What is the role of corticosteroids (specifically hydrocortisone) in the management of sepsis?

Corticosteroid Use in Sepsis

Corticosteroids should be used in patients with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy, but should not be used in patients with sepsis without shock. 1, 2

Sepsis Without Shock

• Corticosteroids are not recommended for patients with sepsis without shock 1, 2
• Evidence from the HYPRESS trial showed no benefit in preventing progression to septic shock when hydrocortisone was administered to patients with sepsis without shock 1, 3
• No significant differences were observed between hydrocortisone and placebo groups in:
  • Mortality at 28 days (8.8% vs 8.2%)
  • Mortality up to 180 days (26.8% vs 22.2%)
  • ICU length of stay
  • Hospital length of stay 1, 3
• Potential harms observed in sepsis without shock include:
  • Secondary infections (21.5% vs 16.9%)
  • Muscle weakness (30.7% vs 23.8%)
  • Hyperglycemia (90.9% vs 81.5%) 1, 3

Septic Shock

Indications for Corticosteroid Use

• Recommended for patients with septic shock who remain hemodynamically unstable despite:
  • Adequate fluid resuscitation
  • Moderate to high-dose vasopressor therapy (>0.1 μg/kg/min of norepinephrine or equivalent) 1, 2

Dosing and Administration

• Recommended regimen: Low-dose IV hydrocortisone <400 mg/day for at least 3 days at full dose 1, 2
• Most common dosing: 200 mg/day, either as:
  • 50 mg IV every 6 hours, or
  • Continuous infusion 1, 2
• Continuous infusion is preferred over bolus dosing 2
• Duration should be at least 3 days at full dose, with longer duration showing better outcomes 1
• Taper hydrocortisone gradually when vasopressors are no longer required 1, 2

Benefits in Septic Shock

1. Shock reversal: Corticosteroids consistently improve shock reversal 1, 4

   • 66.9% vs 58.6% shock reversal at 28 days (RR 1.12,95% CI 1.02-1.23) 4

2. Reduced ICU length of stay: By approximately 4.5 days 4

3. Potential mortality benefit:

   • Cochrane systematic review showed significantly reduced risk of death at 28 days with low-dose corticosteroids 1
   • Most pronounced benefit with lower doses (<400 mg/day) for longer duration (≥3 days) 1

4. Anti-inflammatory effects:

   • Decrease in pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-6) 5
   • Improved hemodynamic stability 5

Adverse Effects

• Hyperglycemia (most common) 1, 4
• Hypernatremia 1, 4
• No significant increase in:
  • Secondary infections 1, 4
  • Gastrointestinal bleeding 4
  • Neuromuscular weakness with short-term use 4

Important Clinical Considerations

ACTH Stimulation Test

• Not recommended to identify which patients with septic shock should receive hydrocortisone 1, 2
• Random cortisol levels are not useful for determining relative adrenal insufficiency in septic shock 1

Common Pitfalls to Avoid

1. Using corticosteroids in sepsis without shock: Provides no benefit and may cause harm 1, 2, 3

2. High-dose, short-course therapy: Less effective than low-dose, longer duration therapy 1, 2, 6

3. Abrupt discontinuation: May lead to hemodynamic and immunologic rebound effects 2

4. Delayed initiation: Consider starting hydrocortisone early in patients with refractory septic shock 2

5. Prolonged use without indication: Discontinue when vasopressors are no longer required 1, 2

Algorithm for Corticosteroid Use in Sepsis

1. Assess for shock: Determine if patient has sepsis with or without shock
2. For sepsis without shock: Do not administer corticosteroids
3. For septic shock:
   • Begin fluid resuscitation and vasopressor therapy
   • If patient remains hemodynamically unstable despite adequate fluid resuscitation and moderate-to-high dose vasopressors:
     • Start IV hydrocortisone <400 mg/day (typically 200 mg/day)
     • Continue for at least 3 days at full dose
     • Taper gradually when vasopressors are no longer required
4. Monitor for adverse effects: Hyperglycemia, hypernatremia
5. Discontinue: When hemodynamic stability is achieved and vasopressors are no longer required