ADRENAL Trial

NEJM

March 1, 2018

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.

Summarized by: 

Mazen Kherallah

What was the research question?

  • Does hydrocortisone reduce 90-day mortality in critically ill patients with septic shock compared with placebo?


How did they do it?

  • A multicenter, double blind, randomized, controlled trial, with a 1:1 ratio assignment with an intent to treat analysis.

  • 69 medical–surgical ICUs in Australia, UK, New Zealand, Saudi Arabia, and Denmark.

  • Adult patients with septic shock requiring vasopressors for ≥4 hours and mechanical ventilation (including non-invasive)

  • 3800 patients underwent randomization with 1:1 assignment.

  • 1832 in the hydrocortisone group and 1826 in the placebo group


What did they find?

  • 90-day mortality (primary outcome) was similar in the hydrocortisone group compared to the placebo group (27.9% vs. 28.8%, P=0.50).

  • Hydrocortisone had faster resolution of shock      compared to placebo (median duration, 3 days vs. 4 days, P<0.001), lower      median time to cessation of initial mechanical ventilation (6 vs. 7 days, P=<0.001),      lower median time to discharge from the ICU (10 vs. 12 days, P=<0.001),  and lower rate of blood transfusion (37% vs 41.7%, p= 0.004).

  • No significant difference in number of days alive and free from mechanical ventilation, mortality at 28 days, the rate of recurrence of shock, the total number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia.


Any limitations?

  • Overall well-designed study with few limitations.

  • Did not monitor all possible secondary infections.

  • Did not assess for Long-term neuromuscular weakness, used reintubation instead as a surrogate for weakness.  as an adverse event was not assessed.

  • Higher than anticipated rate of withdrawal or loss to follow up.

  • Open-label steroids for an indication was given to 7.4% in intervention group and 8.8% of patients in placebo.


What does it mean?

  • Hydrocortisone infusion for up to 7 days does not improve or worsen 90-day mortality rate in patient with septic shock and mechanically ventilated. However, it reduces the time to resolution of shock and may reduce ICU length of stay.

  • This study impacted the practice and now hydrocortisone is added with ongoing need of vasopressors in patients with septic shock.

ADRENAL Trial