for women or binge drinking 5 or more
days the past month (NIAAA).
• Chronic use: Cytopenia (low Hb, WBC, Plt); low K/Mg/Ca/Phos/VitD (EtOH toxic to renal tubules and ↓GI absorp); ketoacidosis (↓
gluconeogenesis → rel. hypoglycemia → ↓ insulin → ketosis); lactic acidosis (↑ratio of NADH/NAD) (NEJM 2017;377:1368)
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Psychiatry Alcohol Use Disorder & Withdrawal

Treatments for Moderate-Severe AUD
• Psychosocial: See above. 12-step progs ↑ rate of continuous abstinence compared to other counseling methods (Cochrane Rev 2020)
• FDA approved first line: naltrexone, acamprosate; second line: disulfiram; data suggests disulfiram efficacy only if dosing is observed
(JAMA 2018; 320: 815)
o Naltrexone (↓reward/cravings) PO 25mg X2d 50mg daily or IM (Vivitrol) 380mg q4w (CI: acute hepatitis/ALF, current opioid
use or on bup or methadone). Naltrexone likely > acamprosate (JAMA 2006;295:2003)
 Assess for OUD first as Naltrexone will block effects of opioids and precipitate withdrawal
o Acamprosate (↓cravings) 666mg TID (Adjust dose at CrCl <50, CI: CrCl<30, pregnancy)
o Disulfiram ( disulfiram-ethanol reaction: nausea, flushing, vomiting, sweating, hypotension, palpitations, rarely serious CV rxs):
Start PO 125-250mg daily  250-500mg/d maintenance dose
 Only for patients in sobriety wishing to abstain. NOT advised to “reduce” active drinking (JAMA 2018; 320: 815)
• Non-FDA approved: topiramate (100-150mg BID), gabapentin (~600mg TID) (Addiction 2019;114:1547), baclofen (5mg TID -> 15mg
TID) (Am J Psych 2018;175:86)
• Success can range from reducing heavy drinking days to abstinence (Addiction 2021;116:1973). Utilize principles of harm reduction.
Set goal with patient and use benchmarks to assess treatment efficacy.
• Risk of malnutrition with continued alcohol use. Assess lytes. Consider prescribing MVI w/ folic acid, thiamine 100 mg daily (Drug
Alcohol Depen 2017;179:229)
Wernicke-Korsakoff Syndrome
• Wernicke encephalopathy (acute):
o Dx: Caine Criteria (85% Sn) requires ≥2: (1) dietary deficiency, (2) oculomotor dysfxn, (3) cerebellar dysfxn (LE ataxia), (4) AMS
or poor memory. Note: Serum B1 NOT diagnostic (J Neuro Nsgy Psych 1997;62:51)
o Tx: Thiamine IV>IM 500mg (infuse over 30 mins to prevent anaphylaxis) TID X7d  100mg qd until no longer at risk (*not per
the Alcohol Withdrawal Orderset. No consensus on dosing or duration of Thiamine. However, adverse effects of excessive
Thiamine are uncommon while untreated W-E  irreversible W-K) (Intern Med J 2014;44:911)
o Ppx in those at risk: IV 200mg X1d > 200mg PO BID X4d (find under Alcohol Withdrawal Orderset – Adjunctive Mediciations)
100mg qd at discharge until no longer at risk
• Korsakoff’s (chronic): Antero+retrograde memory deficits (confabulation), apathy, intact sensorium
ALCOHOL WITHDRAWAL SYNDROME
Pathophysiology: GABA (inhibitory) and glutamate (excitatory) work in balance
• Chronic EtOH use: ↑GABA stimulation → glutamate upregulation. After chronic stim, GABA receptors are less sensitive & require
more EtOH to balance increased glutamate. Abrupt cessation of EtOH: ↓GABA → unbalanced excess glutamate activity →
noradrenergic surge → ↑dopamine release → complicated withdrawal sxs.
• EtOH eliminated via approx 0th-order kinetics: approx. 15-20 mg/dL/hour. Blood EtOH clearance calculator.
• BAC effects vary widely by person and chronicity of EtOH use. For many, BAC can be approximated grossly as: <80 mg/dL: legal
driving limit // 100 mg/dL: impaired judgment // 200 mg/dL: confusion/staggering // 300 mg/dL: stupor // 400 mg/dL: coma/death
Evaluation:
• H&P: Time of last drink, hx severe withdrawal & complications (withdrawal seizures, delirium tremens, alcoholic hallucinosis,
ICU/intubation), hx of patient-initiated discharge, co-ingestions (including BZD), EtOH use hx and tx, including recent changes in use
pattern, assess for active SI and concurrent mental health conditions
• Labs: CMP, CBC, serum osm if HCO3 <15 or AGMA (2/2 ketoacidosis), LFTs, CPK if found down (>5K = rhabdo), tox screen, serum
EtOH (clear ~15-35 mg/dL/h, chronic = faster metab, higher tolerance) (J Forensic Sci 1993;38:104), pregnancy test if of childbearing
potential > consult OB if in third trimester/at risk of pre-term delivery/concern for Fetal Alcohol Syndrome. Consider testing HIV, HCV,
TB if clinically appropriate.
Subtypes and Management: Sx vary by time after last drink, developing within hrs to days after cessation/reduction in use that has been
heavy and prolonged (Diaphoresis, HR>100, hand tremor, insomnia, nausea/vomiting, transient visual/tactile/auditory hallucinations,
agitation, anxiety, GTCs).
• Prediction of Alcohol Withdrawal Severity Scale: PAWSS
• Initial Tx for all EtOH withdrawal: IV/IM thiamine (See Wernicke-Korsakoff above), D5-LR to fix ketoacidosis, replete lytes (esp
Phos/K), folate 1mg qd, MVI, place on CIWA (q1-4h assessment, d/c once CIWA-Ar<8 for 24h), offer ACT (“Substance use team”) c/s
for AUD treatment
• Mild withdrawal (CIWA-Ar <10): Can be managed in ambulatory setting with supportive care (non-ceffeinated fluids, MVI, thiamine
100mg PO 3-5D, RTC precautions) (ASAM 2020); or can consider taper of gabapentin>> PO BZD (Alcohol Clin Exp Res 2009:33:9):
 Gabapentin 1200mg loading dose + 600mg q6h Day 1 or 1200mg/d 1-3D, tapered to 300-600mg/d up to 4-7D (ASAM 2020)
• Mild-moderate withdrawal (CIWA-Ar: 10-18): Within 48h; tremors, sweats, ↑HR, ↑BP, HA, anxiety, intact orientation.
 Treat with Rx. Use EtOH withdrawal order set. Typically BZD >> phenobarbital (unless contraindication to BZD or hx of
comp. withdrawal). Some patients benefit from addition of adjunct medication. Consider carbamazepine or gabapentin in
addition to BZD.
• Severe withdrawal (CIWA-Ar >19): ALWAYS TREAT, can be fatal. IV BZD vs. phenobarb using EtOH withdrawal order set, as
detailed below. Predictors: hx of DT/sz, comorbidities (especially TBI), age>65, ↑BP, ↓Na/↓K, Plt <150 (JAMA 2018;320:825).
 Seizures: 6-48h; typically 1x GTC or burst of multiple GTCs in a short period. If status epi, consider other etiologies. Should be
immediately treated to prevent another seizure. Fast-acting BZD: lorazepam, diazepam
 Alcoholic hallucinosis: 12h-48h; visual/tactile >> auditory (pt typically aware that hallucinations are not real), clear sensorium.
 Delirium Tremens (DT): 72h-3d, up to 2w; tremors, sweats, HR, BP, fever, disorientation, inattention, hallucinations (pt
typically unaware that hallucinations are not real), agitation; usually CIWA >20.

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Psychiatry Alcohol Use Disorder & Withdrawal

A L C O H O L W I T H D R A W A L T R E A T M E N T P R O T O C O L S : Use Epic Alcohol Withdrawal Order Set!
Benzodiazepine (BZD) Phenobarbital (PB)
When Generally 1st line. Mild-mod w/d sx, no Recent (within last 2-3 years) DTs, seizures, ICU admissions for w/d; patient
to use recent (within last 2-3 years) complicated preference for phenobarb; Resistant Alcohol Withdrawal (RAW)/ Refractory
w/d Alcohol Withdrawal: severe or complicated withdrawal or CIWA scores not
improving despite high doses of BZD
Notes CI: Acute angle closure glaucoma CI: hx SJS/TEN; hx AIP; unstable respiratory status
Resistance (>6mg lorazepam/h) or BZD Relative CI: high likelihood of self-dir d/c interrupting therapy, limited period of
toxicity (similar to DTs) w/ escalating dose. recent use (ex: completed withdrawal treatment in last 10 days)
Consider switch to phenobarb if CIWA Side effects: apnea, hypoventilation, ↓HR, ↓BP, laryngeal spasm
scores not improving despite high doses of Medication interactions: CYP3A4 inducer – decreases conc. of many rx
BZD including apixaban. May enhance effects of anti-HTN meds.
Mech. GABA-ergic. t1/2 varies by BZD GABA-ergic and anti-glutamate receptor. Auto-taper, long half-life (1-4d),
predictable effect, wide therapeutic window.
Dose PO > IV if able to take PO Loading dose: 10mg/kg as 3 divided doses (if worried about oversedation i.e.
No evidence showing superiority of older age, other sedating meds, high risk of respiratory compromise). No taper
effectiveness among BZDs in most cases.
Diazepam, chlordiazepoxide: Longer half -dose (6-8 mg/kg) if sedation carries high risk: age>65, TBI, concurrent
life, often preferred for smoother withdrawal sedatives, lung dz, decompensated cirrhosis, Received 8-30mg Ativan (or
course and breakthrough control BZD equivalent):
Lorazepam: (half-life, lower risk of
oversedation if concerned for liver dx) Rescue dose: 2mg/kg for tremor/tongue fasciculations AND one of the
PRN: Use CIWA-Ar scale when patient can following: SBP>165, HR>115, diaphoresis. DO NOT give for agitation,
appropriately communicate. Avoid treating hallucinations
for subjective symptoms only. Consultants
may rec “objective CIWA” if concerned for
BZD-seeking
Standing: If CIWA >19, likely to have
severe w/d > consult ACT for
consideration/implementation
D/C Monitor CIWA score, what sx they are Assess frequently: IM loading dose is split to allow monitoring: 40% 0h, 30%
scoring for, and total daily BZD 3h, 30% 6h. If uncontrolled sx or sedation, call pharmacist.
requirements. Consult ACT team for Rescue dose as above.
assistance w/ pharamacologic and Discharge: phenobarbital increases sensitivity to BZDs/EtOH; drinking after
psychosocial mgmt of AUD, or if IV/IM load can be fatal.
considering standing BZD taper and unsure
of dosing sched.
 Clonidine can be used as adjunct for autonomic hyperactivity and anxiety when not controlled by BZD alone.
 Beta-blockers can be used as adjunct in select patients for persistent hypertension or tachycardia. Should not be used alone in
tx of alcohol w/d

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Psychiatry Opioid Use Disorder & Withdrawal

OPIOID USE DISORDER (OUD)
• Chronic, relapsing disorder of opioid use due to dysfunction of brain reward circuits (J Addict Med 2015;9:358)
• Screen all patients. Confirm diagnosis using DSM-5-TR Criteria for opioid use disorder. Use ≠ SUD. See SUD General Principles.
• Focus on building a therapeutic alliance and performing risk assessment (Med Clin N Am 2018;102:587)
o Assess risk of withdrawal: current opioids, frequency of use, last use PTA, g/day or $ spent/day, recent withdrawal
o Assess treatment readiness: treatment hx (medications, counseling, mutual-aid organizations), social circumstances (housing,
food security, legal issues). Understand patient’s current goals, including safer use vs abstinence
o Assess for high-risk injection practices: history of bacterial/fungal complications (endocarditis, SSTIs, bone/joint infections),
viral complications (HIV, HCV, HBV). If currently injecting, use PCOI harm reduction conversation guide to review injection practices.
Consider PrEP for patients with high-risk injection practices (see HIV/AIDS)
o Assess risk of overdose: h/o OD, h/o psychiatric (i.e. mood) disorder or suicidality, tolerance from recent incarceration or
abstinence-based treatment, access to naloxone, high-dose Rx’d opioids and/or other sedatives (check PDMP), incr alcohol use,
injection use, respiratory disease, severe chronic pain (Addiction 2015;110:996; Lancet 2019; 393: 1765)
• Labs: serum/urine tox (fentanyl now included in urine tox but may take days to result), LFTs, HIV, HBV/HCV, TB, syphilis, EKG.
• Tx: agonist treatment with buprenorphine or methadone is 1st line tx for opioid withdrawal and OUD. Should be offered to every
patient with OUD. Long-term agonist therapy for OUD decreases morbidity and mortality (BMJ 2017;357:j1550). When choosing bup
vs. methadone consider long-term plan: methadone = daily observed administration at clinic. Buprenorphine = transmucosal TID vs.
long acting injectable qmonth vs. subcutaneous injection q6mo prescribed by outpatient provider.
• Pain control: pts w/ OUD and/or chronic opioids likely have developed tolerance and require high doses of opioids to treat pain
o If using non-prescribed opioids: can initiate methadone for withdrawal & add short-acting opioids titrated to pain
o If taking methadone: give usual dose (once confirmed) & add short-acting opioids (e.g. oxycodone) titrated to pain
o If taking buprenorphine: there are several strategies. MGH peri-operative guideline
 For pain of short duration, may continue daily bup & add short-acting opioids (may need high doses, consider PCA)
 Give total daily dose of bup divided 3-4x daily (e.g. 4-8mg q6-8h for mod-severe pain)
 D/c bup & use short-acting opioids to tx acute pain. Blocking effects of bup wear off after 24-72h, so monitor for OD (initial
opioid dose is higher than pt will need). After pain resolved, re-start bup (CMAJ 2016;188:1232; Annals 2006;144:127)
A C U T E O P I O I D O V E R D O S E ( O D ) (NEJM 2012;367:1372)
• Signs: mental status, RR, tidal volume, miosis. Normal pupils do not exclude opioid toxicity  co-ingestions may be
sympathomimetic/anticholinergic. Rare: hypoxic seizure. Acute toxicity is a clinical diagnosis; ⊕ tox screen does NOT confirm toxicity
• Acute stabilization: assess airway (mental status). If apnea and/or stupor, bag valve mask (with O2). Administer naloxone
• Naloxone: goal is to improve mental status, SpO2, and ensure RR>10, NOT to achieve normal level of consciousness
o Dose: 0.4mg IV, if no response increase dose q2 min:0.5mg2mg4mg10mg15mg. Can administer intranasally or IM
o Effect lasts 20-40min, but most opioids last longer. OD can recur after naloxone wears off so may need to redose or start gtt.
o NB: too much naloxone will precipitate opioid withdrawal. Consider diluting 0.4mg in 10cc saline and push 1cc q2-3min
o If failing to respond, consider intubation (STAT RICU consult)
• Post-resuscitation: continuous O2 monitoring, CXR (post-OD pulmonary edema does NOT respond to diuretics, may evolve to
ARDS), APAP level. Examine skin for fentanyl patch (remember fever + patch  overabsorption). Consider naloxone gtt
ACUTE OPIOID WITHDRAWAL
• S/Sx: dysphoria, restlessness/irritability, muscle twitching, yawning, piloerection, mydriasis, rhinorrhea, myalgia/arthralgia, lacrimation,
n/v/d, abd cramping. Onset: 6-12h after short-acting opioids, 24-48h after last methadone, variable for fentanyl analogs (long half-life)
• Buprenorphine: high affinity partial agonist with lower risk of respiratory depression/OD than methadone
o Wait until Clinical Opioid Withdrawal Scale (COWS) >10, usually 10-12h after last heroin use/short acting opioids. Avoid
precipitated withdrawal—rapid, intense withdrawal due to displacement of full agonist by partial agonist
 First dose: 4mg/1mg (1/2 of an 8mg/2mg bup/nal film). Second dose: if continued withdrawal sx, give another 4mg/1mg
after 45-60min. Third dose: if recurrent withdrawal sx, give another 4mg/1mg after 6-12h
 Maximum dose for Day #1 is 12mg buprenorphine (unless PDMP documented recent tolerance of higher doses)
 Prescribe total from Day 1 for Day 2, then reassess later in the day. Can give additional 4mg/1mg for withdrawal
symptoms. Max dose for Day #2 is 16mg buprenorphine
o Microdosing (Bernese Method): start w/ small initial dose of bup (0.5mg) & incrementally increase dose & freq over 7-10d while
pts continue other opioids (prescribed or recreational) until therapeutic bup dose (>8mg daily) achieved (CMAJ 2020;192:E73)
• Methadone: long-acting full agonist. Check and trend ECG for QTc, use with caution with other QTc-prolonging meds.
o Day 1 initial dose: 20mg-40mg x1 (20mg dose for pt >60, c/f ↓tolerance, concurrent sedating meds/BZDs, or liver dysfnx). F/u
COWS q4h. If >2h s/p first dose and COWS >12 or pt reporting w/d, spot dose 10-20mg x1. MUST call ACT if ≥60 mg daily dose
o Day 2: Continue dose if COWS <6; incr. by 10-20mg if COWS 6-12. If not pursing methadone maintenance, consult ACT
• If unable to initiate suboxone/methadone, or if in precipitated wd, offer symptomatic medications and short-acting opioids for pain:
o Autonomic dysreg: clonidine 0.1-0.2mg TID PRN/lofexidine 0.54-0.72mg QID PRN; avoid w/1st bup/methadone dose, watch BP
o GI upset: Bentyl 10-20mg q6h PRN abd cramps; ondansetron 8-16 mg q8-12 PO/IV PRN, promethazine 25-50mg IM PRN N/V;
loperamide 2mg PRN diarrhea
o Anxiety: hydroxyzine 25mg q8h PRN or trazodone 50-100mg q8h PRN; if precip w/d, consider lorazepam 1-2 mg q6h PRN
• Discharge: ensure pts have insurance, PCP, provider to prescribe bup/nal or methadone, list of shelters/needle exchanges, PrEP
o Last dose letter for patients on methadone maintenance (includes date/amount of last methadone dose)
o Prescribe naloxone and teach OD response. Emphasize that naloxone reverses OD for ~30min. After OD  EMS to the ED
o Bridge Clinic: call 617-643-8281 Mon-Fri 8am-4pm to schedule appt or present as walk-in
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Psychiatry Other Substance Use

T O B A C C O (USPSTF: JAMA 2021;325:280, ATS: AJRCCM 2020;202:e5)
Screening: Tobacco: 5A’s framework: Ask about use, Advise to quit, Assess readiness, Assist if ready, Arrange follow up.
Treatment: Combination of counseling and medication is most effective (Cochrane Rev 2016).
• Set a quit date, typically in 2-4w. Abrupt cessation more effective than taper (Annals 2016;164:585).
• Counseling: Individual, group, cessation coach, telephone support lines; smoking cessation resources at MGH.
• Pharmacotherapy: Varenicline is first line and should be started even in patients not ready to quit (AJRCCM 2020;202:e5). For those
patients planning to quit, start pharmacotherapy 1-2w prior to quit date; continue for 3-6mo; monitor tobacco use to see decrease.
o Varenicline: 0.5mg qd x3d  0.5mg BID x4d  1mg BID. SEs: nausea, insomnia/vivid dreams; avoid if hx PTSD/SI, but
recommended in other comorbid psych conditions (AJRCCM 2020;202:e5); monitor for neuropsychiatric symptoms
o Bupropion: 150mg qd x3d  150mg BID. SEs: insomnia, agitation, HA, dry mouth. CI: seizure disorder. Relative CI: ↓GFR
o Nicotine Replacement Therapy (NRT): long acting (patch) + short acting (lozenges/gum/nasal spray)
CANNABIS
• Intoxication: Euphoria followed by relaxation; tachycardia; hallucinations (especially w/ high potency THC, e.g. wax/dab)
• Drug interactions: Research not definitive, cannabis may increase warfarin levels (Basic Clin Pharm Tox 2019;124:28)
• Cannabinoid hyperemesis syndrome: Dysreg of GI cannabinoid receptors  recurrent n/v, abd pain, sx relief w/ hot showers, mild
leukocytosis. Tx: THC cessation, IVF, antipsychotic (haloperidol), BZD, capsaicin cream (Exp Opin Pharmacoth 2022;23:693).
• E-cigarette or Vaping Associated Lung Injury (EVALI): Dx of exclusion in respiratory failure <90d after e-cig/vape use. b/l GGOs;
BAL with lipid laden macrophages. Possibly due to Vit E acetate (NEJM 2020;382:903). Suspected cases must be reported to MA DPH.
• Tx: No FDA-approved meds. Topiramate, NAC, gabapentin, dronabinol, nabilone may help cravings (Pharmacotherapy 2016:511).
SYNTHETIC CANNABINOIDS (SPICE/K2/BATH SALTS)
• Intoxication: Agitation/violence, hallucinations, paranoia, anxiety, tachycardia, arrhythmia, myoclonus, diaphoresis. Variable time to
symptom onset and recovery based on synthetic used, quantity consumed, and route of use (inhalation, ingestion).
• Tx: Low stimulation environment, IVF, consider IV/IM BZD to reduce agitation and prevent seizure (Curr Psychiatry Rep 2016;18:52).
BENZODIAZEPINES
• Intoxication: Memory impairment, disinhibition, Commonly Used BZDs ~ Equiv Dose Half-life (hours)
psychomotor slowing, depression, amplified w/ EtOH. Alprazolam (Xanax) 0.5mg 6-27 (oral peak 1-2)
• Withdrawal: Anxiety, irritability, tremor, HA, nausea, Chlordiazepoxide (Librium) 25mg 5-30 (oral peak 0.5-4)
autonomic instability, photo/phonophobia, seizures, Clonazepam (Klonopin) 0.25mg 18-50 (oral peak 1-2)
paranoia, hallucinations, depersonalization, and Diazepam (Valium) 5mg 20-50 (oral peak 0.5-1)
delirium. Duration depends on half-life of agent, ranges Lorazepam (Ativan) 1mg 10-20 (oral peak 2-4)
from 2-10d (NEJM 2017;376:1147). Can be lethal.
Temazepam (Restoril) 10mg 3-19 (oral peak 1-2)
• Abstinence syndrome weeks after cessation:
Anxiety, tachycardia, restlessness.
• Tx: Manage severe w/d inpt (see Alcohol Withdrawal). Consider taper w/ same BZD. Consider collab w/ outpt prescribers
STIMULANTS: COCAINE, METHAMPHETAMINE, PRESCRIBED STIMULANTS
Cocaine:
• Intoxication: Euphoria, hyperactivity, grandiosity, anorexia, anxiety, psychotic sx (formication, paranoia, AH/VH). ½ life ~1h.
• Withdrawal: Depression, fatigue, nightmares, cravings,sleep/appetite. Acute w/d tx: Supportive care, BZD if symptoms severe.
• Complications: Acute: vasospasm, HTN emergency (Tx: BZD, phentolamine if refractory, nitroglycerin; avoid βB), ACS (Tx: ASA,
nitro, BZD), arrhythmia, ischemic bowel. Chronic: LVH, cardiomyopathy (NEJM 2001;345:351). Intranasal: nasal septum perforation,
ulcers, chronic rhinitis. Inhalation: cough, SOB, hemoptysis, PTX. “Cocaine-Induced Lung Injury”: syndrome of fever, hemorrhagic
alveolitis, respiratory failure, eosinophilic infiltration thought d/t levamisole additive. Injection: discuss harm reduction practices, eg
using vitamin C powder as acidifier over lemon juice (fungal infxn) or vinegar (damages veins), use PCOI guide and Grayken guide.
Methamphetamine:
• Intoxication: Similar to cocaine. Sympathetic activation, executive dysfunction, memory impairment, libido. ½ life ~6-12h.
• Complications: HTN, hyperthermia, rhabdomyolysis, may exacerbate existing psych sx. Tx for severe agitation: BZD first line.
Stimulant Use Disorder Tx: Consult ACT. Limited psychosocial programs in community and mixed evidence for pharmacotherapy.
• Psychosocial: Contingency management is best supported; also consider CBT, community reinforcement, motivational interviewing.
• Pharmacotherapy: No FDA approved meds. Insufficient evidence for replacement therapy, opioid agonists or NAC across all
stimulant use disorders (PLOS ONE 2020;15: e0234809). Replacement therapy may help sustain cocaine abstinence (Cochrane
Review 2016). Consider topiramate and/or baclofen for cocaine cravings/dependence (Psychiatry 2005;2:44). IM ER naltrexone + PO
ER bupropion may reduce meth use (NEJM 2021: 384;140).
HALLUCINOGENS
MDMA/Ecstasy: Intox: Euphoria, HTN, hyperthermia, stimulant properties. ½ life ~2h. Complications: HypoNa, serotonin synd, seizure
LSD: Intox: Euphoria, synesthesia, depersonalization. Complications: Frightening imagery. Rare vital sign abnormalities.
XYLAZINE (TRANQ)
• Intoxication: α2 agonist found as adulterant, thus most overdoses are concomitant with fentanyl. Bradycardia, resp depression,
hyperglyc, miosis, hypothermia, PVCs, transient HTN  sustained hypotension. ½ life ~23-50min Tx: No specific reversal agents for
humans. Treat concomitant opioid OD. (Addiction 2024;119:606)
• Xylazine wounds: necrosis w/ black eschar. Tx: Standard wound care.
CIVIL COMMITMENT FOR SUBSTANCE USE DISORDER TREATMENT (Section 35 in MA - MGL ch.123 §35)
Process by which the court may involuntarily commit someone to inpatient SUD treatment when there is immediate likelihood of serious
harm as a result of the SUD. Petition must be filed by MD, blood relative, spouse, guardian, police officer, or court official.
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Psychiatry Drug Testing

MGH TOXICOLOGY SCREENS
• Basic serum toxicology screen: Quantitative assay for EtOH, salicylates, acetaminophen; Test Turnaround
qualitative assay for TCAs. Serum tox 2 hours
• Urine drug screen (VDAU): Qualitative screen for amphetamines, BZDs, cocaine, opiates, Urine tox 2 hours
fentanyl, oxycodone. Not included: THC, bupe, barbituates, methadone, meperidine, LSD, PCP, SUD 2-24 hours
propoxyphene. If a patient may need a THC test (often needed for transfers to facilities such as Oral tox 2-3 days
McLean or if ordering w/u for depression, mania, psychosis), please include in original utox order
• SUD management panel (VPP2): Same as VDAU + bupe, methadone (24h turn-around).
• Oral drug screen: Amphetamines, buprenorphine, benzos, cocaine & metabolite, opiates, methadone, oxycodone, 6-MAM, fentanyl

ORAL VS. URINE TESTS Detection Time of Drugs in MGH Toxicology Screens*
• Oral drug mass spectrometry: Used for outpatient Urine Oral
testing for chronic opioids or buprenorphine. Urine Tox Panel (VDAU)
Differentiates BZD subtypes and opiates. Superior Amphetamine, methamphetamine 1-3 days 3-6 days
sensitivity/specificity of amphetamines, opioids and Benzodiazepines
cocaine. More expensive than UTox screen. Alprazolam 2-3 days 1-2 days
o ODS technique: Rinse w/ 40 mL water for 30 Chlordiazepoxide 10-20 days 5-10 days
seconds and swallow prior to test, repeated Clonazepam 5-10 days 5-10 days
twice. Wait 10 minutes (early testing  false Diazepam 10-20 days 5-10 days
negative), then place swab under tongue. Lorazepam Not detected 1-2 days
• Urine drug screens: Cheap, easy, noninvasive. Cocaine 2-5 days** 2-7 days**
Used more often on inpatient. Does not differentiate Opiates (morphine, codeine) 2-4 days** 2-4 days**
subtypes of BZDs or opiates. Superior sensitivity for Hydrocodone, hydromorphone 2-3 days 2-3 days
BZDs but does not detect lorazepam. Superior Fentanyl 2-3 days*** 2-3 days***
sensitivity for buprenorphine (detects doses as low
as 2mg/d). THC, barbiturates, and 6-MAM must Oxycodone -2-3 days 2-3 days
be ordered separately. Urine SUD Panel
o Tampering: More common w/ UDS (e.g Buprenorphine 2-3 days 6-10 hours
synthetic urine, smuggling/storing urine in Methadone 5-10 days 5-10 days
bathroom) *Estimates updated 3/2023 from MGH laboratories (James Flood, PhD and Sacha
Strategies to minimize UDS tampering: direct observ, Uljon, MD PhD) Detection times are specific to MGH and are not hard cut-offs.
check specimen cup temp, ask pts to leave belongings **Longer in chronic/high-dose users
***Best available estimates (detection time for chronic/high-dose fentanyl users over
outside bathroom
long period of time is unknown)

Drugs Detected False Positive False Negative Comments

Amphetamines Amphetamine, Beta blockers, Ritalin does not cause
methamphetamine, ranitidine, bath a false positive
ecstasy/MDMA salts, trazodone,
bupropion
Benzos Alprazolam, chlordiazepoxide, Lorazepam, Clonazepam detected
Urine Tox Panel (VDAU)

clonazepam, diazepam, temazepam even at 1mg/day

triazolam
Cocaine Benzoylecgonine None
metabolites
Opiates Morphine, hydromorphone, Poppy products, Oxycodone, Fentanyl, methadone,
codeine, hydrocodone, heroin rifampin, oxymorphone naloxone, naltrexone
levofloxacin do not interfere
Fentanyl Norfentanyl (metabolite),
fentanyl
Oxycodone Oxycodone and metabolite Substances
oxymorphone imparting color to
urine (e.g., Flagyl)
Buprenorphine Parent drug and major
metabolite
Urine SUD

Methadone Methadone Quetiapine, Does not cause false

Panel

tramadol, positive for opiates

vortioxetine,
chlorpromazine
SOURCE: MGH TOXICOLOGY LAB AND PCOI

INTERPRETING RESULTS
Tox screens alone should not be used to dx SUDs as they do not give information on frequency or intensity of use. False positives and
negatives are possible. It is not recommended to alter prescribing meds based on positive tox screens; instead, use these tests to check
for concomitant substance use, monitor opioid use, and initiate conversations around use with patients. The best tox screen is a respectful
history.

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Primary Care Health Screening & Maintenance

G E N E R A L S C R E E N I N G G U I D E L I N E S [Evidence Grade] (aUSPSTF, bADA, cAACE, dACC/AHA, eACCP, fACS)
Age 18 1920 21 25 30 35 40 45 50 55 60 65 70 75+
Cardiovascular Screening/Preventative Health Recommendations
Estimate risk w/ ASCVD calculator Q4-6y [B]d
Assess RFs Q4-6y [B] d If ASCVD risk ≥10% prescribe a statin* [B]a *If ASCVD risk 7.5-10%
CVD Risk (age, sex, Tchol/HDL, HTN, DM, CKD, consider statin [C]a. Insufficient evidence for/against statin for age >75 [I].a
smoking, FHx) PREVENT risk calc (30-79y) will soon replace the above. Provides 10yr and 30yr risk.
Race free. Includes eGFR/UACR, BMI, A1c, and zip code (proxy for SDH)
Consider in 40-59y w/ ASCVD risk
ASA for 1° ppx Not rec for adults >60 [D]a
≥10% w/ no ↑risk of bleedingδ [C]a,d
If HTN or BMI ≥25 (≥23 Asian) w/ ≥1 DM RF^, or Fasting plasma glucose or A1C [B]b Screen minimum Q3y. interval if abnl result
DM
GDM [B]b or new RF (e.g. weight gain) [C]b  annually in pre-DMb
HTN Q3-5y; Q1y if elevated BP reading, obese, AA [A]a Q1y [A]a
M >45, F >55
Insufficient
Men 20-45, women 20-55: screen Q5yr,  if RF [C]c Q1-2y if no RF*
HLD evidence for Screen Q1y [A]c
Q1y in DM [B]c [A]c, Q1y in DM
screening [I]a
[B]c
Obesity Annual BMI [C]d  refer for or offer comprehensive lifestyle program if ≥25 (see Weight & Weight Loss) [B]d
Diet Intensive behavioral counseling if CVD RF* [B]a
Exercise 150min/wk moderate-intensity exercise or 75min/wk intense-exercise & 2d of muscle strengthening activity [A]d
Universal Cancer Screening
Start 10y prior to age of affected family member at 45-49 needs colo Q10y, flex sig Q5y,or FIT testing Q1y [B]a ; if flex sig
Colorectal CA +/-**
dx** or FIT abnx, will need colo. If colo abnx, path determines f/u
(Age 50-80) Q1y low-dose CT if 20 pack-yrs or more
Lung CA
(regardless of quitting date) or if current smoker [B]a***
Infectious Disease Screening
HIV Screen all age 15-65 at least once; repeat based on risk assessment [A]a
HCV Screen all 18-79 at least once; repeat based on risk assessment [B]a
HBV Born in endemic region, getting HD or immunosuppressed, HIV+, IVDU, MSM, close contact w/ HBV+ person [B]a
Latent TB Screen if born or lived in high risk country (see USPSTF recs) or high risk setting (homeless, jail) [B]a
Syphilis Screen in all individuals at increased risk of infection [A]a
Psych/SUD/Social Risk Factor Screening
Q1y [B]a by PHQ-2: in 2w how often (a) little interest/pleasure doing things & (b) down/depressed/hopeless
Depression
(JAMA 2020;323:2290). Not enough evidence to recommend for or against screening for suicide [I]a
Anxiety Screen regularly in adults ages 19-64, various screening tools such as GAD-2 or GAD-7 [B]a
Alcohol Screen regularly with AUDIT-C [B]a
Every encounter [A]a. Advise to quit, Assist doing so (plan, quit date, QuitWorks, meds), Arrange f/u.
Tobacco
Strong evidence to start varenicline (Chantix) over other tx options, despite psych comorbidities or readiness (AJRCCM. 2020;202:e5)
Unhealthy Drug Screening [B]a via asking questions about unhealthy drug use (not drug testing) is beneficial when services for accurate diagnosis,
Use effective treatment, and appropriate care can be offered (JAMA 2020;323:2310)
Inter-partner Screen regularly in women of reproductive age [B]a. Use HITS tool. Assess immediate Consider screening for ongoing IPV, elder
Violence safety & consider HAVEN referral. ↑ rates in LGBT population. abuse screening [I]a
Fall Risk Yearly screening, PT, Vit D [B]a
*If ASCVD borderline risk (5%-7.5%), use risk-enhancing factors [FHx, LDL-C ≥160, metabolic syndrome, CKD, S. Asian race/ethnicity, chronic inflammatory disease
including HIV, menopause <40y, pre-eclampsia or pre-term delivery, abn biomarkers (e.g. hsCRP, Lp(a), apoB, ABI)] or coronary artery calcium score to guide decision about
statin (see Outpatient CV Health)
δHistory of previous GIB or PUD or bleeding from other sites, thrombocytopenia, coagulopathy, CKD, and concurrent use of other medications that increase bleeding risk

(NSAID, steroids, DOACs, Warfarin)

^DM RFs: prior abnl testing (A1c≥5.7), FHx, AA/Latinx/Asian/NA ancestry, Hx GDM, PCOS, CVD, HTN, HDL<35 or TG>250, physical inactivity, other conditions associated
w/ insulin resistance (e.g. obesity)
**Begin at age 40 or 10y prior to earliest dx in fam (whichever comes first) for ≥1st degree relative dx<60 or two 1st degree relatives of any age; Age 40: ≥1st degree relative
dx≥60; 75+: based on life expectancy. Early screening for special populations: hx of high-grade polyp, IBD, prior colon or rectal ca, hx prior pelvic/gut radiation, genetics.
***Consider screening cessation if limited life expectancy or screening would impede surgical candidacy.
A D D I T I O N A L S C R E E N I N G G U I D E L I N E S F O R M E N [Evidence grade] (aUSPSTF, fACS, gEndo, hPCOI)
Age 18-40 40 45 50 55 60 65 70 75+
AAA If +tobacco hx [B]a *
Discuss risk-benefit if Disc. risk-benefit if
Discuss risk-benefit if Q1-2yδ if life expectancy ≥ 10yf
FHx** Q1-2yδf FHx***, AA Q1-2yδf
Prostate CA**,***
PSA 55-69y if pt preference [C]a,
recommend against if >70y [D]a
Testicular CA Recommend against routine screening in all men∑ [D]a
Anal CA# In MSM: anal Pap smears Q1y if HIV+ (space to Q3y after 3 neg Paps); consider Q2-3y if HIV-h
Osteoporosis If RF^g DXAg
In MSM: Q1y, Q3-6mo if multiple/anonymous partners or sex in conjunction w/ drug use; hx re: sexual practice can guide
STIs
screening (pharyngeal, anal, urine). Prescribe PrEP to patient at risk of HIV acquisition [A]a
*Society for vascular surgery recommends screening in men and women **Inform all patients of uncertainties, risks, and potential benefits before starting PSA screening
***Discrepancy between societal guidelines, USPSTF: individual risk-benefits discussion for persons with prostates aged 55-69 [C], stop screening at age 70 [D]. ACS: for
average-risk persons with prostate, start risk-benefits discussion at age 50, stop when life expectancy <10 years
δ Screening frequency varies based on level. PSA < 2.5ng/mL = Q2y. PSA ≥ 2.5ng/mL = Q1yf; Amer Urological Assoc recs Q2y interval

**>1 first-degree relative with history of prostate cancer at early age ***First-degree relative diagnosed with prostate cancer at age <65
^Low body weight, prior fracture, smoking ∑If higher risk (h/o cryptorchidism or orchiopexy, testicular atrophy, or sxs), evaluate, educate & consider periodic testicular exams

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Primary Care Health Screening & Maintenance

#Lacking evidence to inform screening initiation age & intervals. NYS DOH AI includes follow-up algorithm. Stop when life expectancy <10y
A D D I T I O N A L S C R E E N I N G G U I D E L I N E S F O R N O N - P R E G N A N T W O M E N [Evidence grade] (aUSPSTF, fACS)
Age 18 19 20 21 25 30 35 40 45 50 55 60 65 70 75+
Consider BRCA counseling if +FHx.
Breast CA* Q1-2y mammogram age 40-74. Stop if <10y life expectancy a,f
Screening tools available [B]a
Q5y 1° high risk HPV testing (preferred if available); if not available, Q5y
cytology + hrHPV co-testing OR Q3y cytology alonef If neg adequate
Cervical CA^δ∑
Q3y cytology Q5y 1° hrHPV testing (preferred)f OR co-testing (hrHPV & screening, stop
[A]a cytology) OR Q3y cytology alone [A]a,f
Ovarian CA Recommend against routine screening in asx women [D]a (Lancet 2021;397:2182)
STIs ≤24: GC/CT annually [B]a Screen based on risk assessment [B]a
Discuss with everyone including trans ♂ (see Women’s Health for contraception guidelines).
Contraception
Start folic acid at reproductive age if planning/capable of pregnancy [A]a
Osteoporosis Consider earlier screening based on FRAX assessment [B]a (see Osteoporosis) DXA [B]a
∗
Discrepancy btw societal guidelines despite same evidence. USPSTF: 40-74 Q2y [B]; >75 no recommendation [I]. ACS: 40-44 option to start Q2y screening; 45-54 Q1y; ≥55
discuss transitioning to Q2y screening until life expectancy <10y. ACOG: offer mammography at 40; start screening at 50; discuss cessation at 75; screen Q1-2 years
^All screening methods still accepted to promote access to adequate cervical cancer screening. USPTF recommends age 21 start whereas ACS recommends age 25. ACOG
recommends start at age 21 due to underscreening in younger populations.
δWomen w/ HIV require more frequent Paps & Paps preferred (HPV testing w/o cervical cytology is not approved). See NIH guidelines
∑
Subsequent screening dictated by age, prior screening results, and other factors. Use ASCCP Web App for algorithm of next steps.

