HANDBOOK

of
INTERNAL MEDICINE

COC(Medicine)
Hospital Authority

9th Edition
2024
 DISCLAIMER

This Handbook has been prepared by the Co-ordinating Committee (COC) in

Internal Medicine, Hospital Authority and contains information and materials
for reference only. All information is compiled with every care that should
have been applied. This Handbook is intended as a general guide and reference
only and not as an authoritative statement of every conceivable step or
circumstance which may or could relate to the diagnosis and management of
medical diseases.

The information provided in this Handbook on how certain problems may be

addressed is prepared generally without considering the specific
circumstances and background of an individual patient.

The Handbook is an organic document constantly maintained by the concerted

efforts from leading specialists and frontline colleagues working in the public
sector. Its contents are edited and revised by section editors when there are
significant changes in management recommendations from major professional
bodies and/or Hospital Authority, within the shortest period whenever
practical. Please refer to the most updated electronic version.

Users of this Handbook should check the correct dosage and usage of
medications as appropriate to the context of an individual patient, including
any allergic history.

The Hospital Authority and the compilers of this Handbook shall not be held
responsible to users of this Handbook on any consequential effects, nor be
liable for any loss or damage howsoever caused.
 PREFACE TO 9TH EDITION

Internal medicine is a specialty that is continuously expanding and evolving.

This edition of the Handbook has included updates and changes in
recommendations and guidelines over the past four years by experts in
respective sub-specialties and general internal medicine.

We are going paperless! We are very pleased to announce that starting with
this edition, we will no longer produce the physical copy pocket-size
Handbook. All of the content will be via the electronic pdf version.

eKG Internal Medicine page:

https://www.ekg.org.hk/html/gateway/neweKG/newsp/h1-im.jsp

HA Intranet:
https://ha.home/ho/coc_intmed/IM_Handbook.pdf

In this 9th edition, various parts have been revised and in particular, we have
added two new sections on Rehabilitation Medicine and Dermatology. We
would like to express our heartfelt gratitude to every contributors and editors
in the review and revision of this edition.

Finally, we would like to thank the Coordinating Committee in Internal

Medicine in the support of the publication of this Handbook.

Dr LEUNG Moon Ho Alexander

Editor-in-Chief of Handbook of Internal Medicine
Chairman of Training Subcommittee (Internal Medicine)
Editorial Board Members
Editor-in-Chief
Dr. LEUNG Moon Ho Alexander

Special Thanks
Dr. WOO Yu Cho

Co-editors
Cardiology
Dr. CHAN Kwok Keung Dr. FONG Yan Hang
Dermatology
Dr. YEUNG Kwok Hung Dr CHEUNG Man Tung Christina
Dr. WONG Sze Man Christina
Endocrinology
Dr. NG Ying Wai Dr. FOK Chun Kit Vincent
Gastroenterology and Hepatology
Dr. KUNG Kam Ngai Dr. YIU Ka Ling
Prof. WONG Wai Sun Vincent Dr. YONG Xern E Jason
Geriatrics Medicine
Dr. KNG Poey Lyn Carolyn Dr. MAK Ka Pui
Haematology
Dr. KWOK Chi Hang Dr. LAM Ching Pong
Dr. CHEUNG Yuk Man Carol
Immunology and Allergy
Dr. LI Hei Philip
Infections
Dr. TSANG Tak Yin Owen Dr. CHIK Shiu Hong
Dr. LAU Pui Ling
Nephrology
Dr. CHAN Yiu Han John Dr. KWOK Lap Ming
Neurology
Dr. CHAN Hiu Fai Germaine Dr. WONG Ho Ming June
Palliative Medicine
Dr. CHAN Kin Sang Dr. HO Jerry
Rehabilitation
Dr. CHU Chun Kwok Angus Dr. LEE Tsz Heung Herman
Respiratory Medicine
Dr. MIU Pui Ling Flora Dr. KWOK Wang Chun
Rheumatology
Dr. HO Tze Kwan Carmen Dr. HO Cheuk Man
Acute Poisoning
Dr. WONG Siu Ming Raymond Dr. CHAN Chun Man Jones
Critical Care Medicine
Dr. NG Wing Yiu George Dr. WONG Sai Kuen Alfred
Medical Oncology
Dr. HUI Ka Eugenie Dr. KWOK Gin Wai
Advanced Internal Medicine
Dr. CHEUNG Ka Man Carmen

Co-ordinating Committee in Internal Medicine

Hospital Authority
 CONTENTS
Cardiology
Cardiopulmonary Resuscitation (CPR) C 1-3
Arrhythmias C 4-11
Unstable Angina / Non-ST Elevation Myocardial Infarction C 12-13
Acute ST Elevation Myocardial Infarction C 14-21
Acute Pulmonary Oedema C 22
Hypertensive Crisis C 23-24
Aortic Dissection C 25-26
Chronic Heart Failure C 27-28
Pulmonary Embolism C 29-30
Cardiac Tamponade C 31-32
Antibiotic Prophylaxis for Infective Endocarditis C 33-34
Perioperative Cardiovascular Evaluation for Non-Cardiac Surgery C 35-41

Dermatology
Autoimmune Bullous Diseases D 1-3
Cutaneous Vasculitis D 4-5
Drug Reaction with Eosinophilia & Systemic Symptoms (DRESS) Syndrome D 6-7
Eczema/ Dermatitis D 8-9
Erythroderma D 10
Psoriasis D 11-12
Stevens-Johnson Syndrome & Toxic Epidermal Necrolysis D 13-17
Topical Corticosteroids (TCS) D 18

Endocrinology
Diabetic Ketoacidosis (DKA) E 1-2
Diabetic Hyperosmolar Hyperglycaemic States E 3
Perioperative Management of Diabetes Mellitus E 4-5
Insulin Therapy for DM Control E 6-7
Hypoglycaemia E 8
Thyroid Storm E 9
Myxoedema Coma E 10
Phaeochromocytoma E 10
Addisonian Crisis E 11-12
Acute Post-operative/Post-traumatic Diabetes Insipidus E 13
Pituitary Apoplexy E 13

Gastroenterology and Hepatology

Acute Liver Failure G 1-4
Hepatic Encephalopathy G 5-6
Ascites G 7
General Guidelines for Consideration of Orthotopic Liver Transplantation G 8-9
(OLT) in Chronic Liver Disease or Hepatocellular Carcinoma
Variceal Haemorrhage G 10-11
Upper Gastrointestinal Bleeding G 12-14
Peptic Ulcers G 15-16
Management of Gastro-oesophageal Reflux Disease (GERD) G 17-18
Inflammatory Bowel Diseases: Overview G 19-22
Crohn’s Disease G 23-25
Ulcerative Colitis G 26-28
Acute Pancreatitis G 29-31
Hepatorenal Syndrome G 32
Pre-emptive use of Nucleos(t)ide Analogues in Patients with Hepatitis B G 33-34
Infection Receiving Immunosuppressive Therapy
Chronic Hepatitis B G 35-37
Incidental Solid Liver Lesions G 38-40
Non-alcoholic Steatohepatitis (NASH) G 41-43
Antibiotics Prophylaxis for GI Endoscopy G 44-45

Geriatric Medicine
Altered Responsiveness or “Decreased GC” Gr 1-2
Assessment of Mental Competence Gr 3
Care of Dying Gr 4-5
Diabetes Mellitus in Old Age G 6-8
Eating or Feeding Problems in Elderly with Advanced Dementia or Severe Gr 9-10
Frailty
Elder Abuse Gr 11-13
Falls Gr 14-16
Frailty and Sarcopenia Gr 17-20
Hypertension in Old Age Gr 21-22
Musculoskeletal Pain Gr 23-24
Neurocognitive Disorder Gr 25-27
Nursing Home-acquired Pneumonia (NHAP) Gr 28-29
Orthostatic Hypotension Gr 30-31
Osteoporosis in Elderly Gr 32-36
Pharmacotherapy in Old Age Gr 37
Post-operative Delirium Gr 38-39
Pressure Ulcers Gr 40-42
Spasticity Gr 43-44
Syncope Gr 45-46
Undernutrition in Older Adults Gr 47-48
Urinary Incontinence Gr 49-51
Urinary Retention Gr 52-54

Haematology
Haematological Malignancies
Leukaemia H 1-2
 Lymphoma H 2-3
Multiple Myeloma H 3-4
Extravasation Of Cytotoxics H 5
Intrathecal Chemotherapy H 5-6
Performance Status H 6
Haematological Toxicity H 6
Non-Malignant Haematological Emergencies / Conditions
Acute Haemolytic Disorders H 7-8
Immune Thrombocytopenic Purpura (ITP) H 9-10
Heparin Induced Thrombocytopenia (HIT) H 10
Thrombotic Thrombocytopenic Purpura (TTP) H 11
Pancytopenia H 11-12
Thrombophilia Screening H 12
Drugs and Blood Products
Anti-emetic Therapy H 13
Immunoglobulin Therapy H 13
rFVIIa (NovoSeven®) H 14
Direct Oral Anticoagulants (DOACs) H 14-15
Replacement for Hereditary Coagulation Disorders H 16-17
Transfusion H 18-21
- Indications – General Guidelines H 18-20
- Management workflow for patients with suspected acute transfusion H 21
reaction

Immunology and Allergy

Anaphylaxis IA 1-3
Drug Allergy IA 4-5
Drug Reaction With Eosinophilia & Systemic Symptoms (DRESS) Syndrome IA 6-9
Penicillin Allergy IA 10-14
Angioedema IA 15-16
Urticaria IA 17-20
Immunodeficiency IA 21-24

Infections
Community-Acquired Pneumonia (CAP) In 1-2
Hospital Acquired Pneumonia (HAP) In 3
Pulmonary Tuberculosis In 4-6
CNS Infections In 7-8
Urinary Tract Infection (UTI) In 9
Enteric Infections In 10-12
Acute Cholangitis In 13
Spontaneous Bacterial Peritonitis In 14
Necrotizing Fasciitis In 15
Guideline for Clinical Management of Skin and Soft Tissue Infection and In 16
Clinical Syndromes Compatible with Staphylococcal Infection
Septic Shock In 17-18
Treatment of Febrile Neutropenia In 19-21
Malaria In 22-23
Chickenpox / Herpes Zoster In 24-25
HIV/AIDS In 26-28
Rickettsial (Spotted Fever, Typhus) and related Infections In 29
Influenza In 30-31
Infection Control In 32-34
Needlestick Injury, Non-intact Skin or Mucosal Contact with Blood and Body In 35-36
Fluids
Middle East Respiratory Syndrome (MERS) In 37-38
Viral Haemorrhagic Fever (VHF) In 39-40
Zika In 41
Dengue In 42-43
COVID-19 In 44-46

Nephrology
Renal Transplant – Donor Recruitment K 1-2
Electrolyte Disorders K 3-16
Systematic Approach to the Analysis of Acid-Base Disorders K 17-20
Peri-operative Management in Uraemic Patients K 21
Renal Failure K 22-24
Emergencies in Renal Transplant Patients K 25
Drug Dosage Adjustment in Renal Failure K 26-27
Protocol for Treatment of CAPD Peritonitis K 28-31
Protocol for Treatment of CAPD Exit Site Infections K 32
Peritoneal Dialysis K 33

Neurology
Coma N 1-3
Delirium N 4-5
Delirium Tremens N 6-8
Wernicke’s Encephalopathy N 9-10
Acute Stroke N 11-15
Subarachnoid Haemorrhage N 16-17
Tonic-Clonic Status Epilepticus N 18-19
Autoimmune Encephalitis N 20-21
Guillain-Barré Syndrome N 22-23
Myasthenic Crisis N 24-25
Acute Spinal Cord Syndrome N 26
Peri-operative Management in Patients with Neurological Diseases N 27-28
Palliative Medicine
Anorexia PM 1-2
Nausea and Vomiting PM 3
Cancer Pain Management PM 4-5
Guidelines on Use of Morphine for Chronic Cancer Pain Control PM 6-7
Dyspnoea PM 8-9
Delirium PM 10-11
Malignant Bowel Obstruction (MBO) PM 12
Treatment of Venous Thromboembolism (VTE) in Patients with Advanced PM 13-14
Cancer
Wish to Hasten Death (WTHD) PM 15-16
Palliative Care Emergencies: Massive Haemorrhage PM 17
Malignant Hypercalcaemia PM 18-19
Metastatic Spinal Cord Compression PM 20-21
Advance Care Planning PM 22-23
Last Days of Life PM 24-26

Rehabilitation
International Classification of Functioning, Disability and Health (ICF) Re 1
Early Mobilisation in Post-acute Illness Patient Re 2-4
Exercise Management in Cardiac Patients Re 5-6
Rehabilitation Intervention in Stroke Patient Re 7-8
Hemiplegic Shoulder Pain Syndrome (HSP) Re 9
Complex Regional Pain Syndrome (CRPS) Re 10-11
Spasticity Management in Stroke Patient Re 12-13
Medical Complication in Spinal Cord Injury Re 14-15
Autonomic Dysreflexia (AD) Re 16-17
Tracheostomy Weaning Re 18
Medical Complications of Amputee Re 19-20
Orthosis – Ankle Foot Orthosis (AFO) Re 21-22
Common Instruments in Rehabilitation Re 23-25

Respiratory Medicine
Massive Haemoptysis P 1
Spontaneous Pneumothorax P 2-3
Pleural Effusion P 4-5
Oxygen Therapy P 6-7
Adult Acute Asthma P 8-9
Long Term Management of Asthma P 10-13
Chronic Obstructive Pulmonary Disease (COPD) P 14-16
Obstructive Sleep Apnoea P 17-18
Preoperative Evaluation of Pulmonary Function for Resection of Lung Cancer P 19
Mechanical Ventilation P 20-21
Non-invasive Ventilation (NIV) P 22-24
Rheumatology
Approach to Inflammatory Arthritis R 1-2
Gouty Arthritis R 3-4
Septic Arthritis R 5-6
Rheumatoid Arthritis R 7-9
Ankylosing Spondylitis R 10-11
Psoriatic Arthritis R 12-13
Systemic Lupus Erythematosus (SLE) R 14-19
Rheumatological Emergencies R 20-22
Non-steroidal Anti-inflammatory Drugs (NSAIDS) R 23-24

General Internal Medicine

Acute Poisoning GM 1-16
Accidental Hypothermia GM 17
Heat Stroke / Exhaustion GM 18
Near Drowning GM 19
Electrical Injury GM 19
Rhabdomyolysis GM 20
Superior Vena Cava Syndrome GM 21
Malignancy-related Superior Vena Cava Syndrome GM 22-23
Neoplastic Spinal Cord / Cauda Equina Compression GM 24
Hypercalcaemia of Malignancy GM 25
Tumour Lysis Syndrome GM 26
Extravasation of Chemotherapeutic Agents GM 27
Cancer Immunotherapy Related Adverse Events (IrAEs) GM 28-30
Brain Death GM 31-33

Procedures
Endotracheal Intubation Pr 1-3
Setting CVP Line Pr 4
Defibrillation Pr 5
Temporary Pacing Pr 6
Lumbar Puncture Pr 7-8
Bone Marrow Aspiration and Trephine Biopsy Pr 9-10
Care of Hickman Catheter Pr 11-12
Renal Biopsy Pr 13
Percutaneous Liver Biopsy Pr 14-15
Abdominal Paracentesis Pr 16
Pleural Aspiration Pr 17
Pleural Biopsy Pr 18
Chest Drain Insertion Pr 19

Acknowledgement
Cardiology
 CARDIOPULMONARY RESUSCITATION (CPR)

Basic Life Support (BLS)

1. Determine unresponsiveness

2. Call for Help, Call for Defibrillator

3. Wear PPE: N95/ surgical mask, gown ± (gloves, goggles, face shield for
high risk patients)

4. Check for breathing and pulse (no more than 10 seconds)

a) No normal breathing, has pulse → provide rescue breathing; 1 breath
every 6 seconds
b) No breathing or gasping, no pulse → Start CPR

C: Circulation with CPR

 Chest compressions at a rate of 100/min to 120/min
 Target compression depth 2-2.4 inches (5-6 cm)
 CPR 30 compressions and 2 breaths

A: Airway
 Clear airway obstruction/secretions
 Head tilt-chin lift or jaw-thrust
 Insert oropharyngeal airway

B: Breathing
 Bag-mask device ventilation with supplementary oxygen (minimum
flow rate of 10 to 12 L/min)
 Tight seal between face and mask
 Cycles of 30 compressions and 2 breaths before advanced airway

D: When defibrillator arrives: check rhythm

 If shockable rhythm (VF/pulseless VT) → given 1 shock (biphasic:
Manufacturer recommendation, if unknown, use maximum available,
e.g. 200J, or monophasic 360J), resume CPR immediately until next
rhythm check or patient moves.
 If non-shockable rhythm → continue CPR


C1
Advanced Cardiovascular Life Support (ACLS)

A: Place airway devices; intubation if skilled.

 If not experienced in intubation, continue bag-mask ventilation and
call for help.

B: Confirm & secure airway; maintain ventilation.

 Confirm correct placement of endotracheal tube by physical
examination (5-point auscultation) and a confirmation device.
 Continuous waveform capnography is recommended in addition to
physical examination.
 Once advanced airway in place, give 1 breath every 6 seconds with
continuous chest compression.

C: Intravenous access; use monitor to identify rhythm.

D: Differential Diagnosis.

Common drugs used in resuscitation

Adrenaline 1 mg (10 ml of 1:10,000 solution) q3–5 min iv

Lignocaine 1 mg/kg iv bolus, repeat 0.5-0.75 mg/kg iv bolus at 5-
10 mins (max. total dose 3 mg/kg) then 1–4 mg/min infusion
Amiodarone In cardiac arrest due to pulseless VT or VF, 300 mg iv
bolus, further doses of 150 mg iv bolus if required
MgSO4 1–2g in 10 ml D5 iv bolus in torsade de pointes

Intravenous or Intraosseous route of drug administration is preferred over

Endotracheal route.
Tracheal administration of Resuscitation Medications (if iv line cannot be
promptly established):
 Lignocaine, Epinephrine (adrenaline), Atropine, Narcan (L-E-A-N)
 Double dosage
 Dilute in 10 ml NS or water
 Put catheter beyond tip of ET tube
 Inject drug solution quickly down ET tube, followed by several quick
insufflations
 Withhold chest compression shortly during these insufflations

C2
Post-resuscitation care with return of spontaneous circulation (ROSC)

 Correct hypoxia with 100% oxygen to maintain oxygen saturation 92% to

98%
 Consider advanced airway and waveform capnography
 Do not hyperventilate
 Treat hypotension with volume expander or vasopressor
 Consider treatable causes
 Initiate targeted temperature management in comatose patients.
 Treat seizure with anticonvulsant (diazepam or phenytoin)

Reference:
2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care

C3
 ARRHYTHMIAS

(I)
Ventricular Fibrillation or
Pulseless Ventricular Tachycardia

Rapid Defibrillation
360J monophasic shock or manufacturer
recommendation (if unknown, use maximum available
e.g. 200J) biphasic shock
CPR for 2 minutes
Then check rhythm

360J monophasic shock or 200J biphasic shock CPR

for 2 minutes
Adrenaline 1 mg iv (10 ml of 1:10,000 solution)
Repeat every 3-5 min
Then check rhythm

360J monophasic shock or 200J biphasic shock

CPR for 2 minutes

Consider antiarrhythmics

 Amiodarone 300 mg iv bolus, can consider a second dose of 150 mg iv

 Lignocaine 1-1.5 mg/kg iv push, can repeat 0.5-0.75 mg/kg at 5-10
minutes
(maximum total dose 3 mg/kg)

C4
(II)

Asystole / Pulseless Electrical Activity (PEA)

BLS and ACLS

CPR
Adrenaline 1 mg iv (10 ml of 1:10,000 solution)
Repeat every 3-5 min

Consider causes (“5H’s and 5T’s”) and give specific treatment

Hypovolaemia Tension pneumothorax

Hypoxia Tamponade, cardiac
Hydrogen ion (acidosis) Toxins
Hyper / hypokalaemia Thrombosis, pulmonary
Hypothermia Thrombosis, coronary

C5
(III)
Tachycardia with a pulse

- Identify and treat underlying cause

- Maintain patient airway, assist breathing as necessary
- Oxygen (if hypoxaemic)
- Cardiac monitor to identify rhythm; monitor blood pressure and
oximetry
- IV access
- 12-Lead ECG

Unstable?
(Hypotension? Acutely altered mental status? Signs of
shock? Ischaemic chest discomfort? Acute heart failure?)

Yes No

Synchronised cardioversion
Manufacturer recommendation
May consider initial doses:
- Narrow regular: 50-100J
- Narrow irregular: 120-200J
- Wide regular: 100J
- Wide irregular: defibrillation
(not synchronised)

❶ Atrial fibrillation ❷ Regular Narrow ❸ Regular Wide

Atrial flutter Complex Tachycardia Complex Tachycardia

 For immediate cardioversion

- Consider sedation
- If repeat cardioversion needed, remember to resynchronise after each
cardioversion.

C6
❶ Atrial fibrillation / Atrial flutter

1. Correct underlying causes

 hypoxia, electrolyte disorders, sepsis, thyrotoxicosis etc.

2. Control of ventricular rate

 Diltiazem 0.25 mg/kg iv bolus over 2 min, then 5-15 mg/hr;
oral maintenance 120-360 mg daily (ER).
 Verapamil 0.075-0.15 mg/kg iv bolus over 2 min, may give
additional 10mg after 30 min if no response, then
0.005 mg/kg/min infusion.
Risk of hypotension, check BP before 2nd dose.
Oral maintenance 180-480 mg daily (ER).
 Metoprolol 2-5 mg iv bolus over 2 min; up to 3 doses; oral
maintenance 25-100 mg BD.
 Amiodarone 300 mg iv over 1 hour, then 10-50 mg/hour over 24
hours; oral maintenance 100-200 mg daily.
 Digoxin 0.25 mg iv with repeat dosing to a maximum of 1.5
mg over 24 hours; oral maintenance 0.125-0.25 mg
daily.

 For WPW syndrome patients with pre-excited AF, consider IV

Procainamide (all A-V nodal blocking agents should be avoided).
 In AF complicating acute illness e.g. thyrotoxicosis, β-blockers and
verapamil may be more effective than digoxin.
 For impaired cardiac function (EF <40%, CHF), use digoxin or
amiodarone.

3. Anticoagulation
Prompt anticoagulation can be achieved with unfractionated heparin with
maintenance of aPTT 1.5-2 times control or low molecular weight heparin.
Long-term anticoagulation can be achieved with warfarin with
maintenance of PT 2-3 times control (depends on CHA2DS2-VASc Score,
general condition, compliance of patient and underlying heart disease) or
DOAC like Dabigatran, Rivaroxaban, Apixaban or Edoxaban.

4. Termination of Arrhythmia
 For persistent AF, anticoagulated for 3 weeks before conversion and
continue for 4 weeks after (delayed cardioversion approach).

C7
  Pharmacological conversion:
Amiodarone 150 mg over 10 min then 1 mg/min for 6 hr
then 0.5 mg/min for 18 hr or orally 600-800
mg daily in divided doses up to 10 g, then 200
mg daily as maintenance dose.
Flecainide 200-300 mg orally, preferably given beta-
blocker or non-dihydropyridine calcium
channel antagonist ≥30 minutes beforehand
Propafenone 450-600 mg orally, preferably given beta-
blocker or non-dihydropyridine calcium
channel antagonist ≥30 minutes beforehand

Procainamide 15 mg/kg iv loading at 20 mg/min (max 1 g),

then 2-6 mg/min iv maintenance,
or 250 mg po q4h
 Synchronised DC cardioversion
- Atrial fibrillation 120-200J and up
- Atrial flutter 50-100J and up

5. Prevention of Recurrence
 Class Ia, Ic, sotalol, amiodarone or dronedarone.

C8
❷ Stable Regular Narrow Complex Tachycardia

Vagal Manoeuvres *

#
ATP 10 mg rapid iv push

ATP 20 mg rapid iv push

(may repeat once in 1-2 mins)

Blood pressure
Normal or Elevated
Low

Verapamil 2.5-5 mg iv Synchronised DC

15-30 mins Cardioversion
- start with 50J
Verapamil 5-10 mg iv
- increase by 50-100 J increments

Consider
- digoxin
- β-blocker
- diltiazem
- amiodarone

* Carotid sinus pressure is C/I in patients with carotid bruits. Avoid ice water
immersion in patients with IHD.
# contraindicated in asthma & warn patient of transient flushing and chest
discomfort.

C9
❸ Stable Wide Complex Tachycardia

Attempt to establish a specific diagnosis

Confirmed SVT Unknown type Confirmed VT

# Preserved
EF <40%,
ATP 10 mg rapid iv push cardiac
CHF
1-2 mins function

ATP 20 mg rapid iv push

Preserved EF <40%, Amiodarone Amiodarone

cardiac function CHF or or
lignocaine lignocaine,
or then
Sotalol cardioversion
Amiodarone Amiodarone or
or then Procainamide
Sotalol cardioversion
or
Procainamide

Dosing:
 Amiodarone 150 mg IV over 10 mins, repeat 150 mg IV over 10 mins if
needed. Then infuse 600-1200 mg/d (Max 2.2 g in 24 hours).
 Procainamide infusion 20-30 mg/min till max. total 17 mg/kg or
hypotension.
 Lignocaine 0.5-0.75 mg/kg IV push and repeat every 5-10 mins, then
infuse 1-4 mg/min (Max. total dose 3 mg/kg).

# contraindicated in asthma & warn patient of transient flushing and chest

discomfort.

C 10
(IV) Bradycardia with pulse

- Identify and treat underlying cause.

- Maintain patient airway, assist breathing as necessary.
- Oxygen (if hypoxemic).
- Cardiac monitor to identify rhythm; monitor blood pressure and
oximetry.
- IV access.
- 12-lead ECG if available; but don’t delay therapy.

Unstable?
(Hypotension? Acutely altered mental status? Signs of shock?
Ischaemic chest discomfort? Acute heart failure?
No Yes

Atropine *
Monitor and observe First dose: 1 mg bolus
Repeat every 3-5 minutes
Maximum: 3 mg
If atropine ineffective:
 Transcutaneous pacing (TCP)#
 Dopamine infusion (usual infusion rate: 5-20 microgram/kg/min)
 Adrenaline infusion (usual infusion rate: 2-10 microgram/min)

Consider: Cardiac consultation and transvenous pacing.

Remarks:
*Avoid relying on atropine in type II second-degree or third-degree AV block or
in patients with third-degree AV block with a new wide-QRS complex where the
location of block is likely to be in non-nodal tissue (such as in the bundle of His
or more distal conduction system). These bradyarrhythmias are not likely to be
responsive to reversal of cholinergic effects by atropine and are preferably
treated with TCP or β-adrenergic support as temporising measures while the
patient is prepared for transvenous pacing.

# Verify patient tolerance and mechanical capture. Analgesia and sedation prn.

C 11
 UNSTABLE ANGINA / NON-ST ELEVATION
MYOCARDIAL INFARCTION

Aims of Treatment: Relieve symptoms, monitor for complications, improve

long-term prognosis.

Mx:
1. Admit CCU for very high risk / high risk cases*.
2. Bed rest with continuous ECG monitoring.
3. ECG stat and repeat at least daily for 3 days (more frequently in severe cases
to look for evolution to MI).
4. Serial cardiac injury markers (CK-MB, hs-troponin: Consider ESC Rapid
“rule-in” and “rule-out” algorithms using hs-troponin: the 0h/1h algorithm
(blood draw at 0h and 1hr).
5. CXR, CBP, R/LFT, lipid profile (within 24 hours), aPTT, INR as baseline
for heparin Rx.
6. Allay anxiety – Explain nature of disease to patient.
7. Morphine IV when symptoms are not immediately relived by nitrate e.g.
Morphine 2-5 mg iv (monitor BP).
8. Correct any precipitating factors (anaemia, hypoxia, tachyarrhythmia).
9. Stool softener.
10. Supplemental oxygen for hypoxia (SaO2<90%).
11. Consult cardiologist to consider urgent coronary angiogram
/revascularisation, mechanical circulatory support if refractory to medical
therapy or develop shock.

Specific drug treatment:

Antithrombotic Therapy
a) Aspirin 160-320 mg loading, then 80-100 mg daily.
b) Clopidogrel 300-600 mg stat, then 75 mg daily OR
Ticagrelor 180 mg stat, then 90 mg BD
c) Low-Molecular-Weight-Heparin e.g.
Enoxaparin (Clexane) 1 mg/kg sc q12h
Nadroparin (Fraxiparine) sc 0.4 ml BD if <50 kg BW,
0.5 ml BD if 50-59 kg BW, 0.6 ml BD if >60 kg BW.

Anti-Ischaemic Therapy
a) Nitrates
 Reduces preload by venous or capacitance vessel dilatation.
 Contraindicated if sildenafil taken in preceding 24 hours.
 Sublingual TNG 1 tab/puff Q5 min for 3 doses for patients with ongoing
C 12
 ischaemic discomfort.
 IV TNG indicated in the first 48 h for persistent ischemia, heart failure,
or hypertension.
 Isosorbide dinitrate (Isoket) 2-10 mg/hr intravenously.
- Begin with lowest dose, step up till pain is relieved.
- Watch BP/P; keep SBP >100 mmHg
 Isosorbide dinitrate – Isordil 10-30 mg TDS
 Isosorbide mononitrate – Elantan 20-40 mg BD or
Imdur 60-120 mg daily

b) β-blockers (if not contraindicated)

 Reduce HR and BP (titrate to HR <70)

Other Therapies
a) Hydroxymethyl glutaryl-coenzyme A reductase inhibitor (statin)
 Should be given regardless of baseline LDL-C level in the absence of
contraindications.

b) Angiotensin-converting enzyme inhibitor (ACEI)

 Should be administered within the first 24 hours if LVEF <40% and in
the absence of hypotension or contraindications.
 Angiotensin receptor blocker should be used if patient is intolerant of
ACEI.

c) Proton pump inhibitors for patients at high risk of GI bleeding.

*Very high risk/high risk features (Consult Cardiologists)

 Haemodynamically instability
 Cardiogenic shock, acute heart failure
 Recurrent/refractory chest pain despite medical treatment
 Life-threatening arrhythmias
 Established NSTEMI diagnosis
 Dynamic new or presumably new contiguous ST/T segment changes
 GRACE risk score >140 (https://www.mdcalc.com/calc/1099/grace-acs-risk-mortality-calculator)

Reference:
1. Byrne RA et al. 2023 ESC Guidelines for the management of acute coronary syndromes. European
Heart Journal 2023; 44:3720-3826.
2. Collet JP et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients
presenting without persistent ST-segment elevation. European Heart Journal 2021, 42: 1289-1367.
3. Amsterdam EA et al. 2014 AHA/ACC guideline for the management of patients with non-ST
elevation acute coronary syndromes. JACC 2014;64(24):e139-228.

C 13
 ACUTE ST ELEVATION
MYOCARDIAL INFARCTION

Ix – Serial ECG for 3 days

 Repeat more frequently if only subtle change on 1st ECG; or
when patient complains of chest pain

Area of Infarct Leads with ECG changes

inferior II, III, aVF
lateral I, aVL, V6
anteroseptal V1, V2, V3
anterolateral V4, V5, V6
anterior V1 – V6
right ventricular V3R, V4R

 Serial cardiac injury markers (CK-MB, hs-troponin)

 CXR, CBP, R/LFT, lipid profile, HbA1c, FG (within 24 hours)
 aPTT, INR as baseline for thrombolytic Rx

General Mx
 Arrange CCU bed
 Close monitoring: BP/P, I/O q1h, cardiac monitor
 Complete bed rest (for 12-24 hours if uncomplicated)
 O2 by nasal prongs if hypoxic with arterial oxygen saturation (SaO2) <90%;
routine oxygen is not recommended if SaO2 >90%
 Allay anxiety by explanation /sedation
 Stool softener
 Adequate analgesics prn e.g. morphine 2 mg iv (monitor BP & RR)

C 14
Specific Rx Protocol

Prolong ischaemic-type chest discomfort

Aspirin 160-320 mg loading, 80-100 mg daily

ECG

ST elevation1 or new LBBB ST depression ± T inversion

B-Blocker (if not contraindicated)2

Refer to NSTEMI
+ P2Y12 inhibitors3

≤ 12 hour > 12 hour

Eligible for Eligible for Not for Persistent

primary PCI fibrinolytic reperfusion Rx5 Symptoms9

Fibrinolytic No Yes
Primary PCI
therapy4
according to
according to
protocol of
protocol of
individual centre
individual centre
Consider coronary
angiogram ± PCI

Other medical therapy

(ACEI6 + statin LMWH7 Nitrate8)

C 15
1 New ST elevation at the J-point in at least two contiguous leads: ≥2.5 mm
in men <40 years, ≥2 mm in men ≥40 years, or ≥1.5 mm in women
regardless of age in leads V2–V3 and/or ≥1 mm in the other leads (in the
absence of left ventricular [LV] hypertrophy or left bundle branch block
[LBBB]).
2 e.g. Metoprolol 25 mg bd orally if not in decompensated heart failure state.
Consider Bisoprolol, Carvedilol, Metoprolol succinate if LVEF is reduced
when out of decompensated heart failure.
3 For primary PCI, give:
 Clopidogrel loading 600 mg, 75 mg daily maintenance, OR
 Prasugrel loading 60 mg, 10 mg daily maintenance, OR
 Ticagrelor loading 180 mg, 90 mg BD maintenance
For fibrinolytic therapy, give:
 Clopidogrel loading 300 mg, then 75 mg daily maintenance for age ≤
75; and no loading dose for age > 75
4 See “Fibrinolytic therapy” (C19)
5 Not for reperfusion Rx if e.g. too old, poor premorbid state, etc.
6 Starting within the first 24 hrs if not contraindicated, esp. for anterior
infarction or clinical heart failure. Thereafter, prescribe for those with
clinical heart failure or EF < 40%, (starting doses of ACEI: e.g. Acertil 1
mg daily; Ramipril 1.25 mg daily; Lisinopril 2.5 mg daily)
7 For fibrinolytic therapy, if age <75, Enoxaparin 30 mg iv bolus, followed
in 15 min by 1mg/kg sc Q12H; if age ≥75, no loading dose, 0.75 mg/kg sc
Q12H; give up to 8 days or until revascularization.
 For patient undergo PCI, LMWH may not be required.
 For patient not eligible for reperfusion Rx, decision for LMWH
depends on underlying conditions and bleeding risk.
8 Prescribe if persistent chest pain / heart failure / hypertension
e.g. iv isosorbide dinitrate (Nitropohl/Isoket) 2-10 mg/h. (Titrate dosage
until pain is relieved; monitor BP/P, watch out for hypotension,
bradycardia or excessive tachycardia). C/I if sildenafil taken in past 24
hours.
9 Consider mechanical circulatory support ± PCI if haemodynamic
instability or recurrent symptomatic arrhythmia.

C 16
Detection and Treatment of Complications
a) Arrhythmia
 Symptomatic sinus bradycardia
- Atropine 1mg iv bolus
- Pacing if unresponsive to atropine
 AV Block:
- 1st degree and Mobitz type I 2nd degree: Conservative
- Mobitz Type II 2nd degree or 3rd degree: Pacing
(inferior MI, if narrow-QRS escape rhythm & adequate rate,
conservative Rx under careful monitoring is an alternative)
Other indications for temporary pacing:
 Bifascicular block + 1st degree AV block
 RBBB + alternating LAFB/LPFB
 Alternating LBBB + RBBB
 Tachyarrhythmia
(Always consider cardioversion first if haemodynamic compromise or
intractable ischaemia)
PSVT
- ATP 10-20 mg iv bolus
- Verapamil 5-15 mg iv slowly (C/I if BP low or on beta-blocker or
reduced LVEF), beware of post-conversion angina
Atrial flutter/fibrillation
- Digoxin 0.25 mg iv/po stat, then 0.25 mg po q8H for 2 more doses
as loading, maintenance 0.0625-0.25 mg daily
- Diltiazem 5-15 mg iv over 5-10 mins, then 5-15 μg/kg/min
- Amiodarone 5 mg/kg iv infusion over 60 mins as loading,
maintenance 600-900 mg infusion/ 24 h
Wide Complex Tachycardia (VT or aberrant conduction) Treat as VT
until proven otherwise.

Stable sustained monomorphic VT:

- Amiodarone 150 mg infused over 10 minutes, repeat 150 mg iv
over 10 mins if needed, then 600-1200 mg infusion over 24 h.
- Lignocaine 1 mg/kg iv bolus, then 1-4 mg/min infusion.
- Procainamide 20-30 mg/min loading, then 1-4 mg/min infusion
up to 12-17 mg/kg.
- Synchronised cardioversion starting with 100 J.
Sustained polymorphic VT:
- Unsynchronised cardioversion starting with 200 J.

C 17
b) Pump Failure
LV Dysfunction
 Vasodilators (esp. ACEI) if BP OK (± PCWP monitoring)
 Inotropic agents
- Preferably via a central vein
- Titrate dose against BP/P & clinical state every 15 mins initially,
then hourly if stable.
- Start with dopamine 2.5 μg/kg/min if SBP ≤ 90 mmHg, increase
by increments of 0.5 μg/kg/min.
- Consider dobutamine 5-15 μg/kg/min when high dose dopamine
needed.
 Consider mechanical circulatory support and catheterisaton ±
revascularization.

RV Dysfunction
 Consider Swan-Ganz catheter to monitor haemodynamics. If PCWP
low or normal, consider volume expansion with colloids or
crystalloids.
 Consider mechanical circulatory support in refractory cases.

c) Mechanical Complications
 VSD, mitral regurgitation.
 Mx depends on clinical and haemodynamic status.
- Observe if stable (repair later)
- Emergency cardiac catheterisation and repair if unstable, may
require mechanical circulatory support)

d) Pericarditis
 Need to differentiate post-cardiac injury syndrome (Dressler’s
syndrome) from peri-infarct pericarditis.
 High dose aspirin with colchicine or NSAID with colchicine for post-
cardiac injury syndrome (but not peri-infarct pericarditis).
 Colchicine 0.5 mg daily PO (< 70kg) or 0.5 mg BD PO (> 70kg)
 Others: paracetamol

After Care (For uncomplicated MI)

 Advise on risk factor modification and treatment (Smoking, HT, DM,
hyperlipidaemia, exercise)

C 18
 Consider coro ± PCI early if successful thrombolytic therapy
 Drugs for Secondary Prevention of MI
- Β-blocker
- Aspirin 80-100 mg
- ACEI (esp. for large anterior MI, recurrent MI, impaired LV systolic
function of CHF) e.g. Lisinopril 5-20 mg daily; Ramipril 2.5-10 mg
daily; Acertil 2-8 mg daily.
- Angiotensin receptor blocker should be used in patients intolerant of
ACEI and have heart failure of LVEF ≤ 40% or hypertension.
- Consider switching to ARNI if persistent heart failure symptoms
despite ACEI/ ARB in patient with reduce LVEF. Stop ACEI 36 hours
before initiate ARNI.
- Aldosterone blocker should be used in patients without significant
renal dysfunction or hyperkalaemia and who are already on therapeutic
doses of ACEI and beta-blocker, with LVEF ≤ 40% + diabetes or heart
failure.
- Statin should be used in all patients unless contraindicated.
- Consider SGLT2 inhibitor in heart failure.
- Consider double antiplatelet therapy in post PCI patient or medically
treated patients for a period of time.

Fibrinolytic Therapy
Contraindications
Absolute: - Previous haemorrhagic stroke at any time, other strokes or
CVA within 3 months; except acute ischaemic stroke within
4.5 hours.
- Known malignant intracranial neoplasm (primary or
metastatic).
- Known structural cerebrovascular lesion (e.g. AV
malformation)
- Active bleeding or bleeding diathesis (does not include
menses).
- Suspected aortic dissection.
- Significant closed head or facial trauma within 3 months.
- Intracranial or intraspinal surgery within 2 months.
- Severe uncontrolled hypertension (unresponsive to
emergency therapy).
- For Streptokinase, prior treatment within previous 6 months.

C 19
Relative: - Severe uncontrolled hypertension on presentation (blood
pressure >180/110 mmHg) §
- History of chronic, severe, poorly controlled hypertension.
- History of prior ischaemic stoke >3 months or known
intracerebral pathology not covered in absolute
contraindications.
- Traumatic or prolonged (>10 min) CPR.
- Oral anticoagulant therapy.
- Major surgery < 3 weeks.
- Non-compressible vascular punctures.
- Recent (within 2-4 weeks) internal bleeding.
- Pregnancy.
- Active peptic ulcer.
§ Could be an absolute contraindication in low-risk patients with myocardial
infarction.

Choice of fibrinolytic therapy

 TNK-tPA iv bolus, 30 mg (< 60 kg), 35 mg (60-69 kg), 40 mg (70-79 kg),
45 mg (80-89 kg), 50 mg (≥ 90 kg) §
 tPA 15 mg iv bolus, then 0.75 mg/kg (max 50 mg) in 30 mins, then 0.5
mg/kg (max 35 mg) over 1 hr.

§ For age ≥ 75, half dose of weight-based iv bolus of TNK.

Remarks: After clinical assessment, full dose TNK may be considered if

indicated.

Monitoring
 Use iv catheter with obturator in contralateral arm for blood taking.
 Pre-Rx: Full-lead ECG, INR, aPTT, cardiac enzymes.
 Repeat ECG 1. when new rhythm detected and
2. when pain subsided
3. 90 minutes after thrombolytic therapy
 Monitor BP closely and watch out for bleeding
 Avoid percutaneous puncture and IMI.
 If hypotension develops during infusion
- Withhold infusion.
- Check for cause (treatment-related* vs cardiogenic**)
C 20
 * fluid replacement; resume infusion at ½ rate
** consider rescue PCI ± mechanical circulatory support

Signs of Reperfusion
 Chest pain subsides
 Early CPK peak
 Accelerated nodal or idioventricular rhythm
 Resolution of ST elevation of at least 50% in the worst ECG lead at 60-90
minutes after fibrinolytic.

Failed Reperfusion by fibrinolytic

 Need to consider rescue PCI

Reference:
1. Byrne RA et al. 2023 ESC Guidelines for the management of acute coronary
syndromes. European Heart Journal 2023; 44:3720-3826.
2. Ibanez B et al. 2017 ESC guidelines for the management of acute myocardial
infarction in patients presenting with ST-segment elevation. Eur Heart J
2018;39(2):119- 177

C 21
 ACUTE PULMONARY OEDEMA

Acute Management:

General measures Identify and treat

1. Complete bed rest, prop up precipitating causes.
2. Oxygen (may require high flow rate / e.g. arrhythmia, IHD,
concentration) uncontrolled HT, chest
3. Low salt diet + fluid restriction (NPO if infection.
very ill)

BP Stable?

Yes No
BP
stabilised
Medications (commonly considered) Medications (others)
1. Frusemide (Lasix) 40-120 mg iv Inotropic agents
2. IV nitrate e.g. GTN 1 μg/kg/min - Dopamine
3. Morphine 2-5 mg slow iv 2.5-10 μg/kg/min
- Dobutamine
2.5-15 μg/kg/min

Unsatisfactory
response

BP not stabilised or
APO refractory to Rx
Monitor BP/P, I/O, SaO2, CVP, RR
clinical status every 30-60 mins

Consider:
Consider ventilatory support in case of 1. Mechanical circulatory
desaturation, patient exhaustion, support
cardiogenic shock. 2. PCI for ischaemic cause of
1. Intubation and mechanical ventilation CHF
2. Non-invasive ventilation: BIPAP/CPAP 3. Intervention for significant
valvular lesion

C 22
 HYPERTENSIVE CRISIS

Hypertensive emergency
 Severe elevation in BP (>180/120 mmHg) associated with evidence of new
or worsening target organ damage e.g. hypertensive encephalopathy, acute
MI, acute LV failure with pulmonary oedema, unstable angina pectoris,
dissecting aortic aneurysm, acute renal failure, eclampsia (acute ICH and
acute ischaemic stroke not discussed here).
 Admit to ICU/CCU with continuous BP monitor.
 With a compelling condition (i.e. aortic dissection, severe preeclampsia or
eclampsia, or phaeochromocytoma crisis), reduce SBP to <140 mmHg
during the first hour and to <120 mmHg in aortic dissection.
 Without a compelling condition, reduce SBP by no more than 25% within
the first hour; then, if stable, to 160/100 mmHg within the next 2-6 hours;
then cautiously to normal during the following 24-48 hours.

Intravenous medications for Hypertensive emergency

 Labetalol 20 mg iv bolus, followed by 20 to 80 mg every 10 minutes (up
to max total dose of 300 mg) if BP uncontrolled, then 0.5-2 mg/min
infusion in D5, some patients may require titration up to 10 mg/min for
optimal response.
 Na Nitroprusside
- Starting dose 0.25-0.5 microgram/kg/min, increase every 5 mins by 0.5
microgram/kg/min, max dose 10 microgram/kg/min.
- Use with caution in patient with renal impairment, limit infusion rate
to < 3 microgram/kg/min if eGFR < 30 ml/minute/1.73m2.
- High dose (e.g. 8-10 microgram/kg/min) should only be used for the
shortest duration possible to avoid toxicity.
- Protect from light by wrapping. Discard after every 12 hrs.
- Especially good for acute LV failure, rapid onset of action. Do not give
in pregnancy or for > 48 hrs (risk of thiocyanide intoxication).
 Hydralazine 10-20 mg slow iv over 20 mins, repeat every 4-6 hours as
needed (avoid in AMI, dissecting aneurysm). Hydralazine is generally not
recommended as first line agent due to unpredictable and prolonged
antihypertensive effect.
 Phentolamine 5-10 mg iv bolus, repeat 10-20 mins PRN (for
catecholamine crisis).

C 23
Notes on specific clinical conditions
 APO – Nitroprusside/nitro-glycerine + loop diuretic, avoid diazoxide /
hydralazine (increase cardiac work) or Labetalol & Beta-blocker in LV
dysfunction.
 Angina pectoris or AMI – Nitroglycerin, nitroprusside, labetalol, calcium
blocker. (Diazoxide or hydralazine contraindicated)
 Increase in sympathetic activity (clonidine withdrawal,
phaeochromocytoma, autonomic dysfunction (GB Syndrome / post spinal
cord injury), sympathomimetic drugs (phenylpropanolamine, cocaine,
amphetamines, MAOI or phencyclidine + tyramine containing foods) →
Phentolamine, labetalol or nitroprusside. Beta-blocker is contraindicated
(further rise in BP due to unopposed alpha-adrenergic vasoconstriction).
 Aortic dissection – aim: ↓systolic pressure to 100-120 mmHg and
↓cardiac contractility, nitroprusside + labetalol / propranolol IV.
 Pregnancy – IV hydralazine (pre-eclampsia or pre-existent HT),
Nicardipine / labetalol, no Nitroprusside (cyanide intoxication) or ACEI.

Look for causes of HT crisis, e.g. renal artery stenosis.

Hypertensive urgency
 Severe BP elevation in stable patients without acute or impending change
in target organ damage of dysfunction.
 Many of these patients have withdrawn or are non-compliant with anti-HT
therapy; treatment by reinstitution or intensification of anti-HT drugs.

Reference:
1. Whelton PK, et al. 2017 ACC/AHA Guideline for the prevention, detection, evaluation,
and management of high blood pressure in adult. JACC,
doi:10.1016/j.jacc.2017.11.006
2. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task
Force for the management of arterial hypertension of the European Society of
Cardiology (ESC) and the European Society of Hypertension (ESH), European Heart
Journal, Volume 39, Issue 33, 01 September 2018, Pages 3021–3104

C 24
 AORTIC DISSECTION

Suspect in patients with chest, back or abdominal pain and presence of unequal
pulses (may be absent) or acute AR.

Dx - CXR, ECG, Cardiac enzymes

- Transthoracic (not sensitive) ± Transoesophageal echo
- Urgent Dynamic CT scan, MRA & rarely aortogram

Mx
1. NPO, complete bed rest, iv line.
2. Oxygen, to keep SaO2 ≥ 90%
3. Analgesics, e.g. morphine iv 2-5 mg
4. Book CCU or ICU bed for intensive monitoring of BP/P (Arterial line on
the arm with higher BP), ECG & I/O.
5. Look for life-threatening complication – severe HT, cardiac tamponade,
massive haemorrhage, severe AR, myocardial, CNS or renal ischaemia.
6. Medical Management
 To stabilise the dissection, prevent rupture, and minimise complication
from dissection propagation.
 It should be initiated even before the results of confirmatory imaging
studies available.
 Therapeutic goals: reduction of systolic blood pressure to 100-120
mmHg (mean 60-75 mmHg), and target heart rate of 60-70/min.

Intravenous Labetalol
 Labetalol 20 mg iv, followed by additional doses of 20-80 mg every 10
mins (up to max total dose of 300 mg).
 Maintenance infusion: then 0.5-2 mg/min infusion in D5, some patients
may require titration up to 10 mg/min for optimal response.

Intravenous sodium nitroprusside

 Starting dose 0.25-0.5 microgram/kg/min, increase every 5 mins by 0.5
microgram/kg/min, max dose 10 microgram/kg/min.
 Use with caution in patient with renal impairment, limit infusion rate to
< 3 microgram/kg/min if eGFR < 30 ml/min/1.73m2.
 High dose (e.g. 8-10 microgram/kg/min) should only be used for the
shortest duration possible to avoid toxicity.
 Nitroprusside should not be used if heart rate is not controlled, as

C 25
 vasodilatation can lead to reflex tachycardia.
 Diltiazem and verapamil are acceptable alternatives when beta-blockers
are contraindicated (e.g. COAD)
(Avoid hydralazine or diazoxide as they produce reflex stimulation of
ventricle and increase rate of rise of aortic pressure).

7. Start oral treatment unless surgery is considered.

8. Contact cardiothoracic surgeon for all proximal dissection (Type A) and

complicated distal dissection (Type B), e.g. shock, renal artery involvement,
haemoperitoneum, limbs or visceral ischaemia, periaortic or mediastinal
haematoma or haemoperitoneum, persistent or recurrent pain, progression
of dissection. (Endovascular stent graft is an evolving technique in
complicated type B dissection with high surgical risk).

9. Other acute aortic syndrome, e.g. intramural haematoma, penetrating aortic

ulcer should be managed as a classical case of dissection.

C 26
 CHRONIC HEART FAILURE

Classification of HF by Left Ventricular Ejection Fraction (LVEF)

 HFrEF (HF with reduced EF): LVEF ≤ 40%.
 HFimpEF (HF with improved EF): previous LVEF ≤ 40% and a follow-up
measurement of LVEF >40%.
 HFmrEF (HF with mildly reduced EF): LVEF 41-49%.
 HFpEF (HF with preserved EF): LVEF ≥ 50% and evidence of spontaneous or
provokable increased LV filling pressures (e.g., elevated natriuretic peptide,
non-invasive and invasive hemodynamic measurement).

Investigations
Initial investigations
 Blood tests
- CBC, LFT, RFT, clotting profile, TFT, cardiac biomarkers (troponin, CK),
iron profile.
- Natriuretic peptides (NPs) level: <35 pg/mL or NT-proBNP <125 pg/mL →
unlikely HF.
 ECG
 CXR
 Echocardiography

Investigations to determine the underlying etiology

 CMR: recommended for assessment of myocardial structure and function, as
well as characterization of myocardial tissue in suspected infiltrative diseases
and cardiomyopathies.
 Non-invasive testing
- CTCA: considered in patients with low-intermediate pre-test probability of
CAD or those with equivocal non-invasive tests to rule out CAD.
- Non-invasive stress imaging (CMR, stress echocardiography, SPECT, PET):
considered for assessment of myocardial ischemia and viability in patients
with CAD who are considered suitable for coronary revascularization.
 Cardiopulmonary exercise testing: recommended as a part of the evaluation for
heart transplantation and/or MCS; considered to identify the cause of
unexplained dyspnoea and/or exercise intolerance
 Right heart catheterisation: recommended in patients with severe HF being
evaluated for heart transplant or MCS.
 Endomyocardial biopsy (EMB): considered in patients with rapidly progressive
HF despite standard therapy when there is a probability of a specific diagnosis
which can be confirmed only in myocardial samples.
 Invasive coronary angiography
 Genetic evaluation and testing
C 27
Management
HFrEF
 Guideline Directed Medical Therapy (GDMT) – titrate to target dosing as
tolerated.
- ACE-I or ARB; ARNi (A washout period of at least 36 hours after ACEI is
required in order to minimise the risk of angioedema caused by overlapping
ACE and neprilysin inhibition)
- Beta blockers i.e. Bisoprolol, Carvedilol, Metoprolol succinate
- MRA
- SGLT2i
 Diuretics for volume overload
 Additional therapies once GDMT optimised
- Ivabradine: NYHA II-III; HFrEF; normal sinus rhythm, HR ≥70 bpm; on
maximally tolerated beta blocker.
- Vericiguat: NYHA II-IV; LVEF <45%; recent heart failure hospitalization;
or IV diuretics; elevated NP levels.
- Digoxin: symptomatic HFrEF
- Ferric carboxymaltose: iron deficiency
- AF ablation: AF patients when tachycardia-induced cardiomyopathy is
highly probable and selected AF patients with HFrEF.
 Device therapies
- ICD: NYHA I-III; LVEF ≤ 35%; >1 year survival
- CRT-D: NYHA II-III; ambulatory IV; LVEF ≤ 35%; normal sinus rhythm
and QRS ≥150 ms or LBBB with QRS 130-149 ms.
 Selected advanced HF patients
- Heart transplantation
- MCS

HFmrEF and HFpEF

 Diuretics for volume overload
 SGLT2i
 Other medications to be considered: ACE-I or ARB; ARNi; MRA
 Treat underlying etiologies

References
1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the
Management of Heart Failure: A Report of the American College of Cardiology/American
Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.
2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012
2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and
treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.
doi:10.1093/eurheartj/ehab368

C 28
 PULMONARY EMBOLISM

Investigations
 Clotting time, INR, aPTT, Cardiac enzymes, ABG, D-dimer.
 CXR (usually normal, pleural effusion, focal oligaemia, peripheral wedge)
ECG (sinus tachycardia, S1Q3T3, RBBB, RAD, P pulmonale)
 TTE +/- TEE; lower limb Doppler (up to 50% -ve in PE)
 CT pulmonary angiography (CTPA) or Spiral CT scan (sensitivity 91%,
specificity 78%).
 Ventilation-Perfusion scan (if high probability: sensitivity 41%, specificity
97%).
 Use of clinical scores to guide investigations according to probability of
PE, e.g. Revised Geneva Score / Wells score.

Risk Stratification
 Initial stratification is based on clinical symptoms and signs of
haemodynamic instability.
 Signs of haemodynamic instability indicated high risk of early death.
 In patients without haemodynamic instability further risk stratification
includes:
- PE severity according to clinical imaging and laboratory indicates:
 RV dysfunction on TTE/CTPA
 Increased troponin
- Presence of comorbidities can be assessed by PESI score (Pulmonary
embolism severity index).

Treatment
1. Oxygen, to keep SaO2 ≥ 90%
2. Analgesics e.g. morphine iv 2-5 mg.
3. a) Haemodynamically insignificant
 Anticoagulation
 LMWH, e.g. enoxaparin 1 mg/kg q12H (CrCl > 30 ml/min) is preferred
over unfractionated heparin.
Unfractionated heparin can be considered for patients with severe renal
failure (CrCl < 30 ml/min), or patients with high likelihood that acute
reversal of anticoagulation will be needed (procedure or thrombolysis
is being considered), or patients suspected to have poor subcutaneous
absorption (obesity or oedema). 5000 units IV bolus, then 500-1500
units/hr to keep aPTT 1.5-2.5 × control
C 29
  DOAC has been demonstrated to be non-inferior compared with
combination of LMWH and warfarin for the prevention of symptomatic
PE or lethal VTE recurrence, with significantly reduced rates of major
bleeding.

Dabigatran: At least 5 days of a parenteral anticoagulant,

then start 150 mg bd.
Rivaroxaban: For initial therapy or transition from
parenteral anticoagulant: 15 mg bd for 21 days
then 20 mg daily.
Apixaban: For initial therapy or transition from
parenteral anticoagulant: 10 mg bd for 7 days
then 5 mg bd.
Edoxaban: At least 5 days of a parenteral anticoagulant,
then start 60 mg daily.

 When warfarin is used, LMWH should be continued in parallel with

warfarin until INR 2-3 is reached.

b) Haemodynamically significant (no C/I to thrombolytic)

 Book ICU/CCU
 Supportive treatment including cautious IV fluids, vasopressors and
mechanical support, e.g. extracorporeal membrane oxygenation
(ECMO).
 Systemic thrombolysis: rtPA 100 mg IV over 2 hours followed by
heparin infusion 500-1500 units/hr to keep aPTT 1.5-2.5 × control or
refer to local protocol for fibrinolytic treatment.
 Consider surgical embolectomy or percutaneous catheter-directed
treatment (e.g. catheter directed lysis/mechanical thrombectomy) if
condition continues to deteriorate or contraindication to thrombolytic
therapy.

4. Consider IVC filter if PE occurred while on adequate anticoagulation or

who have absolute contraindications to anticoagulation.

C 30
 CARDIAC TAMPONADE

Definition: Cardiac tamponade is defined as a pericardial effusion compression

one or more cardiac chambers and leading to haemodynamic compromise. In
acute conditions, the pericardium cannot distend, and its pressure rises markedly
with small volume changes. This explains how tamponade develops with a small
acute effusion (~200 mL).

Common causes:
 Neoplastic
 Pericarditis (infective or non-infective)
 Uraemia
 Iatrogenic (e.g. cardiac instrumentation)
 Traumatic
 Acute pericarditis treated with anticoagulants
 Idiopathic

Diagnosis: Cardiac tamponade is a clinical diagnosis, i.e. it is diagnosed when a

pericardial effusion is associated with haemodynamic compromise.

Signs & symptoms:

 Tachypnoea, tachycardia, small pulse volume, pulsus paradoxus.
 Raised JVP with prominent x descent, Kussmaul’s sign.
 Absent apex impulse, faint heart sound, hypotension, clear chest.

Investigations:
1. ECG: Low voltage, tachycardia, electrical alternans.
2. CXR: enlarged heart silhouette (when >250 ml), clear lung fields.
3. Echo: RA, RV or LA collapse, distended IVC, exaggerated tricuspid flow
increases & mitral flow decreases during inspiration.

Management:
1. Expand intravascular volume – D5 or NS or plasma, full rate if in shock.
2. Positive pressure mechanical ventilation should be avoided, if possible,
because the positive thoracic pressures can further impair cardiac filling.
3. Pericardiocentesis with echo guidance – apical or subcostal approach, risk of
damaging epicardial coronary artery or cardiac perforation.
4. Open drainage under LA/GA
Permit pericardial biopsy
Watch out for recurrent tamponade due to catheter blockage or reaccumulation.

C 31
**Misdiagnosis of cardiac tamponade as congestive heart failure with
diuretics, ACEI or vasodilators can be lethal!

Additional notes from Medical Oncology:

For patients with malignant pericardial effusion resulting in cardiac
tamponade stabilised by urgent pericardial drainage, please consult oncologist
to determine whether they could be benefited from surgical pericardiectomy
(pericardial window) and to plan the subsequent oncological intervention for
underlying disease control.

C 32
 ANTIBIOTIC PROPHYLAXIS FOR
INFECTIVE ENDOCARDITIS

Antibiotics prophylaxis for infective endocarditis should be considered for patients

at highest risk of infective endocarditis prior to dental procedures requiring
manipulation of the gingival or periapical region of the teeth or perforation of the
oral mucosa.

Highest risk category:

 Prosthetic cardiac valve or material:
- Presence of cardiac prosthetic material, including transcatheter
implantation of prosthetic valves
- Cardiac valve repair with devices, including annuloplasty, rings, or clips
 Durable mechanical circulatory support device, including ventricular assist
devices or artificial heart
 Patients with previous, relapse, or recurrent IE
 Patients with congenital heart disease:
- Unrepaired cyanotic congenital heart disease, including palliative shunts
and conduits
- Repaired congenital heart disease with prosthetic material whether placed
surgically or via percutaneous up to six months after the procedure.
- Repaired congenital heart disease with residual shunts or valvular
regurgitation at the site or adjacent to the site of prosthetic patch or
prosthetic device.
- Surgical or transcatheter pulmonary artery valve or conduit placement.
 Cardiac transplant recipients who develop cardiac valvulopathy.

Antibiotics prophylaxis for dental procedure

Single-dose 30-60
Antibiotics
minutes before procedure
Oral penicillin Amoxicillin 2g
Unable to take oral Ampicillin 2 g IM or IV
medication Cefazolin or Ceftriaxone 1 g IM or IV
Cephalexin* 2g
Allergic to penicillin
Azithromycin or Clarithromycin 500 mg
- oral
Doxycycline 100 mg
Allergic to penicillin
Cefazolin or Ceftriaxone* 1 g IM or IV
– non-oral

C 33
Note: Clindamycin is no longer recommended as an alternative antibiotic regime,
given more frequent and severe reactions associated with this drug compared with
other antibiotic agents

* Cephalosporins should not be used for patients with history of anaphylaxis,

angioedema, or urticaria with penicillin or ampicillin. In such cases, vancomycin
may be used (adults: 15 to 20 mg/kg IV, not to exceed 2 g per dose)

Generally, antibiotics prophylaxis for infective endocarditis is not

recommended for respiratory tract/ gastrointestinal/ urogenital/ skin and soft
tissue procedures unless the invasive procedures are performed in the context
of infection. (See G44)

 Patients in highest risk group (listed above) who undergo an invasive

respiratory tract procedure to treat an established infection should receive
an antibiotic regimen that contains an anti-staphylococcal drug.
 In the case of an established infection associated with a gastrointestinal or
genitourinary tract procedure in highest risk group (listed above), it is
reasonable that the antibiotic regimen includes an agent active against
enterococci.
 For surgical procedures involving infected skin (including oral abscesses),
skin structure or musculoskeletal tissue, it is reasonable that the therapeutic
regimen contains an agent active against staphylococci and beta-
haemolytic streptococci.

Reference:
1. Habib G, et al. 2015 ESC Guidelines for the management of infective endocarditis.
Eur Heart J 2015;36:3075.
2. Sexton D, et al. Antimicrobial prophylaxis for the prevention of bacterial endocarditis,
http://www.uptodate.com/contents/antimicrobial-prophylaxis-for-the-prevention-of-
bacterial-endocarditis.

C 34
 PERIOPERATIVE CARDIOVASCULAR EVALUATION
FOR NON-CARDIAC SURGERY

Basic evaluation by Hx (assess functional capacity), P/E & review of ECG.

Clinical predictors of increased perioperative CV risk (MI, CHF, death)

A) Active cardiac conditions mandate intensive management (may delay or

cancel OT unless emergent)
 Unstable coronary syndrome – recent (< 30 days) or AMI with
evidence of important ischaemic risk by symptom or non-invasive test,
Canadian class III or IV angina.
 Decompensated CHF
 Significant arrhythmias - high grade AV block, symptomatic
ventricular arrhythmia in presence of underlying heart disease,
supraventricular arrhythmia with uncontrolled ventricular rate.
 Severe valvular disease e.g. severe AS or symptomatic MS.

B) Clinical risk factors (enhanced risk, need careful assessment of current

status)
 History of ischaemic heart disease
 History of compensated or prior CHF
 DM
 Renal impairment

C) Minor predictors (not proven to independently increase risk)

 Advanced age, abnormal ECG (LVH, LBBB, ST-T abnormalities),
rhythm other than sinus.
 Low functional capacity, hx of stroke, uncontrolled systemic HT.

D) Surgical risk
It estimates a broad approximation of 30-day risk of CV death, MI and
stroke that takes into account only the specific surgical intervention,
without considering the patient-related risk. It divides into low (< 1%),
intermediate (1-5%), high (>5%) surgical risk. (Details can be found in
2022 ESC Non-cardiac Surgery guideline).

C 35
Stepwise approach to preoperative cardiac assessment for patients with
known or risk factors for coronary artery disease

Need for emergency Yes Clinical risk stratification

Step 1 non-cardiac OT and proceed to surgery

No
Acute coronary Yes Evaluate and treat
Step 2 syndrome according to guideline-
directed medical therapy
No

Estimate perioperative risk of MACE based on

Step 3 combined clinical / surgical risk score

Low risk No further tests

Step 4 Proceed to surgery

No
Yes
Moderate risk Clinical exam + ECG + biomarkers
Step 5 (e.g. hsTnI/ BNP/NT-proBNP), if
abnormal to Step 6
No

High risk Yes Consider TTE +/-

Step 6 Will further testing Pharmacologic stress testing
impact decision making e.g. Thallium / Stress CMR
OR preoperative care?

No Normal Abnormal

Proceed to surgery
Step 7 according to Coronary revascularization
guideline-directed according to existing clinical
medical therapy OR practice guidelines
alternative strategies
(non-invasive
treatment, palliation)

C 36
 General Recommendations on dual antiplatelet therapy in patients
undergoing elective non-cardiac surgery after PCI

1. It is recommended to continue aspirin perioperatively if the bleeding risk

allows, and to resume the recommended antiplatelet therapy as soon as
possible post-operatively.
2. Discontinuation of P2Y12 inhibitors should be considered 3-5 days before
surgery for ticagrelor, 5 days for clopidogrel and at least 7 days for
prasugrel.
3. It is NOT recommended to discontinue DAPT within the first month of
treatment in patients undergoing elective non-cardiac surgery.
4. In patients with recent MI or other high ischaemic risk features (e.g. CKD,
multiple stents etc.) requiring DAPT, elective non-cardiac surgery should
be postponed to at least 3-6 months after PCI, but preferably to 12 months
after PCI.
5. In patients without recent MI or other high ischaemic risk features
requiring DAPT, elective non-cardiac surgery should be postponed at least
1 month after PCI. (Need discussion with cardiologist, consider patient’s
clinical profile, angiographic finding, type of stents etc.), but preferably to
6 months after PCI.

Reference:
2017 ESC focused update on dual antiplatelet therapy in coronary artery disease and 2022
ESC Non-cardiac Surgery guideline

C 37
 Timing of last non-vitamin K antagonist oral anticoagulant intake
before start of an elective intervention

Apixaban/Edoxaban/
Dabigatran
Rivaroxaban

No important bleeding risk and/or adequate local

haemostasis possible: perform at trough level
(i.e. 12h or 24h after last intake)
Low risk High risk Low risk High risk

CrCl ≥ 80 mL/min ≥ 24h ≥ 48h ≥ 24h ≥ 48h

CrCl 50-79 mL/min ≥ 36h ≥ 72h ≥ 24h ≥ 48h

CrCl 30-49 mL/min ≥ 48h ≥ 96h ≥ 24h ≥ 48h

Not Not
CrCl 15-29 mL/min ≥ 36h ≥ 48h
indicated indicated
CrCl < 15 mL/min No official indication for use

No bridging with LMWH/UFH

Resume full dose of DOAC ≥ 24h post low bleeding risk intervention and 48-
72h post high bleeding risk intervention.

(Interventions with high bleeding risk include: complex endoscopy, spinal or

epidural anaesthesia, lumbar puncture, thoracic/abdominal/major orthopaedic
surgery, liver/kidney biopsy, TURP/ESWL).

Reference:
The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin
K antagonist oral anticoagulants in patients with atrial fibrillation, European Heart
Journal, Volume 39, Issue 16, 21 April 2018, Pages 1330–1393

C 38
Disease-specific approach
1. Hypertension
 Control of BP preoperatively reduces perioperative ischaemia.
 Evaluate severity, chronicity of HT and exclude secondary HT.
 Mild to moderate HT with no metabolic or CV abnormality – no evidence
that it is beneficial to delay surgery.
 Anti-HT drug continued during perioperative period.
 Avoid withdrawal of beta-blocker
 Severe HT (DBP >110 or SBP >180)
Elective surgery – for better control first
Urgent surgery – use rapid-acting drug to control (esp. beta-blocker)

2. Cardiomyopathy & heart failure

 Pre-op assessment of LV function to quantify severity of systolic and
diastolic dysfunction (affect peri-op fluid Mx)
 HOCM avoid reduction of blood volume, decrease in systemic vascular
resistance or decrease in venous capacitance, avoid catecholamines.

3. Valvular heart disease

 Antibiotic prophylaxis if required.
 AS
- Postpone elective non-cardiac surgery in severe & symptomatic AS.
Consider AVR or valvuloplasty.
- For asymptomatic severe AS, can proceed in low or intermediate risk
non-cardiac surgery. In high risk non-cardiac surgery, can proceed if
LVEF ≥50%. Consider AVR or valvuloplasty if LVEF <50%.
 AR
- Valve surgery is recommended prior to elective intermediate or high
risk non-cardiac surgery if symptomatic severe AR or asymptomatic
severe AR with LVESD >50mm or resting LVEF <50%.
 MS
- Symptomatic moderate to severe MS or asymptomatic with SPAP
>50 mmHg, PTMC or surgery is recommended before elective
intermediate or high risk non-cardiac surgery.
 MR
- Afterload reduction & diuretic to stabilise haemodynamics before
high risk surgery.
- Symptomatic severe MR or asymptomatic severe MR with LVESD
≥40mm or LVEF < 60%, valve intervention (surgical or transcatheter)
should be considered before elective intermediate or high risk-non-
cardiac surgery.

C 39
4. Prosthetic valve
 Antibiotic prophylaxis if required.
 In minor surgery and other procedures where bleeding can be easily
controlled, it is recommended to perform surgery without interruption
of oral anticoagulant.
 Bridging with LMWH or UFH for mechanical heart valve if warfarin
interruption is needed.

5. Arrhythmia
 Search for cardiopulmonary diseases, drug toxicity, metabolic
derangement.
 High grade AV block – pacing.
 Asymptomatic bifascicular or trifascicular block are NOT
recommended for routine management with a peri-operative temporary
pacing wire.
 Intraventricular conduction delays and no history of advanced heart
block or symptoms – rarely progress to complete heart block.
 AF – if on warfarin, may discontinue for few days; give PCC or FFP if
rapid reversal of drug effect is necessary.
 Ventricular arrhythmia
- Simple or complex PVC or Non-sustained VT
 Usually require no Rx except myocardial ischaemia or
moderate to severe LV dysfunction is present.
- Sustained or symptomatic VT
 Suppressed preoperatively with lignocaine, procainamide or
amiodarone.

6. Permanent pacemaker
 Determine underlying rhythm, interrogate devices to determine its
threshold, settings and battery status.
 If the pacemaker in rate-responsive mode → inactivated.
 Reprogramming to AOO, VOO or DOO if the site of electrocautery is
above umbilicus and the underlying rhythm is pacemaker dependent.
 Electrocautery should be avoided if possible; keep as far as possible
from the pacemaker if used.
 Beware leadless pacemaker do NOT respond to magnet application (i.e.
unable to change to asynchronous pacing such as VOO by magnet).

C 40
7. ICD or antitachycardia devices
 Programmed “OFF” immediately before surgery & “ON’ again post-
op to prevent unwanted discharge.
 Patients with ICDs, whose devices have been pre-operatively
deactivated, should be on continuous cardiac monitor throughout the
period of deactivation. External defibrillation equipment should be
readily available.
 For inappropriate therapy from ICD, suspend ICD function by placing
a ring magnet on the device.
 VF/unstable VT – if no or ineffective therapy from ICD & external
defibrillation/cardioversion is required, paddles preferably >12 cm
from the device.

Perioperative beta-blocker therapy

1. Peri-operative continuation of beta-blockers is recommended in patients
currently receiving this medication.
2. Pre-operative initiation of beta-blockers in advance of high risk non-cardiac
surgery may be considered in patients who have 2 or more clinical risk
factors (CAD, cerebrovascular disease, renal insufficiency, DM), in order
to reduce the incidence of peri-operative myocardial infarction.
3. Pre-operative initiation of beta-blocker in advance of non-cardiac surgery
may be considered in patients who have known CAD or myocardial
ischaemia.

Reference:
1. Halvorsen S et al. 2022 ESC Guidelines on cardiovascular assessment and
management of patients undergoing non-cardiac surgery. European Heart Journal
2022, 43: 3826-3924.
2. Fleisher LA et al. 2014 ACC/AHA guideline on perioperative cardiovascular
evaluation and management of patients undergoing noncardiac surgery. JACC
2014;64(22):e77-137.

C 41
Dermatology
 AUTOIMMUNE BULLOUS DISEASES

Autoimmune bullous diseases are a group of autoimmune skin disorders

characterized by blisters formation due to auto-antibodies. They can be sub-
classified into two groups according to the level of separation:

 Intra-epidermal blister: Pemphigus Vulgaris, Pemphigus Foliaceous,

IgA Pemphigus, Paraneoplastic Pemphigus
 Sub-epidermal blister: Bullous Pemphigoid, Mucous Membrane
Pemphigoid, Linear IgA Bullous Dermatosis, Dermatitis Herpetiformis,
Epidermolysis Bullosa Acquisita

Pemphigus vulgaris (PV):

 Auto-antibodies against desmoglein 1 and 3, causing intra-epidermal
blisters
 Clinical features: flaccid blisters which are easily ruptured, leading to
formation of erosions, Nikolsky’s sign is positive. Mucosal involvement is
common.
 Differential diagnoses: Stevens-Johnson syndrome/ Toxic epidermal
necrolysis, Staphylococcal scalded skin syndrome, other autoimmune
blistering diseases
 Investigations:
- Skin biopsy for histology and direct immunofluorescence (DIF) study.
Site of biopsy for DIF: perilesional skin. Specimen needs to be sent
fresh, avoid formalin fixation
- Indirect immunofluorescence study (serology): Anti-skin antibody
(ASA)
 Management:
- General measures:
 Monitor hydration status ± IVF
 Correct electrolytes disturbance
 Nutritional support: consider dietitian consultation
 Pain control: analgesic ladder
 Wound care:
o Non-adhesive dressings (e.g. petrolatum impregnated
gauze)
o Diluted KMnO4: Dilution 1:10,000 (to light pink in colour),
warm compresses for 5-10mins per day to wounds
o Dental care: e.g. Benzydamine/ chlorhexidine mouthwash

D1
 o Screen for secondary infection: wound swab for bacterial
C/ST, oral swab/ wound swab x HSV PCR; and treat
accordingly
- Consult ophthalmology if ocular involvement is suspected
- Topical therapy: super-potent topical steroid (Clobetasol propionate
0.05% cream LA BD), as adjuvant therapy
- Systemic therapy: (needs dermatologist assessment)
 Systemic steroids (e.g. prednisolone 0.5-1.5mg/kg/day) with
steroid sparing immunosuppressive agents (e.g. azathioprine 2-
2.5mg/kg/day, or mycophenolate mofetil 1g BD)
 Rituximab (e.g. two infusions of 1g two weeks apart) with oral
prednisolone 0.5-1mg/kg/day
- Other systemic therapy:
 Intravenous immunoglobulins (IVIG, 0.4g/kg/day for 5 days)
 Pulsed IV steroids (e.g. methylprednisolone 0.5-1g/ day for 3
days)
 Plasmapheresis/ immunoadsorption (if available)

Bullous pemphigoid (BP):

 Auto-antibodies against antigens BP180/ BP230 (components of hemi-
desmosome), leading to sub-epidermal blisters
 Clinical features:
- Pre-bullous lesions: pruritic fixed urticarial or eczematous papules and
plaques
- Bullous lesions: tense blisters, Nikolsky’s sign is negative
- Late stage lesions: erosions
- Mucosal involvement is less common (10-30%) than in PV
 Differential diagnoses: other autoimmune blistering diseases, bullous drug
eruption, allergic contact dermatitis, mechanical blisters
 Investigations: same as in PV
 Management:
- General measures: same as in PV
- Topical therapy:
 Super-potent topical steroid: Clobetasol propionate 0.05% cream
LA BD (over the entire body except the face)
- Systemic therapy:
 Systemic steroids (mainstay of treatment)
 Mild disease: prednisolone 0.5mg/kg/day
 Severe disease: prednisolone 0.5-0.75mg/kg/day
 Doxycycline 100mg BD (immunomodulatory effect)
D2
  Steroid sparing immunosuppressive agents: methotrexate,
azathioprine, mycophenolate mofetil
- Treatment for steroid resistant BP: (needs dermatologist assessment)
 Immunosuppressive agents as above
 Intravenous immunoglobulins (IVIG, 0.4g/kg/day for 5 days)
 Plasma exchange/ immunoadsorption (if available)

References:
1. P Joly, B Horvath, A Patsatsi, et al. Updated S2K guidelines on the management of
pemphigus vulgaris and foliaceous initiated by the European Academy of
Dermatology and Venereology. JEADV 2020, 34, 1900-1913
2. C Feliciani, P Joly, MF Jonkman, et al. Management of bullous pemphigoid: the
European Dermatology Forum consensus in collaboration with the European
Academy of Dermatology and Venereology. BJD (2015) 172, pp867-877

D3
 CUTANEOUS VASCULITIS

Vasculitis is a heterogeneous group of diseases characterised by inflammatory

cell infiltration and necrosis of blood vessel wall. It may be confined to the
skin (cutaneous vasculitis), or involves any other organ systems (systemic
vasculitis).

Vasculitis is classified by the size of the vessels affected:

 Small vessel vasculitis:
- Cutaneous features: palpable purpura ± haemorrhagic blisters
- Causes:
 Idiopathic
 Secondary to infection, autoimmune connective tissue disease, drug,
haematological neoplasm
 Henoch-Schönlein purpura
 Cryoglobulinaemia (type II/ III)
 ANCA positive vasculitis
 Medium vessel vasculitis:
- Cutaneous features: livedo racemosa, subcutaneous nodules, ulcers,
digital infarct
- Causes:
 Polyarteritis nodosa
 Cryoglobulinaemia (type II/ III)
 ANCA positive vasculitis
 Large vessel vasculitis:
- Cutaneous involvement uncommon
- Causes:
 Giant cell arteritis
 Takayasu’s arteritis

Differential diagnosis for petechia/ purpura:

 Dermal haemorrhage: e.g. trauma, senile purpura, coagulopathies/
thrombocytopenia, drugs (anti-platelets, anticoagulants)
 Septic vasculitis: e.g. infective endocarditis, rickettsia, fungaemia
 Vascular occlusion:
- Thrombosis: e.g. anti-phospholipid syndrome, warfarin necrosis,
cryoglobulinaemia (type I), livedoid vasculopathy, thrombotic
microangiopathy (such as purpura fulminans, thrombotic
thrombocytopenic purpura, haemolytic uraemic syndrome)
- Embolism: e.g. cardiac emboli, septic emboli, cholesterol emboli
- Calciphylaxis
D4
Approach to a case with suspected vasculitis:
 Confirm the diagnosis and determine the size of vessels involved:
- Skin biopsy: specimen should include deep dermis/ subcutaneous fat
if medium vessel vasculitis is suspected
 Screen for extracutaneous involvement and evaluate possible underlying
cause:
- Review of systems (History/ PE): Musculoskeletal/ GI/ renal/
neurological/ respiratory systems, eye, ENT, etc
- Drug history
- Investigations:
 Baseline bloods: CBC d/c, LRFT, CRP, ESR
 ASO titre, Hep B/ C serology, HIV serology
 RF, ANA, DsDNA, ANCA, ENA, C3/C4, Cryoglobulin
 SPE, Ig pattern
 Septic workup as indicated
 Urine multistix ± fresh microscopy

Treatment for cutaneous vasculitis:

 Supportive measures: bedrest, elevation of affected dependent areas
 Topical steroids (for mild cases without tissue loss)
 Colchicine 0.5mg BD
 Dapsone 50mg - 100mg daily (screen for G6PD status)
 For severe cases with tissue loss (e.g. with blisters/ ulcers)
- Consider short course systemic steroids, taper off over 4-6 weeks

Patients with systemic vasculitis should be co-managed with relevant sub-

specialties e.g. rheumatology/ nephrology etc, depending on the systems
involved.

D5
 DRUG REACTION WITH EOSINOPHILIA AND
SYSTEMIC SYMPTOMS (DRESS) SYNDROME

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome

is a rare, severe, idiosyncratic drug hypersensitivity reaction.

Clinical features:
• Fever ≥ 38°C
• Skin rash: highly variable, ranging from maculopapular eruption to
erythroderma. Suggestive features include facial oedema, infiltrative or
purpuric lesions, and psoriasiform desquamation
• Mucositis
• Lymphadenopathy
• Haematological abnormalities: eosinophilia, atypical lymphocytosis
• Visceral involvement:
o Hepatitis (60-80%)
o Any other internal organs might be involved, such as kidney, lung,
muscle, heart, pancreas, etc

DRESS syndrome is a delayed-type drug hypersensitivity. Typical latent period

is 2-6 weeks. A comprehensive drug history of at least 2 months is therefore
recommended.
Any medication might be responsible. Common culprit drugs include:
• Anti-convulsants, e.g. phenytoin, carbamazepine, phenobarbital
• Allopurinol
• Sulphonamides
• Anti-microbials: e.g. vancomycin, minocycline, penicillin, anti-
retrovirals

Investigations:
DRESS syndrome is a diagnosis by exclusion.
• Blood tests: CBC d/c, film comment, LRFT, INR
• ECG, CXR
• Urine multistix +/- urine TP/Cr ratio, 24-hour urine protein
• Skin biopsy
• Exclude other causes with similar presentations:
o Hepatitis serology
o Mycoplasma/ chlamydia serology
o Septic workup including blood culture
o ANA
D6
Management:
• Identification and prompt withdrawal of offending drug
• Avoid cross-reacting medications. Input the allergy history to CMS, print
out the allergy alert sheet to patient as reference for future consultation
• Cutaneous eruptions:
o Anti-histamines, emollients and topical steroids for symptomatic
relief
o If erythrodermic, manage as erythroderma
• Visceral involvement:
o Co-management with relevant sub-specialties is recommended
o Consider high dose systemic corticosteroids: e.g. Prednisolone
1mg/kg/day
o Gradual taper over 3-6 months (rapid taper might result in relapse)
• Symptoms generally take several weeks to resolve after discontinuation
of the offending agent and beginning of treatment

Reference:
1. Z Husain, BY Reddy, and RA Schwartz. DRESS syndrome. Part II. Management and
therapeutics. JAAD 2013;68:709.e1-9.

D7
 ECZEMA/ DERMATITIS
Eczema/ dermatitis is a clinical descriptive term and is characterized by
epidermal disruption of indistinct margin. Histologically, it is characterized by
spongiotic dermatitis.

Causes of eczema:
 Exogenous: irritant or allergic contact dermatitis
 Endogenous: atopic dermatitis, seborrheic dermatitis, asteatotic dermatitis,
discoid eczema, stasis eczema, pompholyx, lichen simplex chronicus
(neurodermatitis)

Regardless of the causes, eczema can be subdivided into three stages:

 Acute: characterized by vesicles, blisters, weeping and intense erythema
 Subacute: characterized by erythema, scaling, with a fissured and dry
appearance
 Chronic: characterized by thickening and lichenification, with scaling and
fissuring

Management of acute eczema flare:

 Skin care advice:
- Frequent use of emollients
- Bathing: use soap substitutes (e.g. emulsifying ointment for bathing), use
lukewarm water and keep bathing time short (<10mins per day), avoid
prolonged hot bath, avoid vigorous rubbing and cleaning of skin, apply
emollients right after bathing
 Look for possible precipitating factors for acute flare:
- Contact allergens (e.g. topical medications/ cream, moisturizers, wash,
cosmetics, wipes, hair dyes, etc), consider patch test if allergic contact
dermatitis is suspected
- New drugs including herbal medicine (watch out for eczematous drug
eruption)
- Infection (e.g. staphylococcal aureus, Group A streptococcus, Herpes
simplex virus – see eczema herpeticum)
 Topical treatment:
- Topical steroids: the mainstay of treatment for inflammatory component
of eczema, the strength and base used depend on the stage and location
of eczema. Examples of common treatment regimen:
 Face/ flexures/ genitalia:
Mildly affected: 1% hydrocortisone cream LA BD
Severely affected: 0.1% mometasone furoate cream LA daily (avoid
prolonged use on face/ flexures/ genitalia)
D8
  Body and limbs:
Mildly affected: synalar cream 0.0125% LA BD
Severely affected: synalar cream 0.025% LA BD; or 0.1%
Betamethasone valerate (Betnovate) cream/ ointment LA BD
 Scalp:
Betamethasone valerate (Betnovate) scalp application LA BD
 Seborrhoeic dermatitis:
Face: Daktacort LA BD
Scalp: Ketoconazole shampoo twice per week; Betnovate scalp
application LA BD
- Consider non-steroidal topical calcineurin inhibitors (e.g. tacrolimus,
pimecrolimus) for face, especially periorbital region (avoid applying too
close to eyes, which can cause irritation and burning sensation)
- Diluted Potassium permanganate (KMnO4):
Dilution 1:10,000 (to light pink in colour), warm compresses for 5-
10mins per day to acute weepy areas
- Consider wet wrap therapy as tolerated
 Treatment for superimposed infection:
- Avoid topical steroids on skin with active infection
- Appropriate systemic antibiotics for bacterial infections according to
wound swab C/ST
 For patients with repeated infected eczema flare due to MSSA/
MRSA, consider MSSA/ MRSA screening and decontamination
therapy
- Eczema herpeticum: Herpes simplex infection (HSV 1/2) in patient with
underlying eczema (usually atopic eczema); systemic antivirals (e.g.
acyclovir) is indicated. For patients with facial involvement,
ophthalmologist assessment is recommended for possible ocular
involvement

Treatment for severe extensive recalcitrant eczema

 Ensure correct diagnosis, consider skin biopsy
 Exclude precipitating factors
 Ensure compliance to appropriate skin care and topical treatment
 Systemic treatment includes:
- Immunomodulatory agents such as azathioprine, methotrexate,
mycophenolate mofetil, cyclosporine A
- Phototherapy
- Biologics: anti-IL4/13 – Dupilumab for atopic eczema
- JAK- inhibitors such as abrocitinib, upadacitinib, baricitinib for atopic
eczema

D9
 ERYTHRODERMA

Erythroderma is defined as generalized erythema and scaling involving more

than 90% of total body surface area.

Causes for erythroderma can be extensive. Common or important causes

are:
 Atopic dermatitis
 Psoriasis
 Drug eruption
 Cutaneous T-cell lymphoma (esp. Mycosis fungoides and Sézary syndrome)
 Idiopathic
 Pityriasis rubra pilaris
 Other (non-atopic) dermatitis: e.g. allergic contact dermatitis, seborrheic
dermatitis, stasis dermatitis with autosensitization, chronic actinic dermatitis

Detailed medical/ drug history is important to aid establishment of the underlying

aetiology. Unless the aetiology is obvious, a skin biopsy is recommended to
exclude drug eruption and cutaneous T-cell lymphoma.

Management of erythroderma:
 Hospitalization is recommended for acute erythroderma
 General supportive measures:
- Monitor hydration status and electrolytes
- Nutritional support
- Watch out for high output heart failure, temperature dysregulation esp.
hypothermia, and secondary bacterial infection
 Topical treatment:
- Avoid potentially irritating topical preparations such as coal tar, salicylic
acid
- Frequent use of bland emollients
- Low- to mid-potency topical steroids (e.g. synalar 0.005%-0.0125% LA
BD)
 Definitive treatment depends on the underlying dermatoses (needs
dermatologist assessment)
- Erythrodermic drug eruption: after stopping offending drug, may take 4-
6 weeks to see any significant response
- Idiopathic erythroderma: consider short tapering course of systemic
steroids; or steroid-sparing immunomodulatory agents: methotrexate,
azathioprine, mycophenolate mofetil, cyclosporine A

D 10
 PSORIASIS

Psoriasis is a chronic inflammatory skin disease characterized by symmetrical

well-defined, circumscribed salmon pink patches and plaques with silvery scales.

Subtypes:
 Chronic plaque psoriasis – commonest subtype, common sites of involvement:
extensor surfaces such as elbows, knees, shins, lower back, and scalp
 Guttate psoriasis – small raindrop-like scaly papules
 Flexural/ inverse psoriasis
 Erythrodermic psoriasis
 Pustular psoriasis (localized or generalized)
 Psoriatic arthropathy (see R12-13)

Management for plaque psoriasis flare:

 Watch out for precipitating factors: drug compliance, infection, systemic
steroid withdrawal, sunburn, new drugs such as interferon, beta-blockers,
lithium, antimalarial, NSAIDs/ aspirin
 Topical treatment and examples of common regimen:
- Emollients: e.g. Aqueous cream LA BD, Vaseline LA BD
- Face/ flexures:
0.1% Mometasone furoate cream LA daily for short course use (avoid
prolonged use of potent topical steroid on face, esp. peri-orbitally)
Topical Vitamin D analogues (e.g. topical calcitriol or topical calcipotriol
LA BD) as maintenance
- Body and limbs:
Mildly affected: synalar 0.025% 1:1 mix 2-4-2 ointment (Salicylic acid
2% + coal tar 4% + Sulphur 2%) LA BD
Severely affected: Betamethasone dipropionate + salicylic acid
(Diprosalic ointment) LA BD; Betamethasone dipropionate +
calcipotriol (Daivobet ointment) LA daily
- Scalp:
Coal Tar/ Pine Tar shampoo twice per week (e.g. Ionil T shampoo;
Sebitar shampoo)
Mildly affected: Betnovate scalp application LA BD
Severely affected: Betamethasone dipropionate + calcipotriol (Xamiol)
gel LA daily
 Systemic treatment:
- Methotrexate
- Cyclosporine A
- Acitretin* (modest effect for plaque psoriasis)

D 11
 Phototherapy
 Biologics: anti-TNF-α, anti-IL12/23, anti-IL17, anti-IL23

Generalized pustular psoriasis (GPP):

 Characterized by widespread sterile pustules on a background of
erythematous painful plaques, coalescence of pustules forming lakes of pus
 Preceding history of chronic plaque psoriasis may not be present
 Systemic symptoms common: e.g. fever, chills, malaise, headache, asthenia
 Main ddx: AGEP (acute generalized exanthematous pustulosis) – an
uncommon pustular drug eruption

Management of generalized pustular psoriasis:

 GPP is potentially life threatening, hospitalization is recommended
 Exclude precipitating factors: infection, systemic steroid withdrawal, drugs,
pregnancy, hypocalcaemia
 Wound/ pustule swab for microscopy + C/ST to exclude infection
 Skin biopsy
 General supportive measures for skin failure:
- Monitor hydration status and electrolytes
- Nutritional support
- Pain control
- Watch out for high output heart failure, temperature dysregulation, and
secondary bacterial infection
 Topical treatment:
- Stop all potentially irritating topical agents such as coal tar, salicylic acid,
topical Vit D analogues; and stop all potent topical steroids
- Use bland emollients and low- to mid-potency topical steroids (e.g.
synalar 0.005%-0.0125% LA BD)
 Systemic treatment is indicated for GPP unless there are contraindications
(needs dermatologist assessment):
- Cyclosporine A
- Acitretin*
- Methotrexate
- Biologics

*Acitretin is an oral retinoid. It is absolutely contraindicated in pregnancy due to its

teratogenicity. Strict contraception is required during treatment and for THREE years
after stopping acitretin. Consider alternative treatment for females of child-bearing age.

D 12
 STEVENS-JOHNSON SYNDROME & TOXIC EPIDERMAL
NECROLYSIS
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) belong to
a spectrum of severe epidermolytic cutaneous adverse drug reaction, characterised
by varying extent of epidermal death with overall mortality rate of ~30%.

