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Sepsis Management Protocol — ICU

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1. Definition & Recognition

• Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection. Defined clinically as suspected/confirmed infection + acute SOFA score increase ≥2.
• Septic shock: Sepsis + persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg + serum lactate >2 mmol/L despite adequate fluid resuscitation.

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

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

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3. Hemodynamic Resuscitation

Fluids

• Initial bolus: 30 mL/kg IV crystalloid within the first 3 hours.
• Preferred agent: Balanced crystalloids (Lactated Ringer's or Plasmalyte). Normal saline acceptable but balanced crystalloids are preferred to limit hyperchloremic acidosis.
• Albumin: Consider adding when large volumes of crystalloid are required (e.g., >3 L).
• Avoid: Hetastarch (HES) — associated with AKI and increased mortality.
• Reassess after each fluid challenge: Use dynamic measures of fluid responsiveness — pulse pressure variation, stroke volume variation, or passive leg raise test.
• Goal: MAP ≥65 mmHg, urine output ≥0.5 mL/kg/hr, lactate clearance.

Vasopressors

Resuscitation Targets

• MAP ≥65 mmHg
• Lactate normalization (<2 mmol/L); serial lactate measurements to guide adequacy of resuscitation
• CVP 8–12 mmHg (less relied upon; dynamic measures preferred)
• ScvO₂ ≥70% (if central access in place)

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4. Antimicrobial Therapy

Timing

• Septic shock: Empiric antibiotics within 1 hour of recognition — every 1-hour delay is associated with ~7–8% increase in mortality.
• Sepsis without shock: Empiric antibiotics within 3 hours if no alternative diagnosis identified after clinical evaluation.

Empiric Regimen Selection

β-Lactam Optimization

• Administer β-lactams before vancomycin.
• Consider prolonged infusion of β-lactams (extended infusion over 3–4 hours) for time-dependent killing — a 2024 JAMA meta-analysis (PMID 38864162) showed prolonged infusions were associated with improved clinical cure and reduced mortality in adults with sepsis or septic shock.

De-escalation & Duration

• Reassess regimen daily; narrow spectrum within 3–5 days once microbiologic data are available.
• Target 7–10 days total course for most infections (shorter if good clinical response).
• Procalcitonin-guided de-escalation: discontinuation when PCT ≥80% reduction from peak or PCT ≤0.5 µg/L on day 5 or later can reduce antibiotic duration and hospitalization without compromising outcomes.
• Do not use procalcitonin to decide when to start antibiotics.

Source Control

• Identify and control surgical/procedural sources as rapidly as possible (abscesses, perforations, cholangitis, pyelonephritis, necrotizing soft tissue infections).
• Remove infected indwelling catheters promptly.

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5. Corticosteroids

• Hydrocortisone 200 mg/day IV (50 mg IV q6h or continuous infusion at 200 mg/24h)
• With or without fludrocortisone 50 µg via NGT once daily for 7 days.
  • The APROCCHSS trial showed hydrocortisone + fludrocortisone improved 90-day all-cause mortality in septic shock; a 2023 patient-level meta-analysis (PMID 38320130) supports this benefit.
  • Hydrocortisone alone shortens shock duration but does not reduce 90-day mortality.

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6. Respiratory Support

• Tidal volume: 6 mL/kg ideal body weight (max 8 mL/kg)
• Plateau pressure: ≤30 cmH₂O
• PEEP: titrated to oxygenation (high PEEP table for moderate-severe ARDS)
• SpO₂ target: 90–96%

• Prone positioning ≥12 hours/day for moderate-severe ARDS (PaO₂/FiO₂ <150)
• Neuromuscular blockade to facilitate prone positioning; prefer intermittent bolus over continuous infusion
• Elevate head of bed 30–45°
• Avoid routine pulmonary artery catheter
• Veno-venous ECMO if refractory hypoxia despite optimal ventilation (at experienced centers)

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7. Organ-Specific Monitoring & Management

Cardiovascular

Renal

• AKI occurs in ~67% of septic patients.
• Avoid nephrotoxins (aminoglycosides, NSAIDs, contrast where possible).
• Renal replacement therapy (RRT): Initiate for refractory metabolic acidosis (pH <7.2), hyperkalemia, oliguria unresponsive to fluids, or uremia.
• Continuous RRT (CRRT) preferred over intermittent hemodialysis in hemodynamically unstable patients.
• Regional citrate anticoagulation preferred during CRRT (extends filter life, reduces bleeding risk).
• Avoid low-dose dopamine for renal protection — no benefit.
• Bicarbonate: Use to correct pH <7.2 in the setting of AKI.

