LandmarkRCT

ADRENAL

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

New England Journal of Medicine, 2018 · Multicenter, randomized, double-blind, placebo-controlled trial.

Clinical question

In mechanically ventilated adults with septic shock, does a continuous hydrocortisone infusion reduce 90-day mortality?

Population: 3,800 mechanically ventilated adults with septic shock requiring vasopressor support.
Intervention: Hydrocortisone 200 mg/day by continuous IV infusion.
Comparator: Placebo.
Primary outcome: 90-day all-cause mortality.
Secondary outcomes: Time to shock resolution.
Duration of mechanical ventilation.
ICU length of stay.
Result: No significant 90-day mortality difference, but hydrocortisone shortened time to shock resolution. (90-day mortality 27.9% (hydrocortisone) vs 28.8% (placebo), OR 0.95, 95% CI 0.82-1.10)

What the trial found

Continuous hydrocortisone infusion did not reduce 90-day mortality compared with placebo, though it resolved shock faster and shortened initial ICU stay.

Current guideline position

The 2026 Surviving Sepsis Campaign guideline suggests using IV corticosteroids in septic shock on conditional, low-certainty evidence — a position that has to weigh ADRENAL's neutral mortality result against APROCCHSS's positive one.

Clinical interpretation

ADRENAL and APROCCHSS tested different steroid regimens (hydrocortisone alone vs hydrocortisone plus fludrocortisone, with some protocol differences) and reached different conclusions about mortality — this is a genuine, unresolved tension in the corticosteroid evidence base, not a case where one trial should be read as simply correct and the other wrong. See Controversies.

Limitations

Used hydrocortisone alone without fludrocortisone, unlike APROCCHSS.
Neutral primary outcome despite a large sample size, which strengthens confidence that any true mortality effect of this specific regimen is small.

High certainty

Clinical Context & Relevant Topics (1)

Disease Reference

Septic Shock

The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.

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