What is the role of corticosteroids (steroids) in the management of septic shock?

Steroids in Septic Shock: Mechanism and Current Evidence

Low-dose corticosteroids are recommended for patients with septic shock who remain hypotensive despite adequate fluid resuscitation and vasopressor therapy, with a recommended dose of 200-300 mg/day of hydrocortisone for at least 3 days. 1, 2

Mechanism of Action in Septic Shock

Corticosteroids work in septic shock through several mechanisms:

1. Vascular responsiveness restoration: They restore vascular sensitivity to norepinephrine, improving hemodynamic stability
2. Anti-inflammatory effects: They modulate the excessive inflammatory response in sepsis
3. Adrenal insufficiency compensation: Approximately 25% of patients with septic shock develop relative adrenal insufficiency, characterized by inadequate cortisol production for the level of physiological stress 2

Current Evidence and Recommendations

When to Use Steroids in Septic Shock

• Primary indication: Septic shock patients who remain hypotensive despite adequate fluid resuscitation and vasopressor therapy 1, 2
• Timing: Should be started immediately after obtaining blood for a random cortisol level 2
• Patient selection: Most beneficial in patients with:
  • High vasopressor requirements
  • Evidence of multiorgan failure
  • Primary lung infections 3

Dosing and Administration

• Recommended dose: 200-300 mg/day of hydrocortisone 1, 2
• Administration options:
  • 50 mg IV every 6 hours
  • 100 mg IV every 8 hours
  • Continuous infusion (may help avoid glucose peaks) 2
• Duration: At least 3 days at full dose, or until vasopressors are no longer required 1, 2

Clinical Benefits

The evidence consistently shows that corticosteroids in septic shock:

• Improve shock reversal: Significantly increase the rate of shock reversal at 7 days (64.9% vs 47.5%; RR 1.41) 4
• Reduce vasopressor duration: Lead to faster reversal of shock 3
• May reduce mechanical ventilation time 3

Mortality Benefit

The evidence regarding mortality benefit is mixed:

• A Cochrane systematic review showed that corticosteroids significantly reduced the risk of death at 28 days compared to placebo, particularly with lower doses (<400 mg hydrocortisone/day) for longer duration (≥3 days) 1
• However, other meta-analyses have shown no statistically significant difference in mortality (42.2% vs 38.4%; RR 1.00) 4
• The ADRENAL and APROCCHSS trials provided valuable but opposing insights, with differences likely related to study design, corticosteroid regimen, and baseline patient characteristics 3

ACTH Stimulation Testing

• Current recommendation: ACTH stimulation testing is not necessary to decide on treatment in septic shock 1, 2
• Rationale: No significant interaction between steroid use and ACTH test results has been demonstrated in recent multicenter trials 1

Side Effects and Monitoring

• Common side effects:

  • Hyperglycemia (most common)
  • Hypernatremia 1, 2

• Safety profile: At low doses, corticosteroids do not appear to increase the risk of:

  • Superinfection (25.3% vs 22.7%; RR 1.11) 4
  • Gastrointestinal bleeding 1

• Monitoring recommendations:

  • Regular blood glucose monitoring
  • Electrolyte monitoring (particularly sodium and potassium) 2

Discontinuation Strategy

• Tapering: Gradually taper steroids when vasopressors are no longer required rather than stopping abruptly 1, 2
• Rationale: Abrupt cessation can lead to hemodynamic and immunologic rebound effects, including recurrent hypotension and increased inflammatory mediators 2

Special Considerations

• Fludrocortisone: The benefit of adding fludrocortisone (50 μg daily enterally) to hydrocortisone remains unclear 3
• Contraindications: Corticosteroids should not be administered for sepsis in the absence of shock (Grade 1D recommendation) 1

By following these evidence-based recommendations, clinicians can optimize the use of corticosteroids in septic shock to improve patient outcomes while minimizing potential adverse effects.