ADRENAL

Population

• Patients with septic shock who were undergoing mechanical ventilation.

Intervention

Hydrocortisone 200 mg per day as a continuous infusion for 7 days or until death or ICU discharge, whichever came first.

Comparator

Placebo.

Key results

• 90-day mortality: 27.9% with hydrocortisone vs 28.8% with placebo; odds ratio 0.95 (95% CI 0.82-1.10; p=0.50).
• Shock resolved faster with hydrocortisone (median 3 vs 4 days; HR 1.32; 95% CI 1.23-1.41; p<0.001).
• The initial mechanical-ventilation episode was shorter with hydrocortisone (median 6 vs 7 days), but days alive and free from ventilation did not differ once recurrences were counted.
• Fewer hydrocortisone-treated patients received a blood transfusion (37.0% vs 41.7%).

Harms

• New-onset bacteremia or fungemia did not differ between hydrocortisone and placebo.

Practice impact

• Hydrocortisone can be used to shorten shock duration, not as a proven mortality intervention in ventilated septic shock.

Applicability

• Most applicable to patients with septic shock who are already on mechanical ventilation and being considered for a hydrocortisone infusion.

Limitations

• Tested a continuous hydrocortisone infusion without fludrocortisone.
• Primary outcome status was ascertained in 3658 of 3800 randomized patients.
• A faster shock-resolution signal did not translate into lower 90-day mortality, 28-day mortality, or more days alive out of the ICU or hospital.

Common misinterpretations

• A negative mortality result does not mean hydrocortisone has no hemodynamic effect; shock resolved faster.
• This trial does not answer whether hydrocortisone plus fludrocortisone changes survival.