Sepsis & SIRS

Wade Woelfle, MD, FAAEM

UW ECC 2016
June 21,2016
 Sepsis Objectives
 Definition

 Why and how it happens

 Identification

 Similar problems

 Monitoring

 Treatments

 New and revisited developments

Sepsis
 Inflammatory syndrome from severe infection
 Vasodilatation
 Increased WBCs
 Leakage of fluid from capillary beds
 Remote from the site of infection

 Infection = invasion of normally sterile tissue by

organisms

 Bacteremia – Presence of viable bacteria in blood

SIRS
 Systemic Inflammatory Response Syndrome
 Identical to sepsis but without infection
 Noninfectious process as a cause
 Pancreatitis
 Autoimmune disease
 Vasculitis
 Thromboembolism
 Burns
 Surgery/trauma
 Pulmonary contusion
Definition of SIRS
 2 or more of the following abnormalities
 Temp
 HR
 RR
 WBC count

 Note the lack of specificity

 Example: Patients with pulmonary edema
Basic Pathophysiology
 Poor regulation of inflammatory mediators

 Chain of events causing tissue injury

 Causes multiple organ dysfunction syndrome

 MODS
 High mortality
More Detailed Pathophysiology
 Bacterial components from site of infection

 Host immune response chemical signals from site of infection

 Both enter the bloodstream

 Vasodilatation and changes in vascular autoregulation
 Direct cellular toxicity

 BP drops and perfusion decreases

 Organ injury and dysfunction at sites away from the infection

 Heart, lungs, kidneys, liver, brain, coagulation cascade, etc.
Sepsis - Diagnostic Criteria
 Infection and some of these
 General variables
 Temp >38.3 or < 36
 HR > 90
 RR >20
 Altered Mental Status
 Edema/positive fluid balance (>20 ml/kg/24 hrs)
 Hyperglycemia
Sepsis - Diagnostic Criteria
 Inflammatory Variables
 WBC count > 12000 or < 4000
 Normal WBC count with > 10% immature cells
 C-reactive Protein > 2 SD above normal
 Procalcitonin > 2 SD above normal
Severe Sepsis - Diagnostic Criteria
 Sepsis + Organ dysfunction variables
 Hypoxemia (PaO2/FIO2 < 300)
 Oliguria (urine < 0.5 ml/kg/hr for 2 hours despite a good
fluid resuscitation)
 Creatinine increase > 0.5 (especially if > 2)
 INR > 1.5 or aPTT > 60 sec
 Ileus (no bowel sounds)
 Thrombocytopenia (plt < 100000)
 Elevated bilirubin > 4
More Organ Dysfunction Variables
 Hemodynamic variables
 Hypotension
 SBP < 90 or decrease > 40 from baseline
 MAP < 70

 Tissue Perfusion Variables

 Elevated Lactate
 Decreased cap refill or skin mottling
Possible Infection Markers
 Procalcitonin level

 TREM-1 receptor

 CD64 expression on WBCs

 Combination of these is best but still experimental

 Procalcitonin level is becoming standard testing
Sepsis or SIRS?
 Early on, it may be hard to tell them apart

 Look for a focus of infection somewhere

 If found, then sepsis
 If none found, then SIRS
 Cover for infection while looking for a source
 50% blood culture positive in severe sepsis
 17% in sepsis
 69% in septic shock
Septic Shock
 Sepsis with hypotension
 Despite 30 ml/kg IV fluid

 MODS
 Multiple abnormalities listed above
 Labs
 BP
 Mental Status
 Urine Output
Sepsis Risk Factors
 Nosocomial infection (antibiotics or ICU stay)
 Bacteremia (positive blood cultures)
 Age 65 or greater
 Immunosuppression
 Cancer, renal/liver failure, AIDS, medications, splenectomy

 Diabetes
 Community Acquired Pneumonia
 Genetics
Sepsis Epidemiology
 US estimate
 1.665 million cases per year (and increasing)

 Older population (60-85% of cases)

 More immunosuppressive meds
 More antibiotic resistance
 Maybe better detection
 Highest incidence is African American Males
 Highest in winter (Respiratory infections/flu)
Sepsis Epidemiology
 Pathogens
 Gram positive bacteria
 Staph (think MRSA, MSSA)
 Strep (Pneumoniae, and Group A Beta)
 C. Diff
 Enterococcus
 Gram negative bacteria (E. Coli, Klebsiella, pseudomonas,
Citrobacter, Enterbacter, etc.)
 Fungal (increasing but still lower incidence)

 Severity increasing (more cases severe sepsis)

