• Balasubramanian Venkatesh, Simon Finfer, Jeremy Cohen, Dorrilyn Rajbhandari, Yaseen Arabi, Rinaldo Bellomo, Laurent Billot, Parisa Glass, Christopher Joyce, Qiang Li, Colin McArthur, Anders Perner, Andrew Rhodes, Kelly Thompson, Steve Webb, and John Myburgh.
• From the George Institute for Global Health, Sydney, New South Wales, Australia (B.V., S.F., D.R., L.B., P.G., Q.L., K.T., J.M.) Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia (B.V., C.J.) Wesley Hospital, Brisbane, Queensland, Australia (B.V.) University of New South Wales, Sydney, New South Wales, Australia (B.V., S.F., J.M.) Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia (S.F.) Royal North Shore Hospital, Sydney, New South Wales, Australia (S.F.) Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Queensland, Australia (J.C.) King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (Y.A.) Austin and Repatriation Medical Center, Melbourne, Victoria, Australia (R.B.) the Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand (C.M.) Rigshospitalet, Copenhagen, Denmark (A.P.) St. George's Hospital, London, United Kingdom (A.R.) Royal Perth Hospital, Perth, Western Australia, Australia (S.W.) University of Western Australia, School of Medicine and Pharmacology, Perth, Western Australia (S.W.) St. George Hospital, University of New South Wales, Sydney, New South Wales (J.M.).
• Anesthesiology. 2019 Dec 1; 131 (6): 1292-1300.

BackgroundTwo recent randomized controlled trials (Adjunctive Glucocorticoid Therapy in Patients with Septic Shock [ADRENAL] and Activated Protein C and Corticosteroids for Human Septic Shock [APROCCHSS]) of corticosteroids in patients with septic shock reported different treatment effects on 90-day mortality. Both trials enrolled patients who met the criteria for septic shock using the second international consensus definitions for sepsis and septic shock (Sepsis-2), but the APROCCHSS trial mandated a greater severity of shock as an inclusion criterion.MethodsThe authors conducted post hoc sensitivity analyses of the ADRENAL trial to determine the effects of hydrocortisone versus placebo in subgroups selected using third international consensus definitions for sepsis and septic shock (Sepsis-3) diagnostic criteria or APROCCHSS inclusion criteria.ResultsThere were 1,950 subjects (973 hydrocortisone and 977 placebo) who met the Sepsis-3 criteria (ADRENAL-Sepsis-3 cohort) and 905 patients (455 hydrocortisone and 450 placebo) who met the APROCCHSS criteria (ADRENAL-APROCCHSS cohort). At 90 days after randomization, in the ADRENAL-Sepsis-3 cohort, 312 of 963 (32.4%) and 337 of 958 (35.2%) patients assigned to hydrocortisone and placebo, respectively, had died (odds ratio, 0.86; 95% CI, 0.70 to 1.06; P = 0.166). The corresponding figures for the ADRENAL-APROCCHSS cohorts were 187 of 453 (41.3%) and 200 of 445 (44.9%), respectively (odds ratio, 0.84; 95% CI, 0.60 to 1.17; P = 0.303). There was no statistically significant difference in the time to death between the groups during the 90 days after randomization (hazard ratio = 0.87; 95% CI, 0.75 to 1.02; P = 0.082 for ADRENAL-Sepsis-3; and hazard ratio = 0.86; 95% CI, 0.71 to 1.06; P = 0.156 for ADRENAL-APROCCHSS cohorts). In both cohorts, patients assigned to hydrocortisone had faster resolution of shock. In the ADRENAL-Sepsis-3 cohort, patients assigned to hydrocortisone had an increase in the number of days alive and free of mechanical ventilation (57.0 ± 37.2 vs. 53.7 ± 38.2 days; 95% CI, 0.40 to 7.04; P = 0.028) and the number of days alive and free of the intensive care unit (54.3 ± 36.0 vs. 51.0 ± 37.1; 95% CI, 0.82 to 7.24; P = 0.014).ConclusionsIn a post hoc analysis of the ADRENAL trial participants who fulfilled either the Sepsis-3 or the APROCCHSS inclusion criteria, a continuous infusion of hydrocortisone did not result in a lower 90-day mortality than placebo in septic shock.

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