Diagnostic Laboratory Tests for Septic Shock
In a patient with suspected septic shock, immediately obtain at least two sets of blood cultures (aerobic and anaerobic), measure serum lactate, complete blood count with differential, comprehensive metabolic panel, and coagulation studies (PT/INR, PTT) within the first hour of recognition. 1, 2
Essential Initial Laboratory Tests (Within 1 Hour)
Blood Cultures - Highest Priority
- Draw at least two sets of blood cultures (both aerobic and anaerobic bottles) before antimicrobial therapy, with at least one drawn percutaneously and one through each vascular access device unless recently inserted (<48 hours). 1
- Blood cultures must be obtained within 45 minutes to avoid delaying antibiotic administration beyond the critical 1-hour window. 1, 2
- Obtain cultures from other potential infection sources based on clinical presentation (urine, sputum, cerebrospinal fluid, wounds, respiratory secretions) if this causes no substantial delay. 1
- Critical pitfall: Never delay antibiotics beyond 1 hour while waiting for cultures—if obtaining cultures is not immediately feasible, start antimicrobials first. 3
Serum Lactate - Mandatory for Diagnosis and Resuscitation
- Measure serum lactate immediately in all suspected sepsis cases as it defines sepsis-induced tissue hypoperfusion and guides resuscitation. 1, 2, 3
- Lactate ≥4 mmol/L defines sepsis-induced tissue hypoperfusion requiring immediate fluid resuscitation with 30 mL/kg crystalloid within 3 hours. 1, 3
- Lactate >2 mmol/L indicates more severe disease and triggers aggressive resuscitation protocols. 2, 3
- Perform serial lactate measurements every 2-4 hours until normalized to guide resuscitation and assess treatment response. 1, 3
Complete Blood Count with Differential
- Assess for leukocytosis, leukopenia, or bandemia as indicators of infection and immune response. 2, 4
- The neutrophil-to-lymphocyte ratio (NLR) has emerged as more useful than white blood cell count alone for diagnostic and prognostic purposes. 3, 5
- Platelet count is essential for assessing sepsis-induced coagulopathy and guiding transfusion decisions. 3
- Critical caveat: White blood cell count alone lacks sufficient sensitivity to distinguish sepsis in hospitalized patients—do not rely on it exclusively. 3, 5
Comprehensive Metabolic Panel
- Evaluate renal function (creatinine, BUN) and hepatic function (transaminases, bilirubin) to assess organ dysfunction. 2, 3
- Measure electrolytes (sodium, potassium, chloride, bicarbonate) to identify abnormalities requiring correction. 2, 3
- Assess glucose levels as hyperglycemia is common in sepsis and requires management. 3
Coagulation Studies
- Obtain PT/INR and PTT to assess for coagulopathy and sepsis-induced coagulopathy (SIC). 2, 3
- Coagulopathy indicates more severe disease—patients with severe sepsis and disseminated intravascular coagulation (DIC) have 20% lower survival. 3, 6
- Monitor coagulation parameters daily for development or progression of sepsis-induced coagulopathy. 2, 3
Adjunctive Biomarkers (Consider Based on Clinical Context)
Procalcitonin (PCT) - Preferred Biomarker
- PCT has higher diagnostic accuracy than CRP (area under ROC curve 0.85 vs. 0.73) and rises within 4 hours of bacterial exposure, peaking at 6-8 hours. 2, 6
- PCT ≥1.5 ng/mL shows 100% sensitivity and 72% specificity for identifying sepsis in ICU populations. 3, 6
- Use low PCT levels to assist in discontinuing empiric antibiotics in patients who initially appeared septic but have no subsequent evidence of infection. 1, 3
- Do not delay antibiotics in high-probability cases while waiting for PCT results—use PCT primarily for antibiotic de-escalation, not initiation. 3, 6
C-Reactive Protein (CRP) - Alternative When PCT Unavailable
- CRP ≥50 mg/L demonstrates 98.5% sensitivity and 75% specificity for probable sepsis. 2, 3
- CRP rises 12-24 hours after inflammatory insult, reaching maximum at 48 hours—slower kinetics than PCT. 3, 6
- CRP is less specific than PCT for bacterial infections but remains widely available and cost-effective. 3, 6
- Critical limitation: CRP cannot reliably differentiate bacterial from viral infections or non-infectious inflammation (specificity only 40-67%). 6
Fungal Biomarkers (When Invasive Candidiasis Suspected)
- Use 1,3-β-D-glucan assay when invasive candidiasis is in the differential diagnosis. 1, 3
- Consider mannan and anti-mannan antibody assays for suspected candidiasis. 1
Monitoring and Follow-Up Testing
Serial Lactate Monitoring
- Repeat lactate every 2-4 hours until normalized as normalizing lactate is a key resuscitation target. 1, 3
- Lactate clearance guides fluid resuscitation and vasopressor titration. 1, 3
Follow-Up Cultures and Biomarkers
- Obtain follow-up blood cultures to document clearance of bacteremia. 2, 3
- Repeat PCT or CRP at 24-48 hours to assess treatment response and guide antibiotic de-escalation. 3
- Reassess CBC and metabolic panel daily to track progression or resolution of organ dysfunction. 2, 3
Hemodynamic Monitoring (If Persistent Shock)
- In persistent hypotension despite volume resuscitation or initial lactate ≥4 mmol/L, consider measuring central venous oxygen saturation (ScvO2) targeting ≥70%. 1
- Further hemodynamic assessment (such as cardiac ultrasound) may be needed to determine the type of shock if clinical examination is unclear. 1
Practical Algorithm for Laboratory Ordering
Hour 1 (0-60 minutes):
- Draw at least two sets of blood cultures from different sites. 1, 2
- Measure serum lactate immediately. 1, 2, 3
- Obtain CBC with differential. 2, 3, 4
- Order comprehensive metabolic panel. 2, 3
- Perform coagulation studies (PT/INR, PTT). 2, 3
- Consider PCT or CRP for low-to-intermediate probability cases (do not delay antibiotics in high-probability cases). 3, 6
Hours 2-4:
- Repeat lactate if initial lactate was elevated. 1, 3
- Continue serial lactate measurements every 2-4 hours until normalized. 1, 3
Hours 6-24:
- Reassess CBC and metabolic panel. 2, 3
- Monitor coagulation parameters for development of DIC. 3, 6
- Repeat PCT/CRP at 24-48 hours to assess treatment response. 3
Ongoing:
- Obtain follow-up blood cultures to document clearance. 2, 3
- Daily reassessment of organ function parameters. 2
Critical Pitfalls to Avoid
- Never delay antibiotic administration beyond 1 hour while waiting for laboratory results—sepsis and septic shock are medical emergencies requiring immediate treatment. 1, 3
- Do not rely solely on white blood cell count—it lacks sensitivity for sepsis diagnosis; use NLR instead. 3, 5
- Negative cultures do not exclude sepsis, especially in patients with prior antibiotic exposure. 3
- Interpret biomarkers within clinical context—no single laboratory test accurately diagnoses sepsis; PCT and CRP should supplement, not replace, clinical judgment. 3, 6
- In cirrhotic patients, lactate clearance is impaired and inflammatory markers are often elevated even without infection, though persistent elevation indicates poor prognosis. 3
- PCT may be elevated in severe viral illnesses including influenza and COVID-19, reducing its discriminatory power. 3