ADDITIONAL SCREENING GUIDELINES FOR TRANSGENDER INDIVIDUALS*

Age 18-40 40 45 50 55 60 65 70 75+
CVD Risk As above; if patient has been on hormones for many years, use hormonal sex in the calculator
Consider at any age if s/p gonadectomy and >5y w/o Consider based on FRAX (no
Osteoporosis DXA
hormone tx guideline on which sex to use)
Trans ♀: Q2y after 5-10y hormone use
Breast CA
Trans ♂: if natal tissue present (incl s/p partial mastectomy), screen per guidelines for non-trans ♀
Cervical CA Trans ♂: if natal tissue present (incl s/p subtotal hysterectomy), screen per guidelines for non-trans ♀^
Prostate CA Trans ♀: screen per guidelines for non-trans ♂. Use lower ULN for PSA if on estrogen
*See Transgender Health
^Cells more likely to be “unsatisfactory” for interpretation on testosterone. On order, note that pt is on testosterone and/or amenorrheic. Self-collected vaginal swabs as
sensitive as provider-collected swab (PLoS 2018;13)

V A C C I N E S (CDC, aNYS DOH AI)

Immunizations 19-21 22-26 27-49 50-64 ≥65
COVID-19 1 or more doses of updated (2023-2024) formula
Annual flu vaccine Annual high dose flu vaccine
Influenza No live (intranasal) if immunocompromised (or contact), pregnant, asplenia, cochlear implant, CSF leak, ≥50; OK for
65+ to get regular adult flu vaccine if high dose not available
Tdap/Td 1 dose Tdap then Td or Tdap booster every 10 years; extra Tdap dose during each pregnancy
RSV Seasonal administration in pregnancy Recommended for adults 60+
1-2 doses based on indication (if born 1957 or later)
MMR*
1 dose in ♀ of childbearing age; 2 doses if HIV & CD4≥200, healthcare personnel, or college students
Varicella* 2 doses (if born 1980 or later)
Immunocompromised: 2 doses of RZV 1-2 mo apart All: 2 doses of RZV 2-6 mo apart
Zoster*
Administer RZV regardless of history of Zostavax (live, no longer available) administration
2-3 doses 27-45y SDM***
HPV**
3 dose series to all people with HIV up to 45ya
If never vaccinated, PCV20 x1 OR
PCV15 x1 followed by PPSV23 x1 ≥1
PCV15/PPSV23 Chronic heart, lung, kidney, or liver dz; DM; AUD; smoking; nephrotic
yr later. If partially/fully vaccinated
OR syndrome; CSF leak; cochlear implant; immunocompromising conditions:
before age 65, may need to repeat
PCV20 PCV20 x1 OR PCV15 x1 followed by PPSV23 x1 ≥ 8 wks or 1 yr later
vaccine. See CDC website for full
details.
Travel to endemic country, HIV, MSM, any drug use (not just IVDU), chronic liver dz, undomiciled, work w/ HAV, close
Hep A
contact to international adoptee, settings for exposure, pregnancy at risk for infxn: 2 doses
Universal vaccination for adults ages 19-59, as well as adults 60+ with risk factors for HBV (travel to endemic country,
HCV, HIV, sexual exposure risk, IVDU, chronic liver dz, incarcerated, mucosal or percutaneous blood exposure (incl
Hep B****
dialysis, DM, work exposure)
Recombivax HB: 3 doses (dose doubled if pre-dialysis or on HD); HEPLISAV-B: 2 doses
Functional/anatomical asplenia, HIV, complement (including by meds), travel to endemic country, freshmen in
Meningococcus**
dorms, military recruits
(MenACWY/MenB)
1-2 doses + Q5Y if risk remains (add MenB for asplenia, complements + Q2-3Y if risk remains)
Hib Functional or anticipated asplenia: 1 dose (if no prior); after HSCT: 3 doses (regardless of vaccination hx)
Any person at risk of monkeypox (persons who are gay, bisexual, and other MSM, transgender or nonbinary people
Monkeypox
who in the past 6 mo. have had a new STD dx or >1 sexual partner): 2 doses
*Hold live vaccines in pregnancy, malignancy, and immunocompromised (incl HIV w/ CD4 <200, cochlear implant). Ok if CD4 ≥200
**Wait until after pregnancy ***Shared decision making (SDM): most likely to benefit adults not yet exposed to HPV or w/ new sex partners
***Conduct complete serologic testing (HBsAg, anti-HBs, and anti-HBc) on all adults over 18 at least once in a lifetime. Boosters not recommended for most people who have
been vaccinated. For patients on HD, if anti-HBs <10 mlU/mL, a booster should be administered. For other immunocompromised people (HIV, stem-cell transplant recipients,
chemotherapy) the need for booster doses is undetermined. Also consider booster in patients with anti-HBs levels <10 mIU/mL with an ongoing risk for exposure.
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Primary Care Transgender Health

G E N E R A L C O N S I D E R A T I O N S (NEJM 2019;381:2451)
Gender Terminology
• Gender identity: a person's sense of one’s gender; can be congruent with or differ from sex assigned at birth
• Transgender/trans: a person whose gender identity is different from cultural expectations based on their sex assigned at birth vs
cisgender: sex assigned at birth and gender are congruent
• Non-binary, gender non-conforming, genderqueer: a person whose gender identity does not fall within the traditional gender binary.
People who are non-binary may see themselves as being both male and female, neither male nor female, or as completely outside of
or unrelated to these categories
History: use “Sexual Orientation/Gender ID” and “Demographics” activities in EPIC to update patient header w/ chosen name/pronouns
• Gender identity data: name and pronouns, gender identity + sex assigned at birth
• Organ inventory: guides screening and physical exam. Note natal and surgical anatomy. Confirm patient’s preferred terms for organs
o Screening: per usual guidelines based on organs present; Consider past/present HRT use; ex): trans women screen breast
CA if >50yo and 5yr HRT
o Include present organs in ddx: e.g., PID, fibroids, endometriosis in trans M w/ uterus/fallopian tubes; prostatitis in trans F
• Sexual history: “What body parts do your sexual partners have?” “What body parts do you use for sex?” “What terms do you use to
refer to your body parts?”
o Use gender neutral language to use for natal parts (i.e., chest wall instead of breast, monthly bleeding instead of menses)
o Self-collected rectal, oropharyngeal and vaginal swabs as sensitive as provider-collected swabs for STIs and HPV (Cyto
2019;63); useful for individuals who want to avoid an invasive exam
o Offer HPV, HBV vaccine series; CDC primary prevention guidelines
o Consider HIV PrEP for patients who use IV drugs or have multiple sexual partners: (AETC prescriber guidelines)
Physical Exam Considerations
• Skin: acne, hair, irritation/infection 2/2 chest binding or penile/scrotal tucking, tattoos at potential skin flap sites, silicone injections
• Abd: complications from tucking include prostatitis, cystitis, epididymo-orchitis,
• GU: pelvic exam in trans M can be traumatizing and painful 2/2 vaginal atrophy on testosterone. Tips: 1-2w vaginal estrogen before
exam; pediatric speculum; trauma-informed care esp physical exam; consider PO benzos 1h before; self-swab if possible.
G E N D E R - A F F I R M I N G C A R E (WPATH Standards of Care; Trans Line; MGH Transgender Health)
Gender dysphoria: distress a person feels due to a mismatch between their gender identity and their sex assigned at birth
• Affirm gender identity and explore options below for expression of identity and alleviation of gender dysphoria
o Psychotherapy: safe space to explore gender expression, impact of internalized transphobia, social support, body image,
strategies for resilience. Not required to pursue hormone tx or surgery
o Changes in name and gender marker on identity documents; voice and communication therapy; hair removal; chest binding or
padding; genital tucking or packing; padding of hips or buttocks; hormone tx; surgery
Hormone therapy: initiate w/ informed consent & shared decision making w/ patient (WPATH standard, Endocrine Reviews Feb 2019,40,97-117)
• Anticipatory guidance: full effects can take 1-5y. Dose titration requires frequent labs and visits in the first year
• Feminization: 17-beta estradiol (PO/SL, transdermal patch, IM) + androgen blocker (spironolactone/leuprolide)
• Masculinization: Testosterone (topical gel/transdermal patch, IM/SQ). Progestins, Aygestin early on may help stop menses
• Fertility: Discuss fertility preservation (egg/embryo freezing, sperm banking) before starting tx
• Testosterone ≠ contraception. If partner makes sperm, discuss birth control: pills, patches, Nexplanon and IUD are all options
• When monitoring treatment, indicate hormonal sex in lab requisition and interpret values using ranges for hormonal, not natal sex.
• Reasonable to provide 1-6 mo of bridge Rx if patient is already on hormones and then refer to another provider who can prescribe.
Contraindication Potential Risks Irreversible changes Reversible changes Monitoring
- VTE^ (HR 1.9) - If spironolactone: BP,
- muscle mass
- Gallstones BMP baseline and q3 mo,
Absolute: estrogen- - fat redistribution
- TG, LFTs - Chest growth then q1y
MtF

sensitive neoplasm, - hair/skin softens

- HTN -  testicular volume - total T, E q3-6mo until at
ESLD - sex drive
- prolactin goal, then q1y
- libido, erections
- Migraines - prolactin PRN if sxs
Absolute: ACS, - Deepening of voice
- Erythrocytosis - menses cessation
polycythemia (Hct -  facial and body hair - Before tx: urine HCG
- HLD, liver -  sex drive
>55%), pregnancy, - Clitoromegaly - CBC q3mo, then q1y
FtM

enzyme -  muscle mass

sex hormone - Vaginal tissue atrophy - total T q3mo, then q1y
- Sleep apnea - acne
sensitive neoplasm - Scalp hair loss**
^Strongly encourage smoking cessation to attenuate risk. Consult UCSF guide for risk-benefit analysis after VTE. Transdermal route may
↓VTE in age >45 or previous VTE **Treatment with 5-alpha reductase inhibitors may reverse some testosterone effect
Surgery: may require 6 mo hormone tx first and support letter from two mental health providers (depends on surgery type). If removing
gonads, establish bone mineral density w/ DEXA.
• Feminization: vaginoplasty, mammoplasty, voice feminization surgery, thyroid cartilage reduction, penectomy, orchiectomy
o Pre-op: no evidence to stop hormone therapy in otherwise low-risk transgender women, electrolysis for hair removal
o Post-op considerations: tissue necrosis, fistulae, urethral stenosis, UTIs, anorgasmia; regular vaginal dilation/penetrative
intercourse to maintain vaginal depth and width
• Masculinization: mastectomy, phalloplasty, metoidioplasty, scrotoplasty, hysterectomy, oophorectomy
o Post-op considerations: tissue necrosis, urinary tract stenoses/fistulae, flap loss

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Primary Care Women’s Health

B R E A S T C O N C E R N S PCOI – Breast Concerns)
Most breast concerns seen in primary care are benign (~90%); evaluation should focus on ruling in/out malignancy.
• Nipple Discharge: Bilateral/milky: eval bHCG, prolactin, Cr, TSH, med review. Unilateral, bloody (associated with mass): <30y U/S,
≥30y dx mammo and U/S. Surgery referral for concerning imaging, MRI vs surgery refer if imaging negative
• Palpable Mass: All palpable masses require imaging. <30y U/S; ≥30y diagnostic mammo and U/S. Next steps pending imaging.
Common ddx: fibroadenoma, cyst, galactocele, breast CA, fat necrosis
• Breast Pain: If palpable mass -> image. Cyclical: wait two cycles. Focal: <30y U/S, ≥30y U/S and BL dx mammo; Diffuse: unlikely
malignant, <30y sxs management (APAP, NSAID, hot/cold, eval for extramammary causes), ≥30y BL dx mammo
V U L V A R / V A G I N A L C O N C E R N S (Obstet Gynecol 2020;135:e1; Obstet Gynecol 2020;136)
Presentation Dx Tx
Wet prep or “Genital culture female” (collect
vaginal swab w/ rayon swab); Gram stain:
Nugent score 7-10 = BV Metronidazole PO 500mg BID x7d or
Bacterial vaginosis (BV): most
vaginal 0.75% x5d, clinda PO 300mg BID
common; malodorous discharge, often
Amsel’s criteria (≥3): 1) homogeneous, thin, x7d or vaginal 2% x7d
asx; RF = sexually active, douching
Recurrent: Metrogel x7d, followed by 2x/w
Recurrent vaginosis defined as: ≥3x/yr grey-white discharge 2) >20% clue cells 3) +KOH
test 4) pH >4.5 (less reliable if post-menopause) maintenance for 4-6 mos
Vaginitis

Candida: curd-like discharge, no odor, Fluconazole 150mg PO x1, miconazole

“Genital culture female” or yeast culture for fungal
pruritus, vulvar erythema ± edema, 2% x7d if pregnant
sensitivity if recurrent. pH normal (3.5-4.5), KOH
dysuria, dyspareunia Complicated: Fluc 150mg q72h x3 doses
microscopy
Complicated: severe sx, pregnancy, non- Recurrent: Fluc 150mg q72h x3 doses +
Recurrent: test for DM2, HIV, fluconazole
c. albicans maintenance or fluc 150mg x 7-14d
resistance, non-c. albicans infect
Recurrent defined as: ≥4x/yr
Other infections: Trichomonas, Gonorrhea, Chlamydia, HSV; See STI. If + STI, consider expeditated partner treatment.
**If collecting samples at MGH, at least 3 separate swabs should be sent: G/C, genital culture (rayon), trichomonas**
Vulvodynia: general or local pain, Pelvic PT, TCA, gabapentin, lidocaine 5%
Q-tip test to localize pain, exclude other etiology
provoked or unprovoked, >3-6mo before sex, steroid/lidocaine inj., sitz bath
Painful

Genitourinary Syndrome of
Wet Mount/ Gram stain: Vaginal pH >4.5, Topical vaginal estrogen, lubricants,
Menopause: vaginal dryness; pain w/
parabasal cells Replens moisturizer, ospemifene
intercourse; thin, pale mucosa
• Contact dermatitis: erythema, swelling, fissures, erosions  r/o candida, remove offending agent
• Lichen simplex chronicus: intense pruritis + lichenified plaque  antihistamines, topical corticosteroids; stop itch/scratch cycle
Dermatoses

• Lichen sclerosus: onset 50-60s, pruritis, irritation, dysuria, dyspareunia; perianal or vulvar white, atrophic papules lead to skin
thinning, labia minora fusion, & clitoral hood phimosis. 5% incidence malignancy  bx to confirm; clobetasol 0.05% taper (qd x4w,
qod x4w, 2x/w x4w), vulvar hygiene, monitor for SCC
• Lichen planus: onset 50-60s, pain/burning, “purple, papular, pruritic,” white lacy striae, vaginal involvement, SCC risk  bx to
confirm & r/o malignancy; high potency steroids, monitor for SCC

U R I N A R Y I N C O N T I N E N C E (Obstet Gynecol 2015;126; PCOI)

• Types: stress (leakage w/ cough, laugh), urge (leakage w/ urge), mixed (stress + urge), overflow (incomplete emptying, constant
dribble), functional (impaired mobility/cognition/neurologic); DDx: UTI, vaginal atrophy
• History: systemic sx (fevers, dysuria, pain), meds (anticholinergics, diuretics, etc.), comorbid conditions (DM, CHF), bowel habits
(constipation), caffeine/EtOH use, voiding diary, multiparity is RF
• Exam: check for prolapse, vulvar/vaginal atrophy, cough/valsalva stress test; rectal exam (fecal impaction, sphincter tone); neuro
exam; Dx: UA/Cx, PVR (abnl >150cc); urethral mobility assessment and urodynamic studies if etiology unclear
• Initial tx: bladder training (timed voiding), lifestyle interventions (e.g., wt loss, fluid/caffeine intake), pelvic floor exercises (e.g.
Kegels; pelvic floor PT). Stress/mixed: pessary, vaginal estrogen (for vaginal atrophy), surgery. Urgency: antimuscarinics (many SE),
β-agonists (e.g. mirabegron) – monitor for urinary retention
• Refer to Urogyn if: hx surgery/radiation, c/f mass/pain/prolapse, no response initial tx, abnl PVR, pessary/surgery/intravesicular botox

M E N O P A U S E (J Clin Endo Met 2015;100:3975)

• Amenorrhea x12mo w/o alt etiology (no need to labs, can help s/p hysterectomy), avg onset at 51, suspect 1° ovarian insuff if <40
• Vasomotor sx (hot flashes): Systemic hormones (estrogen + progestin, estrogen mono-Rx if hysterectomy) first line if <60yo, <10y
since onset & <5y duration. Avoid if: hx or >10% risk CVD, hx/high risk of breast CA/endometrial CA, hx VTE/CVA/TIA, active liver
disease, unexplained vag bleeding, +smoking. Side effects: breast tenderness, vag bleeding; CRC, fracture risk; breast CA, CVD,
VTE (equivocal if risk attenuated with topical Tx); no mortality risk after 5-7y on therapy (JAMA 2017;318:927). If not eligible/desiring
systemic hormones: SSRI/SRNIs (paroxetine best), gabapentin, clonidine.
• Vaginal/vulvar sx (now called genitourinary syndrome of menopause): see above; oral therapy not effective, use topical
• Psych sx: sleep disturbance, poor concentration, new-onset depression. May improve with Rx for vasomotor sx

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2 ° A M E N O R R H E A (AFP 2019;100:39)
• Definition: cessation of regular menses for 3mo or cessation of irregular menses for 6mo]
• Hx: wt ∆, diet/exercise, hot flashes, galactorrhea, hirsutism, stress, systemic illness; Initial labs: HCG, FSH, LH, E2, TSH, PRL
• DDx: pregnancy, hypothalamic (eating disorder, excess wt loss/exercise, stress, prolonged illness), pituitary (hyperprolactinemia 2/2
adenoma, mass effect, meds, breastfeeding, apoplexy), ovary (1° ovarian insufficiency, PCOS), uterine (prior instrumentation  scar
= Asherman Syndrome), other (hypo/hyperthyroidism, DM, celiac, excess androgens [exogenous, Cushing’s])
• If nl/low FSH, consider progestin challenge: medroxyprogesterone acetate 10mg x10d. If no withdrawal bleed, suggests uterine abnl
P O L Y C Y S T I C O V A R Y S Y N D R O M E ( P C O S ) (Obstet Gynecol 2018;131)
• Affects 5-10% of women of reproductive age; often comorbid w/ CVD, DM, HTN, NAFLD, HLD, OSA, depression and anxiety
• Rotterdam Criteria (need 2/3): 1) oligo/anovulation, 2) clinical/biochemical hyperandrogenism, 3) polycystic ovaries on pelvic U/S
• Workup: exclude other dx (hCG, 17-OHP [pre-8AM], prolactin, TSH); DHEAS, total testosterone, SHBG to confirm if dx unclear
• Tx: wt loss, exercise, C-OCP (2nd line = oral progesterone or levo-IUD), spironolactone, metformin (if insulin resistant), fertility referral
P R E C O N C E P T I O N C O U N S E L I N G / I N F E R T I L I T Y (Fertil Steril 2021;116)
• Preconception counseling (PCOI): multivitamin qd w/ 400-800mcg folic acid; review immunizations (Rubella, Varicella, HepB, COVID-
19, RSV at 32-26 wks of pregnancy); optimize mgmt of wt, thyroid (TSH goal 0.5-2.5, recheck after conception), HTN (avoid
ACEi/ARB, check b/l Cr, spot Ur protein/Cr), DM (risk birth defects; metformin/insulin first-line), mood (avoid paroxetine; SSRI safety
debated, engage Psych/MFM), VTE (LMWH preferred), asthma, OUD (methadone & suboxone safe in pregnancy); avoid tobacco,
EtOH, drugs; review medications and check for teratogens
• Infertility: evaluate after 12mo unprotected intercourse in <35yo, 6mo in ≥35, sooner if >40; fertility tx covered by insurance in MA
• Hx: prior OB/GYN hx (menstrual hx, pregnancies, PID, fibroids/polyps, abnl Pap, endometriosis, contraceptive use), sexual hx (timing,
frequency, sexual dysfunction), hx chemo/XRT, meds, substance use, FHx. Ddx: see amenorrhea above
• Dx: ovarian reserve tests, pelvic/transvaginal U/S, PCOS w/u, STI & fallopian tube patency testing, TSH, PRL, semen analysis
• Tx: fertility awareness (intercourse qod cycle d9-14, or from 5d before and day of ovulation); refer to Repro-Endo for other w/u,
induction of ovulation, IVF, or donor oocytes
C O N T R A C E P T I O N (CDC USMEC 2016; CDC 2020 Summary; aSociety of Fam Planning), resource for patients: bedsider.org
• 45% of pregnancies are unplanned  r/o pregnancy before initiating contraception  LARCs (IUD, implant) are most effective
• Hormonal methods (including LARC) take ~1w to take effect  always recommend backup method (condoms) for 7d
1y Failure
Use Pros/Cons Contraindications (A: Abs, R: Rel)
Rate*
Estrogen-progestin^
Combined Pill Daily 9% (0.3%) A: Hx VTE, thrombogenic mutation; Breast
Vaginal Ring 3w in, 1w out 9% (0.3%) Pros: menses, PMS, cramps, acne, or liver CA w/in 5y; Migraine w/ aura or
endometrial/ovarian CA
>35yo & any migraine; >35yo & >15 cig/d;
Weekly x3w, 1w Cons: n/v, breast tenderness, can
Patch (e.g. Xulane, hx CVA; Uncontrolled HTN; DM w/ vascular
off; apply to arm, 9% (0.3%) HTN/TGs, libido, spotting, cannot
Ortho Evra) dz, CAD, CVD,valvular dz, ESLD;
torso, or buttock start if <21d post partum)
R: Obesity (efficacy of some rings/patch)
Progestin-only
IUD
M/L q8y Pros: long-acting, lighter periods, may
(hormone content: A (all): active breast CA or w/in last 5y
Kyleena q5y 0.2% reduce cramping/anemia, discreet
Mirena/Liletta > A (IUD): abnl uterine cavity; unexplained
Skyla q3y Cons: irregular bleeding, requires
Kyleena > Skyla) vag bld; active STI, PID, endometritis at
removal, physical complications (rare)
Implant q3y to upper arm insertion; endometrial or cervical CA
0.05% Pt preference: amenorrhea (~18%)
(Nexplanon) (q5y efficacya)
Pros: long-acting, discreet R (all): APLAS, ESLD, liver CA, breast CA
q3mo IM/SQ to >5y ago
Injection Cons: irregular bleeding; temp BMD;
arm, thigh, or 6% (0.2%) R (implant): unexplained vag bld
(Depo-Provera) prolonged return to fertility (1y); may
buttock R (injection): unexplained vag bld, CV RF,
worsen HA, acne, mood
ischemic heart disease, PVD, uncontrolled
Pill Pros: no effect on breastfeeding HTN, DM w/ end-organ damage, CVA
(e.g. Micronor, Daily 8% (0.3%) Cons: irregular bleeding, HA, acne, R (pill): malabsorption
Slynd) mood sx, timing∑
Hormone-free
Copper IUD q10y Pros: long-acting, safe in ESLD A: Same as progestin IUDs above; copper
0.8% (0.6%)
(Paragard) (12-20y efficacy) Cons: heavier bleeding, cramping allergy, Wilson’s dz
Pros: STI prevention
Male condom Every encounter 18% (2%) R: Oil-based lubricant w/ latex condom
Cons: requires pt adherence
Tubal Ligation 0.5% Pros: available to men and women R: Surgical risk
Permanent
Vasectomy 0.15% Cons: irreversible, surgical R: Pt unsure of decision
* Typical use: % women who will have pregnancy in 1 year on this method (perfect use in parentheses); ∑Newer formulations like Slynd maintain efficacy
with 24h missed window (Curr Obstet Gyn Rep 2022;11); ^Estrogen-progestin methods can be used continuously to avoid withdrawal bleed.
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Oral Contraceptives (OCPs) (Quick Start Algorithm): start anytime (exclude preg + 7d backup method).
• OCP selection: estrogen (ethinyl estradiol) – 30-35mcg: less breakthrough bleeding. 20mcg: less estrogen SE. Progestin – 2gen
(levonorgestrel, norgestrel): VTE risk. 3gen (norgestimate, desogestrel): androgenic SE, VTE risk
• Patient Resources: Bedsider.org is a great resource for patients to explore options
Emergency Contraception (Obstet Gynecol 2015;126:e1; NEJM 2021;384(4); PCOI)
• Plan B (levonorgestrel 1.5mg x1 or 0.75mg q12h x2): OTC, use w/in 72h, less reliable if BMI >25. Ella (ulipristal 30mg x1): requires
Rx, use w/in 120h, less reliable if BMI >30. Paragard/Mirena/Liletta: place within 120h (Paragard okay up to 160h), most effective
• In cases of sexual assault: refer pt to ED for an exam by a trained SANE RN. If IPV: ask if partner has access to online medical
records prior to detailed documentation and prepare safety plan. MGH HAVEN referral: 617-724-0054

O P T I O N S C O U N S E L I N G (TEACH)
Options counseling is an opportunity for the pregnant person to consider, in conversation with a provider, whether to continue the
pregnancy and parent the child, continue the pregnancy with a plan for adoption, or have an abortion. Particular attention to neutralizing
language to avoid potential coercion is imperative. For people who desire abortion, see PCOI or abortionfinder.org for list of providers in
MA. Avg cost ~$500, 50% pay out of pocket. Counseling: 1-866-4-EXHALE.
Medical Abortion (MAB) (95-98% effective)
• Eligibility: ≤10 wks gestation, no ectopic risk (history alone or U/S if equivocal); no (1) IUD in place, (2) mifepristone or misoprostol
allergy, (3) chronic adrenal failure/long-term corticosteroid use, (4) hemorrhagic disorders, on AC, symptomatic anemia, (5) porphyria
• Workup: serum or urine hCG test; no routine pre-MAB lab testing needed if no underlying conditions; LMP can date pregnancy
accurately & safely in most cases (U/S NOT universally required); offer STI testing & immediate post-abortion contraception
• Protocol: PO mifepristone x1  buccal or vaginal misoprostol in 24-48h  pt passes pregnancy at home over hrs. May experience
cramping and bleeding. Tx with NSAIDs. F/u history and home urine pregnancy test OR serial bHCG testing OR U/S in 7-14d
Surgical Abortion (<24wks gestation, 99% effective): same-day office procedure  no f/u unless complications
Parenting: obstetrics
Adoption: resources for public and private agencies

P O S T P A R T U M C A R E (ACOG Postpartum Toolkit, 2018)

Key Screening Items: proactive questions and anticipatory guidance about nl vs abnl mitigates complications and worry; Screen for IPV.
• Vaccines: all vaccines safe while breastfeeding except smallpox (give yellow fever and MenB only if benefits > risks); recommend all
w/ baby contact receive flu & Tdap
• Contraception: can start progestin-only options (IUD, implant, injection, pills) immediately postpartum & estrogen-containing options
21-28d postpartum (42d if VTE risk factor).
• Breastfeeding: see Lactmed for restarting medications. Challenges: nipple pain (tx lanolin, breast shield), plugged ducts (aspiration if
>72h), inadequate milk supply, mastitis (10% breastfeeding mothers; assoc w/ edema, erythema, ± fever/chills; if c/f infection, r/o
abscess w/ exam (tx w/ I&D) and Rx dicloxacillin or keflex; encourage continued breastfeeding). Consider referral to lactation
consultant. Remind mom federal law requires break time & dedicated space at work for lactation
• SUDs/Analgesia: postpartum period high risk for SUD/relapse. Methadone & buprenorphine safe w/ breastfeeding, should be
continued (risk of relapse during postpartum). Screen for AUD. Encourage smoking cessation (pt & all household members).
Acetaminophen and ibuprofen safe during breast feeding; avoid NSAIDs if HTN. Butorphanol, morphine, hydromorphone are
preferred opioids if needed
• Common sx (often self-resolve): vaginal soreness & discharge, constipation, hemorrhoids, cramps, breast engorgement, urinary/fecal
incontinence, hair loss (w/in 5mo), mood swings (“baby blues”)
• Persistent vaginal bleeding: normal to have small amount of red-tinged discharge for 1-2w PP (w/ red, heavy discharge for 1-2d); if
soaking through pad/tampon in <1h ± pain, fever, tenderness, may be signs of infection, refer to ED
• Perineal pain, dyspareunia, and sexual dysfunction: >10% report pain 1y post-vaginal delivery (RF = 3rd/4th degree tears, operative
delivery, vaginal atrophy while breastfeeding). Tx: water-based lubricants, topical estrogen, pelvic floor therapy, scar tissue ablation.
Decreased libido common and normal (50% at 3mo, 30% at 6mo)
• Postpartum depression: w/in 12mo after birth; incidence of 11-20%; screen with PHQ9, Postpartum Depression Scale, or Edinburgh
Postnatal Depression Scale; tx with peer counseling, CBT, SSRI.

Pregnancy-Related Complications of Cardiovascular Disease and Endocrinopathies

• Postpartum period high risk for: flares of underlying autoimmune disease, peripartum cardiomyopathy
• Excessive gestational weight gain, obesity, preterm birth (<32w) risk for CVD in mom; screen annually for modifiable RF
Future Risk Postpartum Screening Risk Mitigation
- risk of recurrent GDM, pre-DM, - 75g OGTT or fasting BG at 4-12w - Encourage breastfeeding
Gestational
T1DM, T2DM (7x higher), CVD, & postpartum (Diab Care 2021;44:S15). If - If overt DM: target A1c 6-6.5, consider ASA
Diabetes/
metabolic syndrome (esp. w/in 5y) ⊕, screen q1y. If ⊝, q3y for life 81mg qd in future pregnancies to pre-
Diabetes
- Uncontrolled DM risk birth defects - If T1DM, TFTs x1 (if never done) eclampsia risk
- Close BP monitoring up to 6w PP - Encourage breastfeeding
Pre- - risk of stroke 48h-10d postpartum - BP >140/90 warrants eval - Early goal BP <160/100, later <120/80
Eclampsia/ - risk of CKD in first 5y - Repeat UACR/UPCR to quantify - Add pre-eclampsia as ASCVD risk-enhancer
HTN - risk of ASCVD (JACC 2019;74:1376) baseline proteinuria, CBC for plt, - Consider ASA 81mg qd in future
CMP for LFTs and creatinine pregnancies to pre-eclampsia risk

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Primary Care Men’s Health

B E N I G N P R O S T A T I C H Y P E R P L A S I A ( B P H ) / L O W E R U R I N A R Y T R A C T S X ( L U T S ) (J Urol 2021;206:806; PCOI)
• Sx: increased urinary frequency, urge, difficulty initiating or weak stream, small amount of urine w/each void, leaking or dribbling,
and/or sensation of incomplete void. Present in >50% of men over 60 y.o. w/increased incidence with older age (~90% >85 y.o.)
• DDx: urethral stricture, bladder neck contracture, prostate ca, bladder ca, bladder calculi, UTI, prostatitis, neurogenic bladder
• Eval: HPI, sexual hx, assess sx burden via International Prostatism Symptom Score (IPSS), perform a PE (DRE), obtain UA (blood,
bacteria, glucose, protein), 24-hr voiding diary, and consider PVR and/or urodynamic testing prior to Rx initiation;
• Possible Complications: urinary retention, persistent gross hematuria, bladder stones, recurrent UTI, hydronephrosis, renal failure
• Screening: BPH/LUTS don’t appear to be RFs for prostate Ca; important to counsel pts & have shared decision-making re: PSA
screening annually vs q2yrs at ages 55-69 given high degree of false positives (~70%) and risks/benefits of side effects vs medical Rx
• Rx: if sx worsening despite initial watchful waiting & behavior changes (avoid alcohol/caffeine, limit PM fluid intake, avoid
antihistamines/decongestants/allergy meds which can worsen sxs), may consider medical therapies including:
o Alpha-blockers (terazosin, doxazosin, tamsulosin, alfuzosin, silodosin): initial therapy; MOA - relax muscles near the
prostate, max efficacy in 1 month; ADEs: headaches, hypotension, dizziness, or feeling lightheaded or tired.
o 5-alpha reductase inhibitors (finasteride or dutasteride): MOA - inhibit testosterone to shrink prostate, max efficacy in 6-12
months; ADEs: decreased libido, problems with erection or ejaculation.
o PDE-5 inhibitors (tadalafil): preferred for men with ED, max efficacy by 4 weeks ADEs: headache and back pain.
o Combination Rx (alpha blocker + 5-alpha reductase inhibitor): consider addition of 5ARI if prostate >30cc, Rx combo
may be more effective for sx reduction & decreasing risk of overall BPH progression than either agent alone
o Saw Palmetto (plant extract): limited data to support efficacy over placebo but anecdotally may help improve sxs
• Procedures: Transurethral resection of prostate (TURP): Most common procedural intervention – involves insertion of thin tube into
urethra & cutting away pieces of prostate causing blockage (often does not require total prostatectomy). Additional minimally invasive
procedures include transurethral needle ablation (TUNA) & transurethral microwave thermotherapy (TUMT).
Potential complications: reverse flow of semen (empties into bladder & not out of penis) – does not affect ability to orgasm but
can affect fertility; less common side effects: urinary incontinence, inability to initiate or sustain erection.

ERECTILE DYSFUNCTION (J UROL2018;200:633; PCOI)

• Sxs: inability to consistently attain or maintain erections rigid enough or of sufficient quality for sexual intercourse. Affects ~22% of
men 60-69 and 30% of men >69.
• DDx: distinguish from decreased libido 2/2 testosterone deficiency (see Endocrine section), MDD, use of prescription/illicit drugs;
ejaculatory dysfunction (ex: premature or retrograde ejaculation); anatomic anomalies (ex: Peyronie’s Dz)
• RFs: CVD/PAD, CKD, HLD, HTN, obesity, smoking, sleep disorders (OSA, RLS), hyperglycemia, DM; should additionally perform
complete medication review as many commonly prescribed meds can cause ED (PCOI, Table 2)
• Rx: First line - lifestyle modifications for pts with above RFs (ex: tobacco cessation, EtOH reduction), may consider Pharm Rx:
All PDE5 inhibitors are contraindicated in pts on nitrates. Co-admin of tamsulosin is less likely to cause hypotension than doxazosin
Medication Dosing Side Effects
Sildenafil (Viagra) • Start: 50 mg, dose range 25-100 mg prn according to side effects. Rarely can cause blue-tinged vision.
• Take 1 hour prior to sex on empty stomach, effective for 4 hours.
Vardenafil (Levitra) • Start: 10 mg, dose range 2.5-20 mg. Can cause QTc prolongation (avoid in
• Take 1 hour prior to sex, effective for 4 hours. Taking with fatty meals may congenital QT prolongation or with additional
cause reduced efficacy. QTc prolonging meds)
Tadalafil (Cialis) • Start: 10 mg, dose range 5-20 mg. More tolerable than other PDE-5 inhibitors with
• Take 30 minutes prior to sex, peaks at 2 hours, effective for 24-36 hours. alpha-blocker tamsulosin 0.4 mg. Myalgias in
15% of users.
Avanafil (Stendra) • Start: 100 mg, dose range 50-200 mg. Fastest onset. Limited side-effect profile.
• Take 15-30 minutes prior to sex with or without food.
When to refer: urology referral for adolescents/young adult w/primary ED (never been able to achieve erection); failure of initial first-line
oral Rx; contraindications to PDE-5 inhibitor Rx; other specialized testing warranted (ex: penile vascular test, nocturnal penile tumescence)

S C R O T A L / T E S T I C U L A R M A S S E S (Am Fam Physician 2014; 89:723)

• Scrotal masses = common presentation in primary care – scrotal pain ~1% of all ED visits.
• Normal PE: firm but not hard testes, nearly equal in size, smooth/ovoid, normal testicle length
~4-5 cm after puberty, epididymis is posterolateral to testicle, vas deferens exits via tail of
epididymis and joins vascular pedicle of testicle to form spermatic cord.
• DDx: helpful to begin assessment by distinguishing painful vs painless:
• Painful: torsion (acute, N/V, abnormal cremasteric reflex, blue dot sign, CRP<24) vs
epididymitis/orchitis (most common, +/- fever & dysuria, erythema, CRP>24) vs
hematocele/testicular rupture (rare, associated with trauma)
• Mixed pain/painless: testicular cancer (ages: 15-34, firm unilateral nodule, hx of
cryptorchidism in childhood or Klinefelter synd.; obtain α-fetoprotein [AFP], ß-HCG, LDH) vs
hernia (painful w/strangulation; test via Valsalva maneuver)
• Painless: hydrocele (transillumination w/pen light) vs varicocele (“bag of worms” feel in 15%
of males affected, typically occurs in adolescence)
Imaging/labs: Scrotal U/S is best for distinguishing above ddx coupled with inflammatory vs
markers as above if there is a high index of suspicion. If c/f torsion, surg emergency. Consult urology immediately (even prior to US).
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Primary Care Sleep Medicine

INSOMNIA (PCOI)
35-50% of population; chronic insomnia >3mo. difficulty initiating or maintaining sleep and compromised daytime function (UTD)
• Hx: evaluate chronicity, stressors, effect on fxn/mood, # awakenings and triggers, sleep hygiene; meds, PMH, sleep log for 1w
• Ddx: Medical: r/o pain, primary medical condition (e.g., PSYCH: PTSD, mood d/o; PULM: COPD, asthma; CV: CHF; GI: GERD; GU:
nocturia), SUDs, medications (e.g., stimulants, steroids, BBs, SSRIs, SNRIs, OCPs, chronic opioids)
o Primary sleep d/o: insufficient sleep syndrome (<7-8h allotted to sleep), psychophysiologic (inability to sleep due to stress or
anxiety about sleep), paradoxical (no e/o sleep d/o), RLS, Periodic Limb Movements of Sleep (PLMS), OSA, idiopathic (starting
in childhood), circadian rhythm disorder (delayed sleep phase; advanced sleep phase-common elderly)
• Rx: Sleep hygiene: regular sleep schedule 7d/wk, exercise, if lying in bed awake get up till sleepy, no reduce/eliminate
caffeine/EtOH/nicotine, quiet/dark BR, eliminate bright lights/screens in pm; CBT-I (first line with strong evidence, hard to access), (J
Clin Sleep Med 2021;2,263). Meds: scant evidence on safety/efficacy but often tried: low dose melatonin, trazodone (UTD); (WEAK
evidence): sleep maintenance (doxepin), sleep onset (ramelteon, triazolam), both (DORA, eszopiclone, zolpidem, zaleplon,
temazepam). Goal is Rx hypnotics for <4w only and careful risk/benefit for BZRA agents (J Clin Sleep Med 2017;13:307); treat mental
health disorders

S L E E P A P N E A (JAMA 2020;14:389, PCOI)

Obstructive (upper airway occlusion) and/or central (resp drive). OSA affects ~10% of adults
• Presentation: daytime somnolence (use Epworth Sleepiness Scale), morning HA, witnessed apnea/gasping, snoring (Sn > Sp),
depression, nocturia, pHTN; RF: obesity, anatomy, incr age, ♂, post-menopausal, EtOH, FHx, CHF. Screen for OSA w/ STOP-BANG
(≥3 symptoms with Sn 90%) (JAMA 2021; epub)
• Dx: sleep study in-lab (polysomnography (PSG); gold standard) vs at home (cannot detect other sleep d/o or central apnea, often
req by insurance over PSG; home sleep study underestimates the degree of sleep apnea); both quantify apnea-hypopnea index (AHI)
= sum of events/h (mild 5-15, mod 16-30, severe >30), minimum O2 saturation, and percent of time below 90%. Apnea/nocturnal O2
requirement often observed inpatients, but can confirm diagnosis o/p only.
• Tx: behavioral: weight loss, avoid ETOH/sedatives, position (avoid supine sleep, elevate HOB); Positive Airway Pressure: CPAP,
BiPAP, ASV (for central, risky in CHF), APAP (most common, auto adjusts PAP); other: oral appliance (dentist referral), surgery,
modafinil (for daytime sleepiness refractory to CPAP). Managed by PCP (HST then APAP), Sleep ENT (PAP, surgery, HGNS), Sleep
Neurology (PAP, meds), or Pulmonary (pHTN). Important to identify preoperatively (JAMA 2019;321;18:1788).

