What are the diagnostic criteria and initial treatment for sepsis, particularly in older adults, young children, or those with compromised immune systems?

Diagnosis of Sepsis

Sepsis is diagnosed when there is documented or suspected infection PLUS evidence of organ dysfunction, operationalized by a Sequential Organ Failure Assessment (SOFA) score ≥2 points or a National Early Warning Score 2 (NEWS2) ≥5. 1, 2

Core Diagnostic Criteria

The diagnosis requires both components simultaneously: infection (documented or suspected) and organ dysfunction. 1, 2 This is not simply infection with fever—it requires evidence that the infection is causing organ damage. 1

Clinical Signs of Organ Dysfunction

General parameters indicating systemic involvement include: 3, 1

• Fever (core temperature >38.3°C) or hypothermia (<36°C) 3
• Tachycardia (>90 bpm or >2 SD above normal for age) 3, 1
• Tachypnea (>20-30 breaths/min) 3, 1
• Altered mental status or new confusion 3, 1
• Significant edema or positive fluid balance (>20 mL/kg over 24h) 3
• Hyperglycemia (>140 mg/dL without diabetes) 3, 1

Hemodynamic dysfunction includes: 3, 1

• Arterial hypotension (SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg) 3, 1
• Mixed venous oxygen saturation >70% 3, 1
• Cardiac index >3.5 L/min/m² 3, 1

Organ-specific dysfunction includes: 3, 1

• Respiratory: PaO₂/FiO₂ <300 (or <250 without pneumonia, <200 with pneumonia) 3, 1
• Renal: Acute oliguria (<0.5 mL/kg/h for ≥2h despite fluids) or creatinine increase ≥0.5 mg/dL 3, 1
• Hepatic: Hyperbilirubinemia (total bilirubin >4 mg/dL) 3, 1
• Hematologic: Thrombocytopenia (platelets <100,000/μL) or coagulopathy (INR >1.5, aPTT >60s) 3, 1
• Gastrointestinal: Ileus (absent bowel sounds) 3, 1

Tissue perfusion abnormalities include: 3, 1

• Hyperlactatemia (>1 mmol/L, with >3 mmol/L being more specific) 3, 1
• Decreased capillary refill or mottling 3, 1
• Peripheral cyanosis 1

Laboratory Markers

Inflammatory markers that support diagnosis: 3, 1

• Leukocytosis (WBC >12,000/μL) or leukopenia (<4,000/μL) 3, 1
• Normal WBC with >10% immature forms (bands) 3, 1
• Elevated C-reactive protein (>2 SD above normal) 3, 1
• Elevated procalcitonin (>2 SD above normal, or ≥1.5 ng/mL for higher specificity) 3, 1, 2

Critical caveat: In neutropenic patients, white blood cell counts cannot be used as diagnostic criteria—rely on other parameters. 3, 1

Risk Stratification Using NEWS2

Use NEWS2 scoring to determine urgency of intervention: 1, 4

• High risk (NEWS2 ≥7): Treat within 1 hour, reassess every 30 minutes 1, 4
• Moderate risk (NEWS2 5-6): Treat within 3 hours, reassess every hour 1, 4
• Low risk (NEWS2 1-4): Treat within 6 hours, reassess every 4-6 hours 1, 4

Critical override criteria that warrant immediate treatment regardless of NEWS2 score: 1, 4

• Mottled or ashen appearance 1, 4
• Non-blanching petechial or purpuric rash 1, 4
• Cyanosis of skin, lips, or tongue 1, 4

Severe Sepsis and Septic Shock

Severe sepsis is sepsis with any of the following: 3, 1

• Sepsis-induced hypotension 3, 1
• Lactate above upper limits of normal 3, 1
• Urine output <0.5 mL/kg/h for >2h despite adequate fluid resuscitation 3, 1
• Creatinine >2.0 mg/dL 3, 1
• Bilirubin >2 mg/dL 3, 1
• Platelet count <100,000/μL 3, 1
• Coagulopathy (INR >1.5) 3, 1

