Management of Sepsis
The cornerstone of sepsis management is early recognition, prompt administration of broad-spectrum antimicrobials within one hour of recognition, and appropriate source control to reduce mortality and morbidity. 1, 2
Initial Management
Immediate Actions (First Hour)
- Obtain appropriate cultures before starting antibiotics (at least 2 sets of blood cultures), but do not delay antimicrobial therapy beyond 45 minutes 1, 2
- Administer IV antimicrobials within one hour of recognizing sepsis or septic shock 1, 2
- Begin fluid resuscitation with 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L 1
- Target initial mean arterial pressure (MAP) of 65 mmHg in patients requiring vasopressors 1
Antimicrobial Therapy
Use empiric broad-spectrum therapy covering all likely pathogens based on:
Recommended empiric regimens:
- For most patients: Extended-spectrum β-lactam (meropenem 1-2g IV q8h or piperacillin-tazobactam 3.375-4.5g IV q8h) 2, 3
- For septic shock: Consider combination therapy with two antibiotics of different classes 1, 2
- For Pseudomonas risk: Extended-spectrum β-lactam plus either aminoglycoside or fluoroquinolone 1, 2
- For S. pneumoniae bacteremia with shock: β-lactam plus macrolide 1, 2
Source Control
- Identify infection source through prompt imaging studies 1
- Implement source control measures within 12 hours when possible 2
- Choose least physiologically disruptive intervention (e.g., percutaneous rather than surgical drainage) 2
- Remove infected devices (e.g., vascular catheters, urinary catheters) 2
Ongoing Management
Antimicrobial Stewardship
- Reassess antimicrobial regimen daily for potential de-escalation 1, 2
- Narrow therapy once pathogen identification and sensitivities are established 1, 2
- Limit combination therapy to no more than 3-5 days 1, 2
- Standard duration of therapy is typically 7-10 days 1, 2
- Consider longer courses for:
Supportive Care
- Implement protocolized blood glucose management targeting upper level ≤180 mg/dL 1
- Provide venous thromboembolism prophylaxis with pharmacologic agents (LMWH preferred over UFH) 1
- Use mechanical ventilation with low tidal volumes (6 mL/kg) for sepsis-induced ARDS 1
- Consider prone positioning for severe ARDS (PaO2/FiO2 <150) 1
- Minimize continuous or intermittent sedation in mechanically ventilated patients 1
- Consider renal replacement therapy for acute kidney injury, especially to facilitate fluid management in hemodynamically unstable patients 1
Common Pitfalls to Avoid
- Delayed antimicrobial administration beyond one hour of sepsis recognition significantly increases mortality 2, 4
- Inadequate source control leads to persistent infection and poor outcomes 2
- Inappropriate antimicrobial spectrum that fails to cover likely pathogens 2, 5
- Dose reduction of antibiotics due to concerns about renal dysfunction can worsen outcomes in septic shock 3
- Failure to de-escalate broad-spectrum therapy once culture results are available 2, 5
- Inadequate monitoring and failure to reassess antibiotic regimen daily 2
Special Considerations
- Neutropenic patients and those with multidrug-resistant pathogens benefit from combination empiric therapy 1
- Biomarkers like procalcitonin may help identify patients with low likelihood of infection and guide duration of therapy 4
- Pharmacokinetic/pharmacodynamic principles should guide antimicrobial dosing, especially in critical illness 5
- Extended or continuous infusion of β-lactams may help achieve therapeutic levels 5
- Higher antimicrobial doses may be needed in septic shock due to increased volume of distribution and augmented renal clearance 3
By following these evidence-based guidelines for sepsis management, focusing on early recognition, prompt antimicrobial therapy, source control, and appropriate supportive care, clinicians can significantly improve patient outcomes and reduce mortality.