What is the role of corticosteroids (steroid hormones) in critical care, specifically in conditions like severe sepsis (systemic inflammatory response syndrome) or acute respiratory distress syndrome (ARDS)?

Corticosteroids in Critical Care

Primary Recommendation

For septic shock not responsive to fluid resuscitation and moderate-to-high dose vasopressors, use intravenous hydrocortisone at doses <400 mg/day (typically 200 mg/day) for at least 3 days at full dose, followed by gradual tapering over 6-14 days when vasopressors are no longer required. 1, 2

---

Sepsis and Septic Shock

When to Use Corticosteroids

• Septic shock with vasopressor dependence: Administer IV hydrocortisone <400 mg/day for ≥3 days when shock persists despite adequate fluid resuscitation and moderate-to-high dose vasopressor therapy 1, 2
• Sepsis without shock: Do NOT use corticosteroids—the HYPRESS trial demonstrated no benefit in preventing progression to shock (difference -1.8%; 95% CI -10.7 to 7.2%) or reducing mortality 1, 2

Dosing Protocol

• Standard regimen: Hydrocortisone 200 mg/day IV, administered either as divided doses (50 mg every 6 hours) or continuous infusion 1, 2
• Duration: Continue full dose for minimum 5 days before initiating taper 2
• Tapering: Reduce gradually over 6-14 days when vasopressors are discontinued to avoid rebound inflammation and hemodynamic deterioration 2

Expected Benefits

• Potential 2% absolute reduction in 28-day mortality (though confidence interval crosses no difference) 1
• Improved shock reversal at day 7 (RR 1.20,95% CI 1.06-1.35) 3
• Reduced ICU length of stay by approximately 2 days 1, 3
• Enhanced organ function at day 7 1

---

Acute Respiratory Distress Syndrome (ARDS)

When to Use Corticosteroids

For early moderate-to-severe ARDS, use IV methylprednisolone 1 mg/kg/day rather than hydrocortisone. 2

Rationale for Methylprednisolone

• Greater penetration into lung tissue and longer residence time compared to hydrocortisone 2
• Improved oxygenation index (PaO2/FiO2) by 61.41 mmHg (95% CI 26.64-96.18) in mechanically ventilated patients 3

Timing and Duration

• Early initiation (≤72 hours) with prolonged therapy (≥7 days) associated with reduced short-term mortality 3
• Reduced duration of mechanical ventilation by 4.24 days (95% CI -6.38 to -2.10) 3
• Increased ventilator-free days at 28 days by 2.83 days (95% CI 1.20-4.47) 3

---

Community-Acquired Pneumonia (CAP)

Severe CAP Requiring Hospitalization

• Use corticosteroids for 5-7 days at daily dose <400 mg IV hydrocortisone or equivalent 2
• Early initiation (≤72 hours), low-dose, and prolonged therapy (≥7 days) associated with mortality benefit 3

---

Critical Monitoring and Adverse Effects

Expected Adverse Effects Requiring Surveillance

Metabolic complications (most common):

• Hyperglycemia occurs more frequently (RR 1.10,95% CI 1.06-1.14) 3
• Hypernatremia—monitor serum sodium levels regularly 1, 2
• Monitor blood glucose and electrolytes throughout therapy 2

Neuromuscular weakness:

• May increase risk by small amount, potentially underestimated in trials 1
• Can compromise independent function and delay recovery 1
• Risk increases with both dose and duration 4

Infection risk:

• No significant increase in secondary infection rates (RR 1.01,95% CI 0.92-1.12) 3
• No increased risk of superinfection (RR 0.93,95% CI 0.73-1.18) 5
• However, corticosteroids mask signs of infection and blunt febrile response 2, 6

Gastrointestinal bleeding:

• No significant increase in GI bleeding risk (RR 1.07,95% CI 0.86-1.33) 3
• Despite theoretical concerns, risk not elevated in critical illness context 4

Infection Surveillance

• Screen for latent tuberculosis before prolonged therapy; reactivation may occur 7, 6
• Rule out strongyloidiasis in patients from endemic areas—corticosteroids can cause fatal hyperinfection syndrome 7
• Screen hepatitis B carriers; reactivation can occur with immunosuppressive doses 7
• Avoid exposure to varicella and measles in non-immune patients; consider prophylaxis if exposed 7, 6

---

Critical Pitfalls to Avoid

Do NOT Use ACTH Stimulation Testing

• The ACTH stimulation test has no role in identifying which patients should receive hydrocortisone or guiding tapering decisions 2

Avoid Abrupt Discontinuation

• Stopping corticosteroids suddenly causes rebound inflammation and hemodynamic deterioration 2
• Always taper gradually over 6-14 days when vasopressors are discontinued 2

Do NOT Use in Sepsis Without Shock

• Provides no benefit and exposes patients to unnecessary adverse effects 1, 2

Avoid High-Dose, Short-Duration Regimens

• Long course, low dose (<400 mg/day hydrocortisone for ≥3 days) superior to high-dose, short-duration therapy 1

Etomidate Consideration

• Prior etomidate use may worsen outcomes; be aware of this interaction 2

---

Special Populations

Combination Therapy in Septic Shock

• For septic shock, combination therapy with hydrocortisone plus fludrocortisone may enhance efficacy 3

Major Trauma

• Corticosteroids NOT recommended for major trauma—no mortality benefit (RR 1.00,95% CI 0.89-1.13) 2

Cardiac Arrest

• May be beneficial with improved return of spontaneous circulation and neurological outcomes 2