Clinical features:
 In general, a prodrome of fever, cough, malaise and headache is followed by
inflammation and ulceration of the ocular, oral and genital mucosa.
 Early phase: Dusky red, greyish skin patches.
 Confluent erythema with local tenderness, targetoid lesions.
 Flaccid blisters prone to erosions; shearing of skin (epidermis)
 Nikolsky’s sign: epidermal separation induced by gentle lateral pressure on the
skin surface.
 Typical time interval of presentation of cutaneous adverse drug reaction: 5 to
28 days.
 Predicted mortality based on SCORTEN (Table 1)
Definition Epidermal detachment
Stevens-Johnson syndrome <10% BSA
SJS/TEN overlap 10-30% BSA
Toxic epidermal necrolysis >30% BSA
*Body surface area (BSA) calculation is based on detached and detachable epidermis.

Causes:
 Drugs are implicated in 70-80% of SJS/TEN.

Common culprit drugs:

 Allopurinol [universal screening test for HLA-B*58:01 allele is recommended
before starting] (please refer to R4)
 Aromatic anti-convulsants [e.g. phenytoin, carbamazepine (HLA-B*1502) and
phenobarbital]
 Antibiotics
 Sulphonamides
 NSAIDs

Other organ involvement complications:

 Secondary bacterial infection and septicaemia (main cause of mortality)
 Dehydration
 Electrolyte imbalance
 Pre-renal azotaemia
 Thermal dysregulation
 Adult respiratory distress syndrome
D 13
Initial assessment and work-up
 Obtain detailed history from patient / relatives including clear drug history.
 Drug history elicited should include: name of medication, reason for intake,
interval between drug administration and cutaneous reaction, duration of
drug administration, prior exposure to same or a cross-reacting medication,
concurrent medications.
 Stop suspected culprit drug if identified.
 Take blood for Mycoplasma serology / swab for Herpes simplex virus
culture / PCR study (if no culprit drug identified).
 Take blood for CBC, LRFT, bicarbonate, glucose, urine microscopy,
perform CXR.
 Skin swab for pyogenic culture.
 Take skin biopsy – send for Histology (lesional) and direct
Immunofluorescence stain (peri-lesional area) in fresh specimen.
 Establish peripheral venous access.
 Consider nasogastric (NG) tube and Foley catheterisation
 Consult ICU, Dermatology, Ophthalmology, ENT, Plastic Surgery / Burns
Team for assessment.
 Additional clinical input to multidisciplinary team may be required from
respiratory medicine, gastroenterology, gynaecology, urology, pain team,
and microbiology (see Treatment).

Prognosis:
 Calculate SCORTEN within first 24 hours (Severity-of-illness score for
Toxic Epidermal Necrosis) for mortality prediction.
SCORTEN prognostic factors Score
Extent of epidermal detachment >10% 1
Age ≥ 40 years 1
Heart rate ≥ 120/min 1
Serum Bicarbonate <20 mmol/L 1
Serum BUN >10 mmol 1
Serum glucose >14 mmol 1
Cancer of haematological malignancy 1

SCORTEN score Predicted mortality rate (%)

0-1 3.2
2 12.1
3 35.3
4 58.3
5 or more > 90

D 14
Treatment:
 Management of SJS & TEN should be multidisciplinary and requires early
diagnosis and withdrawal of suspected / causative drug(s), general
supportive and specific therapies.

General supportive care:

I. Transfer to a burns or specialist intensive care unit.
 Patient with >10% BSA epidermal loss should be considered
admission without delay to ICU/burns unit with experience in treating
patients with SJS/TEN.
 Pressure-relieving mattress in a room with controlled humidity and
temperature.

II. Prompt withdraw of causative drug

III. Prevention, early detection and treatment of infections.

 Major organisms in sepsis-related mortality in TEN patients are
Staphylococcocus aureus and Pseudomonas aeruginosa.
 Reserve barrier nursing to reduce risk of nosocomial infections.
 Antibiotics should only be initiated if there are signs of sepsis.

IV. Wound care:

 Mucosal lesions: oral toilet and hygiene, saline compress,
chlorhexidine wash, Difflam gargle for anaesthetic effect.
 Non-infected skin: non-adherent dressings (e.g. petroleum
impregnated gauzes, silicone dressings (e.g. Mepilex Silicone,
Mepilex transfer, Mepitel).
- Primary dressings should be secured with roller-gauze bandages
and elastic tubular dressings e.g. Tubifast. And be changed every
2-4 days depending on amount of exudate.
 Infected wounds: Consider dressings with antimicrobial properties
such as silver e.g. Mepilex Ag, Aquacel Ag

V. Fluid, electrolytes and nutrition

 Monitor fluid loss and maintain adequate fluid replacement. Urinary
catheterisation should be considered in all cases to guide fluid
resuscitation.
 Goal is to maintain a urinary output of 0.5-1 mL/kg/hr
 Treat hyperglycaemia. Hyperglycaemia has been associated with
increased morbidity and mortality in ICU patients.
D 15
  Consider referral to dietician.
 NG tube feeding should be considered if eating is painful.
 Consider prophylactic low molecular weight heparin (LMWH) in
immobile patients.
 Consider proton-pump inhibitor to reduce stress-related
gastrointestinal ulcerations.

VI. Respiratory care:

 Respiratory toilet – nebulised saline, bronchodilators, physiotherapy.
 Referral to ENT if any signs of dysphonia or dyspnoea
 Hypoxia may indicate respiratory epithelium involvement,
necessitating supplementary oxygen or assisted ventilation.

VII. Ocular involvement:

 Eye involvement may result in blindness, daily ophthalmological
review is needed.
 Referral to an ophthalmologist is essential.
 Supportive treatment includes preservative-free lubricants (every 2
hours in acute illness) ± topical steroids and topical antibiotics.
 In unconscious patients, prevention of corneal exposure is essential.

VIII. Oral involvement:

 Daily oral review
 Apply white soft paraffin ointment to lips every 2 hours through
acute illness.
 Clean the mouth daily with warm saline mouthwashes or oral sponge.
 Use anti-inflammatory oral rinse or spray containing benzylamine
hydrochloride e.g. Difflam mouthwash, every 3 hours, particularly
before eating.
 Use antiseptic oral rinse containing chlorhexidine twice a day.
 Use a potent topical corticosteroid spray to oral sores (e.g.
betamethasone sodium phosphate 500 μg or Fluticasone proprionate
spray 50 μg two dose unit sprays, four times a day).

IX. Urogenital involvement:

 Early gynaecologic examination should be performed in all female
patients with SJS/TEN.
 Daily urogenital review.
 Apply white soft paraffin ointment to the urogenital skin and

D 16
 mucosae every 4 hours through acute illness.
 To the involved but non-eroded surface, use potent topical
corticosteroid ointment once a day.
 To eroded areas, use a silicone or non-adherent dressing e.g. Jelonet
/ paraffin gauze dressing.

X. Pain control:
 Consider referral to pain team, obtain pain score daily.
 Analgesics such as tramadol and morphine may be administered
when necessary.
 Consider patient-controlled analgesia.

Specific treatment:
 There is no randomised controlled trial supporting a specific treatment for
SJS/TEN.
 However potential role of Intravenous immunoglobulin (IVIg), systemic
corticosteroid and cyclosporine have been suggested. (Note: current
evidence is insufficient to advocate one particular treatment over the
others).

Discharge and follow-up:

 Written or printed information about drug(s) given to patient and
emphasise on avoidance. Drug allergy should be documented clearly in
patient’s record/note and entered to CMS record as a structured entry (NO
free text).
 Diagnostic test: Routine drug hypersensitivity testing is not recommended
after an episode of SJS/TEN.
 Seek specialist’s advice on hypersensitivity testing when:
i. culprit drug is not known,
ii. medication avoidance is detrimental to patient or
iii. accidental exposure is possible.

Reference:
1. UK guidelines for management of Stevens-Johnson syndrome/TEN. Br J Dermatol
2016;174:1194-1227 & J Plast Reconstr Aesthet Surg 2016; 69:e119-e153
2. SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis, Journal of
Investigative Dermatology. Volume 115, Issue 2, August 2000, Pages 149-153

D 17
 TOPICAL CORTICOSTEROIDS (TCS)

Factors affecting the choice of topical corticosteroids (TCS):

 Potency of TCS (see table below)
 Vehicle/ base
- Effectiveness of ointment > cream > lotion/ solution/ gel
 Location
- More potent TCS for areas with thick skin: e.g. palms and soles
- Less potent TCS for areas with thin skin, or areas under occlusion:
e.g. face, genitalia, flexures
 Age of patient
- Avoid potent TCS in infants and young children if possible
 Body surface area of involvement
- Avoid use of potent TCS over large body surface area (e.g. over 10-
20% body surface area), consider systemic therapy for severe
dermatoses instead
 Disease status, e.g.
- Super-potent TCS is recommended for bullous pemphigoid
- Cream is preferred to ointment for weepy lesions
- More potent TCS is preferred for chronic lichenified lesions

Side effects of TCS:

 Local cutaneous side effects: skin atrophy, telangiectasia, striae, easy
bruising, delayed wound healing, hypertrichosis, hypopigmentation,
superimposed infection, steroid-induced rosacea/ acne
 Ocular complications: cataract, glaucoma (avoid application to eyelids)
 Systemic complications: adrenal insufficiency, iatrogenic Cushing’s

Classification of TCS according to potency

Potency Topical corticosteroids (examples)
Mild 1% hydrocortisone
Moderate 0.0125% fluocinolone acetonide (half strength Synalar®)
0.1% mometasone furoate (Elomet®)
Potent 0.1% betamethasone valerate (Betnovate®)
0.025% fluocinolone acetonide (full strength Synalar®)
Super-potent 0.05% clobetasol propionate (Dermovate®)

In general, avoid prolonged continuous use of potent TCS for over 3 weeks.
Also avoid TCS to areas with active infection.
D 18
Endocrinology
 DIABETIC KETOACIDOSIS (DKA)

Diagnostic criteria: Plasma glucose >14 mmol/L, arterial pH <7.3, plasma

bicarbonate <15 mmol/L, (high anion gap) and moderate ketonuria or
ketonaemia (or high serum beta-hydroxybutyrate, BHBA).

Remarks:
 Euglycaemic DKA could be associated with the use of SGLT2 inhibitors
in patients with type 2 DM, where glucose concentration may be within or
near the normal range (<14 mmol/L).
 Urine ketones are not a reliable indicator in detecting DKA associated with
SGLT2 inhibitors. Blood ketones measurement is preferable.

Initial Hour Subsequent Hours

Ix Urine & Blood glucose Hourly blood glucose
Urine & plasma BHBA/
Na, K, PO4, urea, blood gas,
ketones
BHBA (till blood glucose <14
mmol/L)
Na, K, PO4, ± Mg
Urea, Creatinine, Hb Repeat ABG if indicated
Arterial blood gas (ABG) (intensive monitoring of
electrolytes and acid/base is
If indicated: crucial in the first 24-48 hours)
CXR, ECG
Blood & urine culture and
sensitivity
Urine & serum osmolality
PT, APTT

Look for precipitating causes

Parameters Hourly BP/pulse, respiratory rate, conscious level, urine output; 2-
to be hourly temperature
monitored ± central venous pressure (CVP)

Ancillary Aspirate stomach if patient is unconscious or vomiting (protect

Measures airway with cuffed endotracheal tube if necessary)
Catheterize bladder and set CVP as indicated
Give antibiotics if evidence of infection
Treat hypotension and circulatory failure

E1
 Rx Initial Hour Subsequent Hours
Hydration 1-2 litre 0.9% saline - 1 litre/hour or 2 hours as appropriate
(NS) - When serum Na >150 mmol/L, use
0.45% saline (modify in patients with
impaired renal function). Fluid in first
12 hrs should not exceed 10% BW,
watch for fluid overload in elderly.
- When blood glucose ≤14 mmol/L,
change to D5.
Insulin Regular human insulin - Regular human insulin iv infusion 0.1
0.15 unit/kg as IV unit/kg/hr.
bolus, followed by - Aim at decreasing plasma glucose by
infusion (preferably 3-4 mmol/L per hour, titrate insulin
via insulin pump) dose to achieve this rate of decrease in
blood glucose if necessary.
- When BG ≤14 mmol/L, decrease dose
of insulin to 0.05-0.1 unit/kg/hr or
give 5-10 units sc q4h, adjusting dose
of insulin to maintain blood glucose
between 8-12 mmol/L.
- ↓monitoring to q2h-q4h.
- Change to maintenance insulin
when acidosis is resolved and
normal diet is resumed. IV insulin
should not be discontinued until at
least 30-60 minutes after the
administration of sc insulin.
K 10-20 mmol/hr Continue 10-20 mmol/hr, change if:
- K < 4 mmol/L, ↑ to 30 mmol/hr
- K < 3 mmol/L, ↑ to 40 mmol/hr
- K > 5.5 mmol/L, stop K infusion
- K > 5 mmol/L, ↓ to 8 mmol/hr
Aim at maintaining serum K between 4-
5 mmol/L
NaHCO3 If pH between 6.9-7.0, give 50 mmol NaHCO3 in 1 hr.
If pH < 6.9, give 100 mmol NaHCO3 in 2 hrs.
Recheck ABG after infusion, repeat every 2 hrs until pH >7.0.
Monitor serum K when giving NaHCO3.

E2
 DIABETIC HYPEROSMOLAR
HYPERGLYCAEMIC STATES

Diagnostic criteria:

Blood glucose > 33 mmol/L (arbitrary), arterial pH >7.3, serum bicarbonate

> 15 mmol/L, effective serum osmolality [(2×measured Na) + glucose] >
320 mOsm/kg H2O, and mild ketonuria or ketonaemia, usually in association
with change in mental state.

1. Management principles are similar to DKA.

2. Fluid replacement is of paramount importance as patient is usually very
dehydrated.
3. If plasma sodium is high, consider to use hypotonic saline
4. Watch out for heart failure (CVP usually required for elderly).
5. Serum urea is the best prognostic factor.
6. Insulin requirement is usually less than that for DKA, watch out for too
rapid fall in blood glucose and overshot hypoglycaemia.

E3
 PERIOPERATIVE MANAGEMENT
OF DIABETES MELLITUS

1. Pre-operative Preparation
a. Screen for DM complications, check standing/lying BP and resting
pulse
b. Glucose, HbA1c, electrolytes, RFT, HCO3, urinalysis, ECG
c. Admit 1-2 days before major OT for DM control
d. Aim at blood glucose of 5-10 mmol/L before operation
e. Well controlled patients: omit insulin / oral hypoglycaemic agents
(OHA) on day of OT
f. Poorly controlled patients:
Stabilise with insulin (+/- dextrose) drip for emergency OT:
Blood glucose (mmol/L) Actrapid HM Fluid
< 20 1-2 units/hr D5 q4-6h
> 20 4-10 units/hr NS q2-4h
(Crude guide only, monitor h’stix q1h and adjust insulin dose, aim to
bring down glucose by 4-5 mmol/L/hr to within 5-10 mmol/L)
* May need to add K in insulin-dextrose drip
* Watch out for electrolyte disorders
* May use sc regular insulin for stabilisation if elective surgery
g. Patients on SGLT2 inhibitors:
 SGLT2 inhibitors should be stopped at least 24 hours prior to a
major elective surgery and planned invasive procedures, and prior
to emergency surgery or situations of extreme stress like major
trauma and acute serious medical conditions.
 Regular monitoring of serum beta-hydroxybutyrate or urine
ketones should be considered in peri-operative period especially
for high risk patients. Blood test is preferred if available.
 SGLT2 inhibitors may be resumed once the patient’s condition has
stabilized with normal oral intake.

2. Day of Operation
a. Schedule the case early in the morning
b. Check h’stix and blood glucose pre-op, if blood glucose >10 mmol/L,
postpone for a few hrs till better control if possible

c. For Major Surgery

 For patients on insulin or high dose of OHA, start dextrose-insulin-
K (DKI) infusion at least 2 hrs pre-operatively or after fasting:
E4
 - 6-8 units Actrapid HM + 10-20 mmoles K in 500 ml D5, q4-6h
(about 1 unit insulin for 4 gm of glucose) (Flush iv line with 40
ml DKI solution before connecting to patient)
- Monitor h’stix q1h and adjust insulin, then q4h for 24 hrs (usual
requirement 1-3 units Actrapid/hour)
- Monitor K at 2-4 hours and adjust dose as required to maintain
serum K within normal range.
- Give any other fluid needed as dextrose-free solutions.
 Patients with mild DM (diet alone or low dose of OHA)
- D5 500 ml q4h alone (usually do not require insulin)
- Monitor h’stix and K as above, may need insulin and K

d. For Minor Surgery

 May continue usual OHA / diet on day of surgery
 For well-controlled patients on insulin:
Either:
- Omit morning short-acting insulin
- Give 2/3 of usual dose of intermediate-acting insulin am, and
the remaining 1/3 when patient can eat.
Or: (safer)
- Use DKI infusion till diet resumed. Then give 1/3 to 1/2 of usual
intermediate-acting insulin
 For poorly-controlled patients on insulin:
- Control first, use insulin or DKI infusion for urgent OT

3. Post-operative Care
a. ECG (serially for 3 days if patient is at high risk of IHD)
b. Monitor electrolytes and glucose q6h
c. Continue DKI infusion till patient is clinically stable, then resume
regular insulin (give first dose of sc insulin 30 minutes before
disconnecting iv insulin) / OHA when patient can eat normally
d. In case of nasogastric tube feeding, give insulin (infusion or sc)
according to feeding schedule

E5
 INSULIN THERAPY FOR DM CONTROL

Common insulin regimes for DM control (Ensure dietary compliance before

dose adjustments):

1. For insulin-requiring type 2 DM

(May consider combination therapy (Insulin +OHA) for patients with
insulin reserve)
a. Fasting Glycaemia alone
 Give bed-time intermediate-acting insulin, start with 0.1-0.2
unit/kg
 Continue metformin and other oral hypoglycaemic agents if
appropriate
b. Daytime Glycaemia
 Start with intermediate-acting or pre-mixed insulin 30 mins before
breakfast (AM insulin) and before dinner (PM insulin)
 Adjust dosage according to fasting and post-meal h’stix
 If fasting glucose persistently high, check blood sugar at mid-
night:
- If hypoglycaemia, reduce pre-dinner dose by 5-10% (Somogyi
phenomenon)
- If hyperglycaemic, may need to consider MDI (multiple dose
insulin) regimes

2. Consult endocrinologist for insulin analogues in difficult cases with wide

glucose fluctuations.

N.B.
 Long-acting insulin analogues Glargine, Detemir and Degludec are
indicated if patients have sub-optimal glycaemic control on NPH with
frequent documented hypoglycaemia or sub-optimal glycaemic control
on NPH with established CHD/PVD/Stroke or renal (eGFR
<60ml/min) complications with reasonable QoL.
 Rapid-acting insulin analogues Aspart, Glulisine and Lispro are
indicated if patients have brittle or poorly control DM despite multi-
dose conventional short acting insulin regimen and good compliance

E6
3. For type 1 DM
 Consider multiple dose basal-bolus regimen
 Consider use of Pens for convenience and ease of administration
 Start with 0.5 unit/kg/d. adjust the following day according to h’stix
(tds and nocte)
a. For multiple daily dose regimes:
- Give 40-60% total daily dose as intermediate-acting insulin
before bed-time to satisfy basal needs. Adjust dose according to
fasting glucose.
- Give the remaining 40-60% as regular insulin, divided into 3
roughly equal doses pre-prandially (slightly higher AM dose to
cover for Dawn Phenomenon, and slightly high dose before
main meal of the day)
b. For difficult cases, consult endocrinologist for considering insulin
analogues or continuous subcutaneous insulin delivered via a
pump.

Sliding scale, if employed at all, must be used judiciously:

1. H’stix must be performed as scheduled
2. Dose adjustment should take into consideration factors that may affect
patient’s insulin resistance.
3. It should not be used for more than 1-2 days

Pharmacokinetics of commonly used insulin preparations

Insulin type Onset Peak effect Duration of action
Rapid-acting (lispro,
<15 mins 1-2 hrs 2-4 hrs
aspart, glulisine)
Regular 30 mins 2-4 hrs 5-8 hrs
NPH 1-2 hrs 6-10 hrs 18-24 hrs
Glargine 1-2 hrs Flat 20-24 hrs
Detemir 1-2 hrs Flat Up to 24 hrs
Degludec 1-2 hrs Flat >40 hrs

E7
 HYPOGLYCAEMIA

1. Treatment
a. For mild and asymptomatic hypoglycaemia patients: administer 15-20
g oral carbohydrate.
b. For more significant hypoglycaemia, if patient is alert and able to feed
orally, D50 40 ml po.
c. If patient is unable to take carbohydrate orally, D50 40 ml iv stat, with
monitoring of possible extravasation, followed by D10 drip.
d. If the patient is unconscious and/or having seizures, check airway,
breathing and circulation, and request immediate assistance from other
medical staff.
e. Glucagon 1 mg IMI (avoid in suspected phaeochromocytoma) or oral
glucose (after airway protection) if cannot establish iv line.
f. Monitor blood glucose and h’stix 15 mins after treatment and every 1-
2 hrs till stable.
g. Duration of observation depends on R/LFT and type of insulin/drug
(in cases of overdose).

2. Tests for Hypoglycaemia

a. Prolonged OGTT
 To document reactive hypoglycaemia, limited use
 Overnight fast
 Give 75g anhydrous glucose po
 Check blood glucose and insulin at 60 min intervals for 5 hrs and
when symptomatic

b. Prolonged Fasting Test

 Hospitalise patient, place near nurse station
 Fast for maximum of 72 hrs
 At 72 hrs, vigorous exercise for 20 mins (if still no
hypoglycaemia)
 H’stix q4h and when symptomatic
 Blood glucose, insulin, C-peptide at 0, 24, 48 and 72 hrs and when
symptomatic or h’stix < 3.0 mmol/L
 Terminate test if blood glucose confirmed to be < 3.0 mmol/L
 Consider checking urine hypoglycaemic agents level in highly
suspected cases

E8
 THYROID STORM

Note: The following regimen is also applicable to patients with uncontrolled

thyrotoxicosis undergoing emergency operation.

1. ICU care with close monitoring and organ support if possible

2. Hyperthermia: paracetamol (not salicylate), physical cooling

Dehydration: iv fluid (2-4 L/d)
iv Glucose, iv vitamin (esp. thiamine)
Supportive: O2, digoxin / diuretics if CHF/AF ± inotropes
Treat precipitating factors and/or co-existing illness

3. Propylthiouracil 150-250 mg q4-6h po / via nasogastric tube

Hydrocortisone 200 mg stat iv then 100 mg q6-8h
β-blockers (contraindicated in CHF / APO / cardiomyopathy/ asthma/
COPD): Propranolol 40-80 mg po q4-6h or 0.5-1 mg iv over 10 min every
several hrs; alternative: Esmolol (50-100 microgram/kg/min)

4. 1 hour later, use iodide to block hormone release

a. Lugol’s solution 10 drops q8h (1 drop = 0.05ml = 6.25 mg iodide/
iodine) or
b. SSKI 5 drops po q6h or
c. NaI continuous iv 0.5-1 g q12h

5. Consider plasmapheresis if ATD is contraindicated or conventional

therapies failed

6. Other therapies:
i. Consider Li2CO3 250 mg q6h to achieve Li level 0.6-1.0 mmol/L if
ATD or iodide therapy is contraindicated. But its use is largely limited
by its potential toxicity and narrow therapeutic range
ii. Cholestyramine: 3-4 g po q6h to decrease reabsorption of thyroid
hormone from enterohepatic circulation (other drugs should be taken at
least 1 hour before or 4-6 hours after cholestyramine to reduce possible
interference with absorption)

E9
 MYXOEDEMA COMA

1. Treat precipitating causes

2. Correct fluid and electrolytes, correct hypoglycaemia with D10
3. NS 200-300 ml/hr ± vasopressors
4. Maintain body temperature
5. Hydrocortisone 100 mg q6h iv with prior checking of serum cortisol
6. T4 200-500 micrograms po stat, then 100-200 micrograms po or
T3 20-40 micrograms stat, then 20 micrograms q8h po
7. Consider 5-20 micrograms iv T3 twice daily if oral route not possible

PHAEOCHROMOCYTOMA

1. Presentations: classic triad of headache, sweating and tachycardia; young/

severe/ resistant hypertension, labile blood pressure, adrenal
incidentaloma, etc
2. Biochemical confirmation by measuring urine catecholamines,
fractionated metanephrines and normetanephrines
3. Pre-operative localisation and staging by anatomical and functional scan.
4. Ensure adequate alpha-blockade before prescription of beta-blocker
5. Commonly used alpha blockers: phenoxybenzamine, prazosin, doxazosin
and terazosin

E 10
 ADDISONIAN CRISIS

1. Investigation:
a. RFT, electrolytes, glucose
b. Spot cortisol (during stress) ± ACTH
c. Normal dose (250 micrograms) short synacthen test (not required if
already in stress)#
d. May consider low dose (1 microgram) short synacthen test if secondary
hypocortisolism is suspected@
e. Look out for the causes and triggers
#
Normal dose short synacthen test
250 micrograms Synacthen iv/im as bolus
Blood for cortisol at 0, 30, 60 mins. Can perform at any time of the day
Normal: Peak cortisol level >550 nmol/L, Abnormal: < 400 nmol/L,
Borderline: 400-550 nmol/L (depends on type of cortisol assay)
@
Low dose short synacthen test
1 microgram Synacthen (mix 250 μg Synacthen into 500 ml NS and
withdraw 2 ml) IV as bolus
Blood for cortisol at 0, 30 mins. Can perform at any time of the day.
Normal: Peak cortisol level > ~400 nmol/L (depends on type of cortisol
assay) (Journal of the Endocrine Society 2017 Feb Vol. 1 Issue 2: 96-108. N.B.
LDCST done in morning and checked at time zero, 30 mins and 60 mins using
immunoassay)
 Correlate with clinical presentation. Consider steroid PRN as stress dose
cover for borderline cases.
 May need to confirm by other tests (insulin tolerance test or glucagon
tests) if borderline results.

2. Treatment
Treat on clinical suspicion, do not wait for cortisol results
a. Hydrocortisone 100 mg iv stat, then 50 mg iv q6h (may consider imi or
continuous iv infusion at 200 mg per day)
b. ±9α-fludrocortisone 0.05-0.2 mg daily po, titrate to normalise K and BP
c. Correct electrolytes
d. Fluid resuscitation 500-1000 ml 0.9% NS in the first hour, followed by
iv isotonic saline rehydration guided by fluid status

E 11
3. Relative Potencies of different steroids (different in different tissues)
Glucocorticoid Mineralocorticoid Equivalent
action action doses
Cortisone 0.8 0.8 25 mg
Hydrocortisone 1 1 20 mg
Prednisone 4 0.6 5 mg
Prednisolone 4 0.6 5 mg
Methylprednisolone 5 0.5 4 mg
Dexamethasone 25-30 0 0.75 mg
Betamethasone 25-30 0 0.75 mg

4. Steroid cover for surgery / trauma

Indications:
 Any patient given supra-physiological doses of glucocorticoids
(>prednisolone 7.5 mg daily) for >2 weeks in the past year
 Patients on steroids of uncertain dose or duration
 Suspected adrenal or pituitary insufficiency
a. Major Surgery
 Hydrocortisone 100 mg iv on call to OT room
 Hydrocortisone 50 mg iv in recovery room, then 50 mg iv q6h + K
supplement for 24 hrs or continuous iv infusion of 200 mg
hydrocortisone per 24 hours
 Post-operative course smooth: Decrease Hydrocortisone to 25 mg
iv q6h on D2, then taper to maintenance dose over 3-4 days
 Post-operative course complicated by sepsis, hypotension etc:
Maintain Hydrocortisone at 100 mg iv q6h (or 200 mg iv infusion
per day) till stable
 Ensure adequate fluids and monitor electrolytes
 Continue maintenance dose as tolerated
b. Minor Surgery
 Examples: Inguinal hernia repair, joint replacement
 Hydrocortisone 100 mg iv one dose
 Continue maintenance dose as tolerated
c. Superficial Surgery
 Example: Dental surgery
 No additional steroid doses

E 12
 ACUTE POST-OPERATIVE /
POST-TRAUMATIC DIABETES INSIPIDUS

1. Remember possibility of a Triphasic pattern:

Phase I: Transient DI, duration hrs to days
Phase II: Antidiuresis, duration 2-14 days
Phase III: Return of DI (may be permanent)

2. Mx
a. Monitor I/O, BW, serum sodium and urine osmolarity closely (q4h
initially, then daily)
b. Able to drink, thirst sensation intact and fully conscious: Oral
hydration, allow patient to drink as thirst dictates
c. Impaired consciousness and thirst sensation:
 Fluid replacement as D5 or ½:½ solution (Calculate volume
needed by adding 12.5 ml/kg/d of insensible loss to volume of
urine)
 DDAVP 1-4 micrograms (0.5-1.0 ml) q12-24h sc/iv
Allow some polyuria to return before next dose
Given each successive dose only if urine volume >200 ml/hr in
successive hours

3. Stable cases
 Give oral DDAVP 100-200 micrograms BD to TDS (tablet) or 60-120
micrograms BD to TDS (lyophilisate) to maintain urine output of 1-2
litres/day
 Watch out for excessive anti-diuresis (e.g. ankle swelling, poor urinary
output, hyponatraemia, etc) and consider dose adjustment or stop the
drug if necessary

PITUITARY APOPLEXY

1. Definite diagnosis depends on CT / MRI

2. Surgical decompression under steroid cover if
 Signs of increased intracranial pressure
 Change in conscious state
 Evidence of compression on neighbouring structures

E 13
Gastroenterology
and
Hepatology
 ACUTE LIVER FAILURE

Definition
 A severe liver injury (coagulopathy with INR ≥1.5)
 With onset of hepatic encephalopathy within 26 weeks of the first
symptoms
 In the absence of pre-existing liver disease

Classification
Hyperacute Acute Subacute
Jaundice to 0 to 1 week >1 to 4 weeks >4 to 26 weeks
encephalopathy interval
Prognosis (Survival) Moderate Poor Poor
Cerebral oedema Common Common Infrequent
PT Prolonged Prolonged Less Prolonged
Bilirubin Least raised Raised Raised

Search for aetiology and assess severity of acute liver failure (ALF)
 History – prescribed medications (e.g. high dose steroid,
immunosuppressants, B-cell depleting agents, chemotherapy), over-the-
counter medications, herbal medicine, mushroom (Amanita phylloides)
ingestion, Ecstasy use
 CBP/ Clotting/ LRFT/ glucose/ ABG/ Lactate
 Hepatitis (A, B, D, E) serology, HBV DNA
 Blood ammonia level (high levels are predictive of complications and
increased mortality)
 Autoimmune markers (ANA, ASMA, anti-LKM1)
 Metabolic markers (Caeruloplasmin for patients < 50 yrs old)
 Toxicology screening especially paracetamol level
 Anti-HIV (with informed consent) if liver transplant is considered
 Review herbal formula by Poison Information Centre (Tel: 2772 2211,
Fax: 2205 1890) or identification of herbal medicine by Toxicology
Reference Laboratory (Tel: 2990 1941, Fax: 2990 1942)
 Transjugular liver biopsy in selected cases

G1
Management
 Close monitoring, preferably in ICU
 Nutritional support: 1 to 1.5 g enteral protein/kg/day (lower level for
patients with worsening hyperammonaemia or at high risk for
intracranial hypertension)
 Avoid use of paracetamol
 Consider N-acetylcysteine (NAC) for both paracetamol- and non-
paracetamol-related ALF.
Alternative NAC regime for non-paracetamol ALF:
Loading dose: NAC 150 mg/kg/hr in D5 over 1 hour,
Then 12.5 mg/kg/hr in D5 over 4 hours,
Then 6.25 mg/kg/hr in D5 infusion for 67 hours (i.e. 72 hrs in total)
 Start nucleos(t)ide analogues for HBV-related ALF
 Liaise with QMH Liver Transplantation Centre if indicated

Hepatic encephalopathy
Grade I/II
 Consider transfer to a liver transplant centre
 CT brain to exclude other causes of altered consciousness
 Avoid stimulation/ sedation
 Lactulose
Grade III/IV
 Early endotracheal intubation and mechanical ventilation
 Choice of sedation: Propofol (small dose adequate; long T½ in patients
with hepatic failure). Avoid neuromuscular blockade as it may mask
clinical evidence of seizure activity
 Elevate head of patient ~30o, limit neck rotation or flexion
 Prophylactic anti-convulsant not recommended. Immediate control of
seizure with minimal doses of benzodiazepine. Control seizure activity
with phenytoin
 Consider ICP monitoring especially if patient listed for liver transplant
with high risk of cerebral oedema

Intracranial hypertension
1. Mannitol
 Dose: 0.5-1 g/kg IV over 30-60 min, can repeat once / twice Q4H if
needed
 Stop if serum osmolality > 320 mosm/L
 Risk of volume overload in renal impairment and hypernatraemia
G2
  Prophylactic use not recommended
 Use in conjunction with RRT in renal failure
2. Hyperventilation
 Indicated when increased ICP not controlled with mannitol
 Keep PaCO2 at 4-6 kPa
 Sustained hyperventilation should be avoided
3. Others (ICU setting preferred if available)
 Hypertonic saline solution and barbiturate for refractory intracranial
hypertension
 Therapeutic hypothermia (cooling to a core temperature of 32-34oC)

Infection
 Screening for sepsis to detect bacterial and fungal infection
 Low threshold to start appropriate wide-spectrum anti-bacterial/
antifungal therapy as usual clinical signs of infection may be absent

Coagulopathy and bleeding

 Spontaneous and clinically overt bleeding uncommon in ALF
 Variceal bleeding in the setting of ALF should raise suspicion of Budd-
Chiari syndrome
 Give prophylactic famotidine or PPI to reduced stress-related GIB
 Give Vitamin K1 10mg IV Q24H
 Replacement therapy for thrombocytopenia (<50-70 x 109/L) and/or
prolonged prothrombin time (INR ≥1.5) only in the setting of
haemorrhage or before invasive procedures

Haemodynamic / Renal failure

 Fluid replacement for intravascular volume deficits (colloids preferred)
 All solutions should contain dextrose to maintain euglycaemia
 Maintain mean arterial pressure (MAP) > 75 mmHg
 Use vasopressor (noradrenaline/dopamine) when fluid replacement fails
to maintain adequate MAP
 Assess adrenal function in patient requiring vasopressors
 Consider pulmonary artery catheterization in haemodynamically unstable
patient to ensure adequate volume replacement
 CVVH preferred for acute renal failure requiring dialysis

G3
Considerations for liver transplantation
King’s College Hospital prognostic criteria
Paracetamol Non-paracetamol
pH < 7.3, or PT > 100 (INR > 6.5), or
All 3 criteria: Three out of 5 criteria:
1. PT > 100s 1. Age < 10 or > 40
(INR > 6.5) 2. Aetiology: Drug-induced, indeterminate
2. Cr > 300 μmol/L 3. Bilirubin > 300 μmol/L
3. Grade III/IV hepatic 4. Jaundice to coma interval > 7 days
encephalopathy 5. PT > 50 (INR 3.5)

Calculate MELD score for reference (see page G8)

Contraindications for liver transplantation

 HIV infection
 Active alcohol or substance abuse (relative contraindications)
 Systemic infections
 Life-limiting co-existing medical conditions: advanced heart, lung or
neurologic conditions
 Uncontrolled psychiatric disorder
 Inability to comply with pre- and post-transplant regimens

G4
 HEPATIC ENCEPHALOPATHY

Child-Pugh Grading of Severity of Chronic Liver Disease

Points: 1 2 3
Parameters:
Encephalopathy None I and II III and IV
Ascites Absent Mild Moderate
Bilirubin (μmol/l) <35 35 – 50 >50
for PBC (μmol/l) <70 70 – 170 >170
Albumin (g/l) >35 28 – 35 <28
Prothrombin time
1–3 4–6 >6
(seconds prolonged)
Grades: A: 5-6 points; B: 7-9 points; C: 10-15 points

Grading (Grade 0-I: Covert HE; Grade II-IV: Overt HE)

0 Psychometic or neuropsychological alteration of tests (psychometric,
psychomotor or neurophysiological) without clinical evidence of mental
change
I Euphoria, mild confusion, mental slowness, shortened attention span,
slurred speech, disordered sleep
II Lethargy or apathy, disorientation, moderate confusion, inappropriate
behaviour, drowsiness
III Marked confusion, incoherent speech, somnolence or semi-stupor,
responsive to stimuli, bizarre behaviour
IV Coma, initially responsive to noxious stimuli, later unresponsive

Management of hepatic encephalopathy in cirrhotic patients

 Initiate care for patients with altered consciousness
 Look for other causes of altered mental state

A. Identify and correct precipitating factors

 Watch out for infection, constipation, gastrointestinal bleeding,
diuretic overdose, electrolyte disorder. (Other possible precipitating
factors: excess dietary intake of protein, vomiting, large volume
paracentesis, recent alcohol binge, vascular occlusion and primary
HCC)
 Avoid sedatives, alcohol, diuretic, hepatotoxic and nephrotoxic drugs
 Correct electrolyte imbalance (azotaemia, hyponatraemia,
hypokalaemia, metabolic alkalosis/acidosis)

G5
B. Treatment
 Tracheal intubation should be considered in patient with deep
encephalopathy.
 Nutrition: In case of deep encephalopathy, oral intake should be
withheld 24-48 hr and iv dextrose should be provided until
improvement. Enteral nutrition by gastric tube can be started if
patients are unable to eat after this period. Protein intake begins at a
dose of 0.5 g/kg/day, with progressive increase to 1.2-1.5 g/kg/day.
Vegetable and dairy sources are preferable to animal protein. Liaise
with dietitian if necessary.
 Oral formulation of branched chain amino acids (BCAA) may
provide better tolerated source of protein in patients with chronic
encephalopathy and dietary protein intolerance.
 Lactulose (oral/via nasogastric tube) 30-40 ml q8h and titrate until 2-3
soft stools/day.
 Rifaximin can be given as an add/on therapy to lactulose for
prevention of recurrent episodes of hepatic encephalopathy.
 Antibiotics in suspected sepsis.
 Consider referral for liver transplantation in selected cases – recurrent
intractable overt HE.

G6
 ASCITES
A. Investigations
 Perform diagnostic paracentesis. Initial laboratory investigation of
ascitic fluid should include an ascitic fluid cell count and differential,
ascitic fluid total protein, SAAG and cytology.
 USG abdomen
 Alpha-fetoprotein

B. Conservation Treatment (aim to reduce BW by 0.5 kg/day)

1. Low salt diet (≤2 g Na/day)
2. Fluid restriction (1-1.5 L/day) if dilutional hyponatraemia Na <120-
125 mmol/L
3. Monitor input/output, body weight, urine sodium
4. Spironolactone starting at 50 mg daily (single morning dose) alone or
with Frusemide 20 mg daily as combination therapy.
5. Increase the dose stepwise (maintaining the 100 mg: 40mg ratio) every
5-7 days to the maximum dose of spironolactone 400 mg/day and
frusemide 160 mg/day if sub-optimal response (if weight loss and
natriuresis are inadequate)
6. Amiloride (10-40 mg/day) can be substituted for spironolactone in
patients with tender gynaecomastia.
7. Once ascites has largely resolved, dose of diuretics should be reduced
and discontinued later whenever possible.
8. All diuretics should be discontinued if there is severe hyponatraemia
<120 mmol/L, progressive renal failure, worsening hepatic
encephalopathy, or incapacitating muscle cramps.
 Frusemide should be stopped if there is severe hypokalaemia (<3
mmol/L)
 Spironolactone should be stopped if there is severe hyperkalaemia
(>6 mmol/L)

C. Therapeutic paracentesis can be used in refractory ascites

 Exclude spontaneous bacterial peritonitis before paracentesis
 Caution in patients with hypotension and raised serum creatinine,
monitor vital signs during paracentesis
 If > 5L fluid removed, give IV albumin 6-8g per litre tapped

D. Consider TIPS in refractory ascites

E. Referrals to liver transplant centre for potential candidate

G7
 GENERAL GUIDELINES FOR
CONSIDERATION OF ORTHOTOPIC LIVER
TRANSPLANTATION (OLT) IN CHRONIC LIVER DISEASE
OR HEPATOCELLULAR CARCINOMA

Chronic liver disease and hepatocellular carcinoma

Patients who have an estimated survival of less than 80% chance after 1 year
as a result of liver cirrhosis should be referred for consideration of liver
transplantation. If any of the following are present, it may be appropriate to
refer the patient:

A. MELD score ≥15 (Model for End-stage Liver Disease)

MELD Score = 10 x ((0.957 x ln(Creatinine)) + (0.378 x ln(Bilirubin)) +

(1.12 x ln(INR))) + 6.43 [uniteds are mg/dL]

https://optn.transplant.hrsa.gov/resources/allocation-calculators/meld-
calculator/

B. Complications of cirrhosis
 Refractory ascites or hydrothorax
 Spontaneous bacterial peritonitis (management see In14)
 Encephalopathy
 Very poor cirrhosis related quality of life
 Hepatorenal syndrome, hepatopulmonary syndrome, or
portopulmonary hypertension
 Portal hypertensive bleeding not controlled by endoscopic therapy or
transjugular intra-hepatic porto-systemic shunt

C. For patients with unresectable hepatocellular carcinoma and those with

hepatocellular carcinoma and underlying cirrhosis
 Solitary tumour of less than 5cm in diameter or those with up to 3
tumours (each of which should be < 3cm)
 For tumours beyond the above criteria, patients may still be eligible for
liver transplantation if:
i. There is a potential living-related donor and
ii. Single tumour not exceeding 6.5 cm, or 2-3 lesions none exceeding
4.5 cm, with the total tumour diameter less than 8 cm.

G8
 Acute liver failure/acute on chronic liver failure
These patient should be referred early to avoid delay in work-up for potential
liver transplantation if they have any of the following criteria:
 Those with rising INR (>2.0)
 Evidence of early hepatic encephalopathy

Relative contra-indications to liver transplantation

 Alcoholic patients with less than 6 months abstinence
 Extra-hepatic malignancy
 Severe/uncontrolled extra-hepatic infection
 Multi-system organ failure
 Significant cardiovascular, cerebrovascular, or pulmonary disease
 Advanced age

If in doubt, discuss with the liver transplant team.

G9
 VARICEAL HAEMORRHAGE

A. Initial Management (as in upper GI bleeding)

 Maintain systolic BP at 90-100 mmHg but avoid excessive volume
restitution (increase portal pressure → early rebleeding and higher
mortality)
 Restrictive blood transfusion, aim at Hb 7-9 g/dL
 Correction of significant coagulopathy and thrombocytopenia may be
considered
 Routine uses of NG tube is not recommended but it may be used in
cases of hepatic encephalopathy

B. Vasoactive agents should be initiated before endoscopy to patient with

suspected variceal bleeding and maintained for 2-5 days after endoscopic
treatment.
 Terlipressin 2 mg IV bolus Q4H (can be titrated down to 1mg IV Q4H
once haemorrhage is controlled)
 Octreotide 50 micrograms iv bolus, then 50 micrograms/hour IV
infusion
 Somatostatin 250 micrograms iv bolus, then 250 microgram/hour IV
infusion
- Beware of side-effects related to vasoconstriction such as bowel
ischaemia, hypertension, myocardial ischaemia, peripheral vascular
ischaemia
- Treatment duration up to maximum of 48 hours

C. IV thiamine for alcoholics

D. Anti-encephalopathy regimen
 Correct fluid and electrolyte imbalances
 Lactulose 10-20 ml q4-8H PO or via NG tube aims at 2-3 bowel
motions per day. It can be given as enema (300 ml in 1L water) retained
for 1 hr with patient in Trendelenburg position.

E. Prevention of sepsis
 Short-term (7 days) prophylactic antibiotic: IV ciprofloxacin 400 mg
BD (patients with preserved liver function), or IV ceftriaxone 1 g/day
(patients with advanced cirrhosis or known quinolone-resistance), or
IV ertapenem 1 g/day (patients with recent ESBL-Enterobacteriaceae
infection)
G 10
F. Endoscopic treatment
 Upper endoscopy should be arranged as soon as possible after
admission once haemodynamic condition is stabilised (SBP >70
mmHg).
 Patients with altered mental state or massive bleeding should undergo
endotracheal intubation and mechanical ventilation prior to endoscopy.
 Esophageal variceal ligation (EVL) for oesophageal varices; Tissue
glue like N-butyl-cyanoacrylate injection for gastric varices.
 Vasoactive agents should be initiated within 30 mins after confirmation
of variceal bleeding if not given prior to endoscopy.
 Proton-pump inhibitor (PPI) should be given for 2 weeks.

G. Uncontrolled/recurrent variceal bleeding

 Recurrent bleeding should be managed by repeated endoscopy
 Refer to emergency surgery (port-systemic shunting, devascularisation)
or TIPS as salvage therapies for uncontrolled bleeding
 Balloon tamponade should only be used as temporary measure (up to
24 hr) until definitive therapy is planned. If haemostasis is not achieved,
other therapeutic options should be considered.

H. Prevention of rebleeding
 EVL combined with a non-selective beta-blocker* (NSBB) is
recommended as secondary prevention.

* NSBB (non-selective beta-blocker): propranolol, nadolol or carvedilol should be

started at low dose and titrated up till 25% reduction in resting heart rate but not lower
than 55 beats/min.

G 11
 UPPER GASTROINTESTINAL BLEEDING

A. Initial Management (Consider ICU if severe bleeding)

 Nil by month
 Insert large bore IV cannula
 Closely monitor BP, Pulse, I/O
 Risk stratification applying Rockall score or Glasgow-Blatchford score
(see page G14)
 Blood transfusion when Hb < 7 g/dL (except for massive bleeding) and
fluid replacement as required.
 Withhold anticoagulants and antiplatelet if possible. Weigh against the
thrombotic risk of an individual patient before REVERSAL of
anticoagulation.
 Cuffed ET tube to prevent aspiration if massive haematemesis or
suspected compromised respiratory or airway condition
 Nasogastric tube if massive haematemesis or signs suggestive of GI
obstruction
 Tranexamic acid is not recommended as evidence is insufficient
 Pre-endoscopy IV proton-pump inhibitor (PPI) treatment is
recommended if early endoscopy (within 24 hours) cannot be arranged.
 IV antibiotics in all cirrhotic patients with GI bleeding: IV Augmentin
1.2 g Q8H/ IV levofloxacin 500 mg Q24H (max 7 days)
 Arrange early (within 24 hours) upper endoscopy after initial
stabilization.

B. Indications for Emergency Endoscopy

 Haemodynamic shock
 Massive haematemesis/bloody NG aspirate
 Suspected gastroesophageal variceal bleeding

C. Contraindications for Endoscopy

 Suspected intestinal perforation
 Unstable cardiac or pulmonary status

D. Post-endoscopy Management
 After endoscopic treatment of patients with actively bleeding ulcer,
ulcer with visible vessel or ulcers with adherent clot resistant to
vigorous irrigation, IV PPI infusion should be given for 72 hours.
 IV PPI Infusion: pantoprazole / esomeprazole 80 mg IV bolus stat
followed by 8 mg/hr infusion
G 12
  Among aspirin users with high cardiothrombotic risk, aspirin should be
resumed as soon as possible within 3-5 days provided haemostasis of
ulcer bleeding is established.

E. Recurrent bleeding
 A repeat endoscopy should be attempted
 If bleeding cannot be controlled or recurs, surgical intervention
becomes necessary.
 Angiographic embolization may be considered as an alternative if
expertise is available.

G 13
Rockall Score (ABCDE)
Variables 0 1 2 3
Age <60 60-79 ≥80
Pre-endoscopic

No shock Tachycardia
Blood Hypotension
SBP ≥100 SBP ≥100
pressure SBP <100
P <100 P >100
CHF, IHD, Renal failure,
Co-morbidity No major liver failure,
diseases metastatic ca
Mallory- All other Dx
Dx at time of GI
Endoscopic

Weiss, no except
OGD malignancy
SRH malignancy
Blood,
Evidence of No, or dark
adherent clot,
bleeding spot only
spurter
Pre-endoscopy score
Full score (Pre-endoscopic +
0: Early discharge or non-admission
endoscopic)
0-1: Low risk
0-3: excellent, consider early discharge
2-3: Moderate risk
>8: high risk of death and rebleeding
>4: High risk of death

Glasgow-Blatchford Score (GBS)

Score
6.5 to <8 2
8 to <10 3
Blood Urea
10 to <25 4
>25 6  0: can be safely managed
Male Female as outpatient without early
12 to <13 10 to <12 1 endoscopy
Hb
10 to <12 3  >0: increased risk for
<10 10 6 intervention and inpatient
100-109 1 management is
Systolic BP 90-99 2 recommended
<90 3  >6: >50% risk of needing
Pulse >100 1 an intervention
Melaena Yes 1
Syncope Yes 2
Hepatic disease Yes 2
Cardiac failure Yes 2

G 14
 PEPTIC ULCERS

A. Ulcer-healing drugs
 H2-antagonist for 8 weeks
Famotidine 20 mg bd or 40 mg nocte
 Proton-pump inhibitors (PPI)* for 4-6 weeks
Pantoprazole 40 mg om
Rabeprazole 20 mg om
Lansoprazole 30 mg om
Esomeprazole 20 mg om
*PPI should be taken 30-60 min before meals

B. Anti-Helicobacter pylori therapy

1. First line therapy
Standard triple therapy PPI (BD) + clarithromycin (500 mg BD) +
amoxicillin (1g BD) for 7-14 days (substitute
amoxicillin with metronidazole 400 mg BD in case
of penicillin allergy)
2. Salvage therapy
Levofloxacin-based triple PPI (BD) + levofloxacin (500 mg daily) +
therapy amoxicillin (1g BD) for 10-14 days
Bismuth quadruple PPI (BD) + bismuth subsalicylate (524 mg four
therapy times a day) + tetracycline (500 mg four times a day)
+ metronidazole (400 mg four times a day) for 10-
14 days
Non-Bismuth quadruple PPI (BD) +_clarithromycin (500 mg BD) +
therapy amoxicillin (1g BD) + metronidazole (400 mg BD)
for 14 days

C. NSAID/ aspirin user with active peptic ulcer

 NSAID user: discontinue NSAID during PPI treatment
 Aspirin user with non-bleeding peptic ulcer: continue aspirin with PPI
treatment; step up dosage of PPI to BD if already on daily PPI
 Aspirin user with bleeding peptic ulcer: resume aspirin with PPI
treatment once haemostasis is secured (usually within 3-5 days) in order
to minimize cardiovascular risk

D. Ulcer prevention
 H pylori ulcer:
- Maintenance acid suppression therapy not necessary after H pylori
eradication
G 15
  NSAID ulcer:
- Avoid NSAID if high GI risk^ or prior complicated peptic ulcer
- Add PPI as prophylaxis with NSAID or COX-2 inhibitor use
 Aspirin ulcer:
- Review the indication for aspirin
- Add PPI as prophylaxis when aspirin is resumed
 Idiopathic ulcer:
- Consider long-term maintenance PPI

^High GI risk = more than 2 of the followings: age >65, previous history
of peptic ulcer, concomitant use of aspirin, corticosteroids or anti-
coagulants

E. Follow-up Endoscopy
 Uncomplicated DU => Unnecessary if asymptomatic
 GU or complicated (bleeding / obstruction) or giant DU (>2cm) =>
Necessary till complete healing confirmed

G 16
 MANAGEMENT OF GASTRO-OESOPHAGEAL REFLUX
DISEASE (GERD)

A. Empirical PPI (Proton-pump inhibitor) trial [BD dose PPI for 4 weeks]:
 For patients with typical GERD symptoms (heartburn and regurgitation)
and without alarming symptoms (see below), an initial trial of empirical
PPI is appropriate.
 Patients with chest pain suspected due to GERD should have IHD
excluded before empirical PPI trial.
B. Indications for endoscopy in GERD
 Not diagnosis of GERD with typical symptom.
 Presence of alarm features (dysphagia, odynophagia, unintentional weight
loss, anaemia, haematemesis and/or melaena, recurrent vomiting, family history
of gastric and/or oesophageal cancer, chronic non-steroidal anti-inflammatory
drug use, age >40 years in areas of a high prevalence of gastric cancer).
 Persistent symptom after empirical PPI trial (need to stop PPI for at
least 1 week prior to endoscopy).
 Diagnosis of complications of GERD including oesophagitis, Barrett’s
oesophagus.
 Severe oesophagitis (LA Grade C-D*) after 8-week PPI treatment to
assess healing and exclude Barrett’s oesophagus.
 History of oesophageal stricture in patients who have recurrent
dysphagia.
 Evaluation before anti-reflux surgery.
C. Indications for oesophageal pH monitoring
 When diagnosis of GERD is in doubt (off PPI for 1 week before test).
 When treatment is ineffective (keep PPI before test) to define those with
or without continued abnormal acid exposure times.
 Evaluation before endoscopic or surgical therapy (off PPI for 1 week
before test).
 Persistent/recurrent symptoms after reflux surgery.
D. Indications for oesophageal manometry
 Not indicated for uncomplicated GERD
 Pre-operative assessment to exclude severe oesophageal motility
disorders before anti-reflux surgery
E. Indications for oesophageal impedance testing
 To detect non-acid reflux when oral PPI therapy is ineffective
F. Management
 Life style modification: body position, food, weight reduction,
behaviour.
G 17
  Severe oesophagitis (LA Grade C-D): standard PPI dose# for 8 weeks.
Doubling the dose to twice daily may be necessary in some patients
when symptoms or oesophagitis are not well controlled. Maintenance
therapy is required in severe oesophagitis/Barrett’s oesophagus and
lowest PPI dose should be used to minimize long term adverse effects.
 Non-erosive GERD (NERD)/ mild oesophagitis (LA Grade A-B):
standard dose H2 antagonists (H2RA) or PPI# for 8 weeks. On-
demand/intermittent H2RA can be used as maintenance treatment.
G. Indications for anti-reflux surgery
 Unresponsive or intolerant to medical treatment
 Complications of GERD unresponsive to medical therapy

*Los Angeles classification of reflux oesophagitis (LA Grade)

A mucosal break(s) <5mm, no extension between tops of mucosal folds
B mucosal break >5mm, no extension between tops of mucosal folds
C mucosal breaks continuous between tops of mucosal folds, but not
circumferential
D mucosal break(s) involving >75% of circumference

#Standard dose acid suppressants for GERD:

Pantoprazole 40 mg daily, rabeprazole 20 mg daily, lansoprazole 30 mg daily,
dexlansoprazole 30 mg daily, esomeprazole 40 mg daily, famotidine 20 mg bd.
All PPIs except dexlansoprazole should be administered 30-60 min before meals to
assure maximal efficacy. (Dexlansprazole can be taken at any time of the day)

G 18
 INFLAMMATORY BOWEL DISEASES: OVERVIEW

Diagnosis
Diagnosis is a based on a combination of clinical, biochemical, endoscopic,
histologic and radiologic parameters with exclusion of infectious causes.

A. History:
 Recent travel, medication (antibiotics, NSAID), sexual and vaccination
 Smoking, prior appendicectomy, family history, recent episodes of
infectious GE
 Bowel habit: stool frequency and consistency (nocturnal, usually >6
weeks duration), urgency, tenesmus, per rectal passage of blood and
mucus
 Abdominal pain, malaise, fever, weight loss
 Perianal abscess / fistulae: current or in the past
 Extra- intestinal manifestations: joint, eye, skin, oral ulcer

B. Physical Examination:
 G/C, hydration, Temp, weight, BMI, nutritional assessment, BP/P,
pallor, oral ulcer
 Abdominal distension or tenderness, palpable masses, perianal
inspection and PR

C. Endoscopy and biopsy for histological evaluation

1. Sigmoidoscopy is sufficient in acute severe colitis, take a minimum of
2 biopsies at rectum and sigmoid colon
2. Ileocolonoscopy:
a. Features suggestive of Crohn’s disease
 Patchy distribution of inflammation with skip lesions, rectal
sparing, stricture, fistula, perianal disease
 Deep ulcers, linear ulcers, multiple aphthous ulcers,
cobblestoning mucosa
 A minimum of 2 biopsies from each of the 6 segments (terminal
ileum, ascending, transverse, descending, sigmoid and rectum)
including macroscopically normal segments
b. Features suggestive of ulcerative colitis

G 19
  Rectal involvement, extend proximally in a continuous,
confluent and concentric fashion; clear and abrupt demarcation
between inflamed and normal mucosa;
 Caecal patch: patchy inflammation in caecum, observed in left-
side colitis
 Backwash ileitis: continuous extension of macroscopic or
microscopic inflammation from caecum to distal ileum,
observed in up to 20% of patients with pancolitis; associated
with a more refractory course
 Severity:
 Mild: mucosal erythema, decreased vascular pattern, mild
friability
 Moderate: marked erythema, absent vascular pattern,
friability, erosions
 Severe: spontaneous bleeding, ulceration
3. Anorectual ultrasound: for assessment of fistulising perianal CD
4. Small bowel capsule endoscopy: high clinical suspicion of CD but –ve
endoscopic/radiologic findings (CT/MR enterography is required to
exclude small bowel strictures first before capsule endoscopy in a
patient with Crohn’s disease, because of the risk of capsule retention).

D. Radiology
1. AXR: small bowel or colonic dilatation (toxic megacolon: transverse
colon diameter >5.5 cm associated with systemic toxicity), assess
disease extent (inflamed colon contains no solid faeces), mass in right
iliac fossa, calcified calculi, sacroiliitis
2. CT/MR enterography/abdomen/pelvis: disease extent and activity,
inflammatory vs fibrotic stricture, extraluminal complication, fistula,
perianal disease
3. Barium fluoroscopy: superior sensitivity for subtle early mucosal
disease but is largely replaced by CTE/MRE

E. Laboratory Ix:
1. Blood test
 CBP and ESR: look for anaemia and thrombocytosis
 LFT, electrolytes, RFT, Mg

G 20
  CRP: correlates with disease activity, response to treatment and risk
of relapse
 Iron studies, vitamin B12 and folate level
 Antibodies: Anti-Saccharomyces cerevisiae antibody (ASCA) and
Anti-neutrophil cytoplasmic antibody (ANCA) have limited role in
diagnosing CD (ASCA +ve / ANCA –ve) and UC (ANCA +ve /
ASCA –ve)
 G6PD status: caution when using sulphasalazine
2. Stool
 Microscopy and culture to rule out infective causes e.g.
Campylobacter spp., E.coli O1457:H7, amoebae and other parasites
 PCR testing for Clostridium difficile toxin
3. Microbiologic study of tissue biopsy
 To exclude Mycobacterium tuberculosis infection
 To exclude cytomegalovirus colitis in severe or refractory colitis
4. Facecal calprotectin
 Marker of colonic inflammation
 Useful to differentiate IBD from functional diarrhoea, monitor
disease activity and predict clinical relapse

Management
1. Nutrition:
 An adjunct to medical treatment
 Dairy free diet in case of active colitis
 Calcium, vitamin D, fat soluble vitamin, zinc, iron, vit B12 as required
2. Correction of fluid and electrolyte disturbance
3. Smoking cessation:
 Smoking as a risk factor of CD: higher risk of flare, need of surgery
and post-operative recurrence
4. An alternative explanation for new symptom should be considered e.g.
infection, bacterial overgrowth, bile salt malabsorption, dysmotility,
gallstones
5. Objective evidence of disease activity should be obtained before starting
or changing medical therapy.
6. Avoid NSAID, anticholinergic, antidiarrhoeal, opioids (precipitate colonic
dilatation).

G 21
7. 5-ASA and steroid formulations for IBD
Mechanism of Site of Unit
Route Formulation Drug Brand
drug release delivery strength
5-ASA linked to
sulphpyridine by
azo bond which 500mg
Tablet Sulphasalazine Salazopyrin EN breaks up by Colon (200mg 5-
azoreductase ASA)
from bacteria in
colon
Pentasa Time dependent
Duodenum to
Prolonged continuous 1g
colon
Release Tablet release
Time dependent
Pentasa Slow Duodenum to
continuous 500mg
Release Tablet colon
release
pH dependent
Mid jejunum 250mg or
Salofalk (Release at
to colon 500mg
pH≥6)
5-ASA
pH dependent
(Release at
Terminal
pH≥7) & Multi-
Mezavant XL ileum to 1.2g
Matrix System
colon
(MMX)
Tablet extended release
pH dependent Terminal
Asacol (Release at ileum to 400mg
pH≥7) colon
Oral Ileum to
Prolonged
Entocort ascending 3mg
release granules
colon
pH dependent
Budesonide (Release at pH
Terminal
>7) & Multi-
Cortiment ileum to 9mg
Matrix System
colon
(MMX)
extended release
Systemic 1mg, 5mg or
Prednisolone Not Applicable Not Applicable
absorption 25mg
Pentasa Time dependent
Duodenum to 1g or 2g
Prolonged continuous
colon sachet
Release Granules release
pH dependent
Granules 5-ASA
(Release at
Salofalk Granu- Mid jejunum 500mg or 1g
pH≥6) &
Stix to colon sachet
prolonged
release granules
Up to
Rectal Foam Budesonide Budenofalk Topical 2mg per
Sigmoid
Up to splenic
5-ASA Pentasa Topical 1g/100ml
flexure
Up to splenic
Enema Salofalk Topical 4g/60ml
Rectal flexure
Up to splenic
Prednisolone Predsol Topical 20mg/100ml
flexure
Pentasa Topical Rectum 1g
Suppository 5-ASA 250mg or
Salofalk Topical Rectum
500mg

G 22
 CROHN’S DISEASE

Risk factors: smoking, prior appendicectomy, family history of IBD, hx of

infectious GE in the prior one year

Montréal phenotypic classification

A. Age of onset: A1 <16 yrs
A2 17 – 40 yrs
A3 >40 yrs
B. Disease location: L1 Ileal
L2 Colonic
L3 Ileocolonic
L4 Isolated upper GI (a modifier that can be
added to L1-L3 when concomitant UGI
disease is present)
C. Disease behaviour: B1 Non-stricturing, non-penetrating
B2 Stricturing
B3 Penetrating
p Perianal fistulae / abscess (added to B1-B3
when concomitant perianal disease is present)

Medical Management: to induce and maintenance remission, taking into

account on activity, site, disease behaviour and patient reference

Disease activity
Mild Moderate Severe
CDAI 150-220 220-450 >450
Ambulatory Eating Intermittent
General
and drinking vomiting
Cachexia, BMI
Weight Loss <10% Loss >10%
<18
Tenderness mass
Abscess
Examination No overt
Obstruction
obstruction
Persistent
Ineffective for mild symptom despite
Treatment
disease intensive
treatment
CRP Usually > ULN >ULN Increased

G 23
 A trend towards early introduction of immunomodulatory and biologics in
patients with adverse prognostic factors:
1. Young age <40
2. Extensive small bowel disease
3. Requiring steroid in initial treatment
4. Perianal disease
5. Stricturing disease
6. Deep colonic ulcers

A. Aminosalicylates:
 No consistent evidence that it is effective in maintenance of remission
 Monitor CBP and RFT
 Sulphasalazine: 3-6 g/day is modestly effective in colonic disease
 Mesalazine: limited efficacy for ileal or colonic disease
B. Antibiotics:
 Septic complications, symptom attributed to bacterial overgrowth,
perianal disease
C. Corticosteroid:
 Effective to induce remission, ineffective in maintenance of remission
 Ca and vit D supplements, +/- osteoprotective therapy if given >12 wks
 Systemic steroid: no evidence to support use of a particular regimen but a
standard tapering strategy is recommended
e.g. Prednisolone 40 mg/day, reducing by 5 mg/day at weekly
intervals
20 mg/day x 4 wks, then reduce by 5 mg/day at
weekly intervals
Budesonide CIR: 9 mg daily, for disease affecting ileum and
ascending colon, extensive first-pass metabolism
with low systemic bioavailability, less effective
than conventional corticosteroid but fewer side
effects
D. Immunomodulator:
 Thiopurines: to maintain remission, steroid-sparing effect check
thiopurine methyltransferase (TPMT) and NUDT15 activity if available
(azathioprine pharmacogenetics test)
Azathioprine 1.5-2.5 mg/kg/day or Mercaptopurine 0.75-1.5 mg/kg/day
Delayed onset of action, takes 8-12 wks, monitor CBC d/c and LFT
 Methotrexate: active or relapsing CD refractory to/intolerant of
thiopurines or anti-TNF, monitor CBP d/c and LFT
Induction: 25 mg once per week for 16 wks, maintenance: 15 mg once per
week, IM or SC

G 24
 Folic acid 5 mg weekly, given oral 3 days after methotrexate
E. Biologics:
1. Anti-TNF
 Contraindications: latent untreated or active TB, NYHA Class III-IV
heart failure, hx of demyelinating disease, optic neuritis, history of
lymphoma.
 Infliximab: chimeric anti-TNF antibody
Loading with 5 mg/kg at 0, 2 and 6 wk, then at 8-weekly intervals IV
infusion
 Adalimumab: humanised anti-TNF
Loading with 80mg/40mg or 160mg/80mg at 0 and 2 wk, then 40mg
every other week, sc
2. Anti-α4β7 integrin
 Vedolizumab: humanized monoclonal antibody
 Loading with 300 mg at 0, 2 and 6 wk, then at 8-weekly intervals IV
infusion
 Gut-selective biologic agent, lower risk of serious infection, onset
slower than anti-TNF agent
3. Anti-IL12/23 p40
 Ustekinumab: human monoclonal antibody
 Initial IV dosing based on BW, administered over at least 1 hr; BW
>85kg 520mg; >55kg to <85kg 390mg; <55kg 260mg
 Then 90mg at 8 wk and then at 12-weekly interval, sc
F. Proton pump inhibitors: for upper GI involvement

Surgical Management: aim at bowel conservation

 An option in localized disease, septic complication, non-inflammatory
obstructive symptom (stricturoplasty for small bowel, endoscopic
dilatation for large bowel)
 Perianal disease: examination under anaesthesia (EUA) to assess extent of
disease, drain collections, seton drainage, advancement flaps, fistula plugs.

G 25
 ULCERATIVE COLITIS

A chronic relapsing and remitting inflammatory condition leading to continuous

mucosal inflammation, affecting the rectum and to a variable extent of the colon.

Protective factors: appendicectomy (for genuine appendicitis), smoking

Risk factors: family history of IBD, non-selective NSAID in exacerbation of UC

Montréal phenotypic classification: according to the maximal extent of

inflammation observed at colonoscopy
 Influences treatment modality, oral and/or topical
 Influences timing of starting surveillance and its frequency
E1 Proctitis involvement limited to the rectum
E2 Left-sided (distal UC) involvement extending up to splenic flexure
E3 Extensive (pancolitis) involvement extends proximal to the splenic flexure

Medical Management
 Depends on disease activity, extent and pattern of disease, taking patient
preference into account

Disease activity Modified Truelove and Witt’s criteria for clinical practice
Mild Moderate Severe
Bloody stools / day <4 ≥4 ≥6
Pulse < 90 bpm ≤ 90 bpm > 90 bpm
Temperature < 37.5 C
o
≤ 37.8 C o
> 37.8 oC
Haemoglobin > 11.5 g/dL ≥ 10.5 g/dL < 10.5 g/dL
ESR < 20 mm/h ≤ 30 mm/h > 30 mm/h
or CRP Normal ≤ 30 mg/L > 30 mg/L
 Immediate admission warranted in severe disease
 Toxic megacolon: total or segmental non-obstructive dilatation of colon
>5.5cm or caecum >9cm, associated with systemic toxicity

Prognostic indicators:
1. Patients diagnosed < age 16 have a more aggressive initial course
2. Older age of diagnosis is associated with a lower risk of colectomy
3. CRP > 45 mg/L on D3 of hospital admission and 3-8 stools/day as predictor
of colectomy
4. CRP > 10 mg/L after a year of extensive colitis predicts ↑ rate of surgery
5. Presence of sclerosing cholangitis increases risk for colorectal cancer

G 26
 Dose/day Induction Maintenance
Mesalazine
Suppository: distal 10cm 500 mg BD/ 1 gm 0.5-1 gm
Enema: to splenic flexure 1-4 gm 1-4 gm
Topical

Steroid enema
Prednisolone 20mg
Budesonide 2gm
Mild to Moderate Disease

Aminosalicylate
Sulphasalazine 4-6 gm 2-4 gm
Mesalazine tab 2-4 gm ≥ 2 gm
Mesalazine granules 1.5-4 gm 1.5-2 gm
Steroid
Oral

Prednisolone 20-40 mg
Budesonide 9 mg
Thiopurine
Azathioprine 1.5-2.5 mg/kg
Mercaptopurine 0.75-1.5 mg/kg
Steroid
IV Hydrocortisone 100 mg Q6-8H
Anti-TNF
Infliximab (IV) 5 mg/kg at wk 0, 2, 6 5 mg/kg every 8 wks
Adalimumab (sc) 160 mg/80 mg at wk 0 & 2 40 mg every other
week, from wk 4
Anti-α4β7 integrin 300 mg at wk 0 and 2 300 mg every 8 wks
Vedolizumab (IV)
Rescue

Calcineurin inhibitor
Cyclosporin (IV) 2 mg/kg
Severe Disease

Tacrolimus (po) 0.05 mg/kg to keep trough

conc of 10-15 ng/mL

Janus Kinase inhibitor

Tofacitinib (po) 10mg BD for 8 weeks 5mg BD

Surgery: no response to rescue therapy in 4-7 days

Mild proctitis / Left-sided disease:

 Start with topical treatment
Extensive disease:
 Combination therapy (oral and topical) is more effective in inducing
remission than either modality alone
G 27
Severe disease:
 Assess response to intravenous corticosteroid by third day
 Consider rescue therapy if failure to show significant improvement within
3-5 days
 Consider colectomy if no improvement within 4-7 days of rescue therapy

G 28
 ACUTE PANCREATITIS

Diagnosis of acute pancreatitis is based on the presence of at least 2 of the

following criteria:
1. Abdominal pain consistent with acute pancreatitis
2. Serum amylase or lipase > 3 x ULN
3. Imaging (CT, MRI, USG) criteria

A. Assessment of severity and prognosis

 Risk factors of severity at admission include age >55, obesity (BMI
>30), altered mental state, and comorbidities
 Clinical Parameters
Ranson Glasgow APACHE II
Variable At within first 48 admission,
0 hrs 48 hrs hrs then daily
Age (years) >55 - >55 +
WBC count (x109/l) >16 - >15 +
Blood glucose >11.1 - >10 -
(mmol/L)
AST (U/l) >250 - - -
LDH (U/l) >350 - >600 -
Serum urea (mmol/L) - ↑>1.8 >16 Creatinine
Serum Ca (mmol/L) - <2 <2 -
Serum Alb (g/l) - - <32 -
PaO2 (kPa) - <8 <8 +
Base deficit - >4 - Arterial pH
Fluid sequestration - >6 L - -
Haematocrit (%) - ↓≥10% - +
Serum Na - - - +
Serum K - - - +
Temperature - - - +
Mean arterial BP - - - +
Heart rate - - - +
Respiratory rate - - - +
Glasgow coma scale - - - (15 – actual
score)
Chronic health score - - - +
Suggested cut off 11 criteria: <3 criteria 8 criteria: ≥3 14 criteria: ≥8
number indicate mild AP criteria points*
indicate indicate
severe AP severe AP

G 29
 *Points system per variable: from 0 (normal) to +4 (very abnormal).
Minimal score: 0, maximum score: 71
 C-reactive Protein: 150 mg/l at 48 hrs predicts a severe attack
 Contrast-enhanced CT pancreas: to diagnose severity of AP and to
identify complications, especially pancreatic necrosis, full extent of
which cannot be appreciated until at least 3 days after symptom onset.
Best done on 72-96 hours after admission.

Balthazer CT severity index = grade of AP (0-4) + percentage of necrosis

(0-6). Score of 7-10 associated with morbidity of 92%, mortality 17%.
Grade of Pancreatitis Points Percentage of Necrosis Points
Normal pancreas 0 0% 0
Focal or diffuse
1 <30% 2
enlargement
Pancreatic or
peripancreatic 2 30-50% 4
inflammation
Single peripancreatic
3 >50% 6
fluid collection
Multiple fluid collection
4
and/or retroperitoneal air

B. Watch out for biliary pancreatitis

 ALT >3 ULN in a non-alcoholic patient would highly suggestive of
gallstone aetiology
 USG hepatobiliary system for detection of gallstone and dilate bile
ducts; pancreas can only be visualized in 50% of cases
 Consider MRCP (plain) to rule out biliary pathology, being non-
invasive compared with EUS
 Arrange early ERCP and sphincterotomy within 24 to 72 hours after
admission, if there is acute cholangitis or evidence of persistent CBD
stones

C. Management (ICU care for severe cases)

 Laboratory Ix for assessment of severity (see above)
 CXR, AXR (erect and supine films for excluding other causes of acute
abdomen, serially for monitoring), ECG
 Closely monitor vital signs, I/O, RFT, Ca, glucose ± ABG
 Adequate intravenous hydration is crucial (to produce urine output of

G 30
 0.5 ml/kg/hr in the absence of renal failure) and supplemental oxygen
 Correct electrolyte and glucose abnormalities
 Cardiovascular, respiratory and renal support as required
 Analgesics – Pethidine for pain control
 Nil by mouth till nausea and vomiting settle. Nasogastric suction if ileus
or protracted vomiting
 Early oral feeding is encouraged in mild acute pancreatitis
 Nutritional support via enteral route is preferred to parenteral route.
Nasogastric or nasojejunal feeding appear comparable in efficacy and
safety.
 Parenteral nutrition should be considered if the enteral route is not
available, not tolerated, or not meeting caloric requirements.

Recommended nutrient requirements in acute severe pancreatitis

Energy 25-35 kcal/kg/day
Protein 1.2-.15 g/kg/day
Carbohydrates 3-6 g/kg/day
Lipids 2 g/kg/day
Fat administration is safe provided hypertriglyceridaemia (>12 mmol/L)
is avoided.
 Antibiotics
- Antibiotics that penetrate pancreatic necrosis (e.g. imipenem)
should be given to patients with infected necrosis
- Prophylactic antibiotic treatment is generally not recommended for
prevention of infectious complications in patients with predicted
severe acute pancreatitis or necrotising pancreatitis
 Look out for complications e.g. pseudocyst or infected pancreatic
necrosis. CT-guided FNA of pancreas for Gram stain and culture if
suspected infection of pancreatic necrosis with ongoing fever,
leucocytosis and worsening abdominal pain
 Consult surgeon in severe cases or when complication arises

G 31
 HEPATORENAL SYNDROME

A. Definition
 Renal failure in a patient with acute liver failure or end stage liver
disease in the absence of an identifiable cause of renal failure

B. Precipitating factors of hepatorenal syndrome (HRS)

 Sepsis (esp. spontaneous bacterial peritonitis)
 Severe alcoholic hepatitis
 Upper GI bleeding

C. A diagnosis of exclusion: exclusion of other potential causes of acute or

subacute kidney injury
 Volume depletion: improvement of serum Cr after 2 days of diuretic
withdrawal and volume expansion with albumin (1 g/kg)
 Haemodynamic shock
 Nephrotoxic drugs (NSAID, aminoglycosides, iodinated contrast)
 Structural kidney diseases: proteinuria (>500 mg/day), microscopic
haematuria (>50 RBCs/hpf), abnormal renal ultrasonography

D. Management
 Treat the underlying cause of liver failure
 Identify any precipitating factors and treat accordingly
 Avoid excessive fluid (risk of fluid overload and hypoNa)
 Albumin: 1 g/kg/day for 2 days, followed by 20-40 g/day
 Terlipressin: a vasopressin analogue which acts as a potent
vasoconstrictor reducing splanchnic/systemic vasodilatation →
increase in MAP and effective arterial blood volume. Dosage: starts at
1 mg q4-6h, can be stepped up to 2 mg q4-6h (max 12 mg daily) if
suboptimal response of serum creatinine.
Contraindications: ischaemic heart disease, peripheral vascular disease,
cerebrovascular disease
 Renal replacement therapy: only a bridge to liver transplant
 Transjugular intrahepatic portosystemic shunting
 Liver transplantation

G 32
PRE-EMPTIVE USE OF NUCLEOS(T)IDE ANALOGUES IN
PATIENTS WITH HEPATITIS B INFECTION RECEIVING
IMMUNOSUPPRESSIVE THERAPY

A. High-risk group (anticipated incidence of reactivation >10%):

RECOMMEND antiviral prophylaxis
1. HBsAg+ or anti-HBc+ patients treated with B cell-depleting agents (e.g.
rituximab, ofatumumab) or haematopoietic stem cell transplant (HSCT)
2. HBsAg+ patients treated with anthracycline derivatives (e.g.
doxorubicin, epirubicin)
3. HBsAg+ patients treated with moderate-dose (10-20 mg prednisone
daily or equivalent) or high-dose (>20 mg prednisone daily or
equivalent) corticosteroids daily for >4 weeks

B. Moderate-risk group (anticipated incidence of reactivation 1-10%):

CONSIDER antiviral prophylaxis
1. HBsAg+ patients treated with tumour necrosis factor alpha inhibitors
(e.g. entanercept, adalimumab, certolizumab, infliximab)
2. HBsAg+ patients treated with other cytokine or integrin inhibitors (e.g.
abatacept, ustekinumab, natalizumab, vedolizumab)
3. HBsAg+ patients treated with low-dose (<10 mg prednisone daily or
equivalent) corticosteroids for >4 weeks

C. Low-risk group (anticipated incidence of reactivation <1%): NOT

recommended antiviral prophylaxis
1. HBsAg+ patients treated with traditional immunosuppressive agents
(e.g. azathioprine, 6-mercaptopurine, methotrexate, tyrosine kinase
inhibitors, intra-articular corticosteroids)
2. HBsAg+ patients treated with any dose of corticosteroids daily for <1
week
3. HBsAg-, anti-HBc+ patients treated with cytotoxic chemotherapy other
than anthracycline derivatives (e.g. doxorubicin, epirubicin) or tumour
necrosis factor alpha inhibitors with low potency (e.g. etanercept).

G 33
 Algorithm of high-risk / moderate-risk groups of patients planned for
corticosteroids, immunosuppressive or immunomodulatory therapy

Source: HAHO document (HAHO-COC-GL-MED-003-v03) 2020 version

G 34
 CHRONIC HEPATITIS B

A. History
Treatment experience, family history of HBV/HCC, pregnancy plan of
child-bearing age female, use of alcohol

B. Investigations
1. Blood tests
 CBC, LRFT, clotting profile, AFP
 HBsAg, Anti-HCV
 HBeAg, anti-HBe, HBV DNA
 Anti-HBc (only in HBsAg-negative patients pending certain anti-
cancer chemotherapy or immunosuppressive therapy)
2. Pregnancy test (child-bearing age female)
3. USG liver
4. Transient elastography (Fibroscan®)
 Measure liver stiffness
Probable Probable
Borderline Probable
minimal advanced
fibrosis cirrhosis
fibrosis fibrosis
Normal ALT <=6 kPa >6.0 – 9.0 kPa >9.0 – 12.0 kPa >12 kPa
Elevated ALT <=7.5 kPa >7.5 – 12.0 kPa >12 – 13.4 kPa >13.4 kPa

 May fail in patient with ascites, obesity, anatomic distortions or

narrow intercostal space
 Likely overestimates hepatic fibrosis when ALT >1-5x upper limit
of normal (ULN), presence of severe steatosis, extrahepatic
cholestasis or congestive heart failure
5. Liver biopsy (in selected cases)

Interpretation of serological tests of HBV infection

Anti-HBc Anti-HBs
HBsAg (not routinely (not routinely Interpretation
tested) tested)
+ + - Chronic hepatitis B
Resolved past
- + +/- infection/
occult HBV infection
- - + Immune/ vaccinated

G 35
C. Treatment
1. Anti-viral therapy
Indications of oral anti-viral therapy
 ALT >ULN and HBV DNA >=2000 IU/ml (if HBeAg-positive,
may consider observing for 3-6 months for spontaneous e-
seroconversion)
 Significant fibrosis or cirrhosis with detectable HBV DNA
 Hepatitis B infection with decompensated liver disease
 HCC with detectable HBV DNA
 Pre-emptive treatment before certain chemotherapy or
immunosuppressive therapy
 Hepatitis B reactivation during chemotherapy
 Pregnant women with HBV DNA >200,000 IU/ml (start at 3rd
trimester and continue for up to 12 weeks after delivery) (Use
Tenofovir disoproxil fumarate/TDF)
 Transplant patient with hepatitis B infection

Options of oral anti-viral therapy

Entecavir (ETV) 0.5mg daily po OR
1mg daily po (if lamivudine refractory or have
decompensated liver disease)
Tenofovir disoproxil 300mg daily po
fumarate (TDF) Preferred when:
- Resistance to prior nucleoside analogues
treatment
- Women at child-bearing age
- Pregnant women with HBV DNA >200,000
IU/ml (start at 3rd trimester and continue for up
to 12 weeks after delivery)
- Underlying HIV infection
Tenofovir 25mg daily po
alafenamide (TAF) Preferred when:
- Resistance to prior nucleoside analogues
treatment
- At risk of deteriorating renal function or low
eGFR; or with bone disease, osteopenia or
osteoporosis
Not recommended when:
- Decompensated (C-P B/C) hepatic impairment
*Dose adjustments are needed in patients with renal dysfunction

G 36
 Creatinine Clearance
Recommended dose
(ml/min)
Entecavir NA naïve LAM resistance/decompensated
>50 0.5 mg daily 1 mg daily
30-49 0.25 mg daily or 0.5 mg q48hr 0.5 mg daily or 1 mg q 48 hr
15-29 0.15 mg daily or 0.5 mg q72hr 0.3 mg daily or 1 mg q 72 hr
<10 or haemodialysis* or 0.05 mg daily or 0.5 mg q7 0.1 mg daily or 1 mg q 7 days
CAPD days
Tenofovir disoproxil
fumarate
>50 300 mg q24 hrs
30-49 300 mg q48 hrs
15-29 300 mg q72-96 hrs
<10 with dialysis 300 mg once a week or after a total of approximately 12 hours
of haemodialysis
<10 without dialysis No recommendation
Tenofovir alafenamide
>15 25mg once daily
<15 with dialysis 25mg once daily, administer after haemodialysis on day of HD
<15 without dialysis Not recommended

Alternative anti-viral therapy

Pegylated-Interferon-α-2A (Peg-IFN-α-2A)
 180 microgram weekly sc for 48 weeks
 Can be considered in patients who desire a finite duration of therapy, such as
young adults and women who are planning to conceive in the future.
 Contraindicated in decompensated liver disease, history of active psychiatric
illness, autoimmune illness, severe leukopenia or thrombocytopenia and
concurrent severe systemic disorders, pregnancy.
 Consult GI specialist for use.

2. Liver transplantation: Refer for liver transplant if decompensated and

transplant candidate

HCC surveillance
At risk group: Men >40 years old, Women >50 years old, first-degree relatives
with HCC
Regular AFP and USG liver, preferably every 6 months

Special group
Pregnant women/ co-infection with HCV, refer to GI specialist.
G 37
 INCIDENTAL SOLID LIVER LESIONS

A. Common differential diagnosis

 Malignant lesions: HCC, intrahepatic cholangiocarcinoma (CCA),
liver metastasis
 Lesions with malignant potential: Hepatocellular adenoma
 Benign lesions: hepatic haemangioma, focal nodular hyperplasia
(FNH)

B. Approach
1. History (to identify risk factors)
 Underlying chronic liver disease, obesity, metabolic syndrome,
Primary sclerosing cholangitis (PSC), history of extrahepatic
malignancy
 Family history of HCC
 Use of oral contraceptive (OC) pills/ androgenic steroid
2. Blood tests
 AFP, +/- Ca 19.9 and CEA (if suspect CCA)
3. Radiological tests
 For patient with chronic liver diseases: Subcentimetre lesion
(<1cm), suggest book FU USG liver in 3 months; lesion (>=1cm),
book contrast cross-sectional imaging

 Options of contrast cross-sectional imaging:

- Triphasic or 4-phase CT scan
- MRI (gadolinium or gadoxetate disodium (PrimovastTM)
contrast)
- Dual tracer PET-CT (FDG + acetate) in selected patients
4. Pathological tests
 Liver biopsy (only if imaging non-diagnostic, decided by multi-
disciplinary team (MDT))

G 38
 Intrahepatic Hepatocellular
HCC
CCA adenoma
Risk Chronic liver PSC Obesity
factors disease Metabolic syndrome
OC pill/ androgenic
steroid
Tumour AFP Ca 19.9 -
markers CEA
Imaging CT or CT or MRI MRI preferred
MRI (gadolinium <
PrimovastTM
contrast, may need
discussion with
radiologist for use
of PrimovastTM in
selected case)
(Can follow
LIRADS
categorization* to
formulate
management or
follow up plan)

Hepatic Haemangioma Focal nodular hyperplasia

Imaging Do not need contrast CT < MRI with gadolinium
imaging if typical on USG contrast
If atypical on USG,
consider CT or MRI
Follow No need for typical and No need for typical lesion and
up asymptomatic lesion asymptomatic lesion
May need follow-up imaging in 6-
12 months in women continue to
take OC pills or oestrogen-
containing preparation

G 39
*LI-RADS categorisation
For patients at risk of HCC (cirrhosis or hepatitis B) undergoing contrast
enhanced imaging
Category Assessment Action
LR-1 Definitely benign Routine surveillance in 6 months
LR-2 Probably benign Consider repeat diagnostic imaging in
<=6 months
LR-3 Intermediate Repeat or alternative diagnostic
probability of imaging in 3-6 months
malignancy
LR-4 Probable HCC Multi-disciplinary discussion for
tailored work up, may need biopsy
LR-5 Definitely HCC HCC confirmed
LR-M Probably or definitely Multi-disciplinary discussion for
malignant, not specific tailored work up, often include biopsy
for HCC

G 40
 NON-ALCOHOLIC STEATOHEPATITIS (NASH)

A. Definitions & Epidemiology

 Non-Alcoholic Fatty Liver Disease (NAFLD) definition: (i) evidence of
hepatic steatosis (imaging or histology) and (ii) absence of other causes
of hepatic fat accumulation e.g. significant alcohol consumption,
hepatitis C, medication (valproic acid, oestrogen, tamoxifen,
corticosteroids, amiodarone, methotrexate) or hereditary disorders (e.g.
Wilson’s disease)
 Alcohol exclusion criteria for Asians: <1 standard drink/day (70g
ethanol/week) for women and <2 standard drinks/day (140g
ethanol/week) for men
 Risk factors for NAFLD: Weight gain, obesity, DM, dyslipidaemia,
metabolic syndrome, hypothyroidism, polycystic ovary syndrome,
obstructive sleep apnoea, hypopituitarism, hypogonadism, genetic
variations (PNPLA3, TM6SF2, etc.)
 Approximately 25% of patients in Asian cohorts with NAFLD are not
overweight or obese (“Lean” NAFLD)
 NAFLD is a spectrum, including Non-Alcoholic Fatty
Liver(NAFL)/steatosis, Non-Alcoholic Steatohepatitis (NASH) and
cirrhosis
 NASH definition: Presence of hepatic steatosis, inflammation, and
hepatocyte injury (ballooning degeneration) on liver biopsy
 NAFLD is believed to be a major cause of cryptogenic cirrhosis because
cryptogenic cirrhosis is more associated with metabolic syndrome than
other causes of cirrhosis
 Risk factors for advanced fibrosis or cirrhosis in NAFLD: advanced age,
diabetes, severe obesity, and transaminase elevation
 Commonest causes of death in NAFLD are cardiovascular disease and
malignancy, followed by liver-related disease

B. Investigations
 Suspect NASH as the cause of liver disease in patients who are
overweight and in whom hepatitis B or C, alcoholic liver disease,
autoimmune liver diseases, and inherited metabolic diseases have been
excluded.
 Clue to NASH: abnormal LFT (usually minor increases in ALT and
GGT) with a clear relationship with fluctuations in bodyweight
 Detection of steatosis: USG (poor sensitivity if mild steatosis),
Controlled attenuation parameter (CAP) by FibroScan®
 To rule out other aetiologies: Lifetime and current alcohol intake, drugs
G 41
 including supplements and herbs, HBsAg, anti-HCV (ANA, SMA,
AMA, LKM1, ceruloplasmin, iron study may be considered if clinically
appropriate)
 Screen for risk factors: Blood Pressure, waist circumference, FG,
HbA1c, lipid profile
 Detection of fibrosis/cirrhosis: Platelet, Transient Elastography
(Fibroscan®) (False+: high ALT, ascites, cholestasis, heart failure)
 Diagnosis cannot be made by clinical, biochemical or imaging measures
 Liver biopsy is the gold standard for differentiating NAFL from NASH
and staging fibrosis but it is invasive
 Who needs liver biopsy?
- Suspected coexisting chronic liver diseases
- When there is a need to distinguish NASH from other chronic liver
diseases especially autoimmune hepatitis
- When noninvasive tests for fibrosis is inconclusive
 In end stage, the characteristic features of NASH may disappear (i.e.
burned-out NASH)
 Regular HCC surveillance USG every 6 months if cirrhosis.

C. Management
1. Lifestyle
 Aim gradual weight loss (up to 1 kg/week)
 Combined diet/exercise strategy is more effective than either
modality alone
 Dose-response relationship between weight loss and improvement in
liver histology [at least 5% weight loss for NASH resolution, 10%
weight loss (in overweight persons) may lead to fibrosis
improvement].

a) Diet: Hypocaloric diet (500–1000 kcal deficit), Mediterranean diet,

reduced red and processed meat, reduced carbohydrates

b) Physical activity:
- Intensity, volume, and type of exercise required are debated.
- General population: 30 min/day of moderate-intensity exercise for
≥ 5 days/week or a total of ≥ 150 min/week or vigorous-intensity
exercise for ≥ 20 min/day on ≥ 3 days/week (≥ 75 min/week)
- Obesity/Poor fitness/Musculoskeletal disorder: Resistance exercise
on 2–3 days/week (Resistance and aerobic exercise training have
similar effects on hepatic steatosis)

G 42
2. Pharmacological
 No drug has been approved for NASH
 Simple steatosis run a benign course. We would target patients
with NASH and/or liver fibrosis.
 Safety and efficacy in cirrhosis are unknown.

a) Vitamin E PO 800IU/day
- May improve LFT and histology in non-cirrhotic non-diabetic
NASH
- Concerns about increase in all-cause mortality, haemorrhagic
stroke and prostate cancer in males older than 50 years old

b) Pioglitazone PO 15-45mg/day
- Consider for patients with pre-diabetes or type 2 diabetes.
- Adverse effects: weight gain, increased fracture risk, congestive
cardiac failure, and bladder cancer.

c) Liraglutide SC 1.8mg/day / Semaglutide SC 0.5-2.4mg/week or PO

7-14mg/day
- Consider in diabetic patients with NAFLD/NASH

3. Bariatric surgery (Asian criteria)

 Age >18 and <65 years
 BMI ≥ 37 kg/m2, or BMI ≥ 32 kg/m2 plus Type 2 Diabetes or two
obesity-related co-morbidities
 Higher perioperative risk if cirrhosis

4. Liver transplant
 Same indications as those for other aetiologies of liver disease
 Overall survival rates post LT are the same as those for other
indications but patients with NASH are more likely to die post-
transplant because of CVD and chronic kidney disease. Hence,
detailed pre-op cardiovascular assessment is a must.

