What are the diagnostic criteria and management strategies for sepsis?

Sepsis Diagnosis

Sepsis is diagnosed when there is documented or suspected infection plus evidence of organ dysfunction, operationalized by a NEWS2 score ≥5 or the presence of any combination of systemic inflammatory markers, hemodynamic instability, or tissue hypoperfusion indicators. 1

Diagnostic Framework

Core Diagnostic Criteria

Sepsis requires two essential components: proven or highly suspected infection PLUS evidence of systemic dysfunction. 2, 3 The diagnosis should not wait for laboratory confirmation but can be made clinically when infection is suspected with abnormal vital signs or evidence of end-organ dysfunction. 4

General variables indicating systemic response:

• Fever >38.3°C or hypothermia <36°C 2, 1, 3
• Tachycardia (heart rate ≥90 bpm) 2, 3
• Tachypnea (respiratory rate ≥20 breaths/min) 2, 3
• Altered mental status or malaise/apathy 2, 1
• Significant edema or positive fluid balance (>20 mL/kg over 24 hours) 2, 3
• Hyperglycemia (>140 mg/dL) in absence of diabetes 2, 3

Inflammatory markers:

• Leukocytosis (WBC >12,000/μL) or leukopenia (WBC <4,000/μL) 2, 3
• Normal WBC with >10% immature forms (bandemia) 2, 3
• Elevated C-reactive protein or procalcitonin (>2 SD above normal) 2, 3

Organ Dysfunction Indicators

Hemodynamic dysfunction:

• Arterial hypotension: SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg 2, 3

Respiratory dysfunction:

• Arterial hypoxemia (PaO₂/FiO₂ <300) 2, 1
• SpO₂ ≤90% with or without oxygen 2
• Signs of respiratory distress (dyspnea, wheezing, crepitations, inability to speak sentences) 2

Renal dysfunction:

• Acute oliguria (urine output <0.5 mL/kg/hr for ≥2 hours despite adequate fluid resuscitation) 2, 1
• Creatinine increase ≥0.5 mg/dL 2, 1

Hepatic dysfunction:

• Hyperbilirubinemia (total bilirubin >4 mg/dL or >70 μmol/L) 2, 3
• Jaundice 2

Coagulation dysfunction:

• Thrombocytopenia (platelet count <100,000/μL) 2, 1, 3
• Coagulation abnormalities (INR >1.5 or aPTT >60 seconds) 2, 3
• Petechiae, ecchymoses, or bleeding from puncture sites 2

Gastrointestinal dysfunction:

• Ileus (absent bowel sounds) 2, 3

Tissue perfusion abnormalities:

• Hyperlactatemia (>1 mmol/L) 2, 1, 3
• Decreased capillary refill or skin mottling 2, 3
• Peripheral cyanosis 2, 1

Risk Stratification Using NEWS2 Score

The NEWS2 scoring system provides structured risk assessment: 1

• NEWS2 ≥7 (high risk): Initiate sepsis diagnosis and treatment within 1 hour; re-evaluate every 30 minutes 1
• NEWS2 5-6 (moderate risk): Initiate sepsis diagnosis and treatment within 3 hours; re-evaluate every hour 1
• NEWS2 1-4 (low risk): Re-evaluate every 4-6 hours 1

Critical override criteria warrant immediate sepsis diagnosis regardless of NEWS2 score: 1

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

Severe Sepsis and Septic Shock

Severe sepsis is defined as sepsis with documented tissue hypoperfusion or organ dysfunction, including: 2, 1

• Sepsis-induced hypotension
• Lactate above upper normal limits
• Urine output <0.5 mL/kg/hr for >2 hours despite adequate fluid resuscitation
• 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
• INR >1.5

Septic shock is defined as severe sepsis with persistent hypotension despite adequate fluid resuscitation or requiring vasopressors to maintain MAP ≥65 mmHg. 1, 4

Pediatric Considerations

In children, sepsis diagnosis requires: 2

• Signs and symptoms of inflammation plus infection
• Hyper- or hypothermia (rectal temperature >38.5°C or <35°C)
• Tachycardia (may be absent in hypothermic patients)
• At least one of: altered mental status, hypoxemia, increased serum lactate, or bounding pulses

Diagnostic Workup

Immediate actions upon sepsis diagnosis: 1

• Measure lactate immediately
• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before antibiotics—one percutaneously and one through each vascular access device (unless inserted <48 hours ago) 1
• Administer IV antibiotics within 1 hour for high-risk patients, 3 hours for moderate-risk, or 6 hours for low-risk patients 1

Imaging should be based on suspected source: 4

• Most common sources: pulmonary, urinary tract, abdomen, skin/soft tissue
• Less common: CNS (meningitis, encephalitis), spine (epidural abscess, osteomyelitis), cardiac (endocarditis), joints (septic arthritis)

Common Pitfalls

Do not rely on biomarkers alone to exclude sepsis. Procalcitonin, C-reactive protein, and lactate should support but not replace clinical judgment. 4 Some patients with ongoing sepsis may not have elevated lactate at presentation. 2

White blood cell count cannot be used as a criterion in neutropenic patients. 1 These patients have increased susceptibility and altered immune responses requiring special consideration. 1

Elderly patients may present with attenuated inflammatory response and fewer peritoneal signs, requiring modified interpretation of diagnostic criteria. 1

Resource-Limited Settings

In settings with limited resources, use simplified clinical criteria: 2

• Focus on physical examination findings: heart rate ≥90 bpm, respiratory rate ≥20 bpm, temperature ≤36°C or ≥38°C, malaise/apathy
• Add signs of organ dysfunction: decreased capillary refill, skin mottling, peripheral cyanosis, arterial hypotension, respiratory distress, oliguria, jaundice, bleeding/oozing, absent bowel sounds
• Clinical diagnosis supported by basic laboratory tests (complete blood count) is acceptable 1
• Ultrasound can be cost-effective when CT is unavailable 1