Latest Sepsis Management Guidelines (2025)
The latest guidelines for sepsis management recommend immediate administration of broad-spectrum antibiotics within 1 hour of recognition, at least 30 mL/kg of crystalloid fluid resuscitation within the first 3 hours, and norepinephrine as the first-choice vasopressor targeting a mean arterial pressure (MAP) of 65 mmHg. 1
Initial Resuscitation and Antimicrobial Therapy
Antimicrobial Management
- Administer broad-spectrum antibiotics within 1 hour of sepsis recognition 1, 2
- Obtain blood cultures before starting antibiotics 1
- Cover all likely pathogens (bacterial, potentially fungal or viral) 1, 2
- Consider empiric combination therapy with at least two antibiotics of different classes for septic shock 1
- De-escalate therapy within the first few days based on:
- Typical duration of antibiotic therapy is 7-10 days 3, 4
- Longer duration may be needed for slow response, inadequate source control, or immunologic deficiencies
Fluid Resuscitation
- Administer at least 30 mL/kg of IV crystalloids within the first 3 hours 1
- Use balanced crystalloids instead of 0.9% saline to reduce adverse renal events 1
- Limit total crystalloid volume to 2.6 L to reduce risk of exacerbating heart failure 1
- Continue fluid administration as long as hemodynamic factors improve 1
- Monitor for signs of improved perfusion after each fluid bolus:
- Reversal of hypotension
- Improved urinary output (>0.5 mL/kg/hour)
- Normalization of capillary refill
- Decrease in serum lactate 1
Vasopressor Support
First-Line Therapy
- Norepinephrine is the first-choice vasopressor (grade 1B recommendation) 1
- Target a MAP of 65 mmHg 1
- Individualize MAP targets for patients with pre-existing hypertension 1
Additional Vasopressor Support
- If additional support needed, consider adding:
- Epinephrine dosing: 0.05 mcg/kg/min to 2 mcg/kg/min, titrated to achieve desired MAP 5
- Reserve phenylephrine for specific situations (e.g., norepinephrine-associated arrhythmias) 1
- Consider ECMO for refractory septic shock 1
Source Control and Monitoring
Source Control
- Implement source control intervention within 12 hours of diagnosis 1
- Promptly remove intravascular access devices that are possible infection sources 1
Ongoing Monitoring
- Reassess for ongoing hypovolemia in cases of persistent hypotension despite high vasopressor doses 1
- Reevaluate antimicrobial therapy daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs 2, 3, 4
Additional Supportive Measures
Blood Transfusion
- Target hemoglobin levels of 10 g/dL during resuscitation of low ScvO2 shock (<70%) 1
- Lower target of <7.0 g/dL after stabilization 1
Corticosteroids
- Consider IV hydrocortisone (200 mg/day) only if adequate fluid resuscitation and vasopressor therapy cannot restore hemodynamic stability 1
- Taper hydrocortisone when vasopressors are no longer required 1
Nutrition
- Initiate early enteral nutrition rather than parenteral nutrition 1
- Provide adequate nutritional support (20-30 kcal/kg/day) 1
- Target upper blood glucose level ≤180 mg/dL 1
Common Pitfalls and Caveats
Delayed antibiotic administration: While the 1-hour window is recommended, this should not compromise appropriate diagnostic workup in patients with uncertain diagnosis 6
Excessive fluid administration: Monitor closely for signs of fluid overload, especially in patients with cardiac or renal dysfunction 1
Failure to de-escalate antibiotics: Continuing broad-spectrum antibiotics unnecessarily increases risk of resistance, toxicity, and costs 2, 3, 4
Inadequate source control: Failure to identify and control the infection source can lead to persistent sepsis despite appropriate antimicrobial therapy 1
Goals of care discussions: Address goals of care early, within 72 hours of ICU admission, and incorporate into treatment planning 1