What are the treatment guidelines for severe sepsis?

Treatment Guidelines for Severe Sepsis

The management of severe sepsis requires immediate implementation of a protocolized approach focusing on early resuscitation, prompt antimicrobial therapy, source control, and supportive care to reduce mortality and improve outcomes. 1

Initial Resuscitation (First 6 Hours)

• Implement protocolized, quantitative resuscitation as soon as tissue hypoperfusion is recognized (defined as hypotension persisting after initial fluid challenge or blood lactate ≥4 mmol/L) 1
• Target the following resuscitation goals:
  • Central venous pressure (CVP): 8-12 mmHg 1
  • Mean arterial pressure (MAP): ≥65 mmHg 1
  • Urine output: ≥0.5 mL/kg/hr 1
  • Central venous oxygen saturation (ScvO2): ≥70% or mixed venous oxygen saturation (SvO2): ≥65% 1
• Target normalization of lactate levels in patients with elevated lactate 1

Early Diagnosis

• Perform routine screening of potentially infected seriously ill patients for severe sepsis to enable earlier intervention 1
• Obtain appropriate cultures before starting antimicrobial therapy if no significant delay (<45 min) will occur 1
• Collect at least 2 sets of blood cultures (both aerobic and anaerobic bottles) with at least 1 drawn percutaneously and 1 through each vascular access device (unless inserted <48 hours prior) 1
• Consider 1,3 β-D-glucan assay, mannan and anti-mannan antibody assays when invasive candidiasis is in the differential diagnosis 1
• Perform prompt imaging studies to identify potential sources of infection 1

Antimicrobial Therapy

• Administer effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) 1
• Use initial empiric anti-infective therapy with one or more drugs active against all likely pathogens and that penetrate adequately into presumed infection source tissues 1
• For patients with septic shock, use appropriate full doses of antimicrobials, as dose reduction may be associated with worse clinical outcomes 2
• Reassess antimicrobial regimen daily for potential de-escalation 1
• Consider using procalcitonin or similar biomarkers to assist in discontinuing empiric antibiotics when no subsequent evidence of infection 1

Special Antimicrobial Considerations:

• Use combination empirical therapy for:
  • Neutropenic patients with severe sepsis 1
  • Patients with difficult-to-treat, multidrug-resistant pathogens (e.g., Acinetobacter, Pseudomonas) 1
  • Patients with severe infections with respiratory failure and septic shock (extended-spectrum beta-lactam plus either aminoglycoside or fluoroquinolone for P. aeruginosa bacteremia) 1
  • Patients with septic shock from bacteremic S. pneumoniae infections (beta-lactam plus macrolide) 1
• Limit empiric combination therapy to 3-5 days and de-escalate to appropriate single therapy once susceptibility profile is known 1
• Typical duration of therapy is 7-10 days; longer courses may be needed for slow clinical response, undrainable infection foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiencies 1
• Initiate antiviral therapy as early as possible when viral etiology is suspected 1

Source Control

• Identify specific anatomical diagnosis of infection requiring source control as rapidly as possible 1
• Implement source control interventions within 12 hours of diagnosis when feasible 1
• Use the least physiologically disruptive approach for source control (e.g., percutaneous rather than surgical drainage when appropriate) 1
• Remove potentially infected intravascular access devices promptly after establishing alternative vascular access 1
• Delay definitive intervention for infected peripancreatic necrosis until adequate demarcation of viable and nonviable tissues 1

Fluid Therapy

• Use crystalloids as the initial fluid of choice for resuscitation 1
• Target initial fluid challenge of 30 mL/kg of crystalloids for hypotension or lactate ≥4 mmol/L 1
• Continue fluid challenges as long as hemodynamic improvement is observed 1

Vasopressors and Inotropic Support

• Use norepinephrine as the first-choice vasopressor 1
• Add vasopressin or epinephrine to norepinephrine when additional agent is needed 1
• Use dobutamine in patients with persistent hypoperfusion despite adequate fluid loading and vasopressor use 1
• Place arterial catheter as soon as practical in patients requiring vasopressors 1

Additional Supportive Measures

• Corticosteroids: Consider IV hydrocortisone (200 mg/day) only for septic shock unresponsive to adequate fluid resuscitation and vasopressors 1
• Blood products:
  • Transfuse RBCs when hemoglobin <7.0 g/dL once tissue hypoperfusion has resolved 1
  • Do not use erythropoietin for anemia treatment 1
  • Administer platelets prophylactically when counts <10,000/mm³ without bleeding or <20,000/mm³ with significant bleeding risk 1
• Mechanical ventilation for sepsis-induced ARDS:
  • Target tidal volume of 6 mL/kg predicted body weight 1
  • Limit plateau pressures to ≤30 cm H₂O 1
  • Apply PEEP to avoid alveolar collapse 1
  • Consider prone positioning for severe refractory hypoxemia (PaO₂/FiO₂ ≤100 mmHg) 1
• Glucose control: Use a protocolized approach targeting blood glucose ≤180 mg/dL 1
• Renal replacement therapy: Consider continuous therapies to facilitate fluid management in hemodynamically unstable patients 1
• DVT prophylaxis: Use daily pharmacologic prophylaxis with LMWH (preferred over UFH) 1
• Stress ulcer prophylaxis: Provide H₂ blockers or proton pump inhibitors for patients with bleeding risk factors 1
• Nutrition: Provide early enteral nutrition rather than complete fasting or IV glucose alone; avoid mandatory full caloric feeding in the first week 1

Setting Goals of Care

• Discuss goals of care and prognosis with patients and families early in the course of treatment 1
• Incorporate goals of care into treatment planning, utilizing palliative care principles where appropriate 1
• Address goals of care no later than 72 hours after ICU admission 1

Common Pitfalls to Avoid

• Delaying antimicrobial therapy beyond one hour of recognition of sepsis 1, 3
• Inadequate source control or delayed intervention for removable infectious sources 1
• Inappropriate antimicrobial dosing, especially underdosing in critically ill patients 2
• Failure to de-escalate broad-spectrum antibiotics when culture results become available 1
• Overuse of vasopressors without adequate fluid resuscitation 1
• Neglecting to reassess treatment goals and response to therapy 1