ICU Sepsis Management Protocol

1. Definitions (Sepsis-3)

2. Immediate Recognition and Triage

• Activate sepsis alert protocol upon qSOFA ≥ 2 or clinical suspicion
• Obtain IV access (peripheral or central venous catheter) immediately
• Target ICU admission within 6 hours of diagnosis in critically ill or shocked patients
• Obtain point-of-care lactate - if > 2 mmol/L, initiate full sepsis bundle

3. Diagnostic Workup (Before Antibiotics Where Possible)

• Two sets of blood cultures (aerobic + anaerobic) from separate sites
• Culture of any relevant site: urine, sputum, CSF, wound, drain fluid
• Cultures should not delay antibiotic administration by > 45 minutes

• CBC with differential, CMP (creatinine, bilirubin, electrolytes)
• Coagulation panel (PT, PTT, fibrinogen)
• Serum lactate (serial measurements every 2-4 h to guide resuscitation)
• Procalcitonin (baseline - do not use to decide when to START antibiotics; useful for de-escalation decisions)
• ABG, D-dimer, LFTs, lipase as clinically indicated

• Prompt chest X-ray (portable)
• CT chest/abdomen/pelvis, echocardiography, or ultrasound to identify infection source
• Prompt imaging is mandatory - do not delay source control workup

4. Antibiotic Therapy

Timing

• Septic shock: empiric antibiotics within 1 hour of shock recognition - every 1-hour delay increases mortality by ~7-8%
• Sepsis without shock: initiate within 3 hours if alternative diagnosis not identified; a time-limited clinical evaluation is appropriate when diagnosis is less certain

Empiric Selection (by scenario)

Antibiotic Optimization

• Administer beta-lactams before vancomycin when both indicated
• Consider prolonged/extended infusion of beta-lactams (3-4h infusion) to maximize time above MIC - a 2024 JAMA meta-analysis (PMID 38864162) demonstrated improved clinical outcomes with prolonged vs. intermittent beta-lactam infusion in sepsis/septic shock
• Pharmacokinetic/pharmacodynamic (PK/PD) optimization in consultation with pharmacy and infectious disease
• De-escalate based on culture and sensitivity results at 48-72 hours
• Use procalcitonin trends to guide antibiotic discontinuation (target < 0.5 ng/mL or > 80% decrease from peak)

5. Source Control

• Identify and control all sources amenable to intervention as soon as possible
• Common sources requiring intervention: intra-abdominal abscess, bowel perforation, cholangitis, pyelonephritis, necrotizing soft tissue infection
• Remove potentially infected indwelling devices (IV catheters, urinary catheters) promptly
• Surgical or percutaneous drainage preferred - choose least invasive effective approach
• If infected vascular access is the source: remove and replace at a new site

6. Fluid Resuscitation

Initial Resuscitation

• Crystalloid: 30 mL/kg IV within the first 3 hours (reassess frequently)
• Use balanced crystalloids (Lactated Ringer's, Plasmalyte) over normal saline where available - reduces hyperchloremic acidosis and AKI risk
• Do NOT use: hetastarch (HES) formulations - associated with renal failure and increased mortality

Albumin

• Consider adding albumin 4-5% when large volumes of crystalloid are required (evidence supports use as adjunct, not first-line)
• May be particularly beneficial in patients with hypoalbuminemia and hepatic dysfunction

Ongoing Fluid Assessment

• Assess volume responsiveness with dynamic measures: pulse pressure variation (PPV), stroke volume variation (SVV), passive leg raise test, point-of-care echo
• Continue fluid challenges only as long as hemodynamic improvement is demonstrated
• Avoid fluid overload - transition to conservative/neutral strategy once resuscitation complete
• Serial lactate measurements guide adequacy of resuscitation (target lactate normalization < 2 mmol/L)

7. Vasopressor and Inotropic Support

Step-Up Approach

• Norepinephrine 0.01-3 mcg/kg/min IV - titrate to MAP ≥ 65 mmHg
• Start via peripheral IV if central access not yet available; convert to central as soon as feasible

• Vasopressin 0.03 units/min IV (fixed dose) - do not titrate, do not use as sole agent
• Mechanism: V1 receptor agonism reverses vasodilation; may spare catecholamine dose and has renal-sparing effects

• Epinephrine 0.01-0.3 mcg/kg/min IV - add when hypotension persists despite norepinephrine + vasopressin
• Caution: tachyarrhythmia, myocardial ischemia, splanchnic hypoperfusion, metabolic acidosis at higher doses

• Add dobutamine 2-20 mcg/kg/min to norepinephrine, OR use epinephrine as sole agent
• Dobutamine: beta-1 inotropy + beta-2 vasodilation (reduces afterload)

• Dopamine as first-line - no survival benefit, increased arrhythmia risk; reserve for highly selected cases (e.g., profound bradycardia)
• Levosimendan and terlipressin - not recommended per current guidelines

8. Corticosteroids

• Do not use corticosteroids in patients who respond to fluid resuscitation and vasopressors
• ACTH stimulation testing is not recommended to guide initiation

9. Respiratory Support

Oxygenation Targets

• Maintain SpO2 92-95% with supplemental oxygen
• High-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) as bridge where appropriate, though NIV evidence is limited in shock

Mechanical Ventilation (when indicated)