OBESITY HYPOVENTILATION SYNDROME

• Presentation: awake alveolar hypoventilation not attributed to other conditions (dx of exclusion: r/o alt etiologies of hypercapnia and
hypoventilation), in an obese individual (AJRCCM 2019;200;3:e6)
o RF: obesity (BMI>30) esp severe (BMI≥40, Class III), central obesity, severe OSA
• DDx: COPD, ILD, neuromuscular disorders, chest wall disorders, hypothyroidism, chronic sedative use
• Dx: VBG CO2>27, PaCO2>45, PaO2<70; also BMP (r/o lyte disorder), CBC (polycythemia may be associated, monitor response to
rx), TSH, PFTs (to exclude other causes – nml does not exclude OHS), CXR, PSG (identify sleep d/o breathing, gold standard)
• Tx: BiPAP and weight loss/bariatric surgery. Assess for complications (pHTN, HTN, CHF, insulin resistance)

RESTLESS LEG SYNDROME (RLS) (PCOI)

• Presentation: URGE: Urge to move legs, Rest induces symptoms, Getting active brings relief, Evening worsens sxs.
• Common triggers: caffeine, nicotine, ETOH, dopamine antag, most antidepressants, antihistamines
• Assoc conditions: iron deficiency (and work up of etiology), CKD, pregnancy, tremor, Parkinson’s, MS, movement disorders, OSA
• Dx: Clinical (PSG if unsure, PLMD), Fe/TIBC/Ferritin/CBC, BMP (CKD); DDx: MS, akathisia, myalgia, PMR/myositis, neuropathy,
stasis/edema, PVD, arthritis, nocturnal leg cramps, positional discomfort, habitual foot tapping
• Tx: stop trigger meds, avoid EtOH/nicotine, treat OSA, iron supplement to ferritin >75; DA agonists (take 1-1.5h before trigger or qhs)
- pramipexole, ropinirole, carbidopa/levodopa (<3x/w, high risk rebound), rotigotine patch; a-2-d Ca channel ligand: pregabalin,
gabapentin; comorbidities may guide Rx; refer to neurology if refractory to monotherapy.

OTHER SLEEP DISORDER

Narcolepsy: chronic daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis (1/3 pts have all three symptoms so
consider narcolepsy even if only chronic daytime sleepiness) (NEJM 2015;373:2654); Dx: PSG (exclude alternative causes) and Multiple
Sleep Latency Test (MSLT). Tx: Requires specialty management. Basics of treatment include good sleep hygiene and trigger avoidance (
BZD, Opiates, Antipsychotics, EtOH, Caffeine, Alpha1Antag).

Parasomnias: complex movements and behaviors during sleep. Associated with NREM (sleepwalking, confusional arousal, sleep terrors,
sleep related eating disorder) and associated with REM (nightmare disorder, REM sleep behavior disorder) (AJM 2019; 132:292).Dx: Mayo
Sleep Behavior Questionnaire can help dx, obtain video PSG if uncertain and consider MRI. Tx: is to improve sleep hygiene (EtOH, stress,
sleep deprivation, Rx OSAS) and assess safety. Melatonin 3-18mg is first line rx.

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Primary Care HEENT Concerns

C H R O N I C C O U G H (AFP 2017;96:575; NEJM 2016;375:1544)
• Time course: acute (≤3w) vs. subacute (3-8w) vs. chronic (>8w)
• Common causes: upper airway cough syndrome (UACS), asthma, GERD; these three account for 90% (18-62% pts have combo)
• General approach:
1) History (smoking, URI, ACEi use, GERD sx); remove possible offending agent
2) Consider CXR if cough >8 weeks, especially if suspicion for UACS/asthma/GERD
3) Start empiric tx for UACS/asthma/GERD sequentially until resolution  tx should be added to initial regimen
4) Consider PFTs, esophageal pH monitoring, chest CT, sputum tests, cardiac studies if sx persist despite treatment of usual causes
Etiology Characteristics Treatment
Upper Airway Formerly post-nasal drip syndrome. Most common cause of Avoid environmental triggers of allergic rhinitis.
Cough subacute/chronic cough. Cough may be only sx. Steroid or antihistamine nasal spray, oral
Syndrome Exam: throat/nose may reveal cobblestoning. antihistamine/ decongestants, and saline nasal
(UACS) Common causes: allergic/non-allergic rhinitis, sinusitis rinse for symptom relief. Improve in wks- 2 mos
Typically p/w episodic wheezing & dyspnea. Cough variant asthma
PRN bronchodilators ± inhaled corticosteroids.
p/w only cough. Pt may have h/o atopy.
Asthma Some pts may use only seasonally.
Exam: ± nasal polyps. Need spirometry w/ bronchodilator
See Asthma for stepwise therapy
response & bronchoprovocation (methacholine challenge) for dx
30-40% of chronic cough. Epigastric burning sensation, sour taste Lifestyle modifications, moderate dose PPI/H2
GERD
in mouth (although sx absent in >40% of patients) blocker. Consider H. pylori testing
H/o recent viral illness. 2/2 postnasal drip/UACS or direct effect of UACS tx as above. 2nd gen (cetirizine) or 3rd gen
Respiratory
virus on bronchial reactivity/cough receptors. Pts have been shown (fexofenadine) antihistamine. If bronchial
tract infection
to experience transient bronchial hyperreactivity as well hyperreactivity, tx w/ usual asthma care
Produces cough in 3-20% of pts. 2/2 ACEi-mediated increase in Withdraw ACEi (resolves within 1-4w), change
ACE Inhibitor
bradykinin. Sx can occur 1w to 6mo after starting to ARB (not associated with cough)
Other causes: post-infxn (self-limited; can last 3+ months, treat sx), COPD, OSA, non-asthmatic eosinophilic bronchitis, chemical irritant
(e.g., cigarette smoke), laryngopharyngeal bronchitis, psychogenic/habitual cough, bronchiectasis, CA, TB, sarcoid
R H I N O S I N U S I T I S (Otolaryngol Head Neck Surg 2015;152:598; NEJM 2016;375:962; Clin Infect Dis. 2012; 54(8):e72)
• Time course: acute (<1mo) vs. subacute (1-3mo) vs. chronic (>3mo); recurrent (4 or more annual episodes)
• Dx: rhinorrhea (viral=clear, bact=purulent) + nasal obstruction or facial pressure/pain/fullness. A/w anosmia, ear fullness, cough, HA
• Acute rhinosinusitis is infectious while chronic is inflammatory (atopy, asthma, granulomatous disease, immunodeficiency, CF)
Etiology Time Frame Treatment
Viral: most common cause 7-10d Symptom control, oral decongestant • NSAIDs/Tylenol for pain
Bacterial: only 0.5-2% of >10d, or worsening w/in Watchful waiting in pts w/ follow-up • Saline irrigation/Netipot
acute rhinosinusitis. 10d after initial vs. amox-clav 875mg BID** or doxy • Topical nasal steroids,
S. pneumo (41%), H.flu (35%) improvement 100mg BID x5-7d decongestant, expectorants
Fungal: mucor (invasive) in Acute (invasive) to more Surgical removal of fungal mucin or “fungal ball” (mycetoma). ENT
DM, immunocompromised chronic (>3mo) emergency if invasive (destruction of sinus, erosion into orbit or brain)
** Higher dose Augmentin (2g BID or 90 mg/kg/d BID) in pts w/ RFs for resistance: regional resistance pattern, age 65+, hospitalized in last 5d, abx use in
last month, immunocompromised, DM/cardiac/renal/hepatic disease, severe infxn (fever >102F, suppurative complication)
• Chronic rhinosinusitis: confirm diagnosis w/ CT or endoscopy; treatment varies by presence or absence of nasal polyps
o No polyps  trial saline irrigation/intranasal steroid
o ⊕ polyps  add short course of PO steroid ± ASA desensitization if concern for ASA-exacerbated respiratory disease
• Complications: meningitis, periorbital/orbital cellulitis (pain, edema, proptosis, painful eye movement, diplopia),
subperiosteal/intracranial/epidural abscess, osteomyelitis of the sinus bones, septic cavernous sinus thrombosis
• Alarm symptoms: persistent fevers >102F; periorbital edema, inflammation, or erythema; CN palsies; abnormal extraocular
movements; proptosis; vision changes (diplopia, impaired vision); severe HA; AMS; meningeal signs

P H A R Y N G I T I S (JAMA 2012;308:1307; NEJM 2011;364:648; CID 2012;55:e86)

• Usually viral (suspect if +conjunctivitis, coryza, cough, diarrhea, hoarseness, discrete ulcerative stomatitis, viral exanthema)
o Only 5-15% of adult sore throat visits are Group A Strep (GAS)
• Exclude dangerous etiologies: epiglottitis, peritonsillar abscesses, infxn in submandibular or retropharyngeal space, acute HIV
• Identify & treat GAS to risk of suppurative complications (peritonsillar abscess, cervical lymphadenitis, mastoiditis), prevent
rheumatic fever (lower risk in adults), transmission, & improve sx. ASO titers useful only in dx of non-suppurative sequelae of GAS
o Centor Criteria: 1 point for each - tonsillar exudates, tender ant. cervical LAD, fever, ∅ cough; (-1pt if age ≥45)
 0-2: no testing, treat sx. 3-4: send Rapid Strep antigen detection test (Sn 70-90%, Sp 95%) ± throat Cx (if neg rapid but
clinical suspicion; not indicated for routine use in adults w/ neg rapid)
o Tx: PO penicillin V 500mg BID x10d; amoxicillin 500mg BID x10d; IM benzathine penicillin G 1.2milliU x1
 PCN-allergic: cephalexin 500mg BID x10d
 β-lactam sensitivity: clindamycin 300mg TID x10d; azithromycin 500mg QD x1d, then 250mg QD x4d
• Symptomatic tx: OTC lozenges (e.g. Sucrets, Cepacol), throat sprays, NSAIDs/Tylenol for pain relief. No PO steroids
• Follow up: if no improvement in sx in 5-7 days, evaluate for other infectious causes (e.g., mono, HIV, GC/chlamydia) or suppurative
complications such as tonsillopharyngeal cellulitis, abscess, or acute otitis media

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Primary Care HEENT Concerns

EYE
General Evaluation: see Ophthalmology
• Initial eye exam: visual acuity (Snellen chart, w/ glasses if worn), pupils (reactivity, APD), confrontational visual fields, EOM,
intraocular pressure (palpate for firmness), color vision (Ishihara cards)
• Red Flags (urgent ophtho eval): severe pain, HA/nausea, photophobia, severely decreased vision, abnormal pupil exam, corneal
opacities, chemical injury, recent eye surgery or trauma, double vision, new onset flashes or floaters
Vision Loss
• Acute, Painless (ED): GCA; non-arteritic ischemic optic neuropathy (~60y, +APD); central retinal artery occlusion (vasculopathy,
+APD, ± amaurosis fugax); central retinal vein occlusion (DM, HTN, hypercoag, glaucoma, OCPs, hyperviscosity, ± RAPD); vitreous
hemorrhage (DM, retinal detachment/tear); retinal detachment (flashes of light, floaters, ± abnl red reflex); pseudosudden vision loss
(gradual monocular loss misperceived as sudden if other eye occluded)
• Acute, Painful (ophtho w/in 24h): optic neuritis (unilateral, <50y, blurry vision, flashes of light, +APD, pain worse w/ eye movt); acute
closed-angle glaucoma (deep brow ache, ± n/v, halos around lights)
• Gradual, Painless (routine referral): refractive error, cataracts (glare, halos, trouble night driving), open-angle glaucoma (RF: age,
FHx, AA/Hispanic), diabetic retinopathy (c/b macular edema, vitreous hemorrhage, macular ischemia, tractional retinal detachment),
age-related macular degeneration (central, RF: tobacco, poor diet, age, FHx), meds, idiopathic intracranial HTN (RF: ♀, obesity,
steroids, OCPs, high-dose VitA, tetracyclines), mild amblyopia
Red Eye (AFP 2010;81:137) for tx see Ophthalmology
• Painless: subconjunctival hemorrhage (unilateral, no vision ∆), episcleritis (painless w/o vision ∆ or discharge, unilateral focal
erythema, self-limited), dry eye syndrome (b/l itching, burning, photophobia, foreign body sensation, diffuse hyperemia),
blepharitis/Meibomian gland dysfunction (b/l lid margin burning, itching, AM crusting)
• Painful: conjunctivitis (itching, burning, FB sensation), keratitis (photophobia, tearing, hyperemia; 2/2 corneal ulcer or VZV/HSV),
severe tear deficiency (Sjogren’s, GVHD), iritis/uveitis (unilateral, photophobia, tearing, sluggish pupils; autoimmune), scleritis (HA,
boggy red/pink sclera, tender globe, pain with EOM, no vision ∆), endophthalmitis (floaters, vision ∆, fixed dilated pupil, hypopyon; c/f
fungemia), acute angle closure glaucoma (unilateral, HA, halos, n/v, vision ∆, fixed dilated pupil, globe firmness)
• Swollen eyelid (AFP 2015;92:106): hordeolum = stye (tender nodule 2/2 occluded Meibomian gland), chalazion (painless nodule 2/2
chronic granulomas), contact dermatitis (caution w/ topical steroids), preseptal or orbital cellulitis (see Orbital and Preseptal Cellulitis)
Conjunctivitis (JAMA 2013;310:1721):
• Viral > bacterial. Very contagious: strict hand hygiene, avoid contacts until sx resolves
• Dx: PCR, GS, or Cx rarely needed – consider if severe purulence, refractory to tx, recurrent, immunocompromised, or c/f GC/CT
• Avoid contact lenses, topical corticosteroids, OTC vasoconstrictors (rebound hyperemia)
Etiology Presentation Dx Tx
Viral History: sick contact, URI sx, watery d/c, gritty
Cool compresses, artificial tears.
(most sensation, itching. Exam: intense hyperemia, Typically adenovirus
If c/f HSV/VZV: topical/PO tx + ophtho
common) ± periocular swelling, preauricular LAD
Typically S. pneumo, Erythromycin ointment 0.5% QID x7d (mild) or
History: mucopurulent d/c, pain/stinging.
Bacterial S. aureus, or H. flu; Polytrim 1-2 drops QID x7d (mod-severe,  time
Exam: crusting, intense hyperemia, LAD rare
consider GC/CT if RF to recovery). GC: PO abx + ophtho
History: intense itching, painless tearing, hx Avoid allergens. Cool compresses, artificial tears.
Allergic atopy, allergic rhinitis. Chronic or seasonal OTC anti-histamine/mast-cell stabilizer drops
Exam: bilateral, mild hyperemia (e.g., ketotifen BID) ± PO anti-H1

E A R (AFP 2018;97:20)
Ear Pain
• Primary (otitis externa/media, foreign body, Eustachian tube dysfunction, barotrauma, cellulitis, cholesteatoma, mastoiditis, Ramsay
Hunt Syndrome 2/2 VZV) vs Secondary (TMJ, Bell’s Palsy, sinusitis, dental work, GERD, tumor, GCA, MI, thoracic aneurysm)
• Red Flags: signs of malignant otitis externa (HA/pain out of proportion to exam, fever, immunosuppressed, granulation tissue in floor
of ear canal) or otitis media spread (mastoid pain/swelling, bloody otorrhea, facial weakness, vertigo, nystagmus, photophobia)
Etiology Presentation Dx Tx
History: otalgia, itching. DM, water exposure, Typically PsA or S. Depends on if TM is intact and severity.
Otitis
cerumen. Exam: tragus/pinna pain, ear canal aureus. Assess for Topical: acetic acid, steroid, abx (FQ) oto-drops
Externa
edema/erythema, ± otorrhea/LAD/TM perf other skin conditions (UTD algorithm)
History: recent URI, smoking, hx Eustachian Viral > bacterial (S. If mild-mod, consider Rx if no improvement at
Otitis
tube dysfunction. Exam: TM bulging ± immobile pneumo, H. flu, M. 2-3d. Amox-clav BID x5-10d (or amox 500 TID).
Media
w/ erythema, conductive hearing loss catarrhalis) ENT if ruptured TM does not close in 6w
Tinnitus: false perception of sound in the absence of acoustic stimulus (NEJM 2018;378:1224; AFP 2014;89:106)
• History: dizziness/vertigo (consider Meniere’s), hearing loss, laterality (c/f schwannoma), meds (ASA, loops, abx), trauma, CVA, HA,
depression/anxiety. Red flags: persistent + pulsatile, unilateral + hearing loss, vertigo, focal neuro deficits – consider audiology
referral, imaging w/ CTA or MRA/MRV
• Tx: r/o underlying etiology. 20-50% have resolution spontaneously. If bothersome: CBT, sound therapy, tinnitus retraining therapy
Hearing Loss: RF - age, ♂, Caucasian, HTN, DM, CKD, immunosuppressed
• Conductive (mechanical): cerumen impaction, otitis externa/media, otosclerosis, ruptured TM, cholesteatoma (middle ear cyst)
• Sensorineural (neuro): presbycusis (age-related, gradual, symmetric, high frequency), noise-induced, Meniere’s (asymmetric,
+tinnitus, +vertigo), sudden sensorineural (acute, asymmetric, +tinnitus, urgent eval), barotrauma, tumor, meds, infxn
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Primary Care Nodules

A D R E N A L N O D U L E S ( > 1 C M ) (Endocr Rev 2020;41:775; PCOI)
• Q: Is it malignant? (<5% 1° carcinoma, <2.5% mets): high-risk imaging findings: diameter >4 cm (93% Sn for adrenocortical CA), >10
HU on CT, heterogeneous, hypervascularity, irregular shape, calcification, T2 signal on MRI, delayed contrast washout
• Q: Is it functionally active? (10-15%): exam & lab testing for all nodules >1cm (unless obvious myelolipoma) to r/o pheo & Cushing’s
syndrome (see table). Also test for hyperaldo if HTN, hypokalemia. Only test for production of excess sex hormones if clinical
stigmata. AVOID testing inpatients due to high false ⊕ rates
Diagnosis Suggestive Clinical Features Laboratory Tests
• HTN, metabolic syndrome, CVD, central obesity, prox muscle Baseline DHEAS. 1mg o/n dex
Cushing's syndrome weakness, facial plethora suppression test (DST): if ⊕ send
(~6-10%) • Glucose intolerance, DM 24h urine free cortisol, then
• Decreased, normal, or increased bone formation confirmatory 8mg o/n DST
• HTN (5-15% don’t have), palpitations, HA, diaphoresis, tremors
Plasma free (after 30m supine) or
• ≥10 HU on unenhanced CT, vascularity, cystic/hemorrhagic
24h urine fractionated metanephrines
Pheochromocytoma changes
& catecholamines (Sn 98%, Sp 98%)
(~3-5%) • Cardiomyopathy
Do not perform DST (above) if
• “Pheo crisis”: HTN/HoTN, psych d/o, multiorgan failure, concerned for pheo
hyperthermia
Plasma aldo & renin activity (correct
• HTN, hypokalemia
Hyperaldosteronism hypoK and d/c aldo antagonists
• risk stroke, CAD, afib, HF
(~1%) before testing). May need adrenal
• mortality (compared to matched population with essential HTN) venous sampling
• ♀: virilization, hirsutism, acne, irregular periods
Hyperandrogenism DHEAS, total testosterone, 17-OHP
• ♂: decreased libido, testicular atrophy, gynecomastia
• Consider adrenalectomy: if risk characteristics, >4cm, malignant, or hormonally active; surgery after hormonal eval
• Consider FNA: cannot distinguish between benign cortical mass & 1° adrenal CA. Useful if c/f adrenal met from another primary
without known metastatic disease (only after excluding pheo)
• Follow up: repeat CT in 12mo. Consider annual DHEAS/1mg DST x4-5y (unknown effectiveness, guidelines do not recommend).
Adrenalectomy if nodule grows >1 cm in 1 year, reaches 4cm, or becomes functional
T H Y R O I D N O D U L E S (Thyroid 2016;26:1; Endocr Pract 2016;22:622; PCOI)
• Q: Is it malignant? risk: h/o irradiation to head/neck, +family hx, h/o thyroid cancer syndromes (i.e., MEN 2), age <30
Workup: Thyroid Ultrasound, TSH • FNA: any nodule w/ extrathyroidal extension, extrusion
TSH normal or TSH low through rim calcs, abnormal cervical LNs, adjacent to
high ↓ laryngeal nerve/trachea OR >1cm + solid/hypoechoic w/
↓ FT4/T3, Thyroid radionuclide (123I) scan irregular margins, microcalcs, rim calc, or taller than wide
r/o hypothyroid ↓ ↓ shape. No FNA for pure cystic nodules. ACR uses TIRADS
(FT4/TPO Ab) “Cold nodule” “Hot nodule” • Follow up (benign): based on U/S characteristics. If highly
↓ ↓ ↓ suspicious U/S findings, repeat US & FNA w/in 6-12mo. If
Consider tx for low-moderate suspicious U/S findings, repeat U/S 12-24mo,
U/S-guided FNA if criteria met hyperthyroidism if sx consider FNA if >1-2cm change. Stop f/u after 2 neg FNAs
I N C I D E N T A L P U L M O N A R Y N O D U L E S ( < 3 C M ) (Radiology 2017;284:228; Chest 2013;143:e93S; Thorax 2015;70 Suppl 2:ii1)
NB: these guidelines are for incidental findings (see Fleischner Society Guidelines); recommendations for f/u of nodules found on LDCT
for lung cancer screening are different as that population is high risk (see Lung-RADS classification)
• Ddx: malignant (primary, met, carcinoid) or benign (majority; infectious granuloma, hamartoma, AVM, inflammatory)
• Is it malignant? Pt characteristics: risk w/ h/o smoking, emphysema, pulmonary fibrosis, extra-thoracic cancer, asbestos exposure,
age. Nodule characteristics: density (part-solid/ground glass>solid), larger size, faster rate of growth (increase >2mm on repeat CT),
borders (irregular/spiculated>smooth), location (upper>lower lobe)
• Is it benign? demonstrates fat (pulmonary hamartoma) or characteristic calcification pattern (granuloma, hamartoma) or stability on
CT for a defined period (>2y for solid and >5y for subsolid nodules)
• Follow-up: tailored to patient and type of nodule. Subsolid (entirely ground glass): if <6 mm, no routine f/u. If >6 mm, CT at 6-12mo,
then CT every 2y until 5y. Part solid: if <6mm, no routine f/u. If >6 mm, CT at 3-6mo, then annual CT for 5y if unchanged and solid
component <6 mm. Solid nodules: see below
• At MGH, consider referral to the Pulmonary Nodule Clinic: refer in Epic or call x38728 for appointment
Nodule type < 6 mm 6-8 mm > 8 mm
Single solid nodule
Low risk No routine follow up CT at 6-12mo, then cons. CT at 18-24mo Cons. CT at 3mo, PET/CT, or tissue sampling
High risk Optional CT at 12mo CT at 6-12mo, then CT at 18-24mo Cons. CT at 3mo, PET/CT, or tissue sampling
Multiple solid nodules
Low risk No routine follow up CT at 3-6mo, then cons. CT at 18-24mo CT at 3-6mo, then consider CT at 18-24mo
High risk Optional CT at 12mo CT at 3-6mo, then at 18-24mo CT at 3-6mo, then at 18-24mo

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Primary Care Musculoskeletal Pain

K N E E P A I N (PCOI)
• History: trauma, acute vs chronic, association with activity, constitutional sx, swelling, stiffness, instability, popping, locking or catching
sensation, sensory/motor changes, BMI, orthopedic or rheumatologic hx. Have pt point to area of pain with one finger
Knee Exam
Test Maneuver Positive in
Lachman (sim. to Pt supine with knee flexed to 20-30°. One hand on pt’s femur, just above knee. Other hand on pt’s tibia.
ACL injury
anterior drawer) Apply anterior pressure. If tibia feels less restrained, ⊕ test
Pt supine with knee flexed, can stabilize foot by sitting on it. Place hands around tibia, apply posterior
Posterior Drawer PCL injury
pressure parallel to femur. If less restrained motion, ⊕ test
One hand over medial joint line with knee fully flexed. Externally rotate foot/tibia, apply valgus stress, Meniscal
McMurray
and gently flex/extend knee. If clicking or pain at around medial joint line, ⊕ test injury
Location Traumatic Related to Activity Atraumatic
Patellofemoral syndrome*, Osgood-Schlatter,
Anterior Quadriceps or patellar injury RA, gout, pseudogout, septic joint
bursitis, quadriceps/patellar tendinopathy
Lateral Lateral meniscal tear, LCL injury Iliotibial band syndrome Lateral OA
Medial meniscal tear, MCL injury, tibial Medial OA, saphenous nerve
Medial Anserine bursitis
plateau fracture entrapment
Popliteal PCL injury Popliteal artery entrapment, Baker cyst Popliteal artery aneurysm, DVT
*Most common etiology in patients <45 yo (pain with patellofemoral joint palpation and compression of patella against femur)
• XR imaging: if trauma <1w, XR indications per Ottawa Knee Rule - Sn 98%, Sp 49% (Annals 2004;140:121)
o If eval of chronic OA: get weightbearing views of both knees; patellar view for patellar problems
• MRI: if suspecting fracture, infection, or internal derangement (e.g. ACL, meniscal tear in younger patients) or pain refractory to 4w
conservative care. Asymptomatic meniscal tears: 13% <45 yo, 36% >45 yo (Clin Ortho Rel Res 1992;282:177)
• Rx: all benefit from rest, ice/heat, NSAIDs (topical/PO) ± APAP, compression, PT, wt loss. For mod-sev OA, young ACL tear, or any
pain refractory to conservative tx, consider surgery. For bursitis, popliteal cyst, or IT band, consider steroid injection

S H O U L D E R P A I N (PCOI)
• General approach: r/o shoulder mimics, then rotator cuff pathology, then bursitis, impingement, OA or tendinopathy
Etiology History Findings Physical exam
Shoulder Mimics Consider cervical/neck pain, biceps pathology, cardiac or GI radiation
- ROM. Painful arc, impingement
- Internal lag test: bring dorsum of patient’s hand against
lumbar region of back. Take forearm and hand away from
the back (~20°). Ask pt to maintain position while
supporting elbow. ⊕ if not maintained
- External lag test: externally rotate shoulder 90°, flex
- Acute = trauma elbow 90°. Ask pt to maintain position. ⊕ if not maintained
- Chronic = age, acromial spurring, overuse - Drop arm: abduct arm to 90°. ⊕ if cannot smoothly
Rotator Cuff - Tendinopathy, partial or full thickness tears adduct shoulder to waist-level
- Pain & weakness, often with overhead arm use - Neer: pronate forearm (thumbs point backwards), bring
- Ortho referral often needed shoulder to full forward flexion. ⊕ if pain
- Hawkins: flex shoulder to 90°, flex elbow to 90°, and
internally rotate the shoulder. ⊕ if pain
- Ext rotation (teres minor, infraspin): flex elbow 90°,
externally rotate shoulder against resistance. ⊕ if pain
- Empty can (supraspin): flex shoulder to 90°, internally
rotate forearm. ⊕ if pain w/ resistance of downward push
Subacromial - Referred pain to deltoid - Pain w/ arc 60°-120° abduction ± impingement
Bursitis - Overuse, heavy lifting - ⊕ Neer & Hawkins
Glenohumeral OA/ - OA: aching, stiff; age >60
- OA: crepitus
Adhesive - Capsulitis: risk w/ DM, thyroid disease,
- Capsulitis: loss of active/passive ROM in all planes
Capsulitis immobilization; age 40-60
- Young: traumatic sprain, fall with separation - Pain, tenderness, swelling over AC joint
AC Joint Pain
- Older: AC evolves into OA & impingement - ⊕ cross arm test
• Imaging: none for bursitis. XR if h/o trauma c/f fracture or dislocation, gross deformity, exam concerning for OA, RTC tear or joint
involvement. Get true AP of glenohumeral joint, axillary lateral, & “Y view” of AC joint w/ stress views for trauma. MRI w/o contrast in
pts w/ ⊕ internal/external lag tests, r/o full thickness RTC tear, previous abnl XR, persistent pain despite 2-3mo of conservative tx
• Rx: conservative tx w/ activity avoidance, NSAIDs (Topical/PO), PT/home exercises ± short-term steroid injections; surgery for
refractory instability, labral/full RC tear, AC joint separation

L O W B A C K P A I N (Acute LBP PCOI)

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Primary Care Musculoskeletal Pain

• Incidence/Prognosis: 84% lifetime acute back pain, 50% sciatica (Mayo Clin Proc 2015;90:1699); 75-90% improve over 4 weeks
• PE: palpation of midline & paraspinal muscles, ROM spine/hip, LE strength/reflexes (L4-5 = foot dorsiflex; L5-S1 = foot plantarflex,
ankle reflex), rectal tone (if c/f cauda equina), SLR/crossed SLR (pain radiates below knee, often to heel, when straight leg raised
while supine; crossed SLR is radicular pain in opposite leg, Sp)
Origin Signs and Symptoms
Nonspecific Paraspinal muscles, Muscle spasm: paraspinal muscle tenderness w/ acute onset, usually unilateral. Disc:
MSK (85%) ligaments, discs, facets young,  w/ spine loading (i.e. sitting). Facet: >40 yo,  w/ extension,  w/ sitting
Radicular/ Disc herniation w/ nerve Sciatica 95% Sn, 88% Sp for herniation: leg > back pain w/ dermatomal distribution of
Spinal stenosis compression (90% L4-S1), lancinating/burning pain, SLR ⊕. Spinal stenosis causes neurogenic claudication: leg
(7%) spinal stenosis pain worse with walking (esp downhill) better with sitting/leaning forward
Vertebrae, discs, Compression fx: older, trauma, osteopenia, steroids. SI pain: MVA/falls, rheum.
Specific spinal
endplates, SI joints, facet Inflammatory: AM stiffness, night pain. Cancer: PMH, weight loss, night pain. Infection:
disorder (8%)
joints fever, night sweats, IVDU, immunosuppression
• Imaging: early MRI or XR if RED FLAGS – focal severe/progressive neuro deficits, cauda equina sx (b/l weakness, urinary
retention/incontinence, saddle anesthesia); trauma; c/f fracture, osteopenia risk (age >50 or <20, PMH, steroids); c/f CA or infxn
o Otherwise, defer imaging until after initial 4-6w tx (Annals 2007;147:478; Choosing Wisely) as herniation, disc bulging, DJD common
findings (Am J Neuroradiol 2015;36:811). See STarT Back Screening tool for further guidance
• Possibly effective and lower-risk therapies:
o Avoid bed rest. Explore social/psychological stressors, psych comorbidities, coping mechanisms
o Non-pharmacologic: acute: heat/cold, massage, acupuncture; chronic: yoga, CBT, mindfulness, rehab (Annals 2017;166:514); PT
& exercise (demonstrated benefit in sciatica (Annals 2021;174:8), though not other acute LBP)
o NSAIDs (ibuprofen 400-800mg TID or naproxen 220-440mg BID) are first line for limited duration if no contraindication
o Muscle relaxants: can add limited supply for acute pain if NSAIDs alone ineffective (JAMA 2015;314:1572)
o Duloxetine and TCAs for chronic LBP; second line after NSAIDs (Annals 2017;166:480)
o Epidural steroids (Pain Med/PM&R): for radicular pain refractory to 6w tx - limited evidence, benefits likely limited, short-term
• Therapies with questionable evidence and/or higher risk of harm:
Acetaminophen: if NSAIDs contraindicated; but little e/o effectiveness (Lancet 2014;384:1586). Oral prednisone taper for acute
sciatica: inconclusive evidence (Annals 2017;166:480). Gabapentin, pregabalin: option for sciatica though efficacy inconclusive
(NEJM 2017;376:1111). Opioids (see below): limited evidence of effectiveness & risk of harm (JAMA 2018;319:872). Surgery: short-
term sx relief in disc herniation w/o clear long-term benefit, side effects in spinal stenosis w/o e/o improved fxn
F O O T A N D A N K L E P A I N (PCOI)
Etiology History and Physical Dx and Tx
- Imaging: use Ottawa Ankle Rule (Sn 96%)
- Trauma history
- Ice, elevation, rest followed by exercise (consider PT)
- Pain/instability/swelling, bruising, focal tenderness over
Ankle sprain - Grade I (stretch, no tear): elastic wrap; grade II (partial
ligament (ATFL most common); squeeze test to r/o
tear, swelling, bruising): aircast or other splint; grade III
syndesmotic sprain
(complete tear, unstable): casting, sports med/ortho c/s
- Overuse or change in activity common - MRI only if uncertain
Achilles
- Pain & thickening at insertion or 2-6cm proximally; calf - Rest, ice, tendon support, PT
tendinopathy
squeeze to r/o complete rupture - Surgical c/s for complete tear
- XR insensitive esp early in course; if ⊝ MRI may be
- Overuse; more common in ♀ esp if amenorrheic,
req
Stress underwt (rel caloric deficiency/overtraining syndrome)
- Rest/non-wt-bearing 2-6w
fracture - Insidious onset of pain after exercising, ± focal
- Consider ortho c/s if high risk for nonunion (anterior
tenderness on exam (tibia > tarsal > metatarsal)
tibia, navicular, talus, 1st or 5th metatarsal)
Plantar - Assoc w/ overuse, pes planus, overweight - If uncertain, US may show thickening
fasciitis - Sharp anteromedial heel pain with activity after rest - Ice, stretching, NSAIDs, heel cups/OTC orthotics
Ddx: tarsal tunnel, Charcot foot (>40yo, obesity/neuropathy, swelling w/ minimal pain), hallux valgus (“bunion”), hallux rigidus (OA of 1st
MTP), interdigital neuroma, non-Achilles tendinopathy, arthritis, gout/CPPD, derm (corns, calluses, warts, paronychia)
LONG-TERM OPIOIDS FOR MUSCULOSKELETAL PAIN
• Before prescribing longer-term opioids: (NB limited evidence; high risks of hyperalgesia, tolerance, dependence, addiction)
o Exhaust non-opioid options. Avoid BDZ, hypnotics. Screen for OSA, SUD, mental health. Stress complete pain relief is
unlikely. Set functional goals. Perform risk assessment (SOAPP-R). Check PDMP. Obtain prior records, speak to prior
prescribers
o Pain agreement (PCOI form) is required. MA law: Must check PDMP and limit 7 days for initial opioid prescription. Discuss 6-8w
initial trial & safe use, storage, & disposal of opioids. Educate that random UTox and pill counts are for pt safety. Agree that
single prescriber will Rx. Rx on 28d cycle ending on weekday to facilitate refills. Rx naloxone
• Follow-up for longer-term opioids: See at least q1-3mo to review pain/function, side effects, adherence
o Discontinue opioids if no significant benefit at 6-8w: significant side effects, risk > benefit, non-adherence
o Caution prescribing >50mg/d morphine equivalents (MME), avoid >90 MME (c/s pain)
o Early refill requests should trigger appointment to assess reason, obtain tox screen, discuss use

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Primary Care Immigrant & Refugee Health

M E D I C A L E X A M I N A T I O N (CDC)
Interpreter Services: In person - x66966, p27403 (M-F 7a-8p; S/Su 8a-6:30p) or via phone service [617-643-3344 Pin #1050]. Speak
in short sentences & make sure to address the patient (not interpreter) when speaking.
History: obtain prior medical records if possible
• SHx: country of origin, travel hx, transit countries, residence in refugee camps/detention centers, time living in US, family
structure/hx of separation, food security, housing stability, home/neighborhood safety, education/literacy, occupational hx
• PMHx: chronic diseases (incl. pain), surgeries, cancer screens, ♀ OBGYN hx, sexual hx, meds (incl traditional/herbal remedies),
smoke/toxin/lead exposures, tobacco/substance use (incl. those legal in country of origin; inform of legality differences in US)
• Mental health: screen for PTSD, anxiety, MDD (on 2nd visit to re-traumatizing). RHS-15 is a consolidated screening tool.
• ROS: fever, wt loss, night sweats, respiratory concerns, diarrhea, abdominal discomfort, pruritis, skin rashes/lesions
Physical Exam: reassure patients this exam is for their health & not regulatory purposes
• Vision, dental, hearing, BMI, BP. Eval for murmurs, hepatosplenomegaly, LAD, skin lesions (rashes, trauma, nutrient deficiency)
• See PCOI for low-cost referral options for dental and eye care:  “Health Care Access”
Vaccinations: if no documentation (translation guide), assume not vaccinated (see Health Screening & Maintenance)
• Can check titers for MMR/VZV/HAV. Incomplete HBV vaccination may result in transiently elevated titers. Assess need for polio.
Screening and Labs: Infection* Signs & Symptoms
• Gen: CBC/diff (eos, anemia), UA (hematuria), BMP (glucose, renal dz), ♀ hCG, Strongyloidiasis,
lead screen if preg/lactating/taking medications, HepB/HepC screen; age- filariasis, Peripheral eosinophilia
appropriate screens (lipids, HIV, etc.) schistosomiasis
• STIs (see STI): syphilis, HIV, GC/CT if ♀≤24+sexually active or ♀>24+RF Hematuria, ♀ infertility,
Schistosomiasis
• TB: ask yearly about sx, recent travel, sick contacts; retest PRN (see Tuberculosis) chronic pelvic pain
Malaria,
• Malaria: Rx if from Sub-Saharan Africa w/o pre-departure Rx or from endemic schistosomiasis
Splenomegaly
country w/sx (Rx resistance info here). If preg/breastfeeding, Dx first (do not Rx Mycetoma,
empirically). Obtain thick/thin smears or PCR (Sn if no sx) onchocerciasis, other Chronic rash or itching
• Intestinal/tissue invasive parasites: varies by country & pre-departure tx. See CDC filarial diseases
guideline. No empiric ivermectin if from Loa loa-endemic country Esoph. dysmotility,
Chagas disease
• Micronutrients (Fe, D, B12, etc): if malnutrition, anemia, h/o food insecurity HF, conduction dz
• Misc: Use CDC regional profiles or CareRef for recs for specific demographics Neurocysticercosis Seizures, CNS sx

L E G A L C O N S I D E R A T I O N S (Boston-area legal services, MGH Chelsea LINC referral if pt @ MGH Chelsea CHC )
• Do NOT document immigration status in EMR
• MassHealth eligibility is NOT contingent on immigration status. Refer all uninsured pts to PFS. Multilingual videos for pts on the ACA
• Know your Rights re: ICE: multilingual infographics from Immigrant Defense Project & Immigrant Legal Resource Center
• Asylum screening questions (yes/no answers sufficient; obtain only as much detail as necessary to refer for legal support; re-telling or
re-living experiences can be re-traumatizing & asylum seekers will have to tell their whole story to lawyers/doctors in the future)
o What led you to leave your home country?
o Were you ever a victim of violence or (verbal, sexual, physical) abuse there?
o If so, was it due to your religion, race, political beliefs, nationality, or particular social group (gender, sexual identity)?
o If so, did you face violence from anyone working for the government, military, or police?
o If yes  refer to legal organization above, PAIR, or the MGH asylum clinic
• Resources on conducting asylum evaluations and working with asylum seekers
• Resources within Boston area: Refugeography (Google map of various food pantries, job training, ESL, social support services, etc.)
• Additional tips: Travel: undocumented pts will now be able to apply for driver’s license (DL) in MA (H4805), however, DL will likely not
meet REAL ID requirements for air travel (to start: 5/7/25) – risk being detained by CBP agents stationed at any US international
airport if trying to fly; Legal: can support pt’s petition for legal status by providing documentation re: medical need for legal status
(coordinate w/legal team if pt/team desires); Advocacy: consider joining Asylum clinic and/or IHC groups
Immigration Statuses Details
Lawful Permanent
Green card recipient; pathway to citizenship. Family can get green card through “family based” immigration
Resident (LPR)
U-Visa, T-Visa Eligible if victim of human trafficking (T) or victim of certain types of crime (U).
VAWA Violence Against Women Act: eligible if abused by spouse, child, or parent who is LPR/citizen
Temporary Protected
Short list of countries where conditions preclude safe return. Cannot be deported while country of origin listed
Status (TPS)
Based on exceptional hardship anticipated to self or LPR/citizen, spouse, parent, child if deported; ineligible with certain
Cancellation of Removal
criminal convictions
Well-founded fear of persecution based on race, religion, nationality, membership in social group, or political opinion.
Asylum
Application due w/in 1y of date of entry. If granted, may apply to spouse/children if they are in US
Same legal standard as asylum, based on persecution or well-founded fear, but granted prior to arrival in US. Maximum
Refugee
set annually by President (no limit to asylum)
Temporary reprieve from deportation for immigrants facing life-threatening medical conditions & other humanitarian
Medical Deferred Action
circumstances
Asylum/CAT/Withholding all part of same application. No 1y rule. Ineligible with certain criminal convictions. No path to
Withholding of Removal
citizenship
CAT Convention Against Torture: similar to Withholding, but still eligible with criminal convictions
Undocumented Patients should seek legal counsel to check for options to apply for alternative statuses
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Primary Care Climate Change & Health

Climate Change Drivers (NASA, CDC): atmospheric CO2 & other greenhouse gases 2/2 human activities

Principal Climate Effects (USGCRP CSSR 2017; IPCC AR6 2021):

temp, sea level, precipitation pattern changes, ocean acidification, extreme weather

Mediators of Climate-Related Health Risks (NEJM 2019;380:263)

Access to quality healthcare Baseline air & water quality Geography Poverty & housing
Age & sex Baseline nutritional status Occupation Racism & discrimination
Agricultural practices Ecosystem & land use change Pre-existing health conditions Warning systems

Poor air quality and Climate-sensitive Imbalanced water

Extreme heat Extreme weather Food insecurity
increasing allergens infectious disease quality and quantity
- Early death PM2.5 (particulates - habitability for - Tropical - Drought: resp - nutritional
- CVD/resp dz ≤2.5µm diameter): Ixodes ticks  storms: direct effects of dust content of staple
exacerbations - Early death expanded Lyme injury, trauma, inhalation crops
- Heat stress - CV disease distribution flooding - Water insecurity - productivity of
nephropathy (NEJM - vectorial - Wildfire: burns  nutrition, fisheries
Health Effects

- Fluid/ 2021;385:1881) capacity for Aedes & injury, sanitation, - Undernutrition,

electrolyte - Worsened resp dz spp mosquitos  inhalational susceptibility to underweight, &
disturbances - Low birth wt dengue & malaria injury, produces violence stunting
- Suicide Ozone: - waterborne dz PM2.5 (see left) - Flooding: - susceptibility
- Mental health - Early death (Vibrio, Leptospira, and other allergenic molds, of food to
- risk - ED visits Shigella, pollutants that diarrheal diseases, spoilage & pests
congenital heart Aeroallergens: Campylobacter) can spread toxic algal blooms
defects -asthma/allergy internationally
- Desertification - Missed school, -strain on public - cost of - crop yields 2/2 - frequency of
- Missed work, workdays health systems for disaster relief & precipitation ∆, salt conflict
Secondary
Impacts

2˚ economic -healthcare costs dz control recovery water intrusion - food prices,

impact (Health Aff -abx resistance - Disrupted - Wildfire risk purchasing
- Power outages 2020;39:2113) w/ temp (Nat Clim health care - Forced migration power of vuln.
Change 2018;8:510) delivery populations

TREATMENT
Counsel Patients on Climate & Health Co-Benefits
Patient-Centered Actions

• Educate patients: help patients understand links between climate and health (Ann Intern Med 2021;174(3):417),
develop an extreme heat plan (CDC Guide, Boston Guide) & disaster-preparedness (PlanetReady, ClimateCrew)
• Co-Benefits: actions that both improve health & mitigate emissions that drive climate change. Examples:
o Red meat consumption  improved CV/renal health, emissions (in 2017, excess red meat consumption
contributed to 990,000 deaths worldwide, & emissions from beef were >400kg CO2e/person)
o Active transportation  improved CV health, transport-related pollution & emissions (BMJ 2020; 368:l6758)
o Inhaler Prescribing: MDIs use HFA propellant w/ potent global warming potential (GWP), MDIs have 10-37x
GWP of matching DPIs. Prescribe DPIs when able, control asthma effectively to limit use of SABA, prescribe
smaller canister SABAs (6.7g) to limit HFA release (BMJ 2019; 9(10):e028763)
Improve Health Care Delivery in a Changing Climate
• Discuss the impacts of climate change w/ colleagues; Climate Resources for Health Education has slides/educational
cases about the effects on most organ systems which are available for use in presentations
Institutional

• Improve resilience: U.S. Climate Resilience Toolkit: best practices for US health care facilities to withstand climate impact
Actions

• Deliver climate-smart healthcare (NEJM 2021;385:2117): US healthcare-associated pollution comprised ~8.5% US

GHG emissions & drove comparable disease as deaths from preventable medical errors (Health Aff 2020;39:2071).
- Health Care Without Harm & Practice Greenhealth (free membership for MGH residents): resources to improve
resource stewardship, decarbonize energy sources, & procure food & materials sustainably
Example Advocacy Topics in Climate and Health
• Paris Agreement: limits warming to 2˚C above pre-industrial levels, with further goal to limit to 1.5˚C in recognition that
Policy & Advocacy

2˚C would be catastrophic for certain populations (IPCC SR1.5 2019). Warming is on track to exceed 2.7˚C by 2100
(UNEP EGR 2021). Current policies and mitigation efforts continue to fall short with global emissions reaching a record
Actions

high (once again) in 2022 (Lancet 2023; 402:2347)

• Equity is critical: people least responsible stand to suffer most (Health Aff 2020;39:2056). Locally, Black and Latinx
Americans inhale disproportionately more PM2.5 than is caused by their consumption (PNAS 2019;116:6001) due to
intentionally racist practices such as redlining (EST 2022;9,4,345–350)
• Massachusetts Climate Action Network is supporting multiple bills currently in MA state legislature
Read NEJM 2019;380:209 & ACP Toolkit for further resources for physicians, patients, and policymakers; PCOI page for tips in primary care and handouts for discussion with
patients
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Primary Care Health Equity & Insurance

SOCIAL DETERMINATES OF H E A L T H (AAFP EveryONE Project)
Accounts for 30-55% of health outcomes with up to 20-year gap in life expectancy between counties with lowest and highest life
expectancy in the US. SDH primarily influence health outcomes through limiting opportunities to live a healthy lifestyle or chronic
stress (JAMA 2017; 117:1003). Structural racism limits opportunities through discriminatory practices in labor, housing and
educational systems with racism and stress being shown to affect both mental and physical health outcomes (Lancet 2017;
389:1453).

