Adjunctive Glucocorticoid Therapy in Patients with Septic Shock
The New England Journal of Medicine (NEJM)
Balasubramanian Venkatesh, M.D., Simon Finfer, M.D., Jeremy Cohen, M.D., Ph.D., Dorrilyn Rajbhandari, R.N., Yaseen Arabi, M.D., Rinaldo Bellomo, M.D., Laurent Billot, M.Sc., M.Res., Maryam Correa, Ph.D., Parisa Glass, Ph.D., Meg Harward, R.N., Christopher Joyce, M.D., Ph.D., Qiang Li, M.Sc., Colin McArthur, M.D., Anders Perner, M.D., Ph.D., Andrew Rhodes, M.D., Kelly Thompson, R.N., M.P.H., Steve Webb, M.D., Ph.D., and John Myburgh, M.D., Ph.D. for the ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group*
From the George Institute for Global Health, University of New South Wales (B.V., S.F., D.R., L.B., M.C., P.G., M.H., Q.L., K.T., J.M.), St. George Clinical School, St. George Hospital (J.M.), Sydney Medical School, University of Sydney (B.V., S.F., J.M.), and Royal North Shore Hospital (S.F.), Sydney, the Princess Alexandra Hospital (B.V., C.J.) and Royal Brisbane and Women’s Hospital (J.C.), University of Queensland, and the Wesley Hospital (B.V., J.C.), Brisbane, Austin Hospital (R.B.), the School of Medicine, University of Melbourne (R.B.), and the Australian and New Zealand Research Centre (R.B.), School of Public Health and Preventive Medicine (R.B., S.W., J.M.), Monash University, Melbourne, VIC, and Royal Perth Hospital (S.W.) and the School of Medicine and Pharmacology, University of Western Australia (S.W.), Perth — all in Australia; King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.A.); the Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand (C.M.); Rigshospitalet, University of Copenhagen, Copenhagen (A.P.); and St. George’s University Hospitals NHS Foundation Trust, St. George’s University of London, London (A.R.).
Year of Publication:
Whether hydrocortisone reduces mortality among patients with septic shock is unclear.
We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days.
From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the 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.
Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)