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JAMA. 2016 Nov 1;316(17):1775-1785. doi: 10.1001/jama.2016.14799.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Author information

1
Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
2
Clinical Trial Centre Leipzig, Leipzig, Germany.
3
Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.
4
Department of Intensive Care Medicine, HELIOS Hospital Bad Saarow, Bad Saarow, Germany.
5
Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.
6
Department of Anesthesiology, Klinikum der Ludwig-Maximilians-Universität, München, Germany.
7
Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.
8
Department of Anesthesia, Intensive Care Medicine and Pain Management, Vivantes-Klinikum Neukölln, Berlin, Germany.
9
Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
10
Department of Anesthesia and Intensive Care, Zentralklinik Bad Berka, Bad Berka, Germany.
11
Department of Anesthesia, Intensive Care Medicine and Pain Management, HELIOS Hospital Erfurt, Erfurt, Germany.
12
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
13
Department of Cardiology and Intensive Care Medicine, Vivantes Humboldt Klinikum, Berlin, Germany.
14
Department of Emergency and Intensive Care Medicine, Klinikum Ernst von Bergmann, Potsdam, Germany.
15
Department of Intensive Care Medicine, HELIOS Hospital Berlin-Buch, Berlin, Germany.
16
Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany.
17
Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Management, Klinikum Oldenburg Medical Campus Carl von Ossietzky Universität, Oldenburg, Germany.
18
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
19
Center for Clinical Studies, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.

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.

PMID:
27695824
DOI:
10.1001/jama.2016.14799
[Indexed for MEDLINE]

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