5. Statins (when indicated)

 Safe for use in those with slightly elevated ALT, i.e. < 3 × ULN or
compensated cirrhosis

G 43
 ANTIBIOTICS PROPHYLAXIS FOR GI ENDOSCOPY

A. Risk
 During endoscopy, there is a risk of bacteraemia but clinically
significant infections are very low except for procedures with high
bacteraemia risk.

Risk of bacteraemia
Procedure
(mean) %
Daily routine Brushing/Flossing 20-68
Use of toothpicks 20-40
Chewing 7-51
Low risk OGD ± biopsy 8(4.4)
Colonoscopy 25(4.4)
Colonic stenting 6.3
Flexible sigmoidoscopy <1
EUS-guided FNA
Upper GI, cystic/solid 4-5.8
Rectal/perirectal, solid 2
High risk Oesophageal dilatation 12-22
Variceal sclerotherapy 52(14.6)
Variceal ligation 1-25(8.8)
ERCP
Non-obstructed 6.4
Biliary obstruction (Stone, stricture) 18
Source: Antibiotic prophylaxis for GI endoscopy. Gastrointestinal Endoscopy, Volume 81,
Issue 6, June 2015, Pages 1503-1504

B. Who needs antibiotics prophylaxis?

1. Prevention of IE (See C33-34)
 Antibiotic prophylaxis not indicated solely to prevent IE unless
there is presence of high risk cardiac conditions + endoscopic
procedure with high bacteraemia risk.
High risk cardiac conditions = (1) prosthetic (mechanical or bioprosthetic)
valves, (2) history of IE, (3) cardiac transplant recipients who develop
cardiac valvulopathy, (4) congenital heart disease (CHD) including
unrepaired cyanotic CHD including palliative shunts and conduits;
completely repaired CHD with prosthetic material or devices, placed
surgically or by catheter, for the first 6 months; and repaired CHD with
residual defects at the site or adjacent to the site of a prosthetic patch or
device
 Antibiotics of choice = active against enterococci e.g. penicillin,
ampicillin, piperacillin, or vancomycin

G 44
2. Prevention of local infection
 ERCP: Liver transplant patients or Anticipated incomplete
drainage e.g. hilar cholangiocarcinoma, primary sclerosing
cholangitis. (Recommended, prevent cholangitis, continue
antibiotics after procedure)
 Percutaneous endoscopic feeding tube placement (Recommended,
prevent peristomal infection, Cefazolin ± MRSA decontamination)
 EUS-FNA of mediastinal and pancreatic cysts (Suggested, prevent
cyst infection, Quinolone, 3-5 days post procedure)
 Peritoneal dialysis and colonoscopy (Suggested, prevent
peritonitis)

G 45
Geriatric Medicine
 ALTERED RESPONSIVENESS OR “DECREASED GC”
May represent the hypoactive form of delirium (DSM-5 major neurocognitive
disorder)

History
 Obtain from OAH staff / family as far as possible.
 Do not assume the patient non-communicable unless proven otherwise.
 Be cautious about sinister conditions if there is an abrupt change in
consciousness level.
 Medication history (CMS / private drugs) reviewed to identify sedative
drugs or recently added or withdrawn drugs.

P/E
 Vitals
- GCS or level of consciousness documentation
- BP/pulse, temperature, RR, SpO2, hydration status
- Colour – cyanosis, pallor, jaundice

 Abdominal exam
- Rule out acute abdomen – ischaemic bowel can be subtle
- Bladder size
- PR – loaded rectum, melena

 Examine 4 limbs for any focal signs and nuchal rigidity (can be difficult
to differentiate from neck contracture).
 Examine covered parts of body for any wound, rash, pressure ulcers and
peripheral ischaemia / gangrene.
 Move 4 limbs to detect unknown fractures / acute arthritis (crystal or septic
arthritis).

Ix
 Haemoglucostix and urine multistix
 Read CXR from AED
 Routine blood tests including electrolytes, RG, WCC, Hb
 Septic workup
 Consider AXR for high faecal impaction or IO
 Judicious use of urgent CT brain, EEG (e.g., non-convulsive status
epilepticus) or LP

Gr 1
Mx
 Search and treat underlying causes (delirium in older adult is not
uncommonly multifactorial).
 Cautiously order NPO on admission and remember to resume feeding later.
 Keep good hydration and oxygenation.
 Withhold some regular medications if not absolutely and immediately
necessary. E.g. statin, vitamins, Ca
 Withhold or tapering medications that may give rise to altered
consciousness.
- Sedatives and other psychotropic drugs
- Anti-hypertensives if BP is low
- Diuretics if dehydrated or poor intake
 Review OHA / insulin regimen according to H’stix.
- Consider splitting long acting insulin into short-acting insulin to avoid
hypoglycaemia in fluctuating oral intake
- Withhold metformin if ill or poor intake
 Remember to resume medications when condition improves and feeding
satisfactory.
 Consider empirical antibiotic.

Gr 2
 ASSESSMENT OF MENTAL COMPETENCE

Mental competence refers generally to an individual’s ability to make an

informed choice with respect to a certain decision. It is an essential step of
obtaining informed consent, advance directive and advance care plan.

Four key elements of informed consent

1. Competence (be aware of cognitive function and consciousness)
2. Voluntariness (free will, independent decision making)
3. Disclosure of information: pros and cons of choices including alternatives
4. Understanding and acceptance of information and consequence

Key steps in assessing mental competence

1. Patient receive and understand information(s) – capable to comprehend.
2. Patient is asked to paraphrase – in order for the clinician to evaluate his/her
understanding of the information, and correct any misconceptions.
3. Capable to analyse the decision(s) to make – seeing both sides of argument
and appreciating consequence(s).
4. Patient make his/her own choice(s) with reasoning.
5. Patient has to express his decision(s) by means of communication
understandable by others.
6. Capable to retain the information and decision, at least for a short period.

Clinical assessment
 Rule out delirium
 Rule out depression
 Facilitate communications, e.g. correction of hearing deficit, presence of
translator (for dialect speaker) and writing in place of speech (for patients
with expressive aphasia).

Gr 3
 CARE OF DYING
Geriatric patients need different EOL care approach because:
a) High unpredictability of complex disease trajectories
b) High prevalence of non-cancer co-morbidities, frailty and dementia
c) Tendency of rapid clinical deterioration and slow recovery in acute illnesses

Practical Notes:
1. Communicate with patient/family for the goals of care (check existing ACP,
AD) and document.

2. Assess care needs encompassing physical, psychological, social and spiritual.

Pay particular attention to patient’s proxy e.g. family members.

3. Non-invasive life sustaining therapy (LST) and palliative care therapy can
coexist in the initial dying process.

4. When death is imminent and inevitable, support family to shift focus to

comfort care. (Also see PM24)

5. Review and discuss with family to de-prescribe inappropriate treatments.

6. Keep reasonable artificial fluid therapy which is regarded as basic care in

Chinese culture.

7. Symptomatic control with opioids and sedatives could be misinterpreted as

deeply sedating or even hastening death for patients. It could be prevented by
close communication with family.

8. Tips to avoid misinterpretation as “euthanasia”:

a) Start low in opiates naïve patients. E.g., 3 mg morphine in 500ml NS
Q24h IV/SC infusion and titrate up closely according to response and
tolerance with 0.5mg-1mg morphine Q2h IV/SC prn.
b) Document failure to control symptoms at current doses before dose
increase and/or switch to more potent medications.
c) If suspected overdose, allow trial of decreasing / withholding medications
to observe any clinical improvement in cognition and respiration vs any
recurrence of distressing symptoms.

9. Regular review on patient’s condition to guide your decision on symptomatic

medication use.

Gr 4
Drug Prescribing in Care of Imminently Dying for Older Adults

May also refer to PM25 (but bear in mind the uniqueness in care for frail older
adults)

Recommended Medication
Maintenance
Symptom Condition
Starting regimen (CSCI=continuous
subcutaneous infusion)
Dyspnoea Morphine 0.5-1mg Q2-4H If ≥3 doses in 24hrs: Morphine
PRN SC 3-6mg Q24H CSCI

Preferred in Fentanyl 12.5microgram If ≥3 doses in 24hrs: Fentanyl

renal failure Q2-4H PRN SC 25-75microgram Q24H CSCI

Pain Morphine 1-2mg Q2-4H If ≥3 doses in 24 hr: Morphine

PRN SC 3-6mg Q24H CSCI

Preferred in Fentanyl 12.5- If ≥3 doses in 24 hr: Fentanyl

renal failure 25microgram Q2-4H PRN 25-75microgram Q24H CSCI
SC
Agitation Haloperidol 1mg Q2-4H If ≥2 doses in 24hrs: Haloperidol
PRN SC 2-6mg Q24H CSCI

Respiratory tract Non-CHF Buscopan 20mg Q8H PRN If ≥2 doses in 24hrs: Buscopan
secretions SC 40-120mg Q24H CSCI

CHF Consider Lasix as needed

(+/- Buscopan)
Nausea/Vomiting Maxolon 10mg Q8H PRN If ≥2 doses in 24hrs:
IV Maxolon 30mg Q24H CSCI

Alternative: Haloperidol 1- If ≥2 doses in 24hrs: Haloperidol

2mg Q8H PRN SC 2-6mg Q24H CSCI
Preferred in Haloperidol 0.5-1mg Q8H If ≥2 doses in 24hrs: Haloperidol
renal failure PRN SC 1-3mg Q24H CSCI

Gr 5
 DIABETES MELLITUS IN OLD AGE
Assessment of DM older adults
 Comprehensive geriatric assessment approach in particular:
- Cognition
- Gait and balance
- Frailty syndrome – gait speed and muscle strength
- Vision
- Mood
- Social reserve
- Hand dexterity
 And other standard complication assessment in adults in the absence of
established complications.

Glycaemic targets
 Glycaemic control in older adults is highly individualized with various
targets, and is particularly loosened in those with established
complications and co-morbidities.

American Diabetes Association / American Geriatrics Society (2012) consensus guideline

for glycaemia goal in elderly people with diabetes
Fasting /
Patient Bedtime
HbA1c preprandial
Patient type characteristics / glucose
target glucose
health status (mmol/L)
(mmol/L)
Few coexisting chronic
Healthy (longer life
illness, intact cognitive <7.5% 5–7.2 5–8.3
expectancy)
and functional status
Complex/
intermediate Multiple coexisting
(intermediate chronic illness or >2
remaining life instrumental ADL
<8% 5–8.3 5.6–10
expectancy, high impairment or mild to
treatment burden, moderate cognitive
hypoglycaemia impairment
vulnerability, fall risk)
Very complex/poor Long term care/end-
health stage chronic illness,
(Limited remaining moderate to severe <8.5% 5.6–10 6.1–11.1
life expectancy makes cognitive impairment,
benefit uncertain) >2 ADL dependencies

Gr 6
Treatment principles:
1. Prevent acute complications of profound hyperglycaemia.
2. Avoid hypoglycaemia.
3. Delay chronic complications but not applicable if already established or in
the presence of limited life expectancy.

Management
Diet and weight control
 Aim at weight stabilization.
 Weight reduction should not be loosely advised to balance against
compromising quality of life.

SMBG (self-monitoring of blood glucose)

 SMBG (usually by OAH staff or family) should not be routinely advised
to monitor post-prandial hyperglycaemia but sometimes indicated to detect
fasting or pre-meal hypoglycaemia.

Pharmacotherapy
1. Metformin is the preferred initial therapy if no contraindications (eGFR
<30 ml/min/1.73m2 or at risk of lactic acidosis). May cause B12 deficiency
and weight loss.
2. Short-acting sulphonylurea to minimize the risk of hypoglycaemia.
3. α-glucosidase inhibitor is safe for hypoglycaemia and good for postprandial
hyperglycaemia but potency is low.
4. Adverse profile of thiazolidinedione in old age – oedema and heart failure,
fragility fractures and possible bladder cancer.
5. Incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists) –
may counteract post-prandial hyperglycaemia. Linagliptin 5mg need no
renal dose adjustment, whereas other DPP4 agents do.
6. In general, insulin therapy for frail older adults should be simple and once
or twice daily dose of intermediate acting insulin is sufficient. Consider
long-acting basal insulin analogue (glargine and detemir) if recurrent
nocturnal or pre-meal hypoglycaemia. May add pre-prandial rapid-acting
insulin analogue (lispro and aspart) if profound post-prandial
hyperglycaemia.
7. SGLT2 inhibitor – favourable cardiovascular & renal outcomes, especially,
heart failure. Risks of urogenital infection, urinary frequency, dehydration,
and euglycaemic diabetic ketoacidosis. Educate – fasting states, poor oral
intake, advise to stop for 3 days pre-operatively. Cut-off eGFR for
individual SGLT2 inhibitor varies from 30 to 45 ml/min/1.732 below which
Gr 7
 should be discontinued.
8. GLP-1 receptor agonist has advantage of associated weight loss but need
injection, adverse effects of nausea, vomiting, and anorexia.

Practical notes to avoid hypoglycaemia

1. Preferred therapy
a) Metformin
b) Incretin-based therapy
c) Glucosidase inhibitor (low potency)
d) Long-acting basal insulin analogue
2. Hypoglycaemia blunt glucose counter-regulatory response to subsequent
hypoglycaemia, leading to recurrent hypoglycaemia. Avoid tight control for
2–3 weeks to restore counter-regulatory response.
3. Infection related hyperglycaemia may need escalation of insulin therapy to
counteract the activation of stress hormones, which can be prolonged for 1–
2 weeks. If discharged with a higher insulin dosage, follow up early to
titrate down insulin or avoid tight control on discharge.
4. Asymptomatic hypoglycaemia is common in old age. Continuous glucose
monitoring study may help.

See also E6.

Gr 8
 EATING OR FEEDING PROBLEMS IN ELDERLY WITH
ADVANCED DEMENTIA OR SEVERE FRAILTY

Feeding problems characterise end-stages of irreversible terminal illnesses

such as dementia and frailty with multi-morbidity. It is important to identify
reversible causes and have good communication with families for goals of care.

Step 1: Explore if the patient has poor oral intake and/or dysphagia
Poor oral intake established from asking carers, I/O chart. Dysphagia of
oropharyngeal type is characterised with difficulty initiating a swallow or
oesophageal type where after a swallow, there is a sensation of food getting
stuck.

Step 2: Identify reversible or underlying causes by clinical assessment

Causes of poor oral intake:
 Oral cavity: Dry mouth, dental issues, candidiasis, TMJ dislocation
 Medication side effects: metformin, tramadol, antibiotics, anticholinergics,
iron supplements, oral bisphosphonates, sedatives
 Systemic: sepsis, organ failure
Causes of dysphagia:
 Structural causes: oesophageal strictures, tumours
 Neurogenic: CVA, dementia, Parkinson, motor neuron disease, myasthenia
gravis
 Behavioural: delirium, dementia, depression

Step 3: Manage feeding problems with a family-oriented & multidisciplinary

approach:
1. Timely management to avoid NPO for long periods
2. Treat underlying causes e.g., review & deprescribe medications if possible,
address oral hygiene and dentition, e.g., moisturise mouth before feeding,
dentures
3. Early communication with patient / family for feeding options and goals
of care
4. Food texture – according to speech therapist’s assessment
5. Feeding techniques, posture, cognitive-behavioural strategies for feeding
6. Nutritional assessment – vitamins, dietician high energy low volume
supplements, relax dietary restrictions
7. Enhance enjoyment of feeding e.g., family engagement, food variety,
condiments, appealing appearance
8. Appetite stimulant infrequently used, selected patients
Gr 9
Step 4: Careful hand feeding option in end-stage irreversible terminal illness,
with goals of care in advance care planning.
 Establish mental competence for decision making.
 Best interest – Most cases lack mental competence for decision making.
Identify legal guardian, any advance directive or advance care plan. HA’s
Guidelines on Life Sustaining Treatments in Terminally Ill states the
ethical basis for ‘best interests’ apply to careful hand feeding if tube
feeding not preferred
 Communication – If patient is mentally incompetent, ‘best interests’ based
on clinical judgement by doctors with family consensus after consider re:
effectiveness*, benefits, burdens of feeding options. Ascertain prior wishes
& values of patient, if possible
 Documentation – advance care plan e.g., goals of care, ‘best interest’
decision, DNA_CPR
 Post-discharge arrangements, carer support and empowerment

*Effectiveness of feeding options – NO evidence that tube feeding is superior

to careful hand feeding in advanced dementia for better outcomes in survival,
aspiration, quality of life or function, hunger or thirst sensation

Gr 10
 ELDER ABUSE

Definition – elder abuse refers to the commission or omission of any act that
endangers the welfare or safety of an elderly person.

Types of Elder abuse

1. Physical Abuse – physical injury inflicted non-accidentally
2. Psychological Abuse - behaviour e.g., scolding, isolation, causing fear,
intrusion into privacy, unnecessary restriction of freedom
3. Financial Abuse – deprivation of his/ her wealth, or not acting in person’s
interests
4. Neglect – severe or persistent lack of attention to basic needs (e.g. food,
shelter, medical/nursing treatment etc.) which endanger health and safety.
5. Abandonment - abandoning without justifiable reasons, which endangers
the elder physically or psychologically
6. Sexual abuse - sexual assault e.g., exposure of sexual organ, indecent
assault, etc.

Risk Factors
 Dependent elder (e.g., need physical assistance, mentally incapacitated)
 Elder with poor social network
 Poor family relationship, change in family dynamics (e.g., emigration)
 Carer stress ± suffer health problems

Clinical Approach to Elder Abuse

 Be awareness to possibility of elder abuse, if positive risk factors, e.g., frail
elder with dementia, carer stress and indicators are present (below)
 Signs of elder abuse may be subtle, and mistaken for aging changes.
 Physical indicators –
- Bruises, fracture, lacerations, burns – unusual injury pattern e.g.,
unexplainable, multiple scars, facial, shape of e.g., belt, different
colours at various stages of healing, repeated
- Serious undernutrition, dehydration, chronic bed sores, frequent illness
 Behavioural indicators – apprehension, withdrawal, low mood, unwilling
to disclose information or have medical examination, attribute injury to
own carelessness, making contradictory statements, attempting suicide
 Environmental indicators – e.g., restraint equipment found at the elder’s
residence, prolonged isolation and not allowed to contact relatives or
friends

Gr 11
 Financial indicators – loss of money, assets or properties, inadequate
resources to cover daily necessities, transfer his/ her bank accounts etc. to
others or open joint bank accounts, suddenly make a will to leave
possessions to a non-related person
 Behaviour of Abuser – seek medical service from different doctors in an
unusual manner, unwilling to disclose information, answer questions on
behalf of elder, withhold/delay treatment for injury, escort elder to make a
will without notifying others

Management
1. Ensure immediate safety of elder
2. Case doctor to carefully examine & document (e.g., clinical photos) the
health conditions or injuries, determine nature of the abuse and provide
appropriate treatment.
3. Refer the case by e.g., clinic, ward, A&E doctor to
 Medical social worker (MSW) and
 Hospital elder abuse geriatrician liaison doctor
4. Geriatrician liaison doctor provide geriatric assessment, advise mental
capacity of elder and follow up as below with MSW
5. MSW roles
 liaise with agencies (e.g., inform the Licensing Office of Residential
Care Homes for the Elderly of the SWD) or other social units
 guide elder to understand his/her right to report the case to the Police.
 Initiate a Multi-disciplinary Case Conference (MDCC) with
concerned professionals
 Report to the “Central Information System on Elder Abuse Cases”
6. Psychogeriatric Service/ Clinical Psychological Service referral if
appropriate
7. Emergency guardianship order – if MIP has no relatives/ guardian, or
relatives/ guardian refuses to allow examination and nursing care
8. Police report
 family or guardian may already have reported to Police
 If not yet reported the case to the Police, refer the case to the MSW.
 if elder’s safety is endangered or serious bodily injuries, case doctor
shall immediately report the case to the Police and inform MSW. If
MIP, the MSW will assist the elder in reporting to the Police.
9. Legal
 No specific offence and legal definition of elder abuse in the Laws of
Hong Kong

Gr 12
  However, Ordinances applicable – e.g., Offences Against the Person
(Cap. 212), Theft (Cap. 210), Residential Care Homes (Elderly
Persons) (Cap. 459)
10. Keep impartial attitude in this complex subject, understand the
perspectives of both the elder and the suspected abuser
11. Encourage reconciliation between abused and the abuser to rebuild the
family relationship where possible.

References
Procedures for Handling Elder Abuse Cases by the Hospital Authority
Chapter 5 of the Procedural Guidelines for Handling Elder Abuse Cases (Revised 2021)
Social Welfare Department
https://www.swd.gov.hk/storage/asset/section/741/en/Procedural_Guidelines_for_Handl
ing_Elder_Abuse_Cases_(Revised_2021)_en_20210331.pdf

Gr 13
 FALLS

Defined as an event that results in the patient or a body part of the patient
coming to rest inadvertently on the ground or other surface lower than the body.
Fall results in injuries, more hospitalizations, clinic visits and emergency
attendance. Moreover, fear of falling, loss of confidence in walking, social
isolation and depression can occur.

Approach to falls: do not just treat the consequences of falls. Find out the
causes of falls. Falls in older people are often due to interaction between
multiple risk and precipitating factors. One practical way is to use a mnemonic
as below:

Risk and precipitating factors for falls

Mnemonic (A E I O U, B C C C D D E F) of risk or precipitating factors for falls
A Anti-drugs: those working on the brain (e.g. Antidepressants,
Antipsychotics, Anticholinergics, Antiepileptics) and those affecting
the cardiovascular system (e.g. Antihypertensives and diuretics)
E Environmental hazards
I Infections: urinary or others
O Osteoarthritis / Musculoskeletal (lower limbs)
U Unwell patients are more prone to deconditioning and falls. In fact,
falls is a poor prognostic factor for cancer.
B Biochemical abnormalities e.g. hyponatraemia, hypoglycaemia
C Cardiovascular
 Postural hypotension (wise to check it a few times over 2 or 3 days
as a single measurement may be falsely negative)
 Carotid sinus hypersensitive / micturition syncope
 Arrhythmia, aortic stenosis, myocardial infarct
C CNS or PNS disorder: stroke, cerebellar impairment, Parkinsonian
syndromes, peripheral neuropathy
C Cognitive impairment: e.g. dementia, delirium
D D vitamin deficiency
D Deconditioning
E Eye diseases (refractive, cataract, macular degeneration)
F Frailty and sarcopenia
Adapted from Chan’s Practical Geriatrics, 4th Edition (by Prof. Daniel KY Chan, Australia)

Gr 14
Fall assessment
 Obtain history on circumstances of fall, precipitating factors and
consequences, ask a witness if available.
 Ask relevant history e.g. living environment, social support, past medical
illnesses, medications, history of falls or near falls, mobility and functional
status.
 Testing gait, balance, lower limb and joint function, cardiovascular and
neurologic examination, if relevant.
 Perform Timed up-and-go test (TUGT)
- A simple test in which older patients are timed while rising from a 46
cm high armchair, walking 3 metres, turning around and returning to
sit in the chair (total 6 metres). Walking aids are allowed and patients
who require more than 20 seconds to complete are at risk for falls.
 Assess for frailty and sarcopenia (refer to Gr17-20)
 Perform ECG and other investigations as guided by history and
examination.

Management of Falls – usually multi-modalities

1. Medication review and minimization
 Minimize medications and in particular psychotropic drugs
 Use standardized tool for drug reconciliation, such as:
- the Beers Criteria for Potentially Inappropriate Medication Use in
Older Adults (https://geriatricscareonline.org/toc/american-geriatrics-
society-updated-beers-criteria/CL001; Mobile App: AGS Beers Criteria®)
- STOPP (Screening Tool of Older Person’s potentially inappropriate
Prescriptions) (https://link.springer.com/article/10.1007/s41999-023-00777-y;
https://www.cgakit.com/m-2-stopp-start)
2. Treatment of cardiovascular risk factors
 Treat underlying cardiovascular causes e.g. carotid sinus
hypersensitivity, vasovagal syndrome, orthostatic hypotension,
postprandial hypotension, arrhythmias.
3. Strength and balance training (including Tai Chi)
 Beware that prescribing inappropriate exercise may on the contrary
increase falls in older people.
 Management frailty and sarcopenia (refer to Gr17-20)
4. Home and environmental hazard modification
5. Foot and footwear check and modifications
6. Vitamin D and Calcium supplementation
 Vitamin D3 800 IU per day with or without calcium supplement is

Gr 15
 recommended for fall prevention.
7. Correction of vision
 Early cataract surgery reduces falls.
 Beware of multifocal lens which may increase fall risk.
8. Strengthen bone to reduce fracture even when falls occur
9. Hip protectors
 Evidence not concrete except in residential care homes and
compliance is the usual limiting factor for its effectiveness.
10. Safety alarms

Interventions that may be ineffective yet harmful

 Restraints do not reduce risk of falling. On the contrary, patients may fall
more frequently and sustain more serious injuries after using restraints.
 Restraints increase the risk of delirium in the hospital and the resulting
immobilization are associated with pressure ulcer occurrence, respiratory
complications, and death via strangulation and asphyxia.
 Bed rails may lead to serious injury e.g. limbs snag on metal bars or older
patients climb over the rail, falling even greater distance onto the floor.

Gr 16
 FRAILTY AND SARCOPENIA

Frailty
Frailty is a clinical condition of reduced resilience and bodily reserve. In face
of any stress, an individual with frailty will decline markedly in functional
level, needs longer recovery duration and may not revert back to his premorbid
state. It is associated with adverse health outcomes: institutionalization,
hospital admissions, disability and death.

Measurement and Identification of frailty

Several commonly used tools are listed below:

 Phenotypic features of frailty (Fried’s Criteria)

1. Unintentional weight loss
2. Self-reported exhaustion
3. Low muscle strength
4. Slow walking speed
5. Low physical activity

0 = robust, 1-2 = pre-frail, 3 or more = frail

In Fried’s criteria, frailty is a pre-disability state and is reversible.

 Frailty Index (Rockwood)

FI = number of deficits divided by the number of health deficits measures

It is a full spectrum measurement of frailty from robustness to disability.

The variation of FI within a group of patients at a certain stage of any
chronic disease will converge with the advancement of that disease. FI
around 0.6 is a limit for survival.

 Screening tool – FRAIL scale (Morley)

Fatigue: Are you fatigue?
Resistance: Any difficulty in walking one flight of stairs?
Ambulation: Any difficulty in walking one block?
Illness: Do you have five or more illnesses?
Loss of weight: do you lose 5% weight over the past 6 months?
0 = robust, 1–2 = pre-frail, 3 or more = frail

Gr 17
 Single physical test to identify frailty
Cut-off values in Hong Kong Older Chinese
- Walking speed: 0.9 m/s (men); 0.8 m/s (women)
- Handgrip strength: 28 kg (men); 18kg (women)

Clinical Applications:
1. Individualise treatment targets in chronic disease management and end of
life care.
2. Stratify risk in high risk surgical procedures and therapy.
3. Triage to various hospital and community services.

Management:
Body weight preservation and preventing muscle weakness are the mainstays
of management.

Gr 18
Sarcopenia
Sarcopenia is a progressive skeletal muscle disease, characterised by low
muscle mass, low muscle strength and poor physical performance. The decline
in muscle strength is faster than muscle mass. It is associated with falls,
disability and mortality.

Diagnosis of sarcopenia:
Asian Working Group for Sarcopenia 2019 algorithm

Gr 19
Screening tool for sarcopenia – SARC-F
Component Question Scoring

How much difficulty do None = 0

Strength you have in lifting and Some = 1
carrying 10 pounds? A lot or unable = 2
How much difficulty do None = 0
Assistance in
you have walking Some = 1
walking
across a room? A lot, use aids, or unable = 2

How much difficulty do None = 0

Rise from a
you have transferring Some = 1
chair
from a chair or bed? A lot or unable without help = 2

How much difficulty do None = 0

Climb stairs you have climbing a Some = 1
flight of 10 stairs? A lot or unable = 2
How many times have None = 0
Falls you fallen in the past 1-3 falls = 1
year? 4 or more falls = 2
Score 0-10, ≥4 at risk of sarcopenia

Management:
 mTOR pathway is responsible for protein synthesis.
 Protein intake (amino acid and leucine are particularly potent) and or
exercise can activate this pathway.
 To overcome anabolic resistance, dietary protein intake should exceed
RDA and at least be 1.0g/kg/day for healthy older adults, and up to
1.5g/kg/day for those with sarcopenia.
 At least around 20g per meal is needed to overcome the threshold of
synthesis and above 40g per meal will exceed the maximum capacity of
synthesis.
 Therefore, it is recommended to evenly distribute the protein intake in
appropriate amount among the 3 meals daily.
 To date, there is little evidence to support pharmacological treatment.

Gr 20
 HYPERTENSION IN OLD AGE

Difference in hypertension between older adults and younger adults:

1. Isolated systolic hypertension (SBP >160 while DBP <90 mmHg) mostly
occurs in older patients.

2. Changes of structure and function of vascular tree in older age make them
more vulnerable to hypotension during common daily activities.
E.g. postural change or meal ingestion; in response to medications and
during volume contraction.

3. Antihypertensive medications can worsen postural hypotension and put

vulnerable older adults at a greater fall risk.

4. Possible and controversial beneficial effects of having higher blood

pressure are consistently observed in ‘survivors’ older than 85 years in
various observational studies.

Hypertension treatment consideration in older adults:

1. Life style modification, in particular about diet and weight control is
difficult to achieve in older persons and has to be balanced against
compromising quality of life.

2. Evidence around anti-hypertensive treatment for older people is imperfect.

Clinical trials of hypertension, exclusively recruiting or also including
patients over the age of 80 years have consistently demonstrated mortality
and cardiovascular benefits. However, participants in clinical trials are
usually healthier than the other older adults. Old and frail individuals with
multiple chronic conditions are usually not included and the balance of risk
and benefits is particularly unclear.

3. While benefits are clear for SBP <150 mmHg (strong evidence), stricter
control in older adults of SBP <120 mmHg has recently been shown to be
beneficial in terms of mortality and morbidity. (SPRINT, NEJM 2015) The
adoption of lower SBP treatment goal (130-140 mmHg) may be considered
in age of 65–80 with little comorbidity and biologically young. Otherwise,
less stringent target e.g. <150 mmHg should be used for those aged above
80 or older people with multiple comorbidities and biologically old.

Gr 21
4. Diastolic blood pressure should be targeted <90 mmHg (strong evidence).
An increased risk of ACS is associated with DBP between 61 to 70 mmHg
and increased further at DBP ≤ 60 mmHg, likely due to myocardium hypo-
perfusion which is diastolic phase dependent. In general, a DBP ≤ 60 mmHg
or in the presence of coronary artery disease, not <65 mmHg, is
recommended.

5. Be aware that the first one to two months of anti-hypertensive therapy in

older patients is associated with increased risk of falls and hip fracture.
Therefore, start low (initial doses approximately one-half that in younger
adults) and go slow (to achieve target BP over a period of weeks to months)
unless in hypotension. The prevalence exceeds 30% after 80 years of age.

6. Exercise clinical judgement rather than clinical guideline in treating blood

pressure in frail older adults with limited life expectancy, where immediate
risk associated with treatment may outweigh long term benefit.

Gr 22
 MUSCULOSKELETAL PAIN
Musculoskeletal pain is common, under-recognized and under-treated in older
people.

Pain Assessment in Older People

Identify
 Cause of musculoskeletal pain,
 Comorbid diseases influencing pain management
 Complicating psychosocial issues
 Pain levels and functional status for optimal pain management
 Mnemonics for pain assessment (PQRSTUVA)
Precipitating / Palliating factors Timing
Quality Upsetting ADL
Radiation Vital sign changes
Severity Associated symptoms
 For cognitively intact older people, self-reported measures (e.g. numerical
and graphic rating scales)

Δ Figure: Numerical Rating Scale Δ Figure: Wong-Baker Faces Pain Scale

 For cognitively impaired older people, non-verbal pain assessment tools (e.g.
Abbey Pain Scale) by observing patient’s vocalization, facial expressions,
changes in body language, behaviours mental status and physiological
parameters.

Common Musculoskeletal Disorders in Older People

 Joints: osteoarthritis of knees, hips, hands; inflammatory arthritis
(rheumatoid arthritis), crystal-induced arthropathy (gout and pseudogout)
 Bones: osteoporotic fractures
 Soft tissues (tendons, bursae, ligaments, muscles): rotator cuff syndrome,
adhesive capsulitis, tendonitis, bursitis and myopathy
 Chronic low back pain (CLBP) due to multiple aetiologies (e.g. lumbar
spondylosis and spondylolisthesis, disk disease, osteoporotic vertebral
fracture, spinal stenosis, paraspinal muscle spasm, referred pain from hip and
sacroiliac joint disease)
Gr 23
Management
 Management should be individualized and requires a multidisciplinary approach
with non-pharmacological and pharmacological modalities addressing physical,
psychological, social and spiritual components of pain.
 Aims: to relieve pain, restore function and maintain quality of life.
 Drug review for iatrogenic rheumatic syndromes (e.g. diuretic-induced gout).

Non-Pharmacological
 Physical therapy (Tai Chi for arthritis, physical modalities e.g. TENS, ultrasound,
heat or ice for pain relief), occupational therapy (for patients’ independence and
hazard reduction with assistive devices, joint rest with splinting for synovitis),
patients’/caregivers’ education (self-management, drug use), lifestyle advice
(weight reduction for osteoarthritis, dietary advice for osteoporosis and gout),
alternative medicine (herbs and acupuncture), psychosocial and spiritual support.

Pharmacological
 Older people are vulnerable to adverse drug reactions. Drug choice should be
based on individual profiles of renal, liver functions, cardiovascular risk factors
and gastrointestinal disorders with alertness to drug-drug and drug-disease
interactions.
 A stepwise pharmacological approach for pain management of osteoarthritis and
CLBP:
(1) Acetaminophen as first-line therapy for mild-to-moderate pain.
(2) NSAIDs as added-on if pain is not relieved or for inflammatory pain. However,
NSADs can cause gastrointestinal bleeding, fluid retention, renal, liver
impairment and precipitate heart failure in older people. The lowest effective
dose should be used for the shortest period of time. COX-2 inhibitors also
have cardiotoxicity, nephrotoxicity and hepatotoxicity similar to NSAIDs.
(3) Weak and strong opioids for moderate-to-severe pain.
 Because of increased toxicities of NSAIDs and colchicine in old age,
corticosteroids have been used more often in treating acute attacks of gout.
 Others: topical analgesics (topical NSAIDs, anaesthetics), adjuncts (anti-
convulsants, anti-depressants)

Injection Therapy:
 Intra-articular infection (e.g. hyaluronic acid for osteoarthritis, corticosteroid for
inflammatory arthritis, adhesive capsulitis), epidural infection of LA or
corticosteroid for CLBP

Surgery:
 Joint replacement and spinal surgery are reserved for people not responding to
medical therapy and with impaired daily activities.

Gr 24
 NEUROCOGNITIVE DISORDER

History (collect history from someone who knows the patient well)
 Past or current occupation
 Years of education
 Smoking and alcohol habit

Chief complaint
 Cognitive deficits / Memory loss
 Duration / onset / course / initial symptom (memory first or another
cognitive domain first)
 Onset – insidious / sudden / progressive

Functional assessment for staging (suggested items)

 Basic ADL – suggested questions: selection of appropriate clothes,
continence status
 Instrumental ADL – telephone, finance (banking, paying bills), shopping,
cooking, medication management, travelling alone
 Social activities and hobbies

Behavioural and psychological symptoms of dementia (BPSD)

 Apathy, sleep disturbances, irritability / agitation, wandering, mood
disorders (depression), psychotic symptoms (hallucination and delusion),
eating / appetite disorders
 Common examples:
- Delusion of theft by domestic maid
- Visual hallucination – seeing many small people or deceased relatives
- Sleep and night-time behaviour disturbance
- Lost interest in past hobbies (e.g. playing Mah-jong, watching TV,
reading newspaper)

Past health:
 Diabetes mellitus, hypertension, stroke, atrial fibrillation (AF)

Drug history

Family history of neurocognitive disorder

Gr 25
Physical examination
 General impression – Apathetic / agitated / sociable
 Pulse regular or in AF, bruits, murmur
 Focal neurological sign, muscle tone, muscle power, tendon reflexes
 Frontal release signs
 Gait and parkinsonian sign
 Do not omit other systemic examination (you could miss a paraneoplastic
syndrome presenting as dementia)

Investigations
 Renal and liver function, complete blood picture
 Blood glucose, lipid profile
 Thyroid function
 Serum vitamin B12 and folate level
 Syphilis serology (optional)
 HIV Ab (if suspicious)
 ECG – note AF (vascular dementia), long QT interval (neuroleptic
treatment precaution), bradycardia
 Neuroimaging / Plain CT brain is basic
 Other potentially useful tests:
- MRI brain
- EEG (esp. for CJD)
- CSF examination for biomarkers
- Functional imaging (FDG-PET, SPECT)
- ± pathological imaging (Pittsburgh Compound B or 18F- Flutemetamol)

Reference to diagnostic Criteria (DSM-5) when making diagnosis

1. Dementia (major neurocognitive disorders)
a) Significant cognitive decline from a previous level of performance in
≥1 cognitive area (memory, language, attention, executive function,
perceptual-motor and social recognition).
b) Interference with independence in everyday activities.
2. Mild cognitive impairment (MCI) or mild neurocognitive disorder
1(a) + no impairment in independence in everyday activities.
3. Not in the context of active delirium

Gr 26
Management
Social
 Prognosis infection
 Financial arrangement
 Advance care planning
 Enduring power of attorney
 Community and Day care resource

Medical
 Vascular risk factors control
 Non-pharmacological treatment (do not ignore this)
 Pharmacological (it may not be the most useful part)

1. Drugs retarding cognitive deterioration / delaying institutionalization:

Donepezil Starting with 5 mg daily
Cholinesterase inhibitor Galantamine (max dose Immediate release: Start
 For mild to moderate 16 mg for moderate renal with 4 mg BD
AD impairment) Extended release: start
 Major side effects: with 8 mg daily
anorexia, nausea,
vomiting, diarrhoea, Rivastigmine Starting with 1.5 mg BD
bradycardia Rivastigmine Start with 4.6 mg/24 hr
(transdermal patch)
NMDA antagonist Memantine Start with 5 mg daily
 Major side effects: (max dose 10 mg daily if
headache, dizziness, CrCl < 30 ml/min)
sedation, agitation,
constipation
*Dose escalation may need to be slower for Asians

2. Management of BPSD (must always use non-pharmacological method first)

 Use antipsychotic only when BPSD is potentially harmful to patient/
caregivers. E.g. haloperidol 0.5mg nocte po (contraindicated for LBD),
quetiapine 12.5mg / 25mg nocte po as starting dose.

Gr 27
 NURSING HOME-ACQUIRED PNEUMONIA (NHAP)

Aspiration plays an important role in the causation of NHAP. Risk factors

include advanced dementia, old CVA, GERD and poor oral hygiene.

Causative agents
 Respiratory viruses (influenza A and B viruses, and RSV), Gram negative
bacilli (GNB) and Staphylococcus aureus are more frequently isolated in
NHAP compared with CAP
 Mycobacterium tuberculosis should be considered in view of its
endemicity in HK.
 Streptococcus pneumonia and Haemophilus influenza are also common
bacterial culprits.
 Atypical pathogens are less commonly implicated in NHAP than CAP.

History
 The symptoms are similar to those of community-acquired pneumonia
(CAP).
 An episode of aspiration may or may not be witnessed.
 Onset of respiratory symptoms occurring shortly after the meal suggests
that aspiration is the likely cause.

Investigations
 CXR: a clear image indicates simple aspiration without pneumonitis
(chemical inflammation of lung parenchyma without infection) or
pneumonia (infection).
 Sputum: routine bacterial cultures, and AFB smear and cultures.
 NPA: a rapid test, should always be considered for infection control and
discharge planning.

Treatment
Non-pharmacological treatments
 Keep good oral hygiene, e.g. regular mouth treatment with normal saline
or oral disinfectants.
 Consult dental surgeon for dental caries or dental abscess.
 Prop up patients during feeding. Add thickener if appropriate.
 Physiotherapy for chest exercise, drainage and collection of sputum
specimens.

Gr 28
Empirical antibiotic treatments
 The recommendations are in line with those for CAP (See In1)
 Empirical broad-spectrum antibiotics may be used with caution in patients
with history of MDR bacterial pneumonia. E.g. vancomycin for MRSA
and ertapenem for ESBL-producing GNB.
 Empirical anti-viral agents, such as oseltamivir and amantadine, should be
considered when viral infection is suspected, especially if outbreak of
influenza-like illnesses in nursing home is reported.
 Report to the Community Geriatric Assessment Team (CGAT) if outbreak
of viral infection in nursing home is suspected or confirmed.

Gr 29
 ORTHOSTATIC HYPOTENSION

Orthostatic (postural) hypotension (OH) is a common, remediable and yet an

under-diagnosed condition, which may result in disability and death.

Definition:
 A drop in systolic blood pressure (BP) of ≥20 mmHg or diastolic BP of
≥10 mmHg within 3 minutes of standing*.

Measurement of orthostatic BP (document any associated symptoms):

 Active standing test: measure baseline BP after 5-minute rest in a supine
position, then measure BPs at 1-minute and 3-minute standing (or in an
upright position if unable to stand).
 Passive head-up tilt test if the active standing test is negative.

Clinical presentation:
 Dizziness on standing, syncope or near syncope, falls, inability to stand or
walk.
 Atypical presentation: stroke or transient ischaemic attack, seizure-like
symptom, cognitive impairment, angina or myocardial infarction, heat or
meal-related symptom, chronic fatigue.

Causes:
 Prolonged immobility
 Hypovolaemia (e.g. acute blood loss, severe dehydration)
 Drug-induced: anti-hypertensives, anti-anginal, vasodilators, diuretics,
anti-adrenergics, anti-cholinergics, anti-parkinsonian drugs, anti-
psychotics, anti-depressants, sedatives and narcotics
 Neurological diseases: Parkinson’s disease, Lewy’s body dementia, multi-
system atrophy, pure autonomic failure, peripheral neuropathy (e.g.
diabetic, alcoholic, paraneoplastic autonomic neuropathy)
 Cardiovascular diseases with low cardiac output: aortic stenosis,
hypertrophic cardiomyopathy, mitral valve prolapse, varicose veins
 Endocrine disorders: adrenal insufficiency, pheochromocytoma, diabetes
insipidus
 Baroreceptor destruction (e.g. neck radiation or surgery)

Notes:
OH is more prominent in early morning or after meals. Supine hypertension
and a loss of diurnal variation in BP are commonly associated in OH due to
Gr 30
autonomic dysfunction.
*A change in heart rate/change in systolic BP ratio <0.5 beats per
minute/mmHg with tilt or active standing can be a screening tool for
neurogenic OH and autonomic dysfunction should be considered.

Management:
 Aims: to improve symptoms and functional status, to reduce fall injuries,
neurovascular and cardiovascular complications
 Identify and treat underlying causes
 Medication review

Non-pharmacological
 Patients and caregivers’ education
 Adequate salt (>10g per day or 24 hours urine Na >170 mmol) and water
(1.5–2.5 L per day) intake
 Water-bolus treatment before standing
 Avoid triggers (e.g. immobility, abrupt posture change, heavy meals, hot
environment)
 Physical counter manoeuvres (exercise before standing)
 Compression therapy (abdominal binders, stockings)
 Elevate the head of the bed during sleep to reduce supine hypertension and
nocturnal diuresis

Pharmacological
 Fludrocortisone (synthetic mineralocorticoid, first line monotherapy):
initial dose: 50 microgram daily orally, increasing up to 300 microgram
daily orally or till mild pedal oedema
- Adverse effects: supine hypertension, hypokalaemia, peripheral
oedema, precipitate heart failure
 Midodrine (alpha 1 adrenoceptor agonist): initial dose: 2.5mg BD or TDS
orally, increasing up to 10mg TDS orally
- Adverse effects: supine hypertension, piloerection, pruritus or
paraesthesia, urinary retention
- Contraindicated in severe heart disease, acute kidney injury, urinary
retention, pheochromocytoma and thyrotoxicosis
 Pyridostigmine (cholinesterase inhibitor) 30–60 mg BD or TDS orally

Gr 31
 OSTEOPOROSIS IN ELDERLY

Definition of osteoporosis
 Low bone mass
 Defined by WHO using DXA scan
Status Hip BMD
Normal T-score ≥ 1
Osteopenia -2.5 ≤ T-score ≤ -1
Osteoporosis T-score ≤ -2.5
Severe
T-score ≤ -2.5 and presence of at least one fragility fracture
osteoporosis

Sites of fragility fracture:

 Hip
 Vertebra
 Distal radius
 Humerus

Indication for treatment

Case selection
1. All patients with fragility fracture
2. Osteoporosis as defined by vertebral (L1–L4) or hip BMD T-score ≤ -2.5
3. In addition, FRAX treatment thresholds as a reference for those who do not
fulfil (1) and (2)
 20% for MOF and 3% for hip # (IOF)
FRAX: https://www.sheffield.ac.uk/FRAX/tool.aspx?country=2

Exclusion criteria
1. Poor premorbid state, chair bed bound
2. Limited life expectancy
3. Severe cognitive impairment

Management protocol
1. History
a) Concomitant medical history
b) Menstrual and reproductive history
c) History of fracture
d) Drug history
e) Pain symptoms, access severity of LBP by 10 points VAS

Gr 32
 f) Smoking and drinking history, coffee intake

2. Investigation
a) CBP, ESR
b) LRFT, Ig pattern, Ca, PO4
c) TFT
d) XR spine
e) DXA
f) 25OH D3, urine Ca excretion, PTH when indicated

3. Management
a) Management should be individualized
b) CaCO3 1g daily and Vit D3 1000U daily to all patients unless
contraindicated
 Vit D3 only if patient has adequate dietary calcium intake
 For those with borderline high serum calcium level or history of
renal stones, can omit Ca supplement
c) All patients with fragility fracture will undergo fall risk assessment and
rehabilitation exercise prescribed to individual needs
d) Basic education, dietetic advice, exercise advice and fall prevention
should be individualized

4. Flowchart on management of osteoporosis

Gr 33
Medically approved drug therapies for the treatment of osteoporosis and
prevention of fractures include:
 Bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid)
 SERM: Raloxifene and bazedoxifene
 Anabolic agents: Teriparatide and abaloparatide (not yet available in HK)
 RANKL inhibitor: Denosumab
 Sclerostin inhibitor: Romosozumab

Important notice before start treatment:

A. Ensure adequate Ca/Vit D supplement before IV zoledronic acid or
denosumab or romosozumab
i) Patient should be taken Ca/D for at least 4/52 beforehand
ii) Consider high dose Vit D loading if indicated
B. Indication for IV zoledronic acid (used under HADF)
i) GI upset with oral bisphosphonates
ii) New fragility # while on BPs
iii) Admitted for operation of 1 fragility # and past history of fragility #
iv) ≥ 2 fragility #
C. Indication for denosumab (under HADF)
i) i, ii, iii, iv – same as IV zoledronic acid
ii) For eGFR < 35 ml/min
D. Teriparatide
i) Included in HADF for severe established osteoporosis
ii) BMD T- score ≤-3.0, ≥2 fragility fractures with poor response (1 new
symptomatic fracture despite ≥12 months’ treatment) or intolerant to
anti-resorptive therapies, for up to 24 months
iii) Contraindicated for hyper PTH, malignancy
E. Romosozumab8
i) Included in HADF for severe established osteoporosis
ii) BMD T- score ≤-3.0, ≥2 fragility fractures in postmenopausal women
with poor response (1 new symptomatic fracture despite ≥12 months’
treatment) or intolerant to anti-resorptive therapies, for up to 12 months
iii) Can be used for those with impair RFT eGFR ≥ 15 ml/min
iv) Contraindicated for patients with history of MI or stroke

Gr 34
Comparison of common anti-osteoporosis medications
SERM Bisphosphonates Denosumab Teriparatide Romosozumab
Mechanism of action Weak anti- Anti-resorptive Anti-resorptive Anabolic Anabolic
resorptive
Dosing method Oral Oral or IV Subcutaneous Subcutaneous Subcutaneous
Dosing frequency Daily Weekly (alendronate, Every 6 months Daily Once per month
risedronate) or monthly
(ibandronate)
Or yearly (zoledronic acid)
Fracture risk
reduction
Vertebral + + + + +
Non-vertebral – + + + +
Hip – + + – +
Renal impairment
eGFR 30-60 ml/min     
eGFR 15-30 ml/min × ×  × 
Atypical femoral 113/100 000 patients years 8/100 000 patients 1/1000-1/10 000
fractures (8-9.9 years exposure)4 years (up to 10
years exposure)5
Avascular necrosis of 1.01-69/100 000 patients 0-30.2/100 000 1/1000-1/10 000
jaw years6 patient years6
Treatment duration Up to 8 years7 Reassess after 5 years for Not recommend Maximum use 24 12 months,
oral and 3 years for IV drug holiday months followed by
Consider drug holiday if T- Maintenance with maintenance with
score >-2.5 and low risk anti-resorptives anti-resorptives
after 24 months
NB: Zoledronic acid contraindicated for eGFR <35ml/min
Oral BPs contraindication for eGFR <30ml/min

PLEASE CALCULATE eGFR by C-G EQUATION or CKD-EPI

Gr 35
5. Monitoring response to therapy
 Follow-up DXA of hip and spine after two years, and if BMD is stable
or improved, less frequent monitoring thereafter.
 Routine bone turnover markers monitoring not recommended.

Notes for patients plan for dental surgery9:

 Inform your dental surgeon.
 Balance the risk and benefits of drug holiday, in general, no need to stop
oral bisphosphonates.
 For those on denosumab, the planned dentoalveolar surgery can be
completed 4-5 months following the last dose of denosumab when the
level of osteoclast inhibition is waning. It can then be reinstituted 6-8
weeks post-surgery.

References:
1. OSHK. HKMJ 2013;19(supp2):1-40
2. Cheung E et al. Osteoporosis int 2014;25:1017-1023
3. Kwok T et al. HKMJ 2020;26:227-35
4. Dell R et. JBMR 2012;27:2544-50
5. Bone HG et al. Lancet Diabetes Endocrinol2017;5:513-523
6. Khan AA et al. JBMR 2015;30:3-23
7. Siris ES et al. JBMR 2005;20:1514-24
8. Cosman F et al. NEJM 2016;375:1532-1543
9. Ruggiero SL et al. J Oral Maxillofac surg 2022;80:920-943

Gr 36
 PHARMACOTHERAPY IN OLD AGE
Adverse drug reaction (ADR):
 Identify patients at risk of or suffering ADR (polypharmacy, high-risk medications)
 Always think of ADR if new symptom develops, rather than prescribing a new
medication to treat the new symptom (prescribing cascade)

Medication adherence:
 Simplify administration regime (aim at once daily).
 Assess patient’s hand function, cognitive function, vision, literacy, swallowing
 Use assistive tools (e.g. pillbox, calendar).
 Empower reliable caregiver to manage medications in patients with cognitive
impairment.
 Refer Community Nursing Service for medication management if necessary.

Prescribing:
 Beware of change in pharmacokinetics and pharmacodynamics in older patients.
 “Start low, go slow” and optimize dosage.
 Define overall goals of care (symptom relief, optimize physical / cognitive function,
preventive).
 Estimate time to benefit and life expectancy.
 Determine absolute benefit-harm thresholds of medications.
 Comprehensive geriatric assessment could help identify complex interactions and
impacts between medications and patient’s co-existing diseases, function and social
problems.
 Beware of drug-drug or drug-disease interactions.

Medications review:
 Accurately ascertain all current medication use (in HA, private sector, GOPC, over-
the-counter, traditional Chinese medicine).
 Verify current indications for ongoing treatment.
 Stop medications that are without net benefits (or gradually wean off medications
that are likely to cause adverse withdrawal events (e.g. benzodiazepines, β-blocker,
steroid).

Iatrogencity – Relationship between geriatric conditions and causative medications:

Geriatric conditions Causative medications
Hypnotics, sedatives, antipsychotics, antidepressants,
Fall antihistamines
Urinary incontinence Diuretics, cholinesterase inhibitors
Delirium Anticholinergics, benzodiazepines
Syncope Cholinesterase inhibitors, tricyclic antidepressants, α-blockers
Anorexia / Weight loss Metformin, cholinesterase inhibitors

Gr 37
 POST-OPERATIVE DELIRIUM
Post-operative delirium occurs in 20-40% of older patients undergoing surgery.
It is an acute mental disorder that is characterised by disturbance in attention,
cognition and awareness after a surgical procedure. Risk factors include
advanced age, multiple co-morbidities, frailty and pre-existing cognitive
impairment. One of the purposes of assessment and treatment is the prevention
and early detection of post-operative complications.

Causes:
 Commonly look for chest infection, blood loss during operation, acute
coronary syndrome, heart failure / fluid overload.
 UTI/ urine retention: palpable urinary bladder; constipation and faecal
impaction.
 Acute stroke: look for facial asymmetry, dysarthria, dysphasia, hemiparesis
or hemisensory loss.
 DVT: look for calf swelling and tenderness.
 Metabolic causes: Rule out electrolyte imbalance, hypoxia and
hypercapnia, hyper or hypoglycaemia.
 Medications/anaesthesia

Diagnosis of delirium (bedside tests):

 Confusion Assessment Method (CAM)
 4 As Test (Arousal, Attention, Abbreviated Mental Test 4, Acute change)
 CAM-ICU (in ICU setting)

Investigations (according to the clinical suspicion):

 Blood tests: CBC D/C, CRP, R/LFT/CaPO4, random glucose, TFTs, B12,
Folate, cardiac enzymes and ABG (anaemia, sepsis, acute renal or liver
failure, poor glycaemic control, fluid overload, acute cardiac event)
 Urine analysis and culture (UTI); Post-void residual urine by bladder scan
for suspected urinary retention
 ECG (ACS/ CHF)
 CXR (pneumonia) and sputum culture
 CT brain (acute CVA/ICH)
 USG Doppler or CT pulmonary angiogram (thromboembolism)

Treatments:
 Treat underlying acute medical events.
 Assess for adequate hydration and nutrition; pain control with analgesia.
Gr 38
 Early removal of unnecessary heparin blocks, lines, drains and catheters.
 Early mobilization/ sit out if no surgical contra-indications.
 Regulation of bladder and bowel function
 Promoting sleep hygiene
 Temporary use of psychotropic drugs for hyperactive delirium, such as
trazadone, quetiapine or risperidone.
 Stop / reduce the dose of psychotropic drugs in hypoactive delirium.
 Allow family and caregiver to visit more often.
 Other measures: fulfil patient’s physical needs, orientation to surrounding
environment, ensure eye glasses & hearing aids to improve sensory
perception.

Follow up:
 Observe and follow up of cognitive status after discharge (50% develop
dementia after 2 years follow up).

Gr 39
 PRESSURE ULCERS
(Also known as Pressure Injuries)

General Management:
 To identify individuals at risk of developing pressure ulcers by:
- Assessing the co-morbid illness and functional status.
- Using risk assessment tools, e.g. Norton scale.
- Vigilant against Medical device-related pressure injury.
 Maintain good hydration, nutrition, oxygenation and optimize glycaemic
control.
 Provide appropriate pressure reliving and redistribution device and avoid
inappropriate bed elevation or sitting.
 Reposition all individuals at risk of, or with existing pressure ulcers.
 Control excessive moisture and contamination due to urinary or faecal
incontinence.
 Look for complications, cellulitis, osteomyelitis or septicaemia.
 Antibiotics if:
- Local infection (cellulitis, lymphangitis streaking, purulence,
malodour, wet gangrene, osteomyelitis, etc.)
- Systemic symptoms (fever, chills, nausea, hypotension,
hyperglycaemia, leucocytosis, delirium)
 Pain Control
- Systemic analgesics, like paracetamol, opioids and/or non-steroidal
anti-inflammatory drugs, can be used 30 minutes prior to dressing and
afterwards.
 Assess life expectancy and chance of wound healing to arrive at an overall
goal of management – healing, symptomatic relief, or odour reduction only.

Wound Assessment and Staging:

 Evaluated for length, width, and depth, presence of sinus tracts or
undermining, exudate, and presence of necrotic or granulation tissue.
 Staged according to NPUAP Pressure Injury Stages
Stage Description
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
Unstageable Obscured full-thickness skin and tissue loss
Deep tissue Persistent non-blanchable deep red, maroon or purple discoloration

Gr 40
Wound bed preparation by TIME Model
 Tissue management
- Debridement and removal of sloughy and necrotic tissue
 Infection and inflammation control
- Management of bacterial bioburden and biofilm
 Moisture balance
- Choosing appropriate dressing materials on dry or moist wounds
 Epithelial edge advancement
- Identifying and managing causes of failure in epithelialization and
epidermal margin migration

Wound Debridement
 To remove the necrotic tissues include: irrigation, surgical debridement,
conservative sharp debridement, autolytic debridement, enzymatic
debridement, and biologic debridement.
 Do not debride stable, hard, dry eschar in ischaemic limbs.
 Immediate surgical debridement to remove the eschar and necrotic
tissue in the presence of advancing cellulitis, crepitus, fluctuance, and/or
sepsis secondary to ulcer-related infection.
 Conservative sharp debridement employs the use of scalpels, curettes,
scissors, forceps, and rongeurs to remove devitalized tissue without pain
or bleeding.
 Non-surgical debridement is preferred when there is no urgency.
- Autolytic debridement using body own enzymes to degrade dead
tissues by placing an occlusive dressing.
- Enzymatic debridement uses proteolytic enzymes that act by
decomposing collagen and liquefying necrotic decries without
damaging granulation tissue.

Wound Dressing
 To protect the wound from contamination and facilitate healing by
absorbing exudate and protecting healing surfaces.
 A moisture retaining dressing, including saline moistened gauze,
transparent films, hydrocolloids, and hydrogels, should be used to keep
moisture for desiccated ulcers.
 Hydrogels to keep moisture for autolytic debridement.
 Foam and low-adherence dressings for the granulation stage.
 Hydrocolloid and low-adherence dressings for the epithelialization stage.

Gr 41
Antiseptics and antimicrobial agents
 Most topically-applied antiseptic and antimicrobial products are irritating,
partially cytotoxic leading to delayed healing.
 Cadexomer iodine and Silver-based dressing are less cytotoxic and more
widely used in the presence of heavy local infection.
 Hibitane® (Chlorhexidine Gluconate) can be used in the presence of heavy
local contamination.
 Use systemic antibiotics for individuals with clinical evidence of systemic
infection, such as positive blood cultures, cellulitis, fasciitis, osteomyelitis,
systemic inflammatory response syndrome (SIRS), or sepsis.

Negative pressure wound therapy (NPWT)

 Enhances wound healing by reducing oedema surrounding the wound,
stimulating circulation, increasing the rate of granulation tissue formation
and wound closure.
 Can be considered as an early adjuvant for the treatment of Stage III and
IV pressure ulcers.
 The pressure ulcer should be debrided of necrotic tissue prior to the use of
NPWT and covered with a foam dressing.

End of Life Care

 Pressure Injuries are common in terminally ill older patients and the wound
is not likely to heal.
 Pain management, odour control, and exudate control are indicated for
comfort care.
 Conservative debridement of slough to control the bioburden.

Gr 42
 SPASTICITY

Definition:
 Involuntary muscle over activity caused by UMN lesions.

Assessment:
 New onset spasticity:
- Identify cause: History, P/E, Imaging studies
- Assessing severity: Modified Ashworth Scale
 Factors exacerbating pre-existing spasticity:
- Pain, Pressure sores, UTI, AROU, Constipation etc.

Management Strategy: (Refer to next page) (Also see Re12)

 Not all spasticity requires treatment.
 Aim at functional gains, symptom relief and carer-stress relief.

Botulinum toxin:
 Maximum dosages:
- BOTOX: ≤ 240 units Upper Limb, 300 units Lower Limb per session.
- Dysport: 1500 units per session
 Effects last for 3-4 months
 Adverse effects:
- Local muscle weakness, dysphagia, respiratory failure etc.
- Adverse effects peak at 2-4 weeks post-infection.

Baclofen:
 Dosage range: start 5 mg tds, max. 80 mg/day in divided dose.
 Cannot be stopped suddenly as risk of hallucinations and seizures.
 Adverse effects: nausea, seizure, hallucination, fatigue.

Diazepam:
 Dosage range: start at 5mg nocte, up to 60 mg/day in divided dose.
 Adverse effects: sedation, weakness, hypotension, amnesia, tolerance and
dependency.

Other medications: Dantrolene, Tizanidine, Clonidine, Gabapentin, Sativex.

Gr 43
Management Strategy for Spasticity

References:
 Spasticity in adults: management using botulinum toxin, National guidelines 2018, Royal College
of Physicians
 Medical Management of Spasticity in Spinal Cord Injury, Thomas Kiser, Rani Lindberg,
TRIUMPH Spinal Cord Injury Guidelines 2019
 Management of spasticity revisited. Laura A. Graham. Age and Ageing 2013;42:435-441
 National Institute of Neurological Disorders and Stroke website.
https://www.ninds.nih.gov/Disorders/All-Disorders/Spasticity-Information-Page
 American Association of Neurological Surgeons website.
https://www.aans.org/Patients/Neurosurgical- Conditions-and-
Treatments/Spasticity#:~:text=and%20Treatments%20Spasticity-,Spasticity,tighten%2C%20prev
enting%20normal%20fluid%20movement
 Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm,
cervical dystonia, adult spasticity, and headache. Report of the Guideline Development
Subcommittee of the American Academy of Neurology. David M. Simpson et al. 2016 American
Academy of Neurology
 Management of spasticity with onabotulinumtoxin A: practical guidance based on the Italian real-
life post-stroke spasticity survey, Giorgio Sandrini et al. Functional Neurology 2018;33(1):37-43
Gr 44
 SYNCOPE

Syncope is a defined as transient loss of consciousness (T-LOC) due to

transient global cerebral hypoperfusion characterized by rapid onset, short
duration, and spontaneous recovery.

* Initial evaluation = Careful history + physical exam + orthostatic BP

measures + 12-lead ECG

Careful history:
 Prior to attack: 3Ps: Provokers (activities), Posture, Prodrome
 During the attack (± witness): duration, skin colour, movements, tongue-
biting
 End of attack: autonomic symptoms, confusion, drowsiness
 Background: Number and details of previous attack(s), family history,
previous cardiac disease, neurological history, metabolic disorder,
medications.

Gr 45
**Short-term high-risk criteria requiring prompt hospitalization or
intensive evaluation
Abnormal ECG:
History:  Acute ischaemia
 Syncope during supine or exertion  Sustained or non-sustained VT
 New onset of chest pain, SOB,  A low AF, BBB, IVCD (QRS ≥120ms),
abdominal pain or headache ventricular hypertrophy, or Q waves
 Palpitations at the time of syncope consistent with IHD or cardiomyopathy
 History of MI, CHF, low LVEF  Inadequate sinus bradycardia (<50 bpm)
 Family Hx of SCD at young age or SA block in the absence of -ve
chronotropic drugs or physical training
 Pre-excited QRS complex, long /
Important co-morbidities: short QT interval
 Acute GIB or severe anaemia  pSVT or AF
 Unexplained SBP <90mmHg  RBBB w/ STE in V1-3 (Brugada pattern)
 OH of acute onset  ARVC: -ve T waves in Rt precordial
 Electrolyte disturbance leads, epsilon waves, ventricular late
potentials

Diagnostic tests according to initial evaluation

 Blood test: CBP, electrolytes, cortisol level, cardiac enzymes, blood gas and d-dimer
 Neurally-mediated test: tilt-table test, carotid sinus massage (>40 years old), active
standing
 Cardiac test: bedside cardiac monitoring, Holter study, other prolonged ECG
monitoring (in loop mode, e.g. external loop recorder or implantable loop recorder),
electrophysiological study, echocardiogram, CT or MRI (structural heart disease),
exercise testing, coronary angiography.
 Neurological evaluation: CT brain, EEG, MRI, MRA head and neck, autonomic
function test.

Treatment of vasovagal syncope

 Maintain adequate hydration ± salt supplementation.
 Avoid triggers (e.g. hot crowded places, dehydration, cough suppression in cough
syncope).
 For patients with prodromal symptoms:
- Employ isometric muscle contraction (e.g. hand-grip, leg crossing) to abort the
episode.
- Take precautionary steps to avoid injury e.g. by maintaining a horizontal position
at those times.
 Stop or reduce hypotensive drugs, targeting SBP of 140 mmHg (class IIa).
 Fludrocortisone 50-300 microgram daily.
 Midodrine 2.5 mg bd – 15 mg tds (S/E: supine HT, bradycardia, piloerection, urinary
retention).
 Dual-chamber cardiac pacing: for selected cases (class IIa/IIb)

Gr 46
 UNDERNUTRITION IN OLDER ADULTS
Undernutrition is common in hospitalized elderly, leading to higher mortality,
functional / cognitive decline, sarcopenia impaired immunity and delayed wound
healing.

Nutritional assessment and screening

 Dietary intake (history from carers)
 BMI (kg/m2) in Asians: Underweight (<18.5), Normal range (18.5-22.9),
Overweight (≥ 23);
- Careful interpretation if oedema, kyphosis, underestimates underweight
for chairbound, estimate height by knee height, arm span etc.
 Serial Body Weight: 5% weight loss in 1 month, or 10% in 6 months.
 Nutrition Screening tools; Malnutrition Universal Screening Tool (MUST),
Malnutrition Screening Tool (MST), Mini-Nutritional Assessment (MNA).
 Specific nutrient deficiencies – Vit B12 (cognition and paraesthesia), Vit D
(muscle weakness and bone pain).

Identify causes & reverse if possible

 Screen oral & dental health
 Drugs causing loss taste / smell – e.g. lipid lowering, antibiotics,
antihistamines, bronchodilators.
 Dysphagia (dementia, stroke, Parkinson’s)
 Disease – malignancy, end-stage organ failure (e.g. COPD, renal / heart
failure, dementia), acute/chronic infection
 Psychosocial – depression, loneliness, finance

Management
 Multifactorial, individualize nutritional plan
 Simple dietary advice – consider food preference, stronger flavours, variety,
small frequent meals.
 Diet liberalization, fortify food with milk powder, egg white.
 Little evidence for restrictive diets e.g. low Na/cholesterol/fat/CHO in frail
undernourished elderly.
 Calorie prescription – usual 25-30 kcal/kg/day, modify for severe
undernutrition, consult dietician.
 Formula for oral nutritional supplement or enteral feeding – polymeric (intact
protein, with or without fibre), partially hydrolysed or hydrolysed (semi-
elemental or elemental with free amino acids and small peptides), energy
dense, high protein or disease specific for diabetes / renal / hepatic /
pulmonary patients, formula with immunonutrition.

Gr 47
 Diarrhoea on enteral feed – identify cause (infection, medication,
malabsorption etc.), reduce strength of formula after consult dietitian, rate of
infusion while maintaining hydration.

Re-feeding Problems
 Re-feeding Syndrome
- Hallmarks include hypophosphatemia, hypokalaemia, hypomagnesemia
(occasionally, hypocalcaemia, hyperglycaemia).
- High risk patients: low BMI or cachexia or alcoholic, unintentional
weight loss, minimal or no food intake in past 10 days, low levels of K+,
PO4, Mg2+ prior to feeding.
- Assess hydration status and correct electrolyte deficiencies. ‘Start low,
go slow’ for calories.
- Refer Dietitian. Feed patient at 5-15 kcal/kg/day, increase by 5-10
kcal/kg/day during 5-10 days.
- Monitor cardiac rhythm in high risk individuals.
- Monitor clinical status, body weight, fluid balance, electrolytes (PO4, K,
Mg, Na, Ca, urea, Creat) for first 2 weeks.
- Supplementation if needed for potassium, phosphate, magnesium,
thiamine (200-300mg oral) and multivitamins.

 Wernicke’s encephalopathy (refer N9-10)

Ethical notes when considering enteral feeding

 Assess decision making capacity and respect wishes of mentally competent
patients (refer Gr3), if not identify surrogate decision makers e.g. or close
relatives for decision using best interest principle.
 Decision making for enteral tube feeding should include discussion on
possible use of restraints and lack of evidence to prevent aspiration or
increase survival.

Gr 48
 URINARY INCONTINENCE

 A syndrome characterized by complaint of involuntary loss of urine.

 Common in elderly patients with chronic physical disabilities, cognitive
impairment and frailty especially in hospital and residential care.
 Aetiology or urinary incontinence in elderly is complex. An intact
micturition pathway is vital but it also depends on patient’s and
environment factors.
 The goal of assessment is to identify transient, persistent and reversible
causes. Some of the underlying conditions are uncommon but serious (e.g.
spinal cord lesion, carcinoma or bladder and prostate, bladder stones and
low compliance bladder).
 Functional incontinence is commonly seen in the elderly patients during
the hospitalisation. It can be “iatrogenic” due to drug, use of restraint,
unfriendly environment for toileting, deconditioning, inadequate
hydration/nutrition.
 Impact or urinary incontinence includes use of diaper, lower self-esteem,
skin problem, infection, prolonged hospital stay and institutionalisation.

History
 Identify the type of urinary incontinence (urgency, stress, overflow,
functional or mixed).
 Assess lower urinary tract symptoms.
- Storage: urgency, frequency, nocturia, incontinence
- Voiding: hesitancy, straining, weak stream, intermittency, incomplete
emptying
 Look out for red flag symptoms/signs (e.g. haematuria, passage of stones,
dysuria and pelvic pain).
 Assess fluid intake and bowel habit.
 Look for coexisting medical conditions that may precipitate or worsen
urinary incontinence (e.g. CHF, stroke, dementia, Parkinson’s disease, DM,
BPH, recurrent urinary tract infection).
 Review medications (e.g. antipsychotic, calcium channel blocker, diuretic,
cough mixture, antihistamine) that may cause or worsen urinary
incontinence.
 Look for environmental barrier for toileting.
 Assess impact of incontinence on the patient and care giver.

Gr 49
Assessment
 General (peripheral oedema, skin change, pressure injury)
 Abdominal/pelvic (palpable bladder, atrophic vaginitis, pelvic organ
prolapse)
 Rectal (perineum sensation, rectal tone, faecal impaction, prostate size and
abnormal mass)
 Neurological (stroke, Parkinson’s disease, cord compression, peripheral
neuropathy)
 Cognitive function and mobility
 I/O chart
 Post void residual urine volume measurement
- Indicate if symptoms suggestive of voiding dysfunction and recurrent
urinary tract infection
- Bladder scan is preferable to catheterization
 Urinalysis
 RFT
 Other optional tests (urine cytology, KUB, ultrasound, uroflowmetry,
urodynamic study)

Management
 The mnemonic DIAPPERS (Resnick 1984) is helpful in management on
reversible causes.
D: Delirium
I: Infection of urinary tract or other infection
A: Atrophic urethritis and vaginitis
P: Pharmaceutical
P: Psychological problems, especially depression
E: Excess urine output
R: Restricted mobility
S: Stool impaction

 Non-pharmacological
- Early mobilisation
- Minimise use of restraint
- Provide appropriate toileting aid and assistance
- Adequate hydration and maintain good bowel habit
- Timed voiding, prompted voiding, bladder training, pelvic floor
exercise

Gr 50
 Pharmacological
- Antimuscarinics (oxybutynin, tolterodine, solifenacin, trospium)
- Beta3-adrenoceptor agonist (mirabegron)
- Alpha-adrenoceptor antagonist (terazosin, alfuzosin, doxazosin,
tamsulosin, silodosin)
- 5-Alpha reductase inhibitor (finasteride, dutasteride)
- Anti-cholinesterase inhibitor (distigmine)
- Others (duloxetine, desmopressin)
 Pay attention to high anticholinergic burden and drug induced hypotension
when starting pharmacological treatment in the elderly. Consult
geriatrician for management if having doubt.

Referral to specialists (geriatrician, urologist)

 Elderly with multiple comorbidities and polypharmacy
 Failed empirical treatment
 If visible or microscopic haematuria, recurrent urinary tract infections,
suspected malignancy of urinary tract

Gr 51
 URINARY RETENTION
Urinary retention is the inability to empty the bladder. Urinary retention can be
acute (AUR) or chronic (CUR). AUR is a medical emergency and can be
complicated by infection and renal failure. Cause of urinary retention is often
multifactorial especially in elderly. Both elderly men and women are prone to have
urinary retention during hospitalisation. Multiple mechanisms may co-exist within
the single aetiology.

Presentation
 Acute abdominal/suprapubic pain
 Weak stream, hesitancy, sense of incomplete emptying, lack of urge to void
 Impaired/Lack of bladder sensation
 Overflow incontinence
 Delirium

Causes
 Bladder outflow obstruction (BOO)
- Mechanical: BPH, malignancy, infection, stones, urethral stricture, pelvic
organ prolapse, post anti-incontinence surgery
- Dynamic: dysfunctional voiding, drug
 Underactive bladder
- DM, chronic BOO, aging, drug (see table Gr54), post-surgical intervention
 Bladder over-distension
- Immobility, constipation, pain, diuresis
 Neuropathic
- CVA, PD, spinal cord or cauda equina lesion, peripheral neuropathy

Assessment
 History and focused exam for underlying causes especially the reversible ones
 Assess cognitive function and mobility
 Review medication
 In men, digital rectal examination to assess prostate size and characteristics
 In women, perineal examination to look for organ prolapse
 Post void residual urine volume (PVR) measurement
- Suggested upper cut-off at 150-300ml (No consensus on normal value)

Investigation
- Urinalysis and RFT
- Imaging of urinary tract (KUB, USG, MRI/CT, cystoscopy, etc.) should be
considered in case of impaired RFT, recurrent urinary tract infections or if renal
stone, malignancy or other anatomical abnormality is suspected.

Gr 52
Management
1. Prevention
a) Encourage early mobilisation
b) Provide appropriate toileting aid and assistance
c) Avoid unnecessary restrain
d) Adequate pain control and bowel routine
e) Beware of over distension of bladder after giving bolus dose of diuretic
2. Prompt Foley catheter insertion for bladder decompression to relieve
symptoms and prevent damage to the upper urinary tract
3. Treat the underlying causes
4. Pharmacological treatment
a) BPH: Alpha blockers and 5-alpha reductase inhibitors (5ARi)
 Uro-selective agents are recommended in patient with multiple co-
morbidities, polypharmacy, high risk of postural hypotension & fall.
 5ARi can be considered if prostate volume >40ml on imaging.
 Non selective Alpha 1 block: Terazosin 1-10mg daily, Doxazosin 1-
8mg daily (IR) or 4-8mg daily (GITS), Alfuzosin 10mg daily.
 Uro-selective Alpha 1A block: Tamsulosin 0.2mg daily (ODT) or
0.4mg daily (OCAS), Silodosin 4mg BD or 8mg daily.
 5ARi: Finasteride 5mg daily, Dutasteride 0.5mg daily.
b) Underactive bladder: Distigmine (Ubretid 5-10mg daily)
 Take >30 minutes before breakfast because of poor absorption and
low bioavailability.
 Avoid use if there is mechanical bowel/urinary tract obstruction.
5. Evaluation of other causes of abdominal/suprapubic pain should be
considered if 1st cath volume < 200ml for patients presented with AUR.
6. The optimal time of Trial Without Catheter (TOWC) is not clear. Factors
including underlying causes, prior detrusor damage due to over-distension
and risk of catheter related urinary tract infections should be considered. It
is reasonable to keep catheter for >3 days if 1st cath volume >400ml to
allow bladder restoration.
7. Clean intermittent self-catheterisation (CISC) is recommended if long term
urinary catheterisation is required.
8. Other alternatives: Foley catheter, suprapubic catheterisation.
9. Consult urologist if hydronephrosis, suspicious of obstructive uropathy,
recurrent urinary retention related to BPH or failed pharmacological
treatment.
10. Consult geriatrician if failed TOWC when no surgical cause is identified
especially in women.

Gr 53
Class Type Examples Mechanisms
Drugs with Antipsychotic Phenothiazines
Anti Thioxanthenes
cholinergic Class I Cl i
Disopyramide
properties Antiarrhythmic Flecainide
Antispasmodic Hyoscine
Antiparkinsonian Artane
Antihistamine (H1) Chlorphenamine Blockade of
Diphenhydramine parasympathetic pathway
Hydroxyzine which impaired detrusor
Promethazine contractility
Loratidine
Bronchodilators Ipratropium
Thiotropium
Drugs for Oxybutynin
detrusor over- Tolterodine
activity Solifenacin
Darifenacin
Antidepressant Tricyclics Amitriptyline Competitive antagonist of
Imipramine muscarinic receptor which
impaired detrusor
contractility
SSRI Fluoxetine Increase external sphincter
Citalopram activity
SNRI Venlafaxine Increase external/internal
Desvenlafaxine sphincter activity
Anxiolytics Benzodiazepine Clonazepam Muscle relaxation
Diazepam
Analgesic Opiates Impair bladder sensation
Opioids analogues Increase sphincter activity
Alpha agonist Nasal decongestant Phenylephrine Increase internal sphincter
Ephedrine activity
Pseudoephedrine
NSAIDs COX/COX2 Naprosyn Inhibit PGE2 synthesis
inhibitors Celecoxib which suppress micturition
reflex
Calcium Nifedipine Reduce detrusor
Channel Amlodipine contractility
blockers

Gr 54
Haematology
 HAEMATOLOGICAL MALIGNANCIES

(1) LEUKAEMIA

1. Investigations at diagnosis
a. Blood tests
 CBP, PT/APTT
 D-dimer, fibrinogen (if suspicious of APL or DIC)
 G6PD, HBsAg, anti-HBc (total), HBV DNA (if HBsAg or anti-
HBc (total) +ve), anti-HCV, anti-HIV, RFT, LFT, Ca/P, Urate,
Glucose, LDH, Type & Screen, HLA-B*58:01
 Anti-CMV IgG if potential HSCT recipients
 Flow cytometry, DAT, Ig pattern, SPE, FISH for CLL
b. Bone marrow aspiration and trephine
 Contact haematologist for cytogenetic and molecular studies
before BM biopsy

2. Initial management
a. Start allopurinol [universal screening test for HLA-B*58:01 allele is
recommended before starting] (please refer to R4) (or febuxostat).
Consider rasburicase in patients at high risk for tumour lysis
syndrome: *note – contraindicated in G6PD deficient patients
b. Ensure adequate hydration
c. Blood product support:
 RBC/blood transfusion if symptoms of anaemia are present.
Platelet transfusion if platelet count ≤10 x 109/L or ≤20 x 109/L if
fever or bleeding (keep platelet ≥50 x 109/L in APL)
 Give plasma if there is evidence of bleeding due to DIC
d. Do sepsis workup if patient has fever
e. Antibiotic therapy:
 Give appropriate antibiotic if there is evidence of infection
 PCP prophylaxis for patients with acute lymphoblastic leukaemia:
i) Septrin 960mg daily three days per week, or
ii) Pentamidine inhalation 300 mg/dose once every 4 weeks
f. Do not give G-CSF to patients with newly diagnosed or suspected to
have APL (acute promyelocytic leukaemia)
g. Record patient’s performance status (PS)

H1
3. Inform haematologist the following medical emergencies
a. Hyperleucocytosis (e.g. WBC >100 x 109/L) for chemotherapy ±
leucopheresis. Avoid blood transfusion till WBC is lowered.
b. APL (acute promyelocytic leukaemia) for early use of all-trans-
retinoic acid (ATRA)

4. Initial treatment for APL

a. Correct coagulopathy:
i) Aggressive platelet transfusion (keep > 50 x 109/L)
ii) Transfuse cryoprecipitate/fibrinogen concentrate if fibrinogen
level <1.5g/l
iii) Transfuse plasma to keep PT and aPTT close to normal
b. Early use of all-trans-retinoic acid (ATRA) (45 mg/m2/d PO)
c. Consult haematologist

5. Subsequent management
a. Consult haematologist for long-term treatment plan
b. Arrange Hickman line insertion if indicated
c. CMV negative blood product for potential HSCT recipient if patient is
CMV seronegative

(2) LYMPHOMA

1. Investigations at diagnosis
a. Blood tests
 CBP, ESR, PT/APTT, G6PD
 RFT, LFT, CaPO4, LDH, Urate, Glucose, DAT
 Serum IgG/IgA/IgM levels, SPE
 HBsAg, anti-HBc (total), HBV DNA (if HBsAg or anti-HBc (total)
+ve), anti-HCV, anti-HIV
b. Biopsy
 Excisional biopsy of lymph node or other tissue (send fresh
specimen, no formalin) for study (markers, EM, DNA)
c. Bone marrow examination
d. Radiology
 PET/CT scan (preferred, especially in aggressive B-cell
lymphoma, Hodgkin lymphoma, T-cell lymphoma, and NK/T-cell
lymphoma)

H2
  CT scan of thorax, abdomen and pelvis or other sites of
involvement
 MRI if CNS involvement by lymphoma
e. Other investigations
 Endoscopic and Waldeyer’s ring exam for GI lymphoma
 LP with cytospin for patients with high risk of CNS lymphoma
(high grade lymphoma, nasal/ testicular/ marrow lymphoma)

2. Initial management
a. Start allopurinol [universal screening test for HLA-B*58:01 allele is
recommended before starting] (please refer to R4) (or febuxostat)
Consider rasburicase in patients at high risk for tumour lysis
syndrome: note – contraindicated in G6PD deficient patients
b. Record patient’s performance status (PS)

3. Note the following medical emergencies

a. SVC obstruction due to huge mediastinal lymphoma
b. Hypercalcaemia
c. Tumour lysis syndrome
d. Spinal cord compression

4. Subsequent management
 Consult haematologist for long-term treatment plan

(3) MULTIPLE MYELOMA

1. Investigations at diagnosis
a. Blood tests
 CBP, ESR, RFT, LFT, Ca/P, LDH, Urate, Glucose
 SPE with immunofixation for paraprotein
 Serum IgG/IgA/IgM level, Serum free light chain level (if SPE –
ve)
 β2microglobin, CRP, HBsAg, anti-HBc (total), HBV DNA (if
HBsAg or anti-HBc (total) +ve), G6PD, HLA-B*58:01
b. Urinalysis
 24 hr urine x Bence Jones Protein (BJP)
c. Radiology
 Skeletal survey, Total body MRI, CT or PET/CT
d. Bone marrow aspiration and trephine with cytogenetic study & FISH
H3
2. Staging
a. Revised International Staging System (R-ISS) (JCO 2015 33(26):
2863-2869)
High-risk CA [del(17p)
Serum Serum β2-
Stage and/or t(4;14) and/or 5 year OS
Albumin (g/l) M (mg/l)
t(14;16)] or high LDH
I > 35 No < 3.5 82%
II Neither stage I or III 62%
III - Yes > 5.5 40%

b. Symptomatic vs asymptomatic myeloma

 Symptomatic:
i) Presence of end-organ damage: CRAB:
Calcium elevation: (corrected serum Ca >2.75 mmol/L)
Renal insufficiency: (creatinine > 177 μmol/L)
Anaemia (Hb <10 or 2g < normal)
Bone disease (lytic lesions)
ii) Or any one of more of the following:
- Clonal marrow plasma cell ≥60%
- Involved: uninvolved serum free light chain ratio ≥100
- >1 focal lesion on MRI studies

3. Initial management
a. Ensure adequate hydration and start allopurinol 300 mg daily
[universal screening test for HLA-B*58:01 allele is recommended
before starting] (please refer to R4) or febuxostat
 Correct hypercalaemia – pamidronate or zoledronic acid
b. Renal dialysis for patients with renal failure
c. Record patient’s performance status (PS)
d. Consult Oncologist or Orthopaedic Team for patients presenting with
skeletal complications (pathologic fracture or spinal cord
compression)

4. Subsequent management
 Consult haematologist for long-term treatment plan

H4
(4) EXTRAVASATION OF CYTOTOXICS
(also see page GM 27 Oncological Emergency)

1. Prevention
a. Extreme care and never give it in a hurry
b. Choose appropriate veins
c. Confirm patency of iv site with NS before injection of cytotoxics
d. Flush with NS on completion of infusion/injection of cytotoxic drugs
e. Stop when patient complains of discomfort, swelling, redness
f. Use central line if indicated

2. Extravasation suspected
a. Leave iv needle in place and suck out any residual drug
b. If there is a bleb, aspirate it with a 25-gauage needle
 Anthracycline – apply ice pack
 Vinca alkaloid – apply warm pack
c. Potential antidotes
 Anthracycline – DMSO or hydrocortisone. Consider dexraxozane
(Savene) for tissue protection
 Vinca alkaloid – hyaluronidase
 Cisplatinum – hydrocortisone cream
d. Record the event in clinical notes/photos in ePR Patient Album; and
inform seniors

(5) INTRATHECAL CHEMOTHERAPY

1. Prescription
a. All intrathecal chemotherapy should be prescribed in a separate
prescription form.
b. Methotrexate, cytarabine and hydrocortisone are the only THREE
drugs that can be prescribed for intrathecal chemotherapy
administration.
c. The route of administration “Intrathecal” must be written in full in the
prescription.
d. Platelet count and clothing profile should be checked beforehand.

2. Dispensing
a. All dispense intrathecal drugs must be labelled with a warning
message “For Intrathecal Use Only”
b. All dispense intrathecal chemotherapy must be dispatched separately
H5
 in a designated container or in a sealed envelope/bag (marked
“Intrathecal drug”).

3. Consent
a. Prior to intrathecal chemotherapy administration, the medical staff
who is responsible for the procedure, must obtain an informed written
consent from the patient.

4. Administration
a. Parenteral drug(s) and intrathecal drug must be administered as
separate procedures, i.e. separated in time in setting up and initiating
the administration.
b. The staff responsible for the drug administration must verify the 5
“Rights” (Right patient, right time, right drug, right dose and right
route) against the prescription. A second trained staff is required to
independently verify the patient identification and drug checking
process.
c. Both staff must sign the medication administration record (MAR).

(6) PERFORMANCE STATUS

WHO/ECOG Performance Status
Score Activities
0 Fully active; able to carry on all pre-disease performance without restriction.
Restricted in physically strenuous activity, but ambulatory and able to carry out
1
work of a light or sedentary nature, e.g. light housework, office work.
Ambulatory and capable of all self-care but unable to carry out any work
2
activities; up and about more than 50% of waking hours.
Capable of only limited self-care, confined to bed or chair more than 50% of
3
waking hours.
Completely disable; cannot carry on any self-care; totally confined to bed or
4
chair.

(7) HAEMATOLOGICAL TOXICITY

WHO Haematological Toxicity Scale
Parameter Grade 0 Grade 1 Grade 2 Grade 3 Grade 4
Haemoglobin (g/dL) ≥11 9.5-10.9 8-9.4 6.5-7.9 <6.5
Leucocytes
≥4 3-3.9 2-2.9 1-1.9 <1
(x 109/L)
Neutrophils
≥2 1.5-1.9 1-1.4 0.5-0.9 <0.5
(x 109/L)
Platelets
≥100 75-99 50-74 25-49 <25
(x 109/L)
Haemorrhage Mild blood Gross blood Debilitating
None Petechiae
loss loss blood loss
H6
 NON-MALIGNANT HAEMATOLOGICAL
EMERGENCIES / CONDITIONS

(1) ACUTE HAEMOLYTIC DISORDERS

1. Approaches
a. Collect evidence of haemolysis
 Evidence of increased Hb break down
↑indirect bilirubin, ↓haptoglobin, ↑LDH
 Evidence of compensatory erythroid hyperplasia
Reticulocytosis, erythroid hyperplasia of bone marrow
 Evidence of damage to red cells
Spherocytosis, Fragmented RBC, Bite cells

2. Investigations
a. Blood tests
 CBP with peripheral blood smear, Reticulocyte count, Hb pattern
RFT, LFT, Bilirubin (direct/indirect), LDH, Haptoglobin, DAT,
clotting profiles
b. Other investigations:
 G6PD assay (may be normal during acute haemolysis, consider
repeating test a few weeks after recovery)
 Screening for malaria, cold agglutinins (arrange with laboratory)
 PNH screening test (arrange with laboratory)

3. Management
a. Identify cause of haemolysis, then treat accordingly
b. Consult haematologist

H7
4. Common agents reported to induce haemolytic anaemia in subjects
with G6PD deficiency
Unsafe for class I, II & III variants Safe for class II & III variants
Acetanilid Acetaminophen (paracetamol)
Dapsone Aminopyrine
Furazolidone Ascorbic acid except very high dose
Methylene blue Aspirin
Nalidixic acid Chloramphenicol
Naphthalene (mothballs, henna) Chloroquine
Niridazole Colchicine
Nitrofurantoin Diphenhydramine
Phenazopyridine Isoniazid
Phenylhydrazine L-DOPA
Primaquine Menadione
Rasburicase Para-aminobenzoic acid
Sulphacetamide Phenacetin
Sulphamethoxazole Phenytoin
Sulphanilamide Probenecid
Sulphapyridine Procainamide
Thiazosulphone Pyrimethamine
Toluidine blue Quinidine
Trinitrotoluene Quinine
Chinese Herbs: Streptomycin
Plum flower (腊梅花) Sulphamethoxpyridazine

Chuan lianzi (川蓮) Sulphisoxazole

Zhen zhu (珍珠末) Trimethoprim

Jin yin hua (金銀花) Tripelennamine

Niu huang (牛黃) Vitamin K

Please note:
Sulphasalazine = Sulphapyridine bonded with 5-aminosalicylic acid
Septrin (Co-trimoxazole) = Sulphamethoxazole + trimethoprim

5. Safety for class I variants is usually not known.

Data from Beutler, E, Blood 1994; 84:3613
Class I (severe deficiency with nonspherocytic haemolytic anaemia)
Class II (severe deficiency with intermittent haemolysis)
Class III (moderate to mild deficiency)

H8
(2) IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

1. Definition
 Isolated thrombocytopenia due to peripheral destruction with no
clinically apparent causes but of presumed autoimmune aetiology
 To look for secondary causes of ITP, e.g:
- Infection: HCV, HIV, H Pylori
- Autoimmune causes e.g. SLE
- Lymphoproliferative disorders
- Drugs related

2. Investigations
a. CBP and blood film (to ensure no red cell fragments, leukaemia),
LRFT, PT/aPTT, Ig pattern, HBsAg, anti-HCV, anti-HIV,
CMVpp65/PCR, G6PD
b. Bone marrow examination not mandatory, indicated if
i) The diagnosis of ITP is not certain
ii) Prior to splenectomy
iii) If response to treatment is poor

3. Management
a. Consult haematologist
b. Initial treatment: Prednisolone 1 mg/kg/day, or
Pulse dexamethasone 20-40 mg/day for 4 days
c. For acute life-threatening bleeding
 IVIg 0.4 g/kg/day for 5 days or 1.0 g/kg/day for 2 days
(80% effective, lasts 2-3 weeks)
 Or Methylprednisolone 1g iv over 1 hour daily for 3 days
 Or Intravenous anti-D
d. second line therapy: thrombopoietin mimetics (Eltrombopag,
Romiplostim), Rituximab, splenectomy
e. Avoid aspirin and other antiplatelet agents and IM injection
f. Platelet transfusion only for life-threatening bleeding

4. Management of ITP in Pregnant Women

a. Consult haematologist
b. During pregnancy
 Platelet count > 30 x 109/L and no bleeding – no treatment till 36
weeks gestation (or sooner if delivery is imminent)
 Platelet count < 30 x 109/L or clinically relevant bleeding – first
H9
 line therapy is steroid (prednisolone are preferred to
dexamethasone, which crosses placenta more readily) or IVIg
c. At delivery
 Mode of delivery according to obstetrical indication.
 Maternal platelet count > 50 x 109/L is sufficient to prevent
complications due to vaginal delivery or Caesarean section.
 Review with anaesthetist if need epidural or spinal anaesthesia.

