Sepsis

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

Indications for Testing

  • Presence of ≥1 risk factors and appropriate clinical presentation (eg, known infection and systemic signs of inflammation or organ dysfunction)

Criteria for Diagnosis

  • Numerous definitions available for sepsis – goal is to identify high-risk patients for early aggressive treatment due to high morbidity and mortality associated with delay
  • Definitions of sepsis (Singer, 2016)
    • Sepsis – dysregulated host response to infection, causing life-threatening organ dysfunction (previously termed severe sepsis)
      • Increase in sequential (sepsis-related) organ failure assessment (SOFA) score of ≥2 points
      • Baseline SOFA score is assumed to be 0, unless patient is known to have preexisting organ dysfunction
    • Septic shock – subset of sepsis with increased mortality due to profound underlying circulatory and cellular/metabolic abnormalities
      • Sepsis in addition to
        • Persisting hypotension (<65 mm Hg) requiring vasopressors to maintain mean arterial pressure of ≥65 mm Hg
        • Serum lactate level >2 mmol/L (>18 mg/dL) in absence of hypovolemia
  • Scoring systems for diagnosis of sepsis

Laboratory Testing

  • Lactate (lactic acid) levels
    • Obtain within 3 hours of ER arrival in suspected sepsis (Rhodes, Surviving Sepsis Campaign, 2017)
    • Increase correlates with poorer prognosis
    • Marker of endogenous catecholamines
    • Concentrations >4 mmol/L increasingly used as indicator for need for early goal-directed therapy in sepsis protocols
  • CBC
    • White blood cell (WBC) count >12,000/mm3, <4,000/mm3, or >10% bands indicates more severe disease (American College of Chest Physicians [ACCP]/Society of Critical Care Medicine [SCCM], 1992; Singer, 2016)
    • Low platelets may indicate coagulopathy
    • Platelet count used in SOFA calculation
  • Cultures (Rhodes, Surviving Sepsis Campaign, 2017)
    • Blood – obtain ≥2 sets from separate sites, at least one being percutaneous, according to standard of care
    • If indicated
      • Urine
      • Cerebrospinal fluid (CSF)
      • Wound or site of known infection
      • Other body fluid cultures (pleural, peritoneal)
    • Not indicated
      • Panculture
  • Comprehensive metabolic panel
    • Electrolytes, creatinine, BUN, eGFR – identify renal dysfunction
    • Glucose – identify hyper or hypoglycemia
    • Bilirubin – used in SOFA calculation to assess organ dysfunction
  • C-reactive protein (CRP)
    • Marker of acute inflammation; nonspecific
    • Frequently elevated, but not diagnostic
    • Use in conjunction with WBC count and differential
    • Single measure may not be helpful
      • Obtain serial quantitative levels 24 hours after onset of symptoms of possible infection; 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; 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 detection of sepsis
      • >2 standard deviations (SD) above normal is typically highly predictive of sepsis
    • Most useful in predicting progression of infection to severe sepsis or septic shock
    • Questionable if this test can distinguish SIRS from sepsis
  • Fluid analysis (eg, CSF, synovial, pleural, peritoneal)
    • Cell count with differential – aid in distinguishing bacterial from viral infection

Differential Diagnosis

  • Lactate (Rhodes, Surviving Sepsis Campaign, 2017)
    • Recheck at 6 hours if elevated >4 mmol/L at presentation
    • Use of norepinephrine may increase lactate levels and make this factor less useful for monitoring response
  • CBC
    • Decreasing leukocytosis suggests response to treatment
  • Procalcitonin (PCT)
    • Decreasing PCT suggests response to treatment
    • Values may assist with decision to shorten duration of antibiotics or to discontinue antibiotic therapy (Rhodes, Surviving Sepsis Campaign, 2016)

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, and 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.

Lactic Acid, Plasma 0020045
Method: Enzymatic

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 University of Utah Health Sciences Center

Typically requires ≥2 sites, one being percutaneous

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

Limitations 

Anaerobe culture is NOT included with this order

Urinalysis, Complete with Reflex to Culture 2007508
Method: Reflectance Spectrophotometry/Microscopy

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

Comprehensive Metabolic Panel 0020408
Method: Quantitative Ion-Selective Electrode/Quantitative Enzymatic/Quantitative Spectrophotometry

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Procalcitonin 0020763
Method: Immunofluorescence

Limitations 

Procalcitonin levels <0.50 ng/mL do not exclude infection, because localized infections (without systemic signs) may also be associated with such low levels

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

Guidelines

American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992; 20(6): 864-74. PubMed

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche J, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson T, Townsend SR, Van der Poll T, Vincent J, Wiersinga J, Zimmerman JL, Dellinger P. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017; 43(3): 304-377. PubMed

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent J, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8): 801-10. 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

Finkelsztein EJ, Jones DS, Ma KC, Pabón MA, Delgado T, Nakahira K, Arbo JE, Berlin DA, Schenck EJ, Choi AM, Siempos II. Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit. Crit Care. 2017; 21(1): 73. 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

Kaukonen K, Bailey M, Pilcher D, Cooper J, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015; 372(17): 1629-38. 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

Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, Pilcher DV, Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes and Resource Evaluation (CORE). Prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit. JAMA. 2017; 317(3): 290-300. 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

Surviving Sepsis Campaign: Updated bundles in response to new evidence. Society of Critical Care Medicine. Mount Prospect, IL [Revised 2015 Apr; Accessed: May 2017]

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

Content Reviewed: 
May 2017

Last Update: August 2017