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Sepsis ICU Management Protocol

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1. Definition & Recognition (Sepsis-3)

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2. Immediate Actions: The "1-Hour Bundle"

In septic shock: initiate all of the following within 1 hour of recognition.

1. Draw blood cultures (≥2 sets, aerobic + anaerobic) before giving antibiotics
2. Measure serum lactate — if >2 mmol/L, remeasure within 2 hours
3. Administer IV broad-spectrum antibiotics — immediately, ideally ≤1 hour of recognition (every 1-hour delay in appropriate antibiotics is associated with an estimated 7–8% increase in mortality)
4. Begin IV fluid resuscitation: 30 mL/kg balanced crystalloid bolus within 3 hours
5. Start vasopressors if MAP remains <65 mmHg after initial fluid

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3. Hemodynamic Resuscitation & Monitoring

3a. Fluid Resuscitation

• Initial: 30 mL/kg IV balanced crystalloid (Lactated Ringer's preferred over normal saline) within 3 hours
• Subsequent: reassess with dynamic measures of fluid responsiveness — passive leg raise, pulse pressure variation, stroke volume variation, or echocardiography
• Albumin: consider adding when large volumes of crystalloid are required (recent 2024 meta-analysis [PMID 39969316] supports albumin in volume-refractory shock)
• Avoid: hydroxyethyl starch (hetastarch) — associated with increased AKI and mortality
• Reassessment targets: lactate clearance, UO ≥0.5 mL/kg/hr, MAP ≥65 mmHg

3b. Vasopressors

• Levosimendan and terlipressin: not recommended
• Invasive arterial monitoring: strongly recommended once vasopressors are started
• Target MAP: ≥65 mmHg (higher targets 70–80 mmHg may be considered in chronic hypertensives)

3c. Monitoring

• Invasive arterial line for continuous BP and arterial blood gas sampling
• Central venous catheter (consider for vasopressor administration and CVP monitoring)
• Echocardiography for assessment of cardiac function and volume status
• Serial serum lactate every 2 hours until normalizing (<2 mmol/L)
• Urinary catheter with hourly UO measurement
• Pulmonary artery catheter in select cases of mixed septic-cardiogenic shock

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4. Antimicrobial Therapy

4a. General Principles

• Culture before antibiotics (blood × 2, urine, sputum/BAL as indicated) — do not delay antibiotics >45 minutes for cultures
• Select empiric antibiotics based on: site of infection, community vs. healthcare exposure, local resistance patterns, prior culture results, and immune status
• De-escalate or narrow spectrum within 48–72 hours based on culture and sensitivity results
• Procalcitonin: do not use to decide when to start antibiotics, but can guide when to stop (level <0.5 µg/L with clinical improvement supports discontinuation)
• Duration: typically 7 days for most infections; shorter courses acceptable for uncomplicated sources with good clinical response

4b. Empiric Antibiotic Selection by Site

4c. Special Situations

• MRSA risk: add vancomycin (target trough 15–20 mg/L or AUC/MIC 400–600) or linezolid
• Suspected fungal (recent abdominal surgery, TPN, liver failure, multi-site Candida colonization): empiric echinocandin (micafungin 100 mg/day or caspofungin)
• SARS-CoV-2 sepsis: add remdesivir; dexamethasone 6 mg IV/PO daily reduces mortality in patients requiring O₂
• Influenza sepsis: oseltamivir 75 mg BID
• β-lactam administration: prolonged infusion strategy (extended/continuous infusion after initial bolus) is associated with improved survival over intermittent dosing, especially for Pseudomonas (JAMA 2024 meta-analysis [PMID 38864162])

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5. Source Control

• Identify and eliminate the source of infection as rapidly as feasible
• Examples requiring urgent intervention: intra-abdominal abscess (percutaneous/surgical drainage), bowel perforation (surgery), pyelonephritis (ureteral stenting if obstructed), cholangitis (ERCP), necrotizing fasciitis (surgical debridement), infected catheter/device (removal)
• Indwelling catheter: remove any vascular catheter that appears to be infected (erythema, purulence); replace at a new site rather than over a wire in confirmed catheter-related bloodstream infection
• Source control should precede or occur concurrent with antibiotic administration where possible

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6. Organ Support

6a. Respiratory

• Avoid: routine pulmonary artery catheter in ALI/ARDS
• HOB elevation 30–45° (semi-recumbent) to reduce VAP risk
• Daily sedation interruption + spontaneous breathing trials
• Conservative fluid strategy once hemodynamics are stabilized

