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Sepsis & Septic Shock: ICU Management Protocol

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1. Definitions (Sepsis-3)

• Respiratory rate ≥22 breaths/min
• Altered mental status (GCS <15)
• Systolic BP ≤100 mmHg

qSOFA is more specific but less sensitive than SIRS criteria; no single screening tool is preferentially endorsed by SSC 2021.

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2. Immediate Actions (First Hour — "Hour-1 Bundle")

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3. Hemodynamic Resuscitation

Fluid Therapy

• First-line: Balanced crystalloids (e.g., lactated Ringer's, Plasma-Lyte) — preferred over normal saline for large-volume resuscitation
• Initial volume: ≥30 mL/kg IV crystalloid in the first 3 hours
• Continued reassessment: Additional fluid challenges as long as hemodynamic improvement is demonstrated by static or dynamic measures (pulse pressure variation, passive leg raise, stroke volume variation)
• Albumin: Consider addition when large crystalloid volumes are required; not as initial fluid of choice
• Avoid: Hetastarch/HES formulations (associated with AKI and increased mortality)
• Resuscitation endpoints: Serial lactate measurements — targeting lactate clearance ≥10% every 2 hours; MAP ≥65 mmHg; urine output ≥0.5 mL/kg/hr

Vasopressors

Central venous pressure (CVP) alone is unreliable for guiding fluid management. Routine pulmonary artery catheter placement is not recommended for ALI/ARDS.

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4. Antimicrobial Therapy

Timing

• Septic shock: Empiric antibiotics within 1 hour of recognition (every 1-hour delay associated with ~7–8% increase in mortality)
• Sepsis without shock: Empiric therapy within 3 hours if no alternative diagnosis emerges

Empiric Antibiotic Selection by Source

Antibiotic Optimization

• Prolonged/extended infusion of β-lactams (over 3–4 hours): improves pharmacodynamic target attainment and is associated with reduced mortality in sepsis/septic shock (JAMA 2024, PMID 38864162)
• Administer β-lactams before vancomycin when both are required
• De-escalate based on culture/sensitivity results at 48–72 hours
• Procalcitonin: Do not use to decide when to start therapy; useful to guide discontinuation
• Duration: Typically 7–10 days; shorter courses acceptable with good source control and clinical improvement

Source Control

• Drain/aspirate abscesses
• Debride necrotizing infections
• Relieve biliary/urinary obstruction
• Remove infected intravascular devices (especially if no alternate source in critically ill patients)

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5. Adjunctive Therapies

Corticosteroids

• Do not use if hemodynamic stability can be achieved with fluids and vasopressors
• Indication: Septic shock refractory to adequate fluid resuscitation and vasopressors
• Regimen:
  • Hydrocortisone 200 mg/day IV (50 mg q6h or continuous infusion)
  • Option: Add fludrocortisone 50 µg daily via NGT — shown to improve 90-day all-cause mortality in septic shock (APROCCHSS trial)
  • Duration: 7 days, then taper
• Hydrocortisone alone shortens shock duration but does not reduce 90-day mortality
• COVID-19 exception: Dexamethasone 6 mg IV once daily reduces ventilator need and mortality ~30% in patients requiring oxygen
• Monitor: Superinfection, hyperglycemia, neuromyopathy, immune suppression

Glucose Control

• Target blood glucose 140–180 mg/dL (7.8–10 mmol/L)
• Avoid intensive insulin therapy (tight glycemic control <110 mg/dL) — associated with increased hypoglycemia risk and possible increased mortality

Transfusion

• Transfuse RBCs when Hgb <7 g/dL in the absence of:
  • Active tissue hypoperfusion
  • Acute coronary syndrome or CAD
  • Active hemorrhage
• Target Hgb 7–9 g/dL
• No benefit demonstrated for targeting supranormal oxygen delivery

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6. Respiratory Support

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7. Renal Support

• AKI is a frequent and serious complication of septic shock
• Continuous renal replacement therapy (CRRT) preferred over intermittent hemodialysis in hemodynamically unstable patients
• Timing of RRT initiation: Early initiation has not shown mortality benefit over standard criteria in large trials — initiate per clinical indications
• Anticoagulation for RRT: Regional citrate preferred (extends filter life, reduces bleeding risk)
• Bicarbonate: Use to correct arterial pH <7.15–7.20 in setting of AKI; not for routine lactic acidosis correction
• Low-dose dopamine for renal protection: NOT recommended

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8. Organ-Specific & Supportive Care Bundles

DVT Prophylaxis

• LMWH preferred over unfractionated heparin (lower PE risk)
• Contraindications: active bleeding, coagulopathy, heparin hypersensitivity → use mechanical prophylaxis (sequential compression devices)

Stress Ulcer Prophylaxis

• Indicated in patients with sepsis/septic shock and risk factors (mechanical ventilation, coagulopathy)
• Proton pump inhibitors (PPIs) or H₂-receptor antagonists acceptable
• Avoid routine use in low-risk patients (increases risk of C. difficile, pneumonia)

Sedation & Analgesia (PADIS Bundle)

• Use analgesia-first approach
• Minimize sedation depth — target light sedation (RASS 0 to −1) unless specific indications
• Daily sedation interruptions (SAT) if using continuous infusions
• Paired with daily spontaneous breathing trials (SBT)
• Assess and manage delirium (CAM-ICU or CPOT) — avoid benzodiazepines as first-line sedation
• Early mobilization when hemodynamically stable

Nutrition

• Initiate enteral nutrition within 24–48 hours of ICU admission when hemodynamically stable
• Avoid overfeeding
• Parenteral nutrition: only if enteral route not feasible after 5–7 days

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9. Monitoring & Reassessment Framework

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10. Goals of Care & Discharge Planning

• Engage patients/families in goals-of-care discussions early — integrate palliative care principles
• Sepsis survivors have markedly elevated risk of:
  • Physical: fatigue, ICU-acquired weakness, functional decline
  • Cognitive: cognitive impairment, dementia
  • Psychological: PTSD, depression
  • Medical: increased risk of MI, stroke, recurrent infection; 50% rehospitalization within 1 year; 1 in 6 die within the first year
• Discharge planning (per SSC 2021): screen for economic/social support; arrange follow-up with providers who can address physical, cognitive, and psychological issues

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References

• Harrison's Principles of Internal Medicine 22E (2025, McGraw Hill) — Initial Sepsis Management, pp. 2363–2364
• Barash, Cullen & Stoelting's Clinical Anesthesia 9E — Table 57-4: Management of Sepsis and Septic Shock, p. 4831
• Goldman-Cecil Medicine — Corticosteroids in Septic Shock; Renal Dysfunction and Dialysis, p. 1099
• Evans L et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;49:e1063
• Abdul-Aziz MH et al. Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: Systematic Review and Meta-Analysis. JAMA 2024 Aug 27 [PMID: 38864162]
• Lewis K et al. Focused Update to Clinical Practice Guidelines for Pain, Anxiety, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult ICU Patients. Crit Care Med 2025 Mar [PMID: 39982143]