(3) HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

The 4Ts: A clinical probability scoring system for diagnosis of HIT
4Ts 2 Points 1 Point 0 Point
Thrombocytopenia Platelet count Platelet count Platelet count
fall >50% and fall 30-50% or fall < 30% or
platelet nadir platelet nadir 10- platelet nadir
≥20 x 109/L 19 x 109/L <10 x 109/L
Timing of platelet Clear onset Consistent with Platelet count
count fall between days 5- days 5-14 fall, fall ≤4 day
14 or platelet fall but not clear without recent
≤1 day (prior (e.g. missing exposure
heparin exposure platelet counts)
within 30 days) or onset after
day 14 or fall ≤1
day (prior
heparin exposure
30-100 days)
Thrombosis or New thrombosis Progressive or None
other sequelae (confirmed); recurrent
skin necrosis at thrombosis;
heparin injection Non-nectrotizing
sites; (erythematous)
anaphylactoid skin lesion;
reaction after IV Suspected
heparin bolus thrombosis (not
confirmed)
OTher causes of None apparent Possible Definite
thrombocytopenia
High probability (6-8 points), intermediate probability (4-5 points), low probability (≤3 points).

Adapted from Lo et al., J Thromb Haemost 2006;4:759

H 10
(4) THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

1. Diagnosis
a. Classical pentad – microangiopathic anaemia, thrombocytopenia,
fever, renal impairment, neurologic symptoms/signs
b. Redefined as a syndrome of Coombs’-negative haemolytic anaemia
and thrombocytopenia in the absence of other possible causes of these
manifestations
c. Important to examine blood film for micro-angiopathic features

2. Investigations
 CBP, Peripheral smear (for features of micro-angiopathic haemolytic
anaemia), reticulocyte count, RFT, LFT, LDH, Haptoglobin, DAT,
Coagulation profile (relatively normal)
 ADAMTS13 activity / Antigen

3. Treatment
a. Consult haematologist
b. Daily plasma exchange with plasma or cryo-reduced plasma (CRP)
should be commenced immediately
c. Steroid (Prednisolone 1 mg/kg/day or pulse Methylprednisolone
1g/day x 3 days)
d. Platelet transfusion is contraindicated

(5) PANCYTOPENIA

1. Approaches to determine the cause of pancytopenia

a. Bone Marrow disorder (defective synthesis)
 MDS
 Aplastic anaemia
 Megaloblastic anaemia
 Marrow infiltration: lymphoma, myeloma, marrow fibrosis,
carcinoma
 Reactive haemophagocytosis
 Disseminated tuberculosis
b. Peripheral destruction
 DIC
 Hypersplenism
 SLE
 Paroxysmal nocturnal haemoglobinuria (PNH)
H 11
2. Investigations
 CBP, Peripheral smear, vitamin B12, folate, TFT, PT/aPTT +/- Bone
marrow aspiration and trephine

(6) THROMBOPHILIA SCREENING

1. Tests
a. Lupus anticoagulant (LA), anti-cardiolipin Ab (aCL), anti-β2-
glycoprotein I antibody (anti-β2 GPI)
b. Protein C (PC), Protein S (PS), anti-thrombin (AT), Activated Protein
C Resistance (APCR), Factor V Leiden, Prothrombin G20210A
mutation

2. Indications
a. Warfarin induced skin necrosis
b. Young patients with idiopathic venous thrombosis
c. Unusual sites of thrombosis (mesenteric, renal, portal veins, cerebral
venous sinus)
d. LA, aCL and anti-β2 GPI as workup of anti-phospholipid syndrome
such as in case of recurrent miscarriage and unprovoked VTE (also see
R15)

H 12
 DRUGS AND BLOOD PRODUCTS

(1) ANTI-EMETIC THERAPY

1. 5-HT3 antagonists (for patients on cytotoxic chemotherapy)

a. Zofran (ondansetron) 8 mg iv Q8H/Q12H or 8 mg po TDS
b. Kytril (granisetron) 3-6 mg iv once daily or transdermal patch
c. Navoban (tropisetron) 5 mg iv/po once daily

2. Maxolon
 10mg iv Q6H prn

3. Emend (Aprepitant)
 Use in combination with corticosteroid or other 5-Ht3 antagonist:
125mg po on day 1; 80mg po daily on day 2-3

(2) IMMUNOGLOBULIN THERAPY

1. Indications
a. As replacement
 Primary immunodeficiencies with significant past infections (See
IA21)
 Secondary Ab deficiencies: CLL, multiple myeloma, post HSCT
patients with chronic GvHD and significant past infections
b. As an immunomodulatory (haematology)
 Proven benefit – ITP with life threatening bleeding or pregnancy
 Probable benefit – autoimmune haemolytic anaemia
Post infectious thrombocytopenia
2. Dosage
a. Replacement – 0.2 g/kg Q3 weeks
b. Immunomodulator e.g. ITP – 0.4 g/kg/day for 5 days or 1 g/kg/day for
2 days

3. Contraindications
a. Previous history of allergy to IVIg
b. Caution but not absolute contraindication in IgA deficiency (See IA
22)

H 13
(3) rFVIIa (NOVOSEVEN®)
 Dosage: 90-120 micrograms/kg/dose; may be repeated every 2-4 hours
 Indications: (Please refer to latest HA drug formulary)
- Congenital haemophilia A or B with inhibitors and active bleeding
- Patients with acquired haemophilia and active bleeding
- Glanzmann’s thrombasthenia
- Factor VII deficiency (15-30 microgram/kg/dose, may be repeated
every 4-6 hours)

(4) DIRECT ORAL ANTICOAGULANTS (DOACs)

1. Indications and dosage

Clinical setting Dabigatran Rivaroxaban Apixaban Edoxaban
Prevention of Knee: 110mg Knee: 10mg Knee: 2.5mg
venous once within 1-4 daily for 12 BD for 12
thromboembolism hr of completed days with or days
post total hip/knee surgery, then without food
replacement 220mg daily for
10 days

Hip: 110mg Hip: 10mg Hip: 2.5mg

once within 1-4 daily for 35 BD for 35
hr of completed days with or days
surgery, then without food
220mg daily for
28-35 days
Non-valvular CrCl CrCl 5mg BD, Or CrCl
Atrial fibrillation >30 ml/min: >50 ml/min: 2.5mg BD >50 ml/min:
150mg BD 20mg daily with any 2 of 60mg daily
with evening the
meal; followings:
 ≥80 years
15-30 ml/min: 15-50 mL/min: old; >15-50 ml/min:
75mg BD 15mg daily  BW 30mg daily
with evening ≤60kg;
meal  Cr ≥132.6
μmol/l
DVT treatment At least 5 days 15mg BD for 10mg BD for At least 5 days of
PE treatment of initial 21 days with 7 days, then initial parenteral
parenteral food, then 5mg BD anticoagulant,
anticoagulant, 20mg daily then 60mg daily
then 150mg BD (BW >60kg);
(CrCl >30 30mg daily (BW
ml/min) ≤60kg)

The table shows the doses of each DOAC in different clinical settings. However, the dose has to be
adjusted if the patient has underlying renal impairment.

H 14
2. Usual time to discontinue DOACs before surgery or invasive
procedures for which anticoagulation needs to be stopped
Renal function Estimated Low bleeding High bleeding
(CrCl, ml/min) half-life (hr) risk (hr) risk (hr)
Dabigatran
≥80 13 24 48
≥50 to <80 15 24-48 48-72
≥30 to <50 18 48-72 96
Rivaroxaban
≥30 9 24 48
<30 48 72
Apixaban
≥30 8 24 48
<30 48 72
Edoxaban
≥30 10-14 24 48
<30 48 72
British Journal of Haematology, 2016, 175, 602-613

Remark: Neuraxial intervention (e.g. spinal / epidural anaesthesia) might warrant

longer cessation time with selected DOACs. Consult Anaesthesiologist for the
cessation time of DOACs if neuraxial technique is contemplated.

3. Specific antidote of DOACs:

 Dabigatran:
- Idarucizumab (Praxbind®) 2.5g iv x 2 doses; slow iv infusion over
10 mins (separated by no more than 15 mins apart)
 Rivaroxaban, Apixaban and Edoxaban:
- Andexanet alpha (not available in Hong Kong at the time of
writing). May consider prothrombin complex concentrate (4
factor): 2000 units or 50 unit/kg.
 Other general management strategies:
- Cessation of treatment
- Tranexamic acid
- Oral activated charcoal may decrease further absorption if
ingestion <2hr
- Dabigatran can be removed by haemodialysis, but NOT
rivaroxaban, apixaban and edoxaban which are all highly protein
bounded.

H 15
(5) REPLACEMENT FOR HEREDITARY COAGULATION
DISORDERS

1. Haemophilia A and B
Hemophilia A Hemophilia B
Type of Peak factor Treatment Peak factor Treatment
haemorrhage level (IU/dL) duration (d) level (IU/dL) duration (d)
Joint 40-60 1-2 a 40-60 1-2 a
Superficial muscle /
no NV compromise 40-60 2-3 a 40-60 2-3 a
(except iliopsoas)
Iliopsoas or deep muscle with NV injury or substantial blood loss
Initial 80-100 1-2 60-80 1-2
Maintenance 30-60 3-5 b
30-60 3-5 b
Intracranial
Initial 80-100 1-7 60-80 1-7
Maintenance 30-60 8-21 30 8-21
Throat and neck
Initial 80-100 1-7 60-80 1-7
Maintenance 50 8-14 30 8-14
Gastrointestinal
Initial 80-100 7-14 60-80 7-14
Maintenance 50 30
Renal 50 3-5 40 3-5
Deep laceration 50 5-7 40 5-7
Surgery (major)
Pre-op 80-100 60-80
Post-op c
60-80 1-3 40-60 1-3
40-60 4-6 30-50 4-6
30-50 7-14 20-40 7-14
Surgery (minor)
Pre-op 50-80 50-80
Post-op d
30-80 1-5 30-80 1-5
a May be longer if response is inadequate.
b Sometimes longer as secondary prophylaxis during physical therapy.
c The duration of treatment refers to sequential days post-surgery. Type of clotting factor concentrate
(CFC and patient’s response to CFC should be taken into account.
d Depending on procedures; the number of doses would depend on the half-life of the CFC used.

Ref: WFH Guidelines for the Management of Hemophilia (3rd edition). Haemophilia. 2020;26(Suppl 6):1-158

 1 unit/kg BW of infused Factor VIII raised plasma level by 2%.

 1 unit/kg BW of infused Factor IX raised plasma level by 1%.
 Start the maintenance dose of factor replacement in the same day of
initial dose.

H 16
  DDAVP is useful for mild haemophilia A if a 3x increase in Factor
VIII suffices. Each patient’s response should be tested prior to
therapeutic use as there are individual variations. 0.3 microgram/kg in
50ml normal saline iv in 20 minutes causes a peak in Factor VIII level
at 30 minutes.
 Prolonged use of DDAVP cases tachyphylaxis.

2. Replacement therapy for Rare Bleeding Disorders

Recommended
Deficient Plasma trough levels to
On demand dosages
Factor half-life maintain
asymptomatic
 Cryoprecipitate 10 bags
Fibrinogen 2-4 d 1g/l (100 mg/dl)
 Fibrinogen concentrate*
Prothrombin
3-4 d PCC 20-40 units/kg >10%
(Factor II)
Factor V 36 h Plasma 15-25 ml/kg 10%
rFVIIa 15-30 microgram/kg every
Factor VII 4-6 h >20%
4-6 h
Factor X 40-60 h PCC 20-30 units/kg >40%
Factor XI 50 h Plasma 15-20 ml/kg 15-20%
Factor XIII 9-12 d Cryoprecipitate 10 bags 30%
PCC, prothrombin complex concentrate
*Dose (mg/kg body weight) = [Target level (mg/dL) – measured level
(mg/dL)]/1.7 (mg/dL per mg/kg body weight)

Based on Palla et al Blood 2015(125):2052-61

H 17
(6) TRANSFUSION

1. Indications – General Guidelines

Whole blood/Blood Dosage Indications
components
Fresh whole blood (≤5 days 1 –2 units Exchange transfusion or massive blood loss in
from donation) neonates
Whole blood / Red cells Dosage depends on clinical There is no single haemoglobin value that must be
situations taken as the transfusion trigger. However, a trend
towards cautious blood transfusion trigger has
One standard unit (derived from been observed but patients’ condition may affect
450ml whole blood donation) clinical decision. The initiation of transfusion is
should raise Hb level by up to a clinical decision by the attending clinician. In
1.2g/dL in a 70kg adult general, the following principles are considered:
1. Haemoglobin concentration <7g/dL and
One small unit (derived from assessment on the rate of ongoing red cell
350ml whole blood donation) loss.
should raise Hb level by about 2. For haemoglobin concentration between 7
0.85g/dL in a 70kg adult and 10g/dL, transfusion strategy is less clear
but general view is that transfusion is often
For children, 4ml/kg should not justified purely based on haemoglobin
raise Hb level by 1g/dL concentration.
3. A higher haemoglobin concentration may be
required in patients who may tolerate anaemia
poorly, e.g. patients over the age of 65 years
and patients with cardiovascular or
respiratory disease.
4. Single unit red cell transfusion is strongly
recommended to be the standard for patients
with no ongoing bleeding except those who
are known to have red cell production
problem (such as thalassaemia major and
bone marrow failure). Additional units
should only be prescribed after re-assessment
of the patients and their haemoglobin values.
Washed red cell Same as other red cell 1. Patients with reactions to transfused plasma
preparations proteins (e.g. IgA deficiency)
2. Patients with severe allergic reactions of
unknown cause
3. Patients with severe reactions despite
leucocyte depletion
4. Patients with paroxysmal nocturnal
haemoglobinuria who experience reactions
despite group-specific leukodepleted red
cells
5. Rarely, severe autoimmune haemolytic
anaemia where excess complement may
worsen destruction
Platelets 4 random donor units (each 1. Platelet <10 x 109/L in stable patients
(either prophylactic or derived from 350ml or 450ml (usually NOT indicated in idiopathic
therapeutic) whole blood donation) for thrombocytopenia, systemic lupus
adults up to 70kg erythromatosis, thrombotic
thrombocytopenia and haemolytic-uraemic
Each unit should raise platelet syndrome)
count by 7-10 x 109/L 2. Platelet <20 x 109/L in patients with fever or
sepsis
5 units/m2 for paediatric patients 3. Platelet <50 x 109/L with diffuse
microvascular / mucosal bleeding, major
1 unit of apheresis platelets is bleeding or before invasive procedures
equivalent to one standard adult 4. Platelet <100 x 109/L with retinal or central
dose (for adults up to 70kg) nervous system bleeding / surgery, or with
active bleeding in postcardiopulmonary

H 18
 bypass.
5. Platelet <50 x 109/L in stable premature
neonates or platelet <100 x 109/L in sick
premature neonates
6. Suspected platelet dysfunction with active
bleeding or before invasive procedures
7. Suspected platelet deficiency with severe
active bleeding or following massive
transfusion
Leukocytes (must be 10 units/day for ≥ 4 days or Neutropenia (<0.5 x 109/L with documented
irradiated) until fever subsides infection unresponsive to broad spectrum
(Require special antibiotics including antifungal agents for at least
arrangement with the 48 hours.
HKRCBTS)
Plasma Typical dosage: 1. Thrombotic thrombocytopenic purpura
2 – 4 units of adults 2. When clotting factors deficiency is suspected
12 – 15 ml/kg for paediatric or anticipated with active bleeding during
patients operation or following massive transfusion
**always reassess for clinical 3. Immediate reversal of warfarin overdose
and laboratory responses (bleeding or impending surgery)
4. Prothrombin time / activated partial
thromboplastin time (PT/APTT) >1.5x control
values with active bleeding or before invasive
procedure in the following situations.
 Single or multiple clotting factor deficiency
(other than haemophilia A/B)
 Disseminated intravascular coagulopathy
 Hepatic failure
Plasma Methylene Blue Supply for paediatric patients As for Plasma, with lower residual infectious risk
treated only
Cryoprecipitate 10 units per dose for adults up 1. von Willebrane disease (if desmopressin or
to 70kg factor concentrate is inappropriate)
For children, 5-10 ml/kg up to 2. Documented fibrinogen deficiency (<1g/L) or
10 units dysfunction
3. Documented factor XIII deficiency
Cryo-reduced plasma Same as plasma Thrombotic thrombocytopenic purpura (CRP can
(CRP) be an alternative to plasma but there is no
conclusive evidence to suggest that it is better than
plasma)
Leukodepleted (filtered) Same as non-leukodepleted As indicated for other cellular components, but
cellular blood components (filtered) counterparts especially indicated for:
1. All thalassaemia patients on regular
transfusion regimens;
2. Haematological diseases;
3. Documented severe febrile non-haemolytic
transfusion reaction (≥ 2 episodes);
4. Paediatric oncology patients;
5. Patients with human immunodeficiency virus
(HIV) disease and are CMV-antibody-
negative
Pooled leukodepleted The platelet dose in one unit of As indicated for platelets, but especially indicated
buffy-coat platelet in this pooled product is equivalent for:
platelet additive solution to 4 units of random donor 1. Patients who need repeated platelet
(PAS) +/- irradiation platelets transfusion
2. Patients who experienced documented Febrile
Non-haemolytic Transfusion Reaction after
platelet transfusion for 2 or more times
Psoralen (Intercept)- Same as plasma / platelets As indicated for plasma / platelets, with priority for
treated plasma / platelets immunocompromised patients (such as post-
haematopoietic stem cells or solid organ
transplantation on immunosuppression)
Irradiated cellular blood Same as non-irradiated For prevention of transfusion-related graft versus
components counterparts host disease in circumstances including:
1. Foetuses requiring intrauterine transfusion

H 19
 2. Neonates who have previously received
intrauterine transfusion undergoing top-up
transfusion till 6 months of age
3. Patients with severe congenital cellular
immunodeficiency
4. Allogeneic haemopoeitic stem cell
transplantation patients
5. Autologous haematopoietic stem cell
transplantation/chimeric antigen receptor
(CAR) T-cell therapy, from at least 7 days
prior to bone marrow/stem cell/lymphocyte
harvest until 3 months’ post-transplantation/
therapy.
6. Patients treated with purine analog drugs
(e.g. fludarabine, cladribine, clofarabine,
bendamustine) until 12 months after
completion of therapy.
7. Patients treated with anti-T-cell treatment
(e.g. anti-thymocyte globuline [ATG],
alemtuzumab and other T-cell monoclonals)
for aplastic anaemia or leukaemia from the
initiation of treatment till 12 months after
completion of therapy.
8. Patients receiving transfusion from close
relatives.

If there is an urgent need for transfusion, this

should not be withheld if no irradiated unit is
available. Leukodepleted (performed pre-storage
or by bedside inline filter) blood products and
older (stored > 2 weeks) red cells/whole blood
units should be used.
Cytomegalovirus (CMV) Dosage according to individual 1. Elective transfusions during pregnancy (not
negative cellular blood cellular blood components during labour, delivery, miscarriages or
components termination of pregnancy) #
2. CMV-antibody-negative recipients of
allogeneic stem cell grafts*
3. Intrauterine transfusions
4. Neonates with birth weight <1.5kg

#In emergency situations, if CMV negative

cellular blood components are not available, life-
saving transfusion should not be withheld and
leukodepleted blood components can be used to
avoid delays.

*If CMV negative cellular blood components are

not available, leukodepleted blood components
can be used.
Rhesus D (RH(D)) negative Same as Rh(D) positive red In this order of priority:
red cells cells 1. Haemolytic disease of newborn due to anti-D
2. Rh(D) negative individuals with anti-D
3. Rh(D) negative females prior to menopause
4. Emergency resuscitation of Caucasian
females in reproductive age with unknown
Rh(D) status
5. Other Rh(D) negative individuals
Source: Transfusion Guideline for HA hospitals 2023 edition (page 12-17)

H 20
2. Management workflow for patients with suspected acute transfusion
reaction

Source: Transfusion Guideline for HA hospitals 2023 edition (page 48)

H 21
Immunology
&
Allergy
 ANAPHYLAXIS

An acute, potentially life-threatening, multisystem syndrome caused by

release of mast cell mediators into the systemic circulation.

Anaphylaxis is likely when: (any one of 2 following criteria)

1. Acute onset of an illness (minutes to several hours) with simultaneous
involvement of the skin, mucosal tissue, or both (e.g., generalized hives,
pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (e.g. dyspnoea, wheeze, stridor, reduce PEF,
hypoxaemia)
b. ↓BP or associated symptoms of end-organ dysfunction (e.g.
collapse, syncope, incontinence)
c. Severe gastrointestinal symptoms (e.g., severe crampy abdominal
pain, repetitive vomiting), especially after non-food allergens
2. Acute onset of hypotension or bronchospasm or laryngeal involvement
after exposure to a known or highly probable allergen for that patient
(minutes to several hours)
Common causes: Food, medications, radiocontrast, venoms, exercise
Symptoms and signs usually occur within 1 hour of exposure

Management
 Administer adrenaline without delay
- 0.01 mg/kg IM into lateral thigh, up to maximum 0.5 mg (0.5 ml of
adrenaline 1:1000)
- May be repeated every 5 minutes as needed
- Consult ICU & adrenaline infusion if refractory
 Initiate acute management and resuscitation (see algorithm)
 Send blood for tryptase (<4 hours after anaphylaxis)
(Can be stored as clotted blood at 4oC prior to consultation)*
- Acute sample: preferably 30 mins to 4 hours following event
- Baseline sample: >24 hours after event
 If risk of recurrence: prescribe adrenaline auto-injector & training
 Referral to Immunology & Allergy for work-up and management
 Advise patient to keep record of future reactions and allergen-event diary
 Accurate diagnosis and appropriate avoidance advice are imperative to
avoid unnecessary avoidance or inadvertent re-exposure

*Blood may be sent to QMH Immunology Lab after consultation

IA 1
 Evaluate Circulation, Airway, Breathing

Cardio-respiratory arrest Yes Cardiopulmonary

resuscitation

No

Airway or cardiovascular No Mucocutaneous

involvement involvement ONLY
(Suggestive of anaphylaxis)

Yes (or in doubt)

First line

INTRAMUSCULAR ADRENALINE  Close observation of vital

Adjunctive measures: (0.01 ml/kg 1:1000 solution or auto- signs
 Remove possible injector) repeat at 5-minute-intervals (Watch out for progression to
trigger / allergen anaphylaxis)
 Sit up or lie down  Oral or IV anti-histamine
patient  Inhaled β2-agonist if known
asthmatic
 Consider IM adrenaline if
Cardiovascular Respiratory
persistent or severe vomiting /
involvement involvement
abdominal pain

Second line Second line Poor

response
Airway compromise:
Circulation impairment /
Poor  Consider intubation
↓BP:
response  Elevate extremities
Breathing difficulty: Observe for at least 4
 IV access / ICU support hours (exclude
 Supplementary oxygen
 IV crystalloid bolus progression to
 Inhaled/nebulized β2
(20ml/kg) anaphylaxis)
agonist
 Consider IV adrenaline
 Nebulized
(1 microgram/kg bolus ±
adrenaline/steroid
infusion)
 Intubation if GCS <8
IV access / consider ICU
support

Close monitoring of vital signs /

cardiac monitoring & reassess for
response after 5 minutes

Good response
Good response

 Consider saving serum for acute tryptase

 Continue observation with close monitoring:
Respiratory involvement: at least 6-8 hours
Cardiovascular involvement: at least 12-24 hours

 Evaluation risk of recurrence & need for adrenaline Third line

auto-injector / training  Consider IV/po anti-histamines for
 Update allergies in medical record (if any) and cutaneous symptoms
educate patient on avoidance measures  Consider IV/po steroids to prevent late
 Referral to Immunology & Allergy for review phase reactions

IA 2
Hong Kong Anaphylaxis Consortium Consensus Statements on
Prescription of Adrenaline Autoinjectors (AAInj)
1. AAInj should be used as first-line treatment and prescribed for all patients
at risk of anaphylaxis.
2. If indicated, AAInj should be prescribed prior to discharge from the
Accident & Emergency Department and an allergy referral should be
triggered immediately.
3. The decision for prescribing AAInj should be based on the severity of
previous reactions; including objective signs of respiratory involvement,
objective signs of cardiovascular involvement and multi-organ involvement
(regardless of severity).
4. The decision for prescribing AAInj should be based on demographics and
co-morbidities; including history of asthma or chronic obstructive
pulmonary disease.
5. Patients deemed requiring AAInj should be offered avoidance advice and
prescribed one AAInj while awaiting allergist review.
6. After patients are prescribed AAInj, demonstration by a healthcare
professional or instructional video and return demonstration by the patient
are required.
7. The long-term decision for the continued need of AAInj should be reviewed
by an allergist.

Unidentified triggers / allergens

 Referral for allergy testing is important for confirmation of allergen
 Always take a careful and complete allergy history
 Aetiology can usually be identified in >90% of patients after workup
 Food-dependent exercise-induced anaphylaxis (especially to wheat)
relatively more common cause of anaphylaxis in Hong Kong adults,
and can sometimes present hours after food intake.
 Watch out for cofactors (physical exertion, NSAIDs, alcohol etc.)
 “Idiopathic anaphylaxis” is a diagnosis by exclusion
 Differential diagnosis: hidden allergens or anaphylaxis mimics (e.g. acute
urticarial/angioedema, asthma, vasovagal, panic attacks)
 Continued risk of recurrence if triggers/allergens are not identified
 Emphasis on patient education & adrenaline auto-injector technique

IA 3
 DRUG ALLERGY

 Drug allergy / hypersensitivity reactions are adverse drug reactions

resulting from specific immune-mediated responses
 ~7-10% of population have drug “allergy” labels, but many are incorrect
 Need to differentiate from other adverse reactions or intolerances
 Idiosyncratic and comprises ~10% of all adverse drug reactions

Gell and Coomb’s classification of hypersensitivity reactions

1. Type I: IgE-mediated
2. Type II: Antibody-mediated (Cytotoxic)
3. Type III: Immune complex-mediated
4. Type IV: Cell-mediated

 Useful to differentiate into immediate vs non-immediate/delayed (from

history) to guide investigation and management
 Details regarding the severity and duration since index reaction also
essential to evaluation risk:benefit ration of subsequent allergy testing

Immediate type hypersensitivity (usually IgE-mediated)

 Reactions typically occur within 1 hour if there has been prior exposure,
but can occur after several days if first treatment course
 Manifestations: urticarial, angioedema, bronchospasm, anaphylaxis
 Initial treatment as per anaphylaxis protocol
 After stabilization, consider saving serum for tryptase
(Can be stored as clotted blood at 4oC prior to consultation)*
- Acute sample: preferably 30 mins to 4 hours after event
- Baseline sample: >24 hours after event
 Strict avoidance in future and watch out for cross-reactivity with other
classes of medication (see section on Penicillin Allergy, IA10)
 Uncertain or suspected allergies may be confirmed by evidence of IgE
sensitization by skin prick/intradermal testing or drug provocation tests
(consider Immunology & Allergy referral)
 Desensitization possible but only considered if confirmed genuinely
allergic AND no alternative medication available

*Blood may be sent to QMH Immunology Lab after consultation

IA 4
Delayed/Non-immediate type hypersensitivity (usually cell-mediated)
 Reaction occurs >1 hour (up to days/weeks) administration and lesions
usually last for days to weeks
 Manifestations: maculopapular exanthems, fixed drug eruptions, Severe
Cutaneous Adverse Reactions (SCAR) (including: Drug reaction with
eosinophilia & systemic symptoms (DRESS) syndrome, acute generalized
exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN)
 Some SCAR may occur weeks to months after drug exposure
 Most reactions resolve after withdrawal of causative agent
 Uncertain allergies may be confirmed by evidence of cell mediated
sensitization (consider Immunology & Allergy consultation)
 SCAR usually contraindicates further re-exposure to drug
 Desensitization seldom possible and “treating through” not routinely
recommended

Other types of drug hypersensitivity

 Type II: Drug-induced cytopenias, hepatitis, nephritis
 Type III: Serum sickness, vasculitis, drug fever
 Drug-induced autoimmune manifestations
 Usually after prolonged exposure and resolve after withdrawal

Indications for Immunology & Allergy evaluation

 No alternative drug available and consideration for desensitization
 Uncertain diagnosis of culprit drugs
 Anticipated need for use of index or similar drugs in future & identify
suitable alternatives (e.g. antibiotics / NSAIDs & aspirin)

IA 5
 DRUG REACTION WITH EOSINOPHILIA & SYSTEMIC
SYMPTOMS (DRESS) SYNDROME

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

syndrome, also known as drug induced hypersensitivity syndrome, is a severe
cutaneous adverse reaction (SCAR) characterized by life-threatening
multiorgan hypersensitivity reaction (HSR) to a medication. DRESS
syndrome occurs in about 1 per 10,000 exposures to medication, and be life-
threatening with mortality reported up to 10%.

Symptoms
DRESS syndrome is a delayed-type (Gel & Coombs Type IVc) HSR,
associated with viral (HHV6) reactivation. Clinical manifestations typically
develop 2 weeks to 2 months following exposure to the causative drug.
Therefore, it is imperative that a comprehensive drug history up to 2 months
prior to onset is obtained when SCAR such as DRESS syndrome are suspected.
The latency period tends be shorter with antibiotics, such as beta-lactams.
Symptoms can occur earlier and more severe following repeated re-exposure
to culprit drug(s).

 Prodromal symptoms are common. High spiking fever almost always

occurs (>90% of cases).
 Skin rash usually begins with a morbilliform eruption but can progress to
a wide range of manifestations including diffuse, confluent, and infiltrated
erythema, oedema, purpuric, pustular or even erythroderma or exfoliative
dermatitis. Typically involves > 50% of total body surface area (TBSA)
and may last for weeks even after discontinuation of offending medication.
 Mucosal involvement (~50%)
 Facial oedema (~50%) and may be confused with angioedema.
 Internal organ involvement usually occurs in ~90% of patients.
- Leucocytosis (eosinophilia ~70%, or atypical lymphocytosis),
thrombocytopenia, anaemia or haemophagocytic syndrome.
- Lymphadenopathy (~30-75%)
- Liver derangement (~75%) – drug-induced liver injury
- Renal involvement (10-30%)
- Lung involvement (10%) – acute respiratory distress syndrome,
pleuritis, pneumonitis
- Cardiac – eosinophilic myocarditis / pericarditis
- Gastrointestinal – pancreatitis, colitis

IA 6
Culprit drugs
The most frequently implicated (but not exhaustive) drugs are:
 Antibiotics / anti-infectives: sulphamethoxazole-trimethoprim (Septrin),
Dapsone, abacavir, minocycline, vancomycin, beta-lactams,
minocyclines, anti-TB drugs, antiretrovirals
 Aromatic anticonvulsants: carbamazepine, lamotrigine, levetiracetam,
phenytoin, phenobarbital
 Allopurinol
 Non-steroidal anti-inflammatory drugs (NSAIDs)

Confirming or excluding DRESS syndrome: RegiSCAR Scoring System

 DRESS syndrome is a constellation of symptoms and laboratory
abnormalities that requires a high clinical suspicion.
 DRESS syndrome is a diagnosis of exclusion.

Score
Criteria
-1 0 +1 +2
Fever ≥38.5oC No Yes
Lymph node enlargement No Yes
Eosinophilia (x 10 /L)
9
>0.7 >1.5
Eosinophilia (%), if leucocytes <4 x 10 /l
9
10-19.9% ≥20%
Atypical lymphocytes No Yes
Extensive rash (>50% TBSA) No Yes
Rash suggestive of DRESS syndrome No Yes
Biopsy suggestive of DRESS syndrome No Yes
Internal organ involvement No Yes*
Resolution in ≥15 days No Yes
Excluding other potential causes No Yes
* Score 1 for each organ involved, maximal score of 2
 Score: <2 (No case); 2-3 (Possible); 4-5 (Probable); >5 (Definite)

Investigations
 CBC (especially leucocytosis, eosinophilia, atypical lymphocytosis)
 LRFT, CK, LDH, cardiac enzymes, amylase, clotting profile, ESR, CRP
 Septic workup including blood culture, urine R/M & culture, CXR
 EBV, CMV, HHV-6 and HHV-7 PCR (if available)
 Serology for mycoplasma and chlamydia
 Hepatitis A, B, C status
 ANA

IA 7
 ECG
 Skin biopsy
 ± Lymph node biopsy
 Exclusion of alternative diagnosis depending on organ involvement

Primary prevention of DRESS syndrome and at-risk HLA allele

screening
 In Hong Kong, HLA B*58:01 and HLA B*1502 genotyping before
initiation of allopurinol and carbamazepine, respectively, has been
recommended.
 For patients who are carriers of HLA-B*58:01 or HLA B*1502, alternative
treatment for allopurinol or carbamazepine should be considered,
respectively.
 Patients who are not carriers of these alleles also have a risk, albeit lower,
of developing SCAR, including SJS/TENS and DRESS. Patients should
be educated about the risk and the need to stop suspected culprit drugs
immediately should he/she develop suggestive symptoms (such as rash).
 It is NOT recommended to perform HLA testing in a patient with
suspected DRESS syndrome in routine practice. HLA testing should NOT
be used to diagnose DRESS syndrome.

Management
1. Immediate Management
a. General measures
 Identify and stop the suspected offending drug and drugs with
potential cross reactivity.
 Evaluation by multidisciplinary team, depending on organ
involvement and preferably with Immunology/Allergy.
 Symptomatic and supportive management: fluid and electrolyte
replacement, emollients, anti-histamines, topical steroids,
antipyretics.
 Avoid empirical antibiotics or non-essential medications.
 Monitor liver and renal function, pulmonary and cardiac function.

b. In severe cases of DRESS (extensive organ involvement):

 Early administration of prednisolone (or steroid equivalent)
1mg/kg/day for 2-3 weeks, then slowly taper over the course of 3-6
months.
 Antivirals in cases of viral reactivation
 Other treatment options for refractory cases:
IA 8
 - IVIG 2g/kg given over 2-5 days
- Immunosuppressants (e.g. cyclosporine)
- Plasmapheresis
- Anti-IL5 (e.g. mepolizumab)

2. Discharge and Follow-up

a. Update the patient’s allergy label.
 Label ALL the suspected offending drug(s) into the electronic
Clinical Management System (CMS).
 Provide an allergy card and/or written documentation to the patient
and indicate clearly which drugs to avoid in the future.
b. Refer cases to Immunology/Allergy for identification/confirmation of
culprit drug(s) and screening/monitoring for other autoimmune sequelae.
c. Patients with DRESS syndrome are at risk for development of future
autoimmune diseases and long-term monitoring is recommended.

3. Identification of culprit drug(s)

a. Identifying the culprit drug is important to prevent recurrent episodes of
SCAR and unnecessary avoidance of non-culprit drugs.
b. This is especially important when there are multiple suspected drug
culprits, which may severely limited future medication choice.
c. In vitro tests:
i. Lymphocyte transformation tests (LTT)
ii. Enzyme-linked immunospot (ELISpot) assay
d. In vivo tests:
i. Patch tests
ii. Intradermal tests
e. Drug provocation tests (DPT) are absolutely contraindicated.
f. Allergist assessment is required prior to possible graded DPT to exclude
less likely culprits (based on prior in vitro and in vivo test results) or
tolerance tests with alternative medications to exclude potential cross-
reactivity.

IA 9
 PENICILLIN ALLERGY

 The most frequently encountered and over-diagnosed drug “allergy”

 Prevalence of reported β-lactam antibiotic allergies in HK is 2% (107
per 100 000 population) but rate of genuine allergy only 14%.
 High rate of initial misdiagnosis and even truly allergic patients may lose
sensitivity with time (~90% in 10 years if no re-exposure)
 Minority of genuine allergic patients are at risk of severe reactions upon
re-exposure (e.g. life-threatening anaphylaxis)
 Misdiagnosis can lead to unnecessary avoidance (over-labelling) or
dangerous inadvertent re-exposure (under-labelling)
 Associated with use of less effective antibiotics, increased treatment
costs/hospital stay and development of multiple drug-resistant micro-
organisms
 Important of accurate and updated allergy records
 Difficult to ascertain genuine allergy on clinical history alone
 A comprehensive allergy history remains the cornerstone for proper risk
stratification prior to allergological investigations
 Penicillin skin±drug provocation testing (DPT) is the most reliable method
for evaluating true allergic penicillin allergy (specificity ~100%)
 Delaying evaluation until an emergency arises increases the risk of illness,
morality and increases overall medical costs
 Non-allergists can play a crucial role in penicillin allergy testing,
especially for low-risk (LR) cases
 For all cases of unconfirmed or suspected penicillin allergy, consider
proactive referral to Hub-and-Spoke Penicillin Allergy Clinics under
Hong Kong Drug Allergy Delabelling Initiative (HK-DADI)

Cross-reactivity with other beta-lactams

 Evaluate likelihood of genuine index allergy and consider referral to
Immunology & Allergy for evaluation
 In true penicillin-allergics, cross-reactivity with cephalosporins and
carbapenems with severe reactions is around ~1-2%
 Ideally, a patient with suspected penicillin allergy requiring
cephalosporins should be tested for penicillin ± cephalosporins first
 Carbapenem/monobactams are dissimilar from penicillins and cross-
reactivity would not be expected
 Can consider graded challenge to carbapenems if a beta-lactam antibiotic
is required without a better alternative
 If in doubt, consider Immunology & Allergy consultation
IA 10
Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus
statements for penicillin allergy testing by non-allergists:

1. The following are essential parts of a penicillin allergy history:

a. Duration since index reaction
b. Onset time of manifestations after penicillin
c. Description of any suspected allergic manifestations after exposure
d. Last exposure to penicillin and reactions (if any)
e. Underlying medical conditions/comorbidities
f. History of chronic urticaria (>6 weeks in duration)

2. Exclusion criteria for LR allergy testing should include:

a. Pregnancy
b. Immunocompromised patient (or on systemic immunosuppression
in past 4 weeks)
c. Active or uncontrolled chronic urticaria
d. Unable to withhold medications potentially interfering with skin
testing (e.g. anti-histamines, tricyclic antidepressants)

3. Patients with LR features of suspected penicillin allergy can proceed

with penicillin allergy testing by a non-allergist

4. LR features of suspected penicillin allergy should include:

a. Unknown or forgotten/untraceable history and event >1 year ago
b. Family history of penicillin allergy only
c. Previously told allergy test positive, but no history of reaction
d. Other non-β-lactam allergies only
e. Isolated gastrointestinal upset
f. Nonspecific (non-immunological) complaints
g. History of non-urticarial rash

5. Patients with any non-LR features of suspected penicillin allergy should

be referred for evaluation by an allergist

6. Non-LR features of suspected penicillin allergy should include history

of the following after penicillin exposure:
a. Anaphylaxis
b. Symptoms suggestive of hypotension
c. Respiratory compromise
IA 11
 d. Urticaria or angioedema
e. Documented SCAR
f. Mucosal involvement
g. Eosinophilia
h. Internal organ involvement
i. Drug induced autoimmune disease or vasculitis

7. Skin testing should be performed prior to DPT

8. Skin testing should be performed at least 8 weeks after (and as soon as

possible) following history of suspected allergic reaction after penicillin
exposure

9. Antihistamines and tricyclic antidepressants should be withheld at least

1 week prior to skin testing

10. Regarding drug dilutions and reagents:

a. Skin prick tests (SPT) followed by intradermal tests (IDT) at the
highest non irritating concentration should be
b. All SPT should be accompanied by a positive and negative control
c. All IDT should be accompanied by a negative control
d. SPT and IDT should be performed using recommended
concentrations of benzylpenicilloyl-poly-L-lysine (PPL), minor
determinant mixture (MDM), benzylpenicillin and amoxicillin

11. Regarding skin test interpretation:

a. SPT is considered positive if a wheal size diameter at least 3 mm
larger than negative control, with surrounding
b. IDT is considered positive if diameter of the wheal is at least 3 mm
greater that the initial wheal, with surrounding
c. Delayed IDT readings at 48 to 72 hours may be considered if a non-
immediate type reaction is suspected
d. Patients with positive SPT or IDT results should be referred for
specialist review

12. DPT is the gold standard to diagnose genuine penicillin allergy or

tolerance

13. DPT should generally be performed when there is a low pre-test

probability following negative skin testing
IA 12
 d. Urticaria or angioedema
e. Documented SCAR
f. Mucosal involvement
g. Eosinophilia
h. Internal organ involvement
i. Drug induced autoimmune disease or vasculitis

7. Skin testing should be performed prior to DPT

8. Skin testing should be performed at least 8 weeks after (and as soon as

possible) following history of suspected allergic reaction after penicillin
exposure

9. Antihistamines and tricyclic antidepressants should be withheld at least

1 week prior to skin testing

10. Regarding drug dilutions and reagents:

a. Skin prick tests (SPT) followed by intradermal tests (IDT) at the
highest non irritating concentration should be
b. All SPT should be accompanied by a positive and negative control
c. All IDT should be accompanied by a negative control
d. SPT and IDT should be performed using recommended
concentrations of benzylpenicilloyl-poly-L-lysine (PPL), minor
determinant mixture (MDM), benzylpenicillin and amoxicillin

11. Regarding skin test interpretation:

a. SPT is considered positive if a wheal size diameter at least 3 mm
larger than negative control, with surrounding
b. IDT is considered positive if diameter of the wheal is at least 3 mm
greater that the initial wheal, with surrounding
c. Delayed IDT readings at 48 to 72 hours may be considered if a non-
immediate type reaction is suspected
d. Patients with positive SPT or IDT results should be referred for
specialist review

12. DPT is the gold standard to diagnose genuine penicillin allergy or

tolerance

13. DPT should generally be performed when there is a low pre-test

probability following negative skin testing
IA 12
14. DPT should be performed in an appropriate setting with resuscitation
facilities readily accessible and under supervision of trained personnel

15. Antihistamines and medications potentially interfering the assessment

should be stopped for 7 days before DPT

16. Uncontrolled asthma, active urticaria/other underlying diseases limiting

use of rescue medications are relative contraindications for DPT

17. Regarding DPT dosing protocols:

a. A 3-step approach (e.g. 10%, 30%, 60% of maximum single unit
dose) in 30 minute intervals is recommended
b. The index penicillin should be used for DPT (if known
c. If the index penicillin is unknown, DPT should be performed with
amoxicillin
d. Patient should be observed of at least 1 hour after final dose of DPT

18. An immediate-type hypersensitivity to the DPT agent is confidently

excluded if there is no reaction after >1 hour after completion of DPT

19. Patients should be called back at least 72 hours later to ensure there were
no non-immediate type manifestations

20. A DPT is considered negative if there is no reaction after at least 72

hours after completion of DPT

21. Patients with reported reactions after DPT should be called back for
review and treated as necessary

22. Patients with reported reactions after DPT should referred for specialist
review

23. Inaccurate penicillin allergy labels should be delabelled following a

negative DPT and with proper patient counselling

24. Requirement of patient counselling should include:

a. Proper patient counselling after both positive and negative workup
b. After negative workup, the risk of penicillin allergy is similar to
subjects without known allergic history, however, this does not
exclude possibility of new sensitization in subsequent years
IA 13
 c. After negative workup, penicillin can be prescribed as for usual non
allergic subjects

25. After negative DPT, medical records should be updated by:

a. Medical records should be properly updated with results of DPT
including: DPT agent, dose and date of DPT
b. Patients should be given updated physical allergy cards/alerts or
alerts or medical alert

26. Positive skin test or DPT results should be clearly documented in

medical records

IA 14
 ANGIOEDEMA

 Non-pitting transient subcutaneous or submucosal swelling

 Exclude airway obstruction, systemic involvement and anaphylaxis first
(for acute management, see section on Anaphylaxis, IA1-3)
 Not all cases with angioedema are allergic reactions
 Differentiate into bradykinin or histamine-mediated (or others)

Histamine-mediated (mast-cell mediated) – most common

Common causes
 “Allergic” type I hypersensitivity reaction; e.g. foods, drugs, venom
 Spontaneous or autoimmune urticarial and angioedema
 Inducible urticarial and angioedema

Clinical features
 Usually concomitant urticarial and pruritus
 Rapid onset and response to therapy (usually <24 hours)
 Cardiopulmonary or systemic involvement in case of anaphylaxis
 Temporal relationship with allergen exposure if allergic reaction
 Usually rapid response to anti-histamines, steroids and adrenaline

Management
 Exclude allergy / eliciting factors (e.g. drugs, diet, physical stimuli)
 First line treatment for spontaneous disease are anti-histamines
 Avoid first-generation anti-histamines (e.g. chlorpheniramine,
hydroxyzine) due to sedative and anti-cholinergic side effects
 Consider regular second-generation anti-histamines if required
 Up-dosing is preferred to combination of different anti-histamines
 Consider specialist referral for second line treatments such as anti-IgE
blockade (omalizumab) or other immunomodulators
 Avoid ACE-inhibitors in patients with history spontaneous angioedema
(consider angiotensin II receptor blockers)
 Adrenaline auto-injectors are not usually needed without a prior history of
anaphylaxis or systemic involvement

IA 15
Bradykinin-mediated
Common causes
 ACE-inhibitor induced angioedema (most common)
 Hereditary angioedema / Acquired C1 esterase inhibitor deficiency

Clinical features
 No concomitant hives or pruritus
 Slower, progressive onset and develop over several hours
 Laryngeal or abdominal involvement more common
 Not responsive to anti-histamines, steroids and adrenaline
 Typically persists for days
 May respond to bradykinin inhibitors (e.g. icatibant)

Management
 Check C4 levels±C1-esterase inhibitor level/function in cases of suspected
C1 esterase inhibitor deficiency
 Consider Immunology & Allergy referrals for uncertain diagnosis and
long-term follow-up
 Patients with hereditary angioedema often present at young age any may
have positive family history (autosomal dominant)
 Acquired forms present in older patients and may be associated with
lymphoproliferative or autoimmune diseases
 First line treatment for hereditary angioedema is C1 esterase inhibitor
replacement, bradykinin inhibitors or kallikrein inhibitors
 C1 esterase inhibitor replacement and bradykinin inhibitors are registered
and available in Hong Kong (refer to Immunology & Allergy)
 Anti-histamines, steroids and adrenaline are not useful
 Watch out for possible paradoxical response with use of FFP
 Angioedema may present anytime (up to years) after starting ACE-
inhibitors and persist for weeks/months after drug cessation
 Consider substitution of ACE-inhibitors with angiotensin II receptor
blockers
 Refer family members to Immunology & Allergy for counselling and
screening in cases of hereditary angioedema

IA 16
 URTICARIA

Definition:
 Urticaria is characterized by development of wheals, angioedema or both.
- Wheals (also known as hives): Sharp, circumscribed superficial central
swelling surrounded by erythema, usually pruritic, and fleeting in
nature (individual wheals typically last <24 hours)
- Angioedema: swelling of the deep dermis / subcutaneous tissue.
Usually tightening, tingling sensation (rather than pruritic) lasting up to
72 hours
 Urticaria can be differentiated into acute (<6 weeks), or chronic (>6
weeks). Chronic urticaria can be further differentiated into:
- Chronic spontaneous urticaria (CSU)
- Chronic inducible urticaria (CIndU)
 Up to 10% of patients with CSU can present with angioedema only
 If patient presents with angioedema only (without wheals), bradykinin-
mediated causes such as ACE-inhibitor induced angioedema must be
excluded. Other causes such as hereditary and acquired angioedema also
needs to be considered. (Refer to IA15-16)

Investigations:
Urticaria is a clinical diagnosis and often do not require extensive
investigations (such as allergy testing). If the clinical history is suspicious,
investigations may help determine other causes of wheals and angioedema

Management of CSU / CIndU

 Avoid use of first-generation H1-antihistamines (such as
chlorpheniramine, hydroxyzine) due to unfavourable side effect profile
 Use second-generation H1-antihistamines only
 If symptoms are frequent and bothersome, regular second-generation H1-
antihistamines
 Avoid mixing different types of H1-antihistamines
 Adjust antihistamine dose according to the severity of urticaria. Doses of
up to fourfold the standard dose may be used for CSU
 CSU activity should be monitored by patient reported outcome measures
(PROM) such as the weekly urticaria activity score (UAS7)
 If the patient has persistent symptoms, despite maximum dose
antihistamines, consider specialist referral
 Other common treatment options for chronic urticaria include anti-IgE
monoclonal antibodies (omalizumab) and cyclosporin.
IA 17
Hong Kong-Macau Severe Hives & Angioedema Referral Pathway
(SHARP)

IA 18
Classifications & definitions
1. We suggest urticaria should be characterized by wheals (hives), angioedema or
both
2. We recommend urticaria is classified as (i) acute (≤6 weeks) or chronic (>6
weeks); and (ii) as spontaneous (no eliciting factor) or inducible (presence of specific
eliciting factor)
3. We suggest “severe urticaria” should be defined by symptoms assessed by patient
reported outcome measures (PROM) equivalent to a weekly urticaria activity score
(UAS7) above 27
4. We recommend acute urticaria is usually self-limiting and does not require routine
investigations, except in the cases of suspected immediate-type hypersensitivity
reactions

Diagnosis
5. We recommend patients with chronic spontaneous urticaria (CSU) to be regularly
assessed with PROM such as the UAS7
6. We recommend angioedema should be classified by its aetiology (mast cell- or
bradykinin-mediated) when possible
7. We suggest CSU is diagnosed clinically and blood tests are not usually necessary
unless other diagnoses are suspected
8. We recommend against routine allergy tests and skin biopsies for patients
diagnosed with CSU
9. We recommend angiotensin-converting-enzyme inhibitor (ACEI) associated
angioedema (ACEI-AE) should be excluded first in all patients presented with
angioedema of any aetiology
10. We recommend C1-esterase inhibitor (C1-INH) deficiency should be considered
in cases of suspected bradykinergic angioedema when ACEI-AE has been excluded
11. We recommend initial screening for low C4 levels in patients with suspected
bradykinin-mediated angioedema

Management & Referral

12. We recommend treatment aim of urticaria should be complete symptom control
and normalization of quality of life
13. We recommend second-generation H1-antihistamines should be taken regularly
for the treatment of CSU

IA 19
14. We recommend second-generation H1-antihistamines up to fourfold in patients
with CSU unresponsive to standard doses, before other treatments are considered
15. We suggest against different combinations of, especially first-generation, H1-
antihistamines, to be used at the same time for treatment of urticaria
16. We recommend against long-term use of systemic steroids in the treatment of
CSU
17. We recommend against the use of ACEI in patients with history of spontaneous
angioedema of any aetiology
18. We suggest against the use of anti-histamines, steroids or adrenaline in patients
with confirmed bradykinergic angioedema
19. We recommend referral to a Dermatology or Immunology & Allergy specialist
centre for patients with severe CSU not responding to fourfold dosing of second-
generation H1-antihistamines
20. We suggest omalizumab for the treatment of severe CSU unresponsive to fourfold
dosing of second-generation H1-antihistamines
21. We suggest cyclosporin for the treatment of severe CSU unresponsive to fourfold
dosing of second-generation H1-antihistamine and omalizumab; or when omalizumab
is unavailable/contraindicated
22. We recommend referral to a Immunology & Allergy specialist centre for patients
with suspected bradykinin-mediated angioedema, where ACEI-AE has been excluded
23. We recommend all patients with confirmed HAE should have access to HAE-
specific medications
24. We recommend against the use of non-HAE specific medications (such as
attenuated androgens, anti-fibrinolytics and fresh frozen plasma) for the treatment and
prophylaxis of HAE

IA 20
 IMMUNODEFICIENCY

 Recurrent infections can be due to anatomical lesions, functional

disorders or immunodeficiency (primary or secondary)
 The number of primary immunodeficiency diseases has expanded in
recent decades, and not as rare as previously thought
 Secondary and iatrogenic immunodeficiencies increasing with the
expanding use of immunosuppressive and biologic therapies
 Many patients remain undiagnosed or present until later in life
 May also present with non-infectious symptoms such as allergy,
autoimmunity or malignancy (immune dysregulation)
 High index of suspicion needed for early diagnosis and intervention
 JM Foundation 10 warning signs of immunodeficiency in adults:
1. >2 ear infections in one year
2. >2 sinus infections in one year in the absence of allergies
3. 1 pneumonia per year for more than one year
4. Chronic diarrhoea with weight loss
5. Repeat viral infections (colds, herpes, warts, condyloma)
6. Recurrent need for intravenous antibiotics to clear infections
7. Recurrent, deep abscesses of the skin or internal organs
8. Persistent thrush or fungal infection on skin or elsewhere
9. Infection with normally harmless tuberculosis-like bacteria
10. Family history of a primary immunodeficiency
 Subcutaneous immunoglobulin (SCIg) replacement is available for
patients with primary & secondary antibody deficiency; and shown to be
more cost-effective then intravenous (IVIg) replacement in Hong Kong

Initial evaluation
 Exclude common causes of secondary immunodeficiency (e.g. diabetes
mellitus, HIV infection, protein-losing states, chronic kidney disease,
malignancies, chemotherapy or medications/ immunosuppression)
 Assess if disproportionately frequent or severe infections
 Assess if any unusual microorganisms or sites of infection
 Check immunization history and any adverse reactions
 Chart family tree and enquire about possible consanguinity
 Documentation of past infections and identification of phenotypes
 Consider Immunology & Allergy referral for workup and follow-up

First-line screening tests

 Complete blood count, differential counts and peripheral smear
IA 21
 Liver and renal function tests
 Immunoglobulin G/A/M/E + electrophoresis
 C3, C4, ANA, anti-ENA ± other autoimmune serology (if indicated)
 Erythrocyte sedimentation rate, C-reactive protein
 HIV status
 CXR, CT thorax, pulmonary function tests

Second-line immunological tests

 Lymphocyte subsets: CD3, CD4, CD8, CD16/56, CD19
 Cell mediated immunity assessment:
- Lymphocyte proliferation responses to mitogen / antigen
 Humoral immune response assessment:
- Vaccine titres, e.g. post-pneumococcal vaccine serology
- Coomb’s test and isohaemagglutinins (anti-A, anti-B)
- IgG subclass, IgD and specific immunoglobulin levels
- B cell immunophenotyping
 Complement function tests: CH50 / AH50
 C1-esterase inhibitor level and function
 Neutrophil function tests (e.g. NBT, DHR)
 Specific molecular/genetics tests & next-generation sequencing

Clinical Pearls
 Record baseline lymphocyte counts and immunoglobulin profile prior to
commencement of any immunosuppressive therapies
 Consider screening for lymphopenia and hypogammaglobulinaemia every
3-6 months while on “stronger” immunosuppression (such as cytotoxic
chemotherapy, B-cell depleting agents)
 Normal immunoglobulin levels or lymphocyte counts cannot exclude
functional deficiencies
 Beware of possible false positive serologic results after patients treated
with immunoglobulin therapy
 Save serum for all relevant serology prior to administration of
immunoglobulin therapy (avoid false positive results later)
 Monitor IgG “trough” levels in patients receiving immunoglobulin
replacement (may take months to reach steady-state levels)
 There is a risk of allergy/anaphylaxis with administration of
immunoglobulin, however IgA deficiency is not a contraindication to
immunoglobulin replacement or therapy
 Anaphylaxis due to anti-IgA antibodies is rare and the majority of IgA
deficient patients can receive immunoglobulin
IA 22
 Long-term immunoglobulin replacement may be preferred to be given via
subcutaneously (SCIg) as home therapy, rather than intravenously (IVIg)
 SCIg may provide more stable and higher IgG trough levels, associated
with lower infection rates
 Empirical replacement SCIg or IVIg dose at ~0.4g-0.6g/kg/month and
titrated according to IgG trough level
 Trough levels individualized according to patient rate of infections or co-
morbidities (e.g. presence of end-organ complications)
 Inactivated/dead vaccines (e.g. influenza vaccination) can be given to all
patients regardless of immune status
 Many PIDs are monogenic diseases with known patterns of inheritance,
consider referring family members to Immunology & Allergy for
counselling and screening

Selected examples of immunodeficiencies

Antibody deficiencies
e.g. Agammaglobulinaemia, common variable immunodeficiency, B-cell
depleting therapies, multiple myeloma, chronic lymphocytic leukaemia
 Clinical features: Recurrent/chronic sinopulmonary and gastrointestinal
infections, esp. encapsulated bacteria
 Exclude presence of thymoma (Good’s Syndrome) and consider
checking B cell subsets in cases of adult-onset antibody deficiency
 Exclude active CMV infection (e.g. retinitis, colitis) and consider
prophylaxis in case of suspected Good’s syndrome
 Hypogammaglobulinaemia after rituximab use occurs in 40% in patients
with history of B-cell malignancy or 25% with autoimmune disease
 Therapies: SCIg (preferred) or IVIg replacement, prophylactic
antimicrobials
 Consider trial or empirical Ig replacement in severe symptomatic
patients, or when IgG <4g/L

Combined immunodeficiencies
e.g. Severe combined immunodeficiency, Hyper IgE syndrome, CD40L
deficiency, Wiskott Aldrich syndrome, ataxia-telangiectasia
 Clinical features: Recurrent bacterial, viral and fungal infections, esp.
opportunistic intracellular pathogens ± syndromic features
 Always screen lymphocyte subsets ± proliferation
 Therapies: Prophylactic antimicrobials, Ig replacement, HSCT

IA 23
Diseases of immune dysregulation
e.g. Autoimmune lymphoproliferative syndrome, haemophagocytic
lymphohistocytosis, polyglandular autoimmune syndrome type 1
 Clinical features: Non-malignant lymphoadenopathy/splenomegaly,
autoimmunity, autoimmune cytopenias and haemophagocytosis
 Therapies: immunomodulation, HSCT

Phagocytic defects
e.g. Chronic granulomatous disease, leukocyte adhesion deficiency
 Clinical features: Recurrent invasive skin and soft tissue
infections/abscesses, esp. catalase-positive organisms and fungi
 Therapies: prophylactic antimicrobials, interferon-γ, G-CSF, HSCT

Defects in Intrinsic and Innate immunity

e.g. Mendelian Susceptibility to mycobacterial disease, chronic
mucocutaneous candidiasis, STAT1 Gain-of-Function defect
 Clinical features: Recurrent and severe mycobacterial, salmonella,
viral/fungal infections, chronic mucocutaneous candidiasis
 Therapies: prophylactic antimicrobials, immunomodulation, HSCT

Auto-inflammatory disorders
e.g. Familial Mediterranean Fever, periodic fever syndromes
 Clinical features: Periodic/recurrent fevers and systemic inflammation
(without infectious or autoimmune cause)
 Therapies: immunomodulation

Complement deficiencies
e.g. early and terminal complement deficiencies, hereditary angioedema
 Clinical features: Recurrent pyogenic infections, disseminated Neisserial
infections, recurrent angioedema without urticarial
 Due to the labile nature of complement proteins – please consult
immunologist prior to sending blood for complement testing
 Therapies: vaccinations, prophylactic antibiotics, C1 esterase inhibitor
replacement

IA 24
Infections
 COMMUNITY-ACQUIRED PNEUMONIA (CAP)

Clinically, pneumonia is defined as (1) a syndrome of fever, chills, shortness

of breath, cough, chest pain (pleurisy), and sputum production etc., with (2)
compatible consolidation on X-ray imaging.

Causative agents
Bacteria Typical
● Streptococcus pneumoniae
● Haemophilus influenzae
● Moraxella catarrhalis
Atypical
● Legionella pneumophila
● Mycoplasma pneumoniae
● Chlamydophila pneumoniae
● Klebsiella pneumoniae and other Gram-negative bacteria
(diabetic, alcoholic or those with aspiration risk)
Viruses Common
● SARS-CoV-2
● Influenza viruses (A, B, C)
● Human respiratory syncytial virus (RSV)
Uncommon or emerging pathogens
● Measles virus
● Avian influenza (e.g. A/H5N1, A/H7N9)
● Middle East respiratory syndrome coronavirus (MERS-
CoV)
Mycobacteria Mycobacterium tuberculosis
Fungi Pneumocystis jirovecii (immunocompromised hosts like AIDS)
Others Klebsiella pneumoniae and other Gram-negative bacteria
(diabetic, alcoholic or those with aspiration risk)

Initial assessment and diagnosis

 Aware of:
- Local endemicity of pulmonary tuberculosis
- Host factors like immunocompromised status
- Risk factors for atypical or emerging pathogens (FTOCC, i.e. fever,
travel occupation, cluster and contact)
- Consider influenza and/or COVID-19
 Early isolation of patients with suspected or confirmed air-borne
pathogens if indicated.

In 1
Empirical treatment
1. Patients who are stable for management in outpatient setting
 PO Amoxicillin-clavulanate (beta-lactam with beta-lactamase
inhibitor) ± macrolide OR doxycycline
2. Hospitalised patients with mild to moderate pneumonia
 PO/IV Amoxicillin-clavulanate ± macrolide OR doxycycline
 Alternatives: IV ceftriaxone, cefotaxime ± macrolide OR doxycycline
 Anti-pseudomonal antibiotics (e.g. IV piperacillin-tazobactam,
cefepime) ± macrolide OR doxycycline for those with chronic lung
condition like bronchiectasis
 Consider oseltamivir (especially during influenza season)
3. Hospitalised patients with severe pneumonia, defined as having any 1 in 3
major criteria OR 2 in 6 minor criteria:
 Major criteria: need of mechanical ventilation, septic shock, acute
renal failure;
 Minor criteria: multi-lobar involvement, mental confusion, respiratory
rate >30 bpm, PaO2/FiO2 <250, SBP <90 mmHg/DBP <60 mmHg,
serum urea level >7 mmol/L)
 IV piperacillin-tazobactam or ceftriaxone or cefepime ± macrolide OR
doxycycline
 Consider oseltamivir (especially during influenza season)

Remarks
 Most patients with CAP will have an adequate clinical response within 72 hours
 In Hong Kong, high prevalence of reduced susceptibility to penicillin and
resistance to macrolides in Streptococcus pneumonia isolates were observed in
both hospital and community settings. Therefore, macrolide/azalide, tetracycline
or co-trimoxazole should not be used alone for empiric treatment of CAP#
 Fluoroquinolone resistance is emerging among the Streptococcus pneumonia,
especially among respiratory isolates from elderly patients with chronic lung
diseases#
 Due to high prevalence of macrolide resistance in Mycoplasma pneumonia in
Asia, doxycycline is preferable to macrolide when clinical suspicion arises#
 Consult infectious diseases specialists if in doubt.

Reference:
#
PL Ho, TC Wu, David VK Chao, Ivan FN Hung, Leo Lui, David C Lung, Tommy HC
Tang, Alan KL Wu (ed). 2017. Reducing bacterial resistance with IMPACT, 5th ed.
HK. http://www.chp.gov.hk/files/pdf/reducing_bacterial_resistance_with_impact.pdf

In 2
 HOSPITAL ACQUIRED PNEUMONIA (HAP)

Pneumonia occurring ≥ 48 hr after admission and excluding any infection

that is incubating at the time of admission.

There are two principles guiding the strategy of antimicrobial therapy for
HAP:
 Choice of empirical antimicrobial regimen should be based upon the
local distribution of pathogens associated with HAP and their
antimicrobial susceptibilities
 De-escalation once the causative pathogen is known.

Organisms Empirical Antibiotics

Onset < 4 days after • S. pneumoniae, • IV/PO Amoxicillin-
admission with no • H. influenzae, clavulanate or
previous antibiotics • M. catarrhalis, • IV Ceftriaxone
• S. aureus
Onset ≥ 4 days after • MRSA; • IV Piperacillin-
admission + had received • P. aeruginosa, tazobactam or
antibiotic recently, • Acinetobacter • IV Cefepime or
OR spp., • IV Meropenem /
onset ≥ 5 days after • Klebsiella spp., Imipenem
admission • Enterobacter spp. ± Vancomycin if at risk
OR of MRSA infection
mechanical ventilation /
septic shock

In 3
 PULMONARY TUBERCULOSIS

I. Notification
 Cases diagnosed as active pulmonary TB should be notified
promptly to DH, particularly once the case is put on treatment.
 If the patient happens to be a health care worker or working in other
relevant occupations with increased risk of exposure to TB,
notification to the Labour Department is required under the
Occupational Safety and Health Ordinance.

II. Treatment
 Pretreatment blood tests for liver function, renal function, HBsAg
and HIV antibody (after counselling and obtaining patient’s
consent) should be performed.
 Short course chemotherapy is the current standard treatment for
active pulmonary TB.
 Directly observed treatment (DOT) should be given as far as
possible.

III. Uncomplicated new cases – 6 months in total

 2 HRZ + (E or S)7 / 4HR7 (When Rx started in hospital or when
3x/week regimen not tolerated)
 2 HRZ + (E or S)7 / 4HR3
 2 HRZ + (E or S)3 / 4HR3 (Government Chest Clinic regimen)

IV. Retreatment cases – 9 months in total

 3 (or 4) HRZES7 / 6 (or 5) HR ± E7

Notations
Figures in front of drug combinations = duration in months.
Subscript ‘3’ = thrice weekly & ‘7’ = daily.
The slash “/” is used to separate different phases of Rx.

In 4
Drugs and dosages
Daily 3x/week
BW Dose BW Dose
H = Isoniazida
- 300 mg - 10-15 mg/kg
R = Rifampicinb <50 kg 450 mg
- 600 mg
≥50 kg 600 mg
Z = Pyrazinamide <50 kg 1-1.5 g <50 kg 2g
≥50 kg 1.5-2 g ≥50 kg 2.5 g
E = Ethambutolc - 15 mg/kg - 30 mg/kg
S = Streptomycin Dosage adjusted according to age
Age ≤50 <50 kg 500-750 mg <50 kg 500-750 mg
≥50 kg 750 mg ≥50 kg 750-1000 mg
Age 50-70 - 500 mg - 500-750 mg
Age ≥70 - - - 500-750 mg

a) i) Some elderly and/or malnourished may only tolerate 200mg

ii) Vitamin B6 at least 10 mg/d for those with malnutrition or risk of
neuropathy, e.g. pregnancy, diabetes mellitus, alcoholism, chronic
renal failure, and HIV infection.
iii) May cause peripheral neuropathy, encephalopathy and convulsions
especially in renal impairment.
iv) Drug interaction with phenytoin & carbamazepine

b) i) Young females should be counselled on pregnancy-related issues,

especially the reduced efficacy of oral contraceptives due to
interaction with rifampicin, and alternative contraceptive methods
may have to be recommended.
ii) Be aware of drug-drug interaction with rifampicin

c) Assess baseline visual symptoms & acuity before starting Rx with close
monitoring during therapy & consult ophthalmologist PRN.

In 5
Important adverse reactions to first-line anti-TB treatment
Isoniazid Hepatitis, cutaneous hypersensitivity, peripheral
neuropathy [Rare: optic neuritis, convulsion, mental
symptoms, aplastic anaemia, lipoid reactions,
gynecomastia, arthralgia]
Rifampicin Hepatitis, cutaneous hypersensitivity, gastrointestinal
reactions, thrombocytopenic purpura, febrile
reactions, ‘flu’ syndrome [Rare: shock, shortness of
breath, haemolytic anaemia, acute renal failure]
Pyrazinamide Anorexia, nausea, flushing, photosensitization,
hepatitis, arthralgia, cutaneous reactions,
hyperuricaemia, gout [Rare: sideroblastic anaemia]
Ethambutol Retrobulbar neuritis, arthralgia [Rare: hepatitis,
cutaneous reactions, peripheral neuropathy]
Streptomycin Cutaneous hypersensitivity, giddiness, numbness,
tinnitus, vertigo, ataxia, deafness [Rare: renal
damage, aplastic anaemia]
 In certain situations, the treatment duration needs to be extended beyond
6 months e.g. some extrapulmonary tuberculosis, in patients with silico-
tuberculosis, in patients with diabetes mellitus, and immunocompromised
patients.
 Anti-TB regimen should be adjusted according to final susceptibility
testing results and patients’ drug tolerability.

Reference:
 Tuberculosis Manual 2006. Tuberculosis, Public Health Services Branch, Centre for
Health Protection, Department HKSAR
https://www.info.gov.hk/tb_chest/doc/Tuberculosis_Manual2006.pdf
 Ambulatory treatment and public health measures for a patient with uncomplicated
pulmonary tuberculosis, an information paper. CHP
https://www.info.gov.hk/tb_chest/doc/Information_paper_ambulatory_tb_2013.pdf

In 6
 CNS INFECTIONS

Consider CNS infections in the presence of sepsis and one or more of the
followings: meningism, seizures, headache, impaired consciousness,
photophobia, confusion, signs of increased intracranial pressure (↑ICP),
focal neurological deficits, presence of parameningeal focus of sepsis. Signs
and symptoms may be subtle or absent in elderly or immunocompromised host.

1. CSF examination is crucial in the diagnosis of meningitis.

2. Watch out for signs of ↑ICP and do urgent CT brain before LP. If LP is
contraindicated, likely to be delayed or fails, empirical antibiotics can be
started after taking blood cultures.
3. CSF analysis: cell count, protein, glucose (simultaneous blood sugar),
gram stain, culture, AFB (smear and C/ST), Cryptococcus (India ink
smear, Ag and culture), viral studies. Do not wait for C/ST results before
starting Rx.
4. Other Ix: CBP, RFT, LFT, CXR, EEG, XR skull, sinuses and mastoid.
5. Look for any predisposing factors: sinusitis, endocarditis, otitis media,
skull fracture, immunocompromised states, etc.

Typical CSF findings in meningitis

Normal Viral Bacterial TB / Cryptococcal
Appearance Clear Clear Tubid Tubid/Viscous
Mononuclear
<5 10-100 <50 100-300
cells (/mm3)
PMN (/mm3) Nil Nil 200-3000 0-200
Protein (g/L) 0.2-0.4 0.4-0.8 0.5-2.0 0.5-3.0
CSF/blood
>½ >½ <½ <½
glucose

In 7
Initial empirical anti-microbial regimes
Bacterial Ceftriaxone 2g q12h OR Cefotaxime 1.5-2g iv q4h iv +
meningitis Vancomycin$ 500-1000mg q6-12h +
Ampicillin 2g iv q4h (if risk of listeriosis anticipated@)
Brain abscess Ceftriaxone 2g q12h OR Cefotaxime 1.5-2g iv q4h iv +
Metronidazole 500mg iv q8h
TB meningitis INAH 300-600mg daily
Rifampicin 450-600mg daily
Pyrazinamide 1.5-2g daily
Ethambutol 15 mg/kg/d daily
Pyridoxine 100mg daily
± Streptomycin 0.75g im daily
Cryptococcal Amphotericin B 0.7-1 mg/kg iv infusion over 4-6 hrs +
meningitis 5-Flucytosine 25 mg/kg q6h po for ≥2 weeks, then
Fluconazole at least 400mg/d for a minimum of 8 weeks
(immunocompetent patients)
Viral encephalitis Acyclovir 10 mg/kg iv q8h (or 500mg iv q8h)
$ Aim at trough concentration 15-20 micrograms/ml
@ Immunocompromised, pregnancy and elderly (age >50 years)

 Consider dexamethasone in patients with TB meningitis (0.3 to 0.4 mg/kg/day

for two weeks, then 0.2 mg/kg/day week 3, then 0.1 mg/kg/day week 4, then
taper 1mg off the daily dose each week) or brain abscess with significant
cerebral oedema.
 Dexamethasone (0.15 mg/kg q6h for 2-4 days with the first dose administered
10-20 min before, or at least concomitant with, the first dose of antimicrobial
therapy) in adults with suspected or proven pneumococcal meningitis.
 Prophylactic anti-convulsant may be considered in cerebral abscess & subdural
empyema.
 Duration of Rx for brain abscess 6-8 weeks.
 Duration of Rx for meningitis: ≥7 days for H. influenza, 10-14 days for S.
pneumoniae, 14-21 days for S. agalactiae, and 21 days for Gram-negative
bacilli, ≥21 days for L. monocytogenes. DO NOT change to oral therapy.
 Consider prophylaxis for contacts in cases of meningococcal meningitis: single
ciprofloxacin 500 mg (not generally recommended for pregnant and lactating
women), rifampicin 600mg q12 hrs for 2 days (not recommended for pregnant
women and beware of drug interaction with oral contraceptives), or single IMI
ceftriaxone 250mg.
References:
 Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-
84. https://doi.org/10.1086/425368
 The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of
America. Clin Infect Dis. 2008 Aug 1;47(3):303-27. https://doi.org/10.1086/589747

In 8
 URINARY TRACT INFECTION (UTI)
Common General
Antibiotics Therapy
Pathogen Management
Acute E coli, Analgesics, Empirical antibiotics choice
Uncomplicated Klebsiella, S Encourage (generally for 7 days):
Cystitis saprophyticus, oral fluid • Amoxicillin-clavulanate
Enterococci, intake • Nitrofurantoin (should be
Group B avoided in patients with
Streptococcus creatinine clearance
<30mL/min)
*U.S. FDA had recently warned
against use of fluoroquinolones in
uncomplicated cystitis due to
concern of serious side effects,
unless there are no alternative
options
Acute E coli and Analgesics, Effective empirical antibiotics
Pyelonephritis other Gram- Anti-pyretic, should be given promptly
negative bacilli Fluid • I.V. amoxicillin-clavulanate OR
resuscitation • I.V. piperacillin-tazobactam (if
and/or suspected P. aeruginosa) OR
inotropic • I.V. meropenem (recommended
support for for severe or rapidly
severe cases deteriorating cases)
Review antibiotics regimens when
culture results are available, and
to complete the antibiotics course
of 14 days
Treatment is NOT recommended in most patients with asymptomatic
bacteriuria, except in pregnant women and in patients undergoing invasive
urological procedures, since it does not offer clinical benefit.

Complicated UTI
 Refers to UTI with underlying urological abnormality. It is a diverse group
of heterogeneous clinical conditions.
 Resistant bacteria and polymicrobial infection are more common, and
persistent or relapsing infections are more likely.

In men with UTI, obstructive uropathy and bacterial prostatitis should be

considered.
In 9
 ENTERIC INFECTIONS

Acute infective diarrhoea may be due to viruses e.g. Norovirus, bacteria and
their toxin, and sometimes protozoa, most are self-limiting.

Clinical presentation

1. Secretory diarrhoea (Non-inflammatory enteritis)

 Commonly caused by salmonellosis
 Norovirus: pronounced vomiting
 Cholera classically presents as acute painless profuse rice water
diarrhoea without blood or mucus

2. Invasive diarrhoea (Inflammatory enteritis)

 Presents as dysenteric syndrome i.e. transient diarrhoea followed by
abdominal colic, tenesmus, fever, blood and mucus in stool
 Commonly caused by shigellosis (bacillary dysentery), non-cholera
vibrios (Vibrio parahaemolyticus and Plesiomonas shigelloides) and
occasionally Entamoeba histolytica (amoebic dysentery)

3. Typhoid and paratyphoid fever (enteric fever)

 Caused by Salmonella typhi (typhoid fever) and Salmonella paratyphi
(paratyphoid fever)
 Suspect in patient of high fever with relative bradycardia, ↓platelet, N
to ↓WCC, no localised focus of infection

4. Clostridioides difficile infection (CDI)

 Common cause of hospital-acquired diarrhoea
 Clinical presentation can range from mild diarrhoea to
pseudomembranous colitis (PMC). Fulminant colitis can result in toxic
megacolon and death
 The most common risk factor is exposure to broad-spectrum antibiotics
(especially 3rd generation cephalosporins, fluoroquinolones &
clindamycin). Other risk factors: old age, prolonged hospitalisation,
antineoplastic chemotherapy, proton-pump inhibitors (PPIs),
gastrointestinal surgery and procedures & severe underlying disease.

5. Enteric infections associated with systemic complications

 E coli O157:H7 – haemolytic-uraemic syndrome
 Campylobacter enteritis – Guillain-Barré syndrome
In 10
  Non-polio enteroviruses – Hand-foot-mouth disease, myocarditis,
encephalitis, etc.

6. Enteric infections are often more severe in immunocompromised

patients, e.g. elderly, diabetes mellitus, cirrhosis, anatomical or functional
hyposplenism, concurrent immunosuppressant therapy.

Management for enteric fever

1. Enteric fever is diagnosed by compatible clinical features and positive
culture from bone marrow aspirate, blood or stool.
2. Antibiotics treatment:
 Empirical treatment:
- 3rd generation cephalosporins, e.g. Ceftriaxone 2g q24h IV or
Cefotaxime 1-2g q6-8h IV
- Carbapenems, e.g. Meropenem 1-2g q8H IV, for patients from
South Asia (especially if severe disease)
- Avoid empirical fluoroquinolone in view of rising resistance
 Options upon availability of sensitivity results:
- Fluoroquinolones, e.g. ciprofloxacin 500mg BD po or Levofloxacin
750mg daily po, 5-7 days for uncomplicated cases & 10-14 days for
severe cases.
- Azithromycin 500mg daily po for 5-7 days
- Continue 3rd generation cephalosporins or carbapenems for 7-14
days if oral options not available.

Management for other bacterial enteric infections

1. Adequate fluid and electrolyte supplement.
2. Routine antibiotic not recommended for mild to moderate gastroenteritis.
3. For cases of febrile dysentery, especially for toxic patients, ciprofloxacin
500mg BD po, or azithromycin 500mg daily po, or ceftriaxone 1-2gm q24h,
for 3-5 days can be considered.
 Prevalence of fluoroquinolone resistance among Campylobacter,
Shigella and Salmonella isolates has been rising.
 For confirmed or suspected Campylobacter enteritis, macrolide (e.g.
azithromycin or clarithromycin) is preferred if antibiotic is indicated.
4. For cases of Cholera, antibiotics can hasten the rate of recovery. Treatment
options include single dose of doxycycline 300mg po, or azithromycin 1gm
po, or ciprofloxacin 1gm po.

In 11
Management of Clostridioides difficile infection
1. Diagnosed by detection of C. difficile toxin or PCR in stool (only unformed
stool should be sent)
2. Discontinuation of inciting and unnecessary antimicrobial therapy.
3. Specific antimicrobial therapy
 First-line treatment: Oral vancomycin 125mg four times a day for 10
days
 Alternative for non-severe cases: Oral metronidazole 400mg TDS for
10-14 days (if oral vancomycin is not available or contraindicated)
 High dose of oral vancomycin (up to 500mg four times a day), together
with intravenous metronidazole 500mg Q8H, can be given for severe
cases
 Intravenous vancomycin is not effective for C. difficile infection
 For fulminant colitis (supported by presence of shock, ileus or
megacolon), surgery may be needed (please consult specialist for advice)
 Relapse is common. Another course of oral vancomycin can be given
for relapse. For repeated relapse, vancomycin taper regimen can be used.
 Other treatment options include rifaximin and faecal microbiota
transplant, (please consult specialist for advice).

Reference
1. HA Factsheet on Typhoid and Paratyphoid Fever (July 2011)
2. HA Factsheet on Cholera (July 2011)
3. HA Factsheet on Management of Shiga toxin-producing E coli (STEC) (June 2011)
4. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and
Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update
Guidelines on Management of Clostridioides difficile Infection in Adults
5. WHO. Technical Note: Use of antibiotics for the treatment and control of cholera
(May 2018)

In 12
 ACUTE CHOLANGITIS

1. Investigations
a) CBP, LFT, RFT
b) PT, APTT, Glucose
c) Blood culture
d) Abdominal USG

2. Management
a) Active resuscitation and monitor vital signs
b) IV antibiotics for mild to moderate cases:
 Amoxicillin-clavulanate (Augmentin) (± Aminoglycoside)
 Cefuroxime + metronidazole (± Aminoglycoside)
 If penicillin allergy, Levofloxacin + metronidazole
 IV antibiotics can be switched to oral formulary for completion of
therapy if clinically stable.
c) IV antibiotics for severe cases: Consider Piperacillin-tazobactam
(Tazocin), carbapenems, 3rd generation cephalosporin or levofloxacin +
metronidazole
d) Duration of treatment: 4-7 days unless difficult to achieve biliary
decompression
e) Early decompression of biliary obstruction by ERCP or PTBD

3. Preparation for ERCP

a) Indications for emergency ERCP
 Increasing pain and guarding in epigastrium or RUQ
 Hypotension despite resuscitation
 High fever (>39oC)
 Mental confusion, which is a predictor of poor outcome
b) Correct coagulopathy
c) Fast patient

4. Watch out for post-ERCP complications including post-ERCP pancreatitis,

perforation and bleeding.

5. Care for patients who have nasobiliary or percutaneous (PTBD) drainage of

obstructed biliary tract
a) Check input/output chart (including NB drain) daily
b) Check hydration status, RFT, HCO3 and correct fluid and electrolyte
derangement as necessary.

In 13
 SPONTANEOUS BACTERIAL PERITONITIS

High index of suspicion is necessary.

1. Cirrhotic patients may have an insidious onset of fever and lack of

peritoneal signs, perform diagnostic paracentesis, send ascitic fluid for:
 Cell count (EDTA bottle to haematology laboratory, request differential
WBC)
 Low protein level is consistent with spontaneous bacterial peritonitis
 Fluid for bacterial culture in blood culture brother
 Cytology

2. Diagnostic criteria:
 Ascitic fluid WCC >500/mm3 or neutrophil >250/mm3
(In traumatic tap, subtract 1 PMN for every 250 RBCs)

3. Perform blood culture

4. Common organisms: E. coli, Klebsiella spp, Strep, pneumonia, Enterococci.

5. Empirical treatment:
 IVI Ceftriaxone 2gm q24h OR IVI Cefotaxime 2gm q8h (q4h if life-
threatening)
 May consider reassessment by repeating paracentesis 48 hours later
 Usual duration of treatment: 5-10 days
 Consider IV albumin 1.5gm/kg at diagnosis and 1gm/kg on day 3,
especially in patients with renal impairment.

6. Watch out for hepatic encephalopathy

7. Prophylactic antibiotics may be considered in selected high risk or recurrent

cases. Please consult relevant specialty for advice.

References:
 The European Association for the Study of the Liver. EASL Clinical Practice
Guidelines for the management of patients with decompensated cirrhosis. J Hepatol
(2018), https://doi.org/10.1016/j.jhep.2018.03.024
 AASLD 2021 Practice Guidance: Diagnosis, Evaluation, and Management of Ascites,
Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome,
https://doi.org/10.1002/hep.31884

In 14
 NECROTIZING FASCIITIS

Necrotizing Fasciitis is a deep-seated infection of the subcutaneous tissue that

results in progressive destruction of fascia and fat, but may spare the skin.
Early recognition is important because there may be a remarkably rapid
progression from an inapparent process to one associated with extensive
destruction of tissue, systemic toxicity, loss of limb or death.

Diagnosis and Management:

1. Difficult to distinguish from cellulitis in early stages.
2. Excruciating pain and presence of systemic toxicity out of proportion to the
local findings.
3. Skin breakdown with bullae and frank cutaneous gangrene can be seen.
4. Risk factors assessment and urgent Gram stain may guide choice of
antibiotics.
5. Immediate surgical intervention and antibiotic therapy are the mainstay of
treatment.

Risk Factors Organisms Antibiotics

Following exposure  Aeromonas spp.  IV Levofloxacin
to freshwater,  Vibrio vulnificus Plus
seawater or seafood  IV Amoxicillin-
clavulanate
Following  Polymicrobial Imipenem or Meropenem
intraabdominal,  Enterobacteriaceae
gynaecological or  Streptococci
perineal surgery  Anaerobes
Following cuts,  Group A  IV penicillin G4
abrasion, recent Streptococcus megaunits q4h Plus
chickenpox, IVDU,  IV Linezolid 600mg
healthy adults q12h*
 IVIG for streptococcal
toxic shock syndrome
(1g/kg on day 1,
0.5g/kg on day 2 & 3)
*Clindamycin can be used instead if the isolate is sensitive to it.

In 15
GUIDELINE FOR CLINICAL MANAGEMENT OF SKIN &
SOFT TISSUE INFECTION AND CLINICAL SYNDROMES
COMPATIBLE WITH STAPHYLOCOCCAL INFECTION

History and Physical Examination

Complicated SSTI: Uncomplicated SSTI: Obtain culture if

Consider admission Impetigo, Cellulitis, “NARES”
Folliculitis, Furuncle, Not responsive to 1st
Abscess involvement line antibiotic
Atypical – body site or
Indications for IV clinical features
Antibiotics Initiate empirical Recurrent SSTI
(Severe sepsis + Any one Extensive – infection
below): Rx ± I & D in multiple sites
Complicated SSTI Ampicillin + Spreading – in close
(e.g. necrotizing Cloxacillin; contacts involvement
fasciitis, carbuncle) 1st generation
Periorbital cellulitis cephalosporin; or Consider topical therapy
Deep intramuscular Amoxicillin- (e.g. chlortetracycline) for
abscess/pyomyositis clavulanate or impetigo or mild
Pyogenic meningitis Ampicillin- folliculitis involvement

Clinical improve: Clinical assessment Little or no

Complete therapy of S/S: improvement
Advice on personal Treat according to Obtain culture (if not
hygiene culture results yet done)

If culture showed CA- Alternative therapy / Review diagnosis

MRSA, please notify consider CA-MRSA Re-assess need for
Department of Health coverage I&D

In 16
 SEPTIC SHOCK

Terminology

Sepsis: Life-threatening organ dysfunction caused by a dysregulated host

response to infection.
Clinical criteria: Suspected or documented infection and an acute increase of
≥2 SOFA points

Sequential (Sepsis-related) Organ Failure Assessment (SOFA) Score

Score 0 1 2 3 4
PaO2/FIO2, < 200 < 100
mmHg ≥ 400 < 400 < 300 (26.7) with (13.3) with
(kPa) (53.3) (40) respiratory respiratory
(53.3)
support support
Platelets
≥ 150 < 150 < 100 < 50 < 20
(103/μL)
Bilirubin,
< 20 20-32 33-101 102-204 > 204
μmol/L
Cardio- Dopamine Dopamine
vascular 5.1-15 or > 15 or
Dopamine
adrenaline adrenaline
MAP ≥ 70 MAP < 70 < 5a or
≤0.1 or > 0.1 or
mmHg dobutamine
mmHg nor- nor-
(any dose)
adrenaline adrenaline
≤0.1a > 0.1a
GCS 15 13-14 10-12 6-9 <6
Creatinine
< 110 110-170 171-299 300-440 > 440
(μmol/L)
Urine
output - - - < 500 < 200
(mL/day)
a
Catecholamine doses as μg/kg/min for at least 1 hour

Septic shock: a subset of sepsis in which underlying circulatory & cellular/

metabolic abnormalities are profound enough to substantially increase
mortality.
Clinical criteria: Sepsis & persisting hypotension requiring vasopressors to
maintain MAP ≥ 65 mmHg and serum lactate level >2 mmol/L despite
adequate volume resuscitation.
In 17
Principles of management
 Hour-1 bundle:
1. Measure lactate level. Re-measure if initial lactate is >2 mmol/L.
2. Obtain blood cultures (and other appropriate microbiologic cultures)
prior to administration of antibiotics.
3. Administer broad-spectrum antimicrobials: choice based on suspected
primary site of infection risk factor(s) for drug-resistant pathogens.
4. Begin 30 mL/kg crystalloid (balanced crystalloids, e.g. Plasma-Lyte,
preferred over normal saline) for hypotension or lactate ≥ 4 mmol/L.
5. Apply vasopressors (e.g. noradrenaline, dopamine) if patient is
hypotensive during or after fluid resuscitation to maintain MAP ≥ 65
mmHg.
 Source control: e.g. removal of indwelling devices, drainage of abscess.
 Proper ventilator management with low tidal volume in patients with
ARDS.
 Target blood glucose level ≤ 10 mmol/L.
 IV hydrocortisone 50mg every 6 hours can be started for those with septic
shock requiring ongoing vasopressor therapy.

References:
1. Singer M et al., The Third International Consensus Definitions for Sepsis
and Septic Shock (Sepsis-3). JAMA 2016;315(8): 801-810.
2. Evans L et al., Surviving Sepsis Campaign: International Guidelines for
Management of Sepsis and Septic Shock 2021 Crit Care Med. 2021 Nov
1;49(11):e1063-e1143
3. Levy MM et al., The Surviving Sepsis Campaign Bundle: 2018 Update.
Crit Care Med 2018;46(6):997-1000.

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 TREATMENT OF FEBRILE NEUTROPENIA

*These recommendations cannot be applied to every clinical situation. All

patients should be examined carefully and treated for suspected focal infection
if identified.

Fever and neutropenia

Fever: Pyrexia >38.3oC or >38oC for >1 hour
Neutropenia: Neutrophil (ANC) ≤0.5 x 109/L or ≤1 x 109/L with predictable
decline to ≤0.5 x 109/L over 48 hours

Prompt detailed assessment and resuscitation if necessary (Note 1)

Administer empirical antibiotic (any of the following) as soon as possible (within

one hour of presentation) after immediate sepsis workup:
Piperacillin-tazobactam 4.5gm q6-8h IVI
Carbapenems (e.g. Meropenem 1gm q8h IVI or 1gm Loading then 500mg q8h
IVI infuse over 3 hours / Imipenem 500gm q6h IVI
Cefepime 2gm q12h or 1gm q8h IVI
(*Adjust dose for patients with renal or hepatic dysfunction)

Risk assessment by clinical judgment and validated score (Note 2)

High risk or patients receiving

Low risk
fluoroquinolone prophylaxis

Oral antibiotics: Fluoroquinolone plus

Continue empirical in-patient
amoxicillin-clavulanate (or plus
intravenous broad spectrum
clindamycin for those with penicillin
antibiotics (Note 3)
allergy)

Regular review and adjust antimicrobials according to culture results, radiological data and
clinical conditions +/- consult infectious disease specialists, e.g. Antifungal agents if persistent
fever after 4-7 days of a Broad-spectrum antibacterial regimen and no identified fever source

In 19
Neutropenia can result from either the disease or treatment e.g. chemotherapy.

Prompt initiation of broad-spectrum antibiotic after immediate sepsis work-up

is important as patients with febrile neutropenia can deteriorate rapidly.

Note 1 Prompt detailed assessment:

 Complete history and physical exam to identify infectious foci
 Lab: CBC with differential counts, LRFT, LDH, CaPO4
 Sepsis work-up: blood cultures (with a set collected from each lumen
simultaneously if CVC present and 1 peripheral site), other cultures, e.g.
urine, sputum, respiratory virus panels, CSF, stool, etc. if clinically
indicated.
 Imaging: CXR ± other imaging modalities if clinically indicated.

Note 2 Assessment of risk for complications of severe infection:

Patients with any of the following features are considered as high risk:
1. Anticipated prolonged (>7 days duration) and profound neutropenia (ANC
<100 cells/mm3 following cytotoxic chemotherapy)
2. Significant medical co-morbidities, e.g.
a. Haemodynamic instability
b. New pulmonary infiltrates / hypoxaemia / known COPD
c. New onset abdominal symptoms e.g. pain, vomiting
d. Change in mental state
e. Advanced age
f. Uncontrolled or progressive malignancies
g. Oral and gastrointestinal mucositis
h. Intravascular catheter infection
i. Hepatic or renal insufficiency
j. Inpatient status at time of development of fever
k. Allogeneic HCT
l. History of infection / colonization of MDRO, e.g. MRSA, VRE, ESBL,
etc.

