Sepsis

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

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

  • Numerous definitions available to define sepsis
  • Most recent definition uses diagnostic criteria from Surviving Sepsis Campaign

    Laboratory Testing

    • CBC – frequently shows leukocytosis or leukopenia with left shift to immature band forms
      • High sensitivity, poor specificity
    • Fluid analysis (eg, cerebrospinal fluid [CSF], synovial)
      • Cell count with differential – aid in distinguishing bacterial from viral infection
    • Cultures
      • Blood – obtain 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 – assessment of organ dysfunction
    • Lactate levels
    • 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 systemic inflammatory response syndrome (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 detection of sepsis
        • Typically >2 SD above normal is highly predictive of sepsis
      • 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

    • CBC – decreasing leukocytosis suggests response to treatment
    • Procalcitonin (PCT) – decreasing PCT suggests response to treatment
    • Decreases in either parameter may not correlate with overall treatment success or survival

    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 – >300/100,000 (Cawcutt 2014)
    • Sex – M:F, equal
    • Age – most common in older individuals (≥65 years) or infants (see neonatal sepsis)

    Risk Factors

    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

    • Highly variable presentation – multiple factors, including host characteristics, site and severity of infection, time course prior to initiation of definitive therapy
    • Nonspecific signs and symptoms – fever, tachycardia, tachypnea
    • May exhibit hypotension and altered mental status
    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.

    CBC with Platelet Count and Automated Differential 0040003
    Method: Automated Cell Count/Differential

    Cell Count, Body Fluid 0095019
    Method: Cell Count/Differential

    Blood Culture 0060102
    Method: Continuous Monitoring Blood Culture/Identification

    Limitations 

    Testing is limited to the University of Utah Health Sciences Center

    Typically requires ≥2 sites

    Wound Culture and Gram Stain 0060132
    Method: Stain/Culture/Identification

    Limitations 

    Anaerobe culture is NOT included with this order

    Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
    Method: Stain/Culture/Identification

    Electrolyte Panel 0020410
    Method: Quantitative Ion-Selective Electrode/Enzymatic

    Lactate Dehydrogenase, Serum or Plasma 0020006
    Method: Quantitative Enzymatic

    C-Reactive Protein 0050180
    Method: Quantitative Immunoturbidimetry

    Limitations 

    Normal CRP does not rule out sepsis

    Does not peak for ≥48 hours after infection starts

    Does not differentiate between sepsis and SIRS

    Procalcitonin 0020763
    Method: Immunofluorescence

    Limitations 

    May not be elevated in severe local infection

    May be elevated in other conditions such as burns, trauma, and extensive surgery

    Does not differentiate between sepsis and SIRS

    Renal Function Panel 0020144
    Method: Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay

    Hepatic Function Panel 0020416
    Method: Quantitative Enzymatic/Quantitative Spectrophotometry

    Guidelines

    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent J, Moreno R, Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013; 39(2): 165-228. PubMed

    General References

    Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008; 36(3): 941-52. PubMed

    Cawcutt KA, Peters SG. Severe sepsis and septic shock: clinical overview and update on management. Mayo Clin Proc. 2014; 89(11): 1572-8. PubMed

    Faix JD. Established and novel biomarkers of sepsis. Biomark Med. 2011; 5(2): 117-30. PubMed

    Gerlach H, Toussaint S. Sensitive, specific, predictive… statistical basics: how to use biomarkers. Crit Care Clin. 2011; 27(2): 215-27. PubMed

    Jones AE, Fiechtl JF, Brown MD, Ballew JJ, Kline JA. Procalcitonin test in the diagnosis of bacteremia: a meta-analysis. Ann Emerg Med. 2007; 50(1): 34-41. PubMed

    Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011; 66 Suppl 2: ii33-40. PubMed

    Meisner M. Update on procalcitonin measurements. Ann Lab Med. 2014; 34(4): 263-73. PubMed

    Schneider H, Lam QT. Procalcitonin for the clinical laboratory: a review. Pathology. 2007; 39(4): 383-90. PubMed

    Schuetz P, Christ-Crain M, Müller B. Biomarkers to improve diagnostic and prognostic accuracy in systemic infections. Curr Opin Crit Care. 2007; 13(5): 578-85. PubMed

    Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007; 7(3): 210-7. PubMed

    References from the ARUP Institute for Clinical and Experimental Pathology®

    Blaschke AJ, Heyrend C, Byington CL, Fisher MA, Barker E, Garrone NF, Thatcher SA, Pavia AT, Barney T, Alger GD, Daly JA, Ririe KM, Ota I, Poritz MA. Rapid identification of pathogens from positive blood cultures by multiplex polymerase chain reaction using the FilmArray system. Diagn Microbiol Infect Dis. 2012; 74(4): 349-55. PubMed

    Medical Reviewers

    Last Update: September 2016