Economic Environmental Education Food Community Health Systems

Employment Housing Literacy Hunger Social integration Insurance coverage
Income Transportation Language Food deserts Support Provider availability
Expenses Safety Early ed. Availability of Discrimination Linguistic/cultural
Debt Parks Higher ed. healthy options Racism competency
Medical bills Playgrounds Vocational Stress Quality of care

Health Outcomes
mortality, morbidity, life expectancy, health expenditures, functional limitations, health status

STRATEGIES TO ADDRESSING HEALTH INEQUITY

1) Understand patient’s community (County Health Rankings and Roadmaps); screen for SDOH (useful dot phrase:
.SDOHSCREEN, if positive refer to MGH SDoH Services aka “Ambulatory Referral to MGH SDH”)
2) Consciously address implicit bias (Harvard Project Implicit); reflect on gut reactions, ask if they are rooted in implicit bias
3) Address patient health literacy; utilize in-person interpreter services when available, schedule longer visits, employ teach back
method, utilize dot phrase .MEDSS for a framework to optimize medication adherence.
4) Identify and utilize resources within your clinics to address SDOH; AAFP Neighborhood Navigator, 211, and FindHelp can help
identify local resources

INSURANCE COVERAGE
• Open enrollment: limited time when one can buy a new insurance plan, varies by employer and insurance system; MassHealth
~Nov-Jan.
• Patient Financial Services can assist patients, both inpatient and outpatient, with applying for state-funded programs such as
MassHealth and Health Safety Net: 617-726-2191.
• MassHealth: federal and state funded healthcare coverage, MA’s interpretation of Medicaid and CHIP; can apply online (if age
<65), by mail or fax, will take 45-90d for approval; must renew households annually
o Basic eligibility requirements: MA resident, eligible citizenship/immigration status, valid SSN
 Can apply for MassHealth Limited for patients who have an immigration status that keeps them from getting
more services.
o Several coverage options available with eligibility for age <65y determined by comorbidities and income, ranging from
≤133-300% federal poverty limit (FPL); age ≥65y eligible if income ≤100% FPL, more lenient for disabled seniors

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Primary Care Disability Competent Care

Authors Comments: Please note that this is an incredibly important and evolving field, which lacks substantial data, publications, and amplification of voices of
individuals with disabilities. We write this page with humility and awareness that we are constantly learning how best to support and care for our patients with
disabilities. We would welcome any feedback. This White Book page is largely adapted from: Kripke C. Adults with Developmental Disabilities: A Comprehensive
Approach to Medical Care. Am Fam Physician. 2018;97(10):649-656.
DEFINITIONS, MODELS, LANGUAGE
● Disability: Differences in cognitive and/or physical function in which individuals benefit from support in areas of major life activity; ie self-care,
language, mobility, self-direction, ability to live independently and economic self-sufficiency. Am Fam Physician. 2018;97(10):649-656
o Disabilities are diverse. They can be related to, but not limited to: developmental conditions, genetic conditions, injuries, strokes,
chronic diseases (eg diabetes), physical and neurologic disorders and psychiatric disorders .Blind/deaf Ablism
● There are many models of care for individuals with disability (i.e medical, social, bio-psychosocial) Current medical practice is moving towards
centering the Neurodiversity & Social Model of care. Am Fam Physician. 2018;97(10):649-656
o Medical model: Disability is a problem of the person, directly caused by disease, trauma or other health condition, which requires
medical care. Management of disability aims at cure or the individual's adjustment and behavior change.
o Neurodiversity Model: Neurocognitive differences are valued components of human neurologic diversity.
o Social Model: Emphasizes that disability is a socially created problem, not an attribute of an individual. Focuses on improving
positive experience in society, emphasizes inclusion and accommodation in physical & social environments
● Individuals with disabilities face tremendous amount of discrimination in society, including the healthcare system.
o Rejection of medical model of disability, which treats disability as an illness that needs to be fixed or overcome.
● Disability Competent Care: A model that focuses on caring for the individual beyond the disability, rooted in 3 core values: “1) the individual
needs of the participant, 2) respect for the participant’s choices, and 3) the elimination of medical and institutional bias.” (RIC DCC Model)
AP PROACH T O HEALT HCARE MAINTENANCE, SEXUAL AND MEN T AL HEA L T H
• Healthcare Maintenance: See section on Age Appropriate Screenings.
● Adults with disabilities face profound healthcare inequities. They are at higher risk for heart disease,
diabetes, obesity & smoking compared to adults without disabilities (CDC Disability & Health in MA 2023)
● Clinicians have conscious/unconscious biases and make assumptions about adults with disabilities’ GOC
and QoL that contribute to disparities in health outcomes. (Health Aff (Millwood). 2021;40(2):297-306)
● Conduct annual physicals, as medical conditions tend to be underrecognized and undertreated,
particularly among nonverbal patients. (see Table from Am Fam Physician. 2018;97(10):649-656)
● At initial encounter, conduct baseline assessment of function, with a focus on: a) cognition b)
communication c) sensory function (eg vision, hearing) d) neuromuscular function e) seizure threshold (if
applicable) f) mental health. Acute illness among individuals with disabilities often presents as a change
from baseline function. (Am Fam Physician. 2018;97(10):649-656)
● Sexual Health: Offer comprehensive sexual and reproductive health services. Do not assume that adults
with disabilities are not sexually active, do not wish to become pregnant or are not at risk for STIs.
● Mental Health: Adults with disabilities report mental health distress 4.6x more frequently than adults
without disabilities. Prioritize mental health screenings, treatment, and lifestyle modifications to promote
wellness (eg sleep, healthy weight, physical activity as able) (MMWR 2020:69(36))
LANGUAGE AND CO M M UNI CAT IO N
● Commitment to person-centered communication and patient autonomy, communicating and acting with
humility towards patients and their families.
● Speak directly to pt regardless of ability to respond. Use of aides to enhance communication: pictural
language, voice amplifiers, demonstrations, alternative formats (large print, braille). View UCSF Communication Toolkit for more resources.
● Language matters: Avoid terminology such as “handicap,” “mental retardation,” and “wheelchair bound” or “confined to a wheelchair.”
Preferred terms are “disabled,” “intellectual disability,” and “wheelchair user”
Examples of patient and family centered language (adapted from: Am Fam Physician. 2018;97(10):649-656, please view for more examples)
Common Pitfall Respectful Alternative
Speaking to supporter: Since she is non-verbal, can you Speaking to patient: Can you show me how you say yes and no? Are you in pain?
share what brings her in today? Thank you for sharing. I would like to gather some more information. Is it ok if I ask
your __ (supporter)?
To supporter: Your son is so lucky to have you—you are a Patients and their families both deserve support. What types of support do you
super dad! (supporter) need?
ACCO M MO DATI O NS AND S E RV I CE S
• FMLA: Family and Medical Leave Act provides 12 weeks of unpaid leave per year. Can be used for personal illness, carrying for a family
member an illness, parental leave after birth/foster/adoption.
• Short-Term Disability: Replaces a portion of income for 3-6months for patients who develop illnesses, disabilities, or injuries not related to jobs
• Long-Term Disability: Replaces a portion of income if patient cannot work for >90 days
• Social Security Disability Insurance: provides monthly payments to individuals who cannot work due to their disability
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Consultants Calling Consults

TIPS FOR CALLING CONSULTS
• To do BEFORE you call:
o Place order in Epic for consult
o Know your patient: review the H&P/chart and see/examine the patient; recommend reviewing last clinic & operative notes if
applicable (Notes → Filters → Specialty); for all below, mention any outpatient providers
 GI: melena/hematochezia, current/prior H/H, plts, coags, transfusions, past EGD/colo, vitals, IV access, NSAID/ASA use,
rectal exam findings; for cirrhosis: any prior work-up, social history, complications, decompensation
 Cards: recent and old ECG, telemetry, prior stress/echo/cath (know anatomy), dry weight, biomarkers, current cardiac meds
 Renal: baseline Cr, CKD stage, on/off HD, dialysis access, electrolyte mgmt, current UOP, nephrotoxins
 Onc: known cancers w/ stage/tx history, clinical trial history, biopsy results (for new dx), current anticoagulants, special
slide; if on immunotherapy, usually on SIC (Severe Immunotherapy Complications) service list at MGH
 ID: current/past micro data, possible sources, current/prior abx (incl # of days), fever curve, hardware, travel, exposures
 Pulm: imaging results, social hx, prior work-up (e.g., autoimmune), prior/current O2 requirements, PFTs
o Know your question – Bigelow JAR should specify consult question in task list. If not there, ASK. It is always OK to clarify
• To do DURING the page/call:
o Call as early in the day as possible (ideally before noon), find out how to page using the paging directory
o At MGH: paging directory → find “On Call Directory”
o In your page to consulting team, include: pt name, MRN, location, call back #, brief consult question +/- level of urgency
o Avoid “curbside” questions unless official curbside consult service. If specific question about management, call a formal consult.
o Tell the consultant the One-Word reason for your call (i.e. hematochezia, hemoptysis, hyponatremia etc.) followed by a brief
HPI, a clear explanation of the team’s thinking, and a clear and specific question
• To do AFTER the call:
o Invite the consultant to find you to relay their recommendations or tell them who will be covering for you
o Consultant will often provide prelim recommendations on phone, follow-up recommendations in documentation/note later
CALLING EMERGENT CONSULTS
• Surgery: STAT = imminently life-threatening emergency (e.g. lost airway, hypotensive from hemorrhage); URGENT = high concern
for urgent surgical question (e.g. acute abdomen, perforated bowel, etc.)
o Page ”Churchill Senior on call” under Emergency General Surgery(Churchill)
• Psychiatry (e.g. pt actively trying to leave AMA w/ unclear capacity; security concerns, major behavioral issues)
o 8am-6pm: p33061 (Emergency Consult Resident). If weekend/Holiday: p17911 (weekend rounding psychiatrist)
o 6pm-8am: Call APS (4-7688) or page APS resident at 27792
• Toxicology (ingestions/overdoses/exposures/interactions): call Poison Control Massachusetts (617-355-6607 or 800-222-1222).
• Cardiac Surgery: page the Attending On Call. Thoracic Surgery: page the Fellow on Call. Vascular Surgery: pg 21469.
CALLING SURGICAL CONSULTS AT MGH
• The patient must be seen when a consult is called. Please try to call early or, if nonurgent, wait until the next day if late.
• In the ED: ED surgery “pit team.” They typically sit in Acute bay across from room #5 & are listed in Amion as ED Surgery Team
o For patients in the Acute bay: pit senior (x44169; p13115). For patients anywhere else in the ED: pit junior (x44187; p20491)
o Once the patient is on the floor, page PGY1 on the consulting team (identified in the consult note)
• New surgery consult (floor or ICU): page the senior resident of the appropriate surgical service
o If patient known to an MGH surgeon, consult senior resident on that team to discuss
o If patient not known to a surgeon, do your best to elucidate the appropriate team based on disease state (Baker surgery teams).
When in doubt, contact the senior resident of the most appropriate team to further triage.
• Follow up on GENERAL surgery consults: page the PGY1 covering the consulted service
• Cardiac Surgery consult  if non-emergent (8:30am-5pm) place order. Also page NP at 30010 from 5pm-8:30am, weekends, and
holidays.
• Ortho consult  page “Floor resident” at 20296 under “Orthopedics” or if ED consult, page 22566
• Transplant Surgery consult  page “Resident” under “Transplant Surgery”
CALLING OTHER SUBSPECIALTY CONSULTS
• ACT (Addiction Consult Team): place consult in Epic (no need to call), page 29967 if need help overnight.
• AMS (Anticoagulation Management Service): for established pts: p30104, or click AMS icon in Epic to determine existing AMS RN.
For discharge – place Epic consult; if urgent or questions, page Discharge Pathway Service: p30104
• Cardiology: login to Amion under “mghcardiology” to identify appropriate fellow (link also in paging directory)
• Chronic pain service for refractory or cancer pain; for interventions (e.g., injections/ketamine/high dose PCA)
• Acute pain service for epidurals, periop pain.
• Diabetes nurse educator: service NP p20737; MD p14364
• ENT: page 22220. Backup/emergency number is 617-523-7900 (MEEI operator) and ask them to page ENT resident on call
• Optimum Care Committee (“OCC,” Ethics): page ethics support pager: p32097 (Mon-Fri, 8am-4pm, except holidays)
• Ophtho: p21004. Backup # 617-573-4063 (MEEI ED). Before calling know if OK to travel to MEEI for exam & if ok to dilate.
• Psychiatry: for non-emergent floor consult: order psych consult in Epic
o Weekday, Weekend Night, Holiday Night: call CL coordinators (6-2984). These consults will be seen within 24 hours.
o Weekend or Holiday 8am-5pm: p17911 (weekend rounding psychiatrist)
• Transfusion reactions: page blood bank resident at 21829

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Consultants Perioperative Medicine

PERI-OPERATIVE CARDIAC RISK STRATIFICATION AND RISK REDUCTION
GOAL: to estimate risk, optimize, and pause for cardiac testing regarding peri-operative cardiac events, NOT to “clear for surgery”
• Peri-op cardiac events: MI (usually clinically silent, NSTEMI>STEMI, POD#0-3, not intraop), CHF, VT/VF, cardiac arrest, death
o Major determinants include: (1) preceding condition of patient (2) risk of procedure (3) functional capacity
• Emphasis on risk stratification. Very few patients need non-invasive/invasive testing, only if testing would change cardiac
optimization management (initiating medical management, PCI, Cardiac Surgery) even in the absence of surgery

P E R I - O P E R A T I V E C A R D I O V A S C U L A R E V A L U A T I O N F O R N O N - C A R D I A C S U R G E R Y (adapted JACC 2014;64:e77)

Emergency non- † Active Cardiac Conditions

cardiac surgery? - Unstable Coronary Syndromes:
unstable/severe angina, acute (<7d) or
recent (<30d) MI
- Decompensated HF
Yes No - Significant Arrhythmias:
symptomatic/new ventricular
arrhythmias, SVT with HR >100 at rest,
Proceed Active cardiac condition? †
symptomatic bradycardia, high-grade
with
surgery AVB
- Severe Valvular Disease: severe sx
Yes No AS (mean grad >40, AVA < 1.0 cm2),
sx MS (progressive DOE, presyncope,
HF)
Estimate perioperative risk
Treat/Test/Stabilize of major adverse cardiac
and reassess risk- events based on combined
benefit of surgery clinical/surgical risk ‡ * 4+ METs:
2 flights stairs;
4 blocks;
Golf, bowl, dance;
‡ 2 Surgical Risk Calculators Duke Activity Status Index
Low risk (<1% per NSQIP Elevated risk
(1) Revised Cardiac Risk Index
(2) Gupta MICA NSQIP Risk Prediction or RCRI score 0-1)

Able to achieve ≥4 METs? *

Proceed to
surgery
No/unknown Yes
Operative Risk without Adjustment for Patient Factors
Intermediate
High Risk >5% Low Risk <1% Discuss risk with pt and surgeon
Risk 1-5%
- Emergent major - HEENT, CEA - Superficial, Optimize comorbidities
surgery, especially - Intrathoracic, cataract, breast Consider TTE or stress if it will change Proceed to
in elderly intraperitoneal, - Endoscopy mgmt (BB or further workup) surgery
- Aortic, peripheral, prostate - Ambulatory Consult Cardiology if LM CAD to
or major vascular - Orthopedic discuss preop revascularization

R E V I S E D C A R D I A C R I S K I N D E X ( R C R I , G O L D M A N ) (Circ 1999;100:1043; Can J Cardiol 2017;33:17)

• Six independent predictors (risk factors) of major cardiac complications
1. High-risk noncardiac surgery (not a clinical RF but incorporated elsewhere in algorithm): OR 2.6
2. CAD (MI, PCI, CABG, angina, nitrate use, ECG with pathologic Q waves, or ⊕ exercise stress test): OR 3.8
3. HF (CHF, pulm edema, bilateral rales, or S3): OR 4.3
4. Cerebrovascular disease (stroke or TIA): OR 3.0
5. Diabetes mellitus with preop insulin therapy: OR 1.0
6. Renal insufficiency with preop Cr >2.0 mg/dL: OR 0.9
• RCRI event rates were re-calculated (and partially validated) in 2017 after multiple trials included troponins ± emergent surgeries
Rate of cardiac death, MI, pulm edema, CHB, cardiac arrest/VF
RCRI 1999 Event Rates (95% CI) 2017 Event Rates (95% CI)
0 0.4-0.5% (0.05-1.5)  ~0.5% 3.9% (2.8-5.4)  ~4%
1 0.9-1.3% (0.3-2.1)  ~1% 6.0% (4.9-7.4)  ~6%
2 3.6-6.6% (2.1-10.3)  ~5% 10.1% (8.1-12.6)  ~10%
≥3 9.1-11.0% (5.5-18.4)  ~10% 15.0% (11.1-20.0)  ~15%

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Consultants Perioperative Medicine

A L T E R N A T I V E C A R D I A C R I S K A S S E S S M E N T ( M I C A , G U P T A ) (Circ 2011;124:381)
• Identified 5 risk factors predictive of risk of STEMI or cardiac arrest w/in 30 days of surgery:
1) Type of surgery/procedure, 2) preoperative functional status, 3) serum Cr >1.5, 4) ASA class, 5) increasing age
• Compared to RCRI, better discriminative predictive value
• Limitations: likely underestimates actual risk because MI was defined in the study based on only ECG changes: STEMI or new
LBBB; biomarkers were NOT monitored post-op, which is necessary to detect more than 50% of perioperative MIs

P R E O P E R A T I V E C O R O N A R Y R E V A S C U L A R I Z A T I O N (NEJM 2004;351:2795)
• CARP: multicenter RCT of 510 high-risk vascular surgery patients, showed prophylactic revascularization w/ BMS/CABG conferred no
survival benefit; data extrapolated to lower risk non-vascular/non-cardiac surgeries
o Exclusion criteria: EF < 20%, unstable angina, LMCA disease > 50%, severe AS

PERI-OPERATIVE β-BLOCKADE AND OTHER CARDIAC DRUGS

• Evaluate for peri-operative β-blockade (Circ 2014;130:278)
o Continue β-blocker: if already taking for other indication (e.g. CAD, arrhythmia, HTN) for goal HR 55-65 (Class I, LOE C)
o Consider initiating β-blocker: ≥3 RCRI RFs or intermediate/high risk preop test (Class IIb, LOE B)
▫ Do not start a β-blocker within 24 hours of surgery! (Lancet 2008;371:1839; JACC 2014;64:2406)
o Uncertain role of β-blocker: if ⊕ stress test or long-term indication without other RCRI risk factors
• Anti-platelet: (NEJM 2014;370:1494; Anesth Analg 2015;120:570)
o 1° prevention: can generally be held prior to surgery
o 2° prevention: continue ASA 81mg unless high risk of bleeding (intramedullary spine, intracranial, hip, knee, possibly prostate)
o DAPT post-PCI: POBA <14d, BMS <30d, DES <6-12mo  discuss with Cardiology
• ACEi/ARB: pts have more transient peri- and post-op episodes of HoTN; no diff in death, post-op MI, stroke;  or  AKI unclear
o Discontinue ACEi/ARB night before surgery (unless used for HF and BP ok). At MGH hold prior to cardiac surgery
o Failure to restart ARB within 48h 30d mortality (Anesthes 2015;123:288)
• Other: consider holding diuretics, other anti-hypertensives should be continued perioperatively to goal BP <180/100 to avoid bleeding
• Anticoagulation and bridging: see Anticoagulation Management

V T E P R O P H Y L A X I S (Mayo Clin Proc 2014;89:394)

• Postop VTE risk assessment: Caparini Score
• Non-orthopedic surgeries: those undergoing general or abdominal/pelvic surgery are at highest risk
• Orthopedic surgeries: all pts at high VTE risk 2/2 tourniquet time + immobilization; minimum duration 10-14d (35d if higher risk)

P E R I - O P E R A T I V E M O N I T O R I N G A N D C O N S I D E R A T I O N S (NEJM 2015;373:2258)
• ACS NSQIP Surgical Risk Calculator can help estimate other post-operative complications including LOS, need for rehab, risk of
non-cardiac post-operative complications (Am J Cardiol. 2018; 121:125)
• ACS: most MIs occur w/in 48h while patients are on analgesics that mask pain  some data show benefit of troponin monitoring
(JAMA 2012;307:2295). Elevated post-op NT-proBNP can be used as a predictor of post-op MI and death (JACC 2014;63:170)
o Myocardial injury after noncardiac surgery (MINS) commonly asymptomatic; variable recommendations for screening with
ongoing studies → MINS is an independent predictor of 30-day mortality (Anesthesiology 2014;120:564)
• AF: may be a more important risk factor than CAD for 30d post-op mortality (Circ 2011;124:289). Associated with higher preop # of
preexisting comorbidities and increased postop LOS, cost, and mortality (Am Heart J 2012;164:918), as well as similar thromboembolism
and death risk to pre-existing NVAF (JACC 2018;72:2027)
o If multiple episodes or lasts > 48h, recommend OAC and close follow up for further decision-making
• Pulmonary Disease: numerous risk factors for postoperative pulmonary complications, including COPD, OSA, pHTN, low albumin.
Multiple risk calculators for different outcomes, including ARISCAT (Anesthes 2010;113:1338), Gupta (for resp failure), and Gupta (for
PNA). Mitigation of risk usually supportive, including incentive spirometry and smoking cessation. Consider Pulmonology consult
• Post-operative PNA: ~20% mortality; pre-op CXR or PFTs not recommended because rarely change management
o Risk factors: COPD, age >60, ASA class ≥II, albumin <3.5, poor functional dependence, weight loss >10% over previous 6
months (Annals 2006;144:575)
• Renal dysfunction: increased risk of complications in ESRD; AKI also a/w high morbidity and mortality (Ann Surg 2009;249:851)
• ESLD: increasing risk of perioperative mortality with increasing MELD & Child-Pugh scores. If Child-Pugh B, optimize VIBES &
consider TIPS for refractory ascites. If Child-Pugh C, optimize, consider transplant, & discuss risk/benefit nonsurgical options (J
Gastroenterol Hepatol 2012;27:1569; Clin Gastroenterol Hepatol 2020;18:2398)
• Low albumin: independent predictor of 30d post-op morbidity and mortality (Arch Surg 1999;134:36)

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Consultants Dermatology
Before Consulting Dermatology: upload photos of rash (ideally pre-treatment) to media tab of EPIC using Haiku
• If consulting for drug rash, note exact timing of rash development and administration of suspect medications
• Note: Erythema in patients with darker skin types can present with a more violaceous or dark brown hue; textural changes are
important to note. Applying gentle pressure to blanch involved skin or use of a bright light may accentuate subtle erythema.

Quick Steroid Guide MGH topical steroid formulary by level of potency

• Face/intertriginous areas: hydrocort. 2.5% Super-potent clobetasol 0.05%, betamethasone dipropionate 0.05%
cream, hydrocort. valerate 0.2% cream Potent fluocinonide-emollient 0.05%
• Body: fluocinolone 0.025% cream if mild, Upper-mid strength betamethasone valerate ointment 0.1%
clobetasol 0.05% ointment if severe  mid Mid-strength fluocinolone ointment 0.025%
strength to super potent depending on Lower mid-strength fluocinolone cream 0.025%, betamethasone valerate
severity cream 0.1%
• Scalp: 0.01% fluocinolone scalp solution or Mild hydrocortisone valerate 0.2%, fluocinolone oil 0.01%
oil (dermasmoothe); oil better for dry scalp Least potent hydrocortisone 2.5%, hydrocortisone ointment 1.0%
Counsel patients: Use BID x2 wks then 1 wk Over the counter hydrocortisone cream 0.5%, 1.0%
“off”, avoid face (risk = skin thinning) Choice of vehicle: ointments ↑ potent, ↑ stickiness, ↓ irritation
COMMON DERMATOLOGIC CONDITIONS
• Allergic contact dermatitis: appears as a geometric shape with well-demarcated borders (i.e. square tape). Usually localized but
may generalize 2/2 autoeczematization (a.k.a. “id reaction”, may also occur 2/2 tinea anywhere on the body). Identify and remove
suspected trigger. Tx w/ high potency topical steroid for limited BSA (low to mid potency for face). Pred taper (>1wk) for more
extensive BSA involvement.
• Eczema/atopic dermatitis: tx depends on severity. Intense BID/TID moisturization (plain hydrated petrolatum, Cetaphil®, CeraVe®).
For affected areas, use mid-strength to super-potent topical steroids BID x 2wks. For face, use least potent to lower mid-
strength steroids BID x 1-2wks. Scalp: mid- to high-potency steroid in solution, foam, or oil vehicles. Erosions/fissures: petrolatum or
mupirocin ointment BID x 1-2wks if concerned for superinfection and/or MRSA positive.
• Cellulitis: consider derm consult if not improved in 48h to distinguish cellulitis mimickers (30% of cases)
o Calculate ALT-70: 5-7 = 82.2% likely cellulitis; 3-4 = consider derm c/s if no improvement by 48h with abx. Consult reduces abx
use + duration (JAAD 2017;76:618; JAMA Derm 2018;154:529). Bilateral LE cellulitis is rare.
• Pressure injury/ulcers: document in H&P with Haiku pics.
o NPUAP Staging: 1) non blanchable erythema of intact skin, 2) partial thickness skin loss with exposed dermis, 3) full thickness
skin loss, 4) full thickness skin and tissue loss. Can be unstageable due to eschar/necrosis
o Wound Nurse consult for: stage 3-4 pressure injury, device related injuries, moisture associated skin damage, edema drainage
management, special bed surfaces (i.e. clinitron, bariatric). Wound Service consult (Plastics/Vascular) for: acute wound issues
such as limb ischemia, wet gangrene, any wound requiring OR debridement. Consider derm c/s to confirm etiology.
• Intertrigo: chronic inflammation in skin folds usually superinfected with yeast or bacteria. Candidal intertrigo outlying papules or
pustules. Eliminate friction, moisture, heat with wicking fabric (Interdry), barrier cream (zinc oxide paste), avoid powders when active.
Topical azole antifungal BID to reduce yeast burden, caution with topical steroids in thin/occluded areas. Immunocompromised
patients with intertriginous lesions should prompt concern for deep fungal infections JAAD 2021;17:92.

OTHER DERMATOLOGIC CONDITIONS

• Calciphylaxis: extreme pain (may precede lesion), violaceous retiform patch/plaque +/- “woody” induration  necrosis, ulcer, eschar.
Can appear at sites of trauma (injection sites, surgical debridement) JAAD;13:57.
o Risk Factors: ESRD on dialysis (most common), warfarin, 1º hyperPTH, malignancy, prior bariatric surgery
o Dx: skin biopsy (gold standard, not sensitive); Ca2+ x phos product, PTH; bone scan w/ increased uptake
o Tx: normalize serum Ca2+/phos/PTH via non-Ca based phos binders (i.e. sevelamer) and cinacalcet; Intralesional or IV sodium
thiosulfate; treat 2° infections (death from sepsis), consider hyperbaric O2 (consult MEEI Hyperbaric Medicine), pain ctrl, wound
care (Medihoney), nutrition consult. D/c warfarin if possible; consider AC if appropriate. Calciphylaxis = indication for HD in CKD
• Cutaneous GVHD: skin pain/pruritus can precede eruption, acral  central; acute vs. chronic based on morphology, not time course
o Acute: follicular erythematous papules. Chronic: morphology varies, can be dry and scaly (asteatotic), pruritic and erythematous
(eczematous), thickened and raised (lichenoid), tight and thick (sclerodermoid), pigment changes and atrophy (poikilodermatous)
o Stage 1: <25% BSA, stage 2: 25-50% BSA, stage 3: >50% BSA, stage 4: erythroderma w/ bullae (TEN-like).
o Tx: immunosuppression with corticosteroids +/- cyclosporine or tacrolimus, supportive care
• Immunotherapy toxicity: result of t-cell activation; most common on PDL-1 inhibitors, highest incidence of adverse immune related
effects are mucocutaneous (~50% of immunotherapy patients, ~2% severe (>grade 2)); usually managed outpatient; variable timeline
o Wide range of severity (grade 0->3)/presentations: maculopapular/lichenoid  pruritis  psoriasiform  bullous, SJS/TEN
o Derm and/or SIC consult warranted if not controlled w/ topical high potency steroids inpatient +/- oral pred 0.5-1mg/kg
o Grade > 2 = hold ICI + monitor, Grade >3 = hold ICI + dose reduction likely req. (SITC Guideline 2021).
• Herpes simplex virus 1/2: always confirm w/ DFA or PCR from vesicle base; cx possible but takes long to result
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Consultants Dermatology
o Uncomplicated orolabial: usually gingivostomatitis  acyclovir 400mg TID x7-10d; if recurrent  valacyclovir 2000 mg PO q12h
x 1d or famiciclovir 1500mg PO x1 at sx onset; periocular skin involvement warrants ophtho c/s to r/o herpetic keratitis
o Uncomplicated genital (immunocompetent): 1º ep (<72hr onset)valacyclovir 1000mg PO BID x10d, acyclovir 400mg PO TID
x10d, or famciclovir 250mg TID; recurrent eps (<24hr onset)valacyclovir 500mg PO BID x3-5d or acyclovir 400mg PO TID x5d.
o Complications: sacral radiculitis (acute urinary retention), proctitis (MSM).
o Ppx for immunosuppressed patients: acutely immunosuppressed, e.g. transplant patients or patients with hematologic
malignancies undergoing induction chemotherapy, HSV seropositive: acyclovir 5 mg/kg IV q8h X 7d  acyclovir 200-400 mg PO
3-5x daily x 1-3 mos; for prevention of recurrence in people living with HIV (NOT primary prevention): acyclovir 400-800 mg PO
BID/TID or valacyclovir 500 mg daily or famciclovir 500 mg BID. Consider high lysine/low arginine diet to prevent HSV recurrence
• Herpes zoster (shingles)
o Uncomplicated, <72 hr (immunocompetent): valacyclovir 1000mg PO Q8H x7d or acyclovir 800 mg PO 5x/d x7-10d
o Disseminated: >20 vesicles and two 1º (non-adjacent) dermatomes; acyclovir 10mg/kg IV q8h; consider immunodeficiency w/u;
droplet precautions
o Immunosuppressed: acyclovir 10 mg/kg IV q8h; IVFs if hypovolemic/CKD to decrease risk of crystalline nephropathy; obtain
DFA/viral culture; monitor for complications (PNA, encephalitis, aseptic meningitis, hepatitis)
o Zoster ophthalmicus: urgent ophtho consult if c/f ocular involvement (“Hutchinson sign” = vesicle on nasal tip)
o Post-herpetic neuralgia: risk  w/ early antiviral treatment (<72 hr); if higher risk (≥50yo w/ mod-to-severe acute pain) consider
preventive tx w/ gabapentin 300mg PO QD, titrate up to 3600mg QD, divided TID as tolerated
o Consider post-episode vaccination
• Erythema multiforme: target lesions (well-defined, circular erythematous macules/papules w/ 3 distinct color zones + central bulla or
crust) on palms/soles +/- mucosal involvement occurs within 24-72 hours; persist for 2wks
o 90% triggered by infection (HSV, mycoplasma, GAS, EBV); less commonly drug rxn
o Tx: treat underlying infxn, NSAIDs, cool compresses, topical steroids, antihistamines; systemic steroids only if severe
• Erythroderma: diffuse redness >90% BSA; caution: can progress to bullous/skin sloughing
o Causes: psoriasis, atopic derm, cutaneous T-cell lymphoma (incl. Sezary), pityriasis rubra pilaris (islands of sparing), drugs
o Work-up: detailed med rec, +/- HIV. Tx: derm c/s; liberal emollients, mid-potency topical steroids, antihistamines; fluids/lytes;
monitor for 2º infections; d/c offending meds.
• Purpura fulminans: “DIC in skin” = true emergency; consult Hematology for possible factor replacement
o Microvascular skin occlusion w/ platelet-fibrin thrombi  retiform purpura
o Causes: infection (Strep, Staph, H. flu, N. meningitidis, Capnocytophaga, VZV, CMV, Babesia); catastrophic APLAS, CTD,
malignancy, protein C/S deficiency
o Work-up: DIC labs, blood cultures, skin bx w/ GS and culture. Tx: broad-spectrum abx + supportive care
• Stasis dermatitis: LE compression (ACE wraps, stockings) with elevation; mid-strength to super potent corticosteroid ointment BID x
1-2wks +/- occlusion with plastic wrap; mupirocin ointment BID x1-2wks to erosions; intensive moisturization (hydrated petrolatum);
for hyperkeratosis can liberally apply ammonium lactate BID until improvement
• Psoriasis: depends severity; avoid PO steroids d/t post-tx flare. Short-term tx incl topical steroids, calcipotriene, intense moisturizing
+/- occlusion w/ plastic wrap; Long-term tx incl phototherapy, acitretin, MTX, biologics w/ outpt derm f/u (JAAD 2011;65:137)
• Seborrheic dermatitis: Face: least potent to lower mid-strength topical steroid BID x 1wk and/or ketoconazole 2% cream BID x4wks,
then 1-2x/wk; Alternative: pimecrolimus cream, tacrolimus 0.03 or 0.1% ointment. Scalp: ketoconazole 2% shampoo QHS
• Tinea pedis: “moccasin distribution”; apply topical imidazole (econazole 1% cream QD or clotrimazole 1% cream BID x 2-4 wks) or
allylamine (terbinafine 1% cream BID x 2 wks) to entire foot and webbed spaces between toes. Predisposes to LE cellulitis

Allergic Contact
Calciphylaxis Erythema Multiforme HSV Purpura fulminans
Dermatitis

DRUG ERUPTIONS
• Step 1: Make timeline to determine time course of drug initiation and development of rash
• Step 2: Discontinue offending agent. Common drugs for each eruption listed, but any drug can be a culprit at any time