• Intubate promptly when respiratory compensation for metabolic acidosis is failing or airway protection is needed

• Tidal volume: 6 mL/kg predicted body weight (range 4-8 mL/kg)
• Plateau pressure: ≤ 30 cmH2O
• PEEP: titrate to oxygenation using ARDSnet PEEP-FiO2 table or individualized titration
• Driving pressure (plateau - PEEP) target: < 15 cmH2O

• Prone positioning ≥ 12 hours/day - significant mortality benefit
• Neuromuscular blockade to facilitate proning (intermittent bolus preferred over continuous infusion)
• Consider venovenous ECMO if refractory to above measures at an experienced center

• Head of bed elevation to 30-45 degrees (semi-recumbent)
• Daily spontaneous awakening trial (SAT) + spontaneous breathing trial (SBT) to minimize ventilator days
• Avoid routine pulmonary artery catheter use in ARDS

10. Sedation and Analgesia (PADIS)

• Analgesia first (pain before sedation): fentanyl or morphine IV PRN/infusion
• Maintain lightest effective sedation - target RASS -1 to 0
• Preferred agents: propofol or dexmedetomidine for light sedation; avoid benzodiazepine infusions where possible
• Daily sedation interruption (SAT) unless contraindicated
• Screen daily for delirium using CAM-ICU or ICDSC
• Early mobilization as soon as hemodynamically stable

11. Blood Glucose Management

• Target blood glucose 140-180 mg/dL (7.8-10 mmol/L)
• Use insulin infusion protocol with frequent glucose monitoring
• Avoid hypoglycemia (< 70 mg/dL) - associated with increased mortality
• Avoid tight glycemic control (< 110 mg/dL) - not beneficial and increases hypoglycemia risk

12. Transfusion Thresholds

• Transfuse PRBCs when hemoglobin < 7 g/dL (target 7-9 g/dL)
• Do not transfuse to supranormal oxygen delivery targets
• Higher thresholds (Hgb < 8-9 g/dL) for: active coronary artery disease, acute hemorrhage, tissue hypoperfusion
• Platelets: transfuse if < 10,000/µL (prophylactic) or < 50,000/µL with active bleeding or procedures
• FFP: only for active bleeding with coagulopathy or pre-procedure with INR > 1.5-2.0

13. Renal Support

• Monitor urine output hourly (target ≥ 0.5 mL/kg/h)
• Avoid nephrotoxic agents (NSAIDs, IV contrast, aminoglycosides when alternatives available)
• Bicarbonate therapy for pH < 7.20 in the setting of acute kidney injury
• Renal Replacement Therapy (RRT): initiate for: severe acidosis not responding to treatment, refractory hyperkalemia, volume overload refractory to diuretics, uremia with AKI
• No proven benefit to early RRT initiation solely based on creatinine rise without complications

14. DVT and Stress Ulcer Prophylaxis

15. Glucose and Nutrition

• Initiate enteral nutrition within 24-48 hours of ICU admission when hemodynamically stable
• Avoid full caloric delivery in first 7 days (permissive underfeeding/trophic feeds) in early sepsis
• Reserve parenteral nutrition for patients with contraindication to enteral route
• Glycine target: 70-180 mg/dL (see glucose management above)

16. Goals of Care

• Discuss prognosis and goals of care with patient and family early and repeatedly
• Integrate palliative care principles - address pain, comfort, and values
• Code status discussion within 24 hours of ICU admission in critically ill patients
• Establish surrogate decision-maker if patient lacks capacity

17. De-escalation and Monitoring

Key Monitoring Parameters

Ongoing De-escalation

• Remove central venous and urinary catheters when no longer needed
• Wean vasopressors as hemodynamics stabilize
• De-escalate antibiotics to narrowest effective agent at 48-72h based on cultures
• Discontinue antibiotics when procalcitonin criteria met (typically 5-7 days for most infections; shorter courses increasingly supported)
• Early mobilization and physical therapy
• Screen for DVT, pressure injuries, ICU-acquired weakness

18. Long-Term Sequelae (Post-ICU)

• 50% of sepsis survivors are rehospitalized within 1 year; 1 in 6 die within the first year
• Discharge plan must include:
  • Screening for economic and social support needs
  • Follow-up for physical sequelae: fatigue, muscle loss, diminished functional capacity
  • Follow-up for cognitive sequelae: cognitive decline, PTSD, depression
  • Cardiovascular risk monitoring (MI, stroke risk elevated post-sepsis)

Key References

• Evans L, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 49:e1063, 2021
• Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 315:801, 2016
• Abdul-Aziz MH, et al. Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock. JAMA. 2024 Aug 27. [PMID: 38864162]
• Brunkhorst FM, et al. S3 Guideline on Sepsis - Prevention, Diagnosis, Therapy, and Follow-up Care - Update 2025. Med Klin Intensivmed Notfmed. 2025. [PMID: 40824313]
• Lewis K, et al. Focused Update to the PADIS Clinical Practice Guidelines. Crit Care Med. 2025. [PMID: 39982143]
• Harrison's Principles of Internal Medicine, 22e (2025), McGraw Hill
• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e
• Goldman-Cecil Medicine, International Edition

Disclaimer: This protocol is for educational and reference purposes. All clinical decisions must be individualized based on patient-specific factors, local antimicrobial resistance patterns, institutional resources, and the judgment of the treating clinician.