What laboratory tests and interventions are recommended for diagnosing and managing sepsis?

Laboratory Tests for Sepsis Diagnosis and Management

Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, measure serum lactate immediately, and perform a complete blood count with comprehensive metabolic panel—all within the first hour of suspected sepsis recognition. 1, 2

Essential Initial Laboratory Tests

Blood Cultures (Priority #1)

• Draw at least two sets of blood cultures before antimicrobial therapy, with one drawn percutaneously and one through each vascular access device (if present <48 hours) 3, 1
• Blood cultures must be obtained within 45 minutes to avoid delaying antibiotic administration 2
• Consider additional cultures from other potential infection sources based on clinical presentation (urine, sputum, wound, cerebrospinal fluid) 2
• Do not delay antibiotics beyond 1 hour if obtaining cultures is not immediately feasible 1, 4

Serum Lactate (Priority #2)

• Measure lactate immediately in all suspected sepsis cases 1, 2, 4
• Lactate >2 mmol/L indicates more severe disease and triggers aggressive resuscitation protocols 1, 2
• Lactate ≥4 mmol/L defines sepsis-induced tissue hypoperfusion requiring immediate fluid resuscitation with 30 mL/kg crystalloid 3, 1
• Perform serial lactate measurements every 2-4 hours to guide resuscitation and assess treatment response 1, 2
• Normalizing lactate is a key resuscitation target 3, 1, 4

Complete Blood Count (CBC)

• Assess for leukocytosis (>12,000/mm³), leukopenia (<4,000/mm³), or bandemia (>10% immature forms) 1, 2
• The neutrophil-to-lymphocyte ratio (NLR) has emerging value as a diagnostic and prognostic marker, superior to white blood cell count alone 5
• Traditional neutrophilia alone lacks sufficient sensitivity to distinguish sepsis in hospitalized patients 4
• Platelet count is essential for assessing sepsis-induced coagulopathy and guiding transfusion decisions 3, 4

Comprehensive Metabolic Panel

• Evaluate renal function (creatinine, BUN) and hepatic function (bilirubin, transaminases) to assess organ dysfunction 1, 2
• Measure electrolytes to identify abnormalities requiring correction 1, 2
• Assess glucose levels, as hyperglycemia is common in sepsis 4
• Rising creatinine and bilirubin indicate progression of organ failure and worse prognosis 6

Coagulation Studies

• Obtain PT/INR and PTT to assess for coagulopathy and sepsis-induced coagulopathy (SIC) 1, 2
• Coagulopathy indicates more severe disease; patients with severe sepsis and DIC have 20% lower survival 4
• Monitor coagulation parameters daily for development or progression of sepsis-induced coagulopathy 2, 4

Adjunctive Biomarkers

Procalcitonin (PCT)

• PCT rises within 4 hours of bacterial exposure and peaks at 6-8 hours, making it valuable for early detection 4
• PCT ≥1.5 ng/mL shows 100% sensitivity and 72% specificity for identifying sepsis in ICU populations 4
• PCT has higher diagnostic accuracy than CRP (area under ROC curve 0.85 vs. 0.73) 2, 4
• Use low PCT levels to assist in discontinuing empiric antibiotics in patients who initially appeared septic but have no subsequent evidence of infection 3, 4
• Caveat: PCT may be elevated in severe viral illnesses including influenza and COVID-19, reducing discriminatory power 4

C-Reactive Protein (CRP)

• CRP rises 12-24 hours after inflammatory insult, reaching maximum at 48 hours 4
• CRP ≥50 mg/L demonstrates 98.5% sensitivity and 75% specificity for probable sepsis 2, 4
• CRP is less specific than PCT for bacterial infections but remains widely available and cost-effective 4

Fungal Biomarkers (When Indicated)

• Use 1,3-β-D-glucan assay when invasive candidiasis is in the differential diagnosis 3, 4
• Consider mannan and anti-mannan antibody assays for suspected fungal sepsis 3, 4

Practical Algorithm for Laboratory Testing

Within First Hour:

• Draw at least two sets of blood cultures (different sites) 1, 2
• Measure serum lactate 1, 2, 4
• Obtain CBC with differential 1, 2
• Order comprehensive metabolic panel 1, 2
• Perform coagulation studies (PT/INR, PTT) 1, 2
• Consider PCT or CRP for low-to-intermediate probability cases; do not delay antibiotics in high-probability cases 4

Serial Monitoring:

• Repeat lactate every 2-4 hours until normalized 1, 2
• Reassess CBC and metabolic panel daily 2
• Repeat PCT/CRP at 24-48 hours to assess treatment response and guide antibiotic de-escalation 4
• Obtain follow-up blood cultures to document clearance of bacteremia 2
• Monitor coagulation parameters for development of DIC 2, 4

Critical Pitfalls to Avoid

• Never delay antibiotic administration beyond 1 hour while waiting for laboratory results 1, 4
• Do not rely solely on white blood cell count; it lacks sensitivity for sepsis diagnosis 4, 5
• Negative cultures do not exclude sepsis, especially in patients with prior antibiotic exposure 2
• Interpret biomarkers within clinical context; no single laboratory test accurately diagnoses sepsis 6
• In cirrhotic patients, lactate clearance is impaired and inflammatory markers are often elevated even without infection 4
• Pre-existing conditions must be considered when interpreting laboratory values 2