Sepsis

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

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 meningitis
  • 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

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

CBC with Platelet Count and Automated Differential 0040003
Method: Automated 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

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

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

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

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

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

Additional Tests Available

Body Fluid Culture and Gram Stain 0060108
Method: Stain/Culture/Identification

Comments

Anaerobe culture is NOT included with this order

Guidelines

Dellinger R, Levy M, Rhodes A, Annane D, Gerlach H, Opal S, Sevransky J, Sprung C, Douglas I, Jaeschke R, Osborn T, Nunnally M, Townsend S, Reinhart K, Kleinpell R, Angus D, Deutschman C, Machado F, Rubenfeld G, Webb S, Beale R, 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 K, Snider R, Nylen E. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008; 36(3): 941-52. PubMed

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

Faix J. 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 A, Fiechtl J, Brown M, Ballew J, Kline J. 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 Q. 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 B, Eslick G, Craig J, McLean A. 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 A, Heyrend C, Byington C, Fisher M, Barker E, Garrone N, Thatcher S, Pavia A, Barney T, Alger G, Daly J, Ririe K, Ota I, Poritz M. 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: December 2015