What are the guidelines for managing sepsis?

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Last updated: November 2, 2025View editorial policy

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Sepsis Management Guidelines

Immediate Recognition and Initial Actions

Sepsis and septic shock are medical emergencies requiring immediate treatment initiation within one hour of recognition. 1, 2, 3

First Hour Bundle (Critical)

  • Administer IV antimicrobials within 60 minutes of recognizing sepsis or septic shock—this is the single most important intervention for reducing mortality 1, 2, 3
  • Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but do not delay antimicrobials beyond 45 minutes if cultures cannot be obtained 1, 2
    • Draw one set percutaneously and one through each vascular access device (if device >48 hours old) 1
  • Measure serum lactate as a marker of tissue hypoperfusion 1, 2
  • Administer 30 mL/kg IV crystalloid fluids within the first 3 hours for sepsis-induced hypoperfusion (hypotension or lactate ≥4 mmol/L) 1, 2, 3

Antimicrobial Therapy Strategy

Initial Empiric Coverage

  • Use broad-spectrum therapy covering all likely pathogens (bacterial, fungal, viral) with adequate tissue penetration to the presumed infection source 1, 3
  • Consider combination therapy (≥2 antibiotics from different classes) for septic shock, particularly for:
    • Pseudomonas aeruginosa infections (extended-spectrum β-lactam + aminoglycoside or fluoroquinolone) 1
    • Bacteremic Streptococcus pneumoniae with shock (β-lactam + macrolide) 1
    • Multidrug-resistant pathogens (Acinetobacter, Pseudomonas species) 1

Critical caveat: Do NOT use routine combination therapy for neutropenic sepsis/bacteremia—this recommendation changed from 2012 guidelines 1

De-escalation and Duration

  • Reassess antimicrobial therapy daily for potential narrowing once pathogen identification and sensitivities are available 1, 2, 3
  • Discontinue combination therapy within 3-5 days and transition to single-agent therapy based on susceptibility profiles 1
  • Target 7-10 days total duration for most infections 1
    • Longer courses warranted for: slow clinical response, undrainable infection foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiency/neutropenia 1
  • Use procalcitonin levels to assist in discontinuing empiric antibiotics in patients without confirmed infection 1

Hemodynamic Resuscitation

Fluid Management

  • Reassess hemodynamic status frequently after initial 30 mL/kg bolus using thorough clinical examination (heart rate, blood pressure, capillary refill, urine output, mental status) 1
  • Use dynamic variables over static variables to predict fluid responsiveness when available 1
  • Avoid excessive fluid administration—the approach has shifted away from aggressive volume loading seen in early goal-directed therapy 4

Vasopressor Support

  • Target mean arterial pressure (MAP) ≥65 mmHg in patients requiring vasopressors 1, 2, 3
  • Use norepinephrine as first-choice vasopressor 2
  • Consider vasopressin (0.01-0.07 units/minute for septic shock) as adjunctive therapy 1, 5
  • Administer hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) for patients requiring escalating vasopressor doses 2

Important shift: Peripheral vasopressor use is now considered safe, reducing need for immediate central access 4

Source Control

  • Implement source control interventions as soon as possible after diagnosis 2, 3
  • Drain or debride infected tissues and remove potentially infected foreign bodies/devices 2
  • Perform imaging studies promptly to confirm infection source 1, 3

Respiratory Support

  • Apply oxygen to achieve saturation >90% 2
  • Position patients semi-recumbent (head of bed 30-45°) to reduce aspiration risk 2, 3
  • Use low tidal volume ventilation (6 mL/kg predicted body weight) for sepsis-induced ARDS 2, 3

Metabolic and Supportive Care

  • Target blood glucose ≤180 mg/dL using protocolized approach 2, 3
  • Target hemoglobin 7-9 g/dL in absence of tissue hypoperfusion, coronary disease, or acute hemorrhage 2
  • Minimize continuous sedation in mechanically ventilated patients 3

Performance Improvement

  • Implement hospital-wide sepsis screening programs for acutely ill, high-risk patients 1, 2
  • Establish multidisciplinary teams including physicians, nurses, pharmacy, and respiratory therapy 2
  • Use sepsis bundles and protocols with regular education and performance feedback 2

Goals of Care

  • Discuss goals of care and prognosis with patients and families, ideally within 72 hours of ICU admission 1
  • Incorporate palliative care principles into treatment planning when appropriate 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Sepsis Management Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Sepsis Management Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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