Sepsis-3 definitions:

  • Sepsis: life-threatening acute organ dysfunction caused by a dysregulated host response
    • Organ dysfunction is defined as an increase in the Sequential Organ Failure Assessment (SOFA) score ≥2 points from baseline.
    • Baseline SOFA score is assumed to be zero unless there is preexisting organ dysfunction.
  • Septic shock: a subset of sepsis where there is underlying circulatory and cellular/metabolic abnormalities profound enough to increase mortality
    • Persistent hypotension despite adequate volume resuscitation
    • Clinically defined as sepsis requiring vasopressors AND a lactate level ≥2 mmol/L
  • SOFA variables:
    • Respiration: PaO2/FiO2 ratio
    • Central nervous system: Glasgow Coma Scale (GCS) score
    • Cardiovascular: mean arterial pressure (MAP), vasopressor administration with type and rate of infusion
    • Renal: serum creatinine, urine output
    • Liver: bilirubin
    • Coagulation: platelet count
  • Quick SOFA (qSOFA) is a new bedside tool used to determine patients who are likely to develop sepsis and prompt further investigation. This tool is intended for use in non-ICU patients.
    • qSOFA variables:
      • Respiratory rate ≥22/min
      • Altered mentation
      • SBP ≤100 mm Hg
  • Sepsis-3 criteria have not yet been widely accepted and are still controversial.
    • Although qSOFA is more specific (and less sensitive) than the Systemic Inflammatory Response Syndrome (SIRS) criteria (1)[A], there is concern that relying on the new criteria may place patients at risk for developing severe sepsis because treatment may be delayed compared to use of SIRS criteria.
    • SOFA score ≥2 points is more predictive of mortality from sepsis over SIRS and qSOFA in ICU patients (2)[B]; utility is lost in centers unable to obtain the required SOFA score variables.
  • The Centers for Medicare & Medicaid Services (CMS) supports definitions of SIRS, sepsis, severe sepsis, and septic shock.

Pediatric Considerations

  • Sepsis is diagnosed with suspected or proven infection in addition to meeting at least 2 SIRS criteria.
  • SIRS in pediatric population requires that abnormality in temperature or WBC be present.
  • Drug metabolism is reduced in children with sepsis. Monitor drug toxicity labs to prevent adverse effects.

Geriatric Considerations
Altered mental status may be presenting sign of infection.



  • Is a leading global cause of mortality and critical illness
  • Increasing incidence with decreasing in-hospital mortality
  • 31 million cases with ~5 million deaths annually worldwide

Etiology and Pathophysiology

  • Complex pathophysiology
  • Multifactorial: Widespread endothelial dysfunction, complement activation, and activation of coagulation cascade lead to tissue hypoperfusion, early hemodynamic changes, and organ dysfunction.
  • An imbalance between proinflammatory and anti-inflammatory mediators leads to relative immunosuppression.
  • Causative organisms (most commonly bacterial)
    • Gram-positive bacteria (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.
    • Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp., and anaerobic bacteria
    • Fungi: Candida sp.
    • Causative organism not identified in 1/3 of cases
    • Nosocomial infections in 50% of cases
  • Common sites of infection: upper/lower respiratory tract (most common), urinary tract, vascular and indwelling catheters, skin/soft tissue, central nervous system, gastrointestinal (GI) tract, bone, joint

Risk Factors

  • Extremes of age (very young or age >60 years)
  • Comorbidities: COPD, cirrhosis, congestive heart failure (CHF), cancer, diabetes, and renal insufficiency/failure
  • Immunosuppression, asplenia
  • Primary bacteremia
  • Complicated labor and delivery: premature labor and/or premature rupture of membranes, untreated maternal group B strep colonization
  • Nosocomial factors: surgical site infections, vascular and indwelling catheters, mechanical ventilation

General Prevention

  • Vaccination: pneumococcal vaccine in children and adults ≥65 years or immunocompromised; Haemophilus influenzae type B (infants, young children), influenza, meningococcal vaccine
  • γ-Globulin for hypo- or agammaglobulinemia
  • Regular hand washing, sterile technique for vascular and indwelling catheter placement
  • Antibiotic prophylaxis for recommended surgical procedures
  • Prompt extubation for patients on mechanical ventilation as soon as clinically appropriate.

Commonly Associated Conditions

  • Immunologic: neutropenia, HIV, hypo- or agammaglobulinemia, complement deficiency, splenectomy, immunosuppressants (corticosteroids, chemotherapy, TNF-α antagonists)
  • Diabetes, alcoholism, malignancy, cirrhosis, burns, multiple trauma, intravenous (IV) drug abuse, malnutrition

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