 ARDS, acute renal failure, DIC
Sepsis Prognosis
 High Mortality Rate (10-52%)
 Increases with severity
 SIRS – 7%
 Sepsis – 16%
 Severe Sepsis - 20%
 Septic Shock – 46%
 Lowest in young (<44 yo) and those with fewer chronic
diseases
 Electronic Medical Record Issues
 Identification
 Not specific
 Overly sensitive
 May help us identify cases that aren’t classic presentations
 Case: 28 yo female with dyspnea and pleuritic chest pain
 Symptomatic for about 12 hours (arrives at midnight)
 On OCPs
 Tachycardic (130), mildly tachypneic (24), no fever, BP wnl
 No crackles on lung exam
Poor Prognostic Factors
 Hypothermia (or failure to spike a fever)

 Leukopenia (especially with Gram negatives)

 Coagulation abnormalities
 Elevated INR and aPTT
 Decreased functional Fibrinogen levels

 Elevated Chloride level

 Elevated Lactate (> 4) = 78% mortality

Comorbidities = Poorer Prognosis
 New Onset Atrial Fib  Age > 40
 Chronic illnesses
 AIDS
 Impaired immunity
 Liver disease  Malnutrition
 Exposure to resistant
 Cancer organisms
 Nursing homes
 Alcohol dependence
 Medical Devices
 Immunosuppression  Indwelling catheters
 Central venous lines
Pitfalls in Evaluation
 Young people may develop a severe, prolonged tachycardia
(170-180) without hypotension until they acutely
decompensate
 Back to our case
 CXR negative, WBC 14K
 Now 3 AM - HR 140, O2 sat now in lower 90s, BP still normal. RR
25-30.
 5 AM CT angiogram performed
 6 AM CT reported as negative, HR now 165-175. More ill
appearing. RR up to 40. BP drops to 90s systolic. Antibiotics
ordered
 7 AM – Patient codes and is pronounced at 830 AM

 Chronic hypertension may cause critical hypoperfusion at a

higher BP than in the typical healthy patient (relative
hypotension)
Site of Infection Correlates Prognosis

 Sepsis w/UTI = lowest mortality (26-30%)

 Unknown, GI, Pulmonary (50-55% mortality)

 GI (ischemic bowel) – 78% mortality

Sepsis Treatment
 Fluids

 Treat infections
 Antibiotics
 Surgical drainage

 Supportive Care
 Correct physiologic abnormalities (Hypoxia, BP)

 Distinguish between sepsis and SIRS

Early Management
 ABCs
 Oxygen
 Monitor pulse ox
 Consider intubation and mechanical ventilation
 Decrease work of breathing
 Airway protection for decreased mental status

 Diagnostics
 ABG
 CXR
 Labs including cultures
Early Management
 Correct decreased tissue perfusion
 Monitor BP (frequently)
 Consider arterial line monitoring, if BP unstable
 Hypotension is most common sign
 Other signs include tachycardia, decreased capillary refill,
decreased mental status/restlessness, decreased urine output
 Modified by preexisting conditions or meds
 i.e. Beta blockers
 Follow Lactate levels
Fluid Management
 Venous Access ASAP
 May need a central line
 Fluids, pressors, blood products
 Blood draws
 Central venous pressure (?)
 Central venous Oxygen saturation (?)
 Pulmonary artery catheter (Swan-Ganz)
 No longer routinely used
 CvP and ScvO2 give similar findings
 More Complications
Fluid Management
 IVFs (crystalloids)
 May need 2-5 L over 6 hours (500 ml boluses)
 Careful if history of CHF
 Assess volume status, perfusion, BP, and signs of pulmonary
edema or ARDS
 Fluid overload is common
 Monitor fluid responsiveness/perfusion and don’t continue
once improvement stops
Fluid and Med Choices
 Crystaloid is best – 1st line therapy
 No differences with Albumin (higher cost)
 Others (starches) may increase mortality

 Pressors – 2nd line therapy

 For hypotension once fluid status is improved
 Norepinephrine preferred (Both alpha and Beta)
 Phenylephrine, if tachycardia or arrhythmias
 Pure alpha agonist
 Dopamine has fallen out of favor
Med Choices – Conflicting
Evidence
 Inotropes (Dobutamine) – 3rd line
 For myocardial dysfunction once BP improves
 Increases cardiac output/tissue perfusion
 Raise CvO2 sat >70
 May worsen hypotension

 Blood transfusion to optimize Oxygen delivery

 Hemoglobin < 7 (unless bleeding or myocardial ischemia)
 No longer performed with hgb 9.
Early Goal Directed Therapy
 IVFs given in the first 6 hours using physiologic targets to
guide management
 Widespread acceptance but best targets aren’t known
(conflicting evidence)
 MAP > 65 (and probably > 80)
 Urine output > 0.5 ml/kg/hr
 Radial pulse showing respiratory variation
 CvP 8 – 12 (if central line placed)
 ScvO2 > 70 (if central line placed)
 Follow lactate levels q6 hr until falling (maybe as good as
ScvO2)
 Once perfusion restored, not helpful unless it begins to rise again
Dynamic Indices - Experimental
 New potential targets to guide fluid management
 Respiratory changes in vena cava diameter
 Radial artery pulse pressure
 Aortic blood flow peak velocity
 Brachial artery blood flow velocity

