Sepsis

Description

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.

Epidemiology

Incidence

• 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