ICU Sepsis Management Protocol

1. Definitions (Sepsis-3)

2. Immediate Recognition and Risk Stratification

• Apply SOFA scoring on all patients with suspected infection
• Obtain serum lactate as a mandatory initial test - lactate >4 mmol/L = high-risk, initiate protocol immediately
• Draw blood cultures x2 (aerobic + anaerobic sets, from separate sites) before antibiotics when this does not delay antibiotic administration beyond 45 min
• Obtain relevant cultures from other suspected sources (urine, respiratory, wound)
• Order chest X-ray, CBC, metabolic panel, coagulation studies, procalcitonin
• Perform point-of-care ultrasound (POCUS) to assess volume status, cardiac function, and identify source

3. Resuscitation Targets (First Hour)

Hemodynamic Monitoring

• Insert arterial line (radial preferred) for continuous blood pressure monitoring and ABG sampling
• Central venous access (internal jugular or subclavian) for CVP, ScvO2, and vasopressor infusions
• Use dynamic measures of volume responsiveness (pulse pressure variation >13%, stroke volume variation) over static CVP targets where possible
• Consider pulmonary artery catheter only in mixed septic/cardiogenic shock

4. Fluid Resuscitation

• Reassess after each fluid challenge using dynamic hemodynamic assessment
• Continue fluid challenges only while there is evidence of hemodynamic improvement
• Do NOT use hetastarch (HES) formulations - associated with increased AKI and mortality
• Albumin (4-5%): Consider adding when large volumes of crystalloid are required; do not use as primary resuscitation fluid (2024 ICTMG guideline, PMID 38447639)
• Follow serial lactate levels to guide adequacy of resuscitation

5. Antimicrobial Therapy

Timing

Empiric Antibiotic Selection by Source

Antibiotic Stewardship

• Reassess antibiotic choice at 48-72 hours using culture results and clinical response - de-escalate aggressively
• Target 5-7 days total course for most sources; extend only if inadequate source control or immunocompromised
• Use procalcitonin to guide de-escalation and discontinuation, not to initiate therapy
• Prolonged/extended infusion of beta-lactams improves target attainment (2024 JAMA meta-analysis, PMID 38864162)

Source Control

• Identify and remove/drain the infectious focus within 6-12 hours of diagnosis
• Remove vascular access devices if suspected source
• Surgical or percutaneous drainage for abscesses, infected fluid collections
• Debridement for necrotizing soft tissue infections (surgical emergency)

6. Vasopressor Therapy

• Do NOT use levosimendan or terlipressin as routine agents (SSC guideline)
• Targeting supranormal oxygen delivery values is not recommended

7. Corticosteroids

• Hydrocortisone 200 mg/day IV (as continuous infusion or 50 mg q6h)
• Do not use high-dose steroids; do not perform ACTH stimulation testing to guide use
• Taper and discontinue when vasopressors are weaned
• Consider adding fludrocortisone 50 mcg/day PO in documented or suspected relative adrenal insufficiency

8. Respiratory Support

Lung Protective Ventilation (Sepsis-induced ARDS)

• Tidal volume: 4-6 mL/kg predicted body weight
• Plateau pressure: ≤30 cmH2O
• Apply PEEP titrated to best compliance/oxygenation (use PEEP/FiO2 tables)
• Maintain SpO2 90-96%; avoid hyperoxia
• Driving pressure target: ≤15 cmH2O

Moderate-Severe ARDS (PaO2/FiO2 <150)

• Prone positioning ≥12 hours/day - reduces mortality (Grade 1B)
• Neuromuscular blockade (cisatracurium) to facilitate prone positioning; intermittent bolus preferred over continuous infusion
• Consider veno-venous ECMO if refractory despite optimal ventilation, at an experienced center

General Ventilator Management

• Head of bed elevation 30-45 degrees (semi-recumbent) at all times
• Use ventilator weaning protocols with daily spontaneous breathing trials (SBT)
• Daily sedation interruption ("wake up and breathe" protocol)
• Avoid routine pulmonary artery catheters in ARDS

