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Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.
JAMA. 2016 Nov 01; 316(17):1775-1785.JAMA

Abstract

Importance

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.

Objective

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.

Interventions

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]).

Results

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.

Authors+Show Affiliations

Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.Clinical Trial Centre Leipzig, Leipzig, Germany.Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany.Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany.Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.Clinical Trial Centre Leipzig, Leipzig, Germany.Department of Anesthesiology, Klinikum der Ludwig-Maximilians-Universität, München, Germany.Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.Department of Anesthesia, Intensive Care Medicine and Pain Management, Vivantes-Klinikum Neukölln, Berlin, Germany.Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.Department of Anesthesia and Intensive Care, Zentralklinik Bad Berka, Bad Berka, Germany.Department of Anesthesia, Intensive Care Medicine and Pain Management, HELIOS Hospital Erfurt, Erfurt, Germany.Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Cardiology and Intensive Care Medicine, Vivantes Humboldt Klinikum, Berlin, Germany.Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.Department of Emergency and Intensive Care Medicine, Klinikum Ernst von Bergmann, Potsdam, Germany.Department of Intensive Care Medicine, HELIOS Hospital Berlin-Buch, Berlin, Germany.Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany.Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany.Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Management, Klinikum Oldenburg Medical Campus Carl von Ossietzky Universität, Oldenburg, Germany.Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.Center for Clinical Studies, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27695824

Citation

Keh, Didier, et al. "Effect of Hydrocortisone On Development of Shock Among Patients With Severe Sepsis: the HYPRESS Randomized Clinical Trial." JAMA, vol. 316, no. 17, 2016, pp. 1775-1785.
Keh D, Trips E, Marx G, et al. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 2016;316(17):1775-1785.
Keh, D., Trips, E., Marx, G., Wirtz, S. P., Abduljawwad, E., Bercker, S., Bogatsch, H., Briegel, J., Engel, C., Gerlach, H., Goldmann, A., Kuhn, S. O., Hüter, L., Meier-Hellmann, A., Nierhaus, A., Kluge, S., Lehmke, J., Loeffler, M., Oppert, M., ... Brunkhorst, F. M. (2016). Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA, 316(17), 1775-1785. https://doi.org/10.1001/jama.2016.14799
Keh D, et al. Effect of Hydrocortisone On Development of Shock Among Patients With Severe Sepsis: the HYPRESS Randomized Clinical Trial. JAMA. 2016 Nov 1;316(17):1775-1785. PubMed PMID: 27695824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. AU - Keh,Didier, AU - Trips,Evelyn, AU - Marx,Gernot, AU - Wirtz,Stefan P, AU - Abduljawwad,Emad, AU - Bercker,Sven, AU - Bogatsch,Holger, AU - Briegel,Josef, AU - Engel,Christoph, AU - Gerlach,Herwig, AU - Goldmann,Anton, AU - Kuhn,Sven-Olaf, AU - Hüter,Lars, AU - Meier-Hellmann,Andreas, AU - Nierhaus,Axel, AU - Kluge,Stefan, AU - Lehmke,Josefa, AU - Loeffler,Markus, AU - Oppert,Michael, AU - Resener,Kerstin, AU - Schädler,Dirk, AU - Schuerholz,Tobias, AU - Simon,Philipp, AU - Weiler,Norbert, AU - Weyland,Andreas, AU - Reinhart,Konrad, AU - Brunkhorst,Frank M, AU - ,, PY - 2016/11/2/pubmed PY - 2016/12/15/medline PY - 2016/10/4/entrez SP - 1775 EP - 1785 JF - JAMA JO - JAMA VL - 316 IS - 17 N2 - Importance: 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. Objective: 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. Interventions: 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]). Results: 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/27695824/Effect_of_Hydrocortisone_on_Development_of_Shock_Among_Patients_With_Severe_Sepsis:_The_HYPRESS_Randomized_Clinical_Trial_ DB - PRIME DP - Unbound Medicine ER -