Septic shock is severe sepsis with persistent hypotension despite adequate fluid resuscitation (typically 30 mL/kg crystalloid). 3, 1

Diagnostic Workup Algorithm

Immediate actions upon suspicion of sepsis: 4, 2

1. Obtain blood cultures (at least 2 sets, aerobic and anaerobic) before antibiotics if this causes no delay >45 minutes 4, 2

   • Draw at least one set percutaneously 4, 2
   • Draw one through each vascular access device (unless inserted <48h ago) 4, 2

2. Measure serum lactate immediately 1, 4, 2

3. Check complete blood count with differential, creatinine, bilirubin, coagulation studies 2

4. Identify infection source with targeted imaging: 3, 2

   • For respiratory symptoms: Start with chest X-ray (sensitivity 58%, specificity 91% for pneumonia) 2
   • If chest X-ray normal/equivocal but suspicion high: Proceed immediately to CT chest with IV contrast (identifies source in 72% of cases, changes management in 45%) 3, 2
   • For abdominal/pelvic symptoms: CT abdomen/pelvis with IV contrast 3, 2

5. Consider procalcitonin and CRP for diagnostic support: 2

   • Procalcitonin ≥1.5 ng/mL has 100% sensitivity and 72% specificity for sepsis 2
   • CRP has 98.5% sensitivity and 75% specificity 2
   • Do not rely on single biomarker alone—use comprehensive clinical assessment 2

Initial Treatment (Within First Hour for High-Risk Patients)

The "Hour-1 Bundle" for sepsis management: 3, 1, 4

1. Administer IV antimicrobials within 1 hour of recognizing septic shock or severe sepsis 3, 1, 4

   • Use broad-spectrum agents effective against all likely pathogens 3, 4
   • Do not delay for culture results—sepsis is a clinical diagnosis 2

2. Give at least 30 mL/kg IV crystalloid within first 3 hours for sepsis-induced hypoperfusion 3, 1, 4

   • Reassess hemodynamic status frequently after initial bolus 4
   • Use dynamic variables to predict fluid responsiveness when available 4

3. Target mean arterial pressure ≥65 mmHg with vasopressors if hypotension persists after fluid resuscitation 3, 4

   • Norepinephrine is first-line vasopressor 1

4. Guide resuscitation to normalize lactate in patients with elevated levels 3, 1

5. Identify and control infection source within 12 hours when feasible 3, 4

   • Drain or debride infection source 4
   • Remove foreign bodies or devices that may be infection source 4

Special Population Considerations

Neutropenic patients: 3, 1

• Cannot use WBC count as diagnostic criterion 3, 1
• Risk factors include severity/duration of neutropenia, disrupted mucosal barriers, malnutrition 1

• 90% of febrile neutropenic episodes meet sepsis criteria 3

Elderly patients: 1

• May present with attenuated inflammatory response 1
• Fewer peritoneal signs require modified interpretation 1
• Higher baseline risk for sepsis 1

Immunocompromised patients (including HIV): 1

• Increased susceptibility and altered immune responses 1
• May not mount typical inflammatory response 1

Young children: 3

• Diagnostic criteria include hyper/hypothermia (rectal temp >38.5°C or <35°C), tachycardia, and altered mental status, hypoxemia, increased lactate, or bounding pulses 3

Common Pitfalls to Avoid

• Waiting for culture results before diagnosis or treatment—sepsis is a clinical diagnosis requiring immediate action 2
• Delaying antimicrobials beyond 1 hour in high-risk patients—every hour delay increases mortality 3, 4
• Inadequate initial fluid resuscitation—must give full 30 mL/kg within 3 hours 3, 4
• Failing to obtain cultures before antibiotics—obtain within 45 minutes or give antibiotics first 4, 2
• Relying on single biomarker—use comprehensive clinical assessment 2
• Missing occult infection sources requiring source control—actively search for drainable collections or removable devices 4
• Not reassessing for antimicrobial de-escalation daily—narrow therapy once susceptibilities known 3, 4