• Didier Keh, Evelyn Trips, Gernot Marx, Stefan P Wirtz, Emad Abduljawwad, Sven Bercker, Holger Bogatsch, Josef Briegel, Christoph Engel, Herwig Gerlach, Anton Goldmann, Sven-Olaf Kuhn, Lars Hüter, Andreas Meier-Hellmann, Axel Nierhaus, Stefan Kluge, Josefa Lehmke, Markus Loeffler, Michael Oppert, Kerstin Resener, Dirk Schädler, Tobias Schuerholz, Philipp Simon, Norbert Weiler, Andreas Weyland, Konrad Reinhart, Frank M Brunkhorst, and SepNet–Critical Care Trials Group.
• Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
• JAMA. 2016 Nov 1; 316 (17): 1775-1785.

ImportanceAdjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.ObjectiveTo determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.Design, Setting, And ParticipantsDouble-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.InterventionsPatients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).Main Outcomes And MeasuresThe primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).ResultsThe intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.Conclusions And RelevanceAmong adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.Trial Registrationclinicaltrials.gov Identifier: NCT00670254.

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