Initial Laboratory Workup for Suspected Sepsis
Obtain blood cultures immediately (within 1 hour of presentation), followed by serum lactate, complete blood count with differential, comprehensive metabolic panel (creatinine, bilirubin, glucose), coagulation studies (platelets, INR/aPTT), and procalcitonin or C-reactive protein. 1, 2
Essential First-Line Laboratory Tests
Microbiologic Studies
- Blood cultures (≥2 sets, aerobic and anaerobic) must be drawn before antibiotics are administered, ideally within the first hour of suspected sepsis 1, 2
- Obtain cultures from all potential infection sources (urine, sputum, wound, cerebrospinal fluid if indicated) 3
Lactate Measurement
- Serum lactate is critical for identifying tissue hypoperfusion and defining septic shock 2, 3, 4
- A lactate >2 mmol/L indicates inadequate tissue perfusion and guides resuscitation intensity 2, 5
- Lactate >4 mmol/L combined with persistent hypotension after fluid resuscitation defines septic shock 2
Complete Blood Count with Differential
- Leukocytosis (WBC >12,000/μL) or leukopenia (WBC <4,000/μL) supports sepsis diagnosis 2
- Bandemia >10% immature neutrophils indicates severe infection 2
- Platelet count <100,000/μL signals coagulation dysfunction and contributes to organ failure assessment 2
Comprehensive Metabolic Panel
- Serum creatinine to assess renal dysfunction; elevation >2.0 mg/dL (176.8 μmol/L) or rise >0.5 mg/dL indicates acute kidney injury 2
- Total bilirubin to evaluate hepatic dysfunction; levels >2 mg/dL (34.2 μmol/L) suggest liver involvement 2
- Glucose to identify stress hyperglycemia; levels >140 mg/dL (7.7 mmol/L) without known diabetes support sepsis 2
Coagulation Studies
- INR >1.5 or prolonged aPTT indicates coagulopathy and organ dysfunction 2
- These values contribute to the Sequential Organ Failure Assessment (SOFA) score calculation 2, 4
Adjunctive Biomarkers
Procalcitonin (PCT)
- PCT ≥1.5 ng/mL demonstrates 100% sensitivity and 72% specificity for sepsis 2
- PCT correlates more closely with sepsis severity and predicts mortality better than other inflammatory markers 2
- Useful for distinguishing bacterial sepsis from other causes of systemic inflammatory response syndrome 2
C-Reactive Protein (CRP)
- CRP ≥50 mg/L has 98.5% sensitivity and 75% specificity for identifying probable or definite sepsis 2
- CRP is a valuable adjunct but cannot alone differentiate sepsis from other inflammatory conditions 2
Organ Dysfunction Assessment
The laboratory workup must enable calculation of the Sequential Organ Failure Assessment (SOFA) score, which requires: 2, 4
- Respiratory: PaO₂/FiO₂ ratio (arterial blood gas) or SpO₂ 2
- Cardiovascular: Blood pressure and vasopressor requirements 2
- Renal: Creatinine and urine output 2
- Hepatic: Total bilirubin 2
- Coagulation: Platelet count 2
- Neurological: Glasgow Coma Scale (clinical assessment) 2
An increase in SOFA score ≥2 points from baseline defines sepsis and is associated with >10% in-hospital mortality. 2, 4
Additional Laboratory Considerations
Inflammatory Markers
- Elevated CRP or procalcitonin >2 standard deviations above normal supports the diagnosis when SOFA cannot be immediately calculated 2
- These markers help guide antibiotic initiation in equivocal cases 2
Arterial Blood Gas
- Obtain if respiratory distress, altered mental status, or lactate elevation is present 3
- Provides PaO₂/FiO₂ ratio for respiratory SOFA component and assesses metabolic acidosis 2
Urinalysis and Urine Culture
- Essential when genitourinary source is suspected (20.5% of sepsis cases) 2
- Obtain before antibiotics if possible 3
Critical Pitfalls to Avoid
- Do not delay blood cultures or antibiotic administration to obtain additional laboratory tests; cultures must be drawn within 1 hour, and antibiotics should follow immediately 1, 3
- Do not rely solely on SIRS criteria (fever, tachycardia, tachypnea, leukocytosis), as these have inadequate specificity and sensitivity for sepsis 4
- Do not wait for procalcitonin or CRP results before initiating treatment; these are adjuncts, not prerequisites for therapy 2
- Do not assume normal lactate excludes sepsis; some patients with organ dysfunction may not have elevated lactate initially 2
- Recognize that elderly and immunocompromised patients may not mount typical fever or leukocytosis responses; maintain high clinical suspicion despite "normal" labs 6, 5
Timing and Workflow
All essential laboratory tests should be obtained within the first hour of suspected sepsis presentation, with blood cultures drawn before antibiotic administration but without delaying antibiotics beyond 1 hour. 1, 3 The laboratory workup should proceed simultaneously with clinical assessment and resuscitation, not sequentially. 1