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3. Multinational Association for Supportive Care in Cancer Risk-Index
(MASCC) Score < 21:
Characteristics Weight
*Burden of febrile neutropenia with no or mild symptoms 5*
No hypotension (systolic blood pressure <90 mmHg) 5
No chronic obstructive lung disease (e.g. chronic active bronchitis, 4
emphysema, etc.)
Solid tumour or hematologic malignancy with no previous fungal 4
infection
No dehydration requiring parenteral fluids 3
Outpatient status 3
Age <60 years 2
*Burden of febrile neutropenia refers to the general clinical status of the
patient as influenced by the febrile neutropenic episode. It should be evaluated
on the following scale: no or mild symptoms (score of 5); moderate symptoms
(score of 3); and severe symptoms or moribund (score of 0). Scores of 3 and
5 are not cumulative.

Note 3 Antibiotics for high-risk patients:

 Vancomycin is not a standard part of empirical antibiotic therapy for
neutropenic fever, except in suspected catheter-related infection, skin and
soft tissue infection, pneumonia, known MRSA carriers,
haemodynamically unstable or in presence of severe oral mucositis.
 Addition of aminoglycosides if haemodynamically unstable.
 Empirical neuraminidase inhibitor (e.g. Tamiflu) if patients presenting
with influenza-like illness during flu season.
 If confirmed with COVID-19, please refer to the latest version of HA
Interim Recommendation on Clinical Management of Adults cases with
COVID-19 for choice of antivirals and immunomodulators.

References:
1. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV,
Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice
guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010
update by the Infectious Diseases Society of America. Clin Infect Dis. 2011 Feb
15;52(4):e56-93.
2. Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA,
Nastoupil LJ, Rajotte M, Rolston K, Strasfeld L, Flowers CR. Outpatient Management of
Fever and Neutropenia in Adults Treated for Malignancy: American Society of
Clinical Oncology and Infectious Diseases Society of America Clinical Practice
Guideline Update. J Clin Oncol. 2018 May 10;36(14):1443-1453.
3. Zimmer AJ, Freifeld AG. Optimal Management of Neutropenic Fever in Patients With
Cancer. J Oncol Pract. 2019 Jan;15(1):19-24.

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 MALARIA

Management of Acute Attack

 Anti-malarial therapy should be administered as soon as possible, even
before the diagnosis is made in a highly suspicious case (e.g. coming back
from an endemic area with fever, chill, & signs of severe malaria)
 Repeat testing if the diagnosis is strongly suspected.
 Maintain fluid and electrolytes balance; avoid over-hydration.
 Severe malaria, defined by the clinical & laboratory evidence of vital
organ dysfunction, should be managed in ICU.
 Avoid sedatives and corticosteroids.
 Watch for relapse (for P. vivax & P. ovale, usually within 2 months) and
signs of peritoneal irritation (splenic rupture).

Anti-malarial Chemotherapy (Please note G6PD status – see H6)

1. Uncomplicated chloroquine-sensitive P. vivax, P. malariae and P. ovale
 Chloroquine base total 25 mg/kg (one tab of 150 mg base = 250 mg
phosphate):
- 1st dose: 10 mg/kg po STAT
- 2nd dose: 10 mg/kg po 24 hours later
- 3rd dose: 5 mg/kg po 48 hours later
 Plus Primaquine 30 mg base (0.5 mg/kg) po daily taken with food for
14 days in P. vivax and P. ovale infection to eradicate hypnozoites in
the liver (radical cure).

Note 1 Chloroquine-resistant P. vivax reported from Oceania,

Indonesia and South America, treatment similar to that of P.
falciparum malaria is required.
Note 2 Primaquine is contraindicated in pregnancy & lactation. In
G6PD deficiency, primaquine is safe at a dosage of 0.75 mg/kg
once a week for 8 weeks. Monitor Hb level.

2. Uncomplicated P. falciparum malaria

 Definition: no signs of severity or evidence of vital organ dysfunction.
 Oral regimens:
a) Artemisinin combination therapy (ACT) is preferred:
1) Coartem® (1 tab = 20 mg Artemether & 120 mg lumefantrine)
4 tablets po BD for 3 days
2) Artequick® (1 tablet = 62.5 mg artemisinin + 375 piperaquine.
Dosage: 2-4 tablets po daily for 3 days (< 45 kg: 2 tablets; 45-
In 22
 70 kg: 3 tablets: > 70 kg: 4 tablets; all po daily for 3 days)
b) Malarone® (1 adult tab = 250 mg Atovaquone + 100 mg proguanil),
4 adult tablets po daily for 3 days
c) Quinine 600 mg salt (10 mg/kg) po 8 hourly for 7 days
plus Doxycycline 100 mg po BD for 7 days

3. Severe P. falciparum malaria

 Definition: presence of ≥1 clinical or laboratory features, after
excluding other obvious causes of their symptoms:
a) Clinical: Prostration, Impaired consciousness, Respiratory distress
(acidotic breathing), Multiple convulsions, shock, Pulmonary
oedema (radiological), significant bleeding, Jaundice,
Haemoglobinuria
b) Laboratory: Severe anaemia (< 7g/dL), Hypoglycaemia, Acidosis,
Renal impairment, Hyperlactatemia, parasite density (PD) >10%

 Treatment:
a) Initial therapy: Artesunate 2.4 mg/kg iv or im given on admission
(time 0), then at 12h and 24h + follow-on therapy.
b) Follow-on therapy:
 If PD ≤ 1% tolerate oral therapy (oral regimes full course,
see Section 2 above)
 If PD > 1%: continue iv or im Artesunate daily until PD ≤ 1%,
can give up to 6 more days, then give oral regime (Section 2).
 If PD ≤ 1% but not tolerate oral therapy: continue iv or im
Artesunate daily until tolerate oral therapy, can give up to 6
more days, then give oral regime (Section 2).
c) Quinine dihydrochloride 20 mg/kg loading dose in 5% dextrose
infused over 4 hours, maintenance dose 10 mg/kg infused over 2-4
hours every 8 hours. Change to oral dose when feasible to complete
a 7-day course.
plus Doxycycline 100mg po BD for 7 days

Note 1 Primaquine 15mg (0.25 mg/kg) single dose to eradicate

gametocytes at the end of treatment of falciparum malaria.
Note 2 Do not use loading dose for quinine if patient has received quinine,
quinidine, or mefloquine in preceding 24 hours.

Reference: HA Factsheet on Malaria (August 2022)

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 CHICKENPOX / HERPES ZOSTER

Diagnosis
1. Clinical presentation
i) Chickenpox (primary infection of varicella zoster virus / VZV): Acute
illness of typical generalised papulovesicular rash without other
apparent cause (the rash may be atypical with few or no vesicle in
vaccinated persons).
ii) Herpes zoster (reactivation of VZV): either localised (along single +/-
adjacent dermatomes) or disseminated papulovesicular rash, often
associated with neuralgia.
2. Confirmed by laboratory test
i) Virus detected by DIR or PCR from clinical specimens.
ii) Paired serology in acute and convalescent phases (retrospective
diagnosis)

Management
1. Keep patients from school/work for at least 5 days after onset of eruption
or until vesicles become dry.
2. Airborne and contact precautions for chickenpox / disseminated zoster
when in hospital until lesions are dry and crusted.
3. Patients with zoster who require airborne isolation:
i) Disseminated zoster – defined as lesions outside the primary or
adjacent dermatomes.
ii) Immunocompromised patients (before disseminated disease can be
excluded).
4. Localised disease in immunocompetent individuals will not require
airborne isolation as long as the lesions can be covered.
5. Acyclovir 10-12 mg/kg q8h IV infusion for 7 days for severe zoster or
chickenpox in elderly or immune-compromised patients.
6. Oral Valacyclovir 1000mg TDS or Acyclovir 800mg 5 times per day
for 7 days can be given for milder cases.
7. Renal function should be monitored while on antiviral with dosage
adjusted accordingly.
8. Therapy for neuralgia usually required for zoster.
9. Watch for development of severe secondary skin infection
(Staphylococcus/Streptococcus) and consider antibiotics (e.g. oral
Augmentin) if necessary.
10. For herpes zoster with ophthalmic involvement, urgent eye consultation
is recommended.
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11. Varicella-zoster immunoglobulin (VZIG) should be administrated as
soon as possible after exposure and within 10 days for high risk
susceptible patients, e.g. immunocompromised persons and pregnant
women.
12. VZV vaccination should be given within 3 to 5 days after exposure as
PEP in persons who:
i) have no evidence of immunity,
ii) eligible for vaccination, e.g. immunocompetent, non-pregnant and
>12 months of age, and
iii) are not indicated for VZIG.

Reference:
 HA Guideline on varicella zoster virus infections. CCIDER. May 2018.
 Prevention of Varicella. Centres of Disease Control and Prevention. 22 June 2007.

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 HIV/AIDS
Diagnosis of HIV/AIDS
1. Informed consent: necessary for all diagnostic HIV tests. Informed consent,
based on the best interests of the patient, is sought from guardian when the
patient is a mentally incompetent person unable to given consent on his own.
2. HIV infection: positive HIV testing with screening (usually by 4th generation
assays) AND confirmatory tests (by immunoassays or Western blot).
3. Advanced HIV infection (including AIDS): positive HIV test + AIDS-
defining illness (clinical diagnosis) or CD4 count less than 200/mm3
(immunological diagnosis).
4. Window period: time between infection and appearance of detectable
antibodies (traditionally quoted as 3 months or 90 days; 4th generation assays
with detection of both p24Ag + antibodies allow earlier diagnosis & hence
shorter window period of 14-21 days).
5. Incubation period: time between infection and appearance of symptoms and/or
signs (average time to AIDS ~8-10 years).
6. Confidentiality: a patient’s HIV result must be kept strictly confidential by all
healthcare workers. Also, the patient’s HIV status should not be included in the
automatic alert in the CMS, to avoid possible stigmatisation of the patient.
7. Disclosure: normally, disclosure of positive HIV status of a patient to his/her
sex partners or family members requires specific consent from the patient. In
respect of a mentally incapacitated patient without a legal guardian, because of
the lack of specific consent, normally there should be no disclosure until the
patient regains capacity and gives specific consent.
8. HA guidelines: For issues related to confidentiality, disclosure and other legal
principles, please refer to the “Ethical guidelines on HIV-related issues in HA
and general legal principles on HIV disclosure. HAHO Operations Circular No.
20/2016” for more details (available at https://ha.home/circular2/Ops-2016-
20.pdf).
9. Reporting: both clinicians and laboratories providing confirmatory HIV tests
are encouraged to report to the Department of Health all cases of newly
diagnosed HIV/AIDS. The HIV/AIDS voluntary reporting system (report from
DH2293 available at http://www.aids.gov.hk/report.htm) has been in place in
Hong Kong since 1984. That is an anonymous system and all data collected is
treated in strictest confidence.

Clinical management of HIV/AIDS

1. There is no cure of HIV infection. However, effective antiretroviral (ARV)
drugs can control the virus and help prevent transmission (treatment as prevent)
so that people with HIV can have restoration of immune function and near
normal life-expectancy.

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2. Initial evaluation
a) The goals of initial evaluation are to confirm HIV diagnosis, obtain baseline
laboratory data, and to initiate primary care and prevention and treatment of
HIV-associated opportunistic infections.
b) Baseline laboratory tests: CD4 count, HIV RNA; CBP D/C, RFT, LFT,
fasting glucose and lipids; G6PD screening; serologies for HAV, HBV,
HCV, syphilis, Toxoplasma; genotypic resistance testing for antiretrovirals
(special arrangement needed); HLA-B5701 testing (if considering to use
abacavir in non-Chinese), IGRA (or Tuberculin skin test).
c) Psychosocial evaluation by a multi-disciplinary approach.

3. Combination Anti-Retroviral Therapy (cART)

a) In principle, cART should be started as soon as possible once HIV or AIDS
is diagnosed, regardless of CD4 count, after discussion and education on the
benefits of cART with patient.
b) In the setting of some opportunistic infections, such as cryptococcal and
tuberculous meningitis, for which immediate cART may increase the risk of
serious immune-reconstitution inflammatory syndrome (IRIS), a short delay
before starting cART may be warranted.
c) cART regimen generally consists of two nucleoside reverse transcriptase
inhibitors (NRTIs) (e.g. tenofovir, abacavir, lamivudine) and a third drug
from one of three drug classes: an integrase strand transfer inhibitor
(INSTI) (e.g. raltegravir, dolutegravir, bictegravir), a non-nucleoside
transcriptase inhibitor (NNRTI) (e.g. efavirenz, rilpivirine, doravirine), or a
protease inhibitor (PI) (e.g. ritonavir-boosted darunavir). Expert opinion
should be obtained from ID/HIV physicians on the choice of drugs.
d) cART should be taken at designated time each day and continued
uninterrupted except in special circumstances (e.g. kept nil by mouth for
surgical emergencies) to prevent development of drug resistances.
Mechanism for inter-hospital transfer of ARVs is available to ensure
availability of cART to patients hospitalised in any HA hospital.

4. Opportunistic infections (OIs) & AIDS-defining illnesses (ADIs)

a) OIs and ADIs mostly occur when CD4 count < 200/μL.
b) Most commonly reported AIDS-defining illnesses in Hong Kong are
Pneumocystis pneumonia, TB, talaromycosis (formerly penicilliosis), CMV
diseases, non-TB mycobacterial infections, Kaposi’s sarcoma.
c) Please consult ID physicians or refer to regularly updated international and
local guidelines for treatment of individual opportunistic infection.
i) Guidelines for the Prevention and Treatment of Opportunistic
Infections in Adults and Adolescents with HIV by U.S. Department of
Health and Human Services, available at
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/a
In 27
 dult-adolescent-oi/guidelines-adult-adolescent-oi.pdf
ii) European AIDS Clinical Society guidelines, available at
http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-
guidelines.html
iii) HIV Manual by Stanley Ho Centre for Emerging Infectious Diseases,
CUHK and CHP, DH, available at http://www.hivmanual.hk

Referral of HIV cases

1. Currently, there are 3 designated HIV clinical services in the public section:
HIV Clinical Service of QEH, Infectious Disease Special Medical Clinic of
PMH, and Kowloon Bay Integrated Treatment Centre (ITC), DH.
2. Contact number for referral arrangement for newly diagnosed HIV patients in
HA:
 QEH (Tel: 3506 5855),
 PMH (Tel: 2990 2065, 6461 0613)

References
1. Virtual AIDS office. Available at http://www.aids.gov.hk/report.htm. Accessed on
18 January 2019.
2. Statistics on HIV Surveillance in Hong Kong. Available at
http://www.aids.gov.hk/english/surveillance/quarter.htm. Accessed on 18 January
2019.
3. HIV/AIDS Fact sheet. Available at https://www.who.int/news-room/fact-
sheets/detail/hiv-aids. Accessed on 13 July 2023.
4. WHO case definitions of HIV for surveillance and revised clinical staging and
immunological classification of HIV-related disease in adults and children. 2007.
Available at https://apps.who.int/iris/handle/10665/43699?show=full. Accessed on 2
August 2023.
5. Principles of consent, discussion and confidentiality required of the diagnostic HIV
test. Advisory Council on AIDS & Scientific Committee on AIDS and STI (SCAS),
Centre for Health Protection, Department of Health. July 2011.
6. Ethical guidelines on HIV-related issues in HA and general legal principles on HIV
disclosure. HAHO Operations Circular No. 20/2016. Hospital Authority Clinical
Ethics Committee. October 2008.
7. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the
Use of Antiretroviral Agents in Adults and Adolescents Living with HIV.
Department of Health and Human Services. Available at
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-
arv/guidelines-adult-adolescent-arv.pdf. Accessed on 18 November 2022.

In 28
 RICKETTSIAL (SPOTTED FEVER, TYPHUS) AND
RELATED INFECTIONS

Background
 Rickettsial infections are caused by Gram-negative bacteria under the genera
like Rickettsia and Orientia.
 Most of them exist as obligate intracellular bacteria inside their mammalian
hosts through transmission by arthropod ectoparasites like ticks and mites.
Humans are incidental hosts in their life cycles.
 Spotted fever (with Rickettsia japonica accounting for some of the cases) and
scrub typhus (caused by Orientia tsutsugamushi) consist of the majority of
the reported rickettsial and related infections in HK.
 Most locally acquired infections could be related to outdoor activities like
hiking.

Clinical presentation
 Symptoms can be non-specific, including fever, headache and myalgia.
 Signs of lymphadenopathy and encephalitis-like presentation may be present.
 Prevalence of eschar varied in the literature and may not be present.
 Mild neutropenia, thrombocytopenia and deranged liver function are
common laboratory findings.

Diagnosis
 High index of suspicion should be raised, especially in those with possible
exposure (e.g. hiking, gardening and working in construction sites).
 Diagnosis is usually based on clinical grounds with paired serology (acute-
and convalescent-phase serum).

Management
 Untreated infections can lead to multi-organ failure and death.
 Beta-lactam and aminoglycoside antibiotics are not effective against these
infections.
 Since these infections can be rapidly progressive, consider empirical
doxycycline (1000mg BD for 7 to 14 days) in suspected cases as soon as
possible.
 Consult infectious disease specialists if necessary.
 Typhus and other rickettsial diseases are listed as statutory notifiable diseases
in the First Schedule to the Prevention and Control of Disease Ordinance.

In 29
 INFLUENZA

An acute viral disease of the respiratory tract caused by influenza A (H3N2,

H1N2, H1N1, H5N1, H7N9 etc.), B and C viruses, with fever, headache, myalgia,
prostration, coryza, sore throat & cough.

Diagnosis
Nasopharyngeal aspirates / tracheal aspirates / broncho-alveolar lavage
specimens for direct antigen detection (immunofluorescence of EIA) or PCR:
 Under HA, PCR for influenza A and B is available as a routine test during
winter surge.
 Lower respiratory tract specimen is preferred in patients with pneumonia
and/or suspicion of novel influenza.

Complications
Primary viral pneumonia, secondary bacterial pneumonia, myocarditis,
myositis, rhabdomyolysis, Guillain-Barré syndrome, transverse myelitis,
Reye’s syndrome (associated with use of aspirin in children); exacerbation of
underlying illnesses, e.g. COPD, coronary artery disease, asthma.

Management
1. Infection control measures: On top of standard precaution, exercise
droplet precautions for cases of seasonal influenza; for novel influenza,
isolate patient in airborne infection isolation room (AIIR) and exercise
airborne, droplet and contact precautions.
2. Treatment
 Antiviral therapy is recommended for patients hospitalized with
influenza, especially those with high-risk conditions or severe disease.
 Effective against influenza A and B
 Oseltamivir 75mg BD po x 5 days
 Zanamivir 10mg BD inhaler puff x 5 days (for uncomplicated cases
that are able to coordinate with use of inhaler)

N.B
 Beneficial effects of treatment are most apparent if started early (i.e.
within 48 hrs of symptom onset). However, in severe, hospitalized cases,
therapy should still be considered beyond the 48-hr window period.
 In complicated cases (e.g. viral pneumonia), one may consider prolonged
duration (e.g. up ot 10 days) ± increased dose of oseltamivir (150-300mg

In 30
 BD po).
 Intravenous preparations of zanamivir and peramivir may be considered
as salvage therapy for critical cases.
 Favipiravir is available as a reserved agent for management of
neuraminidase inhibitor resistance. Please consult infectious disease
physician or clinical microbiologist for advice.

Special points on Novel Influenza (e.g. influenza A/H5N1, influenza

A/H7N9)
1. A statutory notifiable disease
2. Pay attention to epidemiological link (Travel / Occupation / Contact /
Clustering) in evaluation of patients with fever ± respiratory tract
symptoms.
3. In general, neuraminidase inhibitors remain effective as a treatment for
novel influenza. Prolonged duration and/or increased dose of therapy may
be necessary.
4. Intravenous preparation of zanamivir and peramivir may be considered for
critical cases.

Reference
1. HA fact sheet on antiviral therapy against influenza (January 2018)
2. HA Interim Recommendation on Antiviral Therapy for Human Infection due to Avian
Influenza A (H7N9) (December 2019)
3. HA infection on the use of intravenous zanamivir and peramivir (December 2019)

In 31
 INFECTION CONTROL

Hand Hygiene (HH)

Good hand hygiene practices are of utmost importance to prevent health care
associated infections.
“Five moments” for HH (WHO recommendations):
1. Before patient contact
2. Before aseptic task
3. After body fluid exposure risk
4. After patient contact
5. After contact with patient surroundings

Alcohol-based hand rub is preferred if the hands are not visibly soiled.
(Exception: After contact with C. difficile patients and their surroundings,
soap and water is required as alcohol is ineffective for killing spores)

Precautions to prevent transmission of infectious agents

2 tiers of precautions:
1. Standard precautions (SP)
Applied to all patients in all healthcare setting, regardless of suspected or
confirmed presence of an infectious status. HCWs should apply SP when
contact with:
 Blood;
 All body fluids, secretions, and excretions except sweat, regardless of
whether or not they contain visible blood;
 Non-intact skin; and
 Mucous membranes

2. Transmission-based precautions
 Applied to patients who are known or suspected to be infected or
colonised with infectious agents, including epidemiologically
important pathogens which require additional control measures to
effectively prevent transmission. These composed of droplet, contact
and airborne precautions.
 Diagnosis of many infections requires laboratory confirmation.
Appropriate transmission-based precautions should be implemented
when test results are pending based on the clinical presentation and
likely pathogens.

In 32
Precautions Prevent transmission of infectious agents
Contact Spread by direct / indirect contact with patients or patient’s
environment e.g. Norovirus, RSV, C. difficile, multi-drug
resistant organisms (MDROs), e.g. CPE, ESBL producers,
MDRA, MRPA, MRSA, VRE
Droplet Spread through close respiratory or mucous membrane contact
with respiratory secretions
e.g. Influenza, N. meningitides, B. pertussis
Airborne That remain infectious over long distance when suspended in
air
e.g. Measles, Chickenpox, M. tuberculosis
Certain droplet-transmitted pathogens, e.g. influenza, may be
widely dispersed during aerosol generating procedures e.g.
intubation

3. Syndromic & empiric applications of transmission-based precautions

Clinical syndrome Potential pathogens Empiric precautions
Acute diarrhoea with Enteric pathogens Contact
likely infectious cause in
an incontinent/diapered
patient
Abscess/draining wound MSSA, MRSA, Contact
that cannot be covered Group A
Streptococcus
Vesicular rash Varicella zoster, Airborne + Contact
variola
Petechial / ecchymotic N. meningitides Droplet (for 24 hrs. of
with fever; meningitis antimicrobial therapy);
mask and face protection
for intubation
Maculopapular rash with Measles Airborne
cough, coryza and fever
Cough / fever / pulmonary M. tuberculosis Airborne
infiltrate and other clinical
features suggestive of TB

In 33
4. Novel respiratory viruses (SARS-CoV, MERS-CoV and SARS-CoV-2)
 There were sporadic outbreaks due to novel respiratory viruses, for
example, Severe Acute Respiratory Syndrome Coronavirus (SARS-
CoV) during 2002 to 2003, Middle East Respiratory Syndrome
Coronavirus during 2014-2019, and the latest SARS-CoV-2 causing
pandemic outbreak since late 2019.
 These respiratory viruses primarily spread through small droplets.
 Because of the uncertainty of transmission route particularly during
early phase of outbreaks and the potentially high fatality, isolate in
airborne infection isolation rooms (AIIR) with standard, droplet and
airborne precautions for suspected and confirmed patients.

References:
1. HA Safety Manual (Chapter 5) – Infection Control. HA CCIDER. June 2018
2. Interim Recommendation on Clinical Management of Adult Cases with Coronavirus
Disease 2019 (COVID-19). HA CCIDER. June 2020.

In 34
 NEEDLESTICK INJURY, NON-INTACT SKIN OR
MUCOSAL CONTACT WITH BLOOD AND BODY FLUIDS

1. Many pathogens can be transmitted through exposure to blood or body fluids.

The most important of these are HIV, HBV and HCV.
2. After percutaneous exposure from a positive source, the risk of transmission
is 0.3% of HIV (0.1% after mucosal exposure), 2% for HCV, and 6-30% for
HBV (depending on the HBeAg status of the source).
3. Preventing exposures to blood and body fluids is the most important strategy
for preventing occupationally acquired HIV, HBV or HCV. Healthcare
workers (HCW) should adhere to the principles of Standard Precautions:
 Avoid recapping needles
 Dispose sharps immediately and properly (in sharps disposal boxes) after
use
 Plan for safe handling and disposal before beginning any procedure
involving sharps use
 Use protective equipment (e.g. gloves, apron, eye protector, face shield
etc) during procedures that are likely to generate splashes and sprays of
blood, body fluids, secretions, and excretions.

Management of Needlestick Injury, Non-intact Skin or mucosal Contact

with Blood and Body Fluids

Immediate Action
 Puncture wound or skin exposure should be washed with soap and water.
Puncture wound may also be cleansed with an antiseptic such as alcohol-
based hand hygiene agent.
 Exposed mucous membranes should be flushed with copious amount of
water. Eyes should be irrigated with saline or water.
 Attend A&E or staff clinic immediately.

Reporting: Injured HCW should report to his / her senior and Infection Control
Team

Determine HIV/HBV/HCV status of the source patient & injured HCW

 Source patient: HIV / HBV / HCV testing (anti-HIV, HBsAg, anti-HCV)
with consent
 Injured HCW: HIV / HBV / HCV testing (anti-HIV, HBsAg, anti-HBs,
anti-HCV)
 Blood test orders should be marked clearly with “Urgent: NSI source” or
“Urgent: NSI victim” & specimens be sent urgently without delay.
In 35
Post-exposure prophylaxis (PEP) for injured HCW
 PEP should be administered for exposures assessed to carry a risk for HIV
/ HBV transmission.
 HBV: hepatitis B immune globulin (HBIG) and/or hepatitis B vaccine
should be given according to the HBV status of the source patient and the
HCW.
 HCV: PEP is not available; management mainly involves early diagnosis
and treatment of HCV infection should it occur.
 HIV: 4 weeks of antiretrovirals consisting of ≥ 3 drugs should be given as
soon as possible (within hours of exposure) and no later than 72 hours.
 PEP for HIV is available at A&E Department of all HA hospitals.
 Injured HCW started on PEP for HIV should be referred to specialist
clinic for further assessment, counselling and following up:
1. SMC QEH (Tel: 3506 5855)
2. IDSM PMH (Tel: 2990 2065, 6461 0613)

Follow up testing for detection of infection and monitoring

 HIV: HIV testing should be carried out at 6, 12 & 24 weeks post-exposure;
side effects from PEP should also be monitored.
 HBV: HBsAg and anti-HBc should be tested at 24 weeks post-exposure
 HCV: if source patient is HCV positive or known IV drug addict with
unknown HCV status, check HCV RNA at 6-8 weeks for injured HCW to
look for acute HCV infection; if negative, check anti-HCV at 6 months.

References:
 U.S. Public Health Service Guidelines for the Management of Occupational
Exposures to HIV and Recommendations for Postexposure Prophylaxis. U.S. Public
Health Service Working Group. Accessed 30th January 2019.
 CDC Guidance for Evaluating Health-Care Personnel for Hepatitis B Virus
Protection and for Administering Postexposure Management. Centers for Disease
Control and Prevention Morbidity and Mortality Weekly Report Volume 62 /
Number 10, December 20, 2013
 Information for Healthcare Personnel Potentially Exposed to Hepatitis C Virus (HCV)
Recommended Testing and Follow-up. U.S. Department of Health and Human
Services, Centers for Disease Control and prevention. April 2018.
 Recommendations on the Management and Postexposure Prophylaxis of Needlestick
Injury or Mucosal Contact to HBV, HCV and HIV. Scientific Committee on AIDS
and STI (SCAS), and Infection Control Branch, Centre for Health Protection,
Department of Health. January 2014

In 36
 MIDDLE EAST RESPIRATORY SYNDROME (MERS)

Background
 Caused by MERS-coronavirus (MERS-CoV), first reported in the Middle
East in 2012.
 Most cases occurred in Arabian Peninsula. Exported cases to other cities /
countries had been described.
 Suspected animal reservoirs: dromedary camels and bats
 Limited, non-sustained human to human transmission occurred mainly in
healthcare settings.
 Incubation period: 2 to 14 days
 Case fatality rate: around 30%

Clinical manifestation
 Can be asymptomatic
 Common presentation: pneumonia presenting with fever, cough, and
shortness of breath
 Other symptoms: gastrointestinal symptoms, including diarrhoea
 Severe illness: Organ failure e.g. respiratory failure, renal failure, or septic
shock

Investigations
 Upper respiratory tract specimens (NPA, NPS), or lower respiratory tract
specimens (sputum, tracheal aspirate, BAL) in patients with pneumonia,
for MERS-CoV PCR (lower respiratory tract specimens may have a better
diagnostic yield).
 Repeated testing may be necessary to exclude the diagnosis.
 Stool for MERS-CoV PCR in patients with epidemiological link
presenting with diarrhoea.
 Microbiological workup to exclude other infections.

Clinical management
 Isolate the patient(s) in airborne infection isolation room (AIIR) with
standard, contact, droplet and airborne precautions.
 Start empirical antimicrobial agents as for community acquired pneumonia
as appropriate.
 Liaise with ICU early for intensive care if anticipate clinical deterioration.
 Provide supportive treatments: Oxygen, IV fluid, Inotropic support ±
steroid* (septic shock), Mechanical ventilation ± ECMO (respiratory
failure), Renal dialysis (renal failure).
In 37
 Avoid high-dose systemic corticosteroids for viral pneumonitis; consider
administration of intravenous hydrocortisone (up to 200mg/day) or
prednisolone (up to 75mg/day) to patients with persistent shock who
require escalating doses of vasopressors.
 There is no guideline-recommended specific anti-viral treatment at the
moment. One RCT from Saudi Arabia showed a combination of
recombinant interferon beta-1b and lopinavir-ritonavir led to lower
mortality than placebo when started within 7 days after symptom onset.
 Continue isolation and infection control measures till asymptomatic and
specimens negative for MERS-CoV PCR.

Reference:
HA Interim Recommendation on Clinical Management of cases of Middle East
Respiratory Syndrome (January 2020).
Arabi YM et al. Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory
Syndrome. N Engl J Med. 2020 Oct 22;383(17):1645-1656.

In 38
 VIRAL HAEMORRHAGIC FEVER (VHF)

Background
 VHF can be caused by four families of enveloped RNA viruses – Arenaviruses,
Bunyaviruses, Filoviruses and Flaviviruses.
 VHF in general refers to severe febrile illnesses with abnormal vascular
regulation and vascular damage but not all patients infected with a VHF agent
develop this syndrome.
 The routes of transmission are variable:
- Most are zoonotic with spread via arthropod bites or contact with infected
animals.
- Human to human transmission possible e.g. in Ebola virus, Marburg virus,
Lassa virus and CCHF virus infection – usually occur through direct contact
with contaminated blood or body fluids via mucous membrane during case
of sick patients or handling of dead bodies in burial ritual.

Summary of common VHF agents are listed below:

Source of
Disease Natural Incubation
Family Human
(Virus) Distribution (Days)
Infection
Lassa fever Arenaviridae W. Africa Rodent 5-16
Argentine HF Arenaviridae S. America Rodent 7-14
Rift Valley Africa, Middle
Bunyaviridae Mosquito 2-5
fever East
Crimean- Europe, Asia,
Bunyaviridae Tick 3-12
Congo HF Africa
Hantavirus Bunyaviridae Worldwide Rodent 9-35
Marburg virus Filoviridae Africa Fruit Bats 2-21
Ebola virus Filoviridae Africa Fruit Bats 2-21
Africa, South
Yellow fever Flaviviridae & Central Mosquito 3-6
America
Asia, Africa,
Dengue HF Flaviviridae Mosquito 3-15
American

Clinical features
 Vary according to specific viral infection, ranging from minimally symptomatic
to fulminant presentations.
 Common presenting features: fever, myalgia, headache & prostration,
conjunctival injection, mild hypotension, flushing & petechial haemorrhages.
 GI symptoms e.g. nausea, vomiting, diarrhoea and abdominal pain are often

In 39
 present in the pre-haemorrhage stage.
 Severe haemorrhagic manifestations in later stage: bruising, ecchymoses,
bleeding at injection sites, gingival haemorrhage and GI bleeding. It is often
accompanied by renal failure, hepatic damage, multi-organ failure and shock.

Diagnosis
 Suspect VHF based on clinical assessment and travel / exposure history.
 Need to exclude other differential diagnosis e.g. malaria, meningococcaemia.
 Diagnosis of VHF can be confirmed by blood test using PCR method to detect
specific virus.

Management
 Infection control (in those with possible human to human transmission):
i) Isolation in single room (in practice, use an Airborne Infection Isolation
Room (AIIR) with toilet facility);
ii) Standard, Contact and Droplet precautions;
iii) Prevention of sharps injury and mucocutaneous exposure to blood, body
fluids, secretion and excretions; and
iv) Meticulous hand hygiene
 Management is mainly supportive:
i) Fluid and electrolyte management;
ii) Manage severe bleeding complications;
iii) Treat secondary bacterial infections;
iv) Mechanical ventilation and/or dialysis support
 Anticoagulants, aspirin, NSAIDS & intramuscular injections are
contraindicated.
 Ribavirin can be considered in VHF caused by Arenavirus (e.g. Lassa fever) or
Bunyavirus (e.g. CCHF)
 Therapy: Two monoclonal antibodies (Inmazeb, Ebanga) have been approved
by the US FDA for the treatment of Ebola virus disease (EVD). However, these
are not available in Hong Kong.

Vaccination
 Yellow fever vaccine is recommended & required for travellers to some
countries in Africa & South America (refer to CDC/WHO website for details)
 Vaccines for other VHF agents, e.g. Ebola and Dengue virus, are not available
in Hong Kong.

Reference:
Guidelines on Management of Patients with Suspect Viral Haemorrhagic Fever. HA
CCIDER (July 2014)
Interim Recommendation on Clinical Management of Ebola Virus Disease (EVD). HA
CCIDER (Dec 2019)

In 40
 ZIKA
Zika virus infection is a vector-borne disease, mostly transmitted to human by
Aedes mosquitoes. Other modes of transmission include sex, blood product
transfusion & maternal-foetal transmission. Outbreaks of Zika infection have
occurred worldwide & there are ongoing cases in the Americas, the Caribbean &
the Pacific. There were 3 confirmed imported cases in Hong Kong as of 22 Nov
2018. For most updated areas at risk of zika, please refer to CDC website below.

Clinical presentations
 Incubation period can be up to 2 to 14 days
 About 80% of the infected cases are asymptomatic
 Common: Fever, maculopapular rash, myalgia, and headache. Non-purulent
conjunctivitis is a rather distinct feature of zika, when comparing to other
mosquito-borne infections e.g. dengue.
 Zika virus infection may lead to neurological complications such as Guillain-
Barré syndrome, neuropathy and myelitis.
 Zika virus infection has been associated with neurological complications,
including congenital microcephaly, Guillain-Barré syndrome and myelitis.

Diagnosis
 Blood x Zika virus RT-PCR (usually detectable in early viraemic phase, up
to two weeks)
 Urine x Zika virus RT-PCR (up to six weeks after onset of disease)
 Clinical suspicion is based on patient’s clinical features and travel to an
affected area or country within 2 weeks.

Management
 Supportive treatment with adequate hydration and antipyretics, no specific
treatment or vaccine is available.
 Confirmed case should be placed in a vector-free hospital environment
during viraemic phase.
 Pregnant ladies should avoid travelling to areas with Zika transmission.
Sexual partners of pregnant women returning from areas with Zika
transmission should practice safe sex or abstain from sexual activity
throughout pregnancy.

References
1. Fact sheet on Zika Virus. HA Central Committee on Infectious Diseases and Emergency
Response.
2. Centre for Health Protection Website http://www.chp.gov.hk
3. CDC website on Zika virus https://www.cdc.gov/zika/geo/index.html
In 41
 DENGUE

Dengue virus infection is a vector borne disease, transmitted by Aedes

mosquitoes. While most were imported cases, sporadic local cases have
occurred in Hong Kong. Dengue virus infection is caused by four antigenically
distinct, viral serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus
Flavivirus.

Clinical presentations
 Incubation period commonly 4-7 days (from 3-14 days)
 Common features: fever, headache, retro-orbital pain, myalgia, skin rash,
anorexia, nausea and vomiting, leukopenia and positive tourniquet test.
 Dengue with warning signs: abdominal pain or tenderness, persistent
vomiting, clinical fluid accumulation (ascites, pleural effusion), mucosal
bleeding, lethargy and restlessness, hepatomegaly (>2cm), increase in
haematocrit concurrent with rapid decrease in platelet count.
 Severe dengue (at least one of the following):
i) Severe plasma leakage leading to shock, fluid accumulation with
respiratory distress
ii) Severe bleeding
iii) Severe organ involvement: ALT >1000 units/L, impaired
consciousness, organ failure

Diagnosis
 Routine tests: leukopenia and thrombocytopenia, elevated liver enzymes,
atypical lymphocytosis.
 Specific tests
i) Serology: serum IgM (detectable day 4 after onset of symptoms)
ii) Blood x Dengue virus NS1 antigen or RT-PCR in early viraemic phase
(within 1-week onset of symptoms)

Management
 Inpatient management is warranted for patients with:
i) Warning signs
ii) Severe dengue
iii) Coexisting conditions: pregnancy, co-morbid conditions (DM, IT,
peptic ulcer, chronic renal or liver diseases, etc), obesity, infancy or
elderly.
 Mainstay of therapy is supportive: Bed rest, fluid replacement,
antipyretics. No specific antiviral is available.
In 42
 Monitoring: vital signs (blood pressure, pulse, oxygenation, level of
consciousness, urinary output, hydration status; laboratory parameters
(haematocrit, platelet and leukocyte counts, liver and renal functions).
 Critical phase usually occurs around the time of defervescence, lasting for
24 to 48 hours. It is characterised by increase in capillary permeability with
plasma leakage.
 Management of patients with warning signs
i) Use isotonic solutions (0.9% saline, Ringer’s lactate, or Hartman’s
solution)
ii) Obtain haematocrit before intravenous fluids and monitor serially
 Management of patients with severe dengue
i) Consider ICU care
ii) Blood transfusion in case of severe bleeding
iii) Compensated shock (systolic pressure maintained but with signs of
reduced perfusion): replace with isotonic crystalloid solution
iv) Hypotension shock: replace with isotonic crystalloid or colloid
solutions
v) Changes of haematocrit are useful guide to treatment

Criteria of hospital discharge

 Absence of fever for 48 hours
 Improvement in clinical status (general well-being, appetite,
hemodynamic status, urine output, respiratory status)
 Increasing trend of platelet count
 Stable haematocrit without intravenous fluids

References
1. Guideline on Clinical Management of Dengue Fever. HA Central Committee on
Infectious Diseases and Emergency Response (CCIDER)
2. WHO. Handbook for Clinical Management of Dengue 2012.

In 43
 COVID-19

Coronavirus Disease 2019 (COVID-19) is an acute respiratory illness,

transmitted by droplets and contact with contaminated surfaces. The causative
agent is a new strain of coronavirus (SARS-CoV-2). People of older age or
having underlying chronic disease are at a higher risk of deterioration into
serious condition.

Clinical presentations
 Incubation period commonly 4-5 days (generally within 14 days)
 Wide range of symptoms, from asymptomatic to severe illness
- Common symptoms: Fever, malaise, dry cough and shortness of breath
- Other symptoms: nasal congestion, chills, sore throat, runny nose, new
loss of taste or smell, nausea, vomiting, diarrhoea, headache, fatigue
and myalgia

Diagnosis
 Routine tests: CBP, LRFT, RG, LDH, CK, CRP
 Specific tests:
Specimen for RT-PCR of SARS-CoV-2:
- Upper respiratory tract: Combined nasal and throat swab (CNTS),
throat swab alone or deep throat saliva (DTS)
- Lower respiratory tract: sputum or tracheal aspirate or BAL (if
bronchoscopy)
- Stool: For patient fulfilling reporting criteria with diarrhoea

Management
 Isolate patient in airborne infection isolation room (AIIR) with standard,
contact, droplet and airborne precautions.
 Supportive treatments:
- Monitor for any concomitant bacterial infections and start empirical
antibiotics if necessary.
- Oxygen and IV fluid if necessary.
- High-flow nasal oxygen (HFNO) may be considered in selected patients
with hypoxemic respiratory failure.
- Mechanical ventilation with protective lung ventilation +/- consider
ECMO for refractory respiratory failure.

In 44
Specific treatments
 Anticoagulation: consider low molecular weight heparin (LMWH) to
prevent venous thromboembolism in high risk patients hospitalised with
COVID-19, if not contraindicated.
 Specific treatments according to clinical status:
- For cases with or without mild symptoms, but at risk of disease
progression to severe COVID.
a) Oral Nirmatrelvir/ritonavir (Paxlovid®)(300 mg/100 mg) twice
daily for 5 days. Preferred, need dosing adjustment for renal
impairment:
i. For eGFR < 30ml/min/1.73m2 (exclude dialysis): 300 mg nirmatrelvir and 100 mg
ritonavir once on day 1, then 150 mg nirmatrelvir and 100 mg ritonavir once per day
for day 2-5
ii. Dialysis (peritoneal dialysis and haemodialysis)
1. Body weight >= 40 kg: 300 mg nirmatrelvir and 100 mg ritonavir once on day
1, then 150 mg nirmatrelvir and 100 mg ritonavir once per day for day 2-5
2. Body weight < 40 kg: 150 mg nirmatrelvir and 100 mg ritonavir on day 1, then
150 mg nirmatrelvir and 100 mg ritonavir every 48 hours for 2 more doses
iii. For haemodialysis patients, to be taken after haemodialysis
b) Alternative: Oral molnupiravir 800 mg every 12 hours for 5 days;
or Intravenous remdesivir (200 mg loading dose, followed by
100mg maintenance for total 3 days) ± subcutaneous interferon
beta-1b (0.25 mg 8-16 MIU daily 3 doses)
c) Drug-drug interaction:

In 45
 - Moderate symptoms and requires supplemental oxygen
a) IV remdesivir (3-5 days) + dexamethasone (6 mg daily oral or iv up
to 10 days)
b) Use of remdesivir depends on disease stage, guided by symptom
onset and CT value
c) For patients with rapidly increasing oxygen needs (or use of high
flow oxygen device/NIV) and systemic inflammation, consider add
either baricitinib (oral 4 mg daily for up to 14 days, dosing
adjustment according to renal function) or IV tocilizumab (8 mg/kg,
one dose)
- Critical disease and requires mechanical ventilation or ECMO
a) Dexamethasone
b) For patients who are within 24 hours of ICU admission:
dexamethasone + either baricitinib or IV tocilizumab

Monitoring
 Serial blood monitoring: CBP, LRFT, LDH, CRP
 Repeat pooled swab or DTS for SARS-CoV-2 PCR if indicated.
 Blood for SARS-CoV-2 antibody for patients who are asymptomatic or 7
days after symptom onset or with SARS-CoV-2 PCR CT value ≥30.
 Monitor for any concomitant bacterial or fungal infections.
 Observe for any side effects.

Release from isolation

Refer to updated criteria for releasing confirmed COVID-19 patients from
isolation by CHP and HA

The management of COVID-19 and isolation policy are subject to

modifications in alignment with local guidance. Please refer to HA interim
recommendation on clinical management of adult cases with COVID-19 for
updates.

References:
1. Interim Recommendation on Clinical Management of Adult Cases with COVID-19
https://ha.home/ho/cico/Interim_Recommendation_on_Clinical_Management_of_
Adult_Cases_with_COVID-19.pdf
2. Infection Control Plan for COVID-19 https://ha.home/ho/ps/ICplanforcovid19.pdf
3. HA designated website on COVID-19 (Public)
https://www.ha.org.hk/covid/en/index.html

In 46
Nephrology
 RENAL TRANSPLANT – DONOR RECRUITMENT

Protocol for preparation and management of potential organ donor:

Identification of potential organ donor:

a) Definite diagnosis, irreversible CNS damage;
b) Brain death is imminent;
c) Put on mechanical ventilation;
d) GCS 3-5/15;
e) Both pupils fixed to light

Exclusion criteria:
 Uncontrolled fulminant infection;
 Risk of transmission of disease caused by prions, including Creutzfeldt-
Jakob disease, rapid progressive dementia or degenerative neurological
disease;
 History of IV drug abuse;
 HIV +ve cases or has risk factors for HIV infection;
 Presence or previous history of malignant disease (except primary basal
cell carcinoma, carcinoma in-situ of uterine cervix and some primary
tumour of CNS);
 Unknown cause of death;
 Victims of intoxication of toxic substance

Maintenance of organ perfusion of potential donor (Rule of 100s)

Aim:
 Maintain SBP 100-140 mmHg, AR 60-120 bpm
 Maintain Mean BP > 80 mmHg
 Maintain CVP of 8-12 cm H2O
 Maintain hourly urine output ~100 ml
 Maintain intake and output balance and cover insensible loss
 Maintain SaO2 ≥ 95%
 Maintain body temperature >36oC

a) Monitor BP, P, CVP, urine output, SaO2, ventilator status q1h, body
temperature q2h
b) Monitor electrolytes, RLFT, Ca/PO4 q6-8h, H’stix q2-4h
c) Set two good IV lines, preferably one central line
d) Monitor BP:
 If persistently hypertensive (MBP >120 mmHg), start labetalol 5mg
K1
 IV over 1 min and repeat at 5 min intervals if necessary.
 If persistently hypotensive (SBP ≤100 mmHg)
- Start fluid replacement by infusing crystalloid or colloid
- Add dopamine 2.5-10 micrograms/kg/min if BP persistently low
despite adequate fluid replacement
- Add adrenaline (1-60 micrograms/min) or noradrenaline (3-60
micrograms/min) infusion
- If BP persistently low: start hydrocortisone 100mg stat & 100mg
q8h.
e) Monitor urine output:
 If massive urine output (>200 ml/hour)
- Control hyperglycaemia (H’stix >12 mmol/L persistently) by
Actrapid HM infusion at 2-6 units/hour.
- Control diabetes insipidus (serum Na ≥150 mmol/L) by dDAVP 2-
6 microgram IV q6-8h.
- Control hypothermia (body temperature ≤35oC) by applying patient
warming system.
 If oliguric (hourly urine <30ml)
- Check Foley patency
- Oliguria with low or normal CVP, start fluid replacement
- Oliguria with high CVP, start Lasix 20-250 mg IVI
f) Add prophylactic antibiotics after blood culture if fever >38oC.

Routine arrangement:
a) Inform transplant coordinator via hospital operator at any time.
b) Interview family for grave prognosis, do not discuss organ donation with
family until patient is confirmed brain death.
c) Once the patient meets brain death criteria, arrange qualified personnel to
perform brain stem death test. See GM31.

K2
 ELECTROLYTE DISORDERS

Hypokalaemia

Hints:
 Check drug history, in particular diuretic therapy;
 Usually associated with metabolic alkalosis;
 Consider transcellular shift;
 Consider magnesium depletion if hypoK is resistant to treatment;
 Don’t give potassium replacement therapy in dextrose solution.

Investigations:
 Serum RFT, total CO2 content, chloride, magnesium, thyroid function,
cortisol;
 Simultaneous blood and urine for TTKG (trans-tubular potassium
gradient) or 24h urine for potassium or urine [K]/[Cr]
 Urine [Na]/ [Cl] ratio (~1 suggestive of renal loss; > 1.6 may indicate
vomiting; < 0.7 – laxative abuse)
 Aldosterone-Renin ratio if confirmed urinary K loss (after correction of
hypoK)
 Check baseline ECG (esp. those patients on digoxin therapy)

Mx:
If serum K >2.5 mmol/L & ECG changes are absent:
 Oral potassium replacement (e.g. syrup KCl 2-3g ~20-30 mmol q4h for
2-3 doses);
 KCl 10-20 mmol/hour in saline infusion (up to 40 mmol/L) as continuous
IV infusion

If serum K <2.5 mmol/L &/or ECG changes present:

 Consult ICU and cardiac monitor;
 KCl 20 mmol/hour in saline infusion (concentration up to 80-100
mmol/L; given via central vein for high conc KCl);
 May combine with oral KCl 30-40 mmoles (3-4gm syrup KCl) q4h

Hypokalaemia associated with metabolic acidosis:

Give potassium citrate solution (1 mmol/mL) 15-30 mL four times a day in
juice after meals; start K replacement before bicarbonate therapy in separate
IV line if indicated.

K3
Dosage form:
 Syrup KCl (1 gram = 13.5 mmoles K);
 Slow K (8 mmoles K / 600mg tablet);
 Potassium citrate (1 mL = 1 mmole K);
 Phosphate-sandoz (3 mmoles K, 16 mmoles phosphate / tablet)

Common Pre-mixed K-containing solution for maintenance IV infusion

 0.9% NS with 10 mmoles K / 500 mL (K conc: 20 mmol/L)
 0.9% NS with 20 mmoles K / 500 mL (K conc: 40 mmol/L)
 5% D5 with 10 mmoles K / 500 mL (K conc: 20 mmol/L)
 5% D5 with 20 mmoles K / 500 mL (K conc: 40 mmol/L)
 Lactated Ringer’s with 2 mmoles K / 500 mL (K conc: 4 mmol/L)

K4
Hyperkalaemia

Hints:
 Exclude pseudo-hyperkalaemia e.g. haemolysis in blood specimen, esp.
in those with relatively normal renal function; high white cell or platelet
count
 Beware of increase K release from cells / tissue breakdown and
transcellular shift (acidosis)
 Check drug history e.g. K supplement, NSAID, ACEI / ARB, K-sparing
diuretic.

Investigations:
 Blood test for RFT, CO2, chloride
 ECG

Rx:
For urgent cases (serum K > 6.5 mmol/L &/or ECG changes of
hyperkalaemia)
1. For hemodynamically unstable patients, to give 10% Calcium gluconate
up to 30mL or 10% calcium chloride 5-10mL IV over 2-5 minutes with
cardiac monitoring; repeat if no effect in 5 minutes.
For stable asymptomatic patients, to give 10% Calcium gluconate up to
30mL or 10% calcium chloride 10ml in 100ml NS infusion over 1 hour.
Calcium chloride contains ~3x elemental calcium than calcium gluconate
by volume. Beware of extravasation. (onset: 1-3 min; duration: 30-60
min).
2. Dextrose-insulin Dextrose-insulin infusion: give 250 mL D10 or 50 mL
D50 with 8-10 units Actrapid HM over 30-60 minutes; repeat every 4-6
hours if necessary (onset: 30 minutes; duration: 4-6 hours).
3. Sodium bicarbonate 8.4% 100-150 mL over 30-60 min; to be given after
calcium infusion in separate IV line; watch out for fluid overload (onset:
5-10 minutes; duration: 2 hours).
4. Cation exchanger, depending on availability:
i) Resonium C / A: 15-60 g orally q4-6h or as retention enema; may be
given in 100-200 mL 10% mannitol as laxative; one gram of resonium
will bind 1 mmol of K (onset: 1-2 hours; duration: 4-6 hours).
ii) Sodium zirconium cyclosilicate: 5-10 g tds for 48 hours
5. Salbutamol 10-20 mg in 3mL NS by nebulizer (onset: 15-30 minutes;
duration: 2-3 hours). Consider using in areas permitted for aerosol
generating procedures.
6. Diuretics: furosemide 40-80 mg IV bolus.
K5
7. Arrange emergency haemodialysis or peritoneal dialysis if refractory
hyperkalaemia.

For chronic cases:

Investigations:
 Detailed food and drug history
 Consider checking cortisol, plasma renin activity, serum aldosterone
Rx:
1. Low K diet (< 2g/day).
2. Diuretics: furosemide / thiazide
3. Correct acidosis with sodium bicarbonate 300-900 mg TDS (~10-30
mmol/day).
4. Fludrocortisone 0.1-0.2mg daily (for Type IV RTA).
5. May consider Sodium zirconium cyclosilicate for CKD patients (5-
15g/day)

K6
Hypercalcaemia (Also see page PM18 and GM25)
 Common cause: hyperparathyroidism, hypercalcaemia of malignancy,
drug-induced (vit D/ calcium supplement, thiazide diuretics, vit A)
 Commonly associated with dehydration
 Hypoalbuminaemia will lead to hypocalcaemia due to decrease in
protein-bound Ca. (Corrected Calcium = 0.02* (40 g/L – patient’s
albumin (g/L)) + serum Ca)

Investigations:
 Check ionized calcium, PO4, RFT, PTH, Vit D, thyroid function, 24h
urine for calcium or fractional excretion of Ca. ECG

Rx:
1. Off calcium / vitamin D supplement if any.
2. Volume repletion with NS at 100-500 mL/hr infusion (Guided by CVP /
urine output); start furosemide after rehydration 20-40 mg IV q4-12h; aim
at a urine out of ~100-150 mL/h; close monitoring of Na K Ca Mg level
and fluid status.
3. Pamidronate IV 30-90 mg (with reference to patient’s renal function) in
250-500 mL NS infused over 4-6 hrs. Maximum effect will not be seen
for several days; repeat another dose after a minimum of 7 days if
necessary.
4. Zoledronate IV 4 mg infusion over 15 min (maximal effect at 72 hours).
5. Salmon calcitonin 4 units/kg IM/SC q12h; Calcium level begins to fall
within 2-3 hours; tachyphylaxis occurred within 2-3 days.
6. Hydrocortisone 50 mg IV q8h then prednisolone 40-60 mg daily (onset: 3-
5 days; useful in haematological malignancy, vitamin D intoxication,
granulomatous condition).
7. Newer treatment:
 Denosumab (hypercalcemia associated with malignancy)
 Cinacalcet (secondary / tertiary hyperparathyroidism)
8. Consider haemodialysis with zero or low Ca dialysate

K7
Hypocalcaemia

Hints:
 Usually due to chronic renal failure, hypoparathyroidism, resistance to
PTH.
 Consider sequestration of calcium (acute pancreatitis, rhabdomyolysis,
tumour lysis syndrome); Vit D deficiency, medications (bisphosphonate,
cinacalcet).
 Rule out hypomagnesaemia
 Beware of pseudo-hypocalcaemia due to hypoalbuminaemia (check
corrected Ca or ionized Ca).

Investigations:
 Check RFT, Alb, ionized Ca level, PO4, ALP, Mg, PTH, Vit D, amylase,
CK, ECG

Rx:
Symptomatic hypocalcaemia:
 Correct hypomagnesaemia
 IV 10-20 ml 10% Calcium gluconate in 100 ml NS / D5 over 10-15
minutes then 20-30 mL 10% Ca gluconate in 500 mL NS / D5 q4-6h /
pint (~ 50 mg element Ca /hr)
 Monitor Ca level
- 10ml 10% Calcium gluconate contains 1000 mg of Ca gluconate (90
mg element Ca)
- 10% CaCl2 contains 3 times more element calcium than calcium
gluconate (27 mg/ml vs 9 mg/ml and higher osmolality: CaCl2 = 2000
mOsm/L vs Ca gluconate = 680 mOsm/L. It causes more irritation.)

Chronic cases: (Add Vit D if no response after 2-4g elemental Calcium)

1. Ca supplement:
 Caltrate = 600 mg elemental Ca / tablet
 Oscal = 250 mg elemental Ca / tablet
 Ca gluconate = 27mg elemental Ca / tablet
2. Vitamin D: Calcitriol/1-α hydroxycholecalciferol: 0.25-2 microgram daily
3. Correct hypomagnesemia

K8
Hypomagnesaemia

Hints:
 May be associated with hypoK, hypoCa, arrhythmia, seizure
 Due to increase renal loss or decrease GI absorption
 Common in chronic alcoholic
 Check concomitant medication use (cyclosporine, diuretics,
aminoglycoside, amphotericin B; proton-pump inhibitor)
 Check family history

Investigations:
 Check RFT, K, Ca, ECG
 24h urine Mg excretion or Fractional excretion (FE) of Mg
= 100 × (UMg × PCr) / (0.7 × PMg × UCr)

(If HypoMg, FE > 2% indicates renal loss of Mg)

Rx:
Emergency:
 4 mL 50% MgSO4 (2 g or 8 mmol) solution IV in 20 mL NS/D5 infused
over 15-30 min then 10 mL 50% MgSO4 (5 g or 20 mmol) in 500 mL
NS/D5 over 6 hours.

Less urgent cases:

 4 mL 50% MgSO4 (2g or 8 mmol) solution in 500 mL NS/D5 q6-8h for 1
day (up to 50% of the infused Mg will be excreted in urine; slow and
sustained correction of hypoMg is preferred; risk of hyper-Mg in patients
with renal insufficiency).

Chronic cases:
 Normal average daily intake of Mg ~15 mmoles (~1/3 is absorbed)
1. Mg supplement: Mylanta / Gelusil: 3.5 mmoles/tablet; Mg lactate 168
mg BD (better GI absorption).
2. Amiloride: 5-10mg daily PO (decreased urinary Mg loss)
3. Correct the underlying disease if possible e.g. diuretics / PPI

K9
Hypermagnesaemia

Hints:
 Uncommon in the absence of iatrogenic Mg administration or renal
failure
 May cause arrhythmia, hyporeflexia

Mild cases (<1.5 mmol/L) usually require no treatment.

Rx:
 Take off Mg supplement if any
 If symptomatic, 10% Calcium gluconate 10-20ml in 100mL NS over 15
minutes to antagonize the effect of Mg on the myocardium and
neuromuscular junction
 Saline diuresis: NS 300-500ml/hr infusion with furosemide 20-40mg q4h
(aim at urine output ~200mL/hr)
 Urgent haemodialysis if necessary

K 10
Hyperphosphataemia

Hints:
 Usually attributed to chronic renal failure or iatrogenic.
 May cause symptomatic hypocalcaemia
 Extracellular shift in tumour lysis syndrome, rhabdomyolysis,
haemolysis, acidosis

Usually resolved in 6-12 hours if renal function is normal

Investigations:
 RFT CaPO4CO2 ALP, PTH, Vit D

Rx:
1. Low phosphate diet.
2. In CKD patients, start phosphate-binder with meal: calcium containing
e.g. calcium carbonate, or non-calcium containing: e.g. Sevelamer,
Sucroferric oxyhydroxide. (Aluminium containing phosphate binder
should only be used as short term therapy).
3. Treat hyperparathyroidism.
4. Arrange dialysis if necessary.

K 11
Hypophosphataemia

Hints:
 Malabsorption, vitamin D deficiency
 Transcellular shift (insulin, refeeding syndrome, respiratory alkalosis)
 Hungry bone syndrome
 Increase urinary loss: primary hyperparathyroidism, increase
phosphatominins (FGF23), renal tubular defects (Fanconi syndrome)

Investigations:
 Check RFT serum Ca/PO4, ALP, Vit D, PTH
 Fractional excretion (FE) of phosphate:
FE = 100 × (Up × PCr) / (UCr × Pp)
(In the presence of hypoPO4, FE>5% indicates urinary loss)

Rx:
 Usually required no treatment if serum PO4 > 0.5 mmol/L. Rapid IV PO4
replacement may cause symptomatic acute hypocalcaemia
 Suggested rate of replacement ~0.08-0.16 mmol/kg per 6 hours

Mild hypophosphataemia (PO4 <0.5 mmol/L)

 Oral PO4 replacement (e.g. Sandoz-phosphate tab 1 four times a day PO)
(16 mmoles PO4; 20 mmoles Na; 3 mmoles K / per tablet)

If serum PO4 <0.3 mmol/L with symptoms:

 IV 6 ml (8.7 mmol PO4, 15 mmol K) Potassium phosphates (K2HPO4 +
KH2PO4) solution in 500 mL NS/D5 q6-12h infusion [Each 10 mL
Potassium phosphates contains 14.5 mmol PO4 + 25 mmol K]
 IV 10 ml (10 mmol PO4, 20 mmol Na) Glcophos in 500 ml NS/D5 over
6-12h infusion.
 Rapid IV replacement may cause acute symptomatic hypocalcaemia and
CaPO4 precipitation; switch to oral replacement when PO4 >0.5 mmol/L

Chronic therapy:
 Treat Vitamin D deficiency if present
 Sandoz-phosphate 1 tablet four times a day PO
 Dipyridamole 75mg three to four times a day (for renal phosphate
wasting)

K 12
Hyponatraemia

Hints:
 Rule out pseudohyponatraemia and hyperosmolar hyponatraemia. (Check
glucose, lipid, immunoglobulin level).
 Check history of prostatic surgery/uterine surgery
 Check medication history (thiazide, anti-depressants)

Investigations:
 RFT, LFT, uric acid, glucose, serum/urine osmolality, spot urine [Na],
spot urine [K], cortisol, thyroid function
 Calculate FE Na or FE uric acid (>17% suggestive of SIADH)

Isovolaemia:
 Urine Na > 20 mmol/L and urine osmo >100 mOsm/L: SIADH,
hypothyroid, Addison’s disease
 Urine Na < 10 mmol/L and urine osmo <100 mOsm/L: water
intoxication, primary polydipsia, beer potomania

Rx:
 Treat the underlying cause; discontinue culprit medication
 Correction of hypokalaemia
 Restrict water intake for SIADH (Calculate the {urine [Na] + urine [K] /
serum [Na]} ratio; free water loss if ratio <1)
- If (Urine Na +K)/ Serum Na < 0.5, restrict to 1L/day
- If (Urine Na +K)/ Serum Na 0.5-1.0, restrict to 500 ml/day
- If (Urine Na +K)/ Serum Na > 1, might need to consider additional
measures include loop diuretic, increase dietary solute load (NaCl
tab) or vasopressin antagonist
 For refractory cases of SIADH, consider Tolvaptan (Samsca) 7.5-15mg
daily (Beware of over-correction)

For acute symptomatic hyponatraemia (e.g. comatose, seizure):

 Consult ICU
 Close monitoring of serum [Na]
 Very cautiously give IV hypertonic saline (100 ml 3% hypertonic saline
(513 mmol/L) over 20 min or 50 mL 5.85% NaCl (1000 mmol/L) over
30 min
 Repeat if necessary until [Na] increase by 4-6 mmol/L or improvement in
symptoms
K 13
 For patients with severe symptoms, [Na] should be corrected 1-2
mmol/L/hr for 3-4 hours
 Correction should not be >8-12 mmol/L/24hr or >18 mmol/L/48hr to
avoid central pontine myelinolysis. (Consider to give D5 +/- DDAVP if
over-correction).
 Lower rate (4-6 mmol/24h) for patient with high risk of CPM
(alcoholism, liver disease, malnutrition, hypokalaemia, very low [Na] <=
105 mmol/L)

Adrogue formula
Change in serum Na with 1L of infusate = [(Infusate Na + infusate K) –
(serum Na)] / (TBW + 1)

Sodium concentration of commonly use IV fluid

Infusate Infusate Na (mmol/L)
5.85% NaCl 1000
3% NaCl 513
0.9% NaCl (NS) 154
Lactate Ringer’s 130
0.45% NaCl (½NS) 77
D5 0

K 14
Hypovolaemia
 Urine Na <10 mmol/L (FE Na < 1%): diarrhoea, vomiting, third space
fluid loss, dehydration, remote diuretic use
 Urine Na >20 mmol/L: diuretics, adrenal insufficiency, renal salt
wasting, bicarbonaturia

Rx:
 Use isotonic saline (NS) 500 mL/hr till BP normal then replace the
sodium deficit with saline / Na supplement
 Rate of correction should not be >8-12 mmol/L over 24 hrs
(Beware of rapid increase in [Na] after restoration to euvolaemic state)
 Sodium deficit: Na+ requirement (mmol)
= total body water (0.6 × BW) × (desired Na+ − serum Na+)

Hypervolaemia
 Urine Na <10 mmol/L: CHF, cirrhosis; urine Na >20 mmol/L: renal
failure

Rx:
 Treat the underlying cause
 Restrict water intake <1000 mL per day
 Furosemide 40-80mg IV / 20-500mg PO daily

K 15
Hypernatraemia

Hints:
 Investigations: Serum / urine osmolality, serum glucose, Na, K and Ca
 Check drug history e.g. lithium
 Urine osmolality <300 mOsm/L in hypernatraemia is suggestive of DI
 Estimate daily solute excretion (urine osmolality × urine volume) for
osmotic diuresis
 Check response to DDAVP to differentiate between central vs
nephrogenic DI

Hypervolaemia:
(Primary Hyperaldosteronism, Cushing’s syndrome, acute salt overload)
 Treat the underlying disorder
 Start D5 infusion to correct water deficit;
 Add furosemide 40-80 mg IV or PO q12-24h

Isovolaemia or Hypovolaemia:
(Diabetes insipidus, osmotic diuresis, large insensible water loss [sweat],
renal / GI loss)
 For haemodynamic unstable patient – Correct the volume status by
isotonic fluid
 Early administration of water via PO or RT if possible
 Replace fluid with D5 or ½:½ solution q6-8h; more rapid correction is
warranted for acute hypernatraemia.
 Rate of correction: <8-10 mmol/L in 24h. Rapid correction may lead to
cerebral oedema
 Body water deficit (L) = 0.6 × BW(kg) × {(measured [Na]-140)/140}
 Close monitoring of [Na] and glucose during treatment; correction of
hyperglycaemia if necessary.

For acute central DI: give DDAVP 4-8 microgram q4h prn;
For chronic central DI: DDAVP 10-40 microgram daily intra-nasally (in one
to two divided doses)
For chronic nephrogenic DI:
 Decrease sale and solute intake
 Thiazide diuretic, e.g. hydrochlorothiazide 25 mg daily, indapamide 2.5
mg daily; amiloride 5 mg daily for Li-induced DI

K 16
 SYSTEMATIC APPROACH TO THE ANALYSIS OF ACID-
BASE DISORDERS

1. History and P/E for causes of acid-base disturbance

2. Identify the primary acid-base disturbance
3. Assess adaptive response to primary acid-base disorder

Metabolic 10 response Adaptive response

Acidosis ↓HCO3 ↓pCO2: 1.6 kPa per 10 mmol/L ↓in HCO3
pCO2 = (1.5 × HCO3) + 8 ± 2mmHg
Alkalosis ↑HCO3 ↑pCO2: 0.9 kPa per 10 mmol/L ↑in HCO3
Respiratory
Acidosis ↑pCO2 Acute: 0.77 mmol/L
↑HCO3 per 1 kPa ↑pCO2
Chronic: 2.7 mmol/L
↑HCO3 per 1 kPa ↑pCO2
Alkalosis ↓pCO2 Acute: 1.5 mmol/L
↓HCO3 per 1 kPa ↓pCO2
Chronic: 3 mmol/L
↓HCO3 per 1 kPa ↓pCO2

Suspect mixed metabolic / respiratory acid-base disorder if compensation is

not appropriate (common in clinical practice!).

4. Calculate serum anion gap (Na-Cl-HCO3) to look for unmeasured anion

(normal 10±4) (Anion gap should be corrected for severe
hypoalbuminemia)
5. Calculate the osmolar gap for increase AG metabolic acidosis to look for
unmeasured osmoles (e.g. methanol, toxic alcohol ethylene glycol)
Osmolar gap = measured osmolarity – [2 × (Na+K) + urea + glucose]
(Normal <10)
6. For patients with acidosis:
Compare △AG with △serum HCO3 (abnormal if discrepancy >5):
 △AG > △serum HCO3: mixed metabolic acidosis / alkalosis
 △AG < △serum HCO3: mixed normal AG / ↑AG metabolic
acidosis

K 17
7. Measure urine electrolytes / pH:
a) For patients with metabolic alkalosis
 Urine Cl < 20 mmol/L – Chloride responsive metabolic alkalosis,
e.g. vomiting, chronic diuretic use
 Urine Cl > 20 mmol/L – Chloride resistant metabolic alkalosis,
e.g. Mineralocorticoid excess, alkali administration, severe
hypokalaemia during diuretic therapy.
b) For suspected renal tubular acidosis
 Urine anion gap: Na+K–Cl
(appropriate renal response in acidosis: negative)
 Urine osmolar gap: [urine osmolarity–2(Na+K)–urea–glucose]/2
(normal: >40)
- Abnormal value (< 30-40 mOsm/Kg/H2O) indicates low
ammonium excretion (inappropriate renal response to acidosis,
e.g. RTA)
- False positive conditions (large UOG): presence of unusual
anions in urine, e.g. ketone; toluene metabolites (such as
hippuric acid), drug anion, excessive bicarbonaturia, urine pH >
6.5
 Check urine pH (>5.3 for distal RTA)

Causes for High anion gap metabolic acidosis (MULEPAK-P)

M=methanol, U=uraemia, L=lactic acidosis, E=ethylene glycol
P=paraldehyde, A=aspirin, K=ketosis, P=pyroglutamic acid (panadol)

Causes for Normal anion gap metabolic acidosis (USEDCAR)

U=ureteroenterostomy, S=saline infusion, E=endocrinology e.g. Addison
D=diarrhoea, C=carbonic anhydrase inhibitor, A=ammonium chloride,
R=renal tubular acidosis

K 18
Therapeutic Options in patient with metabolic acidosis:

Hints:
 In order to avoid being misled by acute hyperventilation or
hypoventilation, plasma [HCO3] is, in general, a better guide to the need
of NaHCO3 therapy than systemic pH.

1. Treat the underlying cause (e.g. insulin for ketoacidosis, treat sepsis for
lactic acidosis, toxicology consultation for poisoning).

2. Correction of metabolic acidosis with NaHCO3

 Appropriate for normal AG metabolic acidosis (e.g. RTA, diarrhoea)
or for severe acidaemia (e.g. pH <7.1)
 NaHCO3 required (mmoles)
= (desired – measured HCO3) × BW(kg) × 0.5
 Give IV 8.4% NaHCO3 over 1-2 hours (1 mL = 1 mmol HCO3)
 Overcorrection may increase CO2 production, which can aggravate
respiratory acidosis in a poorly ventilated patient. Watch out for
hypercapnia which may cause paradoxical increase in acidaemia after
NaHCO3 therapy.
 Potential adverse effects: pulmonary oedema, hypokalaemia,
hypocalcaemia
 For chronic RTA, use oral NaHCO3 (300mg = 3.6 mmoles/ per tablet)
or K-Citrate
 For type IV RTA, correction of hyperkalaemia +/- fludrocortisone

3. Adequate Ventilation:
 If the patient with severe metabolic / respiratory acidosis is in
pulmonary oedema, one should consider ventilating the patient to
lower PCO2 appropriately to treat acidaemia.
 Acidaemia responses much faster to lowering the PCO2 than to IV
NaHCO3 therapy.

4. Dialysis: for patients with volume overload, poisoning, CKD

K 19
Therapeutic options in patients with metabolic alkalosis:

Hints:
 Metabolic alkalosis is a disorder caused by an initiation event whereby
[HCO3] is elevated; and a maintenance phase, e.g. hypovolaemia,
chloride depletion, hypokalaemia, hyperaldosteronism to maintain an
elevated [HCO3] level.
 Both processes must be corrected if possible, for an optimal response to
therapy.

Chloride-responsive metabolic alkalosis (urine chloride < 20 mmol/L):

 Give NS ± KCl to correct ECF volume;
 Give H2 antagonist /proton pump inhibitor if alkalosis is due to NG
suction;

Chloride-resistant metabolic alkalosis (urine chloride > 20 mmol/L):

 Treat the underlying cause;
 Block mineralocorticoid effect with potassium spring diuretic e.g.
spironolactone 100-400mg daily PO or amiloride
 Acetazolamide 250mg four times a day PO / IV for 4 doses (may
promote K loss) (Especially for fluid overload patient)

K 20
 PERI-OPERATIVE MANAGEMENT
IN URAEMIC PATIENTS

1. Assess fluid status, BP control, bleeding tendency.

2. Blood test (CBP, LRFT, CO2, chloride, Ca, PO4, clotting profile ± arterial
blood gases), CXR, ECG.
3. Consult renal team for need of peri-operative dialytic support
 HD: preferably 1 day before operation (pre-dilution / tight heparin).
 PD:
i) CAPD: Continue CAPD. Cap off Tenckhoff catheter and drained
out PDF for abdominal operation.
ii) APD: Consult renal team to adjust dialysis regime to CAPD, then
follow CAPD patients as above.
4. Transplant recipient: Continue usual dose of immunosuppressive agents.
Steroid cover for those patients on long term oral steroid.
5. Treatment of bleeding tendency: (arrange dialysis if necessary)

Onset
Dosage Remarks
time
Hct >30% might assist
Blood transfusion Correct anaemia
haemostasis
0.3 microgram/kg
(Octostim: 15 ug/ml) SC Tachyphylaxis
DDAVP or IV (in 50 ml NS over 1 hr typically develops
30 mins) 30 min before after the second dose
procedure
Cryoprecipitate 10 units 1 hr Major bleeding
FFP 5 units 1 hr Major bleeding
Conjugated
0.6 mg/kg IV daily for 5 For major surgery or
Oestrogen > 6 hr
days long lasting effect
(Premarin)

K 21
 RENAL FAILURE

Pre-renal cause:
 Hypotension, (effective) volume depletion, e.g. dehydration, cirrhosis,
congestive heart failure, sepsis, third space sequestration.

Post-renal cause:
 Urinary obstruction, stones, urethral obstruction, BPH.

Renal Cause:
 Rapidly progressive glomerulonephritis, vasculitis, acute tubular
necrosis, tubulointerstitial nephritis.

 Careful history taking (esp. drug history) can usually diagnose the
underlying problem.
 Exclude pre-renal cause: orthostatic hypotension
 Exclude post-renal failure: feel for bladder, bedside USG

Investigations:
 CBP, RLFT, CO2, Cl, Ca, PO4, amylase, urate, LDH, arterial blood gas,
CK;
 24 hr urine for Na K Cr, total protein;
(*Assessment of creatinine clearance/eGFR in non-steady state is not
reliable)
 FE Na / FE urea for pre-renal cause
 Autoimmune markers: ANF, Anti-DsDNA, Anti ENA, C3/4, ANCA,
anti-GBM,
 ASOT, cryoglobulin
 Ig pattern, Serum electrophoresis, free light chain, urine electrophoresis
 Spot urine for TP / Cr ratio, dysmorphic RBC, eosinophil
 MSU for microscopy, C/ST, cast
 HBsAg/Ab, anti-HBc, anti-HCV (Urgent HBsAg and anti-HCV if
haemodialysis is anticipated)
 HIV Ab
 CXR, ECG
 Urgent KUB, USG kidneys

K 22
Treatment of acute kidney injury:
1. Assess fluid status
 Fluid intake = 500 mL + volume of urine output; Assess any ongoing
loss
 Optimise pre-load: For hypovolaemia: Fluid challenge: Normal
saline (NS) or balanced crystalloid solution (Plasma-Lyte), 500-1000
mL over 1-2 hrs;
 For fluid overload: Add frusemide up to 80 mg IV bolus or 10 mg/hr
IV infusion;
 Consider to add metolazone 5-10 mg daily PO if refractory;
 Low dose dopamine is not recommended
2. Correct electrolyte disturbances: hyperkalaemia, hypocalcaemia,
hyperphosphataemia, metabolic acidosis
3. Low salt diet (<100 mmoles per day), low K (<20 mmoles/day), low
phosphate diet (<800mg day)
4. Strict I/O chart, daily body weight (<1kg increase in BW per day)
5. Avoid nephrotoxic drugs if possible, e.g. NSAID, aminoglycoside, etc.
6. Consider alternatives to radiocontrast procedures
7. Urgent indications for dialysis: refractory hyperkalaemia; refractory
metabolic acidosis where sodium bicarbonate is contraindicated;
refractory pulmonary oedema; uraemic pericarditis or encephalopathy
8. Treat the underlying disease; obstruction should be relieved if present
9. Consider renal biopsy to ascertain the cause of AKI if the cause is not
apparent

Treatment of chronic kidney disease / End stage kidney disease:

1. Consult nephrologist for assessment of feasibility of long-term renal
replacement therapy.
2. Avoid blood taking / BP measurement from AV fistula arm.
3. For HD patients - Monitor AV fistula function daily.
4. For CAPD patients - Monitor exit site condition and perform exit site
care daily
5. Advise fluid restriction, strict I/O chart, daily BW (<1kg increase in BW
per day).
6. Consult dietitian for Renal diet (low PO4, high biological value protein
diet)
7. Manage Calcium / phosphate disturbance
 Low phosphate diet + phosphate binders with meal
 Activated Vitamin D analogue (Rocaltrol / Alfacalcidol: 0.25-2
microgram/day (For secondary hyperparathyroidism) or Paricalcitol
K 23
  Correct hypocalcaemia with calcium / vit D
 Consider calcimemetic e.g. Cinecalcet according to guideline
indications
8. Control hypertension (<130/80 mmHg): long-acting calcium channel
blocker, ACEI/ARB, diuretic, beta-blocker, mineralocorticoid receptor
antagonist. (Monitor for hyperkalaemia for ACEI/ARB/MRA).
9. Correct metabolic acidosis with NaHCO3.
10. Consider sodium-glucose cotransporter-2 inhibitor (SGLT2i) in CKD
patients according to latest guideline indications. (Once initiated,
SGLT2i can be continued unless it is not tolerated or renal replacement
therapy has been commenced.)
11. Manage hyperkalaemia e.g. resonium/ sodium zirconium cyclosilicate
12. Symptomatic anaemia:
 Erythropoietin stimulating agent (e.g. Darbepoetin, Mircera) for
refractory anaemia
 Replete iron if iron deficiency
 Blood transfusion when symptomatic
- Haemodialysis: transfuse pack cell preferably during dialysis
- Peritoneal dialysis: transfuse pack cell with extra PD fluid cover,
e.g. 4.25% over 2 hours during each unit of pack cell
- CKD with residual urine: give Lasix 20-80mg IV before
transfusion

Refer to reference:
KDIGO 2022 Clinical Practice Guideline For Diabetes Management in
Chronic Kidney Disease
https://kdigo.org/wp-content/uploads/2022/10/KDIGO-2022-Clinical-
Practice-Guideline-for-Diabetes-Management-in-CKD.pdf

K 24
 EMERGENCIES IN RENAL TRANSPLANT PATIENTS
Fever:
Both infection and acute graft rejection can present as fever
a) Infection:
 Can be very subtle and atypical in presentation
 Consider opportunistic infection if <6 months post-transplant
 Usual pattern of infection if >6 months post-transplant
 Search for infection: History, physical examination, culture from wound, urine,
IV lines, sputum, blood, viral culture & serology, AFB, fungal culture
 Check blood for CMV pp65 antigen / CMV DNA, particularly if deranged LFT,
neutropenia or thrombocytopenia
 Check CBP D/C, RLFT, immunosuppressant trough level [Cyclosporin A (CsA)
/ Tacrolimus (FK) / sirolimus / everolimus]
 Avoid macrolide antibiotics / fluconazole (may increase CsA / Tacrolimus level)

b) Acute graft rejection:

 Acute increase in serum creatinine >20% after excluding other causes
 May present as ankle oedema, oliguria, graft tenderness, sudden onset
hypertension, fever, haematuria. Can also be asymptomatic.
 Check CBP, RLFT, CO2, CaPO4, clotting profile, immunosuppressant trough
level, MSU for routine microscopy and culture sensitivity test, urine for decoy
cell, blood and urine for BK virus DNA, CMV pp65/ CMV DNA
 Check G6PD if not done
 Arrange urgent USG graft kidney + graft Doppler study;
 Consider early renal biopsy

Oligouria / Anuria:
 DDx: Acute graft rejection
Acute calcineurin inhibitor toxicity*
Obstructive uropathy
Urinary leakage
Acute tubular necrosis
Acute vascular (arterial or venous) kinking / thrombosis
 Treatment according to the cause
 Check CBP, RLFT, immunosuppressant (CsA / tacrolimus / sirolimus / everolimus)
trough level*, MSU RM C/ST, 24 hr urine for P/Cr
 Save drain fluid for urea and creatinine if suspect urine leakage
 Strict I/O chart, hourly urine output +/- Foley catheter insertion.
 Urgent USG graft kidney + Doppler study
 Arrange standby MAG-3 / DTPA scan
 Early Graft renal biopsy for acute rejection

*Acute gastroenteritis can cuase abrupt increase of calcineurin inhibitor drug level.

K 25
 DRUG DOSAGE ADJUSTMENT IN RENAL FAILURE

Refer to Reference Database in eKG e.g. Lexicomp (in UpToDate) and

Micromedex

Consult pharmacist

Estimation of Creatinine Clearance / estimated glomerular filtration rate

(eGFR)
 CKD-EPI:
- Recommended method for estimating GFR in adults.
- Estimates GFR from serum creatinine, age, sex, and race
- Expressed as mL/min/1.73 m2

 Cockcroft-Gault formula
CrCl (ml/min) = [(140 – Age) × BW (kg)] / [0.82 × Cr (umol/l)]
** value × 0.85 for women

Common Drugs requiring dosage adjustment

Augmentin Allopurinol Atenolol Entecavir
Tazocin Colchicine Valganciclovir
Cefepime Cyclophosphamide Pregabalin Tenofovir
Ceftazidime Gabapentin Acyclovir
Cefotaxime Tramadol
Cefuroxime Transamin
Cefazolin
Vancomycin
Levofloxacin

Common Drugs not requiring dosage adjustment in Renal Failure

Barbiturates Benzodiazepines Bromocriptine Cefoperazone
Ceftriaxone Cholestyramine Cloxacillin Diltiazem
Erythromycin Furosemide* Heparin Ketoconazole
Levodopa Lignocaine Minoxidil Nifedipine
Nitrates Prazosin Propylthiouracil Quinidine
Na valproate Steroids Warfarin Theophylline
Verapamil

*usually need a higher dose

K 26
Drug interaction with calcineurin inhibitor (tacrolimus, cyclosporine)

Increase drug level:

Imidazole Ketoconazole, fluconazole, itraconzole,
Voriconazole
Macrolide Erythromycin, clarithromycin
Calcium Channel blocker Diltiazem, verapamil
Anti-viral drugs Lopinavir, ritonavir, indinavir, darunavir,
ombitasvir-paritaprevir-ritonavir, Viekira Pak
Letetmovir
Grapefruit juice

Decrease drug level:

Anti-TB drugs Rifampicin
Anti-convulsants Phenytoin, phenobarbital, carbamazepine
Anti-viral drugs Efavirenz, etravirine
Lipid lowering drugs Cholestyramine
Sulfamethoxazole
St. John’s Wort
Rifabutin

Additive nephrotoxicity / toxicity:

Aminoglycoside
Amphotericin B
NSAID
Sirolimus
Colchicine
Sulphonamide / trimethoprim

Others:
Hyperkalaemia with ACEI, K-sparing diuretics, NSAID
Myopathy / rhabdomyolysis with HMG-CoA reductase inhibitor, colchicine

K 27
 PROTOCOL FOR TREATMENT OF CAPD PERITONITIS
(BASED ON RECOMMENDATION OF ISPD, 2022)

Definition of CAPD related peritonitis:

 At least 2 of the following are present:
- Clinical features consistent with peritonitis, i.e. abdominal pain and/or
cloudy dialysis effluent;
- Dialysis effluent white cell count >100/mm3 or >0.1×109/L (after a
dwell time of at least 2 hours), with >50% polymorphonuclear;
- Positive dialysis effluent culture
 In APD, use 50% polymorphonuclear count instead of absolute effluent
WCC

1. When symptoms of peritonitis appear in a patient treated with peritoneal

dialysis:
 Send dialysis fluid for absolute white cell count (WCC), Gram smear
 Rapid flush 3 bags of PDF with heparin 500 units/L for symptomatic
relief
 Prescribe adequate analgesia (e.g. Panadol ± tramadol)
 Increase to 4 exchanges per day to improve ultrafiltration
 Add IP heparin: 500-1000 units/L into PDF until S/S subsided or until
fibrin clots no longer visible

2. Empirical antibiotic treatment

 Empiric antibiotics must cover both Gram-positive and Gram-negative
organisms.
 Gram-positive organisms may be covered by vancomycin or a first-
generation cephalosporin, and
 Gram-negative organisms by a third/fourth-generation cephalosporin
(ceftazidime, cefepime), aminoglycoside or carbapenem
 IP antibiotic should dwell for at least 6 hours
 Consider Nystatin oral suspension 5ml (0.5 MU) four times a day
during antibiotic treatment to prevent Candida peritonitis
 Adjuvant oral N-acetylcysteine therapy, 600mg bd, may help to prevent
aminoglycoside ototoxicity

K 28
Examples: CAPD intermittent dosing method

A. Loading dose:
Cefazolin 1 gram + Ceftazidime (Fortum) 1 gram loading IP
Maintenance dose:
Cefazolin 1 gram + Ceftazidime (Fortum) 1 gram into last bag daily

B. Loading dose:
Cefazolin 1 gram and Amikacin 125 mg IP (or 2 mg/kg/day) as loading
dose
Maintenance dose:
Cefazolin 1 gram and Amikacin 125 mg IP (or 2 mg/kg/day) into last bag
Subsequent antibiotic treatment:
Step down antibiotics regime according to sensitivity once culture and
sensitivity result available

K 29
 Organism /
Antibiotics duration and special
Specific Types
remarks
Peritonitis
Gram +ve Corynebacterium At least 14 days
organisms species
Enterococcus At least 21 days
species
Staphylococcus At least 21 days
aureus (MSSA) Substitute vancomycin with Cefazolin
to avoid emergency of VRE
Consider adding rifampicin PO
(450mg daily for <50kg; 600mg daily
for >50kg) for 5-7 days as an adjunct
for the prevention of relapse or repeat
peritonitis
MRSE or MRSA If vancomycin is used (either IP or IV,
1 gram every 5-7 days), check
vancomycin trough aiming 15-20
ug/ml
At least 3 weeks
Other gram +ve At least 14 days
Gram –ve SPICE (Serratia, Give 2 different antibiotics acting in
organisms Pseudomonas different ways that organism is
Indole-positive sensitive to (e.g. IP amikacin + IP
organisms e.g. ceftazidime) for 21 days
Proteus &
Providentia,
Citrobacter &
Enterobacter)
Pseudomonas or Give 2 different antibiotics acting in
Stenotrophomonas different ways that organism is
sensitive to (e.g. PO septrin + PO
levofloxacin for stenotrophomonas);
Duration: 21-28 days

K 30
 Organism /
Antibiotics duration and special
Specific Types
remarks
Peritonitis
Other gram -ve At least 21 days
Poly- Mixed Gram Antibiotics of choice:
microbial positive / Gram Carbapenem/Tazocin or antibiotics
Peritonitis negative or mixed according to sensitivity
Gram negative Duration: 21-28 days (depending on type
organisms of organisms, see above)
Consider further workup of intra-
abdominal pathology
Mixed Gram Antibiotics according to sensitivity result
positive organisms Duration: 21 days (depending on type of
organisms, see above)
Culture If response to initial antibiotics, keep the
negative same regime for 14 days
peritonitis If refractory peritonitis, consider further
workup to rule out mycobacterium
peritonitis, fungal peritonitis or other
non-infectious causes
Fungal Empirical treatment for fungal
peritonitis peritonitis: Amphotericin B 30mg /
200ml D5 IV infusion over 6 hours daily
Duration: at least 14 days after catheter
removed

3. If patient has evidences of septicaemia, admit patient and give parenteral

antibiotics
4. Change antibiotics later according to c/st result and adequate duration of
antibiotics
5. Repeat PDF for absolute WCC and Gram smear, culture on day 3-5 after
started or changed antibiotics with reassessment of S/S.
6. If clinically responds to medical therapy, repeat PDF for absolute WCC and
Gram smear, culture after completion of all antibiotics.
7. Arrange transfer set change when post treatment culture come back to be
negative with WCC <100/mm3
8. Search for underlying reversible causes for peritonitis
9. For refractory peritonitis:
 Arrange early removal of Tenckhoff catheter
 Continue appropriate antibiotics for 2 weeks after catheter removal
 Consider re-insertion of catheter at least 2-3 weeks after removal of
catheter
K 31
 PROTOCOL FOR TREATMENT OF
CAPD EXIT SITE INFECTIONS
(BASED ON RECOMMENDATION OF ISPD, 2017)

Exit site infection:

 Purulent discharge from exit site

Treatment:
1. Equivocal exit site infection
 Chlorhexidine dressing TDS
 Consider local treatment in appropriate case: e.g. 0.1% Gentamycin cream,
2% mupirocin cream to exit site wound TDS

2. Exit site infection (ESI)

 Take exit site swab for microscopy and culture
 Empirical treatment depends on clinical appearance of the exit site
 Oral penicillinase-resistant penicillin (Cloxacillin 500-1000 mg four times
a day) or a first generation cephalosporin (Cephalexin 500mg Q24h) for 14
days if Gram positive organism was suspected.
 Oral fluoroquinolones e.g. levofloxacin 250mg daily (or 500mg alternate
day) po for 14 days if Gram negative organism was suspected. Treatment
for at least 3 weeks is probably necessary for exit site infection caused by
Pseudomonas aeruginosa. Two different kinds of antibiotics of different
classes may be necessary in treatment of Pseudomonas aeruginosa ESI.
 Change antibiotics regime according to culture and sensitivity result once
available.
 For slowly resolving or severe S. aureus exit site infection, add Rifampicin
450mg daily.
 For Gram –ve organisms, if no improvement, parenteral antibiotics may be
needed.
 If ESI + peritonitis: arrange early removal of Tenckhoff catheter.
 Consult nephrologist for assessment if ESI persist before further courses of
antibiotics.
 Refractory ESI:
- For double-cuffed Tenckhoff catheter, consider shaving of external cuff
if the external cuff is eroded and extruded.
 Recurrent ESI:
- Counsel on personal hygiene, review exit site care, avoid excessive
traction on TC.
- Screen for carrier of drug-resistant organisms (e.g. nasal swab for
MRSA) and consider decolonization if appropriate.

K 32
 PERITONEAL DIALYSIS

Relative contraindications to peritoneal dialysis:

1. Severe bleeding tendency
2. Multiple lower abdominal scare, recent abdominal surgery
3. Suspicion of abdominal pathology
4. Respiratory failure
5. Pleuro-peritoneal leak
6. Aortoiliac graft
7. Burns of other hypercatabolic state or life-threatening hyperkalaemia (not
efficient enough)

Preparation for Tenckhoff Catheter Insertion

1. Give laxatives the night before T.C. insertion
2. Correct anaemia
3. Consider DDAVP to correct bleeding tendency
4. Antibiotics prophylaxis (optional):
Regime 1: Cefazolin 1g iv
Regime 2: Vancomycin 1g in 100ml NS, infuse over 1 hour if allergic
to penicillin / cephalosporin
5. Empty urinary bladder before Catheter insertion

K 33
Neurology
 COMA

 A medical emergency characterized by the absence of arousal and

awareness.
 Timely identification and treatment of reversible cause can be life-
saving.
 Mechanisms:
- Structural brain lesion.
- Diffuse neuronal dysfunction.
- Psychiatric (rare).
 Approach:
- Please refer to the flow chart.

