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 (≥2 defines SIRS)
      • Fever or hypothermia (temperature ≥38°C or ≤36°C)
      • Tachycardia (heart rate >90)
      • Tachypnea (respiratory rate >20/min, arterial carbon dioxide tension [PaCO2] <32 mm Hg)
      • Abnormal white blood cell count (>12,000/µL, or <4,000/µL, or >10% band forms)

    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 or hyperlactatemia >1 mmol/L
    • Multiple organ syndrome (severe sepsis) – sepsis with multiple organ dysfunction

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 – 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
  • 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 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
    • 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

Monitoring

  • 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

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 – >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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial testing to help differentiate bacterial from viral etiology

   
Blood Culture 0060102
Method: Continuous Monitoring Blood Culture/Identification

Evaluate for presence of bacteremia

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
Identify causative organism of infected site(s)

Anaerobe culture is NOT included with this order

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

Identify cause of CNS infection

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

Evaluate presence of organ dysfunction

Panel includes anion gap carbon dioxide, chloride, potassium, and sodium

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

Evaluate presence of renal dysfunction

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and urea nitrogen

   
Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Evaluate presence of hepatic dysfunction

Panel includes albumin; ALP; AST; ALT; bilirubin, direct; protein, total; and bilirubin, total

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

May be a helpful in evaluating sepsis, particularly neonatal sepsis

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
Test of choice for differential diagnosis on synovial fluid aspirate    
Procalcitonin 0020763
Method: Immunofluorescence

Proposed at this time as an early marker (<24 hours) for sepsis, particularly in the newborn

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
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Body Fluid Culture and Gram Stain 0060108
Method: Stain/Culture/Identification

Anaerobe culture is NOT included with this order