辅助糖皮质激素治疗脓毒性休克患者。

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.

机构信息

From the George Institute for Global Health, University of New South Wales (B.V., S.F., D.R., L.B., M.C., P.G., M.H., Q.L., K.T., J.M.), St. George Clinical School, St. George Hospital (J.M.), Sydney Medical School, University of Sydney (B.V., S.F., J.M.), and Royal North Shore Hospital (S.F.), Sydney, the Princess Alexandra Hospital (B.V., C.J.) and Royal Brisbane and Women's Hospital (J.C.), University of Queensland, and the Wesley Hospital (B.V., J.C.), Brisbane, Austin Hospital (R.B.), the School of Medicine, University of Melbourne (R.B.), and the Australian and New Zealand Research Centre (R.B.), School of Public Health and Preventive Medicine (R.B., S.W., J.M.), Monash University, Melbourne, VIC, and Royal Perth Hospital (S.W.) and the School of Medicine and Pharmacology, University of Western Australia (S.W.), Perth - all in Australia; King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.A.); the Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand (C.M.); Rigshospitalet, University of Copenhagen, Copenhagen (A.P.); and St. George's University Hospitals NHS Foundation Trust, St. George's University of London, London (A.R.).

出版信息

N Engl J Med. 2018 Mar 1;378(9):797-808. doi: 10.1056/NEJMoa1705835. Epub 2018 Jan 19.

DOI:10.1056/NEJMoa1705835

PMID:29347874

Abstract

BACKGROUND

Whether hydrocortisone reduces mortality among patients with septic shock is unclear.

METHODS

We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days.

RESULTS

From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia.

CONCLUSIONS

Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).

摘要

背景

氢化可的松是否能降低脓毒性休克患者的死亡率尚不清楚。

方法

我们将正在接受机械通气的脓毒性休克患者随机分为接受氢化可的松（每天 200mg）或安慰剂治疗 7 天，或直至死亡或从重症监护病房（ICU）出院（以先发生者为准）。主要结局为 90 天内的任何原因死亡。

结果

2013 年 3 月至 2017 年 4 月，共 3800 例患者接受了随机分组。在 3658 例患者（其中 1832 例分配到氢化可的松组，1826 例分配到安慰剂组）中确定了主要结局的状态。90 天时，氢化可的松组 511 例（27.9%）和安慰剂组 526 例（28.8%）患者死亡（比值比，0.95；95%置信区间[CI]，0.82 至 1.10；P=0.50）。试验方案的效果在六个预先指定的亚组中相似。与安慰剂组相比，接受氢化可的松治疗的患者休克更快得到缓解（中位持续时间，3 天[四分位间距，2 至 5]与 4 天[四分位间距，2 至 9]；风险比，1.32；95%CI，1.23 至 1.41；P<0.001）。氢化可的松组患者首次机械通气的持续时间短于安慰剂组（中位时间，6 天[四分位间距，3 至 18]与 7 天[四分位间距，3 至 24]；风险比，1.13；95%CI，1.05 至 1.22；P<0.001），但考虑到通气复发的情况，两组患者无机械通气天数和生存天数无显著差异。与安慰剂组相比，氢化可的松组接受输血的患者更少（37.0%比 41.7%；比值比，0.82；95%CI，0.72 至 0.94；P=0.004）。两组间 28 天死亡率、休克复发率、生存天数和离开 ICU 天数、生存天数和出院天数、机械通气复发率、肾脏替代治疗率以及新发菌血症或真菌血症发生率均无显著差异。