Absent Responsiveness
Verbal cue/handclap → tactile stimuli (face) →
Noxious stimuli
Exclude feigned / functional unresponsiveness
(resistance to eyelid opening, hand drop test)

Initial Stabilization
ABC, O2, intubation, IV access, saline for # Thiamine 200-500mg IV (refer
to “Wernicke’s Encephalopathy”
hypotension, treat hypoglycaemia (thiamine#
for pre-disposing factors)
with dextrose for patients at risk of WE), C-
spine immobilization until trauma excluded,
§ Naloxone 0.4mg to 2mg IV stat,
head of bed, Naloxones§ if opioid toxicity
then every 2 min prn up to 10mg
suspected

History taking Sudden Onset: stroke, seizure,

poisoning, cardiac event
Onset, past health, drug history, alcohol and
illicit drug use, environmental toxin exposure, Gradual Onset: mass, metabolic,
trauma, seizure, cardiac arrest inflammation, infection

General Exam
BP, P, RR, Temp, skin (dry/sweating, pigmentation, purpura/petechiae, bulla, needle
marks), signs of trauma, breath odour, tongue laceration, goitre, stigmata of chronic
liver disease, bowel sounds, meningismus

N1
 Neurological Exam Oculocephalic reflex can only be
Level of consciousness: GCS performed if there is no suspicion of
cervical trauma / instability.
Motor: spontaneous movement, posturing,
response to verbal command and noxious Vestibulo-ocular reflex can only be
stimuli, Test both sides for localization to pain performed after disease / trauma to
Brainstem: papillary response, corneal reflex, the external auditory canal and
oculocephalic reflex, Vestibule-ocular reflex, tympanum has been ruled out.
gag reflex, cough reflex, eye movement
Breathing pattern
Fundoscopy: subhyaloid haemorrhage,
papilloedema

Laboratory Testing
When there is a high suspicion of
CBP, LRFT, Ca2+, coagulation profile, glucose,
bacterial meningitis, take blood
ABG/VBG, cortisol, thyroid function, culture, give meningitic dose of
ammonia, cultures of blood & urine, antibiotics and dexamethasone
toxicology, CXR, ECG CT brain immediately if before CT and LP.
structural cause (local exam), traumatic cause
or diagnosis uncertain.
Other Ix in selected patients: MRI/MR
venography, CT angiography LP, ECG, EEG,
alcohol, lactate, ketones, osmolality, anti-
convulsant level, co-oximetry

N.B. “head of bed”: 30 degrees for raised ICP; Flat for posterior circulation
stroke

Supportive Care
a) Close monitoring of vital signs and neurological status
b) Proper positioning and turning to avoid aspiration, pressure nerve palsy,
contracture, pressure sore
c) Bladder catheterization
d) Adequate hydration, oxygenation and nutrition
e) Chest and limb physiotherapy
f) Hypromellose eyedrops and secure eyelids if no spontaneous blinking

N2
Prognostication of comatose survivors after cardiac arrest (≥72 hours
after ROSC)
a) Exclusion of confounders (such as residual sedation)
b) Step one: Absence of one or both of the following criteria means poor
outcome highly likely:
i) Pupillary and corneal reflexes
ii) Bilateral N20 SSEP wave
c) If the criteria of step one is not fulfilled, then wait and observe for ≥24
hours before proceeding to step two.
d) Step two: Presence of two out of four of the following criteria indicates
that a poor outcome is likely:
i) Status myoclonus ≤48 hours after ROSC
ii) Unreactive burst-suppression or status epilepticus on EEG
iii) Diffuses anoxic injury on CT / MRI brain
iv) High neuron specific enolase (NSE) level
e) If none of these criteria are met, then continue to observe and re-evaluate.

N3
 DELIRIUM
(Also refer to page PM 10-11 in Palliative Medicine)

An acute neuropsychiatric syndrome characterised by global cognitive

dysfunction and inattention. The diagnosis is clinical, based on bedside
observation. In the elderly, delirium is a common (and often sole)
manifestation of acute illness. It is not always transient and reversible and can
lead to long-term cognitive changes and mortality.

DSM V Diagnostic Criteria

 Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and
shift attention) and awareness.
 Disturbance in cognition (e.g., memory deficit, disorientation, language,
visuospatial ability, perception).
 The disturbance develops over a short period (usually hours to days) and
tends to fluctuate during the course of the day.
 Not better accounted for by another pre-existing, established, or evolving
neurocognitive disorder and do not occur in the context of a severely
reduced level of arousal, e.g., coma
 There is evidence from the history, physical examination, or laboratory
findings that the disturbance is caused by a direct physiologic consequence
of another medical condition, substance intoxication or withdrawal,
exposure to a toxin, or multiple aetiologies.

Other Associated Features: psychomotor disturbances (hyperactive,

hypoactive and mixed), altered sleep-wake cycle, emotional disturbances.

Evaluation according to the clinical presentation

a) History and physical examination: Drug history, features of infection,
dehydration, constipation / urinary retention, recent change of environment,
history of chronic alcohol use, underlying medical history such as dementia
/ depression, features of autoimmune encephalitis such as lip smacking.
b) Investigations: CBP, ESR, RFT, LFT, Ca2+, thyroid function test, blood
glucose, ABG, urine analysis and culture, blood culture, ECG, CXR.
c) In selected cases: CRP, troponin, serum B12, folate, syphilis serology, HIV,
autoantibodies, Mg, ammonia, cortisol, lumbar puncture, toxicology screen,
urinary porphyrins, EEG, CT brain, blood and CSF for NMDA and
autoimmune encephalitis panel.

N4
Management
a) Prevention: orientation; early mobilization; visual and hearing aids; avoid
dehydration, psychoactive drugs and sleep deprivation.
b) Identify and treat underlying causes (often multifactorial).
c) Review medications and remove potential harmful drugs:
 Neuroleptics, benzodiazepines, opioid analgesics, antihistamines, anti-
cholinergics, tricyclic antidepressants are medications with known
delirium potentials.
d) Protect airway, fluid and electrolytes balance, adequate nutrition and
vitamins, mobilization to prevent VTE, skin and bedsore care, avoid
physical restraints and Foley catheters.
e) Reassuring supportive nursing care in well illuminated, quiet places.
Normalize sleep-wake cycle.
f) Reserve pharmacologic management to agitated patients at risk of causing
harm to themselves or others.
 Low dose haloperidol 1 – 3mg daily in divided dose.
*Haloperidol should be avoided in patients with Parkinson’s disease
(PD) because the drug can result in dopamine blockade, which can
worsen the pre-existing PD.
 Atypical antipsychotics (such as quetiapine) as alternatives.
 Lorazepam (second line agent): for withdrawal from alcohol/sedatives.

Reference:
NICE guideline 2019: Delirium: Prevention, diagnosis and management

N5
 DELIRIUM TREMENS

 Characterised by hallucinations, agitation, confusion, disorientation and

autonomic overactivity including fever, tachycardia and profuse
perspiration in the setting of acute reduction or abstinence from alcohol.
 Typically occurs 24 – 48 hours after the last drink and lasts one to five
days.
 Associated with a mortality of up to 5%.
 Diagnosis based on clinical features and exclusion of other causes of
delirium.
- DSM-V Criteria for withdrawal delirium (Delirium Tremens):
1. Criteria for alcohol withdrawal:
 Cessation of or reduction in heavy and prolonged use of alcohol
with at least 2 of 8 possible symptoms after reduced use of
alcohol: autonomic hyperactivity, hand tremor, insomnia, nausea
/ vomiting, transient hallucinations / illusions, psychomotor
agitation, anxiety, generalised tonic-clonic seizures AND
2. Criteria for delirium (see the diagnostic criteria in the section of
delirium N4-5)

Management
1. General supportive care
2. Monitor BP/P, I/O, To, cardiac rhythm
3. Correct fluid and electrolyte disturbance. Watch out especially for
hypomagnesaemia, hypokalaemia, hypoglycaemia and rhabdomyolysis.
4. Treatment with benzodiazepine (according to the disease severity with
Clinical Institute Withdrawal Assessment for Alcohol, Revised [CIWA-Ar])
to treat psychomotor agitation.

Electronic CIWA-Ar calculator is available.

(https://www.mdcalc.com/calc/1736/ciwa-ar-alcohol-withdrawal)

N6
 0 1 2 3 4 5 6 7
Constant nausea,
1. Nausea and No nausea and Mild nausea and no Intermittent nausea with
frequent dry heaves and
vomiting vomiting vomiting dry heaves
vomiting

No visible, but can

Moderate, with patient’s Severe, even with arms
2. Tremor No tremor be felt fingertip to
arms extended not extended
fingertip

Barely perceptible
3. Paroxysmal Beads of sweat obvious
No sweat visible sweating, palms Drenching sweats
sweats on forehead
moist

Equivalent to acute panic

Moderately anxious, or
states as seen in severe
4. Anxiety No anxiety, at ease Mild anxious guarded, so anxiety is
delirium or acute
inferred
schizophrenic reactions

Paces back and forth

Somewhat more than Moderately fidgety and during most of the
Normal activity

N7
5. Agitation
normal activity restless interview, or constantly
thrashes about

Very mild itching, Mild itching, pins Moderate itching,

6. Tactile Moderately severe Severe Extremely severe Continuous
None pins and needles, and needles, burning pins and needles,
disturbances hallucination hallucinations hallucinations hallucinations
burning or numbness or numbness burning or numbness

7. Auditory Very mild harshness Mild harshness or Moderate harshness Moderately severe Severe Extremely severe Continuous
Not present
disturbances or ability to frighten ability to frighten or ability to frighten hallucination hallucinations hallucinations hallucinations

8. Visual Moderately severe Severe Extremely severe Continuous

Not present Very mild sensitivity Mild sensitivity Moderate sensitivity
disturbances hallucination hallucinations hallucinations hallucinations

9. Headache, Not present Very mild Mild Moderate Moderately severe Severe Very severe Extremely severe
fullness in head
10. Orientation and Oriented and can Cannot do serial Disoriented for date Disoriented for date Disoriented for place / or
clouding of additions or is by no more than 2 by more than 2
do serial additions person
sensorium uncertain about date calendar days calendar days
 Mild alcohol withdrawal syndrome (CIWA-Ar < 8): Can be treated with
supportive care ONLY; Benzodiazepine may not be required.
 Moderate to severe withdrawal syndrome (CIWA-Ar ≥ 8): Can be treated
with either:
 Treatment choices: Benzodiazepines - Diazepam / Lorazepam
 Adjust dose according to severity. Reduce dose in elderly. Taper dosage
gradually over 5 – 7 days.

5. Concurrent use with IV thiamine. Give high dose thiamine in IV form, e.g.,
100mg IV q8h.
6. Ensure adequate nutrition and vitamins.
7. Watch out for and treat any concurrent illnesses such as head injury,
subdural haemorrhage, intoxication of drugs (such as anti-depressants,
lithium, and illicit drugs).
8. Regular monitoring ± titration of treatment according to symptom severity
is advised.
9. Reassuring nursing care in well-illuminated, quiet places.

N8
 WERNICKE’S ENCEPHALOPATHY

 An acute or subacute neuropsychiatric disorder due to thiamine (Vitamin

B1) deficiency.
 Delayed diagnosis and treatment can lead to irreversible brain damage
(Korsakoff’s syndrome) and fatal outcome.
 The classical triad ophthalomoplegia, ataxia and confusion occur only in
15 – 30% of patients.
 Difficult to differentiate from acute alcohol intoxication → low threshold
for use of high dose IV thiamine.

Caine’s Criteria in Alcoholics

2 of the following 4 signs:
- Dietary deficiency
- Oculomotor abnormalities
- Cerebellar dysfunction
- Either an altered conscious state or mild memory impairment

Predisposing Factors
 Alcoholics plus malnutrition
 GI surgery including bariatric surgery
 Repeated vomiting including hyperemesis gravidarum
 Cancer
 Systemic illnesses (renal failure on CAPD or HD, AIDS, prolonged
infectious diseases, thyrotoxicosis)
 Dietary restriction e.g., anorexia nervosa, elderly neglect

Investigations
WE is a clinical diagnosis which requires high index of suspicion
 No laboratory studies that are diagnostic of WE
 EEG and CSF are normal or non-specific
 MRI brain may show lesions over midbrain, thalamus and mammillary
bodies. Mammillary body atrophy may appear later in the course.
 A low pre-treatment RBC transketolase activity may support the diagnosis
of WE but normal value could not exclude WE.
 Check serum magnesium as well (a co-factor for normal functioning of
thiamine-dependent enzymes).

N9
Management
 Oral thiamine is poorly absorbed and ineffective
 Use high dose IV thiamine
 Can consider high dose intravenous thiamine up to 500mg thiamine in
100ml normal saline or 5% dextrose over 30 minutes 3 times/day for 2
days.
 If improved, followed by 250mg thiamine IV/IM daily for 5 days, or until
improvement ceased.
 Thiamine must be given before any carbohydrate.
 Resuscitation facilities and adrenaline for rare occurrence of anaphylaxis.
 Monitor BP/P and temperature (hypo-/hyperthermia, hypotension and
tachycardia can occur).
 Monitor neurological signs (ophthalmoplegia can be resolved within
hours).
 Correct any hypomagnesaemia
 Balanced diet
 Treat any concurrent illnesses (e.g., delirium tremens, hepatic
encephalopathy, sepsis).
 Continue oral thiamine as long as the patient is still considered at risk.
 If ophthalmoplegia persists after few days of treatment of thiamine,
consider other pathologies.

N 10
 ACUTE STROKE

It is essential to identify site, subtype, cause and risk factors of stroke.

1. Admit to designated acute stroke unit.

2. Initial assessment: vital signs including airway, respiration,

haemodynamics, conscious level & neurological impairment.

3. Investigations: Urgent non-contrast CT brain, CBP, R/LFT, PT, aPTT,

blood glucose, lipid, CXR, ECG.

4. Special Investigations (in selected cases): Magnetic resonance imaging

(MRI), Magnetic resonance angiography (MRA), Computer tomography
angiography (CTA), Computed tomography venography (CTV),
Echocardiography, Duplex study of carotid arteries, Transcranial Doppler
(TCD), Cerebral angiography, VDRL, Thrombophilia assessment and
autoimmune screening

5. Supportive management:
a) Regular monitoring of neurological and vital signs
b) Swallowing assessment before feeding, positioning ± splinting to
avoid aspiration, contractures, pressure nerve palsy, shoulder
subluxation, pressure sores, etc.
c) Ensure good hydration, nutrition and oxygenation
d) Meticulous control of blood sugar & pyrexia
e) Cautious and gradual lowering of blood pressure
 In ischaemic stroke, lowering of blood pressure is considered:
- When the systolic blood pressure >220 mmHg, or the diastolic
blood pressure is >120 mmHg, according to repeated
measurements 20 minutes apart.
- When thrombolytic therapy is considered/given (BP should be
kept <180/105 mmHg within the first 24 hrs post thrombolytic
therapy).
- In case of hypertensive emergencies (e.g., hypertensive
encephalopathy, aortic dissection, acute renal failure, acute
pulmonary oedema or acute myocardial infarction).
 In haemorrhagic stroke, lowering of blood pressure is considered:
- If systolic blood pressure is between 150 and 220 mmHg, acute

N 11
 lowering of systolic BP to a target of 140 mmHg is safe and may
improve functional outcome, unless there is clinical evidence of
increased ICP.
- If systolic blood pressure >220 mmHg, the optimal blood
pressure target has not been well studied. Though it may still be
reasonable to consider aggressive reduction of BP with a
continuous intravenous infusion with frequent BP monitoring,
unless there is clinical evidence of increased ICP.
- In patients with spontaneous ICH in whom acute BP lowering is
considered, initiating treatment as early as possible to reach BP
target within one hour can be beneficial to reduce the risk of
haematoma expansion and improve functional outcome.
f) Seizures should be treated promptly but prophylactic anticonvulsant is
not indicated.
g) Early allied health therapists’ referral and assessment.

6. Specific therapy:
Ischaemic Stroke
a) Antiplatelet therapy:
 Aspirin 80mg to 300mg po STAT dose. It should be withheld for
the first 24 hrs if thrombolytic therapy was given.
 (If the patient is allergic to aspirin, can give clopidogrel – a loading
dose of 300mg STAT if the patient is clopidogrel naïve, followed by
75mg daily.)
 Dual anti-platelet therapy with aspirin and clopidogrel may be
considered in high-risk TIA or minor stroke patients on individual
basis, preferably for a short course of 3 weeks.
b) Thrombolytic therapy ± mechanical thrombectomy: inform the
thrombolysis team immediately for urgent evaluation for intravenous
thrombolysis ± mechanical thrombectomy if a potential candidate is
identified (see protocol for individual hospital for details).
 Usual indication for intravenous thrombolysis:
o Ischaemic stroke onset within 3 to 4.5 hours
o Good premorbid function
 Usual contraindication for intravenous thrombolysis:
o Presence of extensive early infarct changes or intracranial bleed
noted on CT
o Active internal bleeding
o Use of warfarin with INR > 1.7
o Use of therapeutic dose of LMWH within 24 hours
N 12
 o Use of Anti-Factor Xa inhibitor DOACs within 24 hours
o Clinical presentation suggestive of SAH
 High risk conditions for intravenous thrombolysis (to discuss case
by case with neurology team)
o Prior intracranial haemorrhage
o Any intracranial surgery, serious head injury or previous
ischaemic stroke within 3 months
o Known intracranial AVM or aneurysm
o Use of Anti-Factor Xa inhibitor DOACs within 24–48 hours
 For patients on Dabigatran
o Who are candidates for mechanical thrombectomy: can proceed
directly to endovascular therapy without giving Idarucizumab or
intravenous thrombolysis.
o Who are NOT candidates for mechanical thrombectomy, but are
candidates for intravenous thrombolysis: Idarucizumab 5g IV
bolus STAT dose can be given for reversal of Dabigatran’s effect,
followed by thrombolysis.
 Mechanical thrombectomy (if service provision is available, see
protocol for individual hospital for details).
o Ischaemic stroke onset within 6 hours time window
o Large vessel occlusion presentation and confirmed on CTA
o Good premorbid function
o (Patients with bleeding diathesis may still be candidates for
mechanical thrombectomy despite being contraindicated for
intravenous thrombolysis)
c) Immediate anticoagulation may be considered for acute ischaemic
stroke in:
 Documented cardiac source of embolism (e.g., LV thrombus)
 Cerebral venous thrombosis
 Extracranial carotid or vertebral arterial dissection
Contraindications and precautions
 e.g., BP > 180/110 mmHg, large infarct
 The use of anti-coagulation in acute stroke due to large artery
thrombosis is controversial.
d) Decompressive Hemicraniectomy: urgently consult neurosurgeon to
consider decompressive surgery in patients with malignant MCA
syndrome (massive MCA territory infarct with eye deviation, dense
hemiplegia and progressive drowsiness ± unequal pupil size. Serial CT
will show significant infarct with swelling and midline shift).

N 13
 Intracerebral Haemorrhage
a) Urgent reversal of warfarin effect: for patients with elevated INR due
to warfarin:
 Give vitamin K1 5 to 10mg IV
 Give prothrombin complex concentrate (PCC) 25 to 50 units/kg ±
FFP (see protocol of individual hospital for details)
- If the PCC available in the hospital is a 4-factor PCC (e.g.,
Beriplex), FFP is not needed.
- If the PCC available in the hospital is a 3-factor PCC (e.g.,
Prothombinex-VF), may consider supplementing with FFP.
- Recheck INR about 15 minutes after PCC is given. If INR is still
>1.3, give additional PCC and recheck INR afterwards.
 Give FFP as soon as possible if PCC is not available.
 (PCC can reverse warfarin effect much faster than FFP and will not
cause fluid overload. However, PCC treatment is associated with 1%
risk of thrombosis e.g., DVT, PE, MI. So, it is contraindicated in
patients with active thrombosis or DIC. Transamin (tranexamic acid)
should not be given together with PCC.)
b) Urgent reversal of Anti-Factor Xa inhibitors (Apixaban,
Rivaroxaban, Edoxaban) effect: give prothrombin complex
concentrate (PCC) 50 units/kg
c) Urgent reversal of Dabigatran effect: give Idarucizumab 5g IV bolus
d) Urgent reversal of thrombolytics (e.g., Alteplase, Tenecteplase)
effect: give Cryoprecipitate infusion, and a stat dose of Transamin
(tranexamic acid) 1g slow intravenous infusion over 10 mins. Check
blood for fibrinogen afterwards. Give additional cryoprecipitate if
serum fibrinogen level < 150 mg / dL.
e) Neurosurgical consultation:
 Cerebellar haematoma or large cerebellar infarct with significant
mass effect
 Large cerebral haematoma (>30ml) with mass effect
 Impending or established hydrocephalus / intraventricular
haemorrhage
 Subarachnoid haemorrhage

7. Rehabilitation: (Also refer to page Re7 in Rehabilitation Medicine)

All acute stroke patients should be assessed for rehabilitation potential and
admission to organized rehabilitation programmes.

N 14
8. Secondary prevention:
a) Risk factor modification for all types of stroke
b) Oral anticoagulation in cardioembolic stroke (including AF) and anti-
phospholipid antibody syndrome
c) Aspirin 80–300mg daily for ischaemic stroke if anti-coagulation not
indicated. Aspirin + dipyridamole or clopidogrel are other options for
first line anti-platelet agents.
d) Carotid Endarterectomy (CEA) or carotid stenting is indicated for
symptomatic extracranial carotid stenosis of 70–99%, depending on the
availability of expertise and their own track record of peri-interventional
complication. Intervention for symptomatic stenosis of 50–69% can
only be considered in centres with very low complication rate (less than
3%). Carotid stenting will be preferable in case of: (i) difficult surgical
access, (ii) medical co-morbidities with high risk of surgery e.g., IHD,
(iii) radiation induced arteriopathy, (iv) re-stenosis after CEA. (Please
refer to individual hospital logistic for referral of those patients for
carotid intervention to different involved specialties)

N 15
 SUBARACHNOID HAEMORRHAGE

Investigations
1. CT brain as soon as possible.
2. Lumbar puncture if CT is negative, to look for bloody CSF and send CSF
for xanthochromia. Xanthochromia is expected if LP is performed >12 hr
after presumed SAH onset. If LP is performed within 6 hr from headache
onset, absence of xanthochromia is not reliable to rule out SAH.
3. In patient with high clinical suspicion of CT negative SAH, if LP result is
inconclusive, it is reasonable to proceed to urgent CT angiogram of brain.
4. Urgent cerebral angiogram if early surgery is considered. If DSA cannot be
arranged urgently, CT angiogram of brain should be arranged. Most of the
aneurysm with >5mm can be detected by CTA.

Management
1. Correct any compromised airway, breathing and circulation.
2. Confirm diagnosis (CT ± LP) and consult neurosurgeons.
3. Assess severity, and monitor GCS, pupil size, neurological deficits, cardiac
rhythm and SaO2.
4. Early surgery/endovascular coiling should be considered if aneurysm
demonstrated by DSA/CTA. Factors guiding decision including severity of
SAH and functional state of patient.
5. Begin nimodipine 60mg po q4h PO (or via enteral feeding). Monitor BP. If
oral administration is not possible, intravenous nimodipine can be given at
1 – 2mg/hr, preferably with invasive BP monitoring. The use of nimodipine
should be individualised in poor grade patients.
6. BP should be closely monitored and controlled carefully to balance the risk
of hypertension-related rebleeding, and maintenance of cerebral perfusion
pressure (exact level of target BP is controversial but avoid treating reactive
HT due to raised ICP). A systolic BP <160 mmHg is a reasonable target
before definitive surgical management of the ruptured aneurysm.
7. Antifibrinolytic agent (Transamin): early treatment with a short course of
antifibrinolytic agents (< 72 hours or till the aneurysm is secured by
surgical means, whichever duration is shorter) may be reasonable for
patients in whom definitive surgical treatment for aneurysm treatment has
unavoidable delay and there are no contraindications. Delayed (more than
48 hours after SAH onset) or prolonged (more than 3 days) antifibrinolytic
therapy should be avoided as risk of thrombosis outweighs risk of
rebleeding).
8. Correct for any abnormalities in To, fluid balance, electrolytes, osmolality,
N 16
 blood glucose. Maintenance of euvolaemia is recommended to decrease
the risk of delayed cerebral ischaemia.
9. Anticonvulsant if seizures occur.
10. Prophylactic anticonvulsant use is controversial. If prophylactic
anticonvulsants are used, it is recommended to limit to a short course.
11. Analgesics, sedatives, acid suppressants and stool softener prn.

N 17
 TONIC-CLONIC STATUS EPILEPTICUS

Operational definition:
 Two or more epileptic seizures without full recovery of consciousness
between attacks.
 Continuous seizure lasting more than 5 minutes.

High index of suspicion is needed for diagnosis of non-convulsive status

epilepticus. Consider EEG when patient has impaired consciousness with
no accountable cause.

General Management
 Maintain airway, breathing, circulation
 Ensure good oxygenation and IV access
 Check H’stix
- If H’stix < 4, give thiamine 100mg IV then D50 50ml IV
 Resume usual anti-seizure medications (ASM) for known history of
epileptic disorder; Change to IV formulations if available
 Suppress clinical seizures, identify complications and aetiology search
- Routine blood test including ASM level ± toxicology screening ± CT
brain ± LP
 Consider special test like anti-NMDA receptor antibodies when indicated

(1) Stage 1: Early status (if seizure ongoing for about 5-10 mins)
 Treat with short acting ASM (benzodiazepine)
- Lorazepam IV: 4mg over 2 minutes, repeat once in 5-10 min, if still
seizure, up to 8mg
- Diazepam IV: 5-10mg over 1-2 minutes, up to 20mg (if lorazepam
not available)
- Midazolam 0.2 mg/kg IM, max. 10mg if no IV access
- Note: total dose of benzodiazepine included those given pre-hospital

(2) Stage 2: Established status (if seizure persists about 10-30 mins)
 Treat with IV long-acting ASMs (usually started in the stage of
early status)
Loading Maintenance
ASM Remarks 60kg 60kg
dose dose
Phenytoin  Beware of purple 15 mg/kg 900 mg 5-7 mg/kg/d 100mg
(Dilantin) glove syndrome IV over 30 divided to q8h q8h
 Use large vein Max rate: mins
 Avoid dilution in 50 mg/min
dextrose
N 18
 Valproate  Check NH3 level 20 1200 30-60 600mg
(Epilim)  Avoid in patients mg/kg/IV mg over mg/kg/divided IV q8h
with hepatic failure 10 mins to q8h over 5
 Beware of mins
thrombocytopenia
Levetiracetam  In patients with renal 20 mg/kg 1000mg 2-3 gm/day 1500mg
(Keppra) impairment CrCl < IV in IV divided to in 100ml
15ml/min, max dose: Max rate: 100ml q12h NS IV
500mg q24h 100 mg/min NS over q12h
15 mins over 15
mins
Lacosamide  Look for arrhythmia 200 to 100-300mg
(Vimpat) with cardiac monitor 400mg IV IV q12h over
(alternative  Beware of PR over 30 30 mins
therapy) prolongation mins
 In patients with CrCl
< 30ml/min, max
dose: 300mg daily

(3) Stage 3: Refractory status (Seizure despite benzodiazepine and one

ASM treatment)
 Treat with general anaesthesia, maintain for 24 hours before gradual
withdrawal
 Use EEG as guideline for treatment response
 If seizure recurs, escalate to higher dose and use for longer duration
 If there is no EEG evidence of acute seizure, slowly taper GA therapy
within 24 hours, while maintaining high therapeutic level of ASM
 Repeat EEG to look for NCSE if GCS remains low after GA therapy or
sedation are off
- Midazolam Bolus 0.1-0.2 mg/kg → maintenance infusion 0.05-2
mg/kg/hr
- Propofol Bolus 1-2 mg/kg → maintenance infusion 1-5 mg/kg/hr
- Thiopental Bolus 2-3 mg/kg → maintenance infusion 0.5-5
mg/kg/hr

(4) Stage 4: Super-refractory status epilepticus (SE which has been

continued or recurred despite therapy with general anaesthesia for 24
hours or more)
 Consider use of ketamine, magnesium, immunotherapy
 Immunotherapy (check CSF and blood for autoimmune panel before
start of immunotherapy)
- Including methylprednisolone, IVIg and plasma exchange
 Consider use of ketogenic diet, therapeutic hypothermia and epilepsy
surgery.

N 19
 AUTOIMMUNE ENCEPHALITIS

Autoimmune encephalitis should be considered in patients presenting with

subacute onset (over 1 to 3 months) of cognitive or memory deficits, altered
consciousness, seizures, movement disorders, or other neuropsychiatric
symptoms.

Clinical presentation:
- Diagnostic criteria for possible autoimmune encephalitis can be made if all
three of the following criteria have been met.
1. Subacute onset (rapid progression of less than 3 months) of working
memory deficits (short-term memory loss), altered mental status, or
psychiatric symptoms
2. At least one of the following:
 New focal CNS findings
 Seizures not explained by a previously known seizure disorder
 CSF pleocytosis (white blood cell count of > 5 cells per mm³)
 MRI features suggestive of encephalitis
3. Reasonable exclusion of alternative causes (such as infectious encephalitis
[e.g., HSV], seizure disorders)
- Tumours and viral encephalitis can trigger autoimmune encephalitis.
- Some forms of autoimmune encephalitis have a specific phenotype.
Antibody Key clinical features Tumour associations
Anti-NMDA • Psychiatric features followed by Ovarian teratoma
movement disorder (classically
orofacial dyskinesia)
• Seizures / Encephalopathy
• Autonomic dysfunction
Anti-LGI1 • Faciobrachial dystonic seizures Thymoma
• Amnesia
• Hyponatraemia
Anti-GABAAR Encephalitis with frequent status Thymoma
epilepticus
Anti-GABABR • Seizures Small cell lung carcinoma
• Amnesia
Anti-DPPX • Multifocal encephalitis with tremor / B cells neoplasms (such as
myoclonus / hyperekplexia lymphoma)
• Diarrhoea and weight loss

N 20
Investigations:
1. To confirm the presence of focal or multifocal brain abnormality suggestive
of encephalitis
• MRI brain (with and without contrast)
• EEG
2. To confirm an autoimmune inflammatory aetiology and exclude other
possibilities
• Blood and CSF for anti-NMDA and autoimmune encephalitis panel
3. To screen for underlying malignancy
• Whole body PET-CT
• CT thorax / abdomen / pelvis (with contrast)
• Mammogram
• Pelvic / testicular USG

Treatment:
1. Immunotherapy
• Early immunotherapy can improve outcome
• First line immunotherapy:
 High dose corticosteroids (IV methylprednisolone 1g/day for 3 – 7
days, followed by oral prednisolone with slow taper)
 Intravenous immunoglobulin (IVIg) 0.4g/kg/day for 5 days
 Plasma exchange
• Second line immunotherapy: Can be considered if there is no meaningful
clinical or radiological response to optimised first-line immunotherapy
after 2−4 weeks; Includes IV rituximab / cyclophosphamide
2. Symptomatic treatment
• Apart from immunotherapy, it is important to treat the co-existing
seizures, movement disorders, sleep and autonomic dysfunction.
3. ICU admission may be considered in patients with status epilepticus,
especially when they are intubated.
4. In NMDA encephalitis patients with ovarian teratoma, tumour resection is
associated with faster rate of recovery and reduced relapse rate.

N 21
 GUILLAIN-BARRÉ SYNDROME

Clinical Presentation
1. Rapidly progressive autoimmune motor ± sensory polyneuropathy
2. ± involvement of respiratory / bulbar muscles
3. Generalised areflexia or hyporeflexia
4. ± Autonomic dysfunction (e.g., arrhythmias, swings in blood pressure,
urinary retention, paralytic ileus and hyperhydriasis)
5. Monophasic illness pattern; clinical plateau by about 4 weeks
6. Miller Fisher syndrome: bilateral ophthalmoparesis, ataxia, areflexia
7. Look for preceding infection within 4 weeks, e.g., Campylobacter jejuni,
Mycoplasma pneumonia, CMV/ EBV/ VZV; recent vaccination

Diagnosis
1. Should NOT have new-onset upper motor neuron signs or sensory level.
2. Consider paralysis due to other conditions: toxic neuropathy (e.g., alcohol,
heavy metals, insecticides, solvents, drugs like cytotoxic agents), metabolic
(e.g., hypokalaemic periodic paralysis, hypophosphataemia, acute
intermittent porphyria), vasculitis, lymphomatous infiltration, critical
illness polyneuropathy; or neuromuscular junction disorders (e.g.,
myasthenic crisis, botulism).
3. Arrange nerve conduction study (may be normal in 1st week): Findings
depend on subtypes of GBS: acute inflammatory demyelinating
polyneuropathy (AIDP), acute motor axonal polyneuropathy (AMAN),
acute motor sensory axonal polyneuropathy (AMSAN)
4. Perform lumbar puncture: look for cytoalbuminologic dissociation [Raised
CSF protein (may be normal in 1st week, ~80% abnormal in 2nd week, peak
in 3rd to 4th week) and CSF total white cell count <50 cells/uL]
5. Anti-ganglioside antibodies:
 GQ1b is closely associated with Miller-Fisher Syndrome
 GM1 and GD1a are associated with acute motor or motor-sensory
axonal neuropathy.

Management
1. Monitor vital capacity; consider mechanical ventilation if:
 Hypercarbia and/or hypoxaemia
 FVC <15 ml per kg of BW
 Bulbar weakness, impaired swallowing, ineffective cough, tachypnoea
2. Watch for autonomic dysfunction (potentially fatal):
 Cardiac monitoring (for arrhythmia and severe bradycardia)
N 22
  BP monitoring (fluctuate between severe hypertension and hypotension)
3. Gastrointestinal
 Susceptible to the development of paralytic ileus
 Monitor swallowing ± temporary non-oral feeding
4. Other supportive measures:
 DVT prevention
 Urinary retention, constipation
 Clear secretion
 Early mobilisation
 Medical treatment for pain and paraesthesia
5. Immunotherapy (in severe cases):
 Give intravenous immunoglobulin (IVIg) 0.4g/kg/day for 5 days
 Alternatively start plasma exchange 50 mg/kg/session of plasma for 5
exchanges over 2 weeks
6. Combination of IVIg and PE is not better than PE or IVIg alone. Steroid
treatment has no benefit.

N 23
 MYASTHENIC CRISIS
Definition
 A life-threatening exacerbation of myasthenia gravis (MG) with
respiratory muscle involvement necessitating ventilator support
 Can be the first presentation of MG

Diagnosis
 Muscle weakness with respiratory distress (Dyspnoea, tachypnoea, use of
accessory muscles of respiration)
 Differentiation from cholinergic crisis (increased secretions, bradycardia,
abdominal cramps, muscle weakness ± cramps and fasciculations, miosis)
 Priority to maintain airway, breathing, circulation
 FVC, ABG, ECG, Chest X ray
Remarks: Tensilon test: diagnostic test in untreated disease; not reliable in differentiating
myasthenic and cholinergic crisis and not without risk, hence not recommended.

Management
1. Watch out for respiratory failure in any patient with progressive weakness
and bulbar symptoms.
2. Closely monitor FVC, SaO2 and ABG. Consider mechanical ventilation if:
 Hypercarbia and/or hypoxaemia
 FVC < 15 ml per kg of BW
 Bulbar weakness, impaired swallowing, ineffective cough, tachypnoea
3. Stop anticholinesterase if patient is intubated
4. Identify and treat any precipitating conditions (e.g., infection)
5. Give intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days. An
alternative is plasma exchange 50 ml/kg/session of plasma on alternate days
until adequate response achieved (usually after 5–6 exchanges).
6. Resume anticholinesterase at a smaller dose 48–72 hours after stabilisation
and titrate accordingly.
7. Start prednisolone 1 mg/kg/day; Useful in inducing & maintaining
remission but to be individualized (Beware that early steroid-induced
deterioration may occur).
8. General supportive measures:
 Monitor swallowing ± temporary non-oral feeding
 DVT prevention
 Urinary retention, constipation
 Clear secretion
 Early mobilisation
N 24
9. Beware with the use of any drug that might worsen MG. e.g.,
aminoglycosides, quinolones, quinine, quinidine, procainamide, β-blockers,
muscle relaxants, phenytoin, penicillamine, magnesium.

N 25
 ACUTE SPINAL CORD SYNDROME
(Also refer to page PM20 and GM24)

It is of paramount importance to make an early diagnosis of acute spinal cord

compression, to provide the patient with the best chance for neurological
recovery. “Sensory level” can be falsely localising and urgent imaging of
spinal cord is advisable.

Investigations to delineate level and nature of spinal cord lesion

1. XR spine
2. MRI spine of relevant level if immediately available; otherwise, myelogram
and CT myelogram.
3. Lumbar puncture if transverse myelitis is suspected; send CSF for
microscopy and cell counts culture, AFB culture, biochemistry, viral study
and cytology; VDRL, oligoclonal band and anti-aquaporin-4 antibody (or
NMO IgG) in selected cases.

Management
1. Correct any compromised airway, breathing and circulation.
2. Immobilize relevant level of spine in case of traumatic spinal cord injury
or spine instability.
3. Initiate appropriate treatment for specific spinal cord lesions:
 Neurosurgical / orthopaedic consultation for structural lesions
 Antimicrobial therapy for abscess or other infections
 Consider methylprednisolone (1g IV over one hour daily for 3 days,
with cardiac monitoring) in non-infectious transverse myelitis
4. Institute general supportive care:
 Proper positioning & splinting
 Adequate hydration and nutrition
 Bladder catheterization
 Prevent DVT
5. Close monitoring of respiratory function (FVC, respiratory rate) and
cardiac monitoring in case of high cord lesions.

N 26
 PERI-OPERATIVE MANAGEMENT IN PATIENTS WITH
NEUROLOGICAL DISEASES

High risk of peri-operative pulmonary complications: Parkinsonism,

myasthenia gravis, other neuro-muscular disorders affecting respiratory
muscles and any neurological deficits compromising respiratory effort.

Peri-operative management:
1. Comprehensive pulmonary assessment before operation
2. Optimal control of neurological conditions
3. Vigorous peri-operative chest physiotherapy
4. Regular monitoring of FVC, respiratory rate, SaO2, ABG
5. Continue anti-seizure medications (for epilepsy), anti-cholinesterase (for
myasthenia) and anti-parkinsonism drugs (for Parkinsonism) as close to
normal schedule as possible. Resume as soon as possible after operation.
Alternative preparation or drugs:
 Anti-cholinesterase: Neostigmine 0.5mg IM/IV q4-6h
 Anti-seizure medications: phenytoin / sodium valproate / levetiracetam
/ brivaracetam / lacosamide available in IV form
 Transdermal patch of rotigotine and parenteral apomorphine is
available if anti-parkinsonism drugs cannot be resumed quickly.
[N.B. Abrupt withdrawal of anti-parkinsonism drugs leads to
exacerbation of symptoms as well as withdrawal symptoms /
neuroleptic malignant-like syndrome]
6. a) Bridging therapy is recommended for patients with high risk of
thromboembolic event after warfarin is stopped.
b) Warfarin can be continued for most dental procedures if INR is kept at
a lower range before the procedure and close monitoring in the day ward
after the procedure is available.
c) For whether and when to stop DOAC before surgery or invasive
procedures, please refer to H15.
d) Discontinue anti-platelet agents 1 week before elective surgery, but
aspirin may be continued in the following procedures: (i) dental procedures,
(ii) endoscopies with biopsies and polypectomies, (iii) ophthalmologic
procedures, (iv) peripheral vascular procedures, (v) neuraxial anaesthesia.
7. Avoid aminoglycosides, quinolones, morphine, quinidine, β-blockers,
procainamide, penicillamine for myasthenia gravis.
8. Avoid phenothiazines (e.g., prochlorperazine, chlorpromazine etc.) to treat
nausea and vomiting in patients with Parkinson’s Disease (exaggerate
Parkinson symptoms)
N 27
9. Avoid Pethidine in patients taking MAO-B inhibitors (e.g., selegiline,
rasagiline)
10. For patients with neurostimulators (such as deep brain stimulation, DBS)
implanted, the battery should be turned OFF before undergoing surgery /
MRI and can be turned ON after these procedures with programmer. The
medications (such as anti-PD medications) may need to be titrated when
the battery is turned OFF. Also, monopolar diathermy should be avoided.

Risk of Peri-operative stroke

1. Increase in hypertension
2. Optimize vascular risk factors (e.g., DM, HT, hyperlipidaemia) before
operation.
3. Asymptomatic carotid bruit is not an independent risk factor. Intervention
to asymptomatic carotid stenosis before general surgery (open heart surgery
is excluded) might not be justified since the risk of intervention would
outweigh its potential benefit.
4. Symptomatic severe carotid stenosis (>70%) should be tackled before non-
emergency operation. Symptomatic large vessel stenosis in the posterior
circulation needs to have aggressive intraoperative maintenance of blood
pressure to avoid prolonged hypotension.
5. Decreased by avoiding hypotension, hypovolaemia, polycythaemia and
anaemia.
6. Postpone elective procedures for at least 3 months after an ischaemic stroke;
For low-risk operations, or mild stroke / TIA, individualized judgement to
have operation done earlier if the benefit of early operation outweighs risk.

N 28
Palliative Medicine
 ANOREXIA

Anorexia is the loss of food appetite and desire to eat. It is common in both
advanced cancers and non-cancer conditions. Anorexia may be part of
anorexia-cachexia syndrome, characterized by severe weight loss with marked
deficit of muscle and fat.

Causes of Anorexia:
1. Concomitant symptoms: sepsis, pain, constipation, dyspnoea, dysphagia,
nausea, vomiting, anxiety, depression.
2. Oral problems: dry mouth, candidiasis, ulcers, ill-fitting denture, altered
taste
3. Delayed gastric emptying: hepatomegaly, autonomic neuropathy
4. Metabolic causes: hypercalcaemia, hyponatraemia, uraemia
5. Medications: opioids, antibiotics, chemotherapy
6. Odour: foul smelling discharge, fungating mass, incontinence

General Management:
1. Treat reversible causes and optimize symptom palliation
2. Maintain good oral hygiene
3. Provide frequent small meals or food on demand, allow patient to eat what
they wish, keep company during eating.
4. Dietetic advice with emphasis on taste and food preference.
5. Acknowledge concerns on prognosis, body image, social impact.
6. Proper mood assessment and psychological support.

Pharmacological Interventions:
1. Corticosteroids: e.g. dexamethasone 2-4mg daily for a trial.
 Rapid onset, but effect tails off after 2 weeks.
 Increase food intake, but no weight gain.
 May reduce nausea and improve sense of wellbeing.
 Limited evidence for use in non-cancer conditions
 Discontinue after 1 week if no benefit. If effective, titrate down to
minimum effective dose for 2 weeks. Tail off if effect wears off.
 Look out for DM, TB before starting; give OM or before noon to avoid
disrupting diurnal rhythm; monitor mouth condition for oral candidiasis.

2. Progestogen: e.g. megestrol acetate 80-160mg daily, titrating upwards to no

more than 800mg per day.
 Improve appetite; only a small effect on non-muscle weight gain.
PM 1
  Onset takes 2 to 3 weeks, but action lasts longer than corticosteroid.
 S/E: oedema, thromboembolism and deaths more frequent.
 Poor benefit/risk ratio and patients should be informed of risks,
particularly in conditions other than cancer and AIDS.

3. Prokinetics e.g. metoclopramide 5-10mg TDS.

 For early satiety from hepatomegaly, ascites, and delayed gastric
emptying, due to other causes.

Practical point:
Appetite stimulating agents do not reverse cachexia.
Focus of any nutritional support should be on quality of life
Comfort feeding to be emphasized in end-of-life situations

PM 2
 NAUSEA & VOMITING

Causes:
1. GI related: GI obstruction, constipation, gastric stasis, GERD,
gastroenteritis, gastric irritation, autonomic neuropathy.
2. Metabolic: hypercalcaemia, uraemia.
3. Drugs: opioids, antibiotics, NSAIDs
4. Cancer treatment: chemotherapy, radiotherapy
5. CNS: increased ICP, brain tumour / metastases, vestibular dysfunction

Management:
1. Elucidate and remove cause of nausea and vomiting if possible (e.g.
constipation, hypercalcaemia, medications).
2. Pay attention to environment, odour, food presentation.
3. Manage any anxiety / psychological factors or sequelae.
4. Antiemetics (If oral absorption is in doubt, use other routes).
 Prokinetic: e.g. metoclopramide 5-10mg TDS, domperidone 10mg TDS
(watch out for extrapyramidal side effects).
 Central anti-dopaminergic drugs e.g. haloperidol 0.5-5mg BD (e.g.
uraemia, opioid-induced), prochlorperazine 5-10mg TDS.
 Olanzapine 2.5 -5 mg po daily can be considered for cancer-related
nausea and vomiting as a 2nd line treatment
 Dexamethasone 16mg OM initially for brain tumour while pending
tumour targeted treatment; 8mg OM initially for reducing compression
on gut by tumour masses.
 For emetogenic chemotherapy related nausea and vomiting, consider
5HT3 antagonists e.g. ondansetron, granisetron; neurokinin-1 (NK-1)
antagonist e.g. aprepitant; olanzapine and dexamethasone.

Practical points:
1. Prescribe anti-emetic regularly not prn.
2. Select anti-emetics based on aetiology as far as possible
3. Can consider prophylactic anti-emetics during the initial phase of strong
opioids.
4. Do NOT use prokinetics in complete GI obstruction.
5. Dosage adjustment of anti-dopaminergics is required in renal failure.
6. Avoid combination of metoclopramide and central anti-dopaminergics.
7. Consider continuous subcutaneous infusion or other route if patients are
unable to take medications per orally.

PM 3
 CANCER PAIN MANAGEMENT

Optimum management of cancer pain requires a multidisciplinary approach.

The Basic General Principles are:

1. By the Mouth: oral route the preferred route.
2. By the Clock: regular analgesics.
3. For the individual: guided by the WHO Analgesic Ladder: Start appropriate
analgesic according to the intensity of pain and assess pain control regularly
to adjust the dosage or drugs of choice.

WHO analgesic
Analgesics of choice
ladder step
1
Paracetamol and/or NSAIDs ± adjuvant a
(mild pain)
Weak opioids (e.g. codeine, dihydrocodeine,
2 tramadol) or low-dose strong opioids b
(mild to moderate ± paracetamol and/or NSAIDs
pain)
± adjuvant a
Strong opioids (e.g. morphine, oxycodone,
3 methadone, fentanyl)
(moderate to severe ± paracetamol and/or NSAIDs
pain)
± adjuvant a
a. Adjuvants: antidepressants (e.g. amitriptyline) and anticonvulsants (e.g.
gabapentin and pregabalin)
b. Low-dose strong opioids: oral morphine ≤30mg/day; oral oxycodone
≤20mg/day

Practical Points:
1. Consult palliative care or cancer pain specialist when patient in severe pain
crisis.
2. Pethidine NOT recommended because of adverse S/E profile.
3. Tramadol has similar S/E profile as strong opioids, watch out for drug-drug
interaction e.g. SSRI, TCA, warfarin.
4. Morphine remains the first-line treatment for moderate to severe cancer
pain, oxycodone is an effective alternative.
5. Fentanyl patch is NOT for opioid naïve patients, acute pain or initial

PM 4
 titration. Consult specialists.
6. Caution was recommended on chronic use of NSAIDs, as many cancer
patients are at high risk of GI, renal, cardiac toxicities or bleeding disorders.
7. FDA warns that respiratory depression may occur in patients using
gabapentin or pregabalin who have respiratory risk factors (e.g. using
opioids, COPD, elderly): need to initiate at lowest dose and titrate slowly.
8. Renal impairment:
 Mild renal impairment: weak opioids, morphine, oxycodone,
gabapentin and pregabalin should be used with caution i.e. use lower
dose and increase dose slowly.
 Severe renal impairment (eGFR < 30ml/min): Paracetamol is the first
line drug for mild pain. Weak opioids, NSAIDs (including COX-2
inhibitors), morphine and oxycodone should be AVOIDED. Fentanyl
and methadone are the preferable choices for severe pain – CONSULT
SPECIALIST.

PM 5
 GUIDELINES ON USE OF MORPHINE FOR CHRONIC
CANCER PAIN CONTROL

1. Morphine is the strong opioid of choice for moderate to severe cancer pain.
2. Morphine has no standard upper dose range. The optimal dose is the dose
providing adequate pain relief with minimal or tolerable S/E.
3. Oral route is preferred unless not feasible e.g. GI Obstruction, dysphagia.
4. Start with syrup morphine 5mg q4h regularly and PRN for breakthrough pain.
Some prefer to double the dose at bedtime to avoid waking the patient up at
4am.
5. Consider a lower starting dose of 2mg for patients susceptible to S/E e.g. old
age, COPD, frailty, sleep apnoea.
6. Dose increment: e.g. 5mg→7.5mg→10mg→15mg→20mg→30mg etc.
7. For breakthrough pain, prescribe the SAME dose as the one for regular use
in between the regular intervals, given up to hourly.
8. As an alternative, start with MST (Morphine controlled-release tablet) 10mg
q12h and syrup morphine 2-5mg prn for breakthrough pain.
9. AVOID morphine in severe renal failure as active metabolites are excreted
by renal route. Reduce dose in mild renal impairment.
10. Side effect of opioids and their management:
a) Explanation of the indication and side effect is important.
b) Ensure adequate hydration of patient.
c) give laxatives CONCURRENTLY if not contraindicated, preferably a
combination of stimulant and stool softener e.g. Senna 15mg Nocte and
lactulose 10ml TDS.
d) Nausea may occur initially. May prescribe antiemetic PRN e.g.
metoclopramide 5-10mg TDS, haloperidol 0.5-5mg daily.
e) Consider reduce dose of morphine if pain is well controlled; abrupt
discontinuation may precipitate withdrawal symptom.
f) Consider adjuvant analgesics.
g) Consult specialist to switch to another strong opioid if pain control is not
adequate or with intolerable side effects.

Dose conversion of oral morphine to parenteral route

1. Parenteral route has NO special advantage over oral route.
2. SC route is the preferred alternate route, or IV if access available. No
indication for IMI generally.
3. Dose conversion
 Oral daily dose of morphine÷2 = daily dose of morphine SC
 Oral daily dose of morphine÷3 = daily dose of morphine IV

PM 6
  E.g. Morphine 60mg PO = 30mg SC = 20mg IV
Practical points on Parenteral drugs:
Generally, parenteral drugs for symptom control can be given by:
1. Syringe driver (10ml syringe or specified syringe) OR
2. Infusion pump by adding drugs to parenteral fluid to be given SC (NS only
for SC) or IV.

Practical points on Laxatives:

1. Metamucil requires good fluid intake and has high K content; NOT for frail
patients with reduced water intake.
2. Mg Trisilicate has high Mg content; NOT for ESRD.
3. Fleet enema contains high phosphate content; NOT for ESRD.

PM 7
 DYSPNOEA

Dyspnoea is a subjective experience. Causes of dyspnoea in advanced

cancer:

Common
Cardiorespiratory Systemic
causes
Lung masses, pleural effusion,
major airway obstruction, SVCO, Anaemia, cachexia,
lymphangitis carcinomatosis, respiratory muscle
Malignancy pneumothorax, pericardial weakness, gross
related effusion, pulmonary embolism, hepatomegaly or tense
post-irradiation / post- ascites, metabolic
chemotherapy / immunotherapy- acidosis
induced pneumonitis.

Co-existing COPD, heart failure,

Non-malignant Anxiety
fluid overload, pneumonia

Management:
1. Address disease-specific causes:
 Cancer:
- Identify and treat reversible causes e.g. pleural, pericardial or
abdominal tapping / drainage, antibiotics, anticoagulation, blood
transfusion, bronchodilators, diuretics.
- Dexamethasone 4-8mg daily for lymphangitis carcinomatosis, post-
irradiation or post-chemotherapy pneumonitis; 16mg daily for SVCO,
major airway obstruction.
 Non-cancer:
- E.g. advanced COPD and heart failure
- Optimise disease-specific pharmacological treatment
2. Oxygen only for hypoxaemic patients, nasal prong better tolerated than
face mask.
3. Non-pharmacological measures: prop up, face fan, breathing exercises.
4. Opioid:
 For opioid naïve patients, start with morphine 1-2mg q4h PO or SC.
Increment of 25% of baseline dosage for patient on strong opioid.
 Monitor mental state, RR, SaO2. Withhold opioids if there is sign of
respiratory depression.
 Titrate up in steps according to effect: e.g. 1mg→2mg→3mg→5mg….
PM 8
  Dyspnoea in the terminal phase:
- In opioid naïve patients, start with morphine 5mg SC infused over 24
hours.
- If renal failure, fentanyl 50-100 microgram SC infused over 24 hours.
- For intermittent / breakthrough dyspnoea, add morphine 1-2mg SC
q2h prn; fentanyl 12.5-25 microgram SC q2h prn for renal failure.
5. Anxiolytic: indicated for patient with significant anxiety or panic attacks.
6. For severe dyspnoea refractory to above treatment, consult PM specialist.
The use of palliative sedation should ONLY be prescribed by PM specialist.
Patient and family should be informed about the purpose, possible
impairment in communication, and this is not euthanasia.

**Special warning on combined use of opioid and CNS depressants

 Serious risks and death are reported from combined use of opioid and CNS
suppressants, e.g. benzodiazepines and gabapentinoids.
 When patient is put on opioid and CNS depressants, monitoring of vital signs
including mental state, respiratory rate and SaO2 are recommended.
 Communication with patient and family particularly on risks including extreme
drowsiness, respiratory depression, coma and death is recommended.

Practical points:
1. SaO2 / lung function parameters do NOT correlate with intensity of
dyspnoea.
2. CXR is useful in elucidating most underlying causes.
3. USG guidance is helpful in chest tapping especially in the presence of
loculations.
4. Look out for trapped lung in chest tapping. Stop if patient has coughing,
breathlessness/desaturation or chest pain; document in patient’s record to
guide decision on chest tapping in subsequent admission.

PM 9
 DELIRIUM

Delirium is an acute confusional state with fluctuating course, characterised

by altered consciousness and cognitive deficits. Manifestations can be
hyperactive, hypoactive, or mixed. Delirium is common at terminal stage but
causes may be easily remediable.

Common causes:
1. Drugs: opioid, anticholinergic, steroid, antidepressant, sedatives, anticancer
treatments such as chemotherapy and immunotherapy.
2. Uncontrolled symptoms: e.g. pain, faecal impaction, urine retention.
3. Infections
4. Metabolic: hypercalcaemia, electrolytes disturbance, hyper/hypoglycaemia,
liver failure, uraemia, dehydration, hypoxia, CO2 retention.
5. Organic brain disorder: brain tumour or metastases, cerebrovascular events.

Exacerbating factors:
1. Change of environment or excessive stimuli – temperature, noise, lighting.
2. Insomnia, anxiety, depression, fear.

Management:
1. Calm reassurance and explanation to patient and family.
2. Reduce environmental stimuli, improve visual impairment / hearing
impairment, avoid restraints and keep patient accompanied.
3. Identify reversible causes and treat accordingly.
 Beside examination – include assessing the hydration status,
neurological exam, PR exam, palpating for urinary bladder, checking
temperature, SaO2 and H’stix.
 Take blood for CBP with d/c, RLFT, Ca2+, Mg, cultures as appropriate
and treat accordingly.
 Review drug charts – if drug-related delirium is suspected, stop the drug
if possible or switch to alternatives where available; if opioid toxicity,
reduce dose by one-third to half. Ensure adequate hydration.
 ± CT brain if suspected remediable CNS causes.
4. The use of pharmacological interventions in the management of delirium
by anti-psychotics has no demonstrable benefit in the symptomatic
management of mild to moderate delirium and therefore should be limited
to patients who have distressing delirium symptoms or if there are safety
concerns where the patient is a potential risk to themselves or others. In

PM 10
 order to achieve the appropriate balance between benefit and potential harm,
medications should be used in the lowest effective dose and for a short
period of time only.

Pharmacological interventions:
1. Antipsychotics: e.g. haloperidol 0.5-1mg oral or SC stat then q8-12h if
regular dose required for severe delirium. A typical anti-psychotic drug can
be considered. E.g. quetiapine (immediate release) 12.5-25mg PO stat then
q12h if regular dose required; olanzapine 2.5-5mg PO/SC stat.

2. Benzodiazepines are effective at providing sedations and but may aggravate

agitation; use judiciously in combination with antipsychotic for sedation in
terminal delirium or if symptoms remain refractory. E.g. Lorazepam 0.5-
1mg PO/SL, Midazolam SC 2.5mg stat for acute control then 5-30mg q24
via syringe driver.

**Special warning on combined use of opioid and benzodiazepine. Serious risk and
death are reported from combined use of opioid and benzodiazepine. When patient
is put on opioid and benzodiazepine, monitoring of vital signs including heart rate,
blood pressure, respiratory rate and SaO2 are recommended. Communication with
patient and family particularly on risks including extreme drowsiness, respiratory
depression, coma and death are recommended.

PM 11
 MALIGNANT BOWEL OBSTRUCTION (MBO)

1. Assess if surgical intervention including stenting is feasible. E.g. for patient

with single level obstruction with good performance status. Surgical
intervention also depends on other prognostic criteria (age, comorbidities,
nutritional status and history of radiotherapy to abdomen).
2. For inoperable cases, to differentiate partial from complete obstruction, and
individualised symptomatic medical treatment:
a. Address reversible causes of constipation or obstruction
b. Fasting in complete obstruction, IV/SC rehydration
c. Antiemetics:
 Haloperidol SC: 5-15 mg/ 24h
 Metoclopramide SC 30-60mg/ 24h (contraindicated in complete
obstruction)
 Olanzapine PO: 2.5-7.5 mg/24 hr (in partial bowel obstruction)
 Ondansetron IV: 4-8mg/ 24h in refractory cases
d. Analgesics:
 IV/SC morphine or fentanyl (dose titration as in pain management)
e. Gastric antisecretory:
 Pantoprazole 40mg IV over 24h or single injection
f. Trial of steroids:
 Dexamethasone IV/SC 8mg daily (6-16mg daily), short course 5-10
days.
g. Anticholinergic antisecretory for high output vomiting:
 Hyoscine-N-butylbromide SC 40-120mg/ 24h
 Octreotide SC/IV 300 micrograms/ 24h or in 2 to 3 divided doses for
3 days, up to 600 micrograms/ 24h (total duration < 7 days)
h. Nasogastric tube (NG tube)
 Necessary if abundant vomiting and/or significant gastric distention (>
1 litre/day)
i. The role of parenteral nutrition is limited in most patients except for those
with good prognosis.

Practical Points:
1. Stop stimulant laxatives and prokinetic agents if complete MBO.
2. Use NG tube only as temporary measure, it should be removed as soon as
feasible to minimise patient discomfort.
3. Consider venting gastrostomy in refractory high output MBO as a last resort.

PM 12
 TREATMENT OF VENOUS THROMBOEMBOLISM (VTE)
IN PATIENTS WITH ADVANCED CANCER

General Principles:
1. Commonly used pharmacologic options for VTE treatment and prevention
include low-molecular-weight heparins (LMWHs), warfarin (vitamin K
antagonists), and direct oral anticoagulants (DOACs) (see section H14-15)
2. In 2003 CLOT trial (NEJM): patients randomized to receive 6 months of
therapy with the LMWH, dalteparin, had a reduced risk of recurrent VTE
(9%) compared with those who received initial treatment (5–7 days) with
dalteparin followed by the VKA warfarin (17%). There was no statistically
significant difference in their risk of bleeding or overall mortality.
3. Data in DOAC is non-inferior who are NOT at high risk of gastrointestinal
or genitourinary bleeding, in the absence of strong drug-drug interactions
or of gastrointestinal absorption impairment.
4. Burden of treatment and patients’ preferences are important for decision
making for patients near end-of-life (EOL). Patients may not benefit from
VTE prophylaxis if low baseline VTE risk and high risk of major bleeding.
5. Risk factors for the development of cancer associated VTE:

General Cancer specific

 Cancer type (e.g. stomach, pancreas, lung,

 Increasing age
lymphoma, gynaecological, bladder, renal)
 Immobility
 Metastatic diseases
 Comorbidities
 Chemotherapy (e.g. cisplatin, L-asparaginase)
(e.g. obesity,
 Hormonal therapy (e.g. tamoxifen)
diabetes, chronic
 Targeted therapy (e.g. EGFR inhibitors)
kidney disease)
 Anti-angiogenic therapy (e.g. thalidomide,
 Inherited
lenalidomide)
thrombophilia
 Other therapies (e.g. corticosteroids,
 Prior venous
Erythropoietin stimulating agents)
thromboembolism
 Central venous catheters

PM 13
Dosing and Treatment durations of established cancer-associated VTE:
Anticoagulant a Dosing Treatment period b
175 anti-Xa IU/kg body weight given s.c.
Tinzaparin Six months
once daily
1.5mg / kg once daily or
Enoxaparin Six months
1mg/kg every 12 hours
10mg twice daily for 7 days, followed by
Apixaban Six months
5mg twice daily
Low molecular weight heparin for at least
At least 6 months
5 days, followed by oral edoxaban at a
Edoxaban and up to 12
dose of 60mg once daily (decrease to 30mg
months
daily if BW <60kg or CrCl 15-50mL/min)
15mg twice daily for 3 weeks, then 20mg
Rivaroxaban Six months
once daily
a
DOACs are absorbed primarily in the stomach and proximal small bowel (with the exception of
apixaban, which is partially absorbed in the colon) so they may not be appropriate for patients who
have had significant resections of these portions of the intestinal tract.
b
Anticoagulation should be continued indefinitely while cancer is active or under cancer treatment or if
there are persistent risk factors for recurrent VTE.

In general, DOACs not recommended for patients with

 Creatinine clearance <30 mL/min
 Luminal gastrointestinal lesion
 Luminal genitourinary lesion
 Recent (<3 months) history of peptic ulcer disease or other bleeding
lesion
 Anticancer therapies that significantly affect P-glycoprotein, CYP3A4,
or CYP2J2 pathways
 Severe hepatic impairment with coagulopathy
 Imminently scheduled surgery or invasive procedure
 Body weight <40 or >120 kg

IVC filters
In the initial treatment of VTE, inferior vena cava filters might be considered
when anticoagulant treatment is contraindicated or, in the case of pulmonary
embolism, when recurrence occurs under optimal anticoagulation.

PM 14
 WISH TO HASTEN DEATH (WTHD)

WTHD is defined as patient’s reaction to suffering when facing a life limiting

or threatening condition, from which patient can see no way out other than to
accelerate his/her own death. WTHD should be differentiated from patient’s
acceptance of impending death or a wish to die naturally, even preferably soon.

WTHD may fluctuate among individual patient and not necessarily represent
a genuine wish to die. The clinical spectrum may vary from a vague to explicit
wish to die, from a sporadic to an enduring wish, and finally planning for
suicide or requesting physician assisted suicide (PAS) or euthanasia.

PAS is the practice of providing a competent patient with a prescription for

medication for the patient to use with the primary intention of ending his or
her own life.

Euthanasia is defined as the direct intentional killing of the patient as part of

the medical care provided by the health care practitioner. Both PAS and
euthanasia are illegal in Hong Kong.

The following are NOT PAS or Euthanasia:

1. Withholding or withdrawing life-sustaining treatments in terminally ill
patients.
2. Advance directive for refusal of life sustaining treatments by a mentally
competent adult patient.

The term passive euthanasia should not be used as it has been confused with
withholding or withdrawing life-sustaining treatments.

Underlying reasons for WTHD:

1. Existing or anticipatory distressing symptoms e.g. pain, dyspnoea
2. Psychological distress e.g. depression, hopelessness, anxiety
3. Existential distress e.g. loss of meaning in life
4. Social distress e.g. perceived burden to others, loss of roles

WTHD may serve:

1. As patient’s cry for help in alleviation of his/her sufferings.
2. As patient’s wish to express control or self-determination.

PM 15
Initial management of patient with WTHD
1. Recognise the WTHD as patient’s reaction to suffering in the context of
life-threatening condition.
2. Assess for:
 Underlying reasons for WTHD
 Physical symptoms and their control
 Features of depression and suicidal ideation
3. Maximise symptom control and reassess.
4. Suicidal precaution as indicated.
5. Refer to palliative care team early for:
 Strong and persistent WTHD
 Complex physical, psychological and existential problems

PM 16
 PALLIATIVE CARE EMERGENCIES:
MASSIVE HAEMORRHAGE

Terminal haemorrhage is massive blood loss that rapidly resulting in a

patient’s death and not appropriate for active treatment (e.g. radiotherapy or
endovascular interventions).

Anticipation:
 A “sentinel” or “herald” bleed of often trivial amount may occur 24 to 48
hours before a major arterial bleed.
 Identify patients with risk factors: head & neck tumour, tumour close to
major vessels, fungating tumour, haematological malignancy, repeated
episodes of organ bleeding, thrombocytopenia, coagulopathy, anti-
coagulant medications.
 Communication on the risk of major bleeding with patient / family for
advanced care planning and DNACPR issue.

Management:
 After a herald bleed:
- discontinue anticoagulants, NSAIDs, and aspirin.
- consider use of platelet transfusion, Vitamin K, clotting factor products
and specific reversal agents for DOAC, according to underlying causes.
 Prepare a “crisis pack” containing:
- pre-drawn sedative at bedside for rapid palliation, large dark towels, a
dark basin, gloves, suction device, warm blankets, and face cloth to
clean patient’s face and mouth.
 During massive bleeding episode, comfort measures of ABC algorithm
should be taken: A – Assurance; B – Be There; C – Comfort and Calm:
1. Apply direct pressure with adrenaline (1 in 1000) soaked dressing to
any external bleeding point.
2. Use dark surgical towels to reduce the frightening visual impact of the
bright red blood.
3. Sedate with midazolam 5-10mg SC or diazepam 5-10mg per rectal stat
to relieve panic and fear.
4. Address emotional impact on family and staff.

PM 17
 MALIGNANT HYPERCALCAEMIA
(Also see page K7 and GM25)

Presentation: delirium, malaise, thirst, nausea, constipation

Management:
1. Monitor Ca, PO4, RFT, urine output.
2. Withdraw drugs that promote hypercalcaemia (thiazide diuretics, lithium,
ranitidine, vitamin D and preparations containing calcium).
3. Rehydration with NS 2-3 litres/day, to keep adequate urine output e.g. >2
L/day.
4. Bisphosphonate infusion after correction of dehydration.
 Pamidronate infusion
Ca2+ 3-3.25 mmol/L - 60 mg in 500ml NS over 2-4 hrs
Ca >3.25 mmol/L
2+
- 90 mg in 500ml NS over 2-4 hrs
 Zoledronic acid 4mg IV infusion over 15 min.
 Adjust dose or infusion rate in renal impairment.
 Longer infusion in pamidronate (i.e. >2 hrs and up to 24 hrs) may
reduce the risk for renal toxicity, particularly in patients with pre-
existing renal insufficiency.
 Dose reduction in zoledronic acid:
CrCl ml/min Dose
>60 4mg
50-60 3.5mg
40-49 3.3mg
30-39 3mg
 Bisphosphonate is generally contraindicated if CrCl <30 ml/min
 Denosumab (e.g. 120mg SC repeat 1,2 and 4 weeks later, then monthly
thereafter) if hypercalcemia that is refractory to zoledronic acid or
bisphosphonates are contraindicated.

5. Consider steroid e.g. Prednisolone 60 mg/day for 10 days or hydrocortisone

200 to 400 mg iv/day for 3 to 5 days for hypercalcaemia in myeloma and
lymphoma.
6. Consider calcitonin (e.g. 4 to 8 units/kg IM or SC every 6 to 12 hrs for 48
to 72 hrs) for severe hypercalcaemia > 3.5 mmol/L. (Tachyphylaxis may
occur after 48 to 72 hrs)
7. Haloperidol 0.5-5mg per day for delirium.
8. Maintain IV hydration till patient can maintain oral hydration.

PM 18
Practical points:
1. Allow time to achieve full treatment effect: check calcium level at day 5 to
assess effectiveness. Do NOT repeat bisphosphonate infusion until day 7.
2. Bisphosphonate may not be appropriate at EOL, if in doubt, consult.
3. Effect of bisphosphonate lasts for 2-4 weeks, plan accordingly.

PM 19
 METASTATIC SPINAL CORD COMPRESSION
(Also see page N26 and GM24)

Early diagnosis and timely treatment are of paramount importance to

preserve neurological function and quality of life.
Common primaries: breast, lung, prostate; myeloma, kidney, lymphoma, GI,
melanoma, sarcoma, and unknown primary.
Sites of Compression: thoracic (70%), lumbosacral (20%), cervical (10%).

Presentation:
1. a) New-onset or worsened back pain, referred pain or neuropathic pain in a
cancer patient. (usually the first sign)
b) New motor and sensory deficits (may not correlate with level of
compression).
c) Sphincter disturbances (usually a late sign)
2. Can be the first presentation of advanced cancer.
3. FULL neurological examination in cancer patient with the slightest
suspicion.

Investigation & Management:

1. Plain X ray is not sensitive.
2. Urgent MRI of the whole spine to detect multiple levels of involvement and
aetiology, pay attention to pain and postural symptom(s) during procedure.
(CT myelography if contraindicated for MRI)
3. Start dexamethasone 10mg IV bolus then 4mg IV q6h if not contraindicated,
and adjust according to side-effect profile and taper off over 2 weeks after
definitive treatment.
4. Consult O&T (for surgical intervention) for patient with overall good
prognosis, solitary vertebral metastasis, unstable spine, status of
neurological deficits, and chemo-resistant tumour.
5. Consult Clinical Oncologist for urgent radiotherapy alone or following
surgery +/- chemotherapy or hormonal therapy for selected cases.

Prognosis:
1. Pre-treatment neurological function is the strongest predictor of post-
treatment neurological function
2. Duration of ambulatory loss
3. Sphincter disturbances
4. Better in haematological malignancy, breast and prostate cancer. Worse in
lung cancer.
PM 20
Practical Points:
1. Identify patient’s care goals, preferences & advance care planning.
2. To refer to multidisciplinary team to address patient’s needs: e.g. care for
bowel & bladder dysfunction, PT/OT for rehabilitation; MSW, CP +/-
psychiatrist for psychological sequelae of disabilities.
3. Prevent DVT

PM 21
 ADVANCE CARE PLANNING

Advance care planning (ACP) refer to the process of communication among

patients with advanced progressive disease, their health care providers, and
their family members and caregivers regarding the kind of care that will be
considered appropriate when patients can no longer make those decisions. In
short:
 Advance = in anticipation (given time)
 Care = medical care and personal care
 Planning = informed decision making

ACP is an integral part of health care with aging population and prevalence of
chronic disease. ACP serves to:
 Engage patients and their caregivers
 Facilitate shared decision making and consensus building
 Improve care for the dying

Scope of ACP
 ACP typically emphasizes on the autonomy of the mentally competent
adult patient, but it may be extended to include:
- Family members of the mentally incapacitated adult patients.
- Parents of minors and minors with reasonable understanding of the
situation.

For ACP to work

 Too early, patient may not be ready
Appropriate time
 Too late, patient cannot join discussion
 Health care workers as facilitators
Appropriate participants  Patient and their significant others
 Shared decision making
 Prognosis, burden and risks of various
treatment
Appropriate information
 Ensure palliation is available
given or elicited
 Wishes and values of patient (or prior wish)
and family
 Medical care: Life Sustaining Treatment
Make decisions
(LST) that patient will refuse
Appropriate to goals
 Personal care: place of care and death

PM 22
After ACP
 For mentally competent adult patient, patient may choose to:
- Set a limit to invasive treatments
- Make an advance directive (AD) to refuse specific LST in advance e.g.
CPR, dialysis, artificial nutrition and hydration, ventilators, and doctors
to sign the DNACPR form for non-hospitalised patients if patient
refuses CPR.
- Indicate a family member a potential decision making in future (Family
members are not legal proxies in Hong Kong).
 For mentally incapacitated adult patients and minors:
- No AD will be made.
- Doctors shall sign the DNACPR form for non-hospitalised patients
based on patient’s best interests and with consensus of family members
and parents.
 Document clearly for continuity of care
- Document the ACP discussion in patient’s record, use standardised
form if available. ACP form is not legally binding, but serves to guide
patient’s care in the future.
- Flag up the making of AD in the CMS.
- Flag up the DNACPR for non-hospitalised patients in the CMS, for
mentally incapable patients and minors, only the DNACPR will be
flagged.
- Instruct patient and family to keep the original copy of AD and/or
DNACPR present it to health care professionals as proof.
 Continuous process and regular review
- ACP is not a one-off process and regular review is needed.
- Patient and family should be instructed to inform health care
professionals if they have changed their mind.

PM 23
 LAST DAYS OF LIFE

To trigger care for the dying phase, the health care team has to recognise or
diagnose that patient is entering the last days of life. Timely communication with
patient (if feasible) and with family members is important.

Diagnosis or recognition of the dying phase:

 Increasing tiredness or weakness
 Drowsy mental state or confusion
 Further reduction in oral intake
 Laboured or noisy breathing due to airway secretions (death rattle)
 Cold and dusky hands and feet
 Reversible causes of the above excluded e.g. opioid side effects,
hypercalcaemia, infection

Communication on prognosis and care plan

 Communication with patient (if feasible) and family members of shared
decision making.
 Take into consideration patient’s expressed wishes, including previous
advance care planning, and honour a valid advance directive if any.
 Shift the goals of care from life prolongation to comfort care:
- Minimise or stop investigations that are unlikely to benefit patient
- De-prescribe medications that are unlikely to benefit.

Assisted hydration
 Patient may still be able to tolerate sips of water, and appropriate mouth care
to keep moist.
 Avoid over hydration which may result in respiratory secretions, oedema.
 Consider assisted hydration in individual case for promoting comfort e.g.
reducing opioid side effects due to dehydration.

Anticipatory prescription for timely control of common symptoms at dying

phase (for old frail adults, please also refer to Gr5)
 Change route of administration of drugs from oral to subcutaneous route by
syringe pump or driver for more reliable delivery as indicated.
 Maintain continuous infusion of drugs for persistent symptom e.g. pain.
 PRN doses for breakthrough or episodic symptoms e.g. breakthrough pain,
episodic agitation.
 Watch out for organ failure e.g. fentanyl is a better choice than morphine in
renal failure.
 Review regularly.

PM 24
  If not on opioid: Morphine 2.5-5mg SC prn q1h
or fentanyl 12.5 microgram SC prn q1h
Pain
 If on regular opioid: change to SC route and
step up regular dose if needed
Nausea / Vomiting Haloperidol 0.5-1mg SC prn q1h
Haloperidol 0.5-1mg SC prn q1h, or
Terminal agitation*
Midazolam*** 2.5mg SC prn q1h
Myoclonus Midazolam*** 2.5mg SC prn q1h
Death rattle** Hyoscine butylbromide 20mg SC q4 – 6h prn
 If not on opioid: Morphine 1-2mg SC prn q2h or
fentanyl 12.5-25 microgram SC prn q2h
 If on regular opioid: change to SC route and
step up regular dose if needed
Terminal Dyspnoea
Oxygen is indicated for dyspnoea with hypoxaemia
but poor circulation may not give accurate SaO2;
upward titration of oxygen to achieve a target
oxygen saturation may not be appropriate.

* Terminal agitation
 Delirium is not uncommon during the last days of life. For patients in
severe agitation, neuroleptics may be considered when other measures
failed e.g. discontinue drugs potentially causing delirium, rule out urinary
retention, ensure adequate pain control, exclude hypoxia, providing a calm
environment, informing patient when performing care procedures. The
dose of the neuroleptic should be kept at a minimum if possible and patient
should be reviewed in case delirium increases after administration of
neuroleptics.

**Death Rattle
 Noisy breathing due to excessive respiratory secretions, the noise of which
can be distressing for relatives; explain that is part of the natural dying
process.
 Prophylactic or early use of hyoscine butylbromide may reduce further
secretions but has no action in secretions already formed, for which gentle
suction may be needed.
 Avoid over hydration.

PM 25
***Special warning on combined use of opioid and benzodiazepine
 Serious risk and death are reported from combined use of opioid and
benzodiazepine.
 In the last days of life, if patient is put on opioid and benzodiazepine,
communication with patient and family on goal of care and possible risks
including extreme drowsiness, respiratory depression, coma and death are
recommended.
 Do NOT use morphine for sedation.
 Monitoring of respiratory rate is recommended. Discontinuation of other
vital signs monitoring including blood pressure, SaO2 and heart rate which
may not contribute to the goal of care.

PM 26
Rehabilitation
 INTERNATIONAL CLASSIFICATION OF
FUNCTIONING, DISABILITY AND HEALTH (ICF)
 A classification of the functioning, disability, health components.
 Providing a framework to classify and code information about health, to
standardise language facilitating communication, enable better planning of
services, treatment, and rehabilitation.

Components of ICF
The ICF framework consists of two parts: Functioning and Disability +
Contextual Factors.
Functioning and disability are viewed as a complex interaction between the health
condition of the individual and the contextual factors of the environment as well as
personal factors.

Functioning and Disability includes:

 Body Functions and Structures – describes any anatomical, physiological,
and psychological impairment of the human body.
 Activity – describes the person's limitation in performance of tasks/activities
(at individual level).
 Participation – describes the person’s restriction in participating life situation,
socially expected roles or tasks (at societal level).

Contextual Factors include:

 Environmental Factors – factors that are not within the person’s control, such
as family, work, government agencies, laws, and cultural beliefs.
 Personal Factors – include race, gender, age, educational level, and coping
skill.
Re 1
 EARLY MOBILISATION IN
POST-ACUTE ILLNESS PATIENT

Recommendation for Early Mobilisation

When to stop “bed rest” after acute illnesses?

After acute illnesses, it is important to stop bed rest as soon as possible and
start gentle ambulation / exercise to facilitate patients to regain/maintain
ambulation and basic activities of daily living (ADL) to prevent
deconditioning and facilitate discharge.

Step 1: Has the patient been stabilised?

General CONTRAINDICATIONS for resumption of activity / exercise (i.e. patient may need
to keep bed rest)
A. Cardiovascular Causes:
 Acute coronary syndrome with ongoing symptoms
 Uncontrolled atrial or ventricular arrhythmia, sinus tachycardia (e.g.
>120 beat/min)
 Symptomatic high grade / third degree heart block awaiting
intervention
 Symptomatic severe aortic stenosis (e.g. active heart failure, chest pain)
 Active decompensated heart failure
 Symptomatic active pericarditis / myocarditis
 Uncontrolled hypertension (e.g. resting SBP >180 or resting DBP >110)
 Symptomatic or severe orthostatic hypotension
 Acute aortic dissection / acute intramural haematoma
 Acute pulmonary embolism and deep vein thrombosis before
anticoagulation
B. Critical limb ischemia
C. Unstable neurological condition (e.g. stroke in evolution, unstable
recurrent seizures, status epilepticus, increased intracranial pressure)
D. Uncontrolled medical conditions (severe electrolyte disturbances e.g.
significant hyper/hypokalaemia, uncorrected hypovolemia, active systemic
illness/fever, hypoglycaemia, diabetic ketoacidosis etc.)
E. Significant bleeding tendency e.g. coagulopathy (INR >6 or platelet <15 x
109/L) [1,2] or active bleeding
F. Unstable orthopaedic conditions that prohibit exercise (e.g. unstable
fracture, unstable spinal condition)
G. Unstable ophthalmic conditions (e.g. retinal detachment, active retinal
haemorrhage, very recent laser corrective surgery for retinopathy)

Re 2
H. Significant psychiatric conditions with possible harm to either patient or
others during ambulation
I. Other clinical emergencies (e.g. O&G) before stabilisation

*The above contraindication list only serves as a general guide and are not exhaustive.
Under many situations, individualised considerations are needed while taking into
account of the risk of exercise with the underlying condition(s) and the risk/harm of
further bed rest/deconditioning, e.g. patients with stable high-grade heart block but
determined not for pacing; patients with significant postural hypotension which is not
totally correctable.

Step 2: Before starting gentle exercise

 Review medical conditions and the presence of any symptoms (e.g. new
onset / recurrent chest pain, active heart failure symptoms) and optimise
medical treatment.
 Clarify the range of SpO2 to keep & range of oxygen supplement on
exertion if indicated.
 Clarify weight bearing status if indicated (e.g. lower limb fractures)
 Determine thresholds of blood pressure, heart rate, SpO2, H’stix to
withhold exercise & inform medical staff for conditions that outlying
readings are anticipated e.g. arrhythmia or heart block without treatment.

Step 3: What to monitor during gentle exercise

 Any symptoms and signs that warrant modification or termination of
exercise.
 Monitor patient’s performance and tolerance to current activity and/or
stepping up/down of activities.
 Monitor BP/pulse/SpO2/cardiac rhythm as appropriate with pulse
oximetry or telemetry/wearable devices depending on patient’s medical
condition(s) (e.g. patients with cardiac and pulmonary conditions).

Examples of conditions that may warrant termination of exercise

 SBP >= 220 or DBP >= 110
 Drop in SBP >10 mmHg during exercise with increasing workload
 Uncontrolled ventricular or atrial arrhythmia
 New onset second- or third-degree heart block
 ECG changes suggestive of active ischemia
 Signs and symptoms of myocardial ischemia or inadequate perfusion (e.g.
light-headedness, angina, dyspnoea, nausea, cyanosis, pallor)
 Significant hypoxia SpO2 <88% with/without oxygen

Re 3
Step 4: After gentle exercise
 Ask for any discomfort
 Check blood pressure, heart rate, SpO2 or H’stix if indicated

Other conditions:
 Sternal precaution may be needed for post-op patients with sternotomy
wound. Sternotomy wound in general takes 8-12 weeks to heal. When
appropriate, allow free arm movement postop but keep arm close to body
to reduce stress on sternum. Avoid overhead activities, putting hands
behind back, pulling or pushing through the arms.
 For cardiac patients without formal exercise testing as guide for
exercise prescription (e.g. patients shortly after an acute cardiac event or
in CRP phase one), one may consider starting general activities with an
exercise limit set at resting heart rate (HR) + 20 bpm (e.g. for patient with
recent ACS/heart failure); or resting HR + 30 bpm (e.g. for post-cardiac
surgery during initial mobilisation [3]).
 For recent hip arthroplasty patient, clarify with the operating surgeon the
need and extend of hip precaution. Avoid the combination of hip flexion
>90o, adduction and internal rotation before clarification.
 Severe DM retinopathy patient, avoid Valsalva manoeuvre as risk of
vitreous haemorrhage with increased intracranial pressure.
 Ensure proper foot care in patients with DM, peripheral neuropathy or
impaired sensation. Wear proper shoes for exercise and inspect feet
before and after exercises. Refer podiatrist for foot assessment (for both
the affected and unaffected lower limbs) and refer to the corresponding
management guidelines for lower limb care for corresponding conditions
(e.g. DM).

**The above general instructions mainly focus on the resumption of

gentle/low intensity exercise to regain basic ADL and facilitate discharge after
acute illnesses/bed rest. For patients intended for moderate or higher intensity
aerobic exercises, significant resistance training or other more aggressive
forms of training, please consult the relevant specialty/rehab specialist or refer
to specific rehabilitation programs.

[1] Jeevanantham. Clinical Practice Guidelines Endorsed by the Canadian Physiotherapy Association.
Physical Therapy. 2020;101(1)
[2] Morishita S, Hematology. 2020;25(1):95-100.
[3] Adapted from American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and
Prescription. 11th ed. Philadelphia: Wolters Kluwer;2021

Re 4
 EXERCISE MANAGEMENT IN CARDIAC PATIENTS

I. Comprehensive and Multidisciplinary Approach includes:

Physical Training is only part of the treatment; other interventions are also
important for cardiac patients:

A. Secondary Prevention and Risk Factor Modification

 Lifestyle modification: diet, weight control, smoking cessation
 Monitor and helping achieve good CV risk factor control: BP,
HbA1c & lipid
 Patient education on disease nature and self-management
 For patients with CHF: fluid restriction, body weight monitoring
 Tackle acute problems: e.g. usage of TNG

B. Address Psychological and Social issues

 Stress and anxiety management
 Cognitive behavioural modification program for anxiety
 MSW: Financial support

II. Exercise Prescription in Cardiac Patients (Aerobic Endurance

Training)
Exercise prescription should include FITT: Frequency, Intensity, Time,
Types
 The exercise intensity should be gradually increased according to the
patient’s tolerance, ischemic threshold and exercise goals.
 A pre-program symptom limited exercise test is preferable.
 Special precautions or training modification may be necessary in
patient with other co-morbidities.

Frequency: at least 3 days/week, preferably ≥ 5 days/week

Intensity: guided by heart rate of the patient from exercise test

Maximum Heart Rate (HR max)
- Maximum heart rate achieved in pre-program symptom limited exercise
test (Age predicted formula 220 – age is for healthy persons; cardiac patient
has blunted chronotropic response due to medication of heart disease)
Heart Rate Reserve (HRR)
- HR max – HR resting

Re 5
 Target Heart Rate (THR) during exercise
- 40 to 80% of HRR + HR resting OR
- 70 to 85% of HR max
If no exercise test done before, use rough guide as below:
- HR during exercise aim at: HR resting + 20 to 30 bpm AND/OR
- Patients attained certain level in the Rating of Perceived Exertion (RPE)
 If using 6-20 scale: 12 to 16
 If using 1-10 scale: 4 to 6

Time: 20 – 60 min/session

Types: activities that use large muscle groups in a rhythmic and continuous
fashion. E.g. cycle ergometer, treadmill

III. Contraindications for Aerobic Endurance Training

 Unstable angina
 Decompensated heart failure
 Uncontrolled hypertension – e.g. resting systolic BP (SBP) >180 mm
Hg and/or resting diastolic BP (DBP) >110 mm Hg
 Orthostatic BP drop of >20 mmHg with symptoms
 Uncontrolled atrial or ventricular arrhythmias
 3rd AV block without pacemaker
 Pulmonary arterial hypertension >60 mm Hg
 Pulmonary embolism
 Intramural thrombosis
 Severe obstructive cardiomyopathies
 Severe (AVA <1 cm2) or symptomatic aortic stenosis
 Severe mobility limitation

Re 6
 REHABILITATION INTERVENTION
IN STROKE PATIENT
Body function
Assessment Common Intervention
Impairment
Motor
Power (hemiplegia) Hand grip power, Manual Muscle strength training, resistive exercise,
Muscle Test (MMT) power electrical stimulation, repetitive transcranial
grading magnetic stimulation (rTMS)

Mobility of joint Range of movement (ROM) Stretching program, splinting

(stiffness, contracture)

Treat if cause pain, affect hygiene or

function
Tone (spasticity) Modified Ashworth Scale Stretching program, splinting, physical
(MAS) modalities, oral medication, chemo-
denervation (e.g. botulinum toxin, phenol)

Balance, coordination Berg Balance Scale (BBS) Balance, coordination training in parallel
bars, balance board, partial weight supported
walking

Sensory function
Body sensation Sensation chart Sensory re-education, compensatory
(sensory loss vs strategy. Medications, physical modality
hyperalgesia) (e.g. TENS*) to control central pain

Vision Snellen eye chart, Ophthalmologist’s input: prisms glass

confrontation test Visual scanning to compensate for visual
field loss

Visuospatial perception Copy and drawing test, line Visual scanning training, limbs activation
(neglect) bisection/ line cancellation test training, constraint-induced movement
therapy (CIMT)

Swallowing Bedside swallowing test - Control volume and consistency of food

(Dysphagia) Videofluoroscopic swallowing - Ryle’s tube / gastrostomy
study (VFSS) - Rehabilitation strategies: swallowing
Fiberoptic endoscopic exercises, thermal tactile stimulation,
evaluation of swallowing NMES*
(FEES)

Bladder
Neurogenic detrusor Bladder scan - Rule out transient causes e.g. urinary tract
overactivity Urodynamic study infection
Neurogenic detrusor - Incontinence: bladder retraining, timed
underactivity void schedule, regulation of fluid intake,
Detrusor sphincter diapers, anticholinergics for neurogenic
dyssynergia detrusor overactivity
- Urine retention: clean intermittent
catheterisation, Foley, ubretid, alpha
blockers

Re 7
Bowel
Constipation Timed toileting schedule, use of dietary
fibre, and judicious use of laxatives.

Cognition Abbreviated mental test Cognitive retraining & compensatory

(AMT) strategies by OT, CP
Montreal cognitive assessment
(MOCA)

Activity Limitations &

Assessment Common Intervention
Participation Restriction
Communication
Expressive dysphasia, Aphasia Screening Test Dysarthria/dysphasia training by ST
recessive dysphasia, global Use of communication book
aphasia

Mobility
Bed mobility/ transfer/ Timed Up and GO test PT – strength/ balance training/ gait/ stair
standing/ walking/ stair (TUG) training, walking aids prescription, etc.
climbing Berg Balance Scale OT – Visual perceptual training, prescription of
Use of wheelchair (BBS) wheelchair
Modified Rivermead P&O – AFO* for foot drop/ equinovarus
Mobility Index deformity
(MRMI)
Modified functional
ambulatory category
(MFAC)

Self-care
Basic Activities of Daily Barthel index (BI) OT
Living (BADL): feeding/ Functional - Self-care training, virtual reality assisted
grooming/ dressing/ independence measure training
bathing/ toileting (FIM) - Aids and appliances prescription e.g.
commode, shower chair
- Home modification
- Carer education

Sexual dysfunction Counselling, skill training, positioning

Refer OT specialised in sexual rehab/ urologist

Community, Social and

Civil life
Education - Vocational training by OT
Employment - Mobilize community resources to promote
Recreation and leisure community integration by MSW:
Driving  Rehab/Easy bus or other transport services
 Supported employment
 Financial support
 Voluntary agencies, self-help groups
- Driving rehabilitation

Abbreviations* AFO – ankle foot orthosis

TENS – transcutaneous electrical nerve
stimulation
NMES – neuromuscular electrical stimulation

Re 8
 HEMIPLEGIC SHOULDER PAIN SYNDROME (HSP)

Contributors to post stroke HSP, usually multi-factorial.

Neurological
 Central post stroke pain/ thalamic pain syndrome
 Peripheral neuropathy, brachial plexus injury due to traction injury
 Complex regional pain syndrome (CRPS)

Mechanical
Spasticity, shoulder subluxation, rotator cuffs tendinopathy (impingement,
tendonitis, tear), bicep tendonitis, glenohumeral joint disorders (bursitis, OA),
adhesive capsulitis, myofascial pain.

Diagnosing the causes of HSP

 History, physical examination, special tests/manoeuvres (Neer, Hawkins
and Jobe)
 Imaging (XR for fracture and subluxation; US for tendinopathy, joint
effusion; MRI)
 Electrodiagnosis (NCT, EMG)
 Diagnostic injections (intramuscular, intra-articular)

Management
Prevention: early mobilisation and physiotherapy, proper positioning, correct
transfer techniques.

Pathology based intervention depending on the identified contributors:

Subluxation: strapping, shoulder sling while in upright or walking, functional
electrical stimulation (FES) to deltoid and supraspinatus
muscles
Neurologic: transcutaneous electrical nerve stimulation (TENS), neuropathic
pain drugs
Spasticity: anti-spasticity drugs, botulinum toxin injection
Musculoskeletal factors: arthritis/ tendinopathy/ capsulitis – anti-inflammatory
drugs, steroid injection
Myofascial pain: trigger point injections

Re 9
 COMPLEX REGIONAL PAIN SYNDROME (CRPS)

A disorder of the extremities following an injury, surgery, or vascular event such as

stroke, that is characterised by neuropathic pain, limb swelling, limited range of
motion, vasomotor instability, skin changes, and patchy bone demineralisation.

