When should sepsis be diagnosed?

When to Diagnose Sepsis

Sepsis should be diagnosed when a patient has suspected or documented infection plus evidence of organ dysfunction, operationalized by a NEWS2 score of 5 or higher or any concerning clinical signs, prompting immediate risk stratification and management. 1, 2

Primary Diagnostic Framework

The diagnosis of sepsis requires two essential components working together:

1. Evidence of Infection

• Documented or suspected infection is mandatory for sepsis diagnosis—without infection, the patient has SIRS (systemic inflammatory response syndrome) from another cause, not sepsis. 2, 3
• Common infection indicators include fever (>38.3°C), hypothermia (<36°C), leukocytosis (WBC >12,000/μL), leukopenia (WBC <4,000/μL), or elevated acute phase reactants (CRP or procalcitonin >2 SD above normal). 2, 4

2. Evidence of Organ Dysfunction

Use the NEWS2 score as your initial screening tool in the emergency department or ward setting: 1, 3

• NEWS2 ≥7: High risk—diagnose sepsis and initiate treatment within 1 hour 1
• NEWS2 5-6: Moderate risk—diagnose sepsis and initiate treatment within 3 hours 1
• NEWS2 1-4: Low risk—consider sepsis but may delay treatment up to 6 hours 1
• NEWS2 0: Very low risk—sepsis unlikely 3

Critical override criteria: Diagnose sepsis immediately regardless of NEWS2 score if any of these are present: 1

• Mottled or ashen appearance
• Non-blanching petechial or purpuric rash
• Cyanosis of skin, lips, or tongue

Specific Organ Dysfunction Markers

When NEWS2 suggests risk, confirm organ dysfunction with these specific criteria: 2, 3

Respiratory:

• PaO₂/FiO₂ <300 (or <250 without pneumonia, <200 with pneumonia)
• SpO₂ ≤90%
• Respiratory rate >20 breaths/min

Cardiovascular:

• Systolic BP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg
• Lactate >1 mmol/L (>4 mmol/L indicates severe hypoperfusion)
• Decreased capillary refill or skin mottling

Renal:

• Urine output <0.5 mL/kg/h for ≥2 hours despite adequate fluid resuscitation
• Creatinine increase ≥0.5 mg/dL (or >2.0 mg/dL for severe sepsis)

Hepatic:

• Bilirubin >2 mg/dL (or >4 mg/dL)

Coagulation:

• Platelet count <100,000/μL
• INR >1.5 or aPTT >60 seconds

Neurological:

• Altered mental status
• Glasgow Coma Scale ≤13

Common Diagnostic Pitfalls

Do not wait for positive cultures to diagnose sepsis. 1 The diagnosis is clinical, and several factors undermine microbiological confirmation:

• Prior antibiotic therapy sterilizes specimens 1
• Organisms from non-sterile sites may represent colonization rather than infection 1
• Occult infection sites (sinusitis, deep abdominal abscess) may not be sampled 1

Systematically exclude non-infectious causes of SIRS before diagnosing sepsis: 1

• Surgery/trauma, tissue infarction, hematoma
• Myocardial or pulmonary infarction
• Pancreatitis
• Drug reactions (malignant hyperthermia, neuroleptic malignant syndrome)
• Transplant rejection

Special populations require modified interpretation: 2

• Neutropenic patients: Cannot use WBC criteria; rely on fever, hemodynamic changes, and clinical deterioration
• Elderly patients: May present with attenuated inflammatory response and fewer peritoneal signs 1
• HIV patients: Have increased susceptibility and altered immune responses 1

Biomarker-Assisted Diagnosis

When infection probability is uncertain, use biomarkers to support (not replace) clinical judgment: 4

Procalcitonin (PCT):

• Rises within 4 hours, peaks at 6-8 hours 4
• ≥1.5 ng/mL: 100% sensitivity, 72% specificity for sepsis 4
• More specific than CRP for bacterial infection 4
• Caveat: Can be elevated in severe viral illness (influenza, COVID-19) 4

C-Reactive Protein (CRP):

• Rises 12-24 hours after insult, peaks at 48 hours 4
• ≥50 mg/L: 98.5% sensitivity, 75% specificity 4
• Less specific but widely available and cost-effective 4

Timing of Re-evaluation

Once sepsis is suspected, re-calculate NEWS2 and reassess at these intervals: 1

• High risk (NEWS2 ≥7): Every 30 minutes
• Moderate risk (NEWS2 5-6): Every hour
• Low risk (NEWS2 1-4): Every 4-6 hours

Escalate risk assessment if: 1

• Condition deteriorates
• No improvement despite interventions
• Any new concerning clinical sign appears

Immediate Actions Upon Diagnosis

The moment sepsis is diagnosed: 2, 4, 3

• Obtain blood cultures (≥2 sets) before antibiotics if no delay >45 minutes
• Measure lactate immediately
• Administer IV antibiotics within 1 hour (high risk), 3 hours (moderate risk), or 6 hours (low risk)
• Begin fluid resuscitation with ≥30 mL/kg crystalloid within 3 hours
• Identify and control infection source within 12 hours