Time Common
Rash Signs/Sx Treatment
Course Drugs

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Consultants Dermatology
Pruritic, well-circumscribed, Antihistamines
Immediate erythematous papules/plaques (benadryl + H2)
(min-hr) – with central pallor. Transient + steroids if severe
Urticaria/ Any
delayed lesions (circle and observe) + IM epi if s/s
Anaphylaxis
(days) +/- angioedema, wheezing, anaphylaxis
GI sx, tachycardia, HoTN - Allergy c/s
Solitary sharply demarcated
round red-brown patch or
Abx (sulfa,
edematous plaque recurring
TMP, FQs,
in same location each time
Minutes- TCNs), Topical steroids if
Fixed Drug drug ingested. Can evolve to
hours NSAIDs, symptomatic
Eruption bullae/become disseminated.
barbiturate
Oral/anogenital mucosa
s
commonly, can be anywhere.
Usually asx.
Small non-follic. pustules on
erythema/edematous plaques,
Acute begin on face/intertriginous
Generalized areas → widespread. Usually Anti-pyretic
Abx (PCN,
Exanthematous 2-14 days w/in 24-48hrs med exposure. Topical steroids
macrolides)
Pustulosis Burning, pruritus common.
(AGEP) Fever, marked neutrophilia
+/- oral mucosal erosions,
facial edema
4-14d (if “Classic” drug rash. Pruritic,
prev. erythematous Topical steroids,
Abx (PCN,
exposed macules/papules. Start on antihistamines
sulfa),
Exanthematous/ to the trunk, spread centrifugally to (Note: may take 7-
allopurinol,
Morbilliform drug, symmetric extremities. May 14d after stopping
phenytoin
could be lead to erythroderma. drug to resolve)
sooner) ± low grade fever
Fevers, malaise, myalgias,
arthralgias. Pruritic atypical Cyclosporine
targetoid (amorphous, 2 color (preferred at MGH)
zones) macules Steroids possible
bullae desquamation; <10% Abx (esp. mortality
= SJS, 10-30% = sulfa), AED benefit (JAMA Derm
4-21 days SJS/TEN overlap, >30% = , NSAIDs, 2017;153:514) but
SJS/TEN
TEN. Mucosal bullae, erosions allopurinol, controversial
& crusting, conjunctivitis. phenobarb. IVIG, anti-TNF
+ Nikolsky. Burn level care if
Complications: 2° infection, >30% BSA
resp. compromise, GIB, visual Optho consult
impairment
Dx: obtain CMP,
Morbilliform; spreads down CBC w/ diff, TSH,
symmetric. from face & consider TTE
Abx, AEDs,
mucosal involv. Face often - Supportive care
carbamaze
swollen/painful (can help diff. - IV Solumedrol
DRESS 3-6 wks pine, ARTs
from morbilliform drug) (decreased risk of
(nevirapine,
Fever, arthralgias, eos, internal bowel edema vs.
abacavir)
organ involv. (liver, kidney; PO), SLOW taper (3-
rarely lung, heart), LAD 6 wks), TSH check at
4-6 wks

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Consultants Surgery
See Calling Consults for details on how to call the appropriate surgical service
S M A L L B O W E L O B S T R U C T I O N (J Trauma Acute Care Surg 2015;79:661)
• Causes: adhesions from any previous abd surgery, hernias, cancer >> intussusception, volvulus, foreign bodies, stricture
• Dx: abd distension, nausea/vomiting, obstipation. Labs normal or hypoK/hypoCl metabolic alkalosis from repeated emesis. Examine
for evidence of hernia and abdominal scars. If severe pain or peritoneal signs, consider ischemia from strangulation (lactate, WBC)
• Imaging: KUB – initial, air-fluid levels; CT A/P w/ IV +/- PO contrast (PO only if tolerated) – best, dilated bowel proximal to &
decompressed bowel distal to obstruction. Caution: sending pt with SBO to CT w/o NGT = aspiration risk, empirically place prior to CT
o SBO vs ileus: SBO - transition point between dilated & decompressed bowel; ileus - diffusely dilated loops w/o transition
• Tx: strict NPO (no meds via NGT), large bore NGT (18Fr always) to continuous low suction; consider Gastrografin challenge (90 cc
undiluted GG PO or via NGT; clamp NGT x 1 hr; KUB 6 hrs post). Consider OR if signs of bowel ischemia, s/p RNY gastric bypass
(internal hernia), closed loop, or no improvement in 72 hrs. All pts need strict I/O & IVF resuscitation, accounting for NGT output.
B E N I G N B I L I A R Y D I S E A S E (Prim Care 2017:44(4):575-597), see Biliary Disease
• Indications for cholecystectomy (CCY): symptomatic cholelithiasis; cholecystitis; choledocholithiasis; cholangitis; gallstone
pancreatitis; gallbladder polyps (>1cm or rapidly growing)
o Post-cholecystectomy syndrome (PCS): abdominal pain, dyspepsia recurring/persisting after CCY; early (due to biliary injury,
retained stones, retained cystic duct), late (due to recurrent CBD stones, strictures, stenosis, biliary dyskinesia), consider
alternate non-biliary etiology (Int J Surg 2010;8:15)
• Acute cholecystitis: persistent RUQ pain + tenderness, cholelithiasis, caused by cystic duct obstruction. Dx: RUQUS – GB wall
thickness >3mm, pericholecystic fluid, stones; HIDA scan – confirmatory test, non-visualization of gallbladder = positive.
o Tx: IV abx (CTX/Flagyl or Zosyn), early CCY during hospitalization assoc. with ↓ morbidity (Br J Surg 2015;102:1302). If critically
ill, perc chole → delayed CCY (at least 6 wks later).
• Gallstone pancreatitis: See Pancreatitis; findings include lipase, LFTs (ALT > 3.5x ULN, 95% PPV)
o Consider Urgent ERCP (24 hrs) if cholangitis or CBD obstruction; same-admission CCY +/- IOC in mild cases associated with ↓
readmission for gallstone-related complications compared to delayed CCY (Br J Surg 2016; 103:1695)
• Acalculous cholecystitis: seen in critically ill ICU pts usually with prolonged NPO + biliary stasis, high mortality rate
o Tx: perc chole + IV antibiotics
• Choledocholithiasis: CBD obstruction, jaundice. AST,ALT (<1000), ALP, direct bili. RUQUS with CBD dilation, MRCP.
o Tx: GI c/s for ERCP + surgery c/s for same-admission CCY. Can consider immediate CCY+IOC for select patients.
o If concern for cholangitis (Charcot’s triad – fever, RUQ pain, jaundice, Reynolds’ pentad – + AMS, shock) → IV abx (Zosyn or
CTX/Flagyl), IVF, close monitoring and urgent ERCP, same admission CCY. Can cause rapid clinical decompensation.
N E C R O T I Z I N G S O F T T I S S U E I N F E C T I O N (CID 2007;44:705; Front Surg 2014;1:36)
• Definition: progressive, rapidly spreading infection with secondary necrosis of skin and subcutaneous tissues, +/- fascia & muscle
• Microbiology: majority of cases are polymicrobial (anaerobes, group A strep, S. Aureus, Clostridium, Peptostreptococcus,
Enterobacteriaceae, Proteus, Pseudomonas, Klebsiella)
• Clinical signs: rapidly spreading erythema (hrs to days)  pain disproportionate to exam or beyond borders of erythema, dusky
skin, turbid (“dishwater”) discharge, crepitus, bullae, fever, hypotension; Fournier’s gangrene (perineum) & Ludwig angina (jaw/neck)
• Dx: clinical dx, CT w/ IV contrast has a ~95-100% NPV. Labs for LRINEC score (CRP, WBC, Hg, Na, Cr, Gluc) → score ≥6 has a
92% PPV & 96% NPV (Crit Care Med 2004; 32:1535-41). Bedside I&D if equivocal (dishwater fluid, loss of tissue integrity, malodor)
• Tx: IV abx ([Vanc or Linezolid] + [Pip/Tazo or meropenem] + Clinda (to inhibit toxin production) + emergent surgical debridement
(consult Churchill service immediately)
A C U T E L I M B I S C H E M I A (NEJM 2012; 366:2198)
• Clinical signs: 6 P’s: Pain, Poikilothermia (cool), Paresthesia, Pallor, Pulselessness, Paralysis
• Dx: check pulses & Doppler signals in both affected & unaffected extremities for comparison. Obtain ankle-brachial indices. CTA
o Acute limb ischemia → acute decrease in limb perfusion 2/2 thrombosis or embolism (can be iatrogenic, e.g., s/p vascular
access procedure), needs urgent surgical evaluation
o Chronic limb ischemia → chronic vascular disease from atherosclerotic changes. Exam with cool, hairless extremities,
limited/no pulse/absent Doppler signals that is not acutely painful (perfusion maintained by collaterals). Non-urgent surgical eval
• Tx: if unsure, or acute limb ischemia, IV heparin (unless AC contraindicated); consult Vascular Surgery immediately
C O M P A R T M E N T S Y N D R O M E ( E X T R E M I T Y ) (Lancet 2015;386:1299; Musc Lig Tend J 2015;5:18)
• Definition: excessive pressure within a muscle compartment impairing perfusion; 2/2 crush injury, edema, bleed, ischemia, etc.
• Clinical signs: tight, tender skin; pain out of proportion to exam; pain with passive ROM; lactate or CPK
• Dx: clinical dx, measurement of compartment pressures w/ Stryker transducer needle if equivocal (call Ortho or Churchill Service)
• Tx: surgical emergency (fasciotomy/decompression); consult Churchill Surgery immediately
A B D O M I N A L C O M P A R T M E N T S Y N D R O M E (ICM 2013;39:1190)
• Definition: IAH = IAP ≥12. Abdominal Compartment Syndrome = IAP >20 AND end organ dysfunction (e.g.,airway pressures,
UOP/AKI, lactate, acidemia). IAP measured via bladder pressure (most reliable if paralyzed, done in ICU)
• Typically occurs after massive resuscitation in ICU patients with trauma, burns, s/p liver txp, severe ascites, pancreatitis, sepsis
• Tx: for medically refractory, true Abdominal Compartment Syndrome → decompressive laparotomy with temporary closure
o If IAP 12-20 w/o clinical instability, temporize w/NGT, rectal tube, paralysis, LVP, tidal volume, diuresis, HOB elevation

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Consultants Urology
Who to call: page 11300 for Emergencies, Foleys, SPTs, & gross hematuria; page 10300 for other non-urgent inpatient consults
Consults: note urine color in tube (bag urine appears darker due to volume) before consulting Urology, place urine samples at bedside –
use food/drink comparisons like “pink lemonade,” “fruit punch,” “cranberry juice,” and “merlot” to help characterize
URETERAL OBSTRUCTION (MOST COMMONLY DUE TO KIDNEY STONES OR MALIGNANCY)
• Evaluation/management: Pain usually present only in obstructing stones. +hydronephrosis implies obstruction.
o Imaging: stone-protocol CT scan (I–, O–): evaluates position, density/composition & presence of hydronephrosis
 Alternative: MRI vs combined KUB+US; however, less diagnostic than stone-protocol CT. US helpful to r/o hydronephrosis
o Vitals, CBC, UA/UCx: if concomitant UTI, decompress urgently with stent by urology or percutaneous nephrostomy (PCN) by IR
o Rehydration: patients often volume down, bolus as tolerated and increase maintenance IV fluids  ureteral clearance
o Alpha-Blockers: tamsulosin 0.4mg PO qd (hold for SBP <90)  ureteral relaxation, +evidence for better distal stone passage
o Analgesia: Tylenol, NSAIDs if Cr <1.5, add IV opioids if inadequate pain control; can also use diazepam (2mg Q8 PRN)
o Preoperative workup: NPO, BMP/CBC, continue AC if plan for Urology stent; hold AC & obtain coags if plan for IR PCN
• Urgent urology consults: solitary or transplanted kidney with worsening AKI, UTI, urosepsis in setting of obstruction
• Obstruction + sepsis: Non-con CT A/P ASAP, BCx/UCx, urgent Urology consult; broad IV abx to cover GNRs + enterococcus
• Non-stone hydronephrosis: often stricture or malignancy, can require decompression for renoprotection or need for nephrotoxic
chemo. Same options (stent vs PCN), same indications of urgent/emergent consult. Urology can help determine stent vs PCN
• Relevant History: renal colic is unilateral pain from CVA wrapping around flank radiating towards ipsilateral scrotum/labium
• Indwelling ureteral stents: Need exchange every 3-6 months; if +UCx, need abx treatment prior to exchange; can be done as outpt
HEMATURIA
• DDx: BPH, UTI, INR>3, traumatic catheter placement, bladder CA (5th most common neoplasm), upper urinary tract CA, prostate CA
• Acute Management: Obtain post-void residual bladder scan before consulting Urology. If +foley, can manually irrigate & and aspirate
o DO NOT start CBI if active clot burden. If 3-way clots off, stop CBI and manually irrigate through 3-way until clear
o Manual irrigation removes clots that already exist, while CBI prevents new clots from forming by diluting active bleeding
• Diagnostic Workup (4 C’s): 1) in-house CT hematuria protocol; 2) urine Culture, 3) urine Cytology, 4) outpatient Cystoscopy
OBSTRUCTED CATHETER VS BLADDER SPASM/URGENCY FROM CATHETER
• Obstructed Catheters: bladder feels full, urine spasms around catheter, minimal/no urine through catheter, bladder scan is high
o Tx: disconnect tube from drainage port, gently flush 50cc and aspirate with catheter-tip syringe and reconnect
• Bladder Spasm: bladder feels full, urine spasms around catheter but continued flow through catheter, bladder scan is low
o Tx: antispasmodic agents – restart home meds if they have them normally, otherwise can start tolterodine (anticholinergic with
fewer side effects than oxybutynin), Oxytrol patch and/or belladonna-opium suppository (local anticholinergic)
• Note: bladder scans are inaccurate when patients have ascites because they inappropriately detect the fluid around the bladder
URINARY RETENTION
• Etiology: BPH, UTI, constipation, neurogenic (MS, cord injury), DM, immobility, anticholinergics, opioids, benzos, pelvic surgery
• Treatment: bowel regimen, treat UTI, minimize opioids/anticholinergics, encourage ambulation, (re)start tamsulosin or other α-
blocker. Catheterize as necessary – clean intermittent “straight cath”, preferred long-term to Foley/SPT if possible
URINARY INCONTINENCE
• Classifications: stress (Valsalva), urge (preceded by urgency), mixed (most common), overflow (PVR >150), functional (neurologic)
• Treatment: lifestyle interventions, bladder training (timed voiding), Kegel pelvic floor exercises for all types
o Stress: vaginal estrogen (post-menopausal women w/ vaginal atrophy), pessaries (mixed data), surgery (urethral bulking, slings)
o Urge: antichol (oxybutynin, tolterodine, beware side effects), β3-agonists (mirabegron, avoid w/ HTN, ESRD, ESLD), Botox
• Note: workup of “voiding dysfunction” (retention, incontinence) usually takes weeks/months of outpatient observation ± urodynamics.
T U B E S A N D D R A I N S : see Tube Management for placement and management
• Foley catheter: externally placed tube which travels through urethra and into bladder
o Considerations: BPH, men >50yo  16-18Fr Coudé (gentle curve directs catheter tip through curve of prostate), all RNs are
allowed to place Coudés – the tip (and balloon port) point “up” towards sky; stricture  12-14Fr
 Pro-tip: use 8-10cc lubricant instilled into the urethra via syringe (urojet) for easier catheter placement in men
o Urethral trauma: To avoid, fully hub foley on placement prior to balloon inflation; leave foley in 3-5d to allow for urethral healing
• Suprapubic tubes (SPT): externally placed tube travels percutaneously through ant abdominal wall into bladder
o Placed by IR. First exchange done by IR, change q6-12w similar to Foley, RNs do routine exchange, Urology assists PRN
• Percutaneous nephrostomy tube (PCN): externally placed tube travels percutaneously through flank wall into renal pelvis
o Placed by IR under local vs general anesthesia. Cannot be coagulopathic, thrombocytopenic, or on ASA/anticoag
o Urine collects in external bag. If low UOP into bags, passage of blood or concern for malposition – flush>obtain US/CT>call IR
• Ureteral stent: internally placed tube travels from renal pelvis to bladder inside ureter to drain kidney into bladder
o Placed by Urology in OR with general anesthesia or MAC, requires change every 3-6mo. May cause urinary urgency. NOT
changed in setting of infection unless stent has failed (which becomes a ureteral obstruction c/b UTI, tx usually = PCN with IR)
• Note: if stents/PCNs/chronic catheter or SPT/ileal conduit or neobladder – UTIs diagnosed on symptoms over UCx/UA (colonized)
• Note: there are no good data that Foley/SPT exchange in UTI is helpful because the new tube goes into the same (infected) tract

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Consultants ENT
EPISTAXIS (NOSEBLEED)
Acute management: (UpToDate Epistaxis)
1. Have patient lean forward, pinch nostrils, and hold pressure for 20 min
o Guidance: pinch over the soft portion of the nose; do NOT lean head back or pinch bony part of nose; do NOT “peek” – hold
continuous pressure for 20 min; patient may be unable to hold pinch, best for RN/MD to do
2. Afrin (oxymetazoline 0.025%) nasal spray (after gently clearing clots)
o Guidance: GENEROUSLY SPRAY (5-10 sprays) on both sides then hold pressure again for 20 min as above
3. Control SBP (goal < 120) if much greater than baseline; correct coagulopathy if present and able to
4. Consult ENT if continued bleed after above steps
o Treatment: silver nitrate cauterization, resorbable nasal packing, non-resorbable nasal packing, Neuro IR embolization
o Non-resorbable nasal packing: risk of Toxic Shock very low; put patient on prophylactic cephalexin or clindamycin; packing
typically removed after 5-7d (whether inpt or outpt – can be removed by anyone by pulling on string)
Location: most are anterior bleeds from Kiesselbach’s plexus (90%); posterior bleeds are more rare / serious / difficult to manage
Hx: duration and frequency of bleeding; laterality; EBL; prior episodes (and txs); trauma (fingers, fists, foreign body, etc.); prior nasal
surgery; PMHx or FHx of coagulopathy; medications (in particular anticoagulation); cocaine or intranasal drug use
Exam: rapidity of bleeding; inspect nasal septum and OP for originating site; suction clots from OP to protect airway if rapid bleed
Tests: CBC, PT, PTT, T&S (consider crossmatch pRBC if brisk bleed)
Epistaxis prevention: after resolution x 2 weeks: petroleum ointment; avoid nose blowing / digital manipulation / vigorous exercise; keep
head above heart; sneeze w/ mouth open; humidification (saline nasal spray BID); Afrin / hold pressure PRN re-bleeding
STRIDOR
Acute management:
1. Administer oxygen (low flow = NC, simple face mask, non-rebreather; high flow = venturi mask, HFNC); ensure IV access
2. Racemic epinephrine neb x 1 STAT (lasts ~2h); 10mg dexamethasone IV x 1 STAT (re-dose q8h)
3. Consider Heliox, abx, and humidification; IM / IV epinephrine and Benadryl if allergy suspected (see Angioedema & Anaphylaxis)
4. If unstable  RICU & trauma surgery (x6-3333) for possible surgical airway; if stable  ENT for airway evaluation
Hx: timing/evolution; inspiratory / expiratory / biphasic; inciting events, prior episodes; evidence of infection; allergy; hx EtOH/tobacco
(cancer risks); hx subglottic stenosis; hx of known cancer of head and neck or radiation
DDx (in adults): iatrogenic / post-intubation (laryngeal / vocal cord edema or praxis of the recurrent laryngeal nerve from ET tube);
infectious (epiglottitis, laryngitis, laryngotracheitis [croup], bacterial tracheitis, Ludwig’s angina); allergic / angioedema; mass of larynx
or trachea; neurological (vocal cord spasm / immobility); foreign body; trauma
Imaging: if stable, CT with contrast of head / neck / chest to localize source
D E E P N E C K S P A C E I N F E C T I O N (see Head & Neck Infections)
Acute management: (UpToDate Deep Neck Infection):
1. Ensure protected airway: intubation or surgical airway for threatened airway → consider glucocorticoids
2. Empiric antibiotics: typically need polymicrobial coverage (ensure appropriate anaerobic coverage)
o E.g., amp/sulbactam vs 3rd gen cephalosporin + flagyl; consider vancomycin in pt with risk of MRSA or if sinogenic source
o Vancomycin/cefepime/flagyl if healthcare-associated, severe, or immunocompromised
3. ENT consult for consideration of drainage (localized infection) and airway monitoring
Symptoms: sore throat; trismus (inability to open jaw); dysphagia / odynophagia; dysphonia; dyspnea / stridor
Exam: neck tenderness; lymphadenopathy; trismus, fullness / asymmetry of OP; crepitus; pooled saliva; stridor
Tests: CBC, PT, PTT, T&S; blood cultures; CT neck with contrast; MRI neck with contrast if c/f osteo
Complications: based on location: parapharyngeal: involvement of carotid sheath (CCA, IJV, CN X), carotid blowout (life-threatening),
jugular thrombophlebitis (Lemierre’s); retropharyngeal: extension along deep neck spaces/mediastinum (mediastinitis / empyema);
prevertebral: spine osteomyelitis; submandibular/sublingual: Ludwig’s angina (floor of mouth swelling, rapid resp compromise)
A C U T E S I N U S I T I S (Otolaryngol Head Neck Surgy 2015;152:S2)
Definition: up to 4 weeks of purulent nasal drainage + nasal obstruction or facial pain / pressure / fullness (or both); can be viral or
bacterial (typically bacterial if symptoms > 10 days)
Symptoms: uncomplicated (confined to sinuses): facial pressure / pain, purulent nasal discharge, nasal obstruction, fever, malaise,
anosmia, dental pain, ear fullness; complicated (extra-sinus extension): vision changes, proptosis, mental status changes, severe HA,
facial soft tissue changes; in immunocompromised/critically ill: consider invasive fungal sinusitis, a surgical emergency (see Invasive
Fungal Infections)
Workup: uncomplicated: no imaging required; complicated: CT w/ contrast ± nasal endoscopy to look for evidence of purulence
• If concern for invasive fungal sinusitis, consult ENT for consideration of nasal biopsy with STAT pathology
Treatment:
• Uncomplicated ABRS: amoxicillin ± clavulanate 5-10 days; nasal steroid spray / nasal saline irrigations for symptomatic relief; if no
improvement after 7 days change antibiotic
• Invasive fungal sinusitis: liposomal amphotericin, urgent surgical debridement, ID consultation
S U D D E N H E A R I N G L O S S (Otolaryngol Head Neck Surg 2019;161:S1)
1. Use otoscope to examine ears and ensure no cerumen impaction
2. Determine conductive hearing loss vs sensorineural hearing loss – obtain audiogram, call 617-573-3266 at MEE to schedule
3. If sensorineural hearing loss, consult ENT for initiation of either high dose oral corticosteroids or intra-tympanic steroids if
contraindication to systemic steroids; ideally start steroids within 2 weeks of symptom onset

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Consultants Ophthalmology
Ask PMH abnl vision, eye sx, meds, cataract, glaucoma, macular degen, DM retinopathy, and do basic eye exam prior to consult!
General inpatient consult: check paging directory and page/call listed number; can also call MEEI ED desk 617-573-4063
Basic Eye Exam: “Ocular Vital Signs”
- Visual Acuity (e.g. 20/200, CF) - Extra-ocular movements
- Pupils (4mm  2mm OD, No APD) - Intraocular pressure (nl 10-20mmHg)
- Confrontational visual fields - Color vision testing (Ishihara cards)
Common Abbreviations:
APD Afferent pupillary defect NLP No light perception (VA)
AT Artificial tears NPDR Non-prolif. diabetic retinopathy
cc/sc With/without correction (glasses) NS Nuclear sclerosis (i.e. cataract)
CE Cataract extraction OD/OS Right eye, left eye
CF Count fingers (VA) OU Both eyes
Uvea = iris + ciliary body + choroid CWS Cotton wool spot PDR Proliferative diabetic retinopathy
DES Dry eye syndrome PF Pred Forte gtt (prednisolone)
DFE Dilated Fundal Exam PFAT Preservative-free artificial tears
EOM Extraocular movement PH Pinhole acuity
HM Hand motion (VA) PVD Posterior vitreous detachment
IOL Intraocular lens RD Retinal detachment
IOP Intraocular pressure SLE Slit lamp exam
LP Light perception (VA) SPK Superficial punctate keratitis/dry eye
MGD Meibomian gland dysfunction VA, VF Visual acuity, visual fields
HIGH-YIELD PEARLS
• Vision loss: acute (requires urgent evaluation) vs chronic (outpt referral) – assess patient with their glasses on!
• Glaucoma drops: prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, or alpha 2 agonists – all lower IOP
o If brand-name drops unavailable: fractionate combo meds, ask pharm for substitution advice, or have pt bring in home meds
• Dilating drops: 0.5% tropicamide (parasympathetic antagonist), 1-2 drops placed 15-20 minutes before exam; light-sensitive 4 hours
• Finding the retina: dilate the eye and use the ophthalmoscope; see example Stanford Medicine fundoscopic exam video
COMMON EYE PATHOLOGY
• Red Eye: typically benign; refer to ophtho if no improvement or any “ocular vital sign” changes (see above)
o Viral conjunctivitis: eyes “stuck shut” in AM, itchy, crusty discharge, ± URI symptoms, ± pre-auricular nodes, winter time
 Tx: supportive/isolation (typically adenovirus, highly infectious). Wash hands thoroughly if you suspect this!
o Allergic conjunctivitis: olopatadine 0.1% gtt bid x 5d. Clear Eyes/Visine not rec’d (rebound redness 2/2 alpha agonism)
o Anterior uveitis: pain and true photophobia ± eye injection. Usually perilimbal. Hx autoimmune ds common. Refer to MEEI ED
o Contact lens keratitis: pts remove contacts on admit! P/w red/painful eye; infection until proven otherwise. Refer to MEEI ED
o Acute angle closure glaucoma: common sx include nausea, aching pain, vision loss. Palpation of the eye will be “rock hard” or
elevated pressure with tonopen. Exam: red eye, hazy cornea, mid-dilated pupil. Urgent consult to MEEI.
o Subconjunctival hemorrhage: blood between conjunctiva and sclera from ruptured vessel. No vision changes, not painful. Can
be 2/2 blood dyscrasia, Valsalva (cough, vomit), trauma, AC, spont. Resolves spont. No need to consult if no significant trauma.
• Blepharitis (inflammation of eyelids): p/w crusting, red eye, gritty feeling
o Tx: baby shampoo, warm compresses, abx ointments x 2 weeks, then daily lid hygiene. Tx for hordeolum ("stye") is same
• Dry Eye Syndrome (DES): p/w eye pain or “grit”/paradoxical tearing ± vague “blurriness”
o Tx: preservative-free artificial tears (Refresh) q1h prn , Refer to ophtho if no improvement. Approach to blurry vision
• Corneal abrasion/exposure keratopathy: unilateral, redness, mild light sensitivity, common after sedation
o PPx: intubated patients require lubrication regimen (ophthalmic lubricating ointment QID) ± tape eyelids shut if partially open
o Dx: apply fluorescein (order in Epic) to the affected eye, illuminate with a blue light (e.g. ophthalmoscope, smartphone screen
with Eye Handbook App). Abrasion will light up green; keratopathy will look like “sandpaper” instead of smooth glass
o Tx: abx ointment (Erythromycin 0.5%/bacitracin ophthalmic QID) + Lacrilube qhs. Consult if no improvement after 24h
• Anisocoria (unequal pupils): old (20% population has at baseline) vs. new (can be trivial 2/2 anticholinergic vs. catastrophic from
herniation). Always ask for h/o ocular surgery as surgical pupil is a common benign cause
Miosis (Constricted Pupil) Mydriasis (Dilated Pupil)
Cholinergic (e.g. morphine, pilocarpine) Sympathetic (e.g. atropine, CNIII paralysis)
Sympathetic (e.g. Horner’s) Cholinergic (e.g. epinephrine, cocaine)
o If clinical suspicion for herniation (known bleed, CN3 palsy, obtundation, hemiparesis)  STAT head CT
o Horner’s Syndrome: ptosis, miosis, ± anhidrosis. Wide ddx along pathway from posterior hypothalamus  C8-T2  superior
cervical ganglion  sympathetic chain  internal carotid  orbit. Head and neck CTA/MRA to r/o carotid dissection
• Retinal detachment: presents with flashes/floaters/curtain coming over vision. Risk factors: myopia (near-sighted), trauma, diabetic
retinopathy, prior eye surgery. Tx: Refer to MEEI ED for likely vitreoretinal surgery. Approach to flashes, floaters, spots
• Orbital Cellulitis (see Orbital & Preseptal Cellulitis): most common from sinus disease, periocular edema/erythema + orbital signs
(rAPD, color vision loss, motility disturbance, proptosis). Non-con CT face and orbits for stranding/abscess. Consult MEEI, likely
needs admission for IV abx. Preseptal negative orbital signs, negative scan, can treat with oral abx and reassess symptoms.
• Endophthalmitis: infection within globe. Can be 2/2 trauma, surgery, or endogenous source (bacteremia/fungemia)
o Tx: ophtho c/s, antibiotics/antifungals that will penetrate blood-brain barrier. May require vitrectomy (surgery)
• Optic neuritis: p/w painful EOM, subacute blurry vision (typically monocular), central scotoma. Causes: demyelinating ds (MS),
infection, autoimmune (sarcoid, lupus). Tx: HD steroids; c/s ophtho/neuro. Approach to double vision

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Consultants OB/GYN
HOW TO CONSULT
• Obstetrics/MFM: For inpatient consults for patients with a known intrauterine pregnancy, page the MFM team (p17977)
o If no response, call L&D 617-724-9410
• GYN Onc: if pt has biopsy confirmed GYN malignancy or established GYN onc provider (p31037)
• GYN: Everyone else (e.g., +hCG without confirmed intrauterine pregnancy, undifferentiated ovarian mass, heavy vaginal bleeding).
Obtain pelvic vs. transvaginal U/S. If hCG⊕ but no confirmed intrauterine pregnancy on imaging, should be followed on ectopic list
(p22346)
ABNORMAL UTERINE BLEEDING
• History: verify source of bleeding is vaginal (as opposed to GI or GU), duration and quantity (#soaked pads, tampons), associated sx
(pain, dizziness), triggers (e.g., postcoital), trauma history. Other history: estrogen contraindications (smoking, BMI, HTN, h/o
coagulopathy), LMP/menstrual hx, full pregnancy hx, known GYN conditions (e.g., fibroids), meds (hormones, AC)
o Heavy bleeding = soaking through 1 pad per hour, symptomatic, ∆ VS, Hgb
• Exam: external vulvar exam, speculum exam (note how many scopettes required to clear bleeding, volume of blood in vault, cervical
lacerations, blood actively coming from cervix). Do NOT do digital exam if pregnant.
• Postmenopausal bleeding is never normal and often warrants a workup to rule out malignancy. If premenopausal, rule out pregnancy
and its complications.
Differential Diagnosis for Abnormal Uterine Bleeding
Ectopic pregnancy, miscarriage (including incomplete and septic abortion), subchorionic hematoma, placental
Pregnant
abruption, placenta previa/accreta, vasa previa, trophoblastic disease, cervical/vaginal/uterine pathology (e.g. polyp)
PALM-COEIN: Endometrial/cervical polyp, adenomyosis, leiomyoma/fibroids, malignancy (e.g., endometrial,
Not pregnant cervical), coagulopathy, ovulatory dysfunction, endometrial dysfunction, iatrogenic, not otherwise classified (thyroid
disease, vaginal/vulvar etiologies [e.g., laceration, atrophy]).
• Workup: CBC, T&S, coags, pad count (Epic order, monitors bleeding quantity)
o If premenopausal, first step is urine hCG
 If ⊕, obtain serum quant hCG and pelvic U/S (must rule out ectopic pregnancy in all pregnant women with bleeding)
 If intrauterine pregnancy not confirmed on U/S, measure serial serum hCG q48h (should increase 35-50% in 48h) and
repeat pelvic U/S. Ectopic risk factors: IVF pregnancy, h/o STIs, prior ectopic, h/o tubal surgery, IUD, smoking
o If postmenopausal, pelvic U/S, consider endometrial biopsy if endometrial lining >4mm (difficult to do inpatient) *Regardless of
U/S result, postmenopausal bleeding warrants at least outpatient GYN follow up*
PELVIC PAIN
• History: timeline, severity, LMP, associated sx (N/V, GI, GU, fevers/chills, vag bleeding/discharge, wt loss), pain med requirement
• Exam: abdominal, CVA tenderness, bimanual exam, consider speculum exam if bleeding or discharge
• Differential Diagnosis: non-exhaustive list of most common causes of pelvic pain
o Ectopic: see above; if peritoneal signs on exam or hemodynamically unstable, consider ruptured ectopic (surgical emergency)
o Adnexal lesions: benign (simple, hemorrhagic, dermoid, etc) vs malignant. If high c/f malignancy, obtain CA-125, CA19-9, CEA
o Ovarian torsion: clinical dx, most predicted by acute unilateral pain (<8hr), vomiting, mass (>5cm) (HuRepro 2010;25:2276)
o PID: ascending (e.g., STI) vs descending (e.g., diverticulitis); fevers/chills, vaginal discharge, CMT; complications include TOA
o Endometriosis/chronic: dysmenorrhea, dyspareunia, dyschezia; r/o acute causes, consider outpatient follow up
o Non-GYN: nephrolithiasis, UTI/pyelo, appendicitis, diverticulitis, constipation
• Workup: hCG, pelvic U/S, GC/CT, CBC with diff, UA/UCx; consider alternative abdominal imaging pending H&P (e.g., CTAP)
PREGNANCY AND ITS COMPLICATIONS
Gravida/para (GP), G= #pregnancies, P= #births; TPAL (T=term births, P=preterm births, A=abortions, L=living children)
• Hypertensive complications: BP >140/90 is abnormal, any BP >160/110 is an OB emergency
o Differential: chronic HTN (HTN <20w), gestational HTN (HTN >20w), pre-eclampsia (new HTN + proteinuria or new HTN
>160/110), pre-eclampsia with severe features (unrelenting HA, vision changes, RUQ/epigastric pain, lab abnormalities),
eclampsia (seizure), HELLP
o Workup: CBC, BMP, LFTs, LDH, uric acid, urine protein/Cr ratio +/- coags and hemolysis workup
• Hyperemesis: standing meds most effective, see tx algorithm on UTD
• OUD/SUD: can refer to HOPE Clinic.
• References: Normal lab values by trimester (UTD). Guide to OTC med use/symptom tx during pregnancy: AFP 2014;90:548

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Radiology Radiology Basics

IMAGING ORDERS
Always include brief clinically relevant information to inform the radiologist of your clinical question.
Think of the radiologist as a consultant with the goal of adding valuable diagnostic information to patient care via imaging.
X-RAY

COMPUTED TOMOGRAPHY (CT)

Hounsfield Units (HU): measurement of CT attenuation Phase Time Post-Injection Structures Evaluated
(see table for reference range) CT-PE 5-15 s Pulmonary arteries
Windowing: adjusting contrast (width) and brightness Arterial (CTA) 15-20 s Systemic arteries, no organs
(level) to better visualize specific structures. Arteries, renal corticomedullary
- Window width (“contrast” - range of grayscale): range Late arterial 35-40 s
differentiation
of Hounsfield units. HU < window = black, HU > Late Portal 70-80 s Organs (Routine abdomen)
window = white, within window = gray. Wide windows
Nephrographic 100 s Renal parenchyma
for large diff in density (i.e. air/vessel in lung), narrow
Delayed Active contrast extravasation
for similar density (grey vs white matter) 120 s
(Vascular) (bleeding), peripheral veins
- Window Level (“brightness” - center of grayscale):
HU at center of window, corresponds to attenuation Delayed
10-15 min Ureters, bladder
of structure of interest (e.g. high lvl for bone window, (Urogram)
low lvl for lung window)

Substance HU
Air -1000
Fat -100
“Lung Window” “Bone Window” Water 0
“Brain/Soft Tissue Window”
Wide window 1500, Low level -40 Wide window 160, High level +500; Narrow window 80, Medium level +40 Blood 50
Soft tissue 100
Bone 1000
Metal >2000

MAGNETIC RESONANCE IMAGING (MRI)

MRI safety: search device compatibility at mrisafety.com
Basics of Common MRI Sequences
Sequence Purpose
T2 weighted +/- Identify fluid/edema (e.g. most pathology, malignancy). Fat sat refers to
fat-sat technique to make fat appear hypointense.
T1 weighted +/- Evaluate anatomy; identify T1 hyperintense products, including
contrast hemorrhage, fat, protein & contrast (gadolinium) enhancement.
STIR T2W (fluid/edema) with technique to make fat appear hypointense
(more consistent than fat-sat). Common in MSK MRIs.
MRCP Heavily T2W sequence to eval gallbladder + intrahepatic, extrahepatic,
and pancreatic ducts.
HASTE/SSFSE T2W sequence that is rapidly acquired (fast sequence).
GRE ID hypointense susc (blooming) artifact a/w blood & calcium.
SPACE High resolution 3-D sequence (cor, sag, axial).
DWI Identify restricted motion of intra-/extracellular water molecules
(e.g. acute stroke, abscess, highly cellular tumors like lymphoma).