May consider in hemiplegic stroke patient with subacute or chronic severe

upper limb pain, swelling and increased temperature. (Shoulder Hand
Syndrome)

Causes: Stroke, immobilisation, peripheral nerve injury, fracture, surgery, trauma

 Type I refer to patient without a definable nerve lesion
 Type II where a peripheral nerve injury is present

Diagnosis is largely clinical and by exclusion of other DDx.

Budapest Diagnostic Criteria for CRPS

Criteria (All 4 must be met)
1 Persistent pain disproportionate to inciting event
Categories
Sensory Vasomotor Sudomotor/ Motor/Trophic
Oedema
2 ≥1 Hyperesthesia, Temp asymmetry, Oedema, ↓Joint ROM,
symptom in Allodynia Skin colour Sweating Motor dysfunction,
3 out of 4 asymmetry, asymmetry, Trophic changes
categories Skin colour Sweating change (hair, nail, skin)
change
3 ≥ 1 sign in 2 Hyperalgesia Temp asymmetry Oedema, ↓Joint ROM,
out of 4 (pinprick), (> 1C°) Sweating Motor dysfunction
categories Allodynia (light Skin colour asymmetry, (weakness, tremor,
touch, temp, asymmetry, Sweating change dystonia)
deep somatic Skin colour Trophic changes
pressure, joint change (hair, nail, skin)
movement)

4 No other diagnosis can better explain the patient’s signs and symptoms

Investigation
 To rule out other (DDx)
- WBC, ESR, CRP (soft tissue infection, cellulitis)
- Doppler US (DVT)
- Urate, anti CCP (gout, RA)
- XR joints, limbs (arthritis, bone fracture)
 Triphasic bone scan: ↑regional radiotracer uptake provides clinical evidence
of CRPS, negative scan not rule out diagnosis
Re 10
Treatment
 Goal: allow active participation in rehabilitation to restore limbs
movement and strength.
 Encourage early mobilisation by explaining that the condition usually not
indicate active tissue damage and limb movement is safe.
 Multidisciplinary approach, treatment based on the identified clinical
problem: oedema management (positioning, pressure garments), pain
medications, desensitisation program, transcutaneous electrical nerve
stimulation (TENS), cognitive behavioural therapy.
 Refer pain specialist in severe and refractory cases.

Medication
 NSAID
 Anti-depressant: Tricyclic antidepressant (amitriptyline) / Serotonin and
norepinephrine reuptake inhibitor (duloxetine, venlafaxine)
 Anti-convulsant: Gabapentin, pregabalin
 Prednisolone 30-60 mg/day taper off over 4-12 weeks.
 Bisphosphonate (e.g. alendronate) in patient with regional osteoporosis of
affected limb.

Adjunctive therapy Starting Dose Max dose

Amitriptyline 10 mg/day 75 mg/day
Duloxetine 60 mg/day 120 mg/day
Venlafaxine (Effexor) 37.5 mg BD 187.5 mg BD
Gabapentin 300 mg nocte or 100 mg TDS 600 mg TDS
100 mg nocte (for elderly)
Pregabalin (Lyrica) 50 mg BD 300 mg BD

Re 11
 SPASTICITY MANAGEMENT IN STROKE PATIENT

Assessment
History taking to explore
 Spasm frequency, duration, severity, location

How spasticity affect patient

 Pain symptoms
 Interference of daily care (e.g. skin fold hygiene, dressing, transfer, napkin
change, foley care)
 Difficulty in splint application (e.g. hand splint, ankle-foot-orthosis)
 Walking difficulty (e.g. spastic equinovarus, scissoring gait)
 Psychological: disfigurement, poor self-body image

P/E
 Limbs strength, Range of Movement (ROM) over affected joints
 Modified Ashworth Scale (MAS) to assess degree of spasticity (0-4,
normal to fixed rigidity)
 Muscle’s involvement, pattern of spasticity, clonus (e.g. ankle clonus)
 To look for noxious stimuli (e.g. retention of urine, stool impaction,
ingrown toenail, pressure sore, occult fracture, skin irritation such as
eczema).

Management (Also see Gr43)

 Prevention is paramount: proper positioning, stretching exercise,
splinting programme
 Elimination of noxious stimuli
 Pharmacological treatment:
- Importance on goal setting, whether treatment can help patient e.g. pain
relief, easier daily care, facilitate voluntary movement and physical
training etc.
- Not all spasticity is harmful (e.g. can prevent DVT, extensor tone in
lower limbs may help body weight support for transfer or walking).
- Oral Medication: Benzodiazepines (diazepam, clonazepam), Baclofen,
Dantrolene, Tizanidine, Gabapentin if pain (refer Geriatric Medicine
Section).
- Chemo-denervation:
 Botulinum toxin (Botox, Dysport), phenol injection therapy
 Injection has to be followed by interdisciplinary care, e.g. stretching,
bracing, and exercise to reach achievable goals.
Re 12
Common patterns of spasticity in stroke patient and treatment benefits

Pattern Major muscles involved Treatment benefits

Upper limbs
Shoulder adduction, Pectoralis major *# Sitting posture
internal rotation and Teres muscle group Ease of dressing
retraction Subscapularis Axillary hygiene
Latissimus dorsi Improve UL function
Improve balance and
symmetry of gait
Elbow flexion Brachioradialis * Improve elbow flexion
Biceps brachii * deformity
Brachialis Improve arm reach/retrieve
Pronation of forearm Pronator teres * Improve hand and forearm
Pronator quadratus function

Flexed wrist and Flexor carpi radialis * Palmar skin hygiene

clenched hand Flexor carpi ulnaris * Improve grasp release, hand
Flexor pollicis longus *# function
Flexor digitorum Easier hand splint
superficialis* application
Flexor digitorum
profundus *
Lower limbs
Knee Flexion Medial hamstrings * Improve weight bearing
Biceps femoris * Improve seating posture and
gait pattern
Planter flexed and Gastrocnemius *, soleus * Correct equinovarus
inverted foot Posterior tibialis *# deformity, and foot
inversion to allow heel
strike
Improve gait
* Common target muscle for Botulinum injection
# Ultrasonography guidance is advised

Re 13
 MEDICAL COMPLICATION IN SPINAL CORD INJURY

Spinal shock
 Clinical: areflexia, flaccid paralysis, loss of sensation, loss of
bulbocavernosus reflex
 May have bradycardia, hypotension, if loss of sympathetic tone due to
damage to sympathetic pathways in T6 or above (neurogenic shock)
 Mx: fluid resuscitation, inotropes, complications prevention, rehabilitation

Deep vein thrombosis

 DVT prophylaxis if immobility
 Mechanical: intermittent pneumatic compression, graduated compression
stockings
 Anticoagulation if not contra-indicated

Orthostatic hypotension
 SBP ↓>20 or DBP ↓>10 mmHg
 Patient education: sleep head up to 10-20o, supine to erect position in
gradual stages, avoid prolonged recumbence
 Adequate hydration (e.g. >1.5 L/day), salt intake (6-10 g/day) if not
contraindicated
 PT: standing training, tilt tablet training, isometric exercise
 OT: Pressure stocking, P&O: abdominal binder
 Off offending medications
 Fludrocortisone 50-200 microgram daily, monitor Na/K level
 Midrodrine 2.5 to 10 mg BD to tds

Neurogenic bladder
 Urine c/st, bladder chart, post void bladder scan, urodynamic study,
baseline surveillance of urinary system by ultrasonography
 Retention of urine: intermittent catheterisation preferable to foley
 Neurogenic detrusor overactivity: anticholinergic drugs (oxybutynin,
Detrusitol, Vesicare), mirabegron (β3-adrenoceptor agonist), intravesical
botulinum injection.

Constipation
 Adequate fluid and dietary fibre intake, encourage exercise
 Planned and regularly scheduled bowel time
 Oral and rectal laxative
 Digital rectal stimulation
Re 14
Pressure ulcers
 High risk due to impaired sensation below the level of injury.
 Education importance of turning, positioning, pressure point relief, regular
skin monitoring/care.
 Occupational Therapist for pressure relieving devices (e.g. ripple mattress,
wheelchair seating cushion)
 Dietitian for nutritional support
 Wound dressing, treat wound infection

Re 15
 AUTONOMIC DYSREFLEXIA (AD)

 A medical emergency to be considered in spinal cord injury (SCI)

patients at T6 or above presented with abrupt ↑BP.
 Mechanism: Loss of descending autonomic control, noxious stimulus
below level of injury → trigger sympathetic response and vasoconstriction
in peripheral and splanchnic circulation → ↑BP which then sensed by
baroreceptors → counteract- central parasympathetic response failure to
reach below the level of injury → excessive parasympathetic activity
above level of SCI and unopposed sympathetic activity below level of SCI.
 Common precipitating causes: restrictive clothing, retention of urine,
blocked foley, UTI, faecal impaction, painful pressure sore, ingrown
toenail.
 Sign and Symptoms:
- Abrupt ↑BP (↑SBP >20-40 mmHg or DBP >15 mmHg of baseline)
and bradycardia (but tachycardia also common).
- Flushing, headache, engorged neck vein, sweating, pupillary
constriction (above level of SCI)
- Pale, cool, no sweating, piloerection (below level of SCI)
 Complications: retinal haemorrhage, stroke, SAH, seizure, MI
 Management
- Sit up patient, loosen all tight-fitting clothing and devices
- Identify and remove noxious stimulus
 Check and correct any kinks and obstructions of foley catheter,
remove and replace if not draining.
 Bladder scan, if retention of urine, catheterise with use of xylocaine
jelly.
 If AD persist, including a sustained elevated BP, suspect faecal
impaction. Use xylocaine jelly for gentle digital examination and
perform manual evacuation.
- Close monitor BP, use short acting anti-HT drug if persistent significant
↑BP
 E.g. *sublingual TNG 500 microgram, *transdermal TNG 5 mg
(*the use of nitrates needs to exclude concurrent use of sildenafil
for male patients with erectile dysfunction), oral nifedipine 2.5mg,
hydralazine 10 mg, minipress 1mg.
- Watch out for rebound hypotension once the cause of AD is identified
and treated.

Re 16
Potential Causes - Any painful or irritating stimuli below the level of injury may cause AD.
Bladder and bowel problems are the commonest causes of AD (*).

Urinary System Reproductive System

Bladder retention * Sexual intercourse *
Blocked catheter *
Catheterization *
Ejaculation
Urinary tract infection*
Bladder or kidney stones
Urologic instrumentation, such as
 Epididymitis
Scrotal compression (sitting on scrotum).
cystoscopy Electroejaculation and vibratory
Detrusor sphincter dyssynergia. stimulation to induce an ejaculate.

Menstruation *
 Pregnancy, especially labour and delivery.
Vaginitis

Gastrointestinal System Other Systemic Causes

Bowel impaction * DVT
Appendicitis Excessive alcohol/ caffeine
Gallstones Fractures or other trauma
Gastric ulcers or gastritis Functional electrical stimulation
Haemorrhoid pain * Heterotopic ossification
Surgical or invasive diagnostic procedures
Skin
Constrictive clothing, shoes, or
appliances *
Ingrown toenail *
Pressure ulcers *
Contact with hard or sharp objects.
Burns, sunburn
Insect bites

Re 17
 TRACHEOSTOMY WEANING

Review indication of tracheostomy, assess whether the indication has resolved.

 Carefully weigh the risk/benefit of weaning and seek agreement with next of
kin (esp. in severe neurological impairment, e.g. GCS < 8, usually no benefit in
swallowing/ speech while compromising a secure access for secretion
management).
 Discuss the plan of weaning and management if fail to wean.

Criteria for tracheostomy weaning

 Adequate ventilator effort, i.e. successful prolonged spontaneous breathing, not
depend on mechanical ventilation.
 Adequate level of consciousness and sensorium.
 Adequate cough effort (e.g. peak expiratory flow rate, PEFR / peak cough flow,
PCF >160 L/min)
 Able to handle and swallow own secretion (e.g. tolerate cuff deflation)
 No excessive sputum (e.g. ≤ 4 suction/ 24 hours)
 Airway patency (test by gloved finger occlusion: simply deflating the cuff of
tracheostomy tube [TT], occluding the TT with gloved finger, observe breathing
effort and phonating).
 If necessary, to consult ENT for assessment of airway patency before weaning.
 Hemodynamically stable

Weaning
Capping trial:
1. Capping off non-cuff or deflated TT (preferably fenestrated tube) with
progressive extended duration, depending on patient tolerance.
2. e.g. 15-60 mins → 4 hours → 8 hours → during daytime kept overnight → ≥ 24
hours → off TT (Preferably to start weaning at daytime on weekdays with more
adequate manpower)
3. Continuous SpO2, RR, HR monitoring.
4. STOP capping if note to have sign of distress: HR >120 or ↑HR >20 beats/min,
RR >30 /min, SpO2 ≤ 90%, SBP >180 mmHg, PaO2 <60 mmHg, PaCO2 >50
mmHg, Rating of Perceived Dyspnoea (RPD) >6-10, clinical respiratory distress.

Failure capping trial:

 Review readiness for decannulation.
 Capping re-trial for shorter duration or speaking valve trial.
 Downsize tracheostomy tube (avoid “downsizing” by more than 1 trach size at
a time).
 Consider consult specialist (e.g., ENT) for advice.

Re 18
 MEDICAL COMPLICATIONS OF AMPUTEE

Delayed wound healing

 More common in vascular cause of amputee
 Causes:
- Inappropriate amputation level, inadequate blood supply, trauma, infection,
poor nutritional status.
 Management:
- Dressing, treat infection
- Leave the sutures in place until well approximated
- Debridement / revision

Dermatological lesions
Ulceration
 Excess pressure over bony prominence due to ill-fitting socket, results of
friction associated with loose socket

Folliculitis
 Hair roots infection resulting from poor hygiene, sweating, poor socket fit, may
develop to boils or abscess.
 Tx: clean the area with antiseptic solution, keep it dry, oral antibiotic in severe
case.

Contact dermatitis
 Due to heat and friction at the interface between the prosthetic socket and stump.
 Tx: Barrier creams, emollients and trial of topical corticosteroids.

Epidermoid cysts
 May occur along the brim of prosthesis when the sebaceous glands are plugged
by keratin, causing proliferation of epidermal cells within a circumscribed
space of dermis.
 May be painful and inflamed.
 Treatment
- Prosthesis adjustment to provide pressure relief
- Treat any secondary infection
- May need I&D, surgical resection

Stump oedema syndrome/ verrucous hyperplasia

 Oedema in the distal stump due to proximal constriction in poor prosthesis
fitting, the brim is tight proximally and lose distal contact.
 After prolonged period, “verrucous hyperplasia” develops, which is wart like

Re 19
 skin overgrowth and may ulcerated, rarely may cause squamous cell carcinoma.
 Treatment
- Check fitting of prosthesis
 Relieving the proximal constriction
 Ensure adequate distal socket wall contact
- Stump massage
- Use shrinker stocking, Ace bandage to control oedema

Painful neuromas
 Nerves cut ending may develop neuroma, clinical palpation of firm nodule
resulting in tingling sensation.
 Management:
- Socket modification
- Lignocaine and steroid injection into the neuroma
- Surgical resection

Contractures
 >15º at hip or knee will be difficult to accommodate
 Risk factors
- Limited mobility, delayed wound healing, poor pain control, short residual
limbs
 Management
- Avoid prolonged knee flexion (e.g. use stump board when sitting)
- Aggressive ROM physiotherapy
- Post OT casting / splinting

Phantom pain
 Pain in the amputated limb, i.e. lost part of the limb not the residual limb
 Occurs in 50-80% of amputees, usually diminishes with time, if persistent pain
>6 months, poor prognosis for spontaneous recovery
 Management
- Peripheral stimulation
 Wear the prosthesis
 Gentle manipulation of the stump
 Isometric contraction of the phantom muscles
 TENS
- Psychological therapy
 Relaxation and coping skills
 Mirror image therapy
- Neuropathic pain medication: TCA, gabapentin, pregabalin, SNRI

Re 20
 ORTHOSIS – ANKLE FOOT ORTHOSIS (AFO)

Functions of AFO
For mobile patients
 Provide support for ankle joint weakness, optimal functional alignment
during walking, allow adequate clearance of the foot during the swing
phase of walking
For immobile patients
 Counteract spasticity and prevent deformity
 Provide protection and limit ROM to promote healing of the ankle
structure

Indications:
 Peroneal nerve palsy, foot drop, equinovarus deformity in spastic
paraplegia or hemiplegia patient, fracture ankle.

Different designs of AFO

Non-articulated AFO
Posterior Leaf Spring AFO (Fig. 1)
 Consist of a thin plastic band behind the ankle,
trimmed posteriorly to the malleoli, highly flexible.
 Allow patients to overpower the brace to perform
plantarflexion during the push off and prevent foot
drop during swing phase.
(Fig.1) Posterior leaf spring AFO
 Indicated in patients with flaccid foot drop.

Solid/Rigid plastic AFO (Fig. 2)

 Ankle trim-lined at or anterior to the malleoli
 No motion allowed at the ankle joint
 Indicated in patients with
- Severe spasticity and deformed foot (e.g.
equinovarus deformity)
- Mediolateral instability
- Need of immobilisation at foot and ankle

(Fig.2) Solid AFO

Articulated / hinged AFO
 Limit or assist foot movement by means of stops (pins) or assists (springs)
respectively.
Re 21
Regular check-up for AFO fitness
Necessary as wear and tear of prosthesis, also the shape of the limb may
change.
 The contour of AFO should fit the leg, not too loose or tight.
 No sharp or impingement point.
 Upper brim of AFO should be 1-2 inch (2-3 finger width) below the fibular
head to prevent peroneal nerve compression.
 Malleoli should in the same axis as the orthotic joint.
 Natural position of ankle joint about 90o.
 In stance, the knee should be fully extended, and the sole of the shoe should
be flat on the floor.
 During the swing, adequate toes clearance.

Re 22
COMMON INSTRUMENTS IN REHABILITATION

Rehab-assessment Instrument Description Interpretation #

Activities of daily Barthel Index (BI) - Measure the performance in basic activities of daily 80–100, slight assist to independent
living living 60–79, mild to moderately dependent
- 10 items: 7 items for personal care activities and 3 for 40–59, moderately dependent
mobility, total (0 – 100) 20–39, severely dependent
- Higher score associated with a greater likelihood of < 20, totally dependent.
being able to live at home independently
*MCID = 1.85
Functional - To assess physical and cognitive disability in terms of - less ceiling or floor effect
Independence burden of care FIM >80, 94% sensitivity predict discharge
Measure (FIM) - Assessing 6 areas of function: self-care, sphincter to non-institutional care in stroke patients [1]
control, mobility, locomotion, communication and
social cognition. * MCID = FIM (total) 22, FIM (motor) 17,
- 18 items: Motor FIM (13 items) and cognitive FIM (5 FIM (cog) 3
items)
- Score (1-7) per item, total (18 – 126)
Upper limb Functional Test for - Assess upper limb function based on developmental ≥ Level 4 means regaining certain self-care
function the Hemiplegic stages of stroke recovery in a hierarchy of seven ability with upper limb
Upper Extremity functional levels (1 to 7)
(FTHUE) - Level (1) No voluntary movement, (2) Beginning
active motion, no functional use, (3) Passive
stabilizer, (4) Active stabilizer, (5) Gross motor assist,
(6) Fine motor assist, (7) Dominant with fine motor

Hand dexterity 9-hole peg test - Measure the time of placing 9 pegs into the holes of a
(9HPT) board

Mobility Timed Up and Go - Measure the time to rise from a chair, walk 3 meters < 10 – 15 s = normal mobility
test (TUG) and walk back to the chair to sit down < 20 s within normal limits for frail elderly
- Assess mobility with both static and dynamic balance

Re 23
Balance Berg Balance Scale - Quantitative assessment of the balance in functional > 50 indicate functional balance
(BBS) tasks, E.g., Sitting, transfer, standing, turning and < 45 predict risk of fall [3]
reaching
- 14 items, score (0-4) per item, total (0 – 56)

Unilateral Neglect Line bisection test - To mark the center of a line in front of the patient Scored by measurement of deviation of the
(ULN) marking from the true centre of the line

Line cancelation test - To cross out target symbols presented on a page Fail to cancel stimuli on the side of the page
opposite the brain lesion

Copying and - Copying simple figures (e.g., flowers, starts, cubes) Incomplete drawing or copying with
drawing tasks and drawing from memory (clock, butterfly) omissions or gross distortions on the
contralesional side

Spasticity Modified Ashworth - 4 points scale testing the resistance to passive 0 = normal tone to 4 = fixed rigidity
Scale (MAS) movement about a joint
- Most popular tool for spasticity assessment, simple to
use

Mental Abbreviated Mental - A simple screening test included 10 questions to Cut off for cognitive impairment: < 6
(cognition screening Test (AMT) screen cognitive impairment
instruments) - E.g., age, time, year, address, place, birthday, count
down from 20
- 1 score per question, total (0 – 10)

Mini-Mental State - Widely used screening test for cognitive impairment

Examination - Examine orientation, immediate and short short-term
(MMSE) memory (3 item), attention and working memory,
* copyright issue language and visuoconstructional skills
- Total (0 – 30)

Re 24
 Montreal Cognitive - A handy screening instrument for cognitive < 26, may indicate cognitive impairment [4]
Assessment (MoCA) impairment, in addition to the domain of MMSE, also (local data cut off < 22) [5]
for testing executive function (trail making), verbal + 1 to scored mark if ≤ 12 yrs education
fluency, verbal abstraction -------------------------------------OR
- Need further diagnostic instrument for dementia or Norm-derived age and education corrected
mild cognitive impairment (MCI) if below cut off cutoff: < 2nd percentile (major); < 16th
percentile (mild cognitive impairment)

Depression Geriatric Depression - Brief and easy to use screening tool for depression in ≥ 8 possible depression
screening Scale – elderly ≥ 7 possible depression in stroke patient[6]
Short From (GDS- - False negative in mild depression
SF) - Total (0 – 15)

* MCID = Minimal Clinically Important Difference

# Cut off values provide general idea of possible impairment which are non-diagnostic, values may also vary with
different disease entities. More useful to use as a tool to monitor treatment response.

[1] D. Chumney. et al. J. of rehabilitation research and development., vol 47, p17-29, 2010.
[2] S.-T. Shum et al J. Stroke Cerebrovasc. Dis., vol. 23, no. 8, pp. 2117–2121, 2014.
[3] K. O. Berg. Can. J. Public Health, vol. 83 Suppl 2, pp. S7-11, 1992.
[4] Z. S. Nasreddine et al. J. Am. Geriatr. Soc., vol. 53, no. 4, pp. 695–699, Apr. 2005.
[5] P. Y. Yeung. Hong Kong Med. J., vol. 20, no. 6, pp. 504–510, 2014.
[6] W. K. Tang et al. J. Affect. Disord., vol. 81, no. 2, pp. 153–156, Aug. 2004.

Re 25
Respiratory Medicine
 MASSIVE HAEMOPTYSIS

Definition:
Arbitrary, expectorated blood ranging from >100-200 ml/24 hours. Bleeding
rate and underlying lung function are important factors for management.

Management objectives:
Prevent asphyxia, localize and stop bleeding, determine and treat underlying
cause of bleeding.

Management:
1. Airway protection is most important in massive haemoptysis, close
observation and treatment in ICU/HDU is desirable.
2. Turn the patient into decubitus position with suspected bleeding side
down (if can be determined initially).
3. Closely monitor vital signs, O2 supplement and establish IV access.
4. Avoid sedation and cough suppressant.
5. Correct possible causes of bleeding: antibiotic for infection, stop
anticoagulant or correct coagulopathy.
6. Intubation for suction and ventilation if depressed conscious state with
risk of asphyxia: single lumen ET if urgent; double lumen ET by
anaesthetist is better for isolation of bleeding side.
7. Flexible bronchoscopy may help to localise bleeding site ± therapy.
8. Urgent contrast CT thorax / bronchial arteriogram for bronchial arterial
embolization (BAE) if expertise is available.
9. Consult surgeon for emergency lung resection if bleeding fail to be
controlled.

P1
 SPONTANEOUS PNEUMOTHORAX
(Ref: BTS guideline for pleural disease 2023)

Definition: Air in the pleural space in the absence of trauma or causative

medical intervention.
Size: sufficient (usually ≥ 2cm laterally or apically on CXR or any size on
CT which can be safely accessed with radiological support)
Primary spontaneous pneumothorax (PSP): No underlying lung disease
Secondary spontaneous pneumothorax (SSP): Presence of underlying
lung disease. Those who are ≥ 50 years of age with significant smoking
history can be managed as SSP.

Management depends on symptoms ± presence of high risk

characteristics

High risk characteristics

 Haemodynamic compromise (tension pneumothorax)
 Significant hypoxia
 Bilateral pneumothorax
 Underlying lung disease
 ≥ 50 years of age with significant smoking history
 Haemopneumothorax

Symptomatic and/or presence of high risk characteristics with sufficient

size
Chest drain insertion

Asymptomatic
Conservative care (observation and oxygen therapy)
Consider chest drain insertion if enlarging pneumothorax or worsening of
symptoms

Symptomatic without high risk characteristics

1. Pneumothorax size insufficient
 Conservative care (observation and oxygen therapy)
2. Pneumothorax size sufficient
 Conservative care (observation and oxygen therapy) and monitor OR
 Needle aspiration or chest drain insertion

P2
Indication for surgical pleurodesis
 First pneumothorax presented with tension or first secondary
pneumothorax associated with significant physiological compromise
 Second ipsilateral pneumothorax
 First contralateral pneumothorax
 Synchronous bilateral spontaneous pneumothorax
 Spontaneous haemothorax
 Persistent air leak (despite 5 to 7 days of chest tube drainage) or failure
of lung re-expansion
 Professions at risks (e.g. pilots, divers)
 Pregnancy

Chemical pleurodesis (e.g. Talc, minocycline) may be considered for patients

who refuse or are considered unfit for surgery.

P3
 PLEURAL EFFUSION
(Ref: BTS guideline for pleural disease 2023)

Diagnosis
1. Pleural tapping should not be performed for bilateral pleural effusions in
clinical setting strongly suggestive of a transudate unless presence of atypical
features or failure to respond to therapy.
2. Diagnostic tapping with bedside USG guidance improves success rate and
reduces complications.
3. Differentiate the nature of pleural fluid by the followings:
 Appearance (e.g. Pus→empyema; Milky→consider chylothorax)
 Light’s criteria: (can be “Exudative” if any one of followings met)
- Fluid protein / serum protein >0.5
- Fluid LDH / serum LDH >0.6
- Fluid LDH > 2/3 of the upper limit of the normal range of serum LDH
 Microbiological workup
- Bacterial: gram stain, culture (using blood culture bottle)
- TB: AFB smear/culture, MTB-PCR, ADA, (closed pleural biopsy)
- Fungal: fungal culture
 Send fluid for cytology if malignant effusion is suspected.
 Other tests that might be useful: Triglyceride (>110 mg/dL or >1.24
mmol/L in chlylothorax), pH and glucose (for complicated
parapneumonic effusion)
4. Thoracoscopy (Medical or Surgical with VATS) is the next investigation of
choice in exudative pleural effusions with inconclusive diagnostic pleural tap.
Close pleural biopsy can be considered if there is a high pre-test probability
of TB.

Indications for pleural fluid drainage in pleural infection (empyema and

complicated parapneuonic effusion)
1. Frank pus or turbid / cloudy pleural fluid on diagnostic tapping.
2. Pleural fluid biochemistry:
a) pH ≤7.20
b) pH >7.2 to <7.4 and LDH >900 IU/L, esp if any of the following:
 Large pleural fluid volume
 Pleural fluid glucose ≤4.0 mmol/L
 Septation on USG
 Pleural contrast enhancement on CT (if done)
3. Positive Gram-stain ± positive culture of pleural fluid.

P4
*Consider intrapleural therapies (tissue plasminogen activator + DNase if
available) to facilitate the drainage of multiloculated pleural collections in
patients not fit for surgical decortication.

*For those who do not have immediate need of chest drain insertion,
need to monitor clinical progress, reassess the need for repeated aspiration if lack
of improvement

*Consider surgical decortication if uncontrolled pleural infection after chest

drain insertion/intrapleural therapies.

Antibiotics duration for pleural infection

In general, two to six weeks of antibiotic therapy according to initial presentation,
the amount of pleural effusion, pleural fluid parameters and clinical response.

Management of persistent / recurrent malignant pleural effusion

1. Supportive care
2. Consult respiratory physician for difficult cases
3. Tube drainage and chemical pleurodesis
 Agent: Talc up to 5 g in 100 ml NS (Alternative: Minocycline 300 mg in
50-100 ml NS).
 Must be performed under adequate analgesia ± sedation.
 Clamp drain for 1 to 2 hours post-sclerosant application, then release
clamp.
**If there is co-existing pneumothorax or bubbling present in chest drain
bottle, DO NOT clamp drain. Rather, hang up chest drain to ~50cm above
patient (Rationale: to allow air to be drained but not the sclerosant)
 Chest tube kept unclamped thereafter for drainage until daily output <150
ml/day for 2 days and CXR shows the lung to be re-expanded with most
of the effusion drained.
4. Surgical pleurodesis (can be considered in patients with good performance
status).
5. Long term ambulatory indwelling pleural catheter drainage (including
patients with trapped lung).

Other indication for chest drain insertion (in pleural effusion)

 Haemothorax (surgical consultation is usually indicated)

P5
 OXYGEN THERAPY

Goal of O2 therapy: to deliver the minimum concentration required for

adequate tissue oxygenation with the least risk of toxicity.
 Prescriptions should be precise and adequately monitored (e.g. by SpO2
or ABG).
 Device used should be safe, effective and with the greatest patient
comfort and acceptance at the last cost.

Common oxygen delivery methods

Devices with variable FiO2
 Device flow rate < Patient’s inspiratory flow demand
 The actual FiO2 delivered is variable, depending on multiple factors
including device O2 flow rate, patient’s inspiratory flow rate and volume
of O2 reservoir.
 The FiO2 delivery can be increased by increasing the volume of reservoir
and O2 flow rate.

1. Standard dual-prong nasal cannula (Reservoir: Nasopharynx)

 FiO2 up to ~ 0.44 if O2 flow rate set up to 6L/min
 FiO2 variable, roughly 20% + (4×oxygen litre flow per minute)
 Most comfortable and cost-effective
 Flow rate >6 L/min → wastage of O2 and mucosal dryness
2. Simple face mask with no reservoir bag (Reservoir: nasopharynx and
volume of the face mask)
 FiO2 up to 0.55 if O2 flow rate set at 6 to 10 L/min
 O2 flow rate set below <5 L/min may cause CO2 rebreathing
3. Rebreathing mask with reservoir bag (Reservoir: Nasopharynx/reservoir
bag)
 FiO2 0.70 if O2 flow rate set at 6 to 10 L/min
 O2 flow must be ≥6 L/min to keep reservoir bag inflated throughout
inspiration & expiration
 No one-way valve between reservoir bag and mask
4. Non-rebreathing mask with reservoir bag (Reservoir: Nasopharynx/
reservoir bag)
 FiO2 up to ~ 0.80–1.00 if O2 flow rate set at 10-15 L/min
 Equipped with one-way valves to prevent exhalation into reservoir bag
and inhalation through mask exhalation ports (but usually only one of
the two valves on the mask exhalation ports is installed for safety reason)
P6
Devices with fixed FiO2
 Device flow rate > Patient’s inspiratory flow demand
 Delivery of oxygen at a fixed and pre-set concentration regardless of
patient’s clinical status (e.g. respiratory rate, tidal volume…)

1. Venturi mask
 Accurate FiO2 adjustable from 0.24 to 0.60 if O2 flow rate set at 3-15
L/min (O2 required to drive can be read off from the Venturi device)
2. Humidified high flow nasal cannula, e.g. Optiflow, Airvo systems
 Delivers humidified O2 at fixed FiO2 at high flow (up to 60 L/min)
 Heat & humidified O2 to prevent airway desiccation & epithelial
injury and better patient’s tolerance
 Provide a small PEEP effect that enhances oxygenation.
 Actual FiO2 delivered can be set (by internal oxygen blender) or
determined (by sensor) depending on the device used.
 Set parameters
- Dew-point temperature (37oC, 34oC, 31oC),
- Gas flow rate (10 - 60L/min)
- FiO2 (0.21 – 1.0) – by adjusting source O2 flow rate

Other common oxygen delivery methods

1. T-piece to endotracheal or tracheostomy tube: O2 delivered through the
shorter end, open window by one-third if PaCO2 is high.
2. Thermovent to endotracheal or tracheostomy tube: Avoid using if copious
sputum. Requires daily exchange.
3. Tracheostomy mask: consider using humidification in non-infectious
situation (e.g. heated humidifier).

P7
 ADULT ACUTE ASTHMA
(Ref: GINA 2022)

Definition of asthma exacerbations

 An acute or sub-acute worsening in symptoms and lung function from the
patient’s usual status.
 Occasionally it may be the initial presentation of asthma.

Assessment
Initial assessment:
 Airway, Breathing, Circulation
 Life-threatening features
- Drowsiness, Confusion, Silent chest
 Consult ICU if any +ve
 Prepare for intubation

Further assessment
 According to worst feature identified → Moderate vs Severe Exacerbation
Mild / Moderate Severe
Talks in phrases Talks in words
Prefers sitting to lying Sits hunched forwards
Calm Agitated
Increased respiratory rate RR >30/min
No use of Accessory muscles Use of Accessory muscles
Pulse rate 100-120/min Pulse rate >120/min
SpO2 (RA) 90-95% SpO2 (RA) < 90%
PEF >50% predicted / best PEF ≤ 50% predicted / best

Monitoring
 Vital signs, pulse oximetry, PFR/FEB1, ± ABG, electrolytes, ± CXR

Management
Moderate exacerbation
 Controlled O2 aiming SpO2 93-95% by nasal cannulae or mask
 Short-acting β2-agonists
- Salbutamol 4 puff q4h with spacer + PRN use
- High dose/more frequent dosing may be considered in very symptomatic
patients or those with severe exacerbation
 Oral corticosteroids
 ± Ipratropium bromide

P8
Severe exacerbation
 Same as treatment for moderate episode plus
 Ipratropium bromide 3-4 puffs with spacer
 Oral / IV corticosteroids
 Consider magnesium sulphate 1.2-2g iv over 20 minutes

Reassessment
 Clinical status and response to treatment
 Preferably with lung function measurement (PEF/FEV1)
 In ALL patients 1 hr after initial treatment
 If satisfactory response
- Controlled O2 aiming 93-95%, gradual weaning
- Prednisolone up to 50mg/d (or Hydrocortisone 200mg/d in divided doses)
for 5-7 days, adequate for most patients
- Continue inhaled β2 agonist q4h.
 If unsatisfactory response
- Inhaled β2 agonist 6-10 puffs up to q15min
- Inhaled ipratropium bromide 3-4 puffs then q6-8h

Consider ICU admission if:

 Life threatening features present
 Deterioration in PEF/FEV1
 Worsening or persistent hypoxia or hypercapnia
 Respiratory failure requiring IPPV
 Respiratory or cardiorespiratory arrest

After improvement:
 Stabilize in ward
 Discharge may be considered when symptoms have cleared, improving lung
function PEF >60% predicted / best.
 Actions recommended on discharge include:
- Identifying & avoiding trigger factor(s) that precipitated attack
- Prednisolone tablets (up to 50mg daily for 5-7 days)
- EARLY outpatient follow-up and review of long-term treatment plan
especially inhalational steroids, AND reviewing technique on use of
inhaler and peak flow meter.

Therapies NOT recommended during acute attacks:

 Sedatives (avoid strictly)
 Cough suppressant (avoid as far as possible)
 Mucolytic drug (may worsen cough)
 Chest physiotherapy (may increase patient discomfort)
 Antibiotics (unless strong evidence of lung infection)
 Hydration with large volumes of fluid

P9
 LONG TERM MANAGEMENT OF ASTHMA
(Ref: GINA 2022)

General Notes
a) The goal of asthma care: 1. Symptoms control; 2. Risk reduction (asthma-
related death, exacerbations, airway damage and medication side effects). The
patient’s own goals regarding their asthma and its treatment should also be
identified.
b) Partnership between the patient and the health care providers is needed for
effective asthma management.
 Good communication skills of health care providers are important in
asthma care.
 Patient’s ability to obtain, process and understand basic health
information to make appropriate health decision (health literacy) should
be taken into account during care.
c) A continuous cycle of “assessment / adjust / review response” formed the
basis of asthma management.
d) Each patient is assigned to one of five “treatment steps”. Depending on their
current level of asthma control, treatment should be adjusted (e.g. stepping
up/down), taking into account of the patient’s characteristics and preference.
e) In treatment-naïve patients with persistent asthma, treatment should be started
at Step 2, or Step 3 if very symptomatic.
f) Reliever medication (rapid-onset bronchodilator) should be provided for
quick relief of symptoms at each treatment step.
g) All adults and adolescents with asthma should receive ICS-containing
controller treatment to reduce their risk of serious exacerbation.
h) Patients should avoid or control triggers at all times.
i) Patient education and treatment of modifiable risk factors / comorbidities (e.g.
smoking, obesity, anxiety) should be included in every treatment step.

Assessment of asthma control by Asthma Control Test (ACT)

1. In the past 4 weeks
 Impact of asthma on work, school or home
 Frequency of shortness of breath
 Waken up by asthma symptoms
 Frequency of reliever use
 Self-perceived asthma control
- Well controlled: >20
- Partly controlled: 15-19
- Uncontrolled: 5-14

P 10
2. Assessment on risk factors for poor asthma outcomes / risk of exacerbations
 Uncontrolled symptoms
 Excessive reliever use
 Inadequate ICS: not prescribed, poor compliance, poor inhaler
technique
 Higher bronchodilator reversibility
 Low FEV1, esp. if <60% predicted / best
 Major psychological / socioeconomic problems
 Exposures: e.g. smoking, allergen
 Comorbidities
 Sputum or blood eosinophilia
 Elevated FENO
 Pregnancy
 History of intubation / ICU admission for asthma
 ≥1 severe exacerbation in last 12 months

Treatment
Non-pharmacological interventions:
 Smoking cessation for smokers, regular physical activity, seasonal
influenza vaccinations should not be neglected.

Pharmacological
STEP 1
a) Initial asthma treatment for patients with symptoms < 2/month and no
exacerbation risk factors
b) Step-down treatment from patients whose asthma is well-controlled on Step
2 treatment
c) Preferred: As-needed low dose ICS-formoterol
d) Alternative: Low dose ICS taken whenever SABA is taken

STEP 2
a) Preferred:
 Low dose Inhaled corticosteroids (ICS) + prn SABA, OR
 As-needed low dose ICS-formoterol
b) Alternatives:
 Low dose ICS taken whenever SABA is taken, OR
 Leukotriene receptor antagonists (LTRA), OR
 Add house dust mite sublingual immunotherapy (HDM SLIT)

P 11
STEP 3
a) Preferred:
 Low dose ICS-formoterol maintenance and reliever therapy, OR
 Daily Low dose ICS + long-acting inhaled β2-agonist (LABA) + prn
SABA
b) Alternatives:
 Medium dose ICS
 Low dose ICS + LTRA
 Add HDM SLIT
c) Add-on therapy
 Sublingual allergen immunotherapy in those with allergic rhinitis and
sensitization to house dust mite with exacerbations despites ICS if FEV1
>70% predicted.

STEP 4
a) Preferred:
 Medium dose ICS-formoterol maintenance and reliever therapy,
OR
 Medium/high dose ICS + LABA + prn SABA
b) Add-on therapies:
 LAMA
 LTRA
 HDM SLIT
 High dose ICS + LABA

STEP 5 Phenotypic investigation +/- add-on treatment

a) Preferred: Specialist referral for severe asthma phenotype and consideration
of add-on treatment
 Options
a) Add-on LAMA
b) Anti-IgE treatment
c) Add-on anti-IL-5 or anti IL-5 receptor
d) Add-on anti-IL4R
e) Anti-thymic stromal lymphopoietin (anti-TSLP)
f) Bronchial thermoplasty
g) Long term azithromycin
h) LTRA
i) Low dose oral corticosteroid as last resort

P 12
Step-down
 Review treatment every 3-6 months. If control has been sustained for >3
months, consider a gradual stepwise reduction.
 Aim at finding the patient’s lowest treatment that controls both symptoms
and exacerbations.
 DO NOT completely stop ICS in adults or adolescents with asthma unless
this is needed temporarily to confirm the diagnosis of asthma.

Step-up
 If control is not achieved, consider stepping up AFTER reviewing
patient’s inhaler technique, compliance, environmental control (avoidance
of allergens/trigger factors), comorbidities and alternative diagnoses.

ICS dose
Daily dose (microgram)
Drug
Low Medium High
Beclometasone dipropionate
200-500 >500-1000 >1000
(HFA)
Beclometasone dipropionate
100-200 >200-400 >400
(extra fine particle, HFA)
Budeonide (DPI) 200-400 >400-800 >800
Ciclesonide (HFA) 80-160 >160-320 >320
Fluticasone furoate (DPI) 100 200
Fluticasone propionate (DPI) 100-250 >250-500 >500
Fluticasone propionate (HFA) 100-250 >250-500 >500
Mometasone furoate (DPI) 200 400
Mometasone furoate (HFA) 100 200

P 13
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Management of acute exacerbation of COPD (AECOPD)

1. Workup for precipitating cause (rule out pneumothorax, respiratory
infections, etc)
2. Supplemental oxygen (start with 1-2L/min by nasal prongs) to maintain
SpO2 88-92%. Check ABGs 30-60 mins later.
3. Short acting inhaled salbutamol (Ventolin) ± ipratropium bromide
(Atrovent) with spacer.
4. Corticosteroids (Hydrocortisone 100mg iv q6-8h or oral Prednisolone 30-
40 mg daily). Steroid should be discontinued after the acute episode (e.g.
5-10 days).
5. Antibiotic in patients required invasive or non-invasive ventilation (NIV),
and/or at least two cardinal symptoms (one being ↑ sputum purulence):
 ↑dyspnoea, ↑sputum volume, ↑sputum purulence
6. NIV – to relief dyspnoea by ↓ work of breathing (WOB), improve
respiratory acidosis, avoid complications, consider when:
 Respiratory acidosis (PaCO2 >6.0 kPa and pH ≤7.35)
 Severe dyspnoea with signs of respiratory muscles fatigue and/ or
↑WOB (e.g. use of accessory muscles, paradoxical abdominal motion,
intercostal space retraction)
 Persistent hypoxemia despite supplemental O2 therapy
Check ABG 30-60 mins after initiation of NIV.
Do not delay intubation and mechanical ventilation if no improvement.
7. Invasive mechanical ventilation – consider when:
For patients who are / have:
 NIV failure or intolerance with/without life-threatening hypoxemia
 Diminished consciousness, uncontrolled agitation
 Massive aspiration or persistent vomiting
 Persistent inability to remove respiratory secretions
 Severe haemodynamic instability without response to fluid and
vasoactive drugs; severe arrhythmia
 Status post-respiratory or cardiac arrest

** These patients should be managed in intensive care unit (ICU); if not

available, then preferably in intermediate or special respiratory care units with
expertise in this area **

P 14
Management of stable COPD (GOLD Report 2024)

Assessment of airflow limitation by spirometry

Grade FEV1 (% predicted)

GOLD 1 Mild ≥80
GOLD 2 Moderate 50 - 79
GOLD 3 Severe 30 - 49
GOLD 4 Very severe < 30

1. All patients should have smoking cessation, encouraged physical activity

and vaccination. Refer groups B&E patients for pulmonary rehabilitation.
2. Initial pharmacological treatment according to patient’s group –
determined by symptom level and exacerbation history.

Group E
≥2 moderate
exacerbations or LABA + LAMA*
≥1 leading to
hospitalisation
*consider LABA+LAMA+ICS if blood eosinophil ≥0.3x109/L
0/1 moderate Group A Group B
exacerbation
(not leading to A bronchodilator LABA + LAMA
hospitalisation)
mMRC 0-1, CAT <10 mMRC ≥2, CAT ≥10

LABA, long acting beta-agonist; LAMA, long acting muscarinic antagonist; ICS,
inhaled corticosteroid; CAT, COPD Assessment Test; mMRC, modified Medical
Research Council questionnaire.

3. Follow up pharmacological management

 Review: symptoms (dyspnoea) and exacerbation risk
 Assess: inhaler technique and adherence, and non-pharmacological
approaches
 Adjust: pharmacological treatment
 If still symptomatic
- Dual bronchodilators (LABA+LAMA) (if not already)
- Consider switch inhaler device or molecules
P 15
 - Investigate alternative causes
 If still exacerbates
- Dual bronchodilators (LABA+LAMA) (if not already)
- Consider ICS in those with higher peripheral eosinophil
- Consider Roflumilast (FEV1 <50% and chronic bronchitis)
and/or Azithromycin (in former smoker) (development of
resistant organisms should be factored into consideration).

Non-pharmacological treatment in advanced COPD:

 Consider surgery in suitable candidates
 Lung volume reduction surgery
 Bullectomy
 Lung transplant
 Oxygen/ ventilatory support
 Long-term oxygen therapy (LTOT) (see below)
 Long-term non-invasive ventilation (NIV)
 Consider refer patients to palliative care service

Indications for long-term O2 therapy in COPD

 Start only when clinically stable for 3-4 weeks and after optimisation of
other therapy.
 Continuous oxygen for at least 15 hours/day, improve survival in the
following situations:
 Resting PaO2 ≤7.3 kPa (55 mmHg) or SaO2 ≤88%: to maintain PaO2
≥8 kPa (60 mmHg or SaO2 ≥90%).
 Resting PaO2 7.4 to 7.9 kPa (56 to 59 mmHg) or SaO2 ≥89% in the
presence of any of the following:
- Dependent oedema suggestive of cor pulmonale.
- P pulmonale on ECG (P wave >3mm in standard leads II, III, or
aVF)
- Erythrocythaemia (haematocrit >56%)

**There is no survival benefit in moderate resting desaturation (SaO2 89-

93%) or moderate exercise induced desaturation.

P 16
 OBSTRUCTIVE SLEEP APNOEA

Patients should be evaluated for OSA if:

1. OSA symptoms: snoring choking at night / witnessed apnoea, excessive
daytime sleepiness unexplained by other factors, non-refreshing sleep,
sleep maintenance insomnia, morning headache, impaired concentration /
memory loss.
2. As comprehensive evaluation of patients at high risk of OSA:
 Obesity, pre-operative assessment for bariatric surgery
 Congestive heart failure, atrial fibrillation, young hypertension /
refractory hypertension, stroke, type II diabetes mellitus
 Unexplained pulmonary hypertension
 High-risk occupation e.g. occupational drivers

Diagnosis of OSA:
 Gold standard: Polysomnography
 Portable monitors (level III study, with minimum of 4 channels including
ventilation, ECG and oximetry) may be considered in patients with high
probability of moderate to severe OSA and no comorbid sleep disorder or
major comorbid medical disorders.

Severity of OSA is classified by apnoea-hypopnoea index (AHI)

Mild: 5-15 /hr Moderate: 15-30 /hr Severe: >30 /hr

Treatment of OSA:
1. Lifestyle modification: weight control, sleep hygiene, avoidance of alcohol
and sedatives before bedtime.
2. CPAP
 All patients with moderate to severe OSA
 Mild OSA with symptoms or risk factors
3. Alternative therapy: Positional therapy (sleep in lateral position), Dental
appliance, Surgery.

Early initiation of CPAP therapy should be arranged in:

1. OSA with obesity hypoventilation syndrome (OHS, daytime hypercapnia),
pulmonary hypertension or cor pulmonale.
2. Significant cardiovascular (e.g. malignant arrhythmia) or respiratory
comorbidities.
3. Excessive daytime sleepiness that may impose risk to the patient and/or

P 17
 others e.g. occupational drivers.
Peri-operative management of patients with OSA:
1. High risk factors: major surgery that require general anaesthesia, need of
post-operative opioids, severe OSA, OSA with concomitant
hypoventilation (e.g. COPD, OHS, neuromuscular disease),
cardiovascular comorbidities.
2. Patients with known OSA on treatment: reinstitute therapy (e.g. PAP or
dental appliance) post-operatively.
3. Patients with unknown or untreated OSA:
 Emergency surgery: proceed as indicated
 Elective surgery: proceed with close monitoring for low-risk
procedure; for high risk procedure, consider optimisation before
surgery in patients with significant comorbidities, hypoventilation
syndrome / hypoxaemia / severe pulmonary hypertension.
4. Close monitoring for development of respiratory failure during recovery
period in all OSA patients.
5. Benefit of empirical perioperative PAP in patients with untreated OSA is
uncertain.

Reference: AASM Clinical Guideline for the Evaluation, Management and Long-term
Care of Obstructive Sleep Apnea in Adults 2009.

P 18
 PREOPERATIVE EVALUATION OF PULMONARY
FUNCTION FOR RESECTION OF LUNG CANCER
(ACCP 2013)

ppo: predicted post-operative

SCT: stair climb test
SWT: shuttle walk test
CPET: cardiopulmonary exercise test

Positive low-risk or
negative cardiac
evaluation

Positive high-risk
ppoFEV1% cardiac evaluation
ppoDLCO%

ppoFEV1 or
ppoFEV1 and ppoFEV1 or
ppoDLCO < 60%
ppoDLCO >60% ppoDLCO <30%
AND both >30%

Stair climb or shuttle walk

SCT >22m OR SCT <22m OR CPET

SWT >400m SWT <400m

VO2 max VO2 max VO2 max

>20 ml/kg/min 10-20 ml/kg/min <10 ml/kg/min
or >75% or 35-75% or <35%

Low risk Moderate risk High risk

P 19
 MECHANICAL VENTILATION

1. Indications
 Respiratory failure (defined as insufficient oxygenation, insufficient
alveolar ventilation or both) not adequately corrected by other means.
 Failure to protect the airway (e.g. GCS <8)
 Cardiac and/or respiratory arrest

2. Criteria suggesting the need of Mechanical ventilation

Clinical Laboratory
Apnoea Tidal volume <5 ml/kg
Stridor Vital capacity <10 ml/kg
Impaired consciousness Minute ventilation <10 L/min
Flail chest Rise in PaCO2 >1.33 kPa from baseline
Inability to clear respiratory secretions PaO2 <7.32 kPa despite O2 supplement
Trauma to mandible, larynx or trachea
Respiratory rate >35 breaths/min
Remarks: Clinical assessment is more important than these criteria

3. Suggested initial ventilator settings

Acute Resp *Obstructive
Acute
distress lung disease Restrictive
Disease condition pulmonary
syndrome (COPD/ lung disease
oedema
(ARDS) Asthma)
Tidal volume
(ml/kg predicted 4-6 8-10 6-8 8-10
BW)
10-12 10-12 8-10
Permissive
Pressure control Ensure long 10-12
Frequency or hypercapnia
(PC) +/- pressure enough To achieve
(keep pH just
RR (breath/min) >7.25 as “lung
support (PS) expiratory time desired pH and
mode to achieve to avoid air- ABG
protective
comfort trapping
strategy”)
8-15 High (8-15)
May need >10
PEEP (cmH2O) initially, can be 0-5 5
(open lung
rapid tailed down
approach)
*Peak pressure usually targeted at <35 cmH2O

4. Monitoring during mechanical ventilation

a) General: vital signs, bowel motion, conscious level, psychological
status
b) P/E: Signs of upper airway obstruction (excessive inspiratory efforts,

P 20
 inspiratory in-sucking of lower rib cage), ETT (patency, positioning),
chest wall movement (especially asymmetry), pressure sores, signs of
DVT, hydration & nutritional status.
c) Important parameters:
 Cuff pressure: 20-30 cmH2O
 Ventilatory status:
- Volume-controlled mode or SIMV (VC+PS): avoid excessive
airway pressure
- Pressure-controlled mode or SIMV (PC+PS): monitor tidal
volume which varies with airflow obstruction or lung
compliance
- Pressure support mode: avoid excessive/inadequate tidal volume
and long/short inspiratory time
- Pause or plateau pressure (PP): Barotrauma risk ↑ if PP ≥35
cmH2O
- Auto-PEEP
- Use the lower fraction of inspiratory oxygen (FiO2) sufficient to
meet oxygenation goals (ideally 90-96% unless indications for
higher SpO2 are present).

5. Patient-ventilator asynchrony
 Do not simply sedate a patient who is asynchronous with the ventilator,
look for possible underlying cause(s).

Checklist for trouble-shooting:

Problems Examples
Inappropriate size/position (Normal 4-6 cm above
(a) Airway-related carina) of ET tube, leaky cuff/excessive cuff
pressure, blocked/kinked tube, dislodgement
Inadequate humidification, obstruction/leak in
(b) Ventilator-related
circuit, ventilator malfunction
Inappropriate TV/RR (or I:E) /sensitivity settings,
(c) Inappropriate
inadequate FiO2 and/or ventilation with persistent
ventilator settings
hypoxaemia or hypercapnia
Stiff lungs, low cardiac output, poor cerebral
(d) Underlying disease
perfusion, septic state
(e) Complications of Atelectasis, ventilator-associated pneumonia,
mechanical ventilation pneumothorax, endobronchial intubation
Fear, anxiety, pain, secretion in airway, hunger,
(f) Others
inability to open bowels/to move, pressure sore

P 21
 NON-INVASIVE VENTILATION (NIV)
Synonym: Non-invasive positive pressure ventilation (NPPV, NIPPV)

Levels of evidence for use of NIV in acute respiratory failure

Strongest evidence
1. Acute COPD exacerbation with hypercapnic acidosis (PaCO2 >6.0 kPa
or pH <7.35);
2. Hypercapnic respiratory failure secondary to obesity hypoventilation
syndrome (OHS), chest wall deformity or neuromuscular disease;
3. Cardiogenic pulmonary oedema;
4. To facilitate weaning from invasive ventilation (esp. in COPD);
5. Acute respiratory failure in immunocompromised patients.
Reasonable evidence
1. Post-operative hypoxaemia (except in upper GI surgery);
2. Patients decided not for intubation.
Less efficacious or even harmful
1. Acute severe asthma;
2. Acute respiratory distress syndrome (ARDS);
3. Pneumonia, esp. if purulent sputum.

Contraindications
Absolute
1. Lack of spontaneous breathing in cardiopulmonary arrest; Gasping;
2. Anatomical or functional airway obstruction;
3. Severe facial deformity/ trauma/ burns;
4. Gastrointestinal bleeding or ileus.
Relative (warrants enhanced observation)
1. Haemodynamic instability;
2. Severe acidosis (pH <7.15);
3. Inability to protect airway in severely impaired consciousness (GCS
<8);
4. Inability to cooperate in agitated status;
5. Excessive secretions;
6. Recent upper airway or gastrointestinal surgery.

P 22
Practical Aspects
Ventilator: mode of delivery
1. Single level (CPAP)
2. Bi-level (IPAP+EPAP)
Ventilator: circuit (single vs double limb)
1. Sophisticated ICU ventilator
• independent inspiratory and expiratory limbs
• a non-vented mask has to be used
• high max. flow
2. Smaller-sized ventilator dedicated for NIV delivery
• single inspiratory limb only
• expiratory port can be either a small hole at the tubing near the mask
or a dedicated device, e.g., Whisper-Swivel II valve
Interface
1. Types: nasal mask, nasal pillow, oronasal, total full-face mask, helmet
2. Factors to consider:
• facial anatomy, comfort, leakage, dead-space
• in acute respiratory failure, to start with oronasal (full face) mask
Humidification by heated humidifier

Clinical setting
1. Spontaneous / timed (ST) mode or Spontaneous (S) mode
2. CPAP / EPAP
 Pulmonary oedema: 8-12 cmH2O;
 COPD: 4-5 cmH2O
 Normal lung: 5 cmH2O
3. IPAP:
 Start at 8-15 cmH2O, titrate up to 20 cmH2O;
 Aim at tidal volume (Vt) ~ 6-8 ml/kg (ideal BW) and RR ≤ 25/min
4. Other settings:
 Backup respiratory rate (RR): 6 to 12;
 I:E ratio: 1:2 to 1:4;
 Inspiratory time (Ti) 0.8-1s (shorter for COPD to allow enough
expiratory time)

P 23
Monitoring during use of NIV
1. Patient’s aspects:
 Conscious level
 Mask fit / leakage
 Complications from interface such as skin breakdown, eye irritation,
nose bridge pain, oronasal dryness
 Gastric distension from aerophagia
2. Patient-Ventilator synchrony and trouble-shooting
3. ABG within first 1-2 hours after start of NIV to determine success
 Consider invasive mechanical ventilation if there is no objective sign
of improvement after 1 hour of use.
 Consider repeat ABG at 4-6 hours if first set ABG show little
improvement. If still no response, consider intubation.
4. Look for and treat the reversible causes of acute respiratory failure

Infection Control
 Stringent infection control measures should be taken during NIV for
patients with suspected respiratory infections (Single room with airborne
isolation might be needed, please refer to local hospital guidelines).

Factors associated with NIV failure

Patient factors
1. Poor level of consciousness
2. Edentulous
3. Excessive respiratory secretions
4. Mouth leaks
5. Poor patient-ventilator coordination
6. Poor nutritional status

Disease factors
1. Severity of illness:
 High APACHE II / SAPS II score
 Initial pH <7.25 or PaCO2 >10
2. Diseases conditions:
 ARDS
 Pneumonia

Response to NIV
No improvement in respiratory rate;
No improvement of pH/ PaCO2
P 24
Rheumatology
 APPROACH TO INFLAMMATORY ARTHRITIS
Definition:
 Arthralgia: pain in a joint without demonstrable synovitis
 Inflammatory Arthritis (Synovitis): joint swelling, warmth, pain and
tenderness
 Polyarthralgia / polyarthritis: 5 or more joints
 Chronic polyarthralgia / polyarthritis: more than 6 weeks

Polyarthralgia / polyarthritis – common causes:

 Rheumatoid arthritis
 Spondyloarthritis: ankylosing spondylitis, psoriatic arthritis,
inflammatory bowel disease, reactive arthritis
 Connective tissue diseases: SLE, systemic vasculitis, scleroderma, Still’s
disease
 Crystal-induced arthritis: gout, pseudogout
 Multi-joint osteoarthritis
 Bacterial arthritis (staphylococcal, streptococcal, gonococcal,
meningococcal)
 Bacterial endocarditis
 Viral arthritis
 Others: sarcoidosis, palindromic rheumatism, malignancy,
hyperlipoproteinaemias, Lyme disease, rheumatic fever

Monoarthritis – common causes:

 Septic arthritis
 Crystal-induced arthritis: gout, pseudogout
 Haemarthrosis / trauma / overuse / acquired haemophilia
 Tuberculous arthritis
 Osteoarthritis
 Spondyloarthritis: ankylosing spondylitis, psoriatic arthritis
 Monoarthritic onset rheumatoid arthritis
 Reactive arthritis
 Other uncommon causes: avascular necrosis, pigmented villonodular
synovitis (PVNS)

Relevant investigations:
 CBP, ESR, CRP
 Renal / liver function, calcium, phosphate, urate
 Urinalysis
 ANA, RF (if SLE or RA is suspected)
 Anti-CCP (if RA is highly suspected)

R1
 X-ray of the affected joints, musculoskeletal US (MSUS) & MRI if
indicated
 Joint aspiration
 Synovial biopsy (in undetermined cases)

Joint fluid analysis:

Send fluid for:
 Gram stain (“urgent” if septic arthritis suspected)
 Bacterial culture
 AFB smear and culture (if indicated)
 White cell count
 Crystal microscopy

Joint fluid white cell count:

Classification Clarity WBC/ml % of Neutrophils
Normal Transparent < 200 < 25
Non-inflammatory Transparent < 2000 < 25
Inflammatory Transparent 2,000 – 100,000 25-75
Septic Opaque 50,000 – 300,000 > 90

Crystal microscopy:
 Urate crystals: slender and needle-shaped; negative birefringence under
polarised light
 Calcium pyrophosphate crystals: pleomorphic or rhomboid-shaped;
weakly positive birefringence under polarised light

R2
 GOUTY ARTHRITIS

Clinical features
 Acute gout (monoarticular, polyarticular)
 Chronic tophaceous gout
 Uric acid calculi
 Gouty nephropathy

Diagnosis
 Definite gout: Intracellular negative birefringent urate crystal on joint
fluid microscopy
 Presumed gout: Classical history of episodic acute arthritis rapidly
resolved with NSAID (or colchicine) + history of hyperuricaemia

Management
 Acute Gouty arthritis
1. NSAID/COX2 inhibitors (Note! Check patient’s drug allergy)
High dose, tapering over 5 days, reduce dose in renal impairment:
a) indomethacin 50 mg TDS → 25mg TDS → 25 mg BD
b) naprosyn 500 mg STAT → 250mg TDS → 250 mg BD
c) Etoricoxib 60-90 mg daily (if high GI risk)
2. Colchicine
1 mg stat followed by 0.5 mg one hour after
Caution: Interaction with CYP3A4 inhibitors, severe renal impairment
Not recommend Q1H → Q2H for 10 doses regime
3. Corticosteroid
a) Intra-articular steroid injection after septic arthritis ruled out
b) Prednisolone 30 to 35mg daily for 5 days
4. Interleukin-1 blockers

 Urate lowering therapy

- Lower purine diet advisable but only attain small changes in serum
uric acid.
- Urate lowering therapy is indicated in patients with hyperuricaemia
and ≥2 acute gouty attacks within one year and it can be started during
acute attack
- Patients with one or more subcutaneous tophi; or radiographic damage
(any modality) attributable to gout or urate renal calculi.

R3
1. Xanthine oxidase inhibitors (Do NOT use with azathioprine!)
a) Allopurinol
 Severe cutaneous adverse reactions (SCAR) are associated with
HLA-B*58:01 in Han Chinese (carrier frequency ~14% locally).
An HA Expert Panel Meeting on Allopurinol-induced serious ADR
convened in November 2022 recommended universal screening test
for HLA-B*58:01 allele before starting allopurinol for HA patients.
 Start with low dose 100mg daily; increase weekly to your target
dosage; inform patients to stop if skin reaction (~5%) and seek
medical attention early.
 Further reduce dose (<100 mg daily) in renal impairment, step up
slowly.
 Prophylaxis: add regular colchicine 0.5 mg daily or bd, or NSAID,
for 3 to 6 months, to prevent acute gout attacks.
 Titrate dose to target serum uric acid < 0.36 mmol/L
 FDA approved maximal dose is 800 mg daily.

b) Febuxostat: a non-purine selective xanthine oxidase inhibitor

 Alternative for patients with allopurinol cutaneous adverse reaction
or HLA-B*58:01 gene carrier
 Usual dose 40 mg to 80 mg daily
 Further reduce dose (< 40mg daily) in renal impairment, step up
slowly
 Caution in patients with high cardiovascular thromboembolic risks

2. Uricosuric drugs
a) Probenecid 250 mg BD to 1000 mg TDS
(Contraindications: moderate renal impairment, urate renal stone, and
high 24-hour urine uric acid excretion)
b) Benzbromarone: licensed in HK but not under HA formulary
c) Sulfinpyrazone: not licensed in HK

3. Rasburicase, a recombinant urate-oxidase enzyme, is for pre-

chemotherapy prevention of acute tumour lysis syndrome. Caution in
G6PD deficiency.
Reference
1. Safe Use of Allopurinol. COC in Internal Medicine (11.01.2024). View Document
2. The Hong Kong Society of Rheumatology consensus recommendations for the
management of gout. Clin Rheumatol. 2023 Aug;42(8):2013-2027.

R4
 SEPTIC ARTHRITIS

1. A hot, swollen and tender joint should be regarded as septic arthritis until
proven otherwise, even in the absence of fever, leucocytosis, elevated
ESR or CRP. Septic arthritis can present as monoarthritis (80-90%),
oligoarthritis or polyarthritis. Delay in diagnosis and treatment can result
in irreversible joint destruction or septicaemia.

2. Prompt aspiration of the joint is warranted. Synovial fluid should be sent

for:
 Differential cell counts: Usually >50,000 WBC/ml and often
>100,000/ml, predominantly neutrophils.
 Gram stain
 Culture and sensitivity
 Polarising microscopy for crystals (septic arthritis may co-exist with
crystal arthropathies)

3. Other investigations: CBC with differentials, RFT, LFT, blood culture, X-

ray of the joint. Swabs of pharynx, urethra, cervix and anorectum if
gonococcal infection suspected.

4. Start empirical IV antibiotics immediately according to suspected

organisms and gram stain. Modify according to culture and sensitivity
results. Opinion from microbiologists is helpful. Refer to IMPACT
guideline (available as apps for mobile phone), or
(https://www.chp.gov.hk/files/pdf/reducing_bacterial_resistance_with_im
pact.pdf)

5. Therapeutic joint aspiration to dryness.

6. Consult orthopaedic surgeon for drainage especially for infected

prosthetic joint. Open drainage is usually necessary for hip infection.

7. Start physiotherapy early.

8. NSAIDs for pain relief.

9. IV antibiotics for at least 2 weeks or until signs improved for non-

gonococcal arthritis, then orally for an additional 2-4 weeks.
R5
Suggested choice of antibiotics: (Note! Check patient’s drug allergy)
Synovial fluid
Organism IV Antibiotics
gram stain
Gram +ve cocci Staph aureus MSSA Cloxacillin 1-2g Q6H or
(clusters) Cefazolin 1-2g Q8H
Gram +ve cocci Streptococcus Penicillin 2 megaunits Q4H or
(chains) Cefazolin 1-2g Q8H
Gram –ve Bacilli Enterobacteriaceae Ceftriaxone 2g Q24H or
Cefotaxime 1g Q8H
Pseudomonas Cefepime 2g Q12H or
Piperacillin 3g Q6H or
Imipenem 500mg Q6H
+ Gentamicin
Gram –ve Neisseria gonorrhoeae** Ceftriaxone 2g Q24H or
diplococci Cefotaxime 1g Q8H or
Ciprofloxacin 400mg Q12H
(avoid unless very indicated)
Empirical initial 1. No risk factors for Cloxacillin or
therapy atypical organisms Cefazolin or Ceftriazone
2. High risk for Gram –ve Cloxacillin +
sepsis (elderly, frail, Ceftriaxone or Cefotaxime
recurrent UTI, recent
abdominal surgery,
immunocompromised)
3. Gonorrhoea suspected Ceftrizone or
Cefotaxime or
Ciprofloxacin (avoid unless
very indicated)
4. MRSA suspected Vancomycin 1g Q12H +
Ceftriaxone or Cefotaxime
**Treat possible concurrent Chlamydia trachomatis infection with
doxycycline (100mg BD for 7 days) in patients with gonococcal infection.

R6
 RHEUMATOID ARTHRITIS

1. Clinical presentations & diagnosis

 Symmetrical polyarthritis with synovitis sparing distal interphalangeal
joints with positive rheumatoid factor
 Presentation can be atypical, especially in early RA
 Diagnosis supported by clinical, serological and radiological
assessment after excluding other differential diagnosis

2. Classification criteria

2010 ACR/EULAR classification criteria for RA (more preferred)

6/10 points – classified as having definite RA
 Joint involvement
1 large joint (0)
2-10 large joints (1)
1-3 small joints (with or without large joints) (2)
4-10 small joints (with and without large joints) (3)
>10 joints (at least 1 small joint) (5)
 Serology
Negative RF and negative anti-CCP (0)
Low positive RF or low positive anti-CCP (2)
High positive RF or high positive anti-CCP (3)
 Acute phase reactants
Normal CRP and normal ESR (0)
Abnormal CRP or ESR (1)
 Duration of symptoms
< 6 weeks (0)
≥ 6 weeks (1)

3. Investigations
 ESR and C-reactive protein (CRP)
 RF (sensitivity ~70%)
 Anti-cyclic citrullinated peptide antibody (anti-CCP) – highly specific
for RA, helpful in undetermined situations
 Plain X-ray of the hands and feet for erosion
 MRI or USG may be useful for detecting early bony erosion

R7
4. Clinical assessment
 Arthritis assessment
 Number of tender joints among 28 joints (t28)
 Number of swollen joints among 28 joints (sw28)
 Patient Global Assessment (0-10)
 Evaluator Global Assessment (0-10)
 ESR / CRP
 Radiographic assessment
 Extra-articular manifestations
 Associated co-morbidities
 Cardiovascular disease / risk factors
 Osteoporosis

5. Disease assessment tools

 Disease activity score (DAS)

DAS28 = 0.56×�(t28) + 0.28×�(sw28) + 0.70×Ln(ESR) + 0.014×GH
 Number of tender joints among 28 joints (t28)
 Number of swollen joints among 28 joints (sw28)
 Erythrocyte sedimentation rate (ESR, mm/hour)
 General health status (GH) using a 100-mm visual analogue scale

 Simplified Disease Activity Index (SDAI)

SDAI = t28 + sw28 + CRP + PGA + EGA
 Clinical Disease Activity Index (CDAI)
CDAI = t28 + sw28 + PGA + EGA
 Number of tender joints among 28 joints (t28)
 Number of swollen joints among 28 joints (sw28)
 Erythrocyte sedimentation rate (CRP, mg/L)
 Patient Global Assessment (for disease activity) (PGA, 0-10cm)
 Evaluator Global Assessment (for disease activity) (EGA, 0-10cm)

Disease status:
DAS28-ESR SDAI CDAI
Remission < 2.6 ≤ 3.3 ≤ 2.8
Low disease activity ≤ 3.2 > 3.3 – 11 > 2.8 - 10
Moderate disease activity N/A > 11 - 26 > 10 - 22
High disease activity > 5.1 > 26 > 22

R8
6. Treatment
 Treatment principles
 Early initiation of DMARDs
 Treat-to-target: aim to low disease activity or clinical remission
 Aim to prevent joint damage and preserve daily function
 Disease modifying antirheumatic drugs (DMARDs)
 Methotrexate
- Anchor drug for rheumatoid arthritis
- Common dose 7.5 mg – 15 mg/ week
- Contraindications: Pregnancy, chronic kidney disease
 Low dose corticosteroids
- Consider short course of corticosteroids during the initial
phase of treatment while waiting for methotrexate to take
effect
 Conventional synthetic DMARDs (csDMARDs) combinations
- Indication
 Persistent activity despite methotrexate monotherapy
- Common combinations
 Methotrexate + Leflunomide
 Methotrexate + Sulphasalazine + Hydroxychloroquine
 Biological DMARDs
- Indications
 Persistent activity despite methotrexate monotherapy with
poor prognostic factors for joint damage
 Persistent activity despite combination csDMARDs
- Anti-TNF / Anti-IL6 / Anti-CTLA4/ Anti-CD20
 Target synthetic DMARDs
- JAK inhibitors
- FDA warning: Cancer and cardiovascular risk
 Treat co-morbidities e.g. cardiovascular risk factors, osteoporosis

7. Poor prognostic factors predicting joint damage

 High disease activity at onset (high DAS-28 score)
 High baseline joint damage (erosive disease)
 Persistently high CRP level
 High rheumatoid factor or anti-CCP titre
 Positive family history of RA
 Presence of rheumatoid nodules
 Extra-articular manifestations

R9
 ANKYLOSING SPONDYLITIS
1. Modified New York criteria for definite AS (1984)
a) Radiological criterion
Sacroiliitis: ≥ grade II bilateral or grade III to IV unilaterally
b) Clinical criteria (at least 1 out of 3)
 Low back pain & stiffness for > 3 months that improve with exercise
but not relieved by rest.
 Limitation of motion of lumbar spine in both sagittal & frontal
planes
 Limitation of chest expansion relative to normal correlated for age &
sex

2. ASAS criteria for axial spondyloarthritis (SpA) (2009):

a) Imaging evidence of sacroiliitis (XR, MRI or CT) plus one SpA features*
b) HLA-B27 positivity plus 2 other SpA features*
*SpA features:
 Inflammatory back pain age of onset <40
 Arthritis
 Enthesitis
 Psoriasis
 Uveitis
 Dactylitis
 Crohn’s/colitis
 Good response to NSAIDs
 Family history for SpA
 Elevated C-reactive protein (CRP)
 HLA-B27

3. Other extra-skeletal features – apical fibrosis, aortic insufficiency

4. Measurements
a) Modified Schober test - spinal forward bending (excursion of two points:
PSIS level and 10cm above; normal excursion > 5cm).
b) Note: finger floor distance may be apparently normal when good hips
flexion compensates limited spinal flexion
c) Occiput-to-wall: normal 0 cm
d) Tragus-to-wall: normal < 14cm
e) Chest expansion
f) Cervical rotation
g) Intermalleolar distance

R 10
5. Investigations
a) XR sacroiliac joints and spine
b) MRI SI joints in doubtful cases
c) HLA-B27 (role refers to ASAS criteria)

6. Disease assessment
a) BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), active
disease defined as ≥4 (out of 10).
b) BASFI (Bath Ankylosing Spondylitis Functional Index)
c) BAS-G (Patient’s / Physician’s Global score)
d) BASMI (Bath Ankylosing Spondylitis Metrology Index)
e) Acute phase reactants (ESR/CRP)

7. Treatment
a) Education, stretching exercise & physiotherapy
b) NSAIDs for pain and stiffness at optimal tolerated dose
c) Addition of gastroprotective agents or use selective COX-2 inhibitor in
patients with high GI risks (elderly, history of peptic ulcer,
comorbidity)
d) Analgesics such as paracetamol and tramadol for patients in whom
conventional NSAIDs or COX-2 inhibitor are insufficient,
contraindicated or intolerated
e) Sulphasalazine or methotrexate for patients with peripheral arthritis
f) Biologics (Anti-TNF or anti-IL-17) therapy for patients with persistent
high disease activity despite adequate trial of the above treatment
including 2-3 NSAIDs (at least 2 months for each unless
contraindicated). Refer rheumatologist for assessment of disease
activity and indications for anti-TNF therapy.

8. ASAS 50 Response criteria: ↓ BASDAI by 50%

R 11
 PSORIATIC ARTHRITIS

Diagnostic criteria
The Classification of Psoriatic Arthritis criteria (CASPAR):
Mandatory:
Inflammatory articular disease (joint, spine or entheses)
With 3 or more points from the following:
1. Current psoriasis (scores 2 points)
2. Personal history of psoriasis (if current psoriasis is absent)
3. Family history of psoriasis (if personal history of psoriasis or current
psoriasis absent)
4. Psoriatic nail dystrophy
5. A negative test for rheumatoid factor
6. Current dactylitis
7. History of dactylitis (if current dactylitis absent)
8. Radiological evidence of juxta-articular new bone formation

Clinical features
 30% psoriasis population has arthritis
 60% psoriasis precedes arthritis, 20% arthritis precedes psoriasis, 20%
concurrent
 Also watch out for associated metabolic syndrome e.g. overweight,
diabetes mellitus, hypertension, hyperlipidaemia, hyperuricaemia etc.

Features distinguishing PsA from RA

 Presence of psoriasis
 Hidden lesions common, e.g. scalp, hairline, behind the ear and
inside ear cannel, guttate lesions on back, under the breasts, around
umbilicus, around the perineum or even natal cleft.
 Nail dystrophy
 Onycholysis, pitting, ridging, etc.
 Distal phalangeal joint involvement
 Spondylitis or sacroiliitis
 Enthesitis (inflammation of junction of ligament, tendon or join capsule
to bone)
 Dactylitis

R 12
Treatment
 Oral corticosteroid: risk of psoriasis up upon tapering. So be cautious
with starting oral steroid.
 Early DMARD treatment for psoriatic arthritis
 Active arthritis (>3 tender/swollen joints, dactylitis counted as one
active joint)
DMARD. Methotrexate, sulphasalazine, leflunomide, cyclosporine
Anti-TNFα therapy, anti-IL17, anti-IL12/23, JAK inhibitors (refer to
rheumatologist)
 For skin psoriasis
a) Topical steroid (potency)
 Fluocinolone < betamethasone < clobetasol (to be used by
specialist)
b) Topical tar products, e.g. shampoo, bathing soap
c) Vit D analogues: e.g. Dovonex (calcipotriol) (to be used by
dermatologist)
d) UVA or UVB (to be used by dermatologist)
e) Anti-TNFα therapy, anti-IL 12/23, anti-IL17 and other biologics
(to be used by specialist)

R 13
 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

American College of Rheumatology (ACR) criteria for the classification

of SLE (Tan et al. 1982, revised 1997, Hochberg et al.) ≥ 4 criteria, serially
or simultaneously = classified as SLE (specificity = 96%)

1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis (pericarditis, peritonitis, pleuritis)
7. Renal disease (proteinuria >0.5 g/day, or +++ by dipstick, or cellular
casts)
8. Neurological (seizure, or psychosis)
9. Haematological (haemolytic anaemia, or leucopenia < 4 x109/L,
lymphopenia < 1.5 x 109/L, on two or more occasions, or
thrombocytopenia < 100 x 109/L)
10. Immunological (anti-dsDNA, or anti-Sm, or false +ve VDRL for more
than 6 months, or the presence of the antiphospholipid antibodies)
11. Positive anti-nuclear antibody (ANA)

SLICC (Systemic Lupus International Collaborating Clinics)

Classification criteria for SLE (Petri et al. 2012)
≥ 4 criteria (at least 1 clinical + 1 immunologic criteria) OR biopsy-proven
lupus nephritis with positive ANA or anti-DNA

Clinical Criteria
1. Acute or subacute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral / Nasal ulcers
4. Non-scarring alopecia
5. Inflammatory synovitis with physician-observed swelling of two or
more joints OR tender joints with morning stiffness
6. Serositis
7. Renal: Urine protein/creatinine (or 24 hr urine protein) representing at
least 500mg of protein / 24 hr or red blood cell casts
8. Neurologic: seizures, psychosis, mononeuritis multiplex, myelitis,
peripheral or cranial neuropathy, cerebritis (Acute confusional state)
9. Haemolytic anaemia
R 14
10. Leukopenia (< 4 x 109/L at least once) OR Lymphopenia (< 1 x 109/L at
least once)
11. Thrombocytopenia (< 100 x 109/L) at least once

Immunologic Criteria
1. ANA above laboratory reference range
2. Anti-dsDNA above laboratory reference range (except ELISA: twice
above laboratory reference range)
3. Anti-Sm
4. Antiphospholipid antibody: e.g. lupus anticoagulant, false-positive test for
syphilis, anticardiolipin antibody (at least twice normal or medium-high
titre), anti-β2 glycoprotein 1 antibody.
5. Low complement: e.g. low C3, low C4, low CH50
6. Direct Coombs test in absence of haemolytic anaemia

Anti-ENA antibodies
 Anti-Ro: associated with photosensitivity and an increased risk of
congenital heart block (~2% incidence). Pre-pregnancy counselling and
ultraviolet light protection should be advised.
 Anti-ENA antibodies seldom sero-convert and repeating tests is not
necessary.

Anti-phospholipid antibodies
 Lupus anticoagulant (LAC) and anti-cardiolipin (aCL) antibody (IgG) are
available in most HA hospitals.
 They are strongly associated with cerebrovascular accidents in Chinese
SLE patients. Other associations: thrombocytopenia, livedo reticularis,
valvular heart lesions, recurrent miscarriages, arterial and venous
thrombosis.
 Twice positive tests 12 week apart are necessary for the diagnosis of
antiphospholipid syndrome. Positive LAC and/or high titre of aCL is
clinically relevant.
 Because of the association with recurrent abortions and miscarriages,
these antibodies have to be checked before pregnancy.
 Anti-β2-GPI antibody is more specific than aCL for thrombosis. Because
of its limited sensitivity, anti-β2-GPI should only be considered in
patients in whom antiphospholipid syndrome is suspected but yet aCL
and LAC is negative.

R 15
Monitoring of disease activity
 Clinical assessment (signs and symptoms of disease flares)
 Serology: C3 and C4 level, anti-dsDNA titre

Points to note
 The ANA titre does not correlate with disease activity and is not reliable
for disease monitoring. Thus, there is no need to repeat ANA if it is
already positive.
 C-reactive protein (CRP) is usually not elevated in patients with active
SLE. An elevated CRP in SLE may indicate infection, persistent
synovitis / arthritis, serositis. Infection has always to be considered
before augmentation of immunosuppressive therapy.

Disease activity scoring system

The ACR SELENA-SLEDAI is most widely used disease activity index.
Items can be used as a checklist for disease flares:

Seizure (8) Cerebrovascular accident (8)

Psychosis (8) Retinal haemorrhage / infarct /
Organic brain syndrome (8) optic neuritis (8)
Lupus headache (8) Vasculitis (8)
Cranial nerve disorder (8)
Arthritis (> 2 joints) (4) Oral ulcer (2)
Myositis (4) Pleuritis (2)
Proteinuria (4) Pericarditis (2)
Urine case (4) New skin rash (2)
RBC cast in urine (4) Alopecia (2)
Sterile pyuria (4) ↑anti-dsDNA titre (2)
↓C3 (2)
Fever (1) Leukopenia (< 3 x 109/L) (1)
Thrombocytopenia (1)

*Only new features or manifestations are scored.

**mostly used for research purpose. Flare is defined >4 points increase.

Treatment of SLE

General:
Patient education and counselling, sun-screening (avoid strong sunlight,
R 16
frequent application of SPF 15+ sun lotion), screening and treatment of
cardiovascular risk factors and osteoporosis, vaccination and infection
prevention, early recognition and prompt treatment.

Hydroxychloroquine should be considered for every lupus patient:

 Overall stabilising SLE
 Decreases infection, some anti-thrombotic and lipid lowering effect
 Stabilises pregnant SLE patients and improves foetal outcome
 Recommend < 5 mg/kg/day

Mild SLE manifestations

 NSAIDs - arthritis, serositis, fever
 Hydroxychloroquine – arthritis, skin lupus
 Methotrexate – persistent and refractory arthritis and skin
 Topical steroid – skin lupus
 Small to moderate doses of prednisolone – fever, systemic upset, mild
cytopenias, more severe serositis and skin lupus
 Azathioprine – haematological, mild renal disease, steroid sparing
 Belimumab (Benlysta) – as an alternative for arthritis, skin lupus,
serositis, haematological

Severe SLE manifestations

 Glomerulonephritis, neuropsychiatric lupus, severe cytopenias,
thrombotic thrombocytopenic purpura, pulmonary haemorrhage,
myocarditis, pneumonitis, pulmonary arterial hypertension
 Moderate to high doses of prednisolone
 Intravenous pulse methylprednisolone
 Azathioprine
 Cyclophosphamide (intravenous pulse or oral)
 Mycophenolate mofetil (MMF)
 Cyclosporine A and Tacrolimus
 Plasma exchange
 Intravenous immunoglobulin
 Rituximab
 Vasodilatation (sildenafil, endothelial receptor antagonists, inhaled
iloprost, IV epoprostenol, oral selexipag)
 Anticoagulation

R 17
Lupus nephritis (ISN/RPS Classification 2003)
Class I: Minimal mesangial lupus nephritis
Class II: Mesangial proliferative lupus nephritis
Class III: Focal proliferative lupus nephritis
Class IV-G: Diffuse global proliferative lupus nephritis
Class IV-S: Diffuse segmental proliferative lupus nephritis
Class V: Membranous lupus nephritis
Class VI: Advanced sclerotic lupus nephritis

MMF is used as first line treatment for proliferative lupus nephritis because of
lower frequency of adverse effects compared to cyclophosphamide e.g.
premature ovarian failure and haemorrhagic cystitis. However,
cyclophosphamide remains the conventional treatment for those with rapidly
progressive crescentic GN and those with impaired renal function.

Neuropsychiatric lupus
19 Neuropsychiatric syndromes according to the 1999 ACR classification

Central nervous system Peripheral nervous system

Aseptic meningitis Acute inflammatory demyelinating
polyradiculoneuropathy (Guillian-
Barré syndrome)
Cerebrovascular disease Autonomic neuropathy
Demyelinating syndrome Mononeuropathy
Headache (single/multiplex)
Movement disorder Myasthenia gravis
Myelopathy Cranial neuropathy
Seizure disorder Plexopathy
Acute confusional state Polyneuropathy
Anxiety disorder
Cognitive dysfunction
Mood disorders
Psychosis

Diagnosis of NPSLE
 Till now, no specific confirmatory serological & imaging tests.
 A diagnosis by exclusion (to rule out CNS infections, metabolic
encephalopathy, effects of drugs / toxins including corticosteroids,
electrolyte disturbances, rarely brain tumour).
R 18
 Lupus activity in other systems increases likelihood of active
neuropsychiatric lupus but CNS infection may coexist with active
neuropsychiatric lupus.
 CT brain, MRI brain / spinal cord for anatomical diagnosis.
 Lumbar puncture to rule out CNS infection
 EEG
 Antiphospholipid antibodies
 Anti-ribosomal P antibody (private laboratory) is associated with lupus
psychosis but its usefulness is limited by the low sensitivity.

Treatment for NPSLE

 Symptomatic: anti-convulsants, anti-psychotics, anti-depressants,
sedatives.
 Secondary prophylaxis for atherosclerotic vascular disorders: aspirin /
warfarin
 Immunosuppressive or immunomodulating treatment (e.g. high dose
corticosteroids, pulse methylprednisolone, cyclophosphamide, IVIG,
rituximab): severe psychosis, acute confusional state, myelopathy,
myasthenia gravis, neuropathies, demyelinating syndrome.

Useful apps: RheumaHelper – for Classification criteria and Disease

Activity scoring of many rheumatic diseases. Available free from iTunes
App Store and Google Play Store.

R 19
 RHEUMATOLOGICAL EMERGENCIES

Cervical Subluxation
 Suspect in RA patients with long standing and severe disease
 Commonly presents with neck pain radiating towards the occiput,
clumsiness, abnormal gait, spastic quadriparesis, sensory and sphincter
disturbances. May cause cord compression and death.
 4 forms in descending order of frequency: anterior, posterior, lateral,
vertical.

Investigations:
 Plain AP and lateral XR of cervical spine with flexion and extension
views.
 Anterior subluxation: distance between the posterior aspect of the
anterior arch of the atlas and the anterior aspect of the odontoid process
(Atlanto-dens interval, ADI) ≥4mm.
 Dynamic (flexion-extension) MRI (if surgery indicated).

Management:
Medical
 High-impact exercises and spinal manipulation are contraindicated
 Soft collars may serve as reminder for patients and physicians but
provide little structural support.
 Stiff cervical collars may provide marginal benefit but compliance is a
problem.
 Neuropathic pain relief

Surgical
 Urgent referral to orthopaedic surgeons or neurosurgeons if signs of cord
compression.
 Patients with severe subluxation but without signs of cord compression
are at risk for severe injury and perhaps death due to a variety of insults
including falls, whiplash injuries, and intubation. Surgical decision
should be individualised.
 Surgical options: craniocervical decompression, cervical or occipito-
cervical fusion (alone or in combination).

R 20
Giant Cell Arteritis (GCA)

Presentation: At least 3 of the following 5 criteria

1. Age ≥50 years
2. Localised headache of new onset
3. Tenderness or decreased pulse of the temporal artery
4. ESR >50 mm/hr
5. Biopsy revealing a necrotising arteritis with a predominance of
mononuclear cells or a granulomatous process with multinucleated
giant cells.
 Polymyalgia Rheumatica (PMR) is characterised by aching and morning
stiffness in the shoulder and hip girdles, occurring in 40-50% of GCA
patients.
 Other presentations: jaw or arm claudication, weight loss, PUO
 Complications: Ischaemic optic retinopathy (visual loss 15-20%).
Blindness is abrupt and painless, may be preceded by amaurosis fugax.
 Aneurysms, dissections, stenotic lesions of the aorta and its major
branches.

Investigations:
 Elevated ESR, often >100 mm/hr (5% of GCA has ESR <40 mm/hr)
 Ultrasound of temporal artery to look for “halo” sign
 Temporal artery biopsy of the affected side

Treatment:
 High dose prednisolone (1 mg/kg/day)
 For visual symptoms or signs (e.g. amaurosis fugax, partial or complete
visual loss), start empirical steroid as soon as possible, before temporal
artery biopsy result.
 Acute visual changes – consider IV pulse methylprednisolone (250-
1000mg) daily for 3 days.
 Consider anti-IL6 (Tocilizumab) for refractory cases (used by specialist
only).

Septic Arthritis (see page R5-6)

R 21
Renal Crisis in Scleroderma
 Rapid and progressive in disease course
 Symptoms appear suddenly and are not usually preceded by significant
prodromal symptoms
 Life threatening condition
 Use of steroid is a risk factor especially in diffuse skin involvement
 Presented with malignant hypertension, acute renal failure, less often
microangiopathic haemolytic anaemia
 No consensus diagnostic criteria yet. Clinical vigilance is important
 Treatment: ACEI ± dialysis
 Consult specialist

ANCA Vasculitis – Pulmonary Renal syndrome

Presentation:
 Acute renal failure, signs of acute glomerulonephritis, or
 Acute pulmonary haemorrhage

Investigations:
 Check anti-GBM and ANCA (anti-neutrophil cytoplasmic antibody)
 Check for Anti-PR3 ANCA (proteinase 3) or anti-MPO ANCA
(myeloperoxidase) if ANAC is positive
 Raised ESR/CRP
 Renal biopsy to show pauci-immune glomerulonephritis
 CXR, HRCT, bronchoscopy etc. for pulmonary haemorrhage

Treatment:
 Organ support: dialysis and ventilator care (consult ICU if needed)
 Intravenous pulse steroid or high dose steroid
 Cyclophosphamide or rituximab in refractory patients
 Plasma exchange possible useful in:
 Patients with acute renal failure requiring dialysis support
 Pulmonary haemorrhage
 Concomitant anti-GBM +ve patients

R 22
 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
(NSAIDS)

 Do not use >1 NSAID at a time

 Use the lowest possible dosage and frequency sufficient for pain relief
 Efficacy is similar among various NSAIDs. Conventional ones such as
naproxen, diclofenac and indomethacin are equally effective.
 If one NSAID is not working despite 2-3 week of treatment at full
dosage, shifting to another NSAID may be considered.
 Use with caution when coexisting hypertension, heart failure, fluid
retention and/or renal impairment.

Adverse Effects
Beware of cross allergy between NSAIDs and COX-2 inhibitors
 GI: dyspepsia, peptic ulcer, GI bleeding and perforation
 Renal: renal impairment
 CVS: fluid retention, worsening of hypertension, increased
cardiovascular events
 Liver: raised transaminases
 CNS: headache, dizziness and cognitive impairment, especially use of
indomethacin in elderly
 Skin: may range from mild rash to Stevens-Johnson Syndrome
 Resp: may precipitate or exacerbate bronchospasm in aspirin sensitive
individuals.

Risk factors for gastrointestinal toxicity:

a) Chronically disabled
b) Age >60 years
c) Previous history of proven peptic disease
d) Co-administration of high dose prednisolone or anticoagulation
e) Higher dosage of NSAIDs
f) Extent of inflammatory disease for which NSAIDs is prescribed

COX-2 inhibitors
Efficacy: similar to non-selective conventional NSAIDs
Advantages:
 Reduce gastrointestinal toxicity.
 Less effect on platelet function, hence less bleeding risk.
 Less risk of precipitating bronchospasm.

