ICU Sepsis Management Protocol

1. Recognition & Diagnosis

Sepsis-3 Definitions

Rapid Screening Tools

• qSOFA (≥2 points = high risk): RR ≥ 22/min, GCS < 15, SBP ≤ 100 mmHg
• Full SOFA score: recommended to confirm organ dysfunction in the ICU
• Other tools (NEWS, MEWS, AI-based TREWS) have not been preferentially endorsed by SSC — none outperforms another across all settings

Initial Workup (on suspicion of sepsis)

• Two sets of blood cultures (aerobic + anaerobic) before antibiotics if clinically feasible — do not delay antibiotics >45 min for cultures
• Culture relevant sites: urine, sputum, wound, BAL, CSF as indicated
• Serum lactate, CBC, BMP, LFTs, coagulation panel (PT/INR, fibrinogen)
• Point-of-care ultrasound (POCUS) to assess volume status, cardiac function, and potential source
• Imaging (CXR, CT abdomen/pelvis) to identify source — obtain promptly

2. The "1-Hour Bundle" (SSC Hour-1 Bundle)

1. Measure lactate; remeasure if initial > 2 mmol/L
2. Obtain blood cultures before antibiotics
3. Administer broad-spectrum antibiotics
4. Start 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L
5. Apply vasopressors if MAP < 65 mmHg during/after fluid resuscitation

ICU admission: Target within 6 hours of sepsis/septic shock diagnosis.

3. Antimicrobial Therapy

Timing

• Septic shock: empiric antibiotics within 1 hour of shock recognition — every 1-hour delay carries ~7–8% increased mortality
• Sepsis without shock: empiric antibiotics within 3 hours if no alternative diagnosis is established after clinical evaluation

Empiric Antibiotic Selection by Source

Antibiotic Optimization

• Obtain infectious disease and pharmacy consultation for pharmacokinetic/pharmacodynamic optimization
• Prolonged infusion of β-lactams: a 2024 JAMA meta-analysis (PMID 38864162) showed prolonged vs. intermittent β-lactam infusion significantly reduces 90-day mortality in sepsis/septic shock (NNT ~14)
• De-escalation: reassess at 48–72 h using culture results and clinical trajectory; narrow to targeted therapy
• Procalcitonin: do NOT use to initiate antibiotics; may be used to guide discontinuation when serial levels fall ≥ 80% from peak or to < 0.5 µg/L
• Antifungals: no routine empiric use; consider echinocandin (micafungin or caspofungin) in high-risk patients (recent abdominal surgery, TPN, liver failure, diabetes, multifocal Candida colonization)
• Antivirals: consider remdesivir (SARS-CoV-2) or oseltamivir (influenza) when relevant

Source Control

• Identify and control any anatomic source as rapidly as possible
• Drain abscesses, decompress biliary obstruction, resect necrotic tissue, remove infected catheters/implants
• Remove central venous catheters if infected or if endovascular infection (e.g., endocarditis) is suspected

4. Hemodynamic Resuscitation

Fluid Resuscitation

• Initial bolus: 30 mL/kg IV crystalloid within the first 3 hours
• Preferred fluid: balanced crystalloids (lactated Ringer's or Plasma-Lyte) over normal saline — reduces hyperchloremic acidosis and AKI
• Albumin 4–5%: consider as adjunct when large volumes of crystalloid are required (CHEST 2024 guideline, PMID 38447639)
• Avoid: hydroxyethyl starch (hetastarch) — increased AKI and mortality
• Reassess fluid responsiveness after each bolus using dynamic indicators (pulse pressure variation, stroke volume variation, passive leg raise test) or clinical improvement; stop escalating fluids when no further hemodynamic response
• Target: lactate clearance ≥ 10% every 2 hours; or lactate < 2 mmol/L

Vasopressors

• Target MAP ≥ 65 mmHg (higher targets, e.g. 80 mmHg, do not reduce mortality in most patients)
• Levosimendan and terlipressin are not recommended (SSC 2021)

Hemodynamic Monitoring

• Central venous catheter for vasopressor administration; radial arterial line for continuous MAP monitoring
• Consider advanced hemodynamic monitoring (PICCO, PAC, echocardiography) in refractory shock; routine PA catheter use is not recommended
• Serial POCUS to evaluate volume status and ventricular function

5. Corticosteroids

• Indication: persisting vasopressor-dependent shock despite adequate fluid resuscitation and vasopressor escalation
• Regimen: Hydrocortisone 200 mg/day IV continuous infusion or 50 mg IV q6h
• Do not use for sepsis without shock
• Taper corticosteroids once vasopressors are being weaned; abrupt discontinuation leads to rebound hemodynamic instability
• ACTH stimulation test is not recommended to guide use

6. Respiratory Support

Oxygen and Airway Management

• Provide supplemental O₂ to maintain SpO₂ ≥ 94% (90–96% target acceptable)
• High-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV/CPAP) for early hypoxemic respiratory failure before intubation when appropriate
• Intubate if GCS ≤ 8, refractory hypoxemia, or respiratory fatigue