 Must be in sinus rhythm and mechanically ventilated

 If actively breathing, can measure cardiac output

change via echo with passive leg raising
Protocol Directed Therapy (EGDT)
 ScvO2, CVP, MAP, urine output, and lactate
 Guide fluid resuscitation

 Early administration of antibiotics

 Guide first 6 hours of presentation

 Conflicting evidence
 Central lines originally required (complications)
 Original study funded by company making central lines
 Some studies show no difference from normal care
Bottom Line
 Whether protocols, early goal directly therapy, or usual care
is given
 Fluid resuscitation should begin within 6 hours
 Stopped or reduced when perfusion restored

 Antibiotics given expeditiously when it appears that infection

is present/worked up
 If perfusion deficit/organ failure progresses
 Reassess adequacy of fluids, antibiotics, need for surgical
care, accuracy of diagnosis, complications

 When patient responds, back off of support but monitor the

markers for sepsis (BP, UO, labs, etc.)
 Reevaluate if worsening or not continuing to improve
Dealing with the Focus of
Infection
 Identify site of infection
 Info from History and Physical
 Blood culture 2 sites, aerobic and anaerobic
 Urine cultures, sputum culture and Gram stain
 ? CSF
 CXR
 Infected line, indwelling catheter, site of injury in trauma
patient
Treating Site of Infection
 Early, appropriate antibiotics after cultures
 Started within 6 hours (prefer 1 hour)
 Consider recent antibiotics, comorbidities, and possibility
of hospital/health care acquired infection
 Late/Inadequate/inappropriate antibiotic = poor outcome
Infectious Source Unknown
 Broad Spectrum Antibiotic coverage
 Staph Aureus (and MRSA)
 Vancomycin is 1st line
 Daptomycin, Linezolid, Ceftaroline 2nd line
 If Pseudomonas is unlikely, add 1 of these
 3rd or 4th generation Cephalosporin (Cefepime)
 Beta lactam/beta-lactamase inhibitor (Pip-tazo)
 Carbapenem (imipenem)
 If Pseudomonas is possible, add 2 of the previous
 List could also include Ceftaz, Quinolone (Ciprofloxacin),
Aminoglycoside (Gent), or Aztreonam
Infectious Focus Present
 Drainage/debridement/amputation of site of infection
 May not respond to antibiotics alone

 Remove potentially infected foreign bodies

 Central line, Urinary catheter
Monitor Improvement
 Narrow the antibiotic spectrum when cultures and
sensitivities return

 Watch for antibiotic toxicity, response, superinfection

(hospital acquired)

 Duration of antibiotics 7-10 days

 Longer if response is slow, immunologic deficiency,
undrainable focus, or neutropenic (until neutropenia
resolves)
Additional Therapies
 Steroids (glucocorticoids)
 Treat host inflammatory response
 Most likely to help hypotensive septic shock unresponsive
to fluids and pressors

 Nutrition
 Helps conserve body weight and muscle mass
 May not change clinical outcomes

 Venous thromboembolus prophylaxis

 Reduces risk of DVT/PE
Additional Therapies
 Intensive Insulin
 Hyperglycemia and insulin resistance are common and
promote infection
 Target blood glucose 140-180

 Fever control w/antipyretics (acetaminophen)

 Potential benefits and adverse effects

 External Cooling – unclear benefit

 May lower mortality, decrease pressor requirement, etc.
Effect of Improving Sepsis Treatment
 Some studies now show decreasing mortality
 50% risk reduction
 Possibly due to better therapeutic strategy
 Appropriate antibiotics
 Restoration of perfusion
 Questionable if sepsis bundles/Goal-Directed Therapy make any
difference

 Risk remains post-survival

 Death rate increased at 1 year
 Recurrent sepsis/hospital admission
 Resistant bacteria (especially Gram negatives)
 Long-term care facility admission
 Decreased quality of life
Readmission Diagnoses After Sepsis

 CHF

 Pneumonia

 COPD exacerbation

 UTI

 C. Diff
 References
 UpToDate search was used with “sepsis” as a search
term.

 The following UpToDate articles were used as references

 Sepsis syndromes in adults: Epidemiology, definitions,
clinical presentation, diagnosis, and prognosis
 Evaluation and management of suspected sepsis and septic
shock in adults
 Pathophysiology of sepsis