R 23
Adverse effects:
 Increase risk of cardiovascular events (MI, stroke). Risk proportional to
dosage. May worsen BP control and heart failure
 Nephrotoxicity, hepatotoxicity, cardiotoxicity similar to conventional
NSAIDs.
 Celecoxib should be avoided in patients with sulphonamide allergy

Current recommendations for patients receiving NSAIDs

1. Prescribe lower-risk agents. Weigh GI against CV risk in individual
patient:
 If estimated risk of life-threatening GI bleeding > risk of CV events,
consider use of NSAIDs with gastroprotection e.g. PPIs or the COX-2
inhibitors.
 If risk of CV events > the risk of GI bleeding, COX-2 inhibitors
should be avoided.
2. Limit duration, frequency and dosage
3. Patients with known H pylori infection should undergo eradication before
NSAID therapy.
4. For patients at high risk for GI complications, consider assessing for and
treating H pylori if present and co-therapy with gastroprotective agents.
5. Gastroprotection:
 Proton pump inhibitors (PPIs)
 COX-2 inhibitor alone is beneficial in reducing GI risks, but with the
possible trade-off of increasing CV risk.
 COX-2 inhibitor with concurrent PPI therapy may be considered in
ultra-high risk patients e.g. recurrent ulcer bleeding.

R 24
 General
Internal Medicine
 ACUTE POISONING

The guidelines below are very general and treatment options may not apply
to all patients. For specific poisoning patient management, please call
Hong Kong Poison Information Centre (HKPIC) – 2772 2211 or Prince of
Wales Hospital Poison Treatment Centre (PWHPTC) – 3505 6209.
(Note: all dosages quoted are for adult)

General management of acute poisoning

(1) General measures
 Maintain ABC, close monitor vital signs and neurological status
 External decontamination and beware of secondary contamination
 Obtain history of offending poison, dose, dosage form (e.g. sustained
release (SR) preparation), timing of ingestion
 Ix: CBP, L/RFT, glucose, H’stix, blood gas, lactate, osmolality
Urine, blood, ± gastric contents for toxicology
Specific drug level: paracetamol, ethanol, salicylate, as indicated.
ECG (assess for HR, QRS, QTc, arrhythmia)
Imagining for body packing or massive SR pills poisoning
 Correct fluid, electrolyte, acid/base disturbance and treat arrhythmia.
 Psychiatry consultation, suicidal precautions as appropriate.

(2) Consider GI decontamination

Activated Charcoal (AC)

 Within first 1-2 hr after a toxic ingestion, Dose: 50-100g PO
 Not for small molecules (Fe, Li, toxic alcohols), caustic, hydrocarbon
 Intubation and nasogastric tube needed for unconscious patient
 C/I: absent bowel sound or bowel perforation

Gastric Lavage (GL)

 For potentially life-threatening poisonous ingestion
 Preferably within first hour post ingestion
 Intubation needed for confused, comatose patient
 Conscious patient must be cooperative, consent signed, lying head down
left lateral position, with powerful suction standby.
 36-40F oro-gastric tube, 200-250ml water each time for at least 4-6L or
until return fluid is clear.

GM 1
Multiple dose activated charcoal (MDAC)
 1 g/kg PO, followed 0.5 g/kg q2-4h for 1-2 days
 Consider for Theophylline, Phenobarbital, Phenytoin, Digoxin,
Carbamazepine, Dapsone, GI concretion forming drug; aspirin and
sustained release (SR) preparation.

Whole bowel irrigation (WBI)

 Toxic dose of SR preparation, body packers, and drugs not adsorbed to AC.
 PEG 1-2 L/hr till clear rectal effluent (orally or via a NG tube)
 C/I: absent bowel sound or bowel perforation

(3) Consider use of specific Antidotes

Level I, II, III antidotes kept at acute hospitals, cluster hospitals and HKPIC,
respectively.

(4) Enhanced elimination as needed.

Urinary Alkalinisation
 Useful in Aspirin, Phenobarbital, Chlorpropamide, Formate, Methotrexate.
 1-2 mmol/kg NaHCO3 IV bolus, then 50 mmol NaHCO3 (8.4%) in 500ml
D5 q4-6h IV infusion.
 Works by ion trapping, must get urine pH >7.5 to be effective
 Monitoring serum pH, avoid >7.55, avoid hypokalaemia
Extracorporeal Treatments
Alternatives: CRRT or
Intermittent Haemodialysis
Haemoperfusion (HP)
Methanol / Ethylene Glycol Methanol (CRRT)
Strong
Lithium Lithium (CRRT)
Indication
Aspirin, Theophylline Aspirin, Theophylline (CRRT, HP)
Paracetamol Paracetamol (HP, CRRT)
Barbiturates Barbiturates (HP, CRRT)
Carbamazepine Carbamazepine (HP, CRRT)
Phenytoin Phenytoin (HP)
Valproate Valproate (HP, CRRT)
Metformin Metformin (CRRT)
Rarer
Thallium Thallium (HP, CRRT)
Indication
Gabapentin / Pregabalin (in renal
impaired patient)
Ethanol / Isopropanol
Baclofen
Atenolol, Sotalol
Chloroquine
GM 2
 Treatment of Specific drug poisoning

Benzodiazepine overdose
 Supportive measure is the mainstay of treatment
 Flumazenil: the aim is to reverse respiratory depression.
 Start with 0.2mg IV, wait for 30 secs and titrate up to 1-2mg in total
C/I: patient with undifferentiated coma, epilepsy, benzodiazepine
dependence, co-ingestion of pro-convulsion poisons, e.g. TCA.

Opioid overdose
 Supportive measure is the mainstay of treatment.
 Naloxone: the aim is to reverse respiratory and/or CNS depression.
 Start with 0.4mg IV in opioid naïve user, wait for 60s and titrate up to 2mg
in total.
 For chronic user, start with low dose of 0.1mg.
 Naloxone infusion if repeated administration of naloxone needed. (2/3 of
initial effective naloxone bolus on an hourly basis: i.e. 4 x initial effective
dose + 500ml NS, q6h).

Methamphetamine / Amphetamine / Cocaine overdose

 Agitation, Hyperthermia – Rapid cooling, IV benzodiazepine
 Diazepam 5-10mg IV bolus; cumulative doses up to 50-100mg may be
required.
 HT-Phentolamine 1-5mg IV & repeat every 10 minutes or Nitroglycerin
0.25-0.5 microgram/kg/min.
 Avoid beta-blocker alone for the unopposed α sympathetic effects.
 Cocaine (Na channel blocking effect) – NaHCO3 1-2 mmol/kg IV bolus
till QRS <100ms or pH >7.55

Paracetamol overdose
 Acute toxic dose: >150 mg/kg
 For regular paracetamol: check paracetamol level at 4 hours, LRFT.
 For Panadol (Joint Extended Release / Long Lasting), check paracetamol
level at 4 hours, repeat if it is below Tx line.
 Activated Charcoal if within 1st hour, N-acetylcysteine (NAC) if level
above Tx line.
 NAC has full protection if given within 8 hours post-ingestion, useful even
on late administration.

GM 3
 NAC dose In D5 Rate
Loading 150 mg/kg 200ml In 1 hr
Then 50 mg/kg 500ml In 4 hr
Then 100 mg/kg 1000ml In 16 hr
 With evidence of liver injury, check prognostic markers: PT, APTT, RFT,
blood gas, lactate, PO4, αFP, AST/ALT ratio.

Salicylate overdose
 >150 mg/kg acetylsalicylate (aspirin) – potentially toxic
 Pure methyl salicylate (oil of wintergreen): 10ml contains 14g salicylate
 Ix: R/LFT, blood gas, serial salicylate level, glucose, urine ketone
 Consider GL, AC, MDAC, WBI (depend on amount / formulation)
 Hydration, urine alkalinisation if ASA >40 mg/dL (>2.9 mmol/L)
 HD if end organ failure or ASA >100 mg/dL (>7.3 mmol/L) or failed urine
alkalinisation.

Anti-cholinergic poisoning
 Physostigmine in selected case: 0.5-1mg slow IV, repeat up to 2mg
C/I: TCA, widen QRS, CV disease, asthma, gangrene.

Beta-blocker overdose / Calcium channel blocker overdose

 GI decontamination, haemodynamic and cardiac monitoring
 Treatment options for bradycardia and hypotension:
- Atropine: 0.6mg IV (up to 3mg) and iv fluid
- Glucagon: 2-5mg IV over 1 min (up to 10mg) follow by 2-5 mg/hr in
D5 (for β-blocker poisoning). Titrate with clinical response.
- CaCl2 1g or Ca gluconate 3g over 2 min IV, repeat q10min
Followed by CaCl2 1g/hr infusion and titrate as indicated.
(For CCB poisoning, 2-3 doses can be safely given without checking
Ca level)
- High Dose insulin euglycaemia therapy to enhance tissue perfusion
(early use)
 Regular insulin 1 unit/kg IV bolus + Dextrose 0.5 g/kg IV bolus
(omit dextrose if H’stix >16.7 mmol/L)
 Regular insulin infusion starting at 0.5-2 units/kg/hr and increased
by 2 units/kg/hr every 10 minutes if no increase in cardiac output or
clinical improvement up to 10 units/kg/hr concomitantly with a
continuous dextrose infusion, beginning at 0.5g/kg/hr and titrated to
maintain blood glucose ~5.6-14 mmol/L.

GM 4
  H’stix every 10-30 min until patient is stably euglycaemic, then
every hour.
 Check plasma potassium every hour and keep K >2.8 mmol/L.
- Inotropes: Adrenaline: 0.02 microgram/kg/min and titrate up
Noradrenaline: 0.1 microgram/kg/min and titrate up
Dobutamine: 2.5 microgram/kg/min and titrate up
Isoproterenol: 0.1 microgram/kg/min and titrate up
Vasopressin: 2 IU/hr and titrate
(Dopamine not suggested due to its indirect effect)
- Intravenous lipid emulsion: Intralipid 20% 1.5 ml/kg IV over 1 min,
followed by 15 ml/kg/hr over 30-60 min IV infusion.
(Consider in β-blocker or CCB-induced cardiac arrest, life-threatening
poisoning refractory to other treatment)
- NaHCO3 1-2 mmol/kg IV bolus for propranolol poisoning if QRS
>100ms, repeat as indicated.
(Co-administration of calcium and glucagon is useful in refractory or
mixed cases)
- Methylene blue (consider for refractory vasoplegic shock in CCB
poisoning: 0.1-0.2 ml/kg of 1% (1-2 mg/kg) IV over 5 min (Repeat in 30-
60 min if no response)

Digoxin overdose
 Ix: RFT, digoxin level, ECG
 GI decontamination: consider GL, AC, MDAC
 IVF to correct dehydration
 Bradydysrhythmias – atropine
 Tachydysrhythmia – Tx hypoK, hypoMg, lignocaine, amiodarone
 Cardioversion – may precipitate refractory VT, VF, start with low dose: 10-
25J, pre-Tx with lignocaine or amiodarone
 Digoxin Immune Fab fragments (Digifab® in HA) indications:
 Brady- or Ventricular arrhythmia not responsive to atropine
 Serum K+ >5mmol/L in acute DO
 Digoxin level: 10-15 ng/mL (13-19.5 nmol/L) in an acute DO
 Digoxin ingestion of >10mg
 The recommended dosage of Digifab® can be calculated by any one of the
below formulas (40mg per vial):
Known ingestion amount No. of vials = Amount ingested in mg x 1.6
No. of vials = (digoxin level (ng/mL)) x BW in kg)
Known digoxin level
100
Acute overdose: 10 vials
Empiric dosing
Chronic overdose: 4 vials

GM 5
Warfarin or superwarfarin rodenticide overdose
Asymptomatic Symptomatic, check INR stat

INR at ~48 hours

No severe bleeding Severe / life
threatening bleeding

Normal Prolonged INR

FFP/PCC, Vit K1
Not poisoned (oral, sc, iv -10mg)
Oral Vit K1
No Vit K1 (<1mg/min if IV)
(5-10mg for warfarin, 10-40mg
for superwarfarin in divided
doses)
Monitor INR until plateau
Vit K1 has short duration of
action tds/QID dose needed
FU, may need months for
superwarfarins

Mx guideline for warfarin patient with over anti-coagulation

INR Bleeding Recommendation / Action
< 4.5 No Reduce dose or omit next few doses
If no risk factors for bleeding, omit next few
4.5-10 No doses; if risk factors for bleeding, administer 1.0-
2.5mg oral vit K1
3.0-5.0 mg oral vit K1; if risk factors for
>10 No bleeding, administer prothrombin complex
concentrate (PCC) 15-30 IU/kg
Vit K1 5-10mg IV; PCC 35-50 IU/kg IV; or
>2.0 Yes (significant)
Plasma 15 ml/kg (if PCC not available)
Vit K1 5-10mg IV; PCC 50 IU/kg IV AND FFP
Any Yes (life-threatening)
150-300ml; or Plasma 15 ml/kg (if PCC N/A)
2013 Australasian Society of Thrombosis and Haemostasis updated consensus guidelines
for warfarin reversal

Direct oral anticoagulant (DOAC) overdose

 Inquire about last DOAC intake
 AC if within 2-4 hr of ingestion
 General management: IVF replacement, endoscopic or surgical
haemostasis, blood and plasma transfusion (as plasma expander)
GM 6
 For life-threatening bleeding involving DOAC:
 For rivaroxaban, apixaban or edoxaban: PCC 50 IU/kg IV; consider
rFVIIa (NovoSeven) 90 IU/kg.
 For dabigatran: Idarucizumab 5g IV; may consider haemodialysis or
haemoperfusion.

Theophylline poisoning
 Acute toxic dose: >3g
 Ix: Theophylline level (peak conc occurs >6 hr after ingestion of SR
preparation), electrolytes, glucose, blood gas, lactate, CPK, ECG
 ABC monitoring and supportive measures
 GI decontamination: AC / GL / WBI / MDAC
 Correct hypoK, hypoMg, and metabolic acidosis
 Patient died from tachyarrhythmia, hypotension, hypothermia and seizure.
 Hypotension – IV fluid, α-agonist (Phenylephrine, Noradrenaline)
 Tachyarrhythmia – diltiazem or β-blockers (esmolol, propranolol),
consider Diazepam 5mg IV
 HP/HD indication: Ileus / IO prevents use of MDAC
Theophylline level >80 mg/L (440 μmol/L) (acute)
or 60 mg/L (330 μmol/L) (chronic)
Elderly with level >40 mg/L (220 μmol/L) with
severe symptoms
 Consider CRRT or HP in haemodynamically unstable patient

Sulphonylurea (SU) or insulin secretagogue poisoning

 AC, GL if ingestion <1 hr; consider MDAC / WBI in severe case
 Oral feeding is allowed in conscious patient
 Monitor conscious level, correct hypokalaemia, hypophosphataemia,
hypoglycaemia
 Consider thiamine 100-200mg IV prior to dextrose in alcoholic or
malnourished patient
 D50 0.5-1 g/kg IV bolus preferably through central line
 Glucagon 5mg IM if fail to establish venous access
 In refractory hypoglycaemia (requiring repeated dextrose IV bonus or
escalating concentrated dextrose infusion), consider early use of octreotide
0.05mg q6h SC or IV (to reduce the risk of glucose-induced insulin release
in SU poisoning)
 Urine alkalinisation can be useful in chlorpromazine poisoning

GM 7
Psychiatric Drugs
Antipsychotics poisoning
 Support care, ECG, GI decontamination as indicated.
 Hypotension – IV fluid, inotropes (α-adrenergic agonists)
 Widen QRS interval – treat like TCAs
 Prolong QT interval – risk assessment for TdP with QT nomogram.
Consider MgSO4 2g slow iv infusion in 2-15 min to prevent ventricular
ectopics or TdP
 Dystonia – diphenhydramine 10mg IV or benztropine 1mg IM
 Neuroleptic malignant syndrome (NMS)
 hydration, cooling
 Benzodiazepines: e.g. Diazepam 10-20 mg, Lorazepam 1-2 mg q4-
6h
 Dopamine agonist: e.g. Bromocriptine 2.5 mg q6-8h orally, titrate
up to 40 mg/day
 Dantrolene for severe NMS: 2.5 mg/kg ivi; repeat 1 mg/kg ivi q10-
15min until signs of rigidity resolved or max dose 10 mg/kg/d.
Maintenance: 1 mg/kg ivi q4-6h or 0.25 mg/kg/h iv infusion for up
to 10 days.
 Rhabdomyolysis [refer to GM20].

Tricyclic antidepressant overdose

 Ix: Blood gas, electrolytes, ECG findings of TCA poisoning [widen QRS;
>100msec, terminal 40ms right axis deviation (R in aVr)]; urgent blood
TCA screening.
 Severe cardiotoxicity: hypotension unresponsive to fluid, QRS duration
>160ms.
 Ensure ABC with intensive monitoring
 Consider GL and AC 1g/kg if <1-2 hours post ingestion, MDAC
 Aggressive supportive care & early serum alkalisation by NaHCO3.
Indications QRS > 100ms Ventricular arrhythmia Hypotension
1-2 mmol/kg NaHCO2 IV bolus
Dose May need repeated bolus every 3-5 min or infusion to meet
endpoints
QRS <100ms* Reversal of arrhythmia or Correction of BP
End points
or pH 7.5-7.55 pH 7.5-7.55 or pH 7.5-7.55
pH >7.55 [Consider hypertonic saline]
Contraindication
Intolerable to Na/fluid load [Consider hyperventilation]
*QRS endpoint with reference to patient baseline ECG.
 Physostigmine & Flumazenil are contraindicated.

GM 8
Selective serotonin reuptake inhibitor (SSRI) and related drug poisoning
 Supportive care, ECG, GI decontamination as indicated.
 Treatment for serotonin syndrome (SS) if present
 Remove offending drugs, hydration, cooling
 Benzodiazepines: e.g. Diazepam 10-20 mg, Lorazepam 1-2 mg q4-6h
 Cyproheptadine (8-12mg, then 2mg q2h, up to 32mg in first 24 hr),
neuromuscular blockade.
 Citalopram – observe for >24 hr, cardiac monitoring [for widen QRS,
prolonged QT, torsades de pointes (especially with dose >400mg)]
 Venlafaxine – seizure; esp. with dose >1.5g, widen QRS.
Lithium poisoning
 Ix: RFT, Ca, serial Lithium level (q4h), TFT, AXR, ECG.
 (Serum Li level correlates poorly with CNS toxicities)
 GI decontamination: GL, WBI (AC not indicated)
 Volume replacement and correction of hyponatraemia
 Haemodialysis indication:
 Significant toxicity (depressed consciousness, cerebellar signs,
convulsion, life-threatening dysrhythmia);
 Serum Li level >5 mmol/L in absence of clinical features;
 Serum Li level >4.0 mmol/L with ↓ GFR in patients with acute
overdose;
 Serum Li level >2.5 mmol/L in patients with chronic poisoning
 End point of HD:
 Neurotoxicity subsided; and
 Li level remains stable at <1 mmol/L (Serum Li level may rebound
after stopping HD, continuous monitoring is needed after stopping HD)
 CRRT is an acceptable alternative if HD is not available.
Valproic acid poisoning
 >100-400 mg/kg: potentially toxic; >400 mg/kg: life-threatening
 Ix: LFT, valproic acid (VPA) level q4-6h until a downward trend,
ammonia, blood gas
 Moderate to severe toxicity may occur if VPA level >3100-5900 μmol/L
 ABC monitoring and supportive measures.
 GI decontamination: AC, GL / MDAC / WBI
 Levocarnitine 100 mg/kg [max. 6g] loading PO or IV over 30 min, then
50 mg/kg [max. 3g] q8h PO or IV
 Indication: encephalopathy, hepatotoxicity, hyperammonaemia, or
massive overdose (dose >400 mg/kg) or VPA level >3120 μmol/L (450
mg/L)
GM 9
 Consider naloxone 0.4-2 mg IV for CNS and respiratory depression.
 Consider HD, HP or CRRT (if HD not available) in very severe poisoning
(removing free VPA in blood) if: coma, hyperammonaemia, VPA level
>5900 μmol/L (850 mg/L), or metabolic acidosis pH <7.1
Carbamazepine poisoning
 Ix: carbamazepine level q4-6h until a downward trend, ECG (widen QRS)
 Life-threatening toxicity may occur: carbamazepine level >170 μmol/L
 ABC monitoring and supportive measures.
 GI decontamination: AC / MDAC
 NaHCO3 for widen QRS > 100ms (theoretically beneficial)
 HD, HP or CRRT (if HD not available) in very severe poisoning
Non-Pharmaceutical
Organophosphate poisoning
 Decontamination and staff protection, supportive care.
 Muscarinic and/or nicotinic toxidromes can occur.
 ABC, supportive measures
 Ix: plasma cholinesterase, ABG
 Atropine for reversal of muscarinic toxicity – start with 0.6-1.2 mg IV,
repeat and double the dose every 3-5 min until achieving endpoints: lungs
clear, HR >80 bpm, SBP >80 mmHg, and/or dry axillae (huge dose up to
1000 mg/d may be required).
 Consider early use of pralidoxime to prevent aging of
acetylcholinesterase: 30 mg/kg (up to 2g) into 100ml NS over 30 min IV,
followed by infusion at 8-10 mg/kg/hr (up to 650 mg/hr).
Carbamate poisoning
 Similar to organophosphate poisoning but aging of acetylcholinesterase
does not occur.
 Atropine: 0.6-1.2mg IV, repeat and double the dose q5min until
achieving endpoints.
 Pralidoxime: not usually required in pure carbamate poisoning.
Paraquat poisoning
 >10ml 20% paraquat ingestion is potentially fatal
 GI decontamination: GL in early presentation, AC
 Largely supportive treatment, use lowest FiO2 as possible
 Ix: urgent urine paraquat screening; monitor serial ABG, CXR
 Contact HKPIC or PWHPTC for option of immunosuppression with
cyclophosphamide and methylprednisolone, and charcoal
haemoperfusion in severe paraquat poisoning.
GM 10
Household products
 Disinfectants and multi-purpose cleaners (Dettol®, Salvon®, Swipe®,
Green water, Household hypochlorite bleach, etc.)
 Main toxicities: CNS depression and vomiting causing aspiration
 No antidote, mainstay of treatment is supportive.
 GI decontamination is potentially harmful.
 Can be caustic if large quantity & high concentration is ingested.
 Need OGD if caustic ingestion (drain opener).

Methanol / Ethylene glycol [EG] poisoning

 Ix: Blood – CBP, LRFT, ethanol level, anion gap, osmolar gap, methanol or
ethylene glycol level.
- Urine for Ca oxalate and fluorescence [in EG poisoning]
 Management:
- Consider NG suction, IV NaHCO3 to correct acidosis
- Fomepizole is available as Level III antidote.
[Contact HKPIC / PWHPTC for its indication and mobilisation if needed]
- Ethanol (16g / 20ml), diluted to 10% solution.
 Loading dose: 0.8 g/kg in 30min
 Maintenance: start at 0.1 g/kg/hr, titrate upwards
 (Unstable result in unstable haemodynamic state)
- Folinic acid 50mg q4hr IV (for methanol poisoning)
- Thiamine 100mg and Pyridoxine 50mg q4-6h (for ethylene glycol)
- HD indication: (ADH inhibitor must be continued during HD)
 Features of end-organ toxicity
 Methanol >500 mg/L (15.6 mmol/L); or methanol >700 mg/L (21.8
mmol/L) in the context of fomepizole therapy.
 High osmolar gap without other cause.
 Metabolic acidosis pH ≤7.15, serum anion gap >24 mmol/L
- HD endpoint:
 Methanol <200 mg/L (6.2 mmol/L) and clinical improvement with
correction of metabolic acidosis
- CRRT is an acceptable alternative if intermittent HD is no available for
methanol poisoning.

Cyanide poisoning
 ABC monitoring and supportive measures.
 Surface decontamination and staff protection.
 Treat seizure, hypotension and correct metabolic acidosis.
 GI decontamination: consider AC ± GL if ingestion within 1 hr

GM 11
 Ix: RFT, ABG, lactate, AV O2 gradient (PaO2 – PvO2), CO-Hb, met-Hb,
blood cyanide level (confirm dx but not affect initial mx)
 Early use of antidotes in clinically suspected case: lactate >7 mmol/L, high
anion gap metabolic acidosis, and reduced AV O2 gradient.
 Hydroxocobalamin (antidote of choice): 5g make up to 200ml NS IV in
15min (2nd dose given over 15min to 2hr in severe case); give as IV push
in cardiac arrest.
 Sodium nitrite: 10ml of 3% (300mg) over 3-5min (Single dose only,
adverse effects: hypotension, methaemoglobinaemia)
 Sodium thiosulphate: 50ml of 25% (12.5g) IV over 10-30min or as bolus
in severe case (Give 2nd dose if there is no response in 30min)
[Concomitant use of both sodium nitrite and sodium thiosulphate is an
alternative antidote treatment when hydroxocobalamin is not available]

Methaemoglobinaemia
 Suspect clinically in patient with persistent cyanosis despite oxygenation
and without cardiopulmonary aetiology.
 ABC monitoring and supportive measures.
 Pulse oximeter cannot detect Met-Hb, can be misleading
 Treat seizure, hypotension and correct metabolic acidosis.
 GI decontamination: consider AC if ingestion within 1 hr
 Ix: RFT, ABG, lactate, CO-Hb, met-Hb
 Methylene blue: 0.1-0.2 ml/kg of 1% (1-2 mg/kg) IV over 5min (Repeat
in 30-60min if no response)
 Indications:
- Met-Hb >30%; or
- Met-Hb >20% with symptoms or signs of tissue hypoxia

Carbon monoxide poisoning

 Pulse oximeter cannot detect CO-Hb; can be misleading
 Look for features of tissue hypoxia (CNS, cardiac, metabolic)
 CO-Hb does not correlate clinical severity and/or outcome
 Indications for consideration of Hyperbaric oxygen treatment (HBO)
- Loss of consciousness, coma, seizures
- Confusion, cognitive deficits, focal neurological findings, visual
symptom
- Myocardial ischaemia, life threatening arrhythmias
- Persistent symptoms (after normobaric O2): headache, ataxia, abnormal
neuropsychiatric test
- CO-Hb level >25% or >15% if pregnant woman / child
GM 12
 Contact number of HBOT Centre, PYNEH: 28051295

Suggested guideline for CO poisoning

Acute CO exposure with symptoms

100% O2, CO-Hb level, ABG, ECG

Syncope, coma, seizure, cardiac ischaemia or ventricular arrhythmias

No Yes

CO-Hb ≥25% Yes Consider ICU care

Pregnancy with CO-Hb ≥15% Monitor acidosis
No

Continue 100% O2 therapy Consider HBO*

Yes

Symptomatic (headache, nausea), abnormal mental or neuropsychiatric status

No

Discharge when CO-Hb <10%

Pulmonary irritant inhalation

 Highly water solubility: SO2, Ammonia, HCl, and Chloramine
(cause upper airway, eye and nose irritation, rapid onset)
 Intermediate water solubility: Chlorine
(delayed irritation, potential prolonged exposure, acute lung injury)
 Low water solubility: Phosgene, Nitrogen dioxide
(non-irritating, affect lower airway, lack of noticeable effects →
prolonged exposure and acute lung injury)

Clinical effects ranging from:

 Stridor, bronchospasm → lung injury, bronchiolitis obliterans
 High water solubility irritant → Low water solubility irritant

Monitoring / Ix
 Vital sign / SaO2 / PFR / FEV1 / FVC / voice quality
 ABG, ECG, CXR, Lung function test, fibreoptic bronchoscopy

GM 13
Treatment
 Remove from exposure, ABC monitoring, O2 and supportive care
 Nebulised β-agonists for bronchospasm
 No role for steroids, other than for bronchospasm
 Mechanical ventilation and conventional management of ARDS in severe
case
 Nebulised bicarbonate for Cl2, HCl or other acidic gas
[2ml NaHCO3 8.4% + 2ml water/saline]

Observation
 SO2, NH3, NH2Cl, HCl exposure have no delayed toxicity.
(Improving patients will continue to do well; only need to be observed for
the duration of their symptoms)
 Cl2, COCl2, NO2; Low and intermediate water solubility agents
(Potential for acute lung injury with delayed onset of symptom. Observe
all patients with any symptoms for at least 24 hours. Aware of risk of
bronchiolitis obliterans)

Smoke inhalation management flow-chart

Unconsciousness, stridor, respiratory distress, PaO2 < 8kPa
No Yes

History of unconsciousness Intubation

Close space exposure Use adequate-sized ET tube
Carbonaceous sputum Humidified O2
Facial burn or singed nasal hair Frequent suction
Hoarseness
Oropharyngeal burn, swelling Upper airway
oedema
Yes
No Nasopharyngoscopy / Bronchoscopy

No clinically important oedema

Close monitoring Worsen airway / pulmonary status

 Toxic gases during combustion of organic and inorganic substances may

include: CO, HCN, H2S, SO2, HCl, NH3, phosgene, etc.

GM 14
Snake Bite

Local venomous snakes Toxicity

Viper 蝮 蛇
Bamboo Snake 青竹蛇 Local pain swelling ± bruising,
Chinese Habu 烙鐵頭 Systemic coagulopathy, DIC
Mountain Put Viper 越南烙鐵頭 Hypotension
Elapidae 眼鏡蛇
Banded Krait 金腳帶
Paralysis, minimal local reaction
Many Banded Krait 銀腳帶
Chinese Cobra 飯鏟頭 Early local necrosis
(severe pain and swelling)
King Cobra 過山烏 Rhabdomyolysis, Paralysis
Coral snake 珊瑚蛇 Neurotoxicity with paralysis
Colubridae 游 蛇
Prolonged bite required for effective
Red-necked Keel Back snake 紅脖游蛇
envenomation to cause DIC
Hydrophiidae 海 蛇
Mangrove Water snake 黑班水蛇
Neurotoxic, myotoxic with
Chinese Water snake 中國水蛇
rhabdomyolysis
Plumbeous Water snake 鉛色水蛇

Investigation
 CBP, APTT, PT (esp. whole blood clotting time), RFT, CPK
 Urine for myoglobin and haemoglobinuria
 ECG, Bed side spirometry for FVC if available, serial PFR, CXR

Investigations should be repeated in the following situations

 Progression of local or systemic symptoms.
 Abnormal result from initial test until normal or other cause identified
 After anti-venom administration
 Snake identification is useful (Photographing at safe distance)
[Head, tail, dorsal, ventral feature important for identification]

(Consult HKPIC for urgent contact with biologist for snake identification
and advice on anti-venom use)

Treatment
 Supportive care, analgesic, Tetanus prophylaxis
 Q1/2 hr assessment for local / systemic S/S for first few hours

GM 15
 Antivenoms indications:
- Local progression, necrosis, compartment syndrome.
- Systemic toxicities, i.e. coagulopathies, weakness, rhabdomyolysis,
hypotension etc.
- First S/S of neurotoxicity after krait bite.
Starting
Antivenoms available in HA Snake bite in HK
Dose
Green Pit Viper (Thailand) 3 vials Bamboo snake 青竹蛇
Naja naja (atra) Antivenin 2 vials
Chinese Cobra 飯鏟頭
(Shanghai) 抗眼鏡蛇毒血清 (2000 U)
Bungarus multicinctus Antivenin 1 vial
Many Banded Krait 銀腳帶
抗銀環蛇毒血清 (10000 U)
Banded krait (Thailand) 5 vials Banded Krait 金腳帶
Neuro Polyvalent Snake 5 vials Banded Krait 金腳帶
Antivenin (Thailand) King Cobra 過山烏
Naja Kaouthia 孟加拉眼鏡蛇
Malayan krait 馬來環蛇
King cobra (Thailand) 5 vials King Cobra 過山烏
Russel’s Viper (Thailand) 3 vials Russell’s viper 鎖鍊蛇
Antivenin of P. mucrosquamatus 1 vial Chinese Habu 烙鐵頭,
and T. stejnegeri (Taiwan) 抗 Taiwan bamboo snake 竹葉青,
龜殼花及赤尾鮐蛇毒血清 and probably for
Mountain Pit Viper 越南烙鐵頭
Agkistrodon acutus Antivenin 4 vials
Hundred Pacer 百步蛇
(Shanghai) 抗五步蛇毒血清 (8000 U)
Sea Snake Antivenom (Australia) 1000 units Sea snakes
Cobra (Thailand) – limited stock 10 vials Naja Kaouthia 孟加拉眼鏡蛇
available in some hospitals Cobra 飯鏟頭
Antivenin of B. multicinctus and 1 vial
N. naja atra (Taiwan) 抗雨 Many Banded Krait 銀腳帶
傘節及飯匙倩蛇毒血清 – Chinese Cobra 飯鏟頭
limited stock in some hospitals
Precautions and pre-treatment in anti-venom administration
 Resuscitation equipment stand-by
 Pre-treatment with anti-histamine and hydrocortisone is advised.
 1st dose to 500ml NS, give to 100 ml/hr.
 If no allergy after 5-10min, fasten rate, dose finish in 30min.
 May need further doses if clinically indicated.
 No evidence to support routine prophylactic antibiotic use
 Debridement and surgery for compartment syndrome as indicated.
GM 16
 ACCIDENTAL HYPOTHERMIA
Hypothermia is defined as a core temp of <35oC. (Use low temp thermometer
for core temp)
**Avoid rough handling of geriatric hypothermia patient as this may provoke
cardiac arrhythmia.

Ix: CBP, RFT, blood glucose, H’stix, ABG, amylase, cardiac enzymes,
creatine kinase, serum lactate, coagulation profile, cortisol, TSH, blood
culture (esp. in elderly), CXR, ECG, toxicology screen and CT brain in
comatose patient.

Mx
Assess responsiveness, breathing and pulse

Present Absent
32-35oC (mild hypothermia)
• Passive rewarming
• Active external rewarming
Start CPR
28 - <32 C (moderate hypothermia)
o
Intubate and ventilate with
• Passive rewarming warm, humid O2 (42-46oC)
• Active external rewarming of Warm (38-42oC) NS iv infusion
truncal area only

<28oC (severe hypothermia)

• Active external rewarming

Active internal rewarming:

• Warm iv fluid (38-42oC)
• Warm humid O2 (42-46oC)
• Endovascular warming catheter
• Continuous venovenous haemodialysis
• ECLS: ECMO, Cardiopulmonary bypass
• Peritoneal or pleural lavage (warm fluid
42oC)

Continue active internal rewarming till:

• Core temp ≥35oC; or
• Return of spontaneous circulation or;
• Resuscitative effort ceases
*Give prophylactic broad-spectrum antibiotics (esp. in elderly)
GM 17
 HEAT STROKE / EXHAUSTION

Heat Stroke is caused by over-heating of the body core when sweating is

limited.
Heat Exhaustion is caused by sustained heat stress that causes water and salt
depletion (may be complicated by heat stroke in advanced stage).

Heat Stroke Heat Exhaustion

Drugs or diseases causing limited
Risk Factors
sweating esp. in elderly
Hot and dry in non-exertional heat
Skin stroke. Sweating can occur in Warm and wet
exertional heat stroke.
Core body temp >40oC 38-40oC
CNS features Significant Insignificant
Metabolic acidosis and
Acid-base disorder
respiratory alkalosis
Acute renal injury Common Pre-renal failure

Management
1. Check CBP, RLFT, CaPO4, ABG, coagulation profile, CPK, serum lactate,
urine myoglobin, toxicologic screening, CXR, ECG.
2. Monitor vital signs (esp. urine output) and core temp.
3. Rapid cooling is essential, by removing all clothing, tepid water sponging,
fanning; ice packs to axillae, neck and groins. Cooling blankets and cold
(i.e. room temp) IV fluids are helpful adjuncts.
4. Cooling measures can be stopped once a temperature of 38-39oC has been
achieved to reduce risk of iatrogenic hypothermia.
5. Oral fluid and salt replacement in heat exhaustion (25g NaCl in 5L water).
6. Correction of electrolyte disturbances and hypovolaemia.
7. Seizures are treated with benzodiazepines e.g. midazolam, lorazapam.
8. Look out and support multi-organ failure / complications in heat stroke:
cardiac arrhythmia / heart failure, ARDS, AKI, rhabdomyolysis, hepatic
injury, DIC.

Remarks:
1. Avoid alpha-adrenergic agonist (as vasoconstriction will impair cooling).
2. In Exertional Heat Stroke: paracetamol or NSAID can exacerbate acute
kidney injury or liver derangement.
GM 18
 NEAR DROWNING

The most important consequence of near-drowning is asphyxia which leads to

hypoxaemia, hypercapnia and metabolic acidosis.

1. Monitor and maintain ABC. Clear airway and CPR if necessary. Look for
cardiac arrhythmia.
2. Ix: ABG, RFT, ECG, CXR, SXR and X-ray cervical spine, cardiac
monitoring and body temperature monitoring. Maintain euglycaemia.
3. Beware of head and cervical spine injury and hypothermia.
4. Correct hypoxia and metabolic acidosis. Give O2 therapy (PEEP may be
necessary for severe hypoxia). Treat bronchospasm with β2-agonist.
Bronchoscopy may be necessary if persistent atelectasis or localised
wheezing.
5. Treat seizure with anticonvulsant. Watch out for cerebral oedema.
6. Consider antibiotics for pneumonia.
7. Rule out drug effects e.g. alcohol, hypnotics, narcotics.

ELECTRICAL INJURY

Electrical injuries cause cardiopulmonary arrest, burn, acute renal failure due
to hypovolaemia or myoglobinaemia, injuries to nervous system, damages to
vessels causing thrombosis or haemorrhage. Extent of external injury may not
correlate with severity of internal injury. Alternate current (AC) is more
dangerous than direct current (DC). Current with frequency of 50-60
cycles/sec is more dangerous.

 Ix: ECG, ABG, RFT, troponin, CPK, LDH, urine myoglobin

 Monitor: vital signs, cardiac rhythm, neurological status, urine output and
colour.
 Look for fracture, spinal injury and internal organs damage.
 CPR if necessary.
 Antiarrhythmic drugs depend on nature of arrhythmia.
 IV fluid replacement
 Treat burn and compartment syndrome as appropriate.

GM 19
 RHABDOMYOLYSIS
Dx:
 Red or brown urine +ve for blood but no RBC under microscopy
 Urine +ve for myoglobin
 Pigmented granular casts in the urine
 ↑↑ CK level
 Others: hyperkalaemia, hypocalcaemia, hyperphosphataemia,
hyperuricaemia, metabolic acidosis, DIC, Acute Kidney Injury.

Mx:
 Aim: correction of hypovolaemia, enhance clearance of heme proteins,
mitigate the adverse consequences of heme proteins on the proximal tubular
epithelium.
 Initial fluid resuscitation: NS infusion 1-1.5 L/hr
 Initial rate is continued until BP normalises and patient starts to produce urine
or there is evidence of volume overload.
 Thereafter, continue IV infusion with 500ml NS alternating with D5 1 L/hr.
titrate fluid to maintain urine output at 200-300 ml/hr.
 Continue fluid repletion until CK <5000 IU/L and keeps falling.
 Add NaHCO3 50 mmol/L to each 2nd or 3rd bottle of D5 to keep urinary pH
>6.5. Monitor arterial pH and serum calcium every 2 hours. Stop NaHCO3 if
arterial pH >7.5, or serum HCO3 >30 mmol/L, or hypocalcaemia, or
symptomatic fluid overload.
 Mannitol not routinely administered. May benefit in patients with markedly
elevated CK (> 30,000 IU/L). If given, add 50 ml of 20% mannitol to each
litre of fluid is suggested. Discontinue if osmolar gap > 55 mOsm/kg or
desired diuresis not achieved (200-300 ml/hr).
 May try furosemide if there is volume overload.
 Dialysis for established acute kidney injury.
 Look out and treat significant compartment syndrome.

Notes:
 Regimen is less effective if began after the first 6 hours when renal failure may
have already established.
 Elderly patient may require slower volume replacement.
 Calcium supplement for hypocalcaemia should be avoided unless symptomatic
or for management of hyperkalaemia.
 Look out for hypercalcaemia in recovering phase of AKI.
 Allopurinol [universal screening test for HLA-B*58:01 allele is recommended
before starting] (please refer to R4) if uric acid level >476 μmol/L.
GM 20
 SUPERIOR VENA CAVA SYNDROME

Causes:
 ≥80% due to malignancy
 Non-malignancy aetiologies: e.g. central venous catheter; pacemaker wire,
indwelling cardiac device; infection (e.g. TB, fungal); aortic aneurysm;
post-irradiation.

P/E:
 Dilated superficial veins over anterior chest wall.
 Engorged jugular veins ± facial and arm veins.
 Oedema of face, neck, and upper extremities with cyanosis.

DDx:
 Pericardial effusion with tamponade.

Ix:
 CXR, Duplex ultrasonography, CT, digital subtraction venography,
bronchoscopy.
 Look for secondary pulmonary embolism.

Tx:
 Look out for upper airway obstruction (stridor) – may be life-threatening.
 Malignant SVC syndrome – see pages GM22-23
 Central venous catheter – removal under anticoagulation ±
regional fibrinolytic therapy
 SVC endovenous stenting – consult interventional radiologist for
feasibility.

GM 21
 Medical Oncology
MALIGNANCY-RELATED
SUPERIOR VENA CAVA SYNDROME

(See also SVC SYNDROME, GM21)

Malignancy accounts for 80% of SVC syndrome
Non-small cell lung carcinoma (50%)
Small cell lung carcinoma (25%)
Non-Hodgkin lymphoma (10%)
Others e.g. germ cell neoplasms, breast carcinoma, thymoma etc.

Treatment is tailored to the specific neoplasm; therefore, tissue diagnosis is

essential prior to empirical treatment, which could jeopardise histological
evaluation, e.g. corticosteroid in lymphoma, radiotherapy.

Ix:
 For immediately life-threatening situations e.g. upper airway
obstruction due to tumour compression or severe laryngeal oedema,
impaired conscious state due to cerebral oedema
 Stabilise airway, breathing, circulation
 Urgent Oncology consultation for immediate chemotherapy for chemo-
sensitive tumours.
 Urgent endovascular stenting can provide the most rapid relief without
affecting subsequent tissue diagnosis. Total SVC occlusion and SVC
thrombus are not absolute contraindications for stenting. Post-stenting
short-term anti-thrombotic therapy recommended e.g. dual antiplatelet
agents for 3 months (if no contraindication).

 For stable / stabilised patients

 Clinical examination and investigations targeted to establish tissue
diagnosis by minimally invasive methods.
 Sputum cytology, serum AFP, βHCG levels, LN biopsy, pleural fluid
cytology/pleural biopsy, bone marrow biopsy, endoscopic biopsy,
image-guided biopsy.
 For suspected lymphoma, excisional biopsy of enlarged lymph node is
preferred over fine needle aspiration cytology ± bilateral bone marrow
biopsy.

 Watch out for coexisting pericardial effusion / cardiac tamponade.

GM 22
Tx:
 Empirical
 Prop up for head elevation
 Oxygen supplement
 Dexamethasone 4mg q6h iv

 Disease-specific (Consult Oncology)

 Chemotherapy, immunotherapy or targeted therapy
 Radiotherapy

 Presence of SVC thrombus

 Thrombolysis (mechanical / pharmacologic) may be considered in
patients with extensive thrombus causing severe symptoms, balancing
risks of bleeding.
 Anticoagulation for at least 3-6 months if no contraindication. Extended
anticoagulation beyond 6 months is recommended in patients with
active cancer.
- The direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban,
are the only direct oral anticoagulants (DOACs) that were evaluated
for the treatment of cancer-related thrombosis.
- These DOACs and low-molecular weight heparin (LMWH) are
preferred over warfarin in this population for its lower rate of
recurrent thromboembolism and less drug-drug interactions with
subsequent systemic cancer therapy (except for those with severe
renal impairment).
- Higher bleeding risks associated with DOACs compared with
LMWH have been reported in patients with gastrointestinal and
potentially genitourinary cancers.
(ASCO guidelines 2019 and ASH guidelines 2021)

GM 23
 NEOPLASTIC SPINAL CORD / CAUDA EQUINA
COMPRESSION
(Also see page N26 and PM20)

Aetiologies
 Prostate cancer (20%)
 Breast cancer (20%)
 Lung cancer (20%)
 Others: non-Hodgkin lymphoma, multiple myeloma / plasmacytoma, renal
cell carcinoma etc.
 Prompt diagnosis and immediate treatment important in maximising
neurological outcome.

Ix
 Diagnosis confirmed with MRI of entire thecal sac since multiple level
involvement present in 33% of patients (CT myelography if
contraindicated for MRI)
 For patients without known malignancy, actively search for potential
primary. Tissue diagnosis is essential for subsequent management.

Tx
 General
 Dexamethasone 4mg q6h iv
 Adequate pain control
 Bowel care
 Bladder catheterisation for retention of urine
 Compression stockings
 Prophylactic LMWH in bedbound patients, balancing risks of bleeding

 Specific (Consult Oncology)

 Radiotherapy for most metastatic cancers
 Chemotherapy for chemo-sensitive tumours
 Hormonal therapy for selected cancers
 Surgery for suspected malignancy without tissue diagnosis and no
alternative site for biopsy, presence of spinal instability or radiotherapy
/ chemo-resistant tumours

GM 24
 HYPERCALCAEMIA OF MALIGNANCY

Aetiologies (in decreasing order of frequency)

 Humoral hypercalcaemia of malignancy (PTHrP) e.g. squamous cell /
renal cell / transitional cell carcinomas, breast / ovarian cancers etc.
 Osteolysis from bone metastases
 Calcitriol-secreting lymphoma
 Ectopic PTH secretion

**Initial approach to and control of hypercalcaemia covered in Electrolyte

Disturbances section in K7 and PM18
 Ensure adequate hydration
 Bisphosphonates iv, e.g. zoledronic acid or pamidronate (adjusted to
renal function; CrCl <30 ml/min use caution advised).
 Salmon calcitonin im/sc
 Denosumab sc, in patients with hypercalcaemia refractory to
bisphosphonates, or with chronic kidney disease whom bisphosphonates
are caution advised or contraindicated (please note risk of severe
prolonged hypocalcaemia).

Oncology specific aspects:

 Ensure adequate pain control
 Workup for the cause of hypercalcaemia e.g. previously undiagnosed
malignancy, new development of bone metastasis, recurrence of cancer etc.
 Consult Oncology for disease control of the underlying cancer.
 Systemic corticosteroid can be helpful for calcitriol-secreting lymphoma
in some circumstances, but to be avoided if the specific tissue diagnosis
has not been made yet, please discuss with oncologist first.

GM 25
 TUMOUR LYSIS SYNDROME
TLS can occur after cytotoxic therapy or spontaneously in high-grade
malignancy or high tumour burden, most commonly lymphoblastic leukaemia
/ high-grade lymphomas especially Burkitt’s lymhoma.

Ix / monitoring
 Fluid input / output, ECG / cardiac monitoring, serum potassium, calcium,
phosphate, urate, creatinine, LDH, check G6PD level, HLA-B*58:01

Diagnosis
 Laboratory TLS – At least 2 of the following abnormal serum
biochemistries occurring between 3 days before and 7 days after beginning
chemotherapy despite adequate prophylaxis:
- Potassium ≥ 6mmol/L or 25% increase from baseline
- Urate ≥ 0.5mmol/L or 25% increase from baseline
- Phosphate ≥ 1.45mmol/L or 25% increase from baseline
- Calcium ≤ 1.75mmol/L or 25% decrease from baseline
 Clinical TLS – laboratory TLS AND any of the following:
- Increased serum creatinine to ≥ 1.5 times ULN
- Seizure
- Cardiac arrhythmia
- Sudden death

Prophylaxis
 Adequate hydration 3-4 L/d, aim at urine output ~150 ml/hr, ± diuretics
 Hypouricaemic agents: allopurinol [universal screening test for HLA-
B*58:01 allele is recommended before starting] (please refer to R4)
adjusted for renal function, or febuxostat (in patients with severe renal
impairment / hypersensitivity to allopurinol / HLA-B*58:01 positive), or
rasburicase (in high-risk TLS patients; please note contraindication in
G6PD deficient patients).

Tx
 Correct electrolytes disturbances (see Electrolyte Disturbances section K3)
 Maintain I/O balance
 Monitor and treat arrhythmias
 For persistent hyperkalaemia, hyperphosphataemia, hyperuricaemia,
hypocalcaemia or oliguria, consider dialysis support.
 Rasburicase in selected patients with established TLS on chemotherapy.
GM 26
 EXTRAVASATION OF CHEMOTHERAPEUTIC AGENTS

Definition:
 Escape of an irritant (causing tissue inflammation) or vesicant (causing
tissue necrosis) drug into the extravascular space.

Commonly used vesicants:

 Anthracyclines e.g. doxorubicin, epirubicin, daunorubicin, idarubicin
 Vinca alkaloids e.g. vinblastine, vincristine, vinorelbine

Prevention of extravasation is the best strategy against extravasation injury

 Proper infusion technique is of paramount importance.
 Consider the use of central venous catheter for vesicant infusion.
 For peripheral infusion of chemotherapy, use a newly set IV line in a large
peripheral vein with close monitoring of any evidence of extravasation.

When extravasation is suspected:

 Stop the infusion immediately.
 Leave the catheter in place.
 Aspirate fluid from the extravasation area.
 DO NOT flush the line or apply local pressure.
 Administer antidote if applicable before removal of catheter.
 Access the extravasation kit for specific antidote:
Topical DMSO, consider
Anthracyclines
IV dexrazoxane if available
Mitomycin Topical DMSO
Mechlorethamine, (bendamustine,
SC sodium thiosulphate
dacarbazine, cisplatin, carboplatin)*
Vinca alkaloids, (etoposide, taxane)* SC hyaluronidase
*(specific antidote recommendation is less consistent for drugs in bracket)
 Elevate the extremity with extravasation.
 Apply heat locally for vinca alkaloids and epipodophyllotoxins (e.g.
etoposide); apply cold locally for other agents.
 Take clinical photos of the extravasation injury.
 Document the extravasation process and measures taken.
 Monitor the healing process, full-thickness skin or surrounding tissue
necrosis may necessitate surgical intervention.

GM 27
 CANCER IMMUNOTHERAPY RELATED
ADVERSE EVENTS (IrAEs)
Immune checkpoint inhibitors (ICI) are commonly used in solid organ
malignancies and contribute to improved oncological outcomes. They enhance
anti-tumour cytotoxic T-cell response by acting on the PD1-PDL1 and/or CTLA4
pathway. Off-target disruption to immune tolerance can trigger immune-
mediated injury to lungs, liver, gut, and endocrine glands. Severe IrAEs are life-
threatening and warrant prompt recognition and treatment.

General Principles:
 Life-threatening IrAEs include generalized or bullous skin eruptions,
pneumonitis, enterocolitis, hepatitis, and endocrinopathies. Myocarditis,
nephrological, and neurological IrAEs can rarely occur.
 IrAEs are diagnosed clinically and graded by severity.
 Apart from endocrinopathies, corticosteroid (CS)-based immunosuppression
is promptly initiated to limit inflammation and end-organ dysfunction. Slow
tapering of corticosteroid over several weeks is guided by clinical
improvement (Consider PJP prophylaxis).
 Escalation of immunosuppression or initiation of corticosteroid (CS) sparing
agents is often decided in consultation with specialists and medical
oncologists. A multidisciplinary approach hastens diagnosis, management,
and AE resolution.

IR-Pneumonitis
Up to 4% and 10% for monotherapy and doublet ICI respectively. Presenting
radiological patterns can be cryptogenic organizing pneumonia-like, ground
glass opacities, interstitial, hypersensitivity-like, or pneumonitis NOS. Consider
alternative or co-existing conditions such as COPD exacerbation, pulmonary
embolism, lymphangitis carcinomatosis, drug related lung injury, radiation
pneumonitis, and pulmonary infections such as TB and PJP.

Ix / diagnosis
 Grade 2 or above suspected pneumonitis require contrasted CT thorax and
respiratory consultation.
 Bronchoscopy to exclude microbiological causes.

Management
 Empirical antibiotics
 Withhold/stop ICI
 Definitive treatment for pneumonitis
GM 28
Grade 1 (Asymptomatic, confined to one lobe or <25% of lungs) Observe for
symptomatic and radiological progression every 2-3 days. Save throat swab
for virus, sputum for aerobic cultures, AFB smear and culture. Treat
pulmonary or URT infections.
Grade 2 (Mild symptoms, low dose oxygen therapy) Inpatient monitoring,
start oral prednisolone 1mg/kg and escalate if no improvement in 48 hours.
Grade 3 (Severe symptoms, high dose oxygen) Start IV methylprednisolone
1-2mg/kg/day
Grade 4 (Life threatening, ARDS) as above, consider ICU consultation and
ventilatory support, consider escalate immunosuppression by adding
tocilizumab or other immunosuppressants.

*Consider alternative diagnoses if no improvement with escalating

immunosuppression.

IR-Hepatitis
Up to 10% and 30% in monotherapy and doublet ICI therapy respectively.
Consider in patients with subacute rise in parenchymal liver enzymes. Other
patterns of LFT derangement suggesting IR-Cholangitis can occur. Cholangio-
hepatitis, drug/herb related live injury and flare of occult/chronic viral
hepatitis should be excluded.

Ix / diagnosis
 Ultrasound or other cross-sectional imaging of the liver to exclude tumour-
related complications such as biliary obstruction, hepatic tumour
infiltration, or portal vein thrombosis.

Management
Grade 1 (ALT/AST up to 3*ULN) Monitor every 1-2 weeks, continue ICI
Grade 2 (ALT/AST 3-5* ULN) Withhold ICI, monitor LFT every 1-2 weeks
Grade 3 (ALT/AST 5-20*ULN) Withhold ICI, in-patient monitoring of LFT
and INR, start corticosteroid at 1-2mg/kg/day, escalate if deterioration or no
improvement in 72 hrs.
Grade 4 (ALT/AST >20*ULN) As above, start IV methylprednisolone
2mg/kg/day, escalate immunosuppression if deterioration or no improvement
in 72 hrs.

*Consider alternative diagnoses if no improvement with escalating

immunosuppression.

GM 29
IR-Enterocolitis
Occurs in 1% of monotherapy vs 10-15% in patients on doublet ICI.

Ix / diagnosis
 Exclude infective causes: Save stool for bacterial, viral cultures, and
clostridium difficile toxin; Blood for CMV PCR
 Endoscopy for unexplained ≥G2 diarrhea or symptoms of colitis

Management
Grade 1 (Increase in <4 stools/day) Continue ICI, monitor symptoms
Grade 2 (Increase in 4-6 stools/day) Withhold ICI; Save stool, arrange
colonoscopy, bloods for CBC Electrolytes and CRP, start Prednisolone at
1mg/kg/day p.o. for confirmed cases
Grade 3 (Increase in >=7 stools/day) In-patient monitoring, watch out for
toxic megacolon and perforation, start IV methylprednisolone 1mg/kg/day,
consider escalation therapy if no response in 72 hours
Grade 4 (Life threatening diarrhea, or with abdominal pain, fever, or PR
bleeding/mucus): as above
Infliximab and Vedolizumab are options for escalation therapies with reported
efficacy in corticosteroid-unresponsive disease.

*Consider alternative diagnoses if no improvement with escalating

immunosuppression.

IR-Endocrinopathies
Most patients on ICI undergo regular monitoring of thyroid function and
morning spot cortisol. Overt patterns of hyperthyroidism or hypothyroidism
commonly warrant symptomatic treatment or thyroxine replacement
respectively. A low morning spot cortisol warrants workup with the Short-
Synacthen Test (see E11). Many ICI patients develop thyroid and adrenal
insufficiencies requiring long-term hormonal replacement. In patients without
periodic monitoring, endocrine emergencies such as Addisonian crisis,
thyrotoxicosis, and myxedema coma may occur. Anti-CTLA4 therapy may
give rise to symptomatic or clinically-occult hypophysitis (See relevant
sections in IM Handbook).

Reference
J. Haanen et al., Management of toxicities from immunotherapy: ESMO Clinical
Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology 33,
1217-1238 (2022).

GM 30
 BRAIN DEATH

(Based on Guidelines on Certification of Death Following the Irreversible

Cessation of Brainstem Function issued on 15 November 2017, with this link:
http://ha.home/circular2/Ops-2017-32.pdf)

Use updated Brain Death Certification Form HA0090/MR.

 For patients who are 2 years of age or older.

Concept: Brainstem death equates with death both medically and legally.

1. Pre-conditions and exclusions for considering diagnosis of brainstem

death
*All the following should coexist
a) Diagnosis of severe irremediable brain injury which is consistent with
progression to brain death (the clinical diagnosis is usually confirmed
by neuro-imagining). The diagnosis of a disorder which can lead to
brainstem death should have been fully established.
b) Apnoeic patient on a ventilator
 Muscle relaxants and other drugs should have been excluded as a
cause of such findings.
c) Exclusion of potentially reversible causes of coma
 Depressant drugs or poisons; peripheral nerve stimulator to confirm
intact neuromuscular conduction.
 Primary hypothermia: core temp >35oC before diagnostic tests of
brain stem death are carried out.
 Metabolic and endocrine disturbances (e.g. severe electrolyte or
endocrine disturbances)
 Arterial hypotension as the cause for the coma should be excluded.

2. Tests for confirming brain death

*All brainstem reflexes must be absent.
*The testing of all the following is considered sufficient.
a) Both pupils are fixed, ≥4mm in diameter and non-reactive to light.
b) Absence of bilateral corneal reflexes.
c) Absence of vestibule-ocular reflexes: no eye movement occurs in both
eyes during or after the slow injection of at least 50ml ice-cold water
into at least one external auditory meatus, or preferably into each
external auditory meatus in turn. Clear access to the tympanic
GM 31
 membrane should be established by direct inspection. This test may be
contraindicated on one or other side by local trauma.
d) No motor responses within the trigeminal nerve distribution can be
elicited by adequate pain stimulation of any somatic area.
e) Absence of gag reflex.
f) Absence of cough reflex.
g) Testing for apnoea: should be done last. No respiratory movements
occur when the patient is disconnected from the mechanical ventilator
for long enough to ensure that the PaCO2 rises above the threshold for
stimulating respiration (i.e. PaCO2 >8.0 kPa and arterial pH <7.30). In
patients with pre-existing hypercapnia, it is recommended to wait for a
PaCO2 rise of >2.7 kPa (20mmHg) above the chronic level, with a pH
<7.30. ABG must be available for this test to be performed. The patient
should be disconnected from mechanical ventilator when PaCO2 is
close to normal. Hypoxaemia during disconnection should be prevented
by preoxygenation and administration of oxygen during the test, e.g. by
delivering O2 through a catheter into the trachea.

Period of observation and repetition of tests: 2 full separate examinations

should be performed.
 The first examination should be performed after all pre-conditions met,
and after at least 4 hours of observation of coma (Glasgow Coma Scale of
3) with absent brain-stem function.
 The second examination can be performed any time after the first
examination, so that total period of observation is at least 4 hours. The
minimum period of observation needed to be totally 24 hours after
cardiorespiratory arrest.
 It is recommended that the brain death test be delayed for at least 72 hours
after rewarming if therapeutic hypothermia has been used as post cardiac
arrest care, earlier if brain death is determined by demonstration of absent
cerebral blood flow.

Medical practitioners:
 One of the doctors must be a specialist recognised by the appropriate College
as having demonstrated skill and knowledge in the certification of death
following irreversible cessation of brainstem function (usually an Intensivist,
Critical Care Physician, Neurologist or Neurosurgeon).
 The other doctor should preferably be of the same qualification but should be
at least 6 years after registration and possess the skill and knowledge in the
certification of death following irreversible cessation of brainstem function.

GM 32
 The person authorising removal of tissues and the person removing tissues
MUST NOT be responsible for determining brainstem death.

Confirmatory Ix:
 If the preconditions for clinical diagnosis and confirmation of brainstem
death cannot be satisfied, objective demonstration of absence of
intracranial blood flow is required (after the 4-hour period of observation
of coma and of absent brainstem responses, where these can be tested).

Time of death:
 The time when certification of brainstem death has been completed (i.e.
following the second confirmatory examination) or if a confirmatory
investigation is used, then the time of death should be after the
confirmatory investigation.

Clinical observations COMPATIBLE with diagnosis of brainstem death

 Movements of limbs in response to a stimulus outside the distribution of
cranial nerves.
 Sweating, blushing, tachycardia.
 Normal BP without pharmacologic support
 Absence of diabetes insipidus
 Deep tendon reflexes
 Extensor plantar reflex

Features NOT COMPATIBLE with brainstem death:

 Decerebrate or decorticate posturing
 Seizure

GM 33
 Procedures

For all procedures,

INFORMED CONSENT
must be obtained (also see Gr3)
except in an emergency life-saving situation

Always mark the correct

side before procedure
 ENDOTRACHEAL INTUBATION

Indications
1. Respiratory / ventilation failure, including CPR.
2. To protect airway against aspiration.
3. To manage excessive airway secretions.

Equipment
1. Bag-Mask-Valve device (BMV)
2. IV access* as far as possible
3. Cardiac monitor & pulse oximeter
4. Oropharyngeal / nasopharyngeal airways
5. Direct laryngoscope (Macintosh) with functioning light bulb and blade of
appropriate size (start with size 3, usually size 3-4 for adults)
6. Endotracheal tube (Male 8-8.5mm, female 7.5-8mm internal diameter)
with low pressure cuff.
 With syringe for cuff inflation, check cuff for leakage (Inflate with
10ml syringe, then deflate completely)
 If stylet used, lubricate and insert into ETT. Its tip must be recessed
>1cm from distal end of tube.
7. End-tidal CO2 (ETCO2) monitor if available.
8. Yankauer sucker
9. Bougie if indicated
10. A spare endotracheal tube with size 0.5-1mm smaller.

Note
1. Consult anaesthetists in expectedly difficult case.
2. In patients with suspected unstable cervical spine, leave intubation to
expert hands if possible, otherwise, do in-line stabilisation during
intubation.
3. Do not attempt intubation for >15 sec at a time. Achieve adequate
oxygenation before the next attempt.

Procedure
1. Position patient supine.
2. Place patient in sniffing position (neck flexed, and head extended). Open
airway by head tilt-chin lift / jaw thrust.
3. Remove dentures and other foreign bodies.
4. Fit a face mask tightly on patient’s nose and mouth and ventilate using a
BMV connected to O2 (bag should be inflated with O2).
Pr 1
5. Pre-oxygenate for at least 3 minutes.
6. (Optional) Apply cricoid pressure (Sellick’s manoeuvre)
7. Perform Rapid Sequence Induction (RSI)
 Give a short acting sedative (e.g., midazolam / propofol / etomidate)
 Followed immediately by a paralytic agent (e.g., suxamethonium /
rocuronium).
8. Insert direct laryngoscope: Push tongue to the left, exposure larynx by
pulling jaw towards ceiling (Do not lever laryngoscope at the teeth).
9. Gently slide ETT in between cords. Advance ETT to incisor marking 22-
24cm for males, 20-22cm for females (Or visualising the thick black line
in ETT entering vocal cord)
10. For more difficult case, consult anaesthetist / senior. In selected case,
may consider the use of bougie or McCoy blade for assistance: insert
bougie as a guidewire, then thread ETT through afterwards.
11. Inflate cuff (4-6ml air to achieve cuff pressure 20-24cm H2O) and
remove stylet.
12. Connect ETT to BMV
13. Confirm ETT position with ETCO2 device, if available, and observe for
bilateral lung expansion; and 5-point auscultation (bilateral infra-
clavicular, infra-mammary, and epigastrium). No air movement should
occur over epigastrium.
14. Off cricoid pressure AFTER endotracheal intubation is confirmed if
using Sellick’s manoeuvre.
**In case of failed intubation, maintain mask ventilation and summon help.
DO NOT inject second dose of muscle relaxant for another attempt.

After-care
 Urgent CXR to check ETT position (ETT tip 4 ± 2cm above carina,
exclude pneumothorax / pneumomediastinum / one-lung intubation)

Special precautions when intubating patients with suspected / confirmed

COVID-19
1. Perform intubation in negative-pressure room whenever possible.
2. Limit the number of health care providers in the room or on the scene.
3. Intubation is best done by one experienced in the procedure.
4. Rapid sequence induction (RSI) with adequate muscle relaxant is
preferred. Avoid awake intubation as cough during intubation increases
viral spread.

Pr 2
5. Use video laryngoscope whenever possible.
6. Adjust ventilator settings beforehand. Prepare the ventilator circuit, filter
and ETCO2 device before intubation, so as to minimise disconnections
after intubation.
7. Preoxygenate for 3 to 5 minutes with 100% O2 using low or moderate
flow rates (10 to 15 L/min) and NRB mask.
8. If BMV is required, a filter should be applied between the patient’s mask
and the bag. Hold mask tightly on patient’s face and both hands using an
E-C clamp technique. Avoid manual ventilation if possible but if it is
required, small tidal volumes should be applied.
9. Inflate cuff immediately following ETT placement and prior to initiating
positive pressure ventilation.
10. Confirm placement of ETT with ETCO2 device is preferable.
11. Supraglottic airway is preferred for rescue oxygenation and ventilation,
e.g., during intubation difficulty.

Pr 3
 SETTING CVP LINE

Indications
1. Haemodynamic monitor
2. Administration of TPN, vasopressors

Contraindications
1. Bleeding tendency
2. Ipsilateral carotid artery aneurysm

Common complications
1. Infection 4. Pneumothorax
2. Catheter-induced thrombosis 5. Air embolism
3. Vascular injury 6. Bleeding, venous stenosis, arrhythmia

Internal Jugular Vein (IJV) Puncture

 Preferably US-guide
 Head-down position with the head turned to the opposite side.
 Aseptic technique, use Gauge 14 or 16 angiocatheter.
 IJV runs behind the sternocleidomastoid (SCM) close to the lateral border of
the carotid artery.
 Place patient in a 20º head-down position with the head turned to the opposite
side.
 Right side preferred to avoid injury to the thoracic duct.
(1) Anterior approach: Insert angiocath 0.5-1cm lateral to carotid pulse at
midpoint of the sternal head of SCM.
(2) Central approach: Insert angiocath at apex of triangle formed by two
muscle bellies of SCM and clavicle.
 Advance angiocath towards ipsilateral nipple with the syringe angulated 30-45º
to the skin. Maintain gentle aspiration till a gush of blood (dark red) is aspirated.
 Gently withdraw stylet of angiocath while pushing angiocath into position,
connect infusion set to angiocatheter.
 If the artery is punctured (bright red blood), withdraw everything and apply
firm pressure for at least 5 minutes.
 (Never advance beyond clavicle. Pneumothorax can kill)
 Always make sure that the catheter is in vascular space
(Check siphoning: Venous blood backflows upon lowering infusion set below
the patient & blood level should oscillate with respiration)
 Read the first CVP reading yourself
 Always take a CXR afterwards to exclude pneumothorax.
 Maintain catheter patency with infusion of fluid.

Pr 4
 DEFIBRILLATION

Timely defibrillation for a shockable rhythm and high quality chest

compressions with minimal interruption are keys to successful resuscitation.

1. CPR before defibrillator available.

2. Attach and turn on defibrillator when available.
3. Check rhythm and identify shockable rhythm (VF and pulseless VT).
4. Apply appropriate conductive material to hand-held paddles or use
defibrillator electrode pads. Do not rub the 2 paddles together.
5. Select energy level:
 Monophasic defibrillator – 360 J
 Biphasic defibrillator - device specific; if waveform type unknown,
use 200 J
 (150 J to 200 J for biphasic truncated exponential waveform or 120 J
for rectilinear biphasic waveform)
6. Press charge button on machine or paddle.
7. Apply firm pressure with one paddle at cardiac apex, the other over base
of heart (if paddles are used)*.
8. Warn everybody to stay clear of the patient.
9. Deliver the shock by pressing both discharge buttons simultaneously.
10. Resume CPR immediately after the shock and give two minutes of CPR
(30 chest compressions then 2 breaths if advanced airway has not been
established). Then reassess rhythm.

* For patient with permanent pacemaker, anterior-posterior orientation is

preferred or with paddles > 10 cm from pacemaker. Interrogate pacemaker
after defibrillation to ensure normal functions.

Pr 5
 TEMPORARY PACING

1. Equipment: Venous puncture set, venous access sheath, temporary

pacing wire and pacemaker generator, cardiac monitor,
defibrillator/transcutaneous pacing standby.
2. Select venous access – in general, right internal jugular vein is preferred
if performed at bedside. Other options include femoral or subclavian.
3. Give local anaesthesia and perform venepuncture under aseptic
technique, preferably under real-time USG guidance.
4. Manipulate pacing wire to RV apex ± fluoroscopic guidance.
5. Connect pacing wire to temporary pacemaker.
6. Test pacing threshold with a pacing rate above the patient’s own rate.
Accepted site if threshold <1V. Set output at >3×threshold or 3V
whichever is higher.
7. Test for sensing threshold with pacing rate less than patient’s own rate if
clinically feasible. Set sensitivity to ½ of sensing threshold (i.e. more
sensitive than the sensing threshold).
8. Set desirable pacing rate, e.g. 70-80/min.
9. Secure pacing wire at insertion site and cover with dressing.
10. Record the rhythm.

Aftercare
 Full lead ECG and portable CXR.
 Continue cardiac monitoring.
 Check pacing threshold daily and adjust output accordingly.
 Watch out for complications (infection, bleeding, haematoma,
pneumothorax, thrombophlebitis, etc).

Transcutaneous Pacing (TCP)

 As interim measure before transvenous pacing.
 Anterior TCP patch at cardiac apex and posterior patch over left
infrascapular region. Turn the pacer ON ± consider analgesia.
 Set the rate to ~60/min (adjusted to clinical condition). Set the current
output 2mA above the level with consistent mechanical capture (safety
margin), verified by femoral pulse. (Do not assess carotid pulse to confirm
mechanical capture as muscular jerking may mimic carotid pulse.)

Pr 6
 LUMBAR PUNCTURE

Indications
1. To check intracranial pressure (ICP) and obtain cerebrospinal fluid (CSF)
for diagnosing a wide variety of neurological and neurosurgical conditions
e.g. CNS infection, autoimmune encephalitis, SAH, carcinomatous
meningitis, CNS demyelination, Guillain-Barré syndrome etc.
2. CSF drainage
3. Intrathecal administration of antibiotics or chemotherapy.

Precautions
Always examine the patient for evidence of raised intracranial pressure and
focal cerebral lesion before performing LP (Look for papilloedema, impaired
consciousness, focal neurological deficit, false localising signs).
1. In case of doubt, a CT scan of the brain should be performed first to exclude
contraindications of LP. Perform blood culture and start antibiotic for
bacterial meningitis if such diagnosis is suspected and CT brain cannot be
done shortly.
2. Do not perform LP if there is uncorrectable bleeding tendency (INR >1.4,
severe thrombocytopenia 50-80 x 109/L) or local infection at puncture site.

Procedures
1. Lie patient in left lateral position with back and knees flexed (may try
sitting position if failure after 2-3 attempts).
2. Aseptic technique
3. Infiltrate skin with local anaesthetic.
4. Advance spinal needle (22-25 gauge) between spinous processes of L3/4
or L4/5.
5. At about 4-5cm, a ‘give’ sensation indicates that the needle has pierced
through ligamentum flavum.
6. Remove stylet to allow CSF fluid to come out.
7. Note the appearance of the CSF and measure CSF pressure.
8. Lie patient flat for 4-6 hours after LP (24 hours if ICP increased).
9. A total of 8-15 mL of CSF (divided into several specimen bottles) is
typically removed for routine diagnostic LP; depending on the
provisional clinical diagnosis, CSF fluid can be sent for:
 Biochemistry (protein & glucose) (use fluoride bottle for CSF
glucose, check simultaneous blood glucose / H’stix)
 Microscopy and cell count, Gram stain and culture
 Bacterial antigen (patient already on antibiotics)
Pr 7
  AFB smear and culture ± PCR; ADA
 Syphilis Serology
 Indian Ink, fungal culture and cryptococcal antigen
 Viral isolation and antibody titre, Japanese encephalitis, PCR DNA
HSV, VZV & PCR RNA EV (if indicated)
 Cytology
 Xanthochromia
 IgG / albumin ratio and oligoclonal bands (with serum)
 NMDA and autoimmune encephalitis panel (with serum)
10. Regarding therapeutic LP, the amount of CSF drainage depends on
clinical situations.
11. Imaging guidance (such as ultrasound or fluoroscopy) can be considered
for patients with difficult anatomy or unsuccessful previous LP attempts.

Complications
1. Post LP headache: 10-30%
2. Radicular pain & back pain
3. Infection (very rare)
4. Spinal haematoma (very rare)
5. Cerebral herniation (very rare)

Reference: Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines

for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst).
2017;8:111-126. Published 2017 May 18. doi:10.1016/j.dadm.2017.04.007

Pr 8
 BONE MARROW ASPIRATION & TREPHINE BIOPSY

Bone Marrow (BM) Aspiration & Trephine Biopsy

1. Obtain informed consent
2. Stop anticoagulants ± antiplatelet agents prior to procedure subject to
individual assessment.
3. Use a Jamshidi bone marrow needle.
4. Site: Posterior superior iliac spine (PSIS) with patient in decubitus or prone
positions.
5. Clean the skin overlying the posterosuperior iliac crest with aseptic
technique
6. Infiltrate overlying skin and periosteum with local anaesthetics.
7. Make skin incision with a blade (2-3 mm)

BM Aspiration
1. Hold needle at right angle to iliac crest
2. Advance needle with firm pressure in a clockwise-anticlockwise motion till
needle anchored.
3. Advance needle orientated at an angle laterally in the direction
pointing towards the ipsilateral anterior superior iliac spine (ASIS).
LATERAL NEEDLE DIRECTION approach is the only recommended
technique; Perpendicular needle direction approach is strongly
discouraged.
4. Remove the stylet
5. Apply gentle suction with a 20 ml syringe to aspirate 2-3 ml each pass.
6. Make marrow smear straight into EDTA bottles
7. Send marrow aspirate in appropriate media for additional special tests as
clinically indicated, e.g. cytogenetic studies, microbiological cultures, etc

BM Trephine Biopsy
1. Proceed to trephine biopsy through the same skin incision, advancing
needle further without stylet slowly with firm pressure in rotatory
movements.
2. Advance needle orientated at an angle laterally in the direction
pointing towards the ipsilateral anterior superior iliac spine (ASIS).
LATERAL NEEDLE DIRECTION approach is the only recommended
technique; Perpendicular needle direction approach is strongly
discouraged.

Pr 9
3. Obtain trephine biopsy 1.5-2 cm in length.
4. Rotate and rock and needle several times to break the biopsy specimen from
surrounding marrow.
5. Withdraw needle by rotation with quick full twists.
6. If there is no/inadequate bone marrow aspirate (dry tap), may attempt
obtaining cytology by touch imprint (gently rolling trephine specimen on
glass slides).
7. Send trephine biopsy in formalin bottle.

NB
 For patients with suspected haematological malignancies or
myelodysplastic syndrome, arrange with laboratory Haemato-pathologists
beforehand for cytogenetic and immunophenotyping studies (if available).
 In case of suspected arterial injury, needle should be kept in-situ to
maintain tamponade effect, then seek help immediately. Needle removal
may result in life-threatening arterial haemorrhage.

Pr 10
 CARE OF HICKMAN CATHETER

Hickman Catheter Irrigation & Heparin Lock

1. Wash hands thoroughly with anti-microbial soap and water.
2. Put on non-sterile latex gloves.
3. Draw 5 ml of heparin-saline (50 units / 5 ml) into a 10 ml syringe and 10
ml Normal Saline in another 10 ml syringe. Eliminate air from the syringes.
4. Swab end one-inch of catheter and the junction (catheter with Heparin cap
or with IV tubing) and alcohol wipe vigorously with friction for at least 3
times.
5. Ensure that the catheter clamp is closed.
6. Disconnect the heparin block or IV tubing and swab the hub vigorously
with friction for at least 3 times with Alcohol wipe. Allow the antiseptic to
air dry.
7. Perform each catheter irrigation and catheter cap:
Weekly heparin-saline flushing:
 Connect an empty 10 ml syringe.
 Release clamp, and aspirate 5 ml of blood (3 times the catheter volume)
to clear the catheter.
 Reclamp catheter. Remove the discard the blood syringe.
 Inject 10 ml normal saline, then 5 ml heparin saline.
 Swab the hub with Alcohol wipe and insert a new catheter cap.

Clearing of Blocked Hickman Catheter

Stage I – If infusion rate is slow:
1. Wash hand thoroughly with soap and water.
2. Put on non-sterile latex gloves.
3. Prepare 10 ml Normal Saline in a 10 ml syringe.
4. Wipe end one-inch of catheter and the junction (catheter with Heparin block
or with IV tubing) with alcohol wipe vigorously with friction for at least 3
times. Allow the antiseptic to air dry.
5. Ensure catheter clamp is closed.
6. Disconnect the heparin block or IV tubing. Swab the hub vigorously with
friction for at least 3 times with alcohol wipe. Allow the antiseptic to air dry.
7. Verify catheter occlusion by attaching an empty syringe to catheter and
attempt to aspirate. If all clots in the catheter can be aspirated successfully,
follow with catheter irrigation and heparin block or resume IV infusion.
8. If catheter is still occluded, attempt clearing by using a gentle alternating
irrigation and aspiration (push and pull) with a 20 ml syringe half-filled
with normal saline. If this fails, try with heparinised-saline.
Pr 11
N.B. 1. Do not force fluid as catheter damage may result.
2. If necessary, obtain an X-ray image of catheter to check it is in-situ.

Stage II – If the first procedure has failed or the catheter has been
blocked for over 2 hours:
 Repeat procedure in stage I but with 3 ml pure heparin (1000 units/ml)
by Doctor.

Stage III – If stages I & II have failed:

 A fibrinolytic agent e.g. Urokinase can be used. Please contact
haematologist or haematology nurse.

Pr 12
 RENAL BIOPSY

Relative contraindications:
1. Active infection e.g. acute pyelonephritis
2. Very small kidneys (< 8cm)
3. Single kidney
4. Uncontrolled hypertension
5. Bleeding tendency

Preparation:
1. Check CBP, platelets, clotting profile +/- bleeding time
2. Type and screen / X-match 1 unit packed cells
3. Trace report of USG
4. USG for localisation

Biopsy:
(Preferably done in early morning on a weekday)
1. Platelet count should be >100 x 109/L, PT, aPTT normal
2. Check baseline BP/P
3. Fresh biopsy specimen put into plain bottle with NS and send for
histology, immunofluorescence ± electron microscopy

Post-Biopsy:
1. Close monitoring of BP/P
2. Save urine samples for inspection (for gross haematuria)
3. Appropriate oral analgesics
4. Inform if gross haematuria, falling BP (SBP <100 mmHg), increasing
pulse rate (>100/min), oozing of blood or severe pain at biopsy site.

Pr 13
 PERCUTANEOUS LIVER BIOPSY

Before liver biopsy, educate the patients about their liver disease and
investigations other than liver biopsy. Carefully inform the patients about the
procedure, risks and benefits, limitations and alternatives (if any) before
obtaining consent.

Contraindications
1. PT >4 secs prolonged or INR >1.5; platelet count <60×109/L; bleeding
time >10 mins;
(Consider safer approach like USG-guided plugged liver biopsy or
transvenous liver biopsy)
2. Gross ascites
3. Patient unable to hold breath or cooperate
4. Extrahepatic biliary obstruction, cholangitis.
5. Vascular tumour, hydatid cyst, subphrenic abscess.
6. Amyloidosis
7. Morbid obesity

Procedure
(Biopsy preferably done on a weekday in the morning)
1. If no contraindication, discontinue anti-platelet agents, NSAIDs, warfarin
or new oral anticoagulants for adequate period before procedure. Consider
bridging therapy with heparin in high thrombotic risk patients. Risk of
stopping anti-platelet agents or anticoagulants should be weighed against
the benefit of liver biopsy. Consult relevant specialist(s) if indicated. In
general, stop warfarin for 5 days prior to liver biopsy. Withhold heparin
for 12-24 hours.
2. Check CBP, platelet, INR, APTT ± bleeding time in patients with renal
impairment or chronic liver disease.
3. X-match 2 pints whole blood for reserve and consider antibiotic
prophylaxis in selected cases.
4. Check BP/P before procedure.
5. Instruct patient on how to hold breath in deep expiration for as long as he
can.
6. Palpate the abdomen and percuss for liver dullness in the mid-axillary line.
7. Perform ultrasound for guidance immediately before the liver biopsy, with
marking of the optimal biopsy site. Ultrasound examination by the

Pr 14
 individual performing biopsy is preferred.
8. Choose rib space with maximum liver dullness (ascertain puncture site
with USG is preferred if available).
9. Aseptic technique, anaesthetise skin, make a small incision.
10. Use the Hepafix needle or spring-loaded cutting needle. Follow
instructions in the package.
 Make sure that the patient is holding his breath in deep expiration
before introducing the biopsy needle into liver. Avoid lower border of
ribs.
11. Send specimen for histology in formalin or formalin-saline.
12. One pass is usually enough.

Post-biopsy Care
1. BP/P every 15 mins for 1 hour, then every 30 mins for 1 hour then hourly
for 4 hours, then q4h if stable.
2. Watch out for fall in BP, tachycardia, abdominal pain, right shoulder pain,
pleuritic chest pain or shortness of breath.
3. Complete bed rest for 8 hours; patient may sit up after 4 hours.
4. Simple analgesics prn.
5. Diet: full liquid for 6 hours, then resume regular diet.
6. Avoid lifting weights greater than 5 kg in the first 24 hours.
7. Anti-platelet agents may be restarted 48-72 hours after biopsy.
8. Warfarin may be restarted the day following biopsy.

Pr 15
 ABDOMINAL PARACENTESIS

1. Routine prophylactic use of fresh frozen plasma or platelets before

paracentesis is not recommended because bleeding complications are
infrequent. It is advisable to correct severe thrombocytopenia (platelet
count < 20×109/L) and/or marked coagulopathy (INR ≥2.0) with platelet
transfusion and/or FFP respectively.

2. Abdominal paracentesis should be avoided in patient with disseminated

intravascular coagulation and hyperfibrinolysis.

3. Site: left lower quadrant preferred – 2 finger breadths (3cm) cephalad and
2 finger breadths medical to the anterior superior iliac spine. Right lower
quadrant is suboptimal in the setting of dilated caecum or an appendectomy,
but it is preferred in case of gross splenomegaly.

4. Aseptic technique

5. May infiltrate with 1% lignocaine.

6. Insert needle (#19 or 21) and aspirate fluid or use commercial paracentesis
set.

7. Send for microscopy and C/ST (use blood culture bottle), white cell count
(total and PMN), biochemistry (albumin and protein) for initial screening.
Check serum albumin and calculate SAAG – serum-ascites albumin
gradient.

8. Albumin infusion may not be necessary for a single paracentesis of less

than 4-5L. On the other hand, for large volume paracentesis, consider
albumin infusion of 6-8 g/litre after every 5L ascitic fluid removed.

Pr 16
 PLEURAL ASPIRATION
1. Review latest CXR to confirm diagnosis, location and extent of effusion.
(Pitfall: Be careful NOT to mistake bulla as pneumothorax or collapsed lung
as effusion). Correct side marking is essential before procedure.
2. Patient position:
A) 45º Semi-supine with hand behind head; OR
B) Sitting up leaning over a table with padding
3. Use ultrasound (USG) guidance prior to pleural fluid procedures if
available (to increase yield and reduce complications).
4. Best aspiration site guided by USG or percussion. Aseptic technique. Puncture
lateral chest wall, preferably at safety triangle, along mid- or posterior axillary
line immediately above a rib. (The “triangle of safety” is bordered anteriorly
by the lateral edge of pectoralis major, laterally by the lateral edge of latissimus
dorsi, inferiorly by the line of the fifth intercostal space and superiorly by the
base of axilla).
5. Anaesthetise all layers of thoracic wall down to pleura.
6. Connect a fine-bore needle (21G)/angiocath to syringe for simple diagnostic
tap. 3-way tap may be used if repeated aspiration is expected.
7. Avoid large bore needle.
8. Throughout procedure, avoid air entry into pleural space. (If 3-way tap is used,
ensure proper sealing of all joints of the tap)
9. Withdraw 20-50 ml pleural fluid and send for LDH, protein, cell count & D/C,
cytology (yield improves if larger volume sent), Gram stain & C/ST, AFB
smear & culture. Check fluid pH & glucose (contained in fluoride tube) if
infected fluid / empyema is suspected. Check concomitant serum protein and
LDH. Check adenosine deaminase (ADA) if TB effusion is suspected
10. For therapeutic tap, connect 3-way tap (± connect to bed side bag) and
aspirate slowly and repeatedly. Do not push any aspirated content back into
pleural cavity. DO NOT withdraw more than 1-1.5 L of pleural fluid per
procedure to avoid re-expansion pulmonary oedema.
11. Take CXR and closely monitor patient to detect complications.

Complications
1. Commonest: Pneumothorax (2-15%), Procedure failure, Bleeding (haemothorax,
haemoptysis), Pain, Visceral damage (liver and spleen).
2. Others: Re-expansion pulmonary oedema from too rapid removal of fluid,
pleural infection / empyema, vagal shock, air embolism

CT guidance may be required in some situations, including loculated pneumothorax

with tethered lung, presence of bullae, or posteriorly loculated pleural collections.

Pr 17
 PLEURAL BIOPSY

Contraindications:
1. Uncooperative patient
2. Significant coagulopathy

Procedure:
Correct side marking is essential before procedure.
1. Ensure there is pleural fluid before attempting biopsy. Assemble and
check the Abrams needle before biopsy. A syringe may be connected to
the end hole of Abrams needle.
2. Preparation as for Steps 1 to 4 of Pleural Aspiration
(NB: If fluid cannot be aspirated with a needle at the time of anaesthesia,
do not attempt pleural biopsy)
3. After skin incision (should be made right above a rib), advance a
CLOSED Abrams needle (with inner-most stylet in situ) through soft
tissue and parietal pleura using a slightly rotary movement.
4. Once the needle is in the pleural cavity, rotate the inner tube counter-
clockwise to open biopsy notch (spherical knob of inner tube will click
into position in the upper recess of the groove of the outer tube)
(Aspiration of fluid by the connected syringe confirm pleural placement
of the Abrams needle)
5. Apply lateral pressure on the notch against the chest wall anteriorly,
posteriorly or downwards (but NOT upwards to avoid injuring the
intercostal vessels and nerve) with a forefinger, at the same time slowly
withdraw the needle till resistance is felt when the pleura is caught in the
biopsy notch.
6. Hold the needle firmly in this position and sharply twist the grip of inner
tube clockwise to take the specimen.
7. Repeat Steps 4 to 6 above in the remaining two directions, totally take at
least 3 specimens if possible.
8. Firmly apply a dressing to the wound and quickly remove the needle
when the patient is exhaling.
9. While an assistant presses on wound, remove stylet of needle, open
inner tube and flush specimen(s) out with NS
10. If tapping is necessary, aspirate as for Steps 5-8 of Pleural Aspiration.
11. Take CXR to detect complication(s).

Complications: As for Pleural Aspiration

Pr 18
 CHEST DRAIN INSERTION
Correct side marking is essential before procedure.
1. Preparation as for Pleural Aspiration. (Preferred patient position in BTS
guideline: Semi-supine on the bed, slightly rotated, with arm on the side of
the lesion behind his/her head to expose axillary area.)
2. Always check the number of rib space from sternal angle. Re-confirm
insertion site by percussion, incise skin right above the rib at anterior or mid-
axillary line in 5th or 6th intercostal space. (Alternate site: 2nd intercostal
space, mid-clavicular line, is uncommonly used nowadays.)
3. USG guidance is strongly recommended if available.
4. Insertion site should be within the “safe triangle”. (A space bordered by
anterior border of latissimus dorsi, lateral border of pectoralis major and a
horizontal line superior to nipple or 5th intercostal space.)
5. Anaesthetise all layers of thoracic wall including pleura. (Do not proceed if
needle for anaesthesia cannot aspirate free gas / fluid.)
6. Small-bored intercostal drains (≤14 Fr) can be inserted by Seldinger
technique (i.e. using a guidewire) if appropriate and available, while large-
bored drains by means of blunt dissection.
7. Proceed with blunt dissection of intercostal muscle with artery forceps down
to parietal pleura.
8. Preferred insertion method: Double-clamp outer end of Argyle drain (24 Fr
to drain air/fluid, 28 Fr to drain blood/pus). Apply artery forceps in parallel
with tip of drain. Breach pleura with finger. Insert drain tip, release forceps
& use them to direct drain into place.
9. Alternate method: Insert Argyle drain with inner trocar. Withdraw trocar by
1 cm into drain immediately after puncturing pleura. Match every 1 cm
advancement of drain with 1-2 cm trocar withdrawal. Double-clamp chest
drain when trocar tip appears outside chest wall.
10. Direct drain apically to drain air and basally to drain fluid.
11. Attach chest drain to 2 cm underwater seal. Ensure fluid level swings with
respiration and coughing.
12. Apply a skin suture over the wound and make a knot, leaving appropriate
length on both sides. Form a 2 cm “sling” by tying another square knot 2 cm
from previous knot. Tie the “sling” to the drain; make several knots using
remaining threads to prevent slipping.
13. Apply dressing.
14. Take CXR to confirm tube position and detect complication(s).

Complications: As for Pleural Aspiration

Pr 19
Acknowledgement

The Editorial Board would like to thank the Coordinating Committee (COC) in Internal
Medicine for their support and generous contribution to the publication of this Handbook.
Special thanks to HAHO Quality & Standards Department for the editorial support on
putting the Handbook together.

We would like to extend the heartfelt thanks to all the colleagues who have made
invaluable suggestions to the contents of Ninth Edition of this Handbook.

Finally, we express our special gratitude to the following colleagues for their efforts and
contribution to the Handbook.

Dr. CHAN Chun Man Jones Dr. KWOK Wang Chun

Dr. CHAN Hiu Fai Germaine Dr. LAM Ching Pong
Dr. CHAN Kin Sang Dr. LAM Joanna
Dr. CHAN Kwok Keung Dr. LAU Pui Ling
Dr. CHAN Yiu Han John Dr. LEE Tsz Heung Herman
Dr. CHANG Shek-kwan Richard Dr. LEUNG Moon Ho, Alexander
Dr. CHENG Hei Shun Hilson Dr. LI Hei Philip
Dr. CHEUNG Ka Man Carmen Dr. LO Wai Ting Joyce
Dr. CHEUNG Ka Yin Calvin Dr. MAK Ka Pui
Dr. CHEUNG Man Tung Christina Dr. MIU Pui Ling Flora
Dr. CHEUNG Yuk Man Carol Dr. NG Wing Yiu George
Dr. CHIK Shiu Hong Dr. NG Ying Wai
Dr. CHIU Pui Hing Dr. TONG Chun Wai
Dr. CHOI Cheung Hei Dr. TSANG Tak Yin Owen
Dr. CHU Chun Kwok Angus Dr. WONG Charles
Dr. FOK Chun Kit Vincent Dr. WONG Ho Ming June
Dr. FONG Yan Hang Dr. WONG Sai Kuen Alfred
Dr. HO Cheuk Man Dr. WONG Siu Ming, Raymond
Dr. HO Jerry Dr. WONG Sze Man Christina
Dr. HO Tze Kwan Carmen Prof. WONG Wai Sun Vincent
Dr. HUI Ka Eugenie Dr. WOO Yu Cho
Dr. KNG Poey Lyn Carolyn Dr. WU Tak Chiu
Dr. KUNG Kam Ngai Dr. YEUNG Kwok Hung
Dr. KWOK Chi Hang Dr. YIU Ka Ling
Dr. KWOK Gin Wai Dr. YONG Xern E Jason
Dr. KWOK Lap Ming
COPYRIGHT RESERVED
 Training Subcommittee
of the
Coordinating Committee in Internal Medicine