Mechanical Ventilation for Sepsis-Induced ARDS

• Prone positioning: ≥ 12 hours/day for moderate-to-severe ARDS (P/F ratio < 150); significant mortality benefit
• Neuromuscular blockade (NMB): use to facilitate proning in moderate-to-severe ARDS; prefer intermittent bolus dosing over continuous infusion
• ECMO: consider veno-venous ECMO for severe ARDS failing mechanical ventilation in experienced centers
• Elevate head of bed to 30–45° semi-recumbent unless contraindicated
• Daily spontaneous breathing trials and sedation interruption to minimize ventilator days

7. Analgesia, Sedation & Delirium (PADIS Bundle)

• Analgesia-first: manage pain before sedation (fentanyl, morphine, hydromorphone; avoid high-dose opioids where possible)
• Sedation target: lightest effective level — target RASS −1 to 0 (alert or lightly sedated)
• Preferred sedatives: propofol or dexmedetomidine; avoid benzodiazepines (associated with more delirium and prolonged ventilation)
• Delirium screening: CAM-ICU or ICDSC every shift; address reversible causes (pain, sleep deprivation, hypoxia, urinary retention)
• Early mobilization: passive and active physiotherapy as soon as hemodynamically stable — reduces ICU-acquired weakness and delirium

8. Organ-Specific Support

Acute Kidney Injury (AKI)

• Avoid nephrotoxins (aminoglycosides, NSAIDs, contrast where possible)
• Maintain MAP ≥ 65 mmHg to preserve renal perfusion
• Renal replacement therapy (RRT): initiate for life-threatening indications — refractory hyperkalemia, metabolic acidosis (pH < 7.2 in AKI per Barash), volume overload, or uremia
• Bicarbonate for pH < 7.2 in the setting of AKI

Blood Products & Transfusion

• Red blood cells: transfuse at Hb < 7 g/dL threshold (< 9 g/dL if active coronary ischemia or hemorrhage)
• Platelet transfusion: if < 10,000/µL (prophylactic) or < 50,000/µL with active bleeding or procedure
• FFP: only for documented coagulopathy with active bleeding or prior to procedures

Blood Glucose Management

• Insulin infusion protocol when two consecutive glucose readings > 180 mg/dL
• Target glucose 140–180 mg/dL — avoid tight control (< 110 mg/dL) due to hypoglycemia risk
• Monitor glucose every 1–2 hours until stable on insulin infusion

Stress Ulcer Prophylaxis

• Proton pump inhibitor (PPI) or H₂-blocker in mechanically ventilated patients and those with coagulopathy
• Reassess daily; discontinue when enteral nutrition is tolerating and risk resolves

DVT Prophylaxis

• Low molecular weight heparin (enoxaparin) or unfractionated heparin unless contraindicated
• Mechanical compression devices if pharmacological prophylaxis contraindicated

Nutrition

• Initiate enteral nutrition within 24–48 hours of ICU admission when hemodynamically stable
• Avoid early parenteral nutrition in well-nourished patients
• Target caloric and protein goals per nutritional assessment

9. Antibiotic Stewardship & De-escalation

• Total antibiotic duration for most infections: 5–7 days if source controlled and clinical improvement; longer courses for endovascular infections, osteomyelitis, or undrained abscesses

10. Monitoring & Resuscitation Endpoints

11. Goals of Care

• Discuss goals of care and prognosis with the patient and family early, ideally within 72 hours of ICU admission
• Integrate palliative care principles — symptom management, family communication, advance directives
• Serial reassessment as clinical trajectory evolves
• For refractory septic shock with no reversible cause, consider comfort-focused care in discussion with the family

Key References

• Harrison's Principles of Internal Medicine 22E (2025, McGraw Hill) — Sepsis and Septic Shock management
• Barash, Cullen & Stoelting's Clinical Anesthesia 9e — Table 57-4 Management of Sepsis and Septic Shock
• Current Surgical Therapy 14e — Sepsis and Source Control
• Washington Manual of Medical Therapeutics — Adjunctive Therapies in Sepsis
• SSC 2021 Guidelines — Evans L et al., Intensive Care Med 2021 (the current standard of care framework)
• β-Lactam prolonged infusion: Abdul-Aziz MH et al., JAMA 2024 Aug — PMID 38864162 (Systematic review/meta-analysis: prolonged infusion reduces 90-day mortality)
• PADIS 2025 update: Lewis K et al., Crit Care Med 2025 — PMID 39982143
• S3 Sepsis Guideline Update 2025: Brunkhorst FM et al., Med Klin Intensivmed 2025 — PMID 40824313
• ESICM Circulatory Shock Guidelines 2025: Monnet X et al., Intensive Care Med 2025 — PMID 41236566

Disclaimer: This protocol is a clinical reference tool. All management decisions must be individualized based on the patient's clinical status, comorbidities, local antimicrobial resistance patterns, and institutional resources. Consult infectious disease, pulmonary/critical care, and pharmacy specialists as appropriate.