Description

• Systemic inflammatory response syndrome (SIRS): Inflammatory response due to infectious or noninfectious origin. Suspected signs and symptoms of SIRS due to infectious causes (1):
  • General variables:
    • Temperature >38.3°C or <36°C
    • HR >90 beats/min or >2 SD above the normal value for age
    • Tachypnea (respiratory rate >20 breaths/min or PCO₂ <32 mm Hg)
    • Altered mental status (AMS)
    • Significant edema or positive fluid balance (>20 mL/kg over 24 hours)
    • Hyperglycemia (plasma glucose >110 mg/dL or 6.1 mmol/L) in the absence of diabetes
  • Inflammatory variables:
    • WBC >12,000 cells/mm³, or <4,000 cells/mm³, or normal WBC with >10% bands
    • Plasma C-reactive protein >2 SD above normal
    • Plasma procalcitonin >2 SD above normal
  • Hemodynamic variables:
    • Arterial hypotension (SBP <90 mm Hg; MAP <70; or SBP decrease of >40 mm Hg in adults or <2 SD below age normal)
    • SVO₂ >70%
    • Cardiac index >3.5 L min^-1/M^-23
  • Organ dysfunction variables:
    • Arterial hypoxemia (PaO₂/FIO₂ <300)
    • Acute oliguria (urine output <0.5 mL/kg^-1/hr^-1 or 45 mmol/L for at least 2 hours)
    • Creatinine increase >0.5 mg/dL
    • Coagulation abnormalities (INR >1.5 or aPTT >60 secs)
    • Ileus (absent bowel sounds)
    • Thrombocytopenia (platelet <100,000)
    • Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L)
  • Hypoperfusion variables:
    • Hyperlactatemia (>1 mmol/L)
    • Decreased capillary refill or mottling

• Sepsis: Documented or suspected infection, and some of signs and symptoms listed above (1)
• Severe sepsis: Sepsis complicated by hypoperfusion or organ dysfunction variables (as above)
• Septic shock/sepsis-induced hypotension: Persistent arterial hypotension unexplained by other causes and despite adequate fluid resuscitation:
  • Hypotension is defined as: SAP <90 mm Hg, HgMAP <70 mm Hg, and reduction in SBP >40 mm Hg from baseline

Pediatric Considerations
For SIRS diagnosis, 1 of the criteria must meet the requirement of either temperature or leukocyte abnormalities. Definitions of severe sepsis and septic shock are similar to definitions for adults but not identical. Severe sepsis, in addition to meeting the sepsis criteria, must have 1 of the following: Cardiovascular dysfunction, acute respiratory distress, or ≥2 other organ dysfunction. Hypotension (<2 SD below normal for age) is a sign of late and decompensated shock in children (1).

• Multiple organ dysfunction syndrome: Progressive organ dysfunction in an acutely ill patient necessitating intervention to maintain homeostasis; represents the end stage of both SIRS and sepsis:
  • Synonym(s): Septicemia

Geriatric Considerations
Often more difficult to diagnose; change in mental status/behavior may be only early manifestation

Epidemiology

• 3/1,000 population
• Increasing incidence, with 750,000 new cases annually in the US
• 2% of hospitalized patients; ~75% of ICU patients

Risk Factors

• Medical illness
• Organ dysfunction: COPD, CHF, DM, and cancer
• Bacteremia
• Age extremes (very old or young)
• Immunosuppression (see “Associated Conditions”)
• Community-acquired pneumonia
• Critically ill patients
• Indwelling catheters: Intravascular, urinary, biliary
• Complicated labor and delivery: Premature labor and/or PROM, untreated maternal group B strep colonization
• Ethnicity: African American

General Prevention

• Vaccination: Pneumococcal (Prevnar 13(R) for all children ≤5 and Pneumovax(R) is recommended for use in all adults who are ≥65 and for those ≥2 and at high risk for disease), Haemophilus influenzae type b (infants, young children), influenza (H1N1 in pregnant women), meningococcal vaccine
• γ-Globulin (for hypo- or agammaglobulinemia)
• Treat pregnant group B strep carriers during labor.
• Cleanliness with regular hand washing, sterile technique for catheters, appropriate glove use
• Antibiotic prophylaxis for certain operations (bowel and GU; prosthetic device placement)

Pathophysiology

• An imbalance between pro- and anti-inflammatory mediators yields widespread systemic inflammation that damages distant uninvolved tissues.
• Widespread endothelial damage leads to maldistribution of blood flow, causing impaired tissue oxygenation and resultant organ dysfunction.
• Dysregulated nitric oxide production and activation of the coagulation system cause maldistribution of organ blood flow.
• Initial, overexuberant inflammatory response can progress to significant immunosuppression.

Etiology

• Specific etiologic agents:
  • Gram-positive (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.
  • Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp.
  • Anaerobes
  • Fungi: Candida sp. (incidence increased 207% from 1976–2000)
• Common sources: Lungs (most common), urinary tract, abdomen (biliary tree, abscess, peritonitis), skin (cellulitis, decubitus ulcer, gangrene), heart valves, CNS (meningitis), intravascular catheters
• Unknown source of infection in 20–30% of patients

Commonly Associated Conditions

• Immunologic: Neutropenia, HIV, hypo-/agammaglobulinemia, complement deficiency, splenectomy, immunomodulatory medication (corticosteroids, chemotherapy, TNF-α antagonists)
• DM, alcoholism, malignancy, cirrhosis, burns, multiple trauma, IV drug abuse, malnutrition