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Radiology Contrast
INDICATIONS FOR CT CONTRAST ADMINISTRATION
• IV positive (I+): vast majority of studies more sensitive when given, particularly for infection, tumors, and vessel imaging
• IV negative (I-): urinary tract stones, retroperitoneal hematoma, pulmonary nodule follow-up
• PO positive (O+): bowel obstruction, bowel leak/perforation/fistula, differentiate bowel from other abdominal structures
• PO negative (O-): inflammatory bowel disease, GI bleed, mesenteric ischemia, retroperitoneal hematoma
P R E G N A N C Y A N D B R E A S T F E E D I N G (ACR 2022 Manual)
• Contrast Use in Pregnancy:
o Iodinated contrast for CT studies: no need to withhold (no data to suggest potential harm to fetus, although limited data)
o Gadolinium contrast for MRI studies: do not use unless essential + no suitable alternative (radiology consultation). Req consent.
o Written consent required if predicted fetal dose >0.05mGy. 1 CT = ~25mGy to fetus. No consent for CXR, C/T-spine, mammo
• Breastfeeding: Current rec: I & G* safe for mother & infant, may choose to “pump and dump” for 24h after scan.
o *Exception – EOVIST: unknown if Eovist excreted in milk. Consider “pump & dump”, but likely safe to nurse after 10h
R E N A L F U N C T I O N (ACR 2022 Manual; MGPO 2020 (CIN); MGPO 2020 (NSF); JAMA IM 2020;2:223)
Contrast Induced Nephropathy
Nephrogenic Systemic Fibrosis (NSF)
/ Post Contrast Acute Kidney Injury (PC-AKI)
• Association between intravenous / intra-arterial • Association b/w Gad-based contrast (MRI) in pts with
Definition contrast and development of renal impairment renal impairment & development of systemic fibrosis
• Occurs 48-72 hours after contrast admin • Occurs weeks to months after contrast admin
• 3 classes of contrast based on risk: I (highest risk), II
• CKD (consensus • Diabetes mellitus
(minimal risk), III (likely very low risk but limited data)
most important) • Dehydration
• Some risk with Group I and III (e.g., Eovist) in patients
Risk factors • Diuretic use • Cardiovascular disease
with kidney disease (acute or chronic) and/or DM.
• > 2x contrast doses • Age >60 years
• Risk “sufficiently low or possibly non-existent” w/
in <24 hrs • Hyperuricemia default Group II GBCAs (e.g. Dotarem, Multihance)
Screen if h/o kidney dz or diabetes mellitus Outpatient: not necessary for most scans
Screening Outpatient: eGFR within 30d, ED: eGFR within 30d, Inpatient/ED: eGFR within 24hr for class III agent (e.g.
Inpatient: eGFR within 24h Eovist). None needed for class II agent
eGFR ≥30: contrast per protocol (NO prehydration)
Group II GBCA: given regardless of eGFR
eGFR <30 or AKI  I- or alternative study. Consult
Prevention Group I GBCA: consult radiology if eGFR <30
radiology if I+ is medically urgent. Consider prehydration.
Group III GBCA: do not give if eGFR <30
Dose reduction not considered effective prevention
If maintenance dialysis w/o possible renal recovery:
Consult radiology. Typically Gad withheld.
On Dialysis administer contrast. If possible renal function recovery,
Prompt post-scan HD suggested (PD inadequate)
(e.g temporary dialysis catheter): consult radiology
<24h repeat Decision is clinical and subjective No risk factors: proceed
studies Insufficient evidence to hold contrast for 24h At risk patients: consult radiology
eGFR ≥30: continue metformin
Metformin Continue metformin
eGFR <30 or AKI: hold for 48h after scan
Renal txplt Consult Radiology Consult Radiology
*Post contrast peak effect on creatinine occurs 48-72 hours after administration

Pre-hydration protocol: (ACR 2022) *If you want an I+ CT scan in a patient w/ eGFR <30, speak to radiology
o Prophylaxis indications: eGFR <30 (not on long-term HD), AKI
o PO hydration: Not well-studied. Historical MGH regimen: 1-2L PO non-caffeinated beverage 12-24h prior to scan
o IV hydration: Start 1 hr prior & cont 3-12 hrs after. Fixed volume (250-500 mL NS) before & after vs. weight-based (1-3 mL/kg/hr)
o N-acetylcysteine is NOT recommended for IV contrast prophylaxis
C O N T R A S T R E A C T I O N S (ACR 2022)
Mild Moderate Severe
Limited urticaria Diffuse urticaria Anaphylaxis Indications for
Itchy throat, congestion Facial/laryngeal edema w/o Facial/laryngeal edema w/ Premedication
Allergic • Prior mild-moderate
URI symptoms dyspnea or hoarseness dyspnea or hoarseness
Bronchospasm w/o hypoxia Bronchospasm w/ hypoxia allergic reaction
N/V, flushing/warmth Protracted N/V HTN emergency • Prior unknown contrast
HA/dizziness HTN urgency Arrhythmia reaction
Physiologic • None for prior
Mild HTN Isolated Chest Pain Seizure
Transient vasovagal rxn Vasovagal rxn requiring tx Protracted vasovagal rxn physiologic reactions
Standard contrast allergy pre-medication regimen: 13h • None for shellfish
o You must indicate standard premedication regimen in the imaging order allergies
o Epic orderset – “Contrast Allergy Prophylaxis: Regular Protocol Order Panel” • No cross-reactivity b/w
iodinated contrast and
• Urgent contrast allergy pre-medication regimen: 4h
gadolinium
o Requires discussion with a radiologist before starting regimen
o Epic orderset – “Contrast Allergy Prophylaxis: Urgent Protocol Order Panel”
• See Drugs and Contrast section on pre-medication prior to scan
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Radiology Protocols
ORDERING STUDIES
• All cross-sectional studies are protocoled by radiology – simply provide the necessary information:
o Body part: Head, abdomen only, abdomen and pelvis, etc.
o Modality: Ultrasound, Radiograph, CT, MRI, Fluoroscopy, PET whole body, PET Brain, HIDA Scan, etc.
o Indication: clinical history relevant to the study
o Contrast: “per radiology discretion” unless specific reason otherwise (I+ IV; O+ oral; R+ rectal)
o Contraindications for contrast: renal transplant, kidney injury or prior allergic reaction (see Contrast)
o Questions? - call the appropriate division or page the appropriate on-call radiologist (see MGH Directory)
 Inpatient study questions? - call ED reading room after 7PM weekdays/5PM on weekends (unless STAT study).
Otherwise, call divisions during work hours (8am-7pm weekdays/8am-5pm on weekends; vascular 8am-noon weekend).
• Level of Urgency:
o Routine: order of interpretation depends on acquisition time
o Urgent: takes priority over routine studies (performed within 6 hours)
o STAT: means NOW, high acuity/life threatening emergencies (i.e., trauma patient may be removed from the scanner for
your patient); these studies are typically (not always) performed in White 1 (ED scanners)
 Must call the body or neuro ED radiologist for approval (MGH Directory)
 Patient must be ready for immediate transport. Responding team must transport patient (no transport provided)
 Patient must be accompanied by a responding clinician (≥PGY-2) capable of providing emergency care
 Responding clinician must be present for the entire exam
 Radiology will provide preliminary read: phone call for XR/US, at the scanner for cross-sectionals
OVERNIGHT READS BODY EXT.4-1533 | NEURO EXT.6-8188
• Full interpretation reads overnight: All ED studies
• Preliminary interpretation reads overnight (labeled “Imaging Note” found under the Imaging tab in Epic):
o All acute CT-PE studies (inpatient and ICU)
o By verbal request: inpatient and ICU studies
 Routine/Urgent ICU & inpt studies only reviewed overnight if urgent clinical question. Consider face-to-face c/s in ED.
 STAT ICU and inpatient studies will receive a prelim interpretation.
o After communication with the primary team, all verbalized prelim reads for ultrasound and cross-sectional studies (CT/MRI) will
be documented in the chart. Verbalized prelim reads for radiographs (XR) will be documented as needed.
o All inpatient and ICU full interpretations will be generated the following morning by appropriate division
ED PROTOCOLS BODY X4-1533 | NEURO X6-8188
• Trauma: I+ (IV contrast), single phase (combo of arterial/portal venous – images checked at scanner by rads to decide if need delays)
o Blunt trauma: includes bone kernel reformats for better visualization of bones; +/- Delays for parenchymal bleed
o Penetrating trauma: O+R+ (Oral contrast, rectal contrast) for increased sensitivity of bowel injury
o CT Cystogram: retrograde filling of bladder with contrast via Foley catheter to evaluate for bladder rupture
• Cervical spine: I-, need for follow-up CTA head/neck determined by radiology, bone kernel reformats in all 3 planes
o Images checked at the scanner by radiology only if IV contrast is required for another body part
• Appendicitis: I+, possibly O+ or R+ (if GI contrast requested, please specify PO or PR), image kidneys through pelvis only
• Retroperitoneal Bleed: I-,O-
• Indications for MRI in the ED: Pediatric appendicitis after equivocal ultrasound || Appendicitis suspected in pregnancy || Rule out
occult fracture || Osteomyelitis || Choledocholithiasis (MRCP)
• OB Ultrasound Studies: Covered up until 14 weeks
ABDOMINAL PROTOCOLS X6-5162
• Stone protocol: I-O-, low dose, prone
o Order contrast-enhanced (I+) CT if there is c/f ANYTHING else (e.g. pyelonephritis) as stones likely still visualized
• Retroperitoneal hemorrhage: Routine abdomen/pelvis I-O-
• Routine abdomen/pelvis vs renal mass vs bladder cancer vs hematuria:
o Routine abdomen/pelvis: I+O+, single phase (portal venous)  workhorse protocol
o Renal mass: I+O+, two phases (noncontrast, nephrographic), abdomen only  renal masses or cysts
o Bladder cancer: I+O+, two phases (portal venous, delayed)  workup or monitoring of GU malignancy
o Hematuria: I+O-, “three” phases (noncontrast, nephrographic, urogram)  hematuria, hydronephrosis
• CT urogram vs CT cystogram:
o Urogram: antegrade filling of ureters and bladder via excretion of IV contrast (delayed phase)
o Cystogram: retrograde filling of bladder with contrast via Foley catheter to evaluate for bladder rupture
• Arterially-enhancing tumors: add arterial phase along to usual CT protocol
o MR CHIT: Melanoma, RCC, Choriocarcinoma, HCC, Islet cell (neuroendocrine) tumors, Thyroid
• Time to be NPO: IV contrast CT: 2h || Abdomen/pelvis CT: 8h. || Non-contrast CT: no NPO
• Fluoroscopy protocols:
o Requisition: specify indication, h/o surgery or aspiration
o Barium swallow vs modified barium swallow vs UGI series vs SB follow-through:
 Barium swallow: eval esophagus, GE junction, proximal stomach  dysphagia, GERD
 Modified barium swallow: eval mouth, pharynx, upper esophagus  dysphagia, aspiration
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Radiology Protocols
 UGI series: barium swallow plus stomach, pylorus, and duodenal bulb  bariatric surgery pre-op eval
 SB follow-through: small bowel, terminal ileum, and proximal LB ± UGI series beforehand
CARDIOVASCULAR PROTOCOLS VASC X4-7115 | CARD CT X4-7132 | CARD MR X3-4457
• DVT imaging:
o Compression ultrasound is the best initial test of choice (ACR 2018); Epic order “LENI” (Lower Extremity Non-Invasive)
o CTV/MRV: primarily used for central venous thrombosis when initial US is equivocal or non-diagnostic
• Arterial imaging:
o CTA: three phases (noncontrast, arterial, venous delays)  stenosis, dissection, aneurysm, active bleeding, systemic
embolism/thrombosis (not pulmonary embolism)
o Requisition: specify vessel of interest, field of view, and indication
• Coronary CTA:
o ECG-gated study of the coronary vessels  only performed by cardiovascular CT
 Requires beta blocker and vasodilator administration
 Not performed after 7pm on weeknights or noontime on weekends, as cardiac techs are typically not in house
 On call Cardiac CT Fellow is available for urgent questions after hours: p22122
o Specify if body parts other than the heart should be imaged (thoracic aorta, CABG grafts, etc.)
• Other ECG-gated CTAs:
o Indications: any eval of the heart or ascending aorta. ECG-gating unnecessary for descending thoracic/abd aorta & pulm arteries
• Noncontrast vascular studies:
o Indications: Retroperitoneal hematoma, pre-op aortic calcifications, coronary calcium score, follow-up aortic size
THORACIC PROTOCOLS X3-3899
• All chest CTs are high resolution
• Routine chest vs CT-PE vs CTA chest:
o Routine chest: single phase (late arterial)  workhorse protocol (read by Thoracic)
o CT PE: single phase (pulmonary arterial)  pulmonary arteries (read by Thoracic), prelim by ED during off-hours
o CTA chest: three phases (non-contrast, arterial, delays)  systemic arteries (e.g. aorta) (read by Vascular)
• Double rule out studies: (Clinical concern for PE and aortic dissection)
o Contrast can only be optimized for one (must pick CT-PE or CTA)
• Diffuse lung disease (a.k.a. misnomer “high res CT”):
o Indications: ILD, lung transplant, air trapping, bronchiectasis
o Phases: Inspiratory and expiratory images, plus prone images to differentiate between atelectasis and fibrosis
• Nodule follow-up: (Radiology 2017;284:228; Please refer to Fleischner guidelines)
o Indications: incidental nodule on prior CT, age >35y, AND no hx immune compromise, malignancy or recent infection
• Dual energy esophageal leak (I+/I-): Esophageal perf, postop leak; Tracheal Protocol: Tracheal stenosis, mass, stent
NEURORADIOLOGY PROTOCOLS
• Inpatients: page Neuro IP on-call radiologist at p32535
• Inpatients/ICU Acute Stroke: call x6-3333 & page p21723 acute stroke consult fellow (ED: activated ED2CT group pager)
• Head CT: typically noncontrast
o Indications for contrast-enhanced head CT: infection and/or tumor AND contraindication for brain MRI
• Spine MRI: for more than one segment, please order total spine and specify indication
o Separate MRIs should not be ordered prior to neurology/NSGY consult
• Fluoroscopy-guided LPs: performed by neuroradiology fellows, NOT neuro IR
o Indications: difficult anatomy, and only after LP is attempted on floor
o Typically performed without conscious sedation, although this can be arranged if required for patient safety
NUCLEAR MEDICINE PROTOCOLS NON-PET X6-1404 | PET X6-6737
• Tagged RBC study: BRBPR (NOT guaiac positive stools, melena, or massive bleeding)
o Requirements: consult IR BEFORE STUDY to confirm angiogram will be performed if study is positive
• VQ scan: acute PE (NOT chronic PE), can happen overnight if results will alter management (i.e., AC tonight)
o Technically just a perfusion (Q) scan since COVID; Ventilation (V) portion of the study is no longer performed.
o Requirements: CXR or I- CT chest within 24h, patient stable and can tolerate laying supine for duration of scan (~4h)
• HIDA scan: acute cholecystitis
o Requirements: NPO 4h prior to study, no opiates 12-24h prior to study, bilirubin <10, pt will need to tolerate lying supine
• PET: must be fasting, hold everything but meds and water (NO glucose containing fluids either ex: D5W)
o Overnight is ideal for NPO, but at least 6h for non-DM patients
o At least 4h for DM patients
 Continue long-acting insulin, hold short-acting insulin 4h prior to scan
o Blood sugar thresholds: FDG-PET brain < 175 mg/dL, FDG-PET whole body <250mg/dL
• Gastric emptying study:
o Patient must tolerate PO (consume a standardized meal in 10 minutes), best performed as outpatient study
M U S C U L O S K E L E T A L P R O T O C O L S : if questions: page MSK IR on-call radiologist at p36321

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Radiology Interpretation of Common Studies

CHEST X-RAY
1. Line placement
o ETT positioning: tip 3 - 7 cm above the carina in an adult
o SVC: b/w R tracheobronchial angle and R heart border (Chest 1998;114:820)
o Superior cavoatrial jxn: ~2 vertebral bodies below the carina (JVIR 2008;19:359)
o Line positioning:
 PICC or Central line: tip in the lower SVC or at the superior cavoatrial jxn
 HD catheter: tip in the right atrium
o Post placement: check for pneumothorax, except with PICC/midline (see below)
2. Pneumothorax Red line outlines optimally placed central
o Sensitivities: line. Dotted line denotes carina.
Imaging Position Detectable PTX Size Imaging Findings
Supine/Portable 500 cc (LEAST Sensitive) Deep sulcus sign, lucency along mediastinal border
Upright 50 cc Sharp pleural edge, absence of distal lung vessels
Lateral decubitus 5 cc (MOST sensitive) Nondependent collection of air
o Tension: contralateral mediastinal and tracheal shift, collapse of ipsilateral lung, flattening of ipsilateral hemidiaphragm, widening
of ipsilateral rib spaces
o Artifacts that mimic visceral pleural lines: (BMJ 2005;330:1493)
 Skin folds: form an interface (not a line), extension beyond rib cage,
presence of distal lung vessels
 Medial border of scapula: extension beyond rib cage w/ rest of scapula
3. Pulmonary edema (example images)
o Vascular redistribution (first sign): increased caliber of pulmonary vessels in upper lobes
(“cephalization”)
o Interstitial edema: incr. interstitial opacities, indistinct pulmonary vasculature, Kerley B
lines (peripheral subpleural linear opacities), peribronchial cuffing
o Alveolar edema: perihilar/central opacities, pleural effusions, cardiomegaly Bilateral pleural effusions
o Pearls: typically bilateral and symmetric, rapid appearance/resolution of findings
o Pitfalls: low lung volumes mimic increased interstitial opacities via crowding of normal
vasculature
ABDOMINAL X-RAY (KUB)
1. Line placement
• For Decompression: gastric fundus or dependent
portion of stomach. Side-port AND tip should be 4-6
cm below the GE junction.
• For Feeding: distal duodenum or proximal jejunum;
C-loop of duodenum is only reliable indicator of
post-pyloric placement
• Post placement Assessment: check for
endobronchial placement. Should descend vertically
in midline, pass diaphragm, tip should be visualized
2. Small bowel obstruction (RadioGraphics 2009;29:423) Enteric tube (decompression) – arrow Feeding tube - weighted tip in proximal
• KUB: preferred initial examination shows side port jejunum
o Assess for: small bowel dilatation >3 cm, decompressed distal small/large bowel, air-
fluid levels, stacked loops of bowel, free air as a complication
o Main differential: post operative ileus  often large bowel is also dilated
• CT: equivocal cases / further evaluation
o Findings: SB dilatation with collapse of distal bowel loops and transition point
o Severity:
 Partial: passage of air or contrast beyond the obstruction
 Complete: no passage of air or contrast beyond the obstruction
o Transition point: look for small-bowel feces sign (fecal material mixed with gas Small bowel dilation in case of small
bubbles in small bowel just proximal to transition point) bowel obstruction (SBO)
o Common causes: adhesions, Crohn’s, malignancy, hernias; colon cancer most
common cause in LBO
o Closed loop obstruction: radially oriented bowel loops, engorged mesentery, whirl sign
o Strangulated/incarcerated hernia (ischemia): bowel wall thickening, lack of bowel wall enhancement, pneumatosis
intestinalis, portal venous gas

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Radiology Interpretation of Common Studies

3. Pneumoperitoneum (AJEM 2009;27:320)
o Upright: air beneath the diaphragm
o Left lateral decubitus: air overlying the liver
o Supine: insensitive exam

ULTRASOUND
1. Cholecystitis (AJR 2011;196:W367)
o US is preferred initial examination
o Common findings: gallstones, gallbladder wall thickening >3 mm, gallbladder distension (>4cm
transverse, >8cm longitudinal), peri-cholecystic fluid
o Sonographic Murphy’s sign: 92% sensitivity (analgesics reduce sensitivity, unreliable if recent Pneumoperitoneum
analgesics)
o Gallstones and gallbladder wall thickening: 95% positive predictive value for acute cholecystitis
o Key Differential - Gallbladder wall thickening without stones and without distension is more likely to be from third spacing
(CHF/renal failure/cirrhosis) or underlying liver disease (hepatitis); much less likely cholecystitis
2. Deep venous thrombosis (Cardiovascular Diagnosis and Therapy 2016;6:493)
o Compression U/S: noncompressibility of vein (key finding), echogenic thrombus within vein, venous expansion
o Venous duplex U/S: absence of color Doppler signal, flow phasicity, & response to augmentation maneuvers
o Non-obstructive vs. Obstructive thrombus: both are non-compressible, obstructive lacks color Doppler flow
o CT venogram:
 Alternative to U/S in critically ill patients who have undergone CT PE
 Pros: evaluation of pelvic veins and IVC, which are difficult to assess on US
 Cons: invasive, requires contrast, radiation, possible streak or mixing artifacts

CROSS SECTIONAL IMAGING

Excellent resources for anatomy, image interpretation, and sample cases:
https://radiopaedia.org/; https://radiologyassistant.nl/; https://introductiontoradiology.net/; https://www.learnabdominal.com/ (GI/GU); http://xrayhead.com/
(MSK)
CT Head Example Search Pattern MRI Brain Example Search pattern
1. Brain parenchyma 1. Brain parenchyma
a. Mass lesion: brain window a. Mass lesion: T1, T2, FLAIR
b. Intraparenchymal hemorrhage: brain window b. Intracranial hemorrhage: SWI, T1, T2
c. Infarction: stroke window c. Infarction: DWI, ADC
2. Epidural / Subdural Hematoma 2. Vessels: T2 for flow voids, T1 post-contrast, TOF if non-
3. Vessels contrast MRA
4. CSF spaces: ventricles, sulci, basal cisterns 3. CSF spaces: T2
5. Midline shift or herniation: coronals helpful 4. Midline shift or herniation: coronals helpful
6. Soft tissues (great to start with for trauma head CTs) 5. Soft tissues
7. Bones/sinuses 6. Bones/sinuses

CT Chest Example Search Pattern CT Abdomen/Pelvis Example Search Pattern

1. Lung bases and partially visualized heart
1. Lines and tubes (scout can be very helpful) 2. Liver/gallbladder: focal lesions, biliary dilatation
2. Upper Abdomen 3. Spleen
3. Soft tissues 4. Pancreas: focal lesions, pancreatic ductal dilatation
4. Bones 5. Adrenals
5. Heart and mediastinum: thyroid, lymph node stations, heart 6. Kidneys/ureters: hydronephrosis, stones, focal lesion
and pericardium, asc/desc aorta, great vessels, esophagus 7. Bladder/Prostate/Uterus/Adnexae
6. Pleura: pleural effusion, pneumothorax 8. Peritoneum: free air or fluid
7. Airways: trachea, bronchi, bronchioles 9. Lymph Node Stations
8. Lungs: pathology manifests as changes to the secondary 10. Vessels: AAA
pulmonary lobule (see links) 11. GI tract: bowel distension, bowel wall thickening, appendix,
a. Radiology Assistant  Lung HRCT Basics terminal ileum
b. Radiopedia  Lobule Basics 12. Soft tissues
13. Bones

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Procedures Ultrasound Basics

REMINDER: do not base clinical decisions on POCUS exams unless the exam and decisions are supported by a supervising
provider. Additionally, POCUS should be used in the setting of limited and targeted clinical questions.

EQUIPMENT (NEJM 2011;364:749)

Basic Terminology:
• Frequency: 1Hz = 1 cycle/sec; medical US typically between 2-15MHz
- High frequency (>5MHz): resolution, shallow tissue penetration, ideal for vascular, skin, breast, thyroid
- Low frequency (2–5MHz): resolution, deeper tissue penetration, ideal for abdominal, OB/GYN, cardiac
• Gain: signal amplification; similar to brightness control. Higher gain = brighter image; lower gain = dimmer image
• Depth: depth of field of view (FOV). Excessively large FOV = spatial resolution; tight FOV limits view of nearby structures
• Attenuation: reduced signal transduction through a medium = signal intensity behind it (bone/air/stones have high attenuation)

Transducer (probe): converts electricity into sound waves  transmits sound wave into tissue  receives sound waves echoed
back from tissue. Indicator (denoted by dot or notch on probe) displays on left of the screen. Exception: echocardiography  indi-
cator displays on right side. For most indications, position probe with indicator to patient’s right or cranially
• PHASED-ARRAY (cardiac) probe: good for looking in small windows (i.e. between inter- Phased-array Linear Curvilinear
costal spaces for cardiac or pulm imaging); low resolution, fan-like image
• LINEAR (vascular) probe: good for shallow structures (i.e. vascular, soft tissue). Uses high
frequency with good resolution, produces rectangular image
• CURVILINEAR (abdominal) probe: good for deeper structures (i.e. intra-abdominal). Uses
lower frequency; combines linear and phased-array probe image qualities

COMMONLY USED MODES

• B-mode (brightness mode): standard 2D gray-scale image
B mode
• D-mode (doppler mode): detects flow to or away from transducer. Useful to find and
define vessels, or flow across valve
o Color  direction and velocity are color coded and superimposed on B-mode
image. “BART” (Blue is Away from probe, Red is Towards)
o Power  detects very low flow but not direction, useful in vascular compromise
o Spectral  velocity presented graphically on a timeline
• M-mode (motion mode): takes a slice of a B-mode image over time. Often used in M mode
TTE. Useful to assess lung sliding for pneumothorax

GENERAL IMAGING CONCEPTS

Typical Appearance of Normal Tissue:
• Skin and pleura are smooth and brighter than surrounding tissue (hyperechoic)
• Fat and muscle are darker (hypoechoic), though varies depending on the tissue
• Fluid (e.g. blood, effusion, ascites) is black on US (anechoic), though thick fluids (e.g. pus)
can be brighter than typical fluid. Fluid can have a layered appearance based on density.
• Tendons and nerves are bright (hyperechoic) if perpendicular to probe, dark (hypoechoic)
when angle is changed (anisotropy)
• Bone has a hyperechoic rim (due to reflection) with dark shadow beyond it

Artifacts: elements seen on ultrasound image that do not exist in reality

• Reflection: proportional to the difference in acoustic impedance between two tissues (differ-
ence = reflection)
• Relative acoustic impedance: bone > solid organ > fat > lung > air
• Shadowing: signal beyond strongly attenuating/reflecting structure (e.g. stones, bone)
• Enhancement: signal posterior to weakly attenuating (hypo or anechoic) structure (e.g., cysts)
• Mirror image: structures in front of strong reflector (e.g. diaphragm) appear to lie behind it as
well
• Reverberation: evenly spaced lines at various depths beyond a strong reflector (e.g. A lines
beyond pleura)
• Comet tail: tiny, narrow reverberations beyond very strong reflector (e.g. metal pellet) blending into a line

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Procedures Ultrasound Basics

IMAGING AND TIPS (see The POCUS Atlas for reference)
Diagnostic Use: Normal (Sliding) Lung
• Pneumothorax: use LINEAR (vascular) or CURVILINEAR probe. In supine patient, look in 3rd
Seashore Sign
intercostal space on anterior chest, pointing indicator cranially. Identify hyperechoic rims of the
ribs with posterior shadowing. The pleura is the hyperechoic stripe that is within the intercostal Waves
space. Normal lung will slide along the pleural line with respiration, while pneumothorax will
not. If ambiguous, use M mode to confirm. A lack of lung sliding will change the normal ‘sea- Sand
shore’ sign to a static ‘barcode’ sign. Sn 91%, Sp 98%, superior to CXR. Can also look for
“lung point” (100% specific) (J Emerg Trauma Shock 2012;5:76; Annals EM 2013;61:207)
Pneumothorax
• Pulmonary embolism: use PHASED-ARRAY (cardiac) probe. Bedside US can be used to Barcode Sign
identify right heart strain. Look for RV size ≥ LV size, septal bowing (D-sign in parasternal
short), note Sn 53%, Sp 83% for PE. RV/LV ratio most easily visualized in apical 4 chamber
view, can be misleading based upon slight changes in plane. Assess the cardiac septum verti-
cal and in line with midpoint of probe. Combine with parasternal axes for better reliability (J Am
Soc Echocardiogr 2017;30:714)

• Pulmonary edema: use PHASED-ARRAY (cardiac) or CURVED (abdominal) probe. Evaluate Pulmonary Edema
the lung between rib spaces and across multiple lung fields similar to auscultation. Look for B-
lines: comet like artifacts that shine perpendicular from the pleural line and obliterate A-lines.
≥3 in one interspace is consistent with interstitial fluid, and bilaterally suggests pulmonary B lines
edema. Ddx of B-lines is broad. Operator dependent but can outperform CXR (Intensive Care
Med 2012;38:577; Acad Emerg Med;23:223)

• Pericardial effusion: use PHASED-ARRAY (cardiac) probe. Look for an anechoic collection
between the heart and the hyperechoic pericardium. Hemorrhagic or purulent effusions may
appear more complex. On parasternal long axis, pericardial effusion will be anterior to the de- Pericardial Effusion
scending aorta while a pleural effusion will be posterior. All four views are important but Effusion
subxiphoid often used in emergencies. Look for chamber collapse indicating tamponade: RA is
more sensitive; RV is more specific (Resuscitation 2011;82:671)

• Volume status: use the PHASED-ARRAY (cardiac) probe. IVC collapsibility has been pro-
posed as a proxy for CVP and fluid responsiveness, though data is mixed. There are no con-
sensus guidelines. Start with subcostal view of RA/RV, then rotate probe to the sagittal plane
to find the IVC draining into RA and abutting the liver. Look at IVC 2cm from RA: fluid respon-
siveness or an underfilled IVC is suggested by 1) IVC diameter ≤1.5cm and 2) IVC collapses Volume Status
≥½ its diameter with inspiration. Can use M mode to assess collapsibility. IVC diameter Liver
≥2.1cm with ≤50% inspiratory collapse can indicate elevated CVP. Pair IVC POCUS w/ lung RA
US for volume status evaluation. (Crit Care 2012;16:R188; CCM 2013;41:833; IVC
Shock 2017;47:550)

Procedural Use: refer to pages on specific procedures for more details

• Paracentesis: use CURVILINEAR (abdominal) probe. Locate largest fluid collection, often in
LLQ. Try rolling patient to side to increase pocket size. LINEAR (vascular) probe can help Ascites Abd wall
identify any overlying vessels (particularly inferior epigastric vessels). Bowel appears as hy-
perechoic finger-like projections within the anechoic ascites, ensure prior to procedure scan-
ning in multiple locations and fanning to assess for bowel (to avoid perforation). Measure the
depth of the abdominal wall and compare to your needle to determine when to expect flash.

Bowel
• Central venous access: use LINEAR (vascular) probe. Reduces complications and quality of
placement compared to landmark approach (Crit Care 2017;21:225)
o In-plane (longitudinal): can view entire tip, but harder to keep needle in view
o Out-of-plane (cross sectional): easier to center needle, may underestimate depth

• Peripheral IV: use LINEAR (vascular) probe. Most of your time should be spent finding the
best vein to go for. Evaluate anterior forearm prior to assessing the cephalic in upper arm.
Track along vessel length to determine trajectory, look for large, superficial, compressible ves-
sels that are not immediately adjacent to pulsatile, non-compressible arterial vessels

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Procedures Ultrasound-Guided Peripheral IV

GENERAL CONSIDERATIONS
Indications: non-emergent access in a patient with difficult access. If emergent, obtain IO or central access
Locations: forearm first; then AC, cephalic, basilic, brachial; larger veins offer higher chance of success than smaller veins (see figure)
Contraindications: relative: sensory/motor deficits (clot risk), HD fistula, hx of LN dissection, overlying infection/cellulitis
Materials: angiocath (18 or 20G best; small IVs not well visualized on US), vascular probe, gel/sterile lubricant, tourniquet, alcohol
wipe/chlorhexidine, tegaderm, extension tubing, saline flush, ± vacutainer adapter and tubes/cultures + labels (if labs needed)
• Angiocath selection: standard length (30mm) good for vein <0.8cm deep; long needle (48mm) preferred for ≥0.8cm deep (48mm 18G
[green] stocked in most supply rooms, but 48mm 20G [pink] more difficult to find.
TRANSVERSE TECHNIQUE
NEJM 2012;366:e38: choosing a vein (8:45), transverse (10:05), longitudinal (12:28)
1) Setup: positioning is crucial. Place US on opposite side of pts bed, adjust bed
to appropriate height, obtain seat if needed, abduct & externally rotate pts arm
2) Place tourniquet: place tourniquet proximal, near axilla if possible
3) Confirm anatomy: use vascular probe at minimum depth to locate adequate
superficial veins, M-mode line can be helpful to stay centered
o Find vessels: start at AC and move proximal first, then distal. Key is to
find LARGE vessels (>0.4cm diameter) that are CLOSE to the surface
(depth between 0.3cm – 1.2cm) (J Emerg Med 2010;39:70). Common veins:
basilic, cephalic > deep brachial (see figure)
o Confirm venous: gentle pressure differentiates non-thrombosed veins
(fully compressible, non-pulsatile) and arteries (poorly compressible,
pulsatile); color doppler can confirm; scan both arms if able
o Trace vessel course: follow the vessel course proximally and distally; recognize and avoid branch points, diving veins, and
irregularly coursing veins  identify the trajectory along which the ultrasound probe travels to maintain center of vessel
4) Sterility: use alcohol pad or chlorhexidine swabs to sterilize proposed venipuncture site; clean US probe, then cover with tegaderm;
use sterile lubrication (or sterile US gel) as conduction medium for probe (can also put gel under tegaderm)
5) Orient ultrasound: center target vein on US screen, confirm with compression, confirm vein course is in
line with proposed needle course, stabilize probe by anchoring 5th finger/hand on patient
6) Insert angiocath: with bevel up, puncture skin and advance angiocath 2-3 mm at a 45° angle
o Angiocath needle tip should be centered on US probe – this will be directly over the vein if vein is
centered on screen
o Insertion site at skin is distal to the planned site of insertion into vein
o At skin insertion, eyes should be on the site of venipuncture, not on the US screen, though after
puncture, should be watching screen at all times and not hand
7) Find tip and advance: needle tip (and shadow) should appear on screen  advance PROBE until you lose needle tip  advance
NEEDLE tip until it reappears on US screen; continue to advance until tip is “tenting” the roof of the vein
8) Enter vein: a quick short jab will allow you to enter vein; visualize needle tip as “target sign” (see image)
9) Drop angle and advance: drop your hand to flatten needle angle; continue to advance as above, keep
needle in center of vein (always aim to get “target sign” with each probe then needle advancement) until
angiocath is hubbed to skin, then retract needle
10) Alternative: Slide off catheter: once 3-5mm into vein, can slide catheter off needle into vein and hub, and retract needle
11) Flush: attach extension tubing, pull back on saline flush (ensure drawback), REMOVE TOURNIQUET, flush with saline  can also
confirm lack of extravasation of saline under US visualization
12) Secure: secure catheter and tubing with Tegaderm, +/- additional tape; nurses may redress IV
L O N G I T U D I N A L T E C H N I Q U E : use the following adjustments to the above technique
1) Identify target vein in the transverse view
2) Rotate the probe to obtain a longitudinal view with the indicator towards your needle
3) Align needle in the plane of the probe; puncture skin at 45 degrees, visualize needle tip
4) Advance needle until you can see that the tip of the catheter itself is fully within the vein
5) Do not to go through the back wall. Advance the catheter under direct visualization

Technique Pros Cons

- Faster, requires less finesse with US probe - Harder to visualize the needle tip
Transverse (short axis)
- Allows visualization of adjacent structures - Risk of “through and through”

- Improved visualization of the needle tip (depth) - Challenging to maintain probe/vein/needle in plane
Longitudinal (long axis)
- Can advance catheter under direct visualization - Cannot see adjacent structures

T R O U B L E S H O O T I N G (Transverse Video; Longitudinal Video; written guide: West J Emerg Med 2017;18:1047)
• Can’t see needle: gently bounce the needle tip to generate artifact or slight fanning of the ultrasound probe until the tip is in view
• Too much loose tissue: use tape or have someone assist by putting tension on the tissue w/o applying pressure over target vein
• Vein rolls: reposition directly over the middle of vein, use a slightly steeper angle to take advantage of the sharp edge of the needle
• Trouble finding any veins: try using a blood pressure cuff high in the axilla instead of a tourniquet, but give the patient frequent breaks
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Procedures Central Line

GENERAL CONSIDERATIONS
Indications: hemodynamic monitoring (CVP, CVO2); admin. of noxious meds (pressors, chemo, hypertonic solution, TPN); rapid large
volume resuscitation (Cordis/MAC); inadequate peripheral access; HD/CVVH/pheresis; to introduce other devices (PA line, temp wire)
Contraindications: vein thrombosis or stenosis should prompt another site. Coagulopathy/thrombocytopenia are relative
contraindications. If severe coagulopathy, avoid subclavian (not a compressible site & difficult to effectively monitor for bleed)
Site selection: general preference at MGH is RIJ > LIJ > subclavian/femoral due to historical concern for infection. However, more recent
data suggests no difference between these sites with proper attention to sterile technique (NEJM 2015;373:1220). Additionally, it is helpful
to predict if RIJ may be needed for dialysis catheter, in which case LIJ placement is preferred.
Catheter selection: select based on number of lumens and speed of infusion; if rapid infusion required  large bore, short length
(Cordis/MAC). Right IJ catheter length: 16cm. Left IJ catheter length: 20cm
Alternatives: PICC (if no concern for bacteremia, often requires negative BCx >48hr) or IO (if emergent, should not be used for >24h)
Infection control: scheduled exchange of catheters without evidence of infection is NOT indicated. Cultures drawn from indwelling
catheters have false ⊕ rate; generally not done aside from time of sterile placement (NEJM 2003;348:1123)
I N T E R N A L J U G U L A R V E I N (Video: NEJM 2010;362:e57)
Advantages Disadvantages
Compressible vein Carotid artery puncture 2-10%
Lower risk of pneumothorax (< 1%) than subclavian Less patient comfort
Ability to use real-time ultrasound Anatomy not as consistent as subclavian
All IJ CVCs placed with real-time US guidance at MGH: first attempt failure, procedure time, and failure/complication rate
Positioning: supine + Trendelenburg to engorge veins & risk of air embolus. Towel can be used to elevate shoulder to lateralize IJ. Site
selection (typically R > L, unless preserving right side for HD line).
• Locate triangle formed by medial and lateral portions of SCM with the clavicle as base Transverse ultrasound view
showing RIJ anterior & lateral to
• Find IJ, typically superficial and lateral to carotid, compressible; can also use color Doppler
carotid artery
• RIJ generally preferred due to direct course to SVC, LIJ risk of PTX and thoracic duct injury
Target: aim at ipsilateral nipple, 45 degrees (map out trajectory of vessel using ultrasound)
1) Preparation and positioning are ESSENTIAL; ensure someone is always available to help
2) Obtain consent; perform TIME-OUT with RN; complete checklist with RN assistance
3) Use US to ensure your target anatomy is in good position. Assess LIJ & RIJ
4) Use 2% chlorhexidine solution to prep (in the kit); drape the entire patient in sterile field
5) Place caps on CVC, flush all lines with sterile saline, remove cap from brown port (where
wire will emerge); ensure guide wire advances easily and syringe comes off needle easily
6) Locate IJ vein & carotid artery using ultrasound
7) Anesthetize with lidocaine; can make wheal & inject along tract (aspirate before injecting!)
8) Insert (bevel up) large bore needle at the apex of SCM/clavicle triangle, about 4-5 cm above
suprasternal notch. Advance @ 45° towards ipsilateral nipple visualizing tip with US; apply
negative pressure throughout. Once flash of blood is obtained  stop advancing the needle,
continue to draw back venous flow (dark, non-pulsatile)
• If arterial flow seen, remove needle and compress ~10 min
• If air drawn back, suspect PTX  STAT CXR, 100% FiO2, decompress if tension
9) Once flow obtained, drop US probe and stabilize needle with your non-dominant hand, flatten
needle angle while drawing back to ensure continued flow, remove syringe from locator (occlude
hub with thumb to minimize risk of air embolism in non-ventilated patients)
10) Feed the curved end of the loaded wire into the needle (never feed the opposite end), NEVER LET GO OF THE WIRE.
• If any resistance, remove wire, assess for flow w/ syringe; if good blood flow, try twisting wire or flattening angle of needle
• For RIJ  feed ~25cm of wire (between two and three dark lines)  watch for ectopy (suggests wire in RV  withdraw)
11) Remove needle over guidewire
12) Confirm wire is in vein using US in transverse and longitudinal planes
13) Perform manometry confirmation  advance angiocath from kit over wire, remove wire, connect manometer tubing  leave fluid in
manometer and hold vertically to avoid air embolism  venous blood should be non-pulsatile, dark, and rise <20cm  disconnect
manometer tubing  replace wire through angiocath  remove angiocath
14) Extend puncture site with scalpel (face cutting edge away from wire to prevent cutting wire)
15) Thread dilator over wire (using twisting motion, grip near the skin) until about 1/3 is inserted,
then remove; goal is to dilate skin/subcutaneous tissue, NOT the vessel itself (increased
bleeding); ensure the wire moves back and forth freely while dilating (may otherwise be kinked)
16) Advance catheter over wire (wire comes out brown port); remove wire
17) Draw back vertically off all ports through caps using saline flush (only small amount of flash
needed), flush all lines clean, clamp ports
18) Secure with sutures; place Biopatch prior to securing with dressing
19) Order CXR (ASAP) to assess position, rule out PTX/hemothorax; MUST look at the CXR
yourself to confirm placement; catheters should terminate in superior vena cava or cavo-atrial
junction; may need to pull back if in RA ( ectopy). If adequate position, put in order “OK to use”
20) Write procedure note (create note in notewriter, then select “Central Line”)
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Procedures Central Line

**For subclavian or femoral vein access, please discuss with attending and ensure appropriate oversight prior to procedure!**
S U B C L A V I A N V E I N (Video: NEJM 2007;357:e26)
Advantages Disadvantages
Anatomy more reproducible, incl obesity, w/ bony landmarks Risk of PTX (1-8%), L side slightly > R, higher dome of L pleura
Improved patient comfort; easier to dress and maintain Not easily compressible; more risk a/w bleed if coagulopathic
Risk of subclavian artery puncture/hemothorax (0.5-1%)
Positioning: place in Trendelenburg to engorge vein and consider placing a roll of towels between the scapula to expose subclavicular
area (may distort anatomy for some)
Entry: at MGH  infraclavicular approach (as opposed to supraclavicular); puncture skin 1cm caudal to
junction of medial 1/3 and middle 1/3 of clavicle (where vein flows just under the bone)
Target: bevel up and aim toward sternal notch, 30° to the skin; needle should advance just on the
underside of the clavicle (~3-5cm depending on anatomy); some people “walk down” the clavicle to clavicle
ensure this, but may lead to dulling or bending of needle as well as periosteal pain
Pearls:
• Turning head to ipsilateral side will kink IJ and facilitate wire going down the SVC
• Rotate bevel 90° caudal after needle is in the vein to help direct wire into the SVC
• Ultrasound not always helpful (given acoustic shadowing from bone) SC a. & v.

• Subclavian vessels may be compressed with two fingers squeezing around the clavicle
• Guidewire usually only needs to advance 20cm (two dark lines)

F E M O R A L V E I N (Video: NEJM 2008;358:e30)

Advantages Disadvantages
Compressible Femoral artery puncture 5-10%
No risk of PTX Risk of development of DVT
Can be cannulated more easily during CPR Less patient comfort in hip flexion, requires immobility
Large caliber vein technically easier to cannulate May occlude flow if patient has obesity
Caution in patients with inferior vena cava filters
Positioning: head of bed flat; abduct lower extremity and externally rotate the hip, generally
use 20 cm line
Entry: bevel up, 2-3 cm below inguinal ligament, 1cm medial to palpated medial
pulse  femoral vein lies medial & inferior to the femoral artery
• If non-urgent, best to use US to visualize
• “NAVEL toward the NAVEL”  Nerve, Artery, Vein, Empty,
Lymphatics (alternative: venous  penis)
• Two fingerbreadths lateral to pubic tubercle if pulse not palpable
• DO NOT approach vein above inguinal ligament  increased risk for RP bleed &
peritoneal perforation
Target: directly superior at 30-45°
*No confirmatory imaging needed

HEMODIALYSIS LINES
Sites: IJ (R preferred), subclavian vein, femoral vein
Placement technique: Same steps as CVC placement, additional dilation step is key difference (double dilation). For manometry, can use
catheter from Arrow arterial kit. Note, the wire will come out of the blue colored port.

