Hydrocortisone plus Fludrocortisone for Adults with Septic Shock

作者：Djillali Annane, Alain Renault, Christian Brun‐Buisson, Bruno Mégarbane, Jean‐Pierre Quenot, Shidasp Siami, Alain Cariou, Xavier Forceville, Carole Schwebel, Claude Martin, Jean‐François Timsit, Benoît Misset, Mohamed Ali Benali, Gwenhaël Colin, Bertrand Souweine, Karim Asehnoune, Emmanuelle Mercier, Loïc Chimot, Claire Charpentier, Bruno François, Thierry Boulain, Franck Petitpas, Jean‐Michel Constantin, Gilles Dhonneur, François Baudin, Alain Combes, Julien Bohé, Jean-François Loriferne, Roland Amathieu, Fabrice Cook, Michel Slama, O. Leroy, Gilles Capellier, Auguste Dargent, Tarik Hissem, Virginie Maxime, Éric Bellissant · 发表于：New England Journal of Medicine · 年份：2018 · DOI：10.1056/nejmoa1705716 · 被引用次数：933 · 研究领域：Adrenal Hormones and Disorders、Sepsis Diagnosis and Treatment、Immune Response and Inflammation

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was...