Clinical question: Among patients with septic shock undergoing mechanical ventilation, does hydrocortisone reduce 90-day mortality?
Background: Septic shock is associated with a significant mortality risk, and there is no proven pharmacologic treatment other than fluids, vasopressors, and antimicrobials. Prior randomized, controlled trials have resulted in mixed outcomes, and meta-analyses and clinical practice guidelines also have not provided consistent guidance.
Study design: Randomized, controlled, double-blinded trial.
Setting: Medical centers in Australia, Denmark, New Zealand, Saudi Arabia, and the United Kingdom.
Synopsis: Over a 4-year period from 2013 to 2017, 3,658 patients with septic shock undergoing mechanical ventilation were randomized to receive either a continuous infusion of 200 mg/day of hydrocortisone for 7 days or placebo. The primary outcome, death within 90 days, occurred in 511 patients (27.9%) in the hydrocortisone group and in 526 patients (28.8%) in the placebo group (P = .50).
In secondary outcome analyses, patients in the hydrocortisone group had faster resolution of shock (3 vs. 4 days; P less than .001) and a shorter duration of initial mechanical ventilation (6 vs. 7 days; P less than .001), and fewer patients received blood transfusions (37.0% vs. 41.7%; P = .004). There was no difference in mortality at 28 days, recurrence of shock, number of days alive out of the ICU and hospital, recurrence of mechanical ventilation, rate of renal replacement therapy, and incidence of new-onset bacteremia or fungemia.
Bottom line: Administering hydrocortisone in patients with septic shock who are undergoing mechanical ventilation does not reduce 90-day mortality.
Citation: Venkatesh B et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018 Jan 19. doi: 10.1056/NEJMoa1705835.
Dr. Huang is associate chief of the division of hospital medicine at UC San Diego Health and an associate professor of medicine at the University of California, San Diego.