Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial
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Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. / Keh, Didier; Trips, Evelyn; Marx, Gernot; Wirtz, Stefan P; Abduljawwad, Emad; Bercker, Sven; Bogatsch, Holger; Briegel, Josef; Engel, Christoph; Gerlach, Herwig; Goldmann, Anton; Kuhn, Sven-Olaf; Hüter, Lars; Meier-Hellmann, Andreas; Nierhaus, Axel; Kluge, Stefan; Lehmke, Josefa; Loeffler, Markus; Oppert, Michael; Resener, Kerstin; Schädler, Dirk; Schuerholz, Tobias; Simon, Philipp; Weiler, Norbert; Weyland, Andreas; Reinhart, Konrad; Brunkhorst, Frank M; SepNet Critical Care Trials Group.
In: JAMA-J AM MED ASSOC, Vol. 316, No. 17, 01.11.2016, p. 1775-1785.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - SepNet Critical Care Trials Group
PY - 2016/11/1
Y1 - 2016/11/1
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.
AB - 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.
U2 - 10.1001/jama.2016.14799
DO - 10.1001/jama.2016.14799
M3 - SCORING: Journal article
C2 - 27695824
VL - 316
SP - 1775
EP - 1785
JO - JAMA-J AM MED ASSOC
JF - JAMA-J AM MED ASSOC
SN - 0098-7484
IS - 17
ER -