What are the current guidelines for managing sepsis?

Current Sepsis Management Guidelines

Sepsis and septic shock are medical emergencies requiring immediate treatment within the first hour of recognition, with the most critical intervention being administration of IV antimicrobials within 60 minutes, as each hour of delay decreases survival by approximately 7.6%. 1, 2

Immediate Recognition and Initial Actions (Hour-1 Bundle)

The following five actions must be completed within the first hour of sepsis recognition:

1. Measure Lactate Immediately

• Obtain serum lactate as a marker of tissue hypoperfusion 3, 1, 4
• Remeasure within 2-4 hours if initially elevated (≥2 mmol/L) 2
• Target lactate normalization as a resuscitation endpoint 3, 1

2. Obtain Blood Cultures Before Antibiotics

• Draw at least two sets (aerobic and anaerobic bottles) before antimicrobial administration 1, 4, 2
• Never delay antibiotics beyond 45 minutes if cultures cannot be obtained quickly 2

3. Administer Broad-Spectrum Antimicrobials Within 60 Minutes

• Give IV antibiotics within one hour of sepsis recognition 1, 4, 2
• Use empiric broad-spectrum therapy covering all likely pathogens with adequate tissue penetration to the presumed infection source 1, 4
• For septic shock, consider combination therapy with ≥2 antibiotics from different classes, particularly for Pseudomonas aeruginosa infections 1
• Limit combination therapy to 3-5 days maximum, then de-escalate to single-agent therapy once susceptibility profiles are known 1
• If IV access is delayed in children, give first doses intramuscularly, orally, or rectally 2

4. Aggressive Fluid Resuscitation

• Administer at least 30 mL/kg IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion 3, 1, 4
• Use crystalloids (either balanced crystalloids or normal saline) as the initial fluid of choice 4, 2
• Give 20 mL/kg boluses over 5-10 minutes in children, titrated to reverse hypotension and restore perfusion 1
• Continue fluid administration as long as hemodynamic factors improve based on dynamic variables (pulse pressure variation, stroke volume variation) or static variables (arterial pressure, heart rate, capillary refill, skin mottling) 2
• Consider albumin when patients require substantial amounts of crystalloids 2
• Never use hydroxyethyl starches—they are contraindicated in sepsis 2

5. Initiate Vasopressors for Persistent Hypotension

• Start vasopressors if hypotension persists despite adequate fluid resuscitation 2
• Use norepinephrine as the first-choice vasopressor 1, 4, 2
• Target mean arterial pressure (MAP) ≥65 mmHg 3, 1, 4, 2
• Add vasopressin as second-line agent if hypotension persists, followed by epinephrine 1, 4

Hemodynamic Monitoring and Reassessment

After initial resuscitation, frequent reassessment is essential:

• Use dynamic over static variables to predict fluid responsiveness where available 3
• Reassess heart rate, blood pressure, arterial oxygen saturation, respiratory rate, temperature, urine output (target ≥0.5 mL/kg/hour), capillary refill, skin temperature, mental status, and lactate clearance 3, 1, 2
• Stop fluid resuscitation if no improvement in tissue perfusion occurs or if signs of fluid overload develop 1
• Perform hemodynamic assessment (such as assessing cardiac function) if clinical examination does not lead to a clear diagnosis 3
• Administer positive inotropes when cardiac failure persists (low cardiac index and mixed venous oxygen saturation) despite adequate volume expansion—this occurs in 10-20% of adult sepsis cases 2

Source Control

Identify the anatomic source of infection and implement source control intervention as soon as medically and logistically practical, ideally within 12 hours of diagnosis. 1, 4, 2

• Perform imaging studies promptly to confirm potential infection sources 1, 4
• Use the least physiologically invasive effective intervention (e.g., percutaneous drainage rather than surgical drainage of an abscess) 4, 2
• Remove intravascular access devices promptly after establishing alternative vascular access if they are a possible infection source 2

Corticosteroid Therapy

• Consider IV hydrocortisone only for patients with septic shock unresponsive to fluid resuscitation and vasopressor therapy 1, 4, 2
• Avoid corticosteroids for sepsis without shock 4

Blood Product Management

• Transfuse red blood cells only when hemoglobin decreases to <7.0 g/dL in the absence of extenuating circumstances 1, 4
• Target hemoglobin 7-9 g/dL (or 8-9 g/dL for acute anemia, adjusting based on clinical tolerance and central venous oxygen saturation) 1, 2
• Avoid erythropoietin for treating sepsis-associated anemia 4

Mechanical Ventilation for Sepsis-Induced ARDS

• Administer oxygen to achieve saturation ≥90% and position patients semi-recumbent or laterally 2
• Use non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy 2
• Use low tidal volume ventilation at 6 mL/kg predicted body weight 1, 4, 2
• Limit plateau pressures to ≤30 cm H₂O 1, 4, 2
• Apply higher PEEP in patients with moderate to severe ARDS 1, 4

Metabolic Management

• Target blood glucose ≤180 mg/dL using a protocolized approach 1
• Avoid hypoglycemia 3

Nutrition

• Initiate early enteral nutrition rather than complete fasting or IV glucose alone 1, 4
• Consider either early trophic/hypocaloric or early full enteral feeding 1, 4
• Resume oral food intake after resuscitation and regaining of consciousness 2
• Advance enteral feeds according to patient tolerance, and consider prokinetic agents in patients with feeding intolerance 1
• Do not use omega-3 fatty acids as an immune supplement, do not use IV selenium, do not use glutamine, and avoid arginine 1

Antimicrobial De-escalation and Duration

• Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available 2
• Narrow antimicrobial therapy once pathogen identification and sensitivities are established and/or clinical improvement is noted 4
• Use procalcitonin levels to support shortening antimicrobial duration or discontinuing empiric antibiotics in patients with limited clinical evidence of infection 2
• Optimize dosing strategies based on pharmacokinetic/pharmacodynamic principles 4

Additional Supportive Care

• Provide pharmacological or mechanical deep vein thrombosis prophylaxis 2
• Initiate early mobilization and active weaning of invasive support 2
• Use careful dosing of opioids and sedatives 3

Performance Improvement and Screening

• Implement hospital-wide sepsis screening programs for acutely ill, high-risk patients 1, 4
• Establish multidisciplinary teams including physicians, nurses, pharmacy, and respiratory therapy 1

Goals of Care

• Discuss goals of care and prognosis with patients and families, ideally within 72 hours of ICU admission 1, 4
• Incorporate palliative care principles into treatment planning when appropriate 1, 4

Common Pitfalls to Avoid

The most critical error is delaying antimicrobial administration—each hour of delay decreases survival by approximately 7.6%, making this the single most important modifiable factor affecting mortality. 1, 2

Other key pitfalls include:

• Inadequate initial fluid resuscitation (failing to give the full 30 mL/kg bolus within 3 hours) 3
• Excessive fluid administration without proper reassessment for signs of fluid overload 1
• Using hydroxyethyl starches, which are contraindicated 2
• Delaying source control interventions beyond 12 hours when feasible 1, 4, 2
• Failing to de-escalate antibiotics once culture results are available 2
• Inappropriate use of vasopressors without adequate fluid resuscitation first 2
• Overlooking the importance of early enteral nutrition 1, 4
• Neglecting to discuss goals of care with patients and families 1, 4