CORDIS (AKA VENOUS INTRODUCER SHEATH)

Combined dilator and sheath w/ side port for IV access
Indications: rapid resuscitation, introducer sheath for PA catheter, temp wire placement
Sites: IJ (R preferred for PA line), subclavian vein, femoral vein
Placement technique: uses Seldinger technique (advance catheter over a wire) but dilator and sheath are advanced over wire together as
unit; dilator and wire then removed together; side port aspirated and irrigated prior to use

CVC COMPLICATIONS
Arterial puncture: hold pressure x10min; compress 1 inch inferior (IJ) or 2 inches superior (femoral) to puncture mark
*Methods for ensuring venous placement include manometry/waveform measurement, ABG sampling
Dilation/line placement in an artery: consult vascular surgery BEFORE removing line; consider CT if pt stable
Pneumothorax (IJ & subclavian): suspect if hypoxemia, hypoTN, difficult stick; obtain STAT CXR  consult thoracic surgery if PTX or
hemoTX; if tension physiology (shock)  immediate decompression with 16G angiocath at 5th ICS, mid-axillary line (enter above the rib)
Retroperitoneal bleed (femoral): suspect if hematoma or hypotension; STAT CT  consult vascular medicine
Loss of wire or wire stuck in vessel: remove needle, DO NOT use excessive force to pull out wire if it is stuck  leave in place, hold
pressure to prevent exsanguination  STAT KUB/CXR if wire loss  consult vascular medicine

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Procedures Arterial Line

GENERAL CONSIDERATIONS
Indications: real-time BP monitoring (pressors, HTN emergency, CVA); frequent ABGs, softer indication for lab draws (≥3 per day)
Locations: radial > femoral > dorsalis pedis > axillary; brachial not recommended given lack of collaterals unless placed by anesthesia
Contraindications: lack of sufficient collaterals (abnormal Allen test), h/o arterial grafts/stents, Raynaud’s/scleroderma
Risks: pain, infection, bleeding, ischemia, vasospasm, arterial dissection, embolization, necrosis, loss of limb
Materials: arm board, tape, Chux, chlorhex prep, 4 x 4 sterile gauze, pack of sterile towels, sterile gloves, mask, eye protection, bouffant,
20G angiocaths, guide wire, Tegaderm, US probe cover (if needed). Pre-assembled kits available.
• If pt awake  consider lidocaine w/o epi (small syringe and 25G needle)
• Use PINK SOLID STRIPE angiocath; do NOT use pink interrupted stripes, which has a one-way valve
so can’t pass wire
• Alt: use Arrow arterial line / Micropuncture kit; the kit’s longer catheter is preferable for femoral site

R A D I A L T E C H N I Q U E (Video: NEJM 2006;354:e13)

1) Obtain consent and perform TIME OUT; ask RN to prepare for A-line
2) Confirm anatomy by palpating pulses or with US. Test for collateral circulation of the hand:
• Allen test: make fist for ~30sec, then occlude ulnar & radial arteries; pt opens hand (palm should be blanched); then release
pressure from ulnar artery  palm should regain color within ~5-10 sec
• Modified Allen test: place pulse oximeter on index finger or thumb; occlude radial and ulnar arteries until wave form lost;
release ulnar artery  should get arterial tracing if good collateral flow
3) Proper positioning: adjust bed to appropriate height for operator comfort. Put Chux under wrist; extend pt’s wrist; secure arm board
(bendable arm boards in CCU and MICU). Consider taping hand to bed/table to stabilize; note the course the artery travels.
4) Sterilize wrist widely with 2% chlorhexidine swabs for ~30 seconds; open towel packet to create sterile field
5) Prepare field: drop angiocath & guide wire (and sterile US supplies) on sterile field; don sterile gloves and drape widely w/ sterile
towels. Prepare US with gel and probe cover, if utilizing. Leave on sterile field
6) Prepare angiocath/guidewire: check angiocath to ensure catheter slides easily off needle; pull one side of wire slightly out of paper
7) Pick your target: palpate radial artery (or visualize with US) with non-dominant hand; plan to puncture distal to the pulse you palpate.
Note: Avoid catheterizing very distal (near angle of extension) as A-line more likely to displace later when pt moved
8) Insert angiocath: with bevel up, advance angiocath needle at a 45° angle toward pulse until flash is obtained (similar to ABG)
9) Once flash obtained, go "through-and-through”: advance ~0.5cm through artery; hold the top of the plastic catheter with non-dominant
hand; push button to retract needle, while steadying the catheter (should be no blood flow)
10) Hold guide wire close to head of angiocath w/ dominant hand
11) Level and pull back : lower angiocath as parallel to skin as possible and SLOWLY pull it back until pulsatile blood flow is obtained,
then hold angiocath very still to avoid pulling out of vessel
12) Advance wire: insert the wire into the angiocath; should not feel resistance; if unable to advance wire, DO NOT LET GO OF GUIDE
WIRE; TRY SPINNING THE WIRE  avoids side branches of artery (where wire commonly gets caught)
13) Advance angiocath into the artery over the wire (Seldinger technique)
14) Remove guidewire: apply pressure to radial artery proximal to cath; remove guide wire; occlude opening of the angiocath with finger
15) Connect transducer: ask RN for A-line setup and connect transducer to angiocath; RN will flush; confirm placement w/ art. waveform
16) Clean the area with gauze and dress with a Tegaderm; MICU RNs will often re-dress afterwards, so ask their preference; in ED,
suture to the wrist; NWH has snap dressings
ALTERNATIVES AND TROUBLESHOOTING
• If using Doppler, mark out course of artery with marking pen
• If using US, can try advancing needle under US guidance and once firmly in vessel, advance catheter over needle (no guide wire;
similar to PIV)
• After multiple attempts, the artery may spasm or hematomas may form. Pursue alternative site (or more distal site).
• If unable to thread guide wire after attempting spinning during insertion, consider micropuncture wire (with supervision). May help with
atherosclerotic arteries at risk of perforation. Kit includes introducer needle, microwire, and microcatheter w/inner stylet.
o Use micropuncture needle to puncture vessel under US guidance until flash, can walk forward in vessel, then drop probe
o Thread microwire (more pliable end first) through needle, then remove needle
o Thread microcatheter over the wire
o Once hubbed, unscrew to remove inner stylet and microwire
• Femoral artery access can be considered in difficult cases. Use the long catheter in the Arrow
arterial line kit. Puncture must occur distal to the inguinal ligament to prevent RP bleed. Too distal,
however, and the femoral artery will bifurcate into superficial and deep femoral vessels. The
femoral artery usually transverses the inguinal ligament ~1/3 distance from pubic symphysis to the
ASIS. Optimal point of skin puncture is 1-2 cm below the inguinal ligament at point where pulse is
palpated, or aiming to insert immediately proximal to femoral bifurcation (see graphic)

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Procedures Intraosseous Line

G E N E R A L C O N S I D E R A T I O N S (Video: NEJM 2014;370:e35)
• Anatomy: veins that drain medullary sinuses of bones; veins supported by bones do not collapse in patients in shock
• Indication: patients without available IV access with urgent need (arrest, shock, status epilepticus, trauma, etc). Used for delivery of
fluids/medications; labs (but tenuous – clots off quickly). Faster access than CVC, low complication risk (Resuscitation 2012;83:40)
• Contraindications: fractured or penetrated bone (fluids exit site), local vascular compromise (e.g. trauma or cutdown). Should be
avoided in areas of cellulitis, burns, osteomyelitis, bone disease (e.g. osteogenesis imperfecta), RL intracardiac shunts (TOF, pulm
atresia) due to risk of fat emboli, failed IO insertion within 24h at same site
• Complications: extravasation, compartment syndrome, fracture, growth plate injury, infection, fat emboli, osteomyelitis (rare)
• Notes: infusion rate roughly 160mL/min at tibia or humerus with use of pressure bag, half the rate without. IO samples only accurate
for some studies (Hgb, T&S, drugs, Cx). NOT for PaO2, WBC, K, AST/ALT, iCal, after drug admin
SET-UP
• Materials: ALL IN KIT  EZ-IO Power Driver, IO needle-set,
connector tubing, 10cc syringe with saline flush,
chlorhexidine/povidone iodine, sterile gloves. If awake, 3cc
syringe with 1% lidocaine via 25G needle
• Replace: Blake 7 MICU, Materials Management (Lunder LL019)
• Location:
• Proximal tibia (preferred): find the flat surface 2cm below
tibial tuberosity, 1-2cm medial along tibia
• Proximal humerus: position pt palm on abdomen (elbow
flexed, shoulder internally rotated), greater tubercle 2cm
below acromion process
• Other sites: distal tibia, distal femur, iliac crest
P R O C E D U R E (Crit Care 2016; 20:102)
1. Don surgical mask, eye protection, sterile gloves
2. Flush connector tubing with NS or lidocaine if patient is awake
3. Identify injection site
4. Clean injection site with antiseptic (chlorhexidine or iodine)
5. If patient is awake, create wheal with 1% lidocaine
6. Choose proper needle size: generally blue (25mm); yellow (45mm) is for excess tissue or for
humerus approach
7. Magnetic pole holds the needle in place; turn the safety cap clockwise for removal
8. Hold drill perpendicular to bone if proximal tibia; hold 45° to the anterior plane and posterior
medial if proximal humerus
9. Manually press the needle through the skin until it touches the bone. Confirm you see one
black line on the needle (5mm mark); if not, use a longer needle (see illustration)
10. Apply gentle, steady, downward pressure while holding the trigger; allow drill to do the work
11. Release trigger when decreased resistance felt (“give” or “pop”) as you enter into medullary space
12. While holding catheter in place, pull straight up to remove driver
13. Unscrew the needle stylet by rotating counterclockwise (both stylet and needle are
encased in colored plastic)
14. Aspirate marrow to confirm placement. Prior to attaching tubing, send labs; blood
samples may only be obtained in patients with spontaneous cardiac activity or
during initial CPR before drug and fluid infusion through the IO
15. Attach connector tubing and flush IO w/ NS or 1% lidocaine over 45s if the patient
is awake (IO infusions are VERY painful); if the patient is unconscious, rapid 10mL
NS. Look for superficial swelling and note that no flush means no flow!
16. Apply IO dressing stabilizer – FYI each size needle has a different dressing, will not
fit if using dressing for different size needle
17. Administer rapid NS bolus/blood/pressor with a pressure bag or syringe
18. Always return the IO kit to unit for resource nurse to refill
REMOVAL
Remove within 24 hours of insertion once other access is obtained (not good for long term access), or if signs of erythema, swelling or
extravasation. To remove: don procedure mask, goggles, non-sterile gloves. Remove IV extension tubing from needle hub. Then, place
sterile syringe on needle hub (acts as handle for removal). Grasp at needle hub and rotate clockwise while pulling gently at 90-degree
angle from the bone. Do not rock the syringe. Once the needle hub is out, place needle hub in sharps container. Apply pressure over IO
site until bleeding has stopped and dress with gauze and tegaderm.
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Procedures Paracentesis
I N D I C A T I O N S (Video: NEJM 2006;355:e21)
• Diagnostic: new-onset ascites, unknown etiology of ascites, rule out SBP. Low threshold for patients with cirrhosis, consider
concurrent RUQUS with Doppler to rule out venous thrombosis. Para w/in 24hr = better outcomes (Liver Transpl 2023;29;919).
• Therapeutic: Performed for abdominal pain/discomfort, diuretic-refractory ascites, respiratory compromise, abdominal compartment
syndrome, adjunctive treatment of esophageal variceal bleeding (can lower portal pressures). Larve volume para ≥ 5L removed.
CONTRAINDICATIONS
• Overlying cellulitis, inability to demonstrate ascites on US, bowel obstruction/distention, acute abdomen, 2nd or 3rd trimester pregnancy
• INR, plt are NOT contraindications in cirrhosis (INR in patients with cirrhosis is NOT reflective of the risk of bleeding). There is no
need to correct coagulopathy w/ FFP or platelets unless severe DIC (Hepatology 2021;74:1014).
MATERIALS
• Sterile gloves, bouffant, face shield, chlorhexidine, sterile towels, US, 1% lidocaine (10cc syringe, SQ 25G needle, 1.5inch 20-22G
needle), two 18G needles, 60cc syringe, diagnostic assay tubes as below, gauze, bandage or Tegaderm dressing
• Diagnostic: 20G two-way (pink) angiocath or 18–22G 1.5inch needle. In obese pts, may use angiocath from femoral art line kit.
Purple and green top tube, black top tube (for micro)
• Therapeutic: safe-T-Centesis kit (preferred, pigtail minimizes perforation risk) or paracentesis kit (straight rigid needle), 1L vacuum
bottles, 25% albumin dosed 6-8g per liter of fluid removed if >5L (Hepatology 2021;74:1014)
SITE SELECTION/POSITIONING
• Position patient supine, turned slightly toward the side of the paracentesis, and angled upright at 30°
• Use abdominal probe to identify fluid pocket ≥2-3cm in all dimensions by rotating/fanning probe to ensure
absence of bowel loops. Simulate planned angle of needle insertion with probe. Measure subcutaneous
tissue and fluid pocket.
• Avoid superficial veins or prior surgical incisions and use vascular probe with Doppler to avoid SQ vessels 1 2 1
• Approaches:
o LLQ > RLQ (1): most commonly used; LLQ risk of bowel perf, use caution if pt with splenomegaly;
avoid inferior epigastric vessels that run along lateral borders of rectus muscles
Infraumbilical (2): midline, 2cm below umbilicus; must be certain to differentiate urine in bladder from intra-
abdominal free fluid (in practice, rarely used) Approaches
INSTRUCTIONS
1. Identify best site with abdominal/curvilinear US probe and mark site with pen or round base of needle; avoid applying excess pressure
to ensure accurate pocket size is visualized. Use vascular/linear US probe with doppler to ensure no blood vessels in identified site.
2. Open sterile OR towels package. Use light blue covering as sterile field to drop sterile supplies. Don PPE (gloves, mask, bouffant cap)
& clean skin vigorously with chlorhexidine. Create sterile field over patient with OR towels or open kit and use dressing provided.
3. Anesthetize overlying skin using ~0.5cc lidocaine (SQ 25G needle) to make a wheal. For LVP, use 1.5 inch 20-22G to anesthetize
deeper tissues with lidocaine in 10cc syringe. Use Z-line technique (below) and aspirate while advancing needle. Once ascitic fluid
begins to fill syringe, stop advancing the needle & inject remainder of lidocaine to anesthetize the highly sensitive parietal peritoneum.
Z-line technique: Reduces risk of ascites leak by using skin as Therapeutic paracentesis instructions
barrier. With non-dominant hand, pull skin ~2cm caudad to deep a) Prepare Safe-T-Centesis kit: place catheter on needle,
abdominal wall while para needle is being slowly inserted. attach syringe, and prep tubing
b) Use scalpel to make small superficial incision (enlarge PRN)
Diagnostic paracentesis instructions c) Advance needle/catheter while pulling back on syringe until
a) Insert 20G two-way (pink) angiocath through wheal at same ascitic fluid return is visualized, then advance 0.5 cm
angle as US probe and advance until slightly past when flash seen d) Advance catheter until hubbed (only with Safe-T Centesis
b) Advance the catheter without moving the needle kit!), hold rigid needle in place
c) Retract needle, attach 60cc syringe, and fill syringe e) Retract needle, attach 60cc syringe for dx sample PRN
d) Withdraw the catheter and apply pressure with sterile gauze f) Connect tubing to catheter and puncture vacuum bottles
e) Apply dressing using folded gauze under Tegaderm g) Withdraw catheter and apply gauze/Tegaderm dressing
f) Attach 18G needle to 60cc syringe and fill diagnostic tubes h) Give 25% albumin (6-8g/L removed) if ≥5L removed
D I A G N O S T I C A S S A Y S : (see Fluid Analysis for interpretation)
Tube Lab Tests
Green top Chem Fluid albumin (send serum albumin to calculate SAAG), fluid total protein
Purple top Heme Fluid cell count
Blood culture bottles Micro Can send for aerobic & anaerobic fluid culture, clean top with alcohol and inoculate at bedside for max yield
Black top Micro Gram stain and culture plates
Other tests to consider: glucose, amylase, LDH, bilirubin, triglyceride, AFB smear, mycobacterial culture, adenosine deaminase, pH, cytology

COMPLICATIONS
• Flow stops/slows: roll patient slightly to side of para, rotate catheter, slightly withdraw catheter, flush catheter, new vacuum container
• Flash of blood in catheter: use vascular probe to avoid SQ vessels  withdraw, apply pressure, & insert new catheter at different site
• BRB return: injury to mesentery or inferior epigastrics  stop, assess for hematoma w/ US, IR or surgery consult if HD unstable
• Hypotension: likely vasovagal or fluid shift (>1500cc tap)  Trendelenburg, hydrate, and consider 25% albumin
• Bowel perforation: may lead to polymicrobial bacterascites/sepsis  surgery consult for potential laparotomy
• Fluid leak: prevent with Z-line technique or up-front dermabond  apply pressure dressing, seal w/ Dermabond or single stitch

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Procedures Lumbar Puncture

INDICATIONS
Diagnostic: suspicion for CNS infection (most common), CNS malignancy/mets, SAH, CNS demyelinating/inflammatory process, or ICP
Therapeutic: idiopathic intracranial hypertension, NPH, ICP in cryptococcal meningitis, intrathecal meds/chemotherapy/anesthesia
Contraindications: no absolute contraindications; high risk if skin infection over puncture site, epidural abscess, ICP 2/2 mass lesion or
obstruction (risk of brain herniation), spinal cord tumor or AVM, thrombocytopenia (<50K) or coagulopathy (INR>1.5) of any etiology
Preparation:
• Time frame needed to hold AC prior to LP: IV heparin (4-6h, PTT<35), LMWH therapeutic (24h), LMWH ppx (12h), plavix (5-7d),
DOAC (3d), warfarin (3d, goal INR <1.5). OK to proceed if on SQ heparin daily dose <10,000U, ASA, or NSAIDS. If urgent: weigh
risks and benefits. For details (including when to restart AC): Ellucid
• Head CT: only obtain if ≥1 of the following: age >60, hx CNS disease, seizure <7d ago, immunocompromised, AMS, aphasia,
cranial nerve deficit. If none of these, then 97% NPV for no mass lesion risking herniation (NEJM 2001;345:1727)

T E C H N I Q U E (Video: NEJM 2006;355:e12)

Equipment: LP kit, sterile towels, sterile gloves, face shield, pillows to position patient
• LP kit: 1% lidocaine (25G needle, 5cc syringe), sterile drape, iodine/chlorhex, 20-22G needle/stylet, 4 collection tubes, manometer
Positioning: proper positioning is the key to a successful and smooth LP!
• Use L4–L5 (level of iliac crests), L5–S1, or L3–L4 interspaces (conus
medullaris at L1–L2).
• Lateral (if opening pressure needed): place pt in fetal position (maximize neck
and hip flexion), no hip/shoulder rotation; keep back parallel to edge of bed
• Upright (easier): sit on bed, head/arms rest on table, spine flexed
• To identify target: place a hand on each iliac crest, mark where thumbs
meet at midline or draw line between crests. Confirm location by palpating
spinous processes above/below. Ensure needle midline before inserting
• Sitting while performing LP is often easier than standing, as the needle is in your line of sight
Protocol: (JAMA 2006;296:2012)
1) Prep: sterilize and drape widely. Re-identify target with palpation (betadine will make this easier). Make lidocaine wheal w/ 25G, then
inject track (aspiration before injecting, goal is not spinal anesthesia). Keep CSF collection tubes in order nearby. If checking
pressure, have manometer connected and ready
2) Tap: check needle/stylet mobility. Bevel should face ceiling when pt is lateral. Needle angles slightly toward the head (as if aiming for
umbilicus), straight at the back. Stabilize with your hand against the skin and advance with your dominant hand. Remove stylet
frequently to check for CSF flow but always keep stylet in place when advancing or withdrawing
3) Troubleshoot: if hitting bone, partially withdraw (needle shouldn’t leave skin), adjust angle, re-advance. Try space below if no luck.
If patient has pain, DO NOT withdraw  ASK “where?” If pain is shooting down the left side, withdraw slightly and go slightly more to
the patient’s right. If hitting bone early, more likely to be superior or inferior; if hitting bone late, more likely to be too lateral
4) Measure opening pressure: once flow is established, remove stylet and connect manometer to measure opening pressure (must be in
lateral decubitus position). Pt must extend legs to obtain accurate pressure. If performing therapeutic LP, drain until pressure normal
5) Collect: collect CSF tubes 1 to 4; if flow slows, try rotating needle or minimally advancing or withdrawing with stylet in place
6) Finish: re-insert stylet prior to needle removal (associated w/ post-LP headache)

*If unable to obtain LP (ie overnight) and suspicion for meningitis is high, empirically treat while awaiting diagnostic study*

D I A G N O S T I C A S S A Y S (see Fluid Analysis)

Tube Lab Tests
1 (1mL) Heme CSF cell count
2 (1mL) Chem Total protein, glucose
3 (3-5+ mL, depending Gram stain/Cx. Consider: HSV PCR, VZV PCR, CrAg, viral Cx, AFB stain, VDRL. Ask lab
Micro
on # of tests) to save extra CSF. If you need flow cytometry, DO NOT FREEZE CSF!
4 (1mL) Heme CSF cell count (should have fewer RBCs than tube 1 unless hemorrhage)
Additional tests: cytology & flow cytometry (meningeal carcinomatosis), oligoclonal bands (MS), paraneoplastic Abs, 14–3–3 & RT-
QuIC (prion dz); can collect extra black top tubes for these purposes; if c/f prion dz: contact materials management for instruction on
special disposal of materials (highly contagious!)

COMPLICATIONS
Cerebral herniation (acute AMS, Immediately replace stylet and do not drain more CSF beyond what is in manometer. STAT
fixed pupils, BP, brady, arrest) consult NSGY and treat with ICP-lowering agents (e.g. mannitol)
Shooting pains during procedure usually transient. Withdraw slightly and adjust position away from
Nerve root injury
direction of pain. Consider dexamethasone if pain is persistent
Post-LP headache (10-30% Onset 72h, lasts 3-14d. Give fluids, caffeine, and pain meds. No evidence for bed rest. If
incidence; likely 2/2 dural leak) persistent, c/s anesthesia for epidural blood patch (65-98% success, often quick relief)
Spinal hematoma Suspect if on AC w/ persistent back pain or neuro sx  STAT MRI  IV dex + NSGY c/s

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Procedures Thoracentesis
INDICATIONS
Diagnostic: to establish etiology of ≥1cm pleural effusion visualized by US (not necessary for small effusions w/ probable alternative dx)
• pleural effusions are visible on CXR when >200mL of fluid is present (i.e. lower sensitivity)
Therapeutic: large effusions  resp compromise or sx (e.g., dyspnea), hemothorax, empyema, complicated parapneumonic effusion
Relative Contraindications: no absolute (Chest 2013;144:456)
• Consider reversing coagulopathy (INR >1.5, recent LMWH) or thrombocytopenia (plt <50k), but no data to support
• Skin infection (cellulitis or herpes zoster) over site of entry risk of pleural space infection
• Positive pressure ventilation risk of PTX by 1-7% (Crit Care 2011;15:R46). US guidance associated with lower risk.

PREPARATION
• Materials: skin cleansing agent, gauze, sterile gloves/drape, hemostat, 1-2% lidocaine, 10cc syringe with 22 & 25G needle,
thoracentesis kit with 18-20G over-the-needle catheter, 60cc syringe, 3-way stopcock, drainage tubing, specimen tube, evacuation
container, occlusive dressing
• At MGH: IP (p23710), Pulmonary, or IR perform thoracentesis (not AMPS). Attending MUST be present for bedside thoracentesis

T E C H N I Q U E (Video: NEJM 2006;355:e16)

• Position: patient at edge of bed, leaning forward with arms resting on table
• Identify: height of effusion determined by auscultation & percussion of chest
wall. Use US to confirm location of effusion
o Mark 5-10cm lateral to spine & 1-2 ICS below effusion meniscus.
Lowest level recommended is 8th ICS (above diaphragm)
o In patients who cannot sit upright  mid-axillary approach (patient
supine) or posterior axillary with patient lateral decubitus
• Prep & drape: set up thoracentesis kit, put on sterile gown and gloves,
sterilize patient w/ chlorhexidine, then drape
• Using 25G needle, place wheal 1% lidocaine over superior edge of the rib
• Using 22G needle, walk needle over superior aspect of the rib while
intermittently aspirating and injecting perpendicular to the pleural space
• When pleural fluid aspirated, withdraw slightly then anesthetize the parietal
pleura (highly sensitive) w/ 2-3cc of lidocaine. Note penetration depth
• Attach 18G over-the-needle catheter to syringe & advance over superior
aspect of the rib, pulling back plunger while advancing
• When fluid aspirated, stop advancing & guide plastic catheter over needle
Catheter has valve preventing fluid or air from entering the pleural space,
so may use both hands to prepare for your next step
• Attach 60cc syringe to 3-way stopcock connected to catheter, withdraw full
syringe of fluid, and put in appropriate tubes for lab & micro studies
• Attach tubing to 3-way stopcock, affixing longer tube to large evacuation
container & shorter tube to the syringe. Tubing is all one-way
• Aspirate fluid slowly into the syringe and inject back into bag, never fully
empty the syringe as it can lead to difficulty on repeat aspiration. Stop if:
patient experiences chest pain, dyspnea, cough. Do not remove more than
1.5L fluid as risk of post-expansion pulm edema
• When done, withdraw catheter while patient is humming (to avoid air entry into pleural space); cover site with occlusive dressing
• Obtain post-procedure CXR to assess for pneumothorax or hemothorax

D I A G N O S T I C A S S A Y S (see Fluid Analysis for interpretation)

• Send fluid for: TP, LDH, chol, glucose, pH, cell count, Gram stain/Cx, anaerobic Cx, fungal wet prep w/ Cx
• Consider: TG (chylothorax), Cr (urinothorax), amylase (pancreatitis, esophageal rupture), ADA (TB), AFB Cx, modified AFB Cx, cytology

COMPLICATIONS
1. Hemothorax/intercostal vessel injury: risk if inferior approach to rib or elderly (tortuous vessels). CXR, H&H. Consider chest tube
2. PTX: 5-20% risk; most can be monitored with serial CXR; monitor for signs of tension PTX and obtain STAT expiratory CXR; if PTX is
large or patient is symptomatic and/or in distress  STAT page IP for bedside needle decompression with 16G angiocath at 5th ICS mid-
axillary line (always above nipple). A chest tube is indicated in 20% of cases  consult IP or thoracic surgery
3. Vasovagal syncope/pleural shock: caused by needle penetrating parietal pleura. Tx: Supportive care
4. Re-expansion pulmonary edema: to avoid, stop thoracentesis if cough, CP, or dyspnea occurs. Limit volume removal to <1.5L. Do
not attach to vacuum. Remove fluid slowly without excessive negative pressure. Tx: O2, diuretics, and/or BiPAP

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Procedures Pericardial Drain

INDICATIONS
• Pericardial effusion with tamponade physiology (or at high risk for development of tamponade physiology)
• Diagnostic or palliative drain of stable pericardial effusion
R E L A T I V E C O N T R A I N D I C A T I O N S : no absolute contraindications
• Coagulopathy: INR>1.7, platelets<20, PTT>60 or on heparin gtt. Consider FFP/platelets when on call for procedure
• Effusion associated with aortic dissection or myocardial rupture, as decompression could lead to extension of injury
• Effusion associated with severe pHTN (controversial), as decompression could lead to RV dilation and acute RV failure /
hemodynamic collapse (Pulm Circ 2013;3:467)

M A N A G E M E N T O V E R V I E W : if in doubt about management, page the Cardiology team that placed the drain
• Pericardiocentesis does not completely evacuate a pericardial effusion. A pericardial pigtail catheter is often left in for 24-
72h to allow for serial drainage, preventing re-accumulation and repeat pericardiocentesis
• Frequency of drainage depends on chronicity and size of the effusion, usually q6-q12h. Recommendations are often
found in the report from the cath lab when the drain was initially placed. Typically space out as output decreases.
• Post-procedural antibiotic prophylaxis not indicated per MGH guidelines (MGH peri-procedural abx guidelines)
• Monitor effusion resolution and recurrent tamponade. Check serial hemodynamics/pulsus paradoxus.
• If >100cc output/d for 3d s/p placement, aggressive tx may be indicated (e.g. pericardial window, sclerosing agents, etc.)
• Consider removal of pericardial drain if <50cc output over 24h. Limited TTE. Remove with cardiology fellow/attending
present

MATERIALS
• Sterile technique: sterile gloves, mask, hat
• Identify assistant (must be MD, NP, or PA)
• Sterile towels
• Chlorhexidine swabs (at least 3)
• 60cc Leur lock (screw-on) syringe (x2-3 if high output)
• New blue cap for 3-way stopcock
Heparin (10U/mL) pre-mixed syringe (in MICU/CCU/SDU med rooms)
T E C H N I Q U E : mask and hat required (gown is optional)
1. Open sterile towel wrap carefully. Open supplies onto sterile field. Don sterile gloves
2. Ask assistant to lift the catheter off the skin (holding end of port). Place sterile OR towels around and underneath
pericardial drain. Sterilize distal exposed catheter and stopcock with chlorhex swab. Once finished, hold the recently
sterilized area and take catheter from assistant to sterilize remaining distal portion. Once fully sterilized, lay the catheter
down on the sterile field of blue OR towels.
3. Ensure the stopcock is turned towards the patient. This means the catheter line is closed.
4. Remove and throw away one blue cap (does not matter which). There will be one capped tip and one open tip
5. Sterilize open stopcock tip with iodine or chlorhex swab
6. Hold up flush port for the assistant to connect heparin syringe (syringe itself is not sterile) to open/sterilized tip. Turn
stopcock toward the remaining capped valve (opens flush port/catheter), and assistant will infuse 2cc heparin
7. Turn stopcock towards the patient, remove (do not discard) heparin syringe, and connect 60cc Luer lock syringe
8. Turn stopcock to the remaining capped valve and slowly withdraw pericardial fluid. Gently pull back on syringe, but
may require significant neg pressure. Consider different patient positions (Trendelenburg, lateral decubitus, etc.) to
mobilize fluid. Patient may experience chest discomfort. Monitor hemodynamics and telemetry
9. Can stop draining once fluid flow diminishes/ceases/severe pain. Turn stopcock towards patient then remove syringe
10. Save/transfer pericardial fluid if needed for analysis. Otherwise discard
11. Repeat step 6 (flush port with another 2cc heparin). Turn stopcock to the patient (to close catheter)
12. Remove heparin syringe and attach new sterile blue cap to open flush port
13. Consider re-sterilizing distal exposed catheter and stopcock with chlorhex swab
14. Write a procedure note. Be sure to deduct the 4cc infused heparin (2cc from prior drainage, 2cc from current drainage)
when calculating amount of fluid removed

F L U I D S T U D I E S : typically not needed routine, serial drainage

• Gram stain and bacterial/fungal culture
• Specific viral studies/PCR
• Cytology
• AFB stain, mycobacterial culture, adenosine deaminase, IFN-gamma, or lysozyme (if considering TB pericarditis)
• Protein, LDH, glucose, red/white cell count are not helpful for fluid characterization

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Procedures Fluid Analysis

LUMBAR PUNCTURE INTERPRETATION
Pressure Predominant cell Glucose
Condition WBC/mL Protein (mg/dL) Further CSF Testing
(cm H2O) type (mg/dL)
Normal 9–18 0–5 Lymph 50–75 15–40 N/A
Bacterial meningitis 20–50 <100 to >10k >80% PMN <40 100–1000 Cx, Gram stain
Viral meningitis Lymph; early >45; low in HSV/VZV PCR, consider
(Enteroviruses, HSV, 9–20 50–1000 echovirus/HSV can LCM and <200 further viral PCR or Ab if
VZV, arboviruses) have 80% PMN mumps clinical suspicion; d/w ID
Ab testing paired with serum
Lyme meningitis 9–20 10–300 Lymph Normal 50–100
ab
50-300 MTb Cx <60% S n , NAAT not
TB meningitis 18–30 50-300 Lymph <50 >2000 if subarach approved by FDA, discuss w/
block ID
Fungal meningitis 18–30 < 300 Lymph <50 40–300 Fungal wet prep + Cx, d/w ID
Fungal wet prep + Cx, CrAg;
Cryptococcal meningitis 18–30+ 5–500 Lymph <40 >45
d/w ID need for India ink stain
Epidural/Brain abscess 18–30 10–300 Lymph Normal 50–400 Gram stain not sensitive
WBC correction for RBCs (i.e. traumatic tap) = measured WBC – (measured RBC / 500)

PARACENTESIS INTERPRETATION (SEE ASCITES)

⊕ Ascites culture ⊝ Ascites culture
Spontaneous Bacterial Peritonitis (SBP)
PMN ≥250/µL* Culture Negative Neutrocytic Ascites (CNNA)
(Secondary Peritonitis  polymicrobial)
PMN <250/µL Non-neutrocytic Bacterascites (NNBA) Normal
Culture Negative Neutrocytic Ascites (CNNA) : has similar clinical presentation and prognosis as SBP, thus treat for suspected SBP after
diagnostic PMN count without waiting for Cx (ddx: peritoneal carcinomatosis, tuberculosis, pancreatitis)
*Does not apply to PD pts. Effluent fluid WBC >100 w/ >50%PMNs (after >1-2 hr dwell) is concerning (see ellucid for sampling protocol)
Calculations: # of PMNs = Total nucleated cells x % of PMNsz
Correction for RBCs (RBC count >50,000/mm3, seen in “traumatic tap”) = measured PMN – (measured RBC / 250)
Clues for SBP vs. Secondary Peritonitis:
- Runyon’s Criteria: if ≥2 present, suspicion for secondary peritonitis: 1) ascitic total protein >1; 2) ascitic glucose <50; 3) ascitic LDH > ULN
- Fluid CEA >5 or Alk Phos >240 (92% Sn, 88% Sp for secondary peritonitis) (J Hepatol 2001;34;215)
- Consider repeat paracentesis after 48h of antibiotic treatment: if PMN  and only 1 org. on prior culture, likely SBP; if PMN  and
polymicrobial growth on prior culture, then likely secondary peritonitis. Higher risk for secondary peritonitis if recent operation, trauma, or
perforation
SAAG ≥1.1g/dL SAAG <1.1g/dL
(etiology related to portal HTN) (etiology NOT related to portal HTN)
Fluid total protein < 2.5 g/dL Cirrhosis Nephrotic syndrome
Pancreatitis
Heart failure
Fluid total protein ≥ 2.5 g/dL Peritoneal carcinomatosis
Budd-Chiari syndrome
TB
SAAG = Serum Albumin – Ascites Albumin (from samples obtained on the same day)
PLEURAL FLUID INTERPRETATION
Transudate (due to Starling forces) vs. Exudate (due to increased capillary leak) (NEJM 2002;346:1971)
If ≥ 1 of these, fluid is exudate with 98% Sn, 70% Sp:
Light’s Criteria: exudate if ≥1 criteria present (98% Sn, 83% Sp)*
 Pleural fluid protein >2.9, LDH >95, cholesterol >45
1. Pleural fluid protein / serum protein >0.5
More specific criteria for confirming exudate:
2. Pleural fluid LDH / serum LDH >0.6
 Pleural fluid cholesterol >60 (54% Sn, 92% Sp)
3. Pleural fluid LDH >2/3 ULN of serum LDH (i.e. >140)
 Serum albumin – pleural albumin ≤1.2 (87% Sn, 92% Sp)
*Diuretics cause ~25% of transudates to be misclassified as exudates
 Pleural NT-proBNP <2,300pg/mL (>80% Sn, >70% Sp)
• Other tests: adenosine deaminase, amylase, triglyceride, cholesterol, Gram stain/Cx, cell count, IFN-γ, NT-proBNP, pH, tumor markers
• Complicated parapneumonic effusion/empyema = ⊕ Gram stain/Cx/purulent OR pH <7.2 OR glu <60  drainage w/ chest tube

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Procedures Tube Management

NASOGASTRIC TUBES
Indications: Contraindications:
• Decompression of SBO or minimize vomiting in ileus • Head/maxillofacial trauma, basilar skull fracture, or recent
• Enteral feeding/med administration; charcoal admin (OD), oral neurosurgical intervention
contrast or colonoscopy prep (if can’t take PO) • Esophageal stricture or ≥grade 2 varices/recent banding
• Lactulose (hepatic encephalopathy) (if can’t take PO) (discuss w/ GI if uncertainty regarding varices/banding)

Supplies:
• NGT, lubricant/viscous lidocaine (“UroJet”), Chux, emesis basin, cup of water with ice and straw, 60mL syringe, tape
• If NGT needed for decompression: use 14 to 16 Fr Salem sump NGT (larger diameter, clogging)

NGT Placement: TYPES OF NGTs & USES

• Assess patency & symmetry of nares by direct visualization
• Consider topical anesthetic (e.g. 4% lidocaine) pre-treatment • Dobhoff: PO formula, meds
• Position patient in upright “sniffing” position with neck flexed & chin to chest • 14, 16 Fr S-s: decompression
• Estimate distance of NGT insertion by measuring from xiphoid processearlobenose tip
• Apply lubricant/ice to tip of NGT and/or apply viscous lidocaine directly into the nares
• Insert NGT into nares along floor & apply pressure posterior & slightly inferomedial, not upward. Frequently takes troubleshooting.
• After passage of NGT into oropharynx (will feel curve & resistance), have patient swallow water via straw while advancing rapidly
o If patient excessively coughs, gags, has change in voice or dyspnea, or increased resistance, STOP (never force), suspect
improper location (in airway or coiled), & immediately withdraw. Look in posterior oropharynx for coiling
• Advance to predetermined depth. Can insufflate air w/ 60cc syringe while auscultating over stomach for rush of air. May also see
return of gastric contents. Inspect oropharynx to ensure no coiling before securing tube w/ tape or bridle if risk removal (AMS)
• Confirming position: MUST confirm placement with KUB prior to feeding/meds given risk of placement in trachea/lungs.
KUB ideally shows NGT sideport below diaphragm. Optional for KUB if bilious return when NGT for decompression (bile =
stomach)

Dobhoff tube/Enteroflex: thinner, more flexible; more comfortable but risk of placement into lung
• Requires 2-step 2-CXR placement method. Placement at MGH must be supervised by an attending
1. Measure from nose to earlobe to mid-sternum  insert tube this distance  secure  obtain CXR
2. If CXR shows tip (1) past carina & (2) midline  advance into stomach  repeat CXR  remove stylette once confirmed
- Caution: never administer tube feeds or medications prior to confirmation. Dobhoff can pass into mainstem bronchus.

General Troubleshooting:
• If tube coiling repeatedly in oropharynx on insertion, soak tip in ice water to make tube more rigid prior to insertion
• NGT to suction should “sump” – air should audibly enter blue port and exit main port; if not: (1) flush blue port with air (never
fluids), (2) flush main port with water (not NS, does not need to be sterile), (3) aspirate from main port  if not able to withdraw
flush, NGT needs to be advanced vs. withdrawn (KUB can guide)
• To prevent clogging or adherence to gastric wall, NGTs should be flushed with 30cc water & air q8h. If clogged, can try methods to
unclog tube as below in “Gastrostomy Tubes”
• Consider bridling tube if patient is frequently pulling out tube or if experiencing skin breakdown from security sticker. Plan ahead,
as easier to place bridle prior to NG placement. Beware, very uncomfortable for the patient.