Hematologic

• Transfusion threshold: Hemoglobin 7–9 g/dL in the absence of tissue hypoperfusion, active hemorrhage, or coronary artery disease.
• Platelet transfusion: ≥10,000/µL prophylactically, or ≥20,000/µL if bleeding risk; ≥50,000/µL for procedures.
• Avoid routine use of fresh frozen plasma unless active bleeding or invasive procedure required.

Neurologic

• Sepsis-associated encephalopathy (SAE) occurs in >50% of patients; associated with increased mortality and long-term neuropsychiatric sequelae.
• Minimize sedation; use SAT (Spontaneous Awakening Trials) and SBT (Spontaneous Breathing Trials) daily.
• Avoid benzodiazepines where possible (delirium risk); prefer propofol or dexmedetomidine.
• If seizures suspected: EEG; if stroke: brain MRI/CT; if meningoencephalitis: lumbar puncture.

Glycemic Control

• Hyperglycemia is common; target blood glucose 140–180 mg/dL with insulin protocol.
• Avoid tight control (<110 mg/dL) — increases hypoglycemia and may increase mortality.
• Frequent glucose monitoring (q1–2h) during insulin infusion.

Gastrointestinal / Nutrition

• Initiate early enteral nutrition within 24–48 hours if hemodynamically stable.
• Parenteral nutrition if enteral route unavailable or contraindicated.
• Stress ulcer prophylaxis: PPI or H₂ blocker for high-risk patients (mechanical ventilation, coagulopathy).

VTE Prophylaxis

• Low-molecular-weight heparin (LMWH) preferred; unfractionated heparin if renal impairment.
• Mechanical prophylaxis (SCDs) if pharmacologic is contraindicated.

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8. De-escalation & Ongoing Monitoring

• Lactate trend (target clearance ≥10% per 2 hours, or normalization)
• Urine output, creatinine, BUN
• Hemodynamics, vasopressor weaning
• Ventilator parameters and oxygenation
• Blood cultures and procalcitonin trend
• Daily SOFA score

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9. Goals of Care

• Early family/surrogate communication regarding prognosis.
• Integrate palliative care principles — address patient and family suffering.
• Reassess goals of care if no clinical improvement despite maximal therapy.
• Document code status on admission to ICU.

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Quick Reference Summary

Hour 1:
  ✓ Lactate level
  ✓ Blood cultures × 2 (before antibiotics)
  ✓ Broad-spectrum antibiotics
  ✓ 30 mL/kg crystalloid bolus
  ✓ Norepinephrine if MAP <65 despite fluids

Ongoing:
  ✓ ICU admission ≤6 h
  ✓ Source control ASAP
  ✓ Lactate reassessment
  ✓ Daily antibiotic review → narrow 3–5 days
  ✓ Lung-protective ventilation if ARDS
  ✓ Steroids if vasopressor-refractory shock
  ✓ Glucose 140–180 mg/dL
  ✓ DVT + stress ulcer prophylaxis
  ✓ Daily SAT/SBT
  ✓ Goals of care discussion

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• Harrison's Principles of Internal Medicine 22E (2025) — Chapter 315: Initial Sepsis Management
• Goldman-Cecil Medicine — Corticosteroids, Renal Dysfunction in Sepsis
• Barash's Clinical Anesthesia 9E — Table 57-4: Management of Sepsis and Septic Shock
• Surviving Sepsis Campaign 2021 Guidelines
• Abdul-Aziz MH et al. JAMA 2024 — Prolonged vs Intermittent β-Lactam Infusions [PMID: 38864162]
• Pirracchio R et al. NEJM Evidence 2023 — Low-dose hydrocortisone in septic shock [PMID: 38320130]