Sepsis

Diagnosis

Indications for Testing

• Presence of one or more risk factors and appropriate clinical presentation (eg, known infection and systemic signs of inflammation or organ dysfunction)

Criteria for Diagnosis

• American College of Chest Physicians/Society for Critical Care Medicine
• Scoring system for systemic inflammatory response syndrome (SIRS); adapted from ACCP/SCCM

  Scoring System for SIRS (ACCP, SCCM)
  Criteria Fever or hypothermia (T ≥38°C or ≤36°C) Tachycardia (HR >90) Tachypnea (RR >20/min, PaCO2 <32) Abnormal WBC (WBC >12,000/mm3, or <4,000/mm3, or >10% bands)
  Maximum score is 4 SIRS – diagnosed if ≥2 criteria present Sepsis – SIRS plus clinically suspected infection by culture Septic shock – sepsis with hypotension unresponsive to fluids Multiple organ syndrome – sepsis with multiple organ failure

Laboratory Testing

• CBC – frequently shows leukocytosis or leukopenia with left shift to immature forms
  • High sensitivity, poor specificity
• Fluid analysis (eg CSF, synovial)
  • Cell count with differential – aid in distinguishing bacterial from viral meningitis
• Cultures
  • Blood – multiple sets from separate venipuncture sites
  • Wound or site of known infection – negative cultures do not rule out sepsis
  • CSF
• Electrolytes, renal and liver function tests – assess organ dysfunction
• C-reactive protein (CRP) – frequently elevated, but not diagnostic
  • Use in conjunction with white blood cell count and differential
  • Single measure may not be helpful
    • Obtain serial quantitative levels 24 hours after onset of symptoms of possible infection and obtain second measurement 24 hours later
  • Levels ≤10 mg/L indicate low probability of infection
  • Does not peak for 48 hours from beginning of sepsis and does not correlate with severity or prognosis in sepsis
  • Does not differentiate between SIRS and sepsis
  • Good evidence supports use of CRP to rule out neonatal sepsis in full-term infants
    • Recent studies suggest similar efficacy in preterm infants
• Procalcitonin (PCT)
  • Acute phase reactant
  • Levels increase within 2 hours of sepsis and normalize within 2-3 days after start of treatment, making PCT an excellent marker for early sepsis detection
  • Most useful in prediction of progression of infection to severe sepsis or septic shock
  • Questionable if this test can distinguish SIRS from sepsis

Differential Diagnosis

• SIRS
• Adrenal insufficiency
• Connective tissue disease
• Vasculitis
• Drug overdose
• Malignancy
• Myocardial infarcts
• Pancreatitis
• Severe metabolic derangement (eg, metabolic acidosis)
• Transplant rejection
• Venous thromboembolism/pulmonary infarcts

Monitoring

Clinical Background

Sepsis is a severe illness characterized by a systemic, whole-body response to infection and is a frequent cause of morbidity and mortality in hospitalized patients. Early differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is imperative for appropriate therapy.

Epidemiology

• Incidence – >750,000 cases per year in the U.S. (NIH, 2009)
• Sex – M:F, equal
• Age – most common in older individuals (≥65 years) or infants (see neonatal sepsis)

Risk Factors

• Bacteremia
• Diabetes mellitus
• Hospitalization
• Immunocompromised state (HIV/AIDS, cancer, organ transplantation)
• Invasive medical device
• Pancreatitis
• Pneumonia
• Severe injury (eg, burns, trauma)
• Surgery

Pathophysiology

• Physiologic response to an infectious agent leads to an inflammatory immune response, which causes a release of multiple inflammatory mediators, including cytokines and chemokines
  • These are opposed by anti-inflammatory mediators (eg, IL-4, IL-10), resulting in a negative feedback mechanism
• Vasoactive mediators cause blood flow to bypass capillary exchange vessels, decreasing delivery of O₂ and impairing removal of CO₂ and waste products
  • Decreased perfusion of O₂ leads to organ dysfunction and potential failure of one or more organs        

Clinical Presentation

• Nonspecific signs and symptoms – fever, tachycardia, tachypnea
• May exhibit hypotension and altered mental status

Treatment

• Rapid initiation of antibiotics and supportive therapy – crucial to positive outcome
• Important to distinguish sepsis from SIRS – empiric antibiotics are not indicated for all patients with SIRS

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Body Fluid Culture and Gram Stain 0060108 Method: Stain/Culture/Identification