Hydrocortisone Therapy for Patients with Septic Shock
Charles L. Sprung, M.D., Djillali Annane, M.D., Ph.D., Didier Keh, M.D., Rui Moreno, M.D., Ph.D., Mervyn Singer, M.D., F.R.C.P., Klaus Freivogel, Ph.D., Yoram G. Weiss, M.D., Julie Benbenishty, R.N., Armin Kalenka, M.D., Helmuth Forst, M.D., Ph.D., Pierre-Francois Laterre, M.D., Konrad Reinhart, M.D., Brian H. Cuthbertson, M.D., Didier Payen, M.D., Ph.D., Josef Briegel, M.D., Ph.D., for the CORTICUS Study Group
Background Hydrocortisone is widely used in patients with septicshock even though a survival benefit has been reported onlyin patients who remained hypotensive after fluid and vasopressorresuscitation and whose plasma cortisol levels did not riseappropriately after the administration of corticotropin.
Methods In this multicenter, randomized, double-blind, placebo-controlledtrial, we assigned 251 patients to receive 50 mg of intravenoushydrocortisone and 248 patients to receive placebo every 6 hoursfor 5 days; the dose was then tapered during a 6-day period.At 28 days, the primary outcome was death among patients whodid not have a response to a corticotropin test.
Results Of the 499 patients in the study, 233 (46.7%) did nothave a response to corticotropin (125 in the hydrocortisonegroup and 108 in the placebo group). At 28 days, there was nosignificant difference in mortality between patients in thetwo study groups who did not have a response to corticotropin(39.2% in the hydrocortisone group and 36.1% in the placebogroup, P=0.69) or between those who had a response to corticotropin(28.8% in the hydrocortisone group and 28.7% in the placebogroup, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisonegroup (34.3%) and 78 of 248 patients in the placebo group (31.5%)had died (P=0.51). In the hydrocortisone group, shock was reversedmore quickly than in the placebo group. However, there weremore episodes of superinfection, including new sepsis and septicshock.
Conclusions Hydrocortisone did not improve survival or reversalof shock in patients with septic shock, either overall or inpatients who did not have a response to corticotropin, althoughhydrocortisone hastened reversal of shock in patients in whomshock was reversed. (ClinicalTrials.gov number, NCT00147004
[ClinicalTrials.gov]
.)
Source Information
From Hadassah Hebrew University Medical Center, Jerusalem (C.L.S., Y.G.W., J. Benbenishty); Raymond Poincaré Hospital, University of Versailles, UniverSud Paris, Garches, France (D.A.); Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin (D.K.); Hospital de St. António dos Capuchos, Centro Hospitalar de Lisboa Central, Lisbon, Portugal (R.M.); Bloomsbury Institute of Intensive Care Medicine, University College London, London (M.S.); Analytica International, Loerrach, Germany (K.F.); Klinikum Mannheim, Mannheim, Germany (A.K.); Zentralklinikum Augsburg, Augsburg, Germany (H.F.); St. Luc University Hospital, Université Catholique de Louvain, Brussels (P.-F.L.); Friedrich Schiller Universität, Jena, Germany (K.R.); Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom (B.H.C.); Hôpital Lariboisière, Denis Diderot University of Paris, Paris (D.P.); and Klinikum der Universität, Ludwig Maximilians Universität, Munich, Germany (J. Briegel).
Address reprint requests to Dr. Sprung at the General Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, P.O. Box 12000, Jerusalem, Israel 91120, or at sprung{at}cc.huji.ac.il.
Corticosteroids for Septic Shock
Daley M. R., Seam N., Luboshitzky R., Qupti G., Bollaert P.-E., Marik P. E., Pastores S. M., Kavanagh B. P., Manoach S., Sprung C. L., Singer M., Annane D., the CORTICUS Study Group
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N Engl J Med 2008;
358:2068-2071, May 8, 2008.
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