Initial Management of Sepsis
The initial management of sepsis requires immediate administration of broad-spectrum antibiotics within 1 hour of recognition, along with at least 30 mL/kg of IV crystalloids within the first 3 hours, followed by vasopressor therapy if fluid resuscitation is inadequate to restore perfusion. 1
Immediate Interventions
Fluid Resuscitation
- Administer at least 30 mL/kg of IV crystalloids within the first 3 hours 1
- Use crystalloids (balanced crystalloids or saline) as the fluid of choice for initial resuscitation 1
- Avoid hydroxyethyl starches due to potential harm 1
- Implement frequent reassessment of hemodynamic status to guide ongoing fluid therapy 1
Antibiotic Therapy
- Obtain blood cultures before starting antibiotics (if no substantial delay) 1
- Administer broad-spectrum antibiotics within 1 hour of recognition of sepsis 1, 2
- Cover gram-positive, gram-negative, and anaerobic organisms based on suspected source 1, 3
- Consider previous risk of multidrug-resistant (MDR) pathogens when selecting antibiotics 2
Hemodynamic Support
Vasopressor Therapy
- Begin norepinephrine as first-choice vasopressor if fluid resuscitation is inadequate 1
- Target a mean arterial pressure (MAP) of 65 mmHg 1
- Consider adding vasopressin (0.03 units/minute) to improve blood pressure or decrease norepinephrine requirements 1
- For refractory shock, consider adding epinephrine as an additional agent 1
Monitoring Tissue Perfusion
Monitor for signs of adequate tissue perfusion:
- Normal capillary refill time
- Absence of skin mottling
- Warm and dry extremities
- Well-felt peripheral pulses
- Return to baseline mental status
- Urine output >0.5 mL/kg/hour in adults 1
Source Control
- Identify source of infection as rapidly as possible 1
- Implement source control interventions as soon as practical 1
Ongoing Management
Antibiotic Stewardship
- Reassess antibiotic therapy daily for potential de-escalation 1, 2
- De-escalate antibiotics once culture results are available (typically within 3-5 days) 2, 4, 3
- Limit antibiotic duration typically to 7-10 days unless response is slow or source control is inadequate 4, 5
Supportive Care
- Use lung-protective ventilation strategies for sepsis-induced ARDS (tidal volume of 6 mL/kg) 1
- Provide stress ulcer prophylaxis for patients with risk factors 1
- Maintain glucose levels between 110-149 mg/dL (6.1-8.3 mmol/L) 1
- Provide adequate nutritional support (20-30 kcal/kg/day) 1
Phases of Fluid Therapy
- Resuscitation phase: Rapid fluid administration to restore perfusion
- Optimization phase: Carefully evaluate risks and benefits of additional fluids
- Stabilization phase: Administer fluid only when there is evidence of fluid responsiveness
- Evacuation phase: Implement conservative fluid strategy to prevent fluid overload 1
Common Pitfalls and Caveats
- Delay in antibiotic administration: The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started 3
- Fluid overload: Target fluid removal to prevent >10% total body weight fluid overload 1
- Antibiotic overuse: While immediate antibiotics are crucial, be aware that some patients initially diagnosed with sepsis may have non-infectious conditions 6
- Inadequate source control: Failure to identify and address the infection source can lead to treatment failure despite appropriate antibiotics 4, 5
- Standard dosing vs. individualized dosing: Consider individualized antibiotic dosing according to pharmacokinetics/pharmacodynamics and organ dysfunction 2
Special Considerations
- For sepsis patients with heart failure, the same initial fluid resuscitation (30 mL/kg) is still recommended, but with more careful monitoring 1
- Consider continuous renal replacement therapy (CRRT) promptly for anuric AKI with fluid overload 1
- CRRT is preferred over intermittent hemodialysis in hemodynamically unstable patients 1
- Consider combination therapy for Pseudomonas infections and in neutropenic patients 4, 5