[Source: JAMA, full page: (LINK). Abstract, edited.]
Original Investigation / Caring for the Critically Ill Patient / November 1, 2016
Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis
The HYPRESS Randomized Clinical Trial
Didier Keh, MD1; Evelyn Trips2; Gernot Marx, MD3; et al Stefan P. Wirtz, MD4; Emad Abduljawwad, MD4; Sven Bercker, MD5; Holger Bogatsch, MD2; Josef Briegel, MD6; Christoph Engel, MD7; Herwig Gerlach, MD, PhD, MBA8; Anton Goldmann, MD1; Sven-Olaf Kuhn, MD9; Lars Hüter, MD10; Andreas Meier-Hellmann, MD11; Axel Nierhaus, MD12; Stefan Kluge, MD12; Josefa Lehmke, MD13; Markus Loeffler, MD7; Michael Oppert, MD14; Kerstin Resener, MD15; Dirk Schädler, MD16; Tobias Schuerholz, MD3; Philipp Simon, MD5; Norbert Weiler, MD16; Andreas Weyland, MD17; Konrad Reinhart, MD18; Frank M. Brunkhorst, MD19; for the SepNet–Critical Care Trials Group
Author Affiliations: 1Department of Anesthesiology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany; 2Clinical Trial Centre Leipzig, Leipzig, Germany; 3Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany; 4Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany; 5Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany; 6Department of Anesthesiology, Klinikum der Ludwig-Maximilians-Universität, München, Germany; 7Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany; 8Department of Anesthesia, Intensive Care Medicine and Pain Management, Vivantes-Klinikum Neukölln, Berlin, Germany; 9Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany; 10Department of Anesthesia and Intensive Care, Zentralklinik Bad Berka, Bad Berka, Germany; 11Department of Anesthesia, Intensive Care Medicine and Pain Management, HELIOS Hospital Erfurt, Erfurt, Germany; 12Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 13Department of Cardiology and Intensive Care Medicine, Vivantes Humboldt Klinikum, Berlin, Germany; 14Department of Emergency and Intensive Care Medicine, Klinikum Ernst von Bergmann, Potsdam, Germany; 15Department of Intensive Care Medicine, HELIOS Hospital Berlin-Buch, Berlin, Germany; 16Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany; 17Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Management, Klinikum Oldenburg Medical Campus Carl von Ossietzky Universität, Oldenburg, Germany; 18Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; 19Center for Clinical Studies, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
Copyright 2016 American Medical Association. All Rights Reserved. Applicable ARS/DFARS Restrictions Apply to Government Use.
JAMA. 2016;316(17):1775-1785. doi:10.1001/jama.2016.14799
- Question – Does adjunctive early hydrocortisone therapy prevent the development of septic shock in patients with severe sepsis who are not in shock?
- Findings – In this randomized clinical trial that included 380 adults, occurrence of septic shock was not significantly different between patients who received hydrocortisone or placebo (21.2% vs 22.9%, respectively).
- Meaning – Administration of hydrocortisone did not prevent the development of shock in patients with severe sepsis.
Adjunctive 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.
To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.
Design, Setting, and Participants
Double-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.
Patients 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 Measures
The 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]).
The 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 Relevance
Among 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 Registration clinicaltrials.gov Identifier: NCT00670254
Keywords: Sepsis; Corticosteroids.