6b. Corticosteroids

• Indication: septic shock with ongoing vasopressor requirement despite adequate fluid resuscitation
• Regimen: Hydrocortisone 200 mg/day IV (50 mg q6h or continuous infusion at 200 mg/24h)
• Optional addition: fludrocortisone 50 µg/day via nasogastric tube for 7 days — may improve 90-day all-cause mortality (APROCCHSS trial data)
• Stop once vasopressors are discontinued
• Do not use corticosteroids if hemodynamic stability is restored with fluids and vasopressors alone
• Caution: risk of superinfection, hyperglycemia, ICU-acquired neuromyopathy

6c. Renal

• Maintain adequate renal perfusion (MAP ≥65 mmHg)
• Avoid nephrotoxic agents (aminoglycosides, NSAIDs, IV contrast where possible)
• Renal replacement therapy (RRT): indicated for progressive AKI with hyperkalemia, metabolic acidosis, uremia, or refractory volume overload
• CRRT preferred over intermittent hemodialysis in hemodynamically unstable patients
• Timing: standard/clinical criteria-based initiation — no mortality benefit shown with early initiation in RCTs
• Sodium bicarbonate: consider if pH <7.2 in the setting of AKI (not for lactic acidosis alone — no hemodynamic benefit)
• Low-dose dopamine: not recommended for renal protection

6d. Hematologic / Transfusion

• RBC transfusion threshold: Hgb <7 g/dL (restrictive strategy), except in patients with active coronary artery disease, acute hemorrhage, or evidence of tissue hypoperfusion (target Hgb 7–9 g/dL)
• Platelet transfusion: consider if <10,000/µL (prophylactic) or <20,000/µL with bleeding risk; <50,000/µL if active bleeding or planned procedure
• DIC: treat underlying sepsis; FFP/cryoprecipitate for active bleeding

6e. Glycemic Control

• Target glucose: 140–180 mg/dL (7.8–10 mmol/L)
• Initiate insulin infusion when glucose ≥180 mg/dL
• Avoid tight glycemic control (glucose 81–108 mg/dL) — increases hypoglycemia and may increase mortality
• Check glucose every 1–2 hours when on insulin infusion

6f. Neurologic

• Use light sedation protocols targeting RASS –1 to 0; avoid deep sedation unless indicated
• Analgesia-first approach: treat pain before sedation
• Assess for delirium daily using CAM-ICU or CPOT
• Minimize benzodiazepines (associated with increased delirium)
• Early mobilization as tolerated

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7. Supportive & Preventive Care

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8. Organ-Specific Complications: Summary Table

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9. ICU Admission & Stepdown

• Target ICU admission within 6 hours of recognition for patients requiring vasopressors or mechanical ventilation
• Reassess necessity of all invasive lines, catheters, and drains daily — remove when no longer required
• Antibiotics: reassess at 48–72 hours; de-escalate based on culture results and clinical trajectory
• Transition from vasopressors: wean when MAP is stable; reassess fluid balance; consider diuresis once hemodynamics permit

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10. Post-ICU & Survivorship

• Physical: fatigue, ICU-acquired weakness, functional decline
• Cognitive: delirium, cognitive impairment, dementia
• Psychological: PTSD, depression, anxiety

• Screening for economic and social support needs
• Structured follow-up (4–8 weeks) to assess physical, cognitive, and psychological recovery
• Rehabilitation referral as appropriate
• Clear communication of diagnosis with patient and family (many patients leave ICU unaware they had sepsis)

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Quick Reference: Sepsis Hour-1 Bundle Checklist

□  Blood cultures ×2 before antibiotics
□  Serum lactate (remeasure if >2 mmol/L)
□  Broad-spectrum IV antibiotics within 1 hour
□  30 mL/kg IV balanced crystalloid bolus (within 3 hours)
□  Vasopressors for MAP <65 mmHg despite fluids (norepinephrine first)
□  ICU admission within 6 hours
□  Source control: identify and plan intervention
□  Daily: reassess antibiotics, remove unnecessary lines, glycemic control, VTE/GI prophylaxis, sedation/analgesia, nutrition

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• Harrison's Principles of Internal Medicine 22E (2025) — Chapter 315, Sepsis Management
• Barash, Cullen & Stoelting's Clinical Anesthesia 9e — Table 57-4, Management of Sepsis and Septic Shock
• Goldman-Cecil Medicine — Chapter 94, Septic Shock
• Evans L et al. Surviving Sepsis Campaign: International Guidelines 2021. Crit Care Med 49:e1063, 2021
• Abdul-Aziz MH et al. Prolonged vs Intermittent β-Lactam Infusions in Sepsis. JAMA 2024 [PMID 38864162]
• Bai Z et al. Human albumin for adults with sepsis. Medicine (Baltimore) 2024 [PMID 39969316]