血管扩张性休克的血管紧