What are the diagnostic criteria and management strategies for sepsis?

How to Diagnose Sepsis

Sepsis is diagnosed when there is suspected or documented infection plus evidence of organ dysfunction, operationalized by a Sequential Organ Failure Assessment (SOFA) score ≥2 points or a quick SOFA (qSOFA) score ≥2 in non-ICU settings. 1

Primary Diagnostic Approach

Step 1: Identify Suspected or Documented Infection

• Look for clinical evidence of infection including fever (>38.3°C) or hypothermia (<36°C) 1
• Document tachycardia (heart rate >90 bpm) and tachypnea (respiratory rate >20 breaths/min) 2, 1
• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before administering antimicrobials—draw one percutaneously and one through each vascular access device unless inserted <48 hours prior 1
• Assess for altered mental status, which may manifest as confusion, apathy, or malaise 2

Step 2: Assess for Organ Dysfunction Using SOFA Score

The SOFA score is the gold standard for diagnosing sepsis, particularly in ICU settings, with a score ≥2 indicating organ dysfunction. 2, 3

The SOFA score evaluates six organ systems 2:

• Respiratory: PaO₂/FiO₂ ratio <400 mmHg (1 point), <300 (2 points), <200 with mechanical ventilation (3 points), <100 with mechanical ventilation (4 points)
• Neurological: Glasgow Coma Scale 13-14 (1 point), 10-12 (2 points), 6-9 (3 points), <6 (4 points)
• Cardiovascular: MAP <70 mmHg (1 point) or requiring vasopressors at escalating doses (2-4 points based on dopamine, epinephrine, or norepinephrine requirements)
• Hepatic: Bilirubin 1.2-1.9 mg/dL (1 point) up to >12.0 mg/dL (4 points)
• Coagulation: Platelets <150,000/μL (1 point) down to <20,000/μL (4 points)
• Renal: Creatinine 1.2-1.9 mg/dL (1 point) or urine output <500 mL/day (3 points) up to creatinine >5.0 mg/dL or urine output <200 mL/day (4 points)

Step 3: Use qSOFA for Rapid Screening Outside the ICU

For non-ICU patients with suspected infection, use qSOFA (score ≥2) as a bedside screening tool to identify those requiring closer monitoring and further evaluation with full SOFA scoring. 1, 3

The qSOFA assigns 1 point each for 3:

• Systolic blood pressure ≤100 mmHg
• Respiratory rate ≥22/min
• Altered mental status

Important caveat: qSOFA has low sensitivity (41-63%) for identifying sepsis and should NOT be used to rule out sepsis 4, 5. A qSOFA score <2 does not exclude sepsis—maintain clinical suspicion and proceed with full SOFA assessment if infection is suspected 6, 5.

Resource-Limited Settings Adaptation

When laboratory testing is unavailable, diagnose sepsis using simplified clinical criteria 2:

• Infection plus ≥2 of the following: heart rate ≥90 bpm, respiratory rate ≥20 bpm, temperature ≤36°C or ≥38°C, malaise/apathy
• Evidence of organ dysfunction assessed by: decreased capillary refill or skin mottling, peripheral cyanosis, systolic BP ≤90 mmHg or drop ≥40 mmHg, SpO₂ ≤90%, signs of respiratory distress, acute oliguria (<0.5 mL/kg/h for ≥2 hours), jaundice, petechiae or bleeding from puncture sites, absent bowel sounds 2

Critical Additional Diagnostic Elements

Lactate Measurement

• Measure serum lactate immediately upon sepsis diagnosis—elevated lactate >1 mmol/L indicates tissue hypoperfusion and warrants aggressive resuscitation 2, 1
• Lactate >4 mmol/L combined with hypotension despite adequate fluid resuscitation defines septic shock 2

Inflammatory Markers

• Leukocytosis (WBC >12,000/μL), leukopenia (WBC <4,000/μL), or normal WBC with >10% immature forms supports the diagnosis 2, 1
• Elevated C-reactive protein or procalcitonin (>2 standard deviations above normal) provides additional diagnostic support 2, 1
• Note: White blood cell count cannot be used as a criterion in neutropenic patients 1

Severe Sepsis and Septic Shock Criteria

Severe sepsis is diagnosed when sepsis is accompanied by evidence of tissue hypoperfusion or acute organ dysfunction 2, 1:

• Sepsis-induced hypotension (SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg)
• Lactate above upper limits of normal
• Acute lung injury (PaO₂/FiO₂ <250 without pneumonia or <200 with pneumonia)
• Creatinine >2.0 mg/dL
• Bilirubin >2 mg/dL
• Platelet count <100,000/μL
• Coagulopathy (INR >1.5)
• Urine output <0.5 mL/kg/h for >2 hours despite adequate fluid resuscitation

Common Pitfalls to Avoid

• Do not rely solely on qSOFA for diagnosis—it was designed for prognostication, not diagnosis, and has poor sensitivity for identifying sepsis in ED settings 4, 5
• Do not delay antibiotics while waiting for cultures—administer effective IV antimicrobials within 1 hour of recognizing septic shock or severe sepsis 1
• Do not use SIRS criteria alone—they have been superseded by SOFA/qSOFA and have lower predictive validity for mortality 3
• Do not overlook atypical presentations in elderly patients—they may have attenuated inflammatory responses and fewer peritoneal signs 1
• Do not assume normal lactate excludes sepsis—some patients with ongoing sepsis may not have elevated lactate levels 2

Special Population Considerations

• Pediatric patients: Diagnostic criteria include signs of inflammation plus infection with hyper/hypothermia (rectal temperature >38.5°C or <35°C), tachycardia, and altered mental status, hypoxemia, increased lactate, or bounding pulses 2
• Neutropenic patients: Main risk factors include severity/duration of granulocytopenia, disruption of skin/mucosal barriers, and malnutrition—adapt diagnostic criteria accordingly 1
• HIV patients: Have increased susceptibility and altered immune responses requiring modified interpretation 1