What is the recommended management for undifferentiated sepsis?

Management of Undifferentiated Sepsis

The management of undifferentiated sepsis requires immediate implementation of a bundle of interventions including fluid resuscitation, early antimicrobial therapy within 1 hour, source control, and supportive care to reduce mortality and improve outcomes. 1

Initial Resuscitation and Hemodynamic Support

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 1
• Avoid hydroxyethyl starches due to potential harm 1
• Implement frequent reassessment of hemodynamic status to guide ongoing fluid therapy 1
• Monitor for clinical indicators of adequate tissue perfusion 2:
  • 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 (adults) or >1 mL/kg/hour (children)

Vasopressor Support

• Begin norepinephrine as first-choice vasopressor if fluid resuscitation is inadequate to restore perfusion 1
• Target a mean arterial pressure (MAP) of 65 mmHg 1
• Consider adding vasopressin (0.03 units/minute) to norepinephrine to improve blood pressure or decrease norepinephrine requirements 1
• For refractory shock, consider adding epinephrine as an additional agent 1
• In resource-limited settings, dopamine or epinephrine can be used for persistent tissue hypoperfusion despite fluid resuscitation 2

Corticosteroids

• Consider hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) for patients requiring escalating vasopressors 2

Infection Management

Antimicrobial Therapy

• Administer broad-spectrum antibiotics within 1 hour of recognition of sepsis 1
• Obtain appropriate cultures before starting antimicrobials if no substantial delay occurs 1
• Ensure antimicrobial coverage for gram-positive, gram-negative, and anaerobic organisms 2, 1
• Reassess antimicrobial regimen daily for potential de-escalation 1
• Narrow antimicrobial therapy once pathogen identification and sensitivities are established 1

Source Control

• Identify source of infection as rapidly as possible 1
• Drain or debride the source of infection whenever possible 2
• Remove any foreign body or device that may potentially be the source of infection 2
• Implement source control interventions as soon as practical 1

Respiratory Support

Oxygen Therapy and Ventilation

• Apply oxygen to achieve an oxygen saturation >90% 2
• Place patients in a semi-recumbent position (head of the bed raised to 30-45°) 2
• For mechanically ventilated patients with ARDS 2:
  • Use a target tidal volume of 6 mL/kg predicted body weight
  • Maintain plateau pressures ≤30 cm H2O
  • Consider higher PEEP for moderate to severe ARDS
  • Consider prone positioning for severe ARDS (PaO2/FiO2 <150)
• For patients without ARDS, use lower tidal volumes over higher tidal volumes 2
• If available and staff is adequately trained, use non-invasive ventilation in patients with dyspnea and/or persistent hypoxemia despite oxygen therapy 2

Supportive Care

Glucose Control

• Implement a protocolized approach to blood glucose management 2
• Start insulin when two consecutive blood glucose levels are >180 mg/dL 2
• Target an upper blood glucose level ≤180 mg/dL 2
• Monitor blood glucose every 1-2 hours until stable, then every 4 hours 2

Nutrition

• Initiate early enteral feeding rather than complete fast or IV glucose only 1
• Consider either early trophic/hypocaloric or early full enteral feeding 1
• Advance feeds according to patient tolerance 1

Deep Vein Thrombosis Prophylaxis

• Provide pharmacological or mechanical deep vein thrombosis prophylaxis 1

Sedation and Analgesia

• Minimize continuous or intermittent sedation in mechanically ventilated patients 2
• Target specific sedation endpoints 2
• Avoid neuromuscular blocking agents if possible in septic patients without ARDS 2
• Consider a short course of neuromuscular blocking agents (≤48 hours) for early sepsis-induced ARDS with PaO2/FiO2 <150 mm Hg 2

Special Considerations

Sepsis Due to Specific Causes

• For malaria-associated sepsis 2:

  • Prompt start of parenteral artesunate
  • In children, add parenteral antibiotics to antimalarial treatment
  • Manage fluid more restrictively than in bacterial sepsis
  • Consider blood transfusion for severe anemia (Hb <6 g/dL)

• For sepsis in HIV/AIDS patients 2:

  • For Pneumocystis jiroveci pneumonia, use trimethoprim/sulfamethoxazole for 3 weeks
  • Add prednisolone for hypoxemic patients
  • In malnourished patients, restart energy supply slowly with stepwise increase of daily caloric intake

Early Mobilization and Weaning

• Encourage mobilization as soon as the patient is stable 2
• Use spontaneous breathing trials in mechanically ventilated patients ready for weaning 2
• Implement a weaning protocol for mechanically ventilated patients who can tolerate weaning 2
• Actively reduce invasive support as soon as the patient has stabilized 2

Implementation Strategy

• Use a bundle approach to implement sepsis management protocols 2
• Establish hospital-based performance improvement programs for sepsis 1
• Consider using checklists and multidisciplinary approaches to improve adherence to guidelines 2

By following this comprehensive approach to sepsis management, focusing on early recognition, prompt intervention, and appropriate supportive care, mortality and morbidity from sepsis can be significantly reduced.