9. Organ-Specific Supportive Care

Renal

• 67% of septic patients develop AKI
• Maintain adequate MAP (≥65 mmHg) to preserve renal perfusion
• Avoid nephrotoxins (NSAIDs, IV contrast, aminoglycosides where alternatives exist)
• Initiate continuous renal replacement therapy (CRRT) for: fluid overload refractory to diuretics, severe acidosis (pH <7.1), hyperkalemia >6.5 mEq/L, uremic complications
• Use sodium bicarbonate to correct arterial pH <7.2 in the setting of AKI

Hematologic

• Transfuse pRBCs when hemoglobin <7 g/dL (target 7-9 g/dL); use <8 g/dL threshold if active CAD or acute hemorrhage
• FFP only for active bleeding or planned invasive procedures with INR >2.0
• Platelet transfusion if <10,000/µL (prophylactic) or <50,000/µL with active bleeding/surgery
• VTE prophylaxis: UFH or LMWH + compression stockings unless anticoagulation contraindicated

Glucose Management

• Target blood glucose 140-180 mg/dL (7.8-10.0 mmol/L) using insulin infusion protocol
• Avoid hypoglycemia (<70 mg/dL) - associated with increased mortality
• Monitor glucose every 1-2 hours during insulin infusion

Gastrointestinal / Nutrition

• Early enteral nutrition within 24-48 hours of ICU admission when hemodynamically stable
• Avoid routine parenteral nutrition in the first 7 days if EN is feasible
• Stress ulcer prophylaxis with PPI or H2-blocker in ventilated or high-risk patients

Neurologic

• Sepsis-associated encephalopathy occurs in >50% of patients
• Minimize sedation (RASS target -1 to 0); use propofol or dexmedetomidine over benzodiazepines
• Screen for delirium (CAM-ICU) - if present, treat precipitants, consider haloperidol or quetiapine
• Investigate other CNS pathology (LP, MRI, EEG) if encephalopathy is out of proportion to metabolic derangements

10. Monitoring and Reassessment

11. Goals-of-Care and Communication

• Discuss prognosis and goals of care with patients and families early (within 24-48 hours of ICU admission)
• Integrate palliative care principles to address patient and family needs
• Document patient wishes and advance directives
• If withdrawal of life-sustaining therapy is considered, ensure ethics consultation is available

12. ICU Discharge and Post-Sepsis Planning

• ICU admission target: within 6 hours of sepsis diagnosis
• Screen survivors for post-intensive care syndrome (PICS): cognitive impairment, psychiatric morbidity, physical disability
• Hospital discharge plan should include:
  • Screening for economic and social support needs
  • Established follow-up with primary care and relevant specialists
  • Physiotherapy and rehabilitation referral
  • Mental health assessment (PTSD, depression, anxiety are common)

Quick Reference: "Hour-1 Bundle" (SSC)

1. Measure lactate - repeat if >2 mmol/L
2. Blood cultures before antibiotics (do not delay antibiotics >45 min)
3. Broad-spectrum antibiotics within 1 hour for septic shock
4. 30 mL/kg IV crystalloid for hypotension or lactate ≥4 mmol/L
5. Vasopressors (norepinephrine) for MAP <65 mmHg despite fluids

Key References

• Harrison's Principles of Internal Medicine 22e (2025) - Chapter 315: Sepsis and Septic Shock
• Barash Clinical Anesthesia 9e - Table 57-4: Management of Sepsis and Septic Shock
• Bailey & Love's Short Practice of Surgery 28e - Surviving Sepsis Campaign / Sepsis Bundle
• Evans L et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021
• Abdul-Aziz MH et al. Prolonged vs Intermittent Infusions of Beta-Lactam Antibiotics in Sepsis. JAMA 2024 [PMID 38864162]
• Brunkhorst FM et al. S3 Guideline on Sepsis 2025 Update. Med Klin Intensivmed Notfmed 2025 [PMID 40824313]
• Monnet X et al. ESICM Guidelines on Circulatory Shock and Hemodynamic Monitoring 2025. Intensive Care Med 2025 [PMID 41236566]

Disclaimer: This protocol is for educational and reference purposes. Always apply clinical judgment and adapt to local antimicrobial resistance patterns, institutional formulary, and individual patient circumstances.