Complications ( with longer duration):

• GI: malposition, coiling, knotting anywhere along course of tube, nasal/GI tract perforation. risk acid/stomach content reflux and
aspiration  consider PPI. Chronic suction  gastritis/pressure necrosis: consider removal if grossly bloody
• Pulm: insertion into lung  inadvertent med, contrast, TF administration  PNA, pulm abscess, tracheal perforation, PTX, death
• HEENT: nasal irritation, epistaxis, intracranial placement, skin erosion, sinusitis, alar necrosis, tracheoesophageal fistula/perf

Removal:
If for ileus/SBO, consider removal when passing flatus or resolved n/v. Alternatively, may remove when NGT output <1L over 24h.
Consider clamp trial before removing (clamp 4h, then check residual. Remove if <150cc)
• Remove tape. Flush tube w/ 10mL air or NS. Turn OFF suction & clamp. Fold Chux around tube insertion site. Gently remove tube

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Procedures Tube Management

GASTROSTOMY TUBES
Description: Troubleshooting:
• Clear, soft, graduated tubing held in place • Clogging: only tube feeds & elixir meds should be given through J tube
w/ plastic mushroom-shaped ring/balloon in o Attach 3cc syringe w/ warm H2O to female Leur adaptor. Pulse plunger
stomach (~3cm deeper in obese pts) to force through debris. Flush w/ 30cc warm H2O to ensure not clogged
• May be replaced at bedside after o Can also try Seltzer, ginger ale, Coca-Cola. If persistent, can try
epithelialized track forms (~2-4w; delayed pancrealipase (Viokase) with sodium bicarb
by malnutrition, steroids, • Leaking: retract balloon or mushroom back to skin level; do NOT insert larger
immunosuppression) size tube (can cause stoma to enlarge); call service who placed G tube if
• Gastrojejunostomy (GJ) tubes have 3 persistent
access ports: G tube port, J tube port, & • Migration: can cause n/v (w/ or w/o feeds), dumping syndrome. Confirm
balloon port placement w/ tube injection study (30-60mL gastrograffin f/b KUB)
• Secured with vertical Hollister device • Falling out: replace w/ similar-sized Foley or feeding tube. Obtain tube study
• Venting means access port is attached to a • Local infection: try topical abx ± antifungal before systemic (cephalexin, clinda)
foley bag so contents/gas can flow out as • Granulation tissue: check tube size (not too long or short); tx w/ warm
needed compresses & silver nitrate (w/ barrier cream on surrounding normal skin)

FOLEY CATHETER
Choosing Catheter: (order from Central Supply, ED, or Ellison 6 if not on floor) Special Circumstances:
• Many contain latex, use silicone if allergy; silicone also risk CAUTI Required urology catheter consults at
• 2-way Foleys (drainage & balloon ports): MGH: any patient with an artificial urinary
16F (stock), 12F if stricture, use an ~18Fr coudé if BPH or men >50yo  insert sphincter (AUS – prosthetic sphincter for
curve up toward umbilicus (balloon port points towards sky) – MGH RNs can place men with incontinence), prostatectomy or
coudés other prostate/urethral surgery w/in past 3-
• 3-way Foleys (drainage, balloon, irrigation ports): 20F/22F used for continuous 4mo, known urethral stricture. See hospital
bladder irrigation (CBI) in gross hematuria to minimize intra-vesicular clots policy for full details.
•
Placement: • Troubleshooting:
1. Lay patient flat, prep, hold penis upright (keep on stretch while advancing) • Difficulty in female patient: likely
2. Instill 10cc viscous lidocaine (“UroJet”) or other lubricant syringe into urethra (men) poor positioning. Place sheets under
3. In men, insert catheter to the hub. In women, insert until urine return + 5cm more hips & place pt in Trendelenburg
4. Fill balloon w/ 10cc sterile H2O only if catheter hubbed (in men) and urine return. • Urethral trauma: blood at meatus.
5. If no urine when inserted, can verify position by flushing/aspirating the catheter with Leave catheter in for ~3-5 days
a 50cc catheter-tip syringe (“GU gun”). Inability to aspirate suggests: (ensure balloon is in proper place)
a. Bladder empty and catheter sucking against bladder mucosa (instill 50-100 cc • Foley is leaking:
if patient does not feel like bladder is full and re-aspirate) o Bladder spasms 2/2 infection,
b. Catheter in urethra or false passage (instill 50-100 cc – if catheter is in the mucosal irritation, overactive
urethra, what you flush in may come around catheter but you cannot aspirate) bladder. Start anticholinergic
c. Catheter outside bladder (undermined bladder neck in pt s/p (tolterodine 4mg qd PRN)
prostatectomy/TURP – this is rare) o Foley obstructed 2/2 sediment,
6. If in the bladder, gently withdraw catheter after inflating the balloon until balloon kinked, dome of bladder, clot.
engages the bladder neck Flush catheter & bladder US
7. Secure the catheter with a little slack to the leg (attach it in the inner thigh between o Urethra patulous (women w/
balloon and drainage ports so the catheter can slide down the attachment) chronic indwelling catheters)
8. Don’t forget to reduce foreskin (if not, may cause paraphimosis = urgent problem)
Suprapubic Tubes:
Continuous Bladder Irrigation (CBI): consult Urology to initiate • Many different types although usually
• Indications: gross hematuria (when you cannot see your hand through the foley due a standard Foley catheter
to presence of blood). DO NOT start CBI if urine has clots without manually • Know type & size catheter, who
irrigating the clots out first exchanges, how exchanged, how
• Titrate flow to “fruit punch” colored urine (should be able to see through) frequently
• When d/c’ing, usually start with clamp trial to ensure resolution before removal • First exchange performed by IR.
Subsequent exchanges should be
Bladder Pressure: only done in the ICU performed by RNs. Urology available
Indications: concern for intra-abdominal hypertension (≥12mmHg) or frank abdominal to assist PRN
compartment syndrome (>20mmHg) • If need to reinsert, decompress balloon
1. Ensure patient position correlates between measurements (head position as flat as and remove indwelling SPT tube. Use
possible) and pressure transducer set-up is arranged Foley kit, prep area, apply lubricant to
2. Drain bladder and clamp drainage tube of Foley new tube, insert through tract (may
3. Inject 25cc of NS into drainage port, wait 30-60s (allows detrusor muscle to relax) have to use some force) until urine
4. Connect pressure transducer to aspiration port, measure pressure at end-expiration return, inflate balloon and ensure tube
is mobile, attach to Foley bag
• See hospital policy
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Procedures Tube Management

CHEST TUBES
Indications: drainage of air (PTX), blood (hemothorax), pus (empyema), or lymph (chylothorax)

Chest Tube Logistics:

• Drainage: measured by gradations in 3 columns; if significant drainage, watch for re-expansion pulmonary edema
• Daily CXR while hospitalized until removal
• Suction control: adjusts negative pressure applied to pleural space
o Suction determined by setting on the device [A], NOT at the
wall; if working properly, suction verification window [E] orange
bellows will be at triangle marker
o “Suction” vs “water seal”: if disconnected from wall suction, it
is on water seal (i.e. “to gravity”) and will allow for one-way flow
of air out of chest, [E] orange bellows not expanded

Troubleshooting:
• Air leaks: if bubbles present in the water
seal chamber [C], indicates air in pleural
space. Higher level in chamber, greater
leak. Ask patient to cough to assess for
leak if bubbles are not continuous
o Ddx: air in pleural space (parenchymal
lung injury or bronchopleural fistula) vs
leak in chest tube (check tubing and
connections to Pleur-evac)
o Note: “Tidaling” (movement w/ respiratory variation in water seal chamber) [C] is normal – i.e. not an air leak
• Clogging: look for debris in tube, lack of tidaling, can try “stripping the tube” by compressing it with your fingers while
pulling TOWARDS the drainage system, helpful to have an alcohol prep pad for lubrication, might require tPA
(alteplase) for clot or Pulmozyme (dornase) for fibrinolysis  involve IP/thoracic surgery (whoever placed tube)

Removal:
• General criteria: no active air leak, pt off positive pressure ventilation, <150cc of drainage over 24h
• Steps to removal: place on suction (-40mmHg to -10mmHg)  place on water seal  clamp trial (clamp tube with
hemostat)
o With each step, wait 4h, then obtain CXR to ensure stable or improving PTX
• After stable on clamp trial, tube should be removed during exhalation (patient humming). Large chest tubes often
require surgical knot to close hole covered by occlusive dressing (xeroform, 4x4 gauze, large tegaderm) for 48h

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Procedures Exposures & Needle Sticks

Please follow the steps below IMMEDIATELY in the event of an exposure to bodily fluids while on duty

1. Stop the procedure

2. Immediately clean the affected area
• Sharp stick: wash site immediately with soap/water. Alcohol-based agents are also virucidal to HBV, HCV, HIV
• Splash to open wound: wash site immediately with soap/water
• Splash to eye(s): irrigate liberally for up to 5 minutes
• Notify your department supervisor; the charge nurse is often a very helpful resource
3. Call occupational health (OHS)
• Monday-Friday 7am-5pm call 617-726-2217, located at 165 Charles River Plaza (CRP) Suite 404 (4th floor)
• If outside of normal business hours, page the on-call occupational health provider at p21272 and go to ED
• Have the following information available for the OHS staff member at the time of your call:
o Source patient: name, MRN, DOB, location, MD, diagnosis, known Hx, exposure to HBV/HCV/HIV, meds
o Needle: brand, size, gauge, specific device/kit, device manufacturer, safety design type
4. Test the patient for HBV, HCV, and HIV
• HBV/HCV: one gold top tube
o Order HBsAg and HCV qualitative Ab; if patient known HCV+, also send HCV RNA
o If using paper form (available from OA), mark with BILLING NUMBER CL00009 so pt not charged
• HIV: another gold top tube
o Order HIV 1/2 Ag/Ab (4th generation test)
o By law in Massachusetts (M.G.L. c. 111, §70F), written consent is required to release HIV results to a third party.
In the event of an exposure, since HIV status is being released to the exposed individual, written consent is
assumed to be required
• Send the HIV tube to STAT lab (results ~60min once received), send HBV/HCV tube to standard core lab

If source patient HAS capacity to consent: If source patient DOES NOT have capacity to consent:
1. A valid and invoked health care proxy (you need paperwork!) can
1. Obtain a special HIV occupational exposure sign the occupational exposure consent form OR
consent form/lab requisition from the OA 2. Facility legal staff can assume temporary guardianship
2. Write STAT result in the comment section If the exposure occurs to a member of the primary team, the
3. Have the patient sign, then sign it yourself implication of the law is unclear, as that person is not technically a third
4. Ensure form is marked with BILLING party. Be conservative, obtain written consent anyway. If this is not
NUMBER CL00009 so patient is not charged possible, consider contacting HIV needlesticks fellow (p36222) or the
chief residents for guidance

5. Decide if you will initiate post-exposure prophylaxis (PEP)

***Post-exposure prophylaxis is most effective if started within 1-2 hours of exposure***
• Transmission factors increasing risk: hollow-bore needle, lack of barrier protection/direct skin penetration, depth of
needle penetration, increased amount of blood on the needle
• Starting PEP is recommended if: patient has known HIV or testing is expected to take >2 hours
o M-F 7a-5p, PEP can be obtained at the OHS office. At all other times, you must go to the Emergency
Department (page the on-call OHS provider at p21272 to be fast-tracked in the ED for treatment)
o HIV fellow can be paged to discuss PEP specifics at p36222
PATHOGEN TRANSMISSION RISK POST-EXPOSURE PROPHYLAXIS (PEP)
PEP can vary but usually includes 3 anti-retroviral drugs:
Percutaneous (blood): 0.3% • 2 NRTI tenofovir PLUS emtricitabine AND INSTI raltegravir
Mucocutaneous (blood): 0.09% • 28 days of treatment recommended but optimal length unknown
HIV There has only been 1 • Regimen usually well-tolerated, side effects include:
confirmed case of occupational o Common but mild: n/v/d, fatigue, HA
transmission since 1999 (CDC) o Rare: hepatitis, hyperglycemia, fevers, rash, pancytopenia
• Serial testing at 6w, 12w, and 6mo if patient has HIV
HCV Percutaneous: 1-2% No PEP; serial testing at 4w, 12w, and 6mo if patient has HCV
AHBV Percutaneous: 30% Positive immune titers usually are an employment requirement
Vaccine non-responders should be seen in occupational health

6. Always file a safety report

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Logistics Monitoring & Prophylaxis

C A R D I A C M O N I T O R I N G (MGH Clinical Guidelines for Cardiac Monitoring)
Low Risk Moderate Risk High Risk
• Continuous cardiac monitoring
• Cardiac monitoring for
Monitoring • May be off monitor ONLY in presence • Continuous cardiac monitoring
diagnostic purposes only
of licensed clinical personnel
Pt Location General care unit General care unit Step-down or ICU
• No cardiac monitor • With cardiac monitor • With cardiac monitor
Travel
• Unaccompanied • Accompanied by MD, PA, NP, or RN • Accompanied by MD, PA, NP, or RN
• Typical chest pain syndrome • Early ACS
• Indicated to make dx or guide
• Acute decompensated HF • S/p cardiac arrest
treatment
• Uncontrolled AF • Critical care patients
Example • Post-op AF
• 24 hrs s/p PPM/ICD placement and • Temporary PPM/pacing pads
indications* • Post-stroke AF
not PPM-dependent • s/p PPM/ICD and PPM-dependent
• Routine syncope evaluation
• Suspected cardiogenic syncope • Advanced 2nd deg. HB, complete HB
• Low risk chest pain syndrome
• Actual or risk for QTc prolongation • Unstable arrhythmias
*See 2017 AHA guidelines on ECG monitoring for more detailed indications/monitoring duration (Circ 2017;136:e273). See Telemetry.
O 2 S A T U R A T I O N M O N I T O R I N G (MGH Clinical Guidelines for O2 Saturation Monitoring)
Low Risk Moderate Risk High Risk
• Spot check O2 sats as • Continuous O2 sat monitoring
Monitoring frequently as clinically • May be off monitor ONLY in presence of • Continuous O2 sat monitoring
indicated licensed clinical personnel
Pt Location General care unit General care unit Step-down or ICU
• No O2 sat monitor • With O2 sat monitor • With O2 sat monitor
Travel
• Unaccompanied • Accomp by MD, PA, NP, RN, or RRT • Accompanied by MD, PA, NP, RN, or RRT
• Stable chronic
• Acute respiratory distress
respiratory disease • COPD exacerbation
Example • High-risk airway
• Post-procedure • OSA not on CPAP
Indications • NIPPV or intubation
• Opioid naïve patients • PCA use
• Continuous narcotic infusion
receiving PO narcotics
DVT PROPHYLAXIS
Low Risk Moderate Risk High Risk
• Ambulatory • Major surgery (>45min, not craniotomy,
• Major surgery (craniotomy, ortho, spine, or
• Estimated LOS <48h ortho, spine, or for cancer)
Risk for cancer)
• Not meeting • Acute illness; immobility w/ est. LOS >48h
factors • Critical illness in ICU
moderate- or high-risk • H/o VTE, thrombophilia (incl. hormone tx)
• 2+ moderate risk factors
criteria • Active malignancy
Prophylaxis Ambulation Pharmacologic OR mechanical Pharmacologic AND mechanical (SCDs)
• 30 / 30 / 30 Rule
o Pharmacologic prophylaxis: can be administered if platelets >30K
o Mechanical prophylaxis: SCD boots should not be off the pt for >30% of the day
o Ambulation: pts should ambulate 30min/shift (60min/d)
• Pharmacologic prophylaxis options:
o Enoxaparin (Lovenox): 40mg SC q24h; default in patients with CrCl >30 and BMI <40
o Heparin (UFH): 5,000units SC q8h-q12h; preferred in pts with CrCl <30 or BMI >40; q8h pref. in cancer patients
o Fondaparinux: 2.5mg SC q24h (can be used if concern for HIT)
o Alternatives to UFH during shortage: apixaban 2.5mg PO q12h, rivaroxaban 10mg PO q24h (avoid if CrCl <30)
 Do not use if critically ill (ICU), trauma/spinal cord injury; avoid if recent/high risk for bleeding, anticipated invasive
procedure, GI/GU CA and active intraluminal lesions, Childs B/C cirrhosis or any liver disease with coagulopathy
G I P R O P H Y L A X I S (MGH Stress Ulcer Prophylaxis Guidelines, HCICU)
• Indications (Crit Care Med 2016;44:1395):
o Admitted to ICU AND one of the following: 1) mechanically ventilated >48h, 2) coagulopathy (plt <50, INR >1.5, PTT >2x ULN),
3) GI bleed in the last year, 4) TBI, spinal cord injury, or burns, 5) 2+ of the following: sepsis, occult GIB >6d, steroids >60mg
prednisone daily (or equivalent), ICU LOS >7d
o HCICU Additions: 5) mechanical circulatory support 6) DAPT/triple therapy 7) scheduled NSAIDs 8) Heart and Lung transplant
patients
• Prophylaxis options (PO unless contraindicated): PPI (omeprazole, esomeprazole, pantoprazole) or H2 blocker (famotidine)

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Logistics Peri-Procedural Anticoagulation

GENERAL ANTIPLATELET & ANTICOAGULATION GUIDELINES FOR ELECTIVE PROCEDURES
• ASA: hold for 1 week prior if for primary prevention, continue if for secondary prevention
• P2Y12: hold clopidogrel and ticagrelor 5 days prior; prasugrel 7 days
• Warfarin: hold 5 days prior (see Anticoagulation Management for indications for and guidance on bridging)
• DOAC: hold 1-3 days prior, depending on agent, renal function, & procedural bleeding risk (see below for guidance for Cath Lab & IR)
• Note: NO SGLT2i for 72h prior to cases requiring cardiac anesthesia

CARDIAC CATH LAB ANTICOAGULATION GUIDELINES

Medication Hold Pre-Procedure* Resume Post-Procedure
Therapeutic (>15k U/d): 1h or on call to lab
Heparin 4h after sheath removal; no bolus
Prophylactic: continue
Enoxaparin (Lovenox) Therapeutic (1mg/kg): 24h; Prophylactic (≤60mg/d): 12h Next morning
Bivalirudin 1h or on call to lab 4h after sheath removal; no bolus
Argatroban 1h or on call to lab 4h after sheath removal; no bolus
Dalteparin Therapeutic: 24h; Prophylactic (≤5000 U/d): 12h Next morning
Warfarin 5 days or INR ≤1.8 Night of cath
Apixaban, rivaroxaban,
CrCl ≥30: ≥2 days; CrCl <30: ≥3 days Next morning
edoxaban
Dabigatran CrCl ≥50: ≥2 days; CrCl <50: ≥5 days Next morning
Fondaparinux CrCl ≥50: ≥4 days; CrCl <50: ≥7 days Next morning
*Guidelines for endomyocardial biopsy differ. See MGH Cardiac Cath Lab Anticoagulation Guidelines (Ellucid)

INR Guidelines for Cardiac Catheterization VAD Peri-Procedural Cardiac Catheterization Guidelines
Planned Access Site INR INR goal 1.8-2.5; continue warfarin
Femoral artery or vein ≤ 1.8 PTT goal ≤80; continue UFH pre-, intra-, & post-procedure
Internal jugular vein ≤ 1.8
Radial artery ≤ 2.0 Cangrelor and Antiplatelet Agents
Subclavian vein ≤ 1.5 • See ACS for switching/bridging P2Y12 inhibitors
Brachial or basilic vein ≤ 2.0 • Generally, prasugrel is held on day -7, clopidogrel/ticagrelor on day -5,
Pericardiocentesis ≤ 1.5 & cangrelor is started on day -3. Cangrelor is held 1-6h pre-procedure

IR PROCEDURES
• NPO guidance: NPO (no solid food; ok to take medications with sip of water) for 8h if will receive sedation (e.g. port placement,
biopsies, tube placement) or if a patient-specific need for sedation
• Low bleeding risk procedures: paracentesis, thoracentesis, chest tube, PleurX, PICC placement/exchange/removal, non-tunneled
central catheter, transjugular liver biopsy, IVC filter placement & simple removal, non-vascular catheter/tube exchange, dialysis
access interventions, superficial bx/aspiration (thyroid, LN, breast, superficial bone), embolization for bleeding control
o AC goals: INR <3, plt >20k; if cirrhosis/liver disease: INR <3, plt >20k, fibrinogen >100. No need to hold AC
• High bleeding risk procedures: tunneled central access catheter placement/removal, G- or J-tube placement, nephrostomy tube
placement, biliary interventions, TIPS, solid organ/deep tissue biopsies, LP/spine procedures (Ellucid), arterial
interventions/angiography, intrathoracic venous interventions (SVC/IVC), portal vein interventions, catheter-directed lysis, complex
IVC filter removal
o AC goals: INR <1.8, plt >50k; if cirrhosis/liver disease: INR <2.5, plt >30k, fibrinogen >100. AC management per table below

Medication Hold Pre-Procedure** Resume Post-Procedure

Heparin Therapeutic: 4-6h; Prophylactic: 6h 6-8h
Enoxaparin (Lovenox) Therapeutic: 24h / 2 doses; Prophylactic: 12h / 1 dose 12h
Dalteparin 24h / 1 dose 12h
Fondaparinux CrCl ≥50: 2-3 days; CrCl <50: 3-5 days 24h
Bivalirudin 2-4h 4-6h
Argatroban 2-4h 4-6h
Day after procedure; bridge
Warfarin 5 days or INR ≤1.8
if high-risk
Apixaban, edoxaban CrCl ≥50: ≥2 days / 4 doses; CrCl <50: ≥3 days / 6 doses 24h
Rivaroxaban CrCl ≥30: ≥2 days / 2 doses; CrCl <30: ≥3 days / 3 doses 24h
Dabigatran CrCl ≥50: ≥2 days / 4 doses; CrCl <50: ≥3-4 days / 6-8 doses 24h
**See MGH Interventional Radiology Periprocedural Management (Ellucid)

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Logistics Senior On Encounters

CODES AND RAPID RESPONSES (Consider MGH STAT App and MGH Heart App in Partners App Catalog)

MGH CODE ROLES CODE TASKS Call CODE BLUE (x6-3333, blue button on wall)
- Code leader: Senior On - Access (IV>>IO), Airway Call for defibrillator, backboard, ambu bag
- Code Whisperer: - Backboard Establish monitoring: tele, defib pads, cont O2, BP cuff
AM = Consult SAR - Code status
PM = Units NT - Defibrillator, Drips Compress 2-2.4” deep, 100-120BPM,
- Pulse: SDU JAR - Epi/ECMO/Embolus Early: minimize interruptions & allow full recoil
- Compressions: Interns o page ECMO <10min of coding W/o ETT: 30:2 compressions to mask vent
- Bring Lucas/IO: MICU o Consider tPA (takes 30 min to W/ ETT: ∆ compressors q2min, breaths q6-8s, ETCO2 > 10
Intern prepare) Rhythm check as soon as pads are on
- Family (call HCP) for both witnessed and unwitnessed arrest
NON-SR ON TASKS
- Glucose
- Confirm code status
- Confirm/stop IV infusions LABS TO ORDER Epi: 1mg IV/IO q3-5m Amiodarone (VT/VF): 300150 mg
- Run tele/print strips STAT ABG with K & Hgb, CBC, Post Arrest: Pressors: if bradylevophed, if tachyneo, bring Epi
- Check labs, med list BMP, LFTs, lactate, T&S, coags,
- Notify attending, family fibrinogen, cardiac enzymes IF INTUBATING
Prior intubations, difficult airway?, hemodynamics (RV/LV), aspiration risk
(last meal), x63333 STAT RICU
REVERSIBLE CAUSES (H&Ts)
Hypoxemia, Hypothermia, Hypovolemia, Hypoglycemia,
ECMO FOR CARDIAC ARREST
Consider if possible reversible cause to arrest and ECMO a bridge to
Hemorrhage, Tamponade, Hypoxia, Tension PTX, H+ ion
definitive treatment; at MGH, recommend contacting ECMO team <10
(acidosis), Thrombosis – MI/PE, HypoK, hyperK, Toxin/drugs
minutes from code initiation. STAT page “ECMO Consult MGH.”
CODE/RAPID DATA TO OBTAIN
Preceding events, code status, access, vitals, focused exam, PHONE NUMBERS
POCT glucose, one-liner, PMH, recent procedures, last TTE, run ICU resource RN (x6-6718), Cardiac Access RN (x4-2677), MICU
MAR, infusions, ECG, telemetry, last labs, ABG/VBG Intensivist (p26955), HCICU Intensivist (p29151), RRT/Code x6-3333

SPECIFIC SCENARIOS (see linked pages for details)

ACS HYPOTENSION
ASA 325, heparin, statin, TNG, BB Cardiogenic: MI, ADHF, BB/CCB tox, acute myocarditis, valvular dz (AS)
Serial ECGs, ensure telemetry Distributive: sepsis, anaphylaxis, liver dz, toxin, adrenal insuff, spinal
Cath lab if HD unstable, refractory CP, VT; STEMI: x6-8282 shock, sleeping
Discuss with interventional attending; decides on cath Hypovolemic: bleed, trauma, diuresis, removal w/ HD, insensible losses
Obstructive: PE, tamponade, tension PTX
BRADYCARDIA PULMONARY EMBOLISM
Conduction disease, R-sided MI, vagal, med effect, ICP, Intermediate-High risk: PE w/ abnl VS (↑HR, ↓BP), evidence of R heart
hypothyroidism, hypoxemia strain (TTE, ECG, or +biomarkers), central or saddle PE → PERT x4-7378
Exam: vitals, mentation, pupils, warm/cold Order: TTE, ECG, CBC, coags, lactate, D-dimer, trop, NT-proBNP, T&S
Place pacing pads, establish IV access tPA: Pulse50-100mg/2h | follow w/ heparin gtt when PTT <x2 ULN
- Atropine 0.5-1mg q3-5m, max 3mg (will not help in setting of TNK: Pulseless Weight based: 30-50mg | follow with hep as above
CHB and Mobitz II) C/I: prior ICH, isch. CVA <3mo., active bleed, CNS surg./trauma (<2-3mo)
- Dopamine 5-20mcg/kg/min
- Epinephrine 2-10mcg/min ACUTE HYPOXEMIA
- Isoproterenol 2-10mcg/min aspiration, mucus plug, PNA, pulm. edema, PE, PTX, pleural effusion
- Transcutaneous pacing (midaz/fentanyl or ativan/dilaudid); GASTROINTESTINAL BLEED
turn to PACER → set RATE: 100BPM at first + set OUTPUT: 2 large-bore IV, T&S, IVF, pRBC, IV PPI 40mg. Octreotide 50mcg + CTX if
select 100 at first portal HTN. Correct coagulopathy. RICU if hematemesis
- Transvenous pacing (cards consult)
HYPERCARBIA
TACHYCARDIA RR: sedatives, central sleep apnea, OHS, brainstem stroke, tumor,
Narrow: AVRT/AVNRT, AF/Aflutter, AT, MAT infection, hypothyroidism
Wide: MMVT, PMVT, SVT w/ aberrancy, PPM-mediated VT: OSA, pleural effusion/fibrosis, obesity, kyphosis/scoliosis, abd dist,
Medications PTX, neuropathy, NMJ disorder, myopathy
Narrow/reg: vagal maneuvers; adenosine; IV BB/dilt VD and/or VT: COPD, asthma, OSA, ILD, CHF, PNA, PE
Narrow/irregular: IV BB/dilt, amio (rhythm), digoxin (rate) ALTERED MENTAL STATUS
Wide/reg: CNS: CVA, ICH, sz, infxn, PRES
- Amio: 150mg →1mg/min Metabolic toxins: NH3, CO2, BUN, Na, glucose For seizure: lorazepam
- Lido: 100mg → 50mg q5 x3 1-2 mg/min Exogenous toxins: meds, drugs, w/d 2-4mg IV x2, midazolam
- Procainamide: 20-50mg/min until hypoTN or QRS ↑50% Vitals: HTN/HoTN, hypoglycemia, hypoxemia 10mg IM, or keppra
- Consider adenosine unless WPW Misc: TTP, AI, hypothyroid 20mg/kg
Wide/irregular:
- PMVT: amio, lido; evaluate and treat for ischemia
ANAPHYLAXIS
- Torsades: Mg 2mg, ↑HR (isoproterenol, over-drive pacing) Epi 0.3-0.5 IM (1:1000; 1mg/mL) repeat q3-15min; other agents: benadryl
50mg, methylpred 12mg, aluberol
- AF+WPW: procainamide, ibutilide (1mg)

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Logistics Post-Acute Care

P O S T - A C U T E C A R E : post-hospital care of patients
• Largest source of Medicare regional variation. High cost growth (NEJM 2014;370:689) & risk of readmission (Health Aff
2010;29:57)
• Risk factors for use: living alone, impaired mobility, depression, comorbidity (JAMA Intern Med 2015;175:296)
• Note: do not have capability for rapid diagnostics (CT), procedures, or significant acute issues (hypoxemia, hypotension)
• Rely on Case Management, PT, & OT to help determine who qualifies for each of the below post-discharge destinations

Setting Patients / Avg Therapy /

Description MD
(most to least intensive) Diagnoses LOS Ancillary Services
- Tracheostomy
Long Term Acute Care - RT
High intensity hospital- - Chemotherapy 20+
Hospital Daily MD visits - PT/OT PRN
level care - ≥3d ICU stay days
(LTACH) - HD
required
- Post-stroke
Inpatient Rehabilitation 2-4x/week MD - 3+h of therapy/d
Intensive therapy for - Spinal cord injury 7-21
Facility visits; PM&R (pt must be able to
recovery of function - Specific dx codes days
(IRF, “acute rehab”) presence participate)
required
“Sub-acute” ~1x/week MD
- CHF, PNA, UTI
rehabilitation; visits;
- Generally older - 1-2h of therapy/d
Skilled Nursing Facility looks/feels like nursing 3-21 very limited
patients with (pt must be able to
(SNF) home; must have 3- days capacity for
functional decline / progress)
night hospital stay to management
unsafe at home
qualify under Medicare changes
- Wound care Managed by
Home-based services - IV antibiotics PCP or - 4-8 PT/OT visits
Home Health post-hospitalization or - Post-hospital N/A prescribing - RN visits as
via PCP referral functional decline outpatient needed
- Home safety eval clinician
Home Hospital Alt. Admit Pathway:
Daily through
(Home within ~8 mile Hospital level care
Simple HF, cellulitis, Hospitalist NP/PA visit x1/day,
radius of MGH. Separate at home with daily N/A
UTI, PNA, COPD team RN x2/day
BWH/NWH/Salem labs and daily/BID
(pg 29694)
programs) IV treatments

SPECIAL CASES
• Hospice: see Comfort Focused Care & Hospice
o Criteria: pt must have a terminal illness with prognosis of ≤6mo as certified by a physician. Depending on the hospice
agency, pt may need to forego curative treatments (i.e., chemo, expensive antibiotics, etc.)
o Home hospice: fully funded by Medicare. RNs visit, but patients need full-time caregiver support in the home, which
can be a barrier to home hospice discharge
o Inpatient hospice (SNF or dedicated inpatient hospice facility): room & board (~$400 per day) only covered by
MassHealth, but not other insurers
o GIP (in-hospital hospice care): fully funded by Medicare, patient must qualify
• Long-term care:
o Patients residing in nursing homes with stably poor functional status and who require assistance with ADLs/IADLs,
but do not require post-acute level care
o Private pay or covered by MassHealth, but not funded by Medicare
• Alternative programs: if patient is in Partners ACO, discuss additional home-based care options with case manager

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Logistics Bias, Patient-Directed Discharge, ICE

MANAGING MICROAGGRESSIONS & BIAS
Microaggression: a brief & common indignity (statement, action, or incident) that communicates hostile, derogatory, or negative slights to
target a person or group. Despite the name, “micro” does not speak to the severity of the impact on the target
Bias: an attitude projecting favorable/unfavorable dispositions towards people. Bias/microaggressions can be implicit or explicit
Common examples in medicine: questioning of credentials/abilities, assumption of non-physician status, requests to change providers,
belittling comments, inquiries into racial/ethnic background, inquiries into relationship status/sexual orientation/gender identity, inquiries into
family/pregnancy status, comments on appearance, assumptions of religious affiliation
Upstander: a person who chooses to intervene when witnessing bias/microaggressions
Responding to microaggressions OR bias from patients (JGME 2019;11:371):
1) Prepare before the encounter:
Within your team, talk explicitly about how leadership should address the situation. For example, team leader: “In our two weeks together,
we may encounter a patient who discriminates against one of our team members. It can sometimes feel safer to have the JAR/attending
address the behavior, but I want to empower you all to act if you feel comfortable. What do you think?”
2) During the encounter:
1) Ensure the patient is stable and assess decision making capacity: if unstable, call for help to provide care. If lacks capacity (see
Consent & Capacity), consider redirection. If stable and has capacity, proceed
2) Check your emotions and psychological safety: if you’re not in a space to respond, it is OK to step out, process, ask for support
3) If you respond, address the aggression explicitly: “I’m surprised to hear you say __.” “I’m disappointed you’d say that.” “What do you
mean by that?” “That’s frustrating to hear from a patient.”
4) Align with the patient: “Our team is here to focus on your health.” “We are all here to treat your ___.”
5) Align with your team: “Our team is doing our best to respect you. We ask that you respect Dr. ___/me as well.”
6) Set boundaries: varies by aggression. “I’d ask that you refrain from commenting on ___.” “Please call them/me Dr.___.” “Let’s keep
the focus on you.” “We do not accommodate staff changes based on [race/ethnicity/religion/etc], Dr. __/I will be in charge of your care
today.” “Our institution does not tolerate that behavior/language/etc.”
7) Give space: if patient or team member is unable to continue the encounter, leave the situation with a defined time to come back. “We
are going to give you space for 30 minutes and when we come back, we can focus on your health.”
3) After the encounter:
1) Attend to emotion: if you were the target of the aggression, seek support, debrief however feels right to you. If you were a bystander,
explicitly acknowledge what you witnessed, offer to support your colleague. Support can range from listening to holding their pager so
they can step off the floor to decompress. Ask what they need from you
2) Discuss the encounter: once emotions have been attended to, if the target is willing, discuss as a team how the interaction went. What
went well? What didn’t? What would you do differently next time? Practice future phrasing together
3) Involve others: ensure attending, other providers, and unit-based leadership are aware
4) If the behavior continues: reconvene to discuss next steps as a team (attending, residents, other colleagues)

PATIENT-DIRECTED DISCHARGE (HISTORICALLY KNOWN AS AMA)

All patients have the right to discharge from treatment when they have capacity. It is the duty of the physician to obtain informed
consent of discharge after discussing the risks and benefits to discharging from care. Common reasons why patients request discharge
include: financial concerns, communication issues, insufficient management of pain/cravings/withdrawal, family obligations
Approach to a safe patient-directed discharge (JGIM 2013;28:1657):
1) Is the patient on section 12a or under guardianship? If yes, these patients cannot choose to leave. Involve psychiatry and security as
needed to help the patient stay safely. See Psychiatry: Agitation. If no, proceed
2) Perform a capacity evaluation: see Consent & Capacity. If patient has capacity, proceed
3) Determine why the patient is motivated to leave: acknowledge their reasons for leaving, validate their emotions. Use a harm reduction
lens, negotiate to meet their needs as able. If time allows, involve SW and CM to help brainstorm solutions
4) Discuss risk and benefits of leaving: ask them what they believe are the risks and benefits. Explain your recommendation. Discuss not
only the immediate medical impact of their options, but the impact on their longer-term values/goals
5) Offer alternatives: if the primary recommendation of staying is rejected, offer other reasonable options. Acknowledge this may require
sub-optimal care, for example, admission for IV antibiotics vs PO antibiotics with outpatient follow up or a home visit
6) Summarize recommendations, confirm understanding: Example language: “I understand you’d like to leave the hospital today to ____.
As we have discussed, remaining in the hospital will __*benefits here*___. That is my primary recommendation for you. Another
potential option we discussed is _____. While it is not ideal medically, it is a reasonable option and care should align with your goals.”
7) Confirm contact information and give return precautions: coordinate follow up, remind the pt they are always welcome back for care
8) Complete paperwork: avoid documenting “AMA”  stigmatizing and has no medicolegal benefit (JHM 2017;12:843)

INFORMATION ON IMMIGRATION AND ICE/DHS

When should a patient’s immigrant status be documented in the EHR?
NEVER. EHR can be accessed by law enforcement/immigration officials and used as evidence

What to do if ICE/DHS inquires about a patient?

If an Immigration and Customs Enforcement (ICE) or Department of Homeland Security (DHS) Agent asks for a patient or patient
information, do not provide any information about the patient. Immediately contact your attending and the Partners Office of
General Counsel (available 24/7; during normal business hours, call 857-282-2020. During off hours, call MGH Page Operator)

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Logistics MGH Directory

Main Number
617-726-2000 (MGH prefix: -724, -726, -643)
R ADIOLOGY
Emergency Numbers • Life Images
Senior On (Med Sr)/Bauer Room 3-1388, p22337 o Upload images to LifeImage and Epic: Partners
6-2333: x75360, Applications  Utilities  MGH Upload Image to
ED Triage Sr (ED Sr) Radiology (LifeImage)  Access LifeImage 
p28786
Med Consult Pager (Code Backup) p13480 find exam on CD/DVD  Upload images
RICU Team (intubation), Code Stroke 6-3333 o Send images to MGH PACS: upload to MGH 
857-310-0335, request read
ECMO Consult
p24252 / p29151 o Retrieve images from The Cloud:
SHOCK Consult p11511 ISDrequests.partners.org  file urgent ticket or
STEMI Team (CCL activation) 6-8282 request changes to existing ticket
PERT (massive PE) 4-7378 o Additional information:
Critical Care Consult pg 26955  Urgent reads: contact ISD (p34188, x30003)
IV Nurse (urgent access) 6-3631, p26571  Multiple body parts: interpretations only
ED Radiology (STAT imaging) 6-3050
given for selected body parts
RT (on call) p24225
 Multiple LifeImages of the same body part:
ICU Nursing Supervisor 6-6718, p25213
upload all images  request a read only on
Poison Control (ingestion) 617-232-2120
Pharmacy the most recent
Outpatient pharmacy (fax: 6-3789) 4-3100, pg 38121  Exams will not be read if: requisition was for
Laboratories a different body part than the uploaded
General lab info 4-LABS images; study >6 months old; a more recent
Chemistry/Hematology (Core LifeImage is available; US, fluoroscopy, or
6-2345
Lab)/Toxicology mammography
STAT Chemistry/Hematology 4-7617
Serology 4-7645 Radiology Reading Rooms
Special coagulation 4-2969 Dodd Reception 44212
Blood gas / STAT lab – Bigelow 5 6-3856 Cardiac CT 47132
Blood bank – Bigelow 2 6-3623 Cardiac MRI 66947
Blood bank – Lunder 8-5280 Chest CT 33899
Microbiology – Bigelow 5 6-3613 CXR Inpatient 42051
Micro after hours (blood culture room) 6-7919 CXR Outpatient 62197
Parasitology 6-3861 ED 41533
Virology 6-3820 GI CT 65162
Surgical Pathology – Blake 3 4-1449 GI Fluoro/KUB 32605
Immunopath (Flow, ANCA, EM) 6-8487 GI MR 49919
Cytology / Cytopathology – Warren 1 6-3980 IR (GI & VIR) 34723
Cardiology Studies Mammography 40228
Cath Lab 6-7400 MSK 40516
Echo Lab 6-8871 Neuroradiology 41931
Stress Lab 4-3600 Nuclear Cardiology 43600
Holter Lab 6-7737 Nuclear Medicine 61404
EP Lab 6-5036 PET 66737
Pulmonary Studies Vascular 47115
PFTs – Cox 2 6-1200/3-9680
Sleep Study (inpatient/outpatient) 4-7426 Technologists
GI Studies CT Blake 2 48518
Endoscopy Lab – Blake 4 6-3732 CT ED 66760
Neurology Studies ED Radiology 63050
EEG – Blake 12 6-3640 GI Fluoro 44295
EMG/NCS – Blake 12 6-3644 Mammography 63092
Subspecialties MRI ED 49867
Anticoagulation (AMS) 6-2768 MRI Inpatient 85692
Boston Healthcare for the Homeless 781-221-6565 Nuclear Medicine 68350
Brace Shop (White 10) 6-3248 PET 64209
Mass Eye and Ear Infirmary Scheduling 4XRAY
Page Operator 617-523-7900, 0 US White 2 53074
11th floor (Inpatient) Above plus x2480
MEEI ED (for ENT transfers) 617-573-3431
Interpreter Services
In Person 6-6966, p27403
Phone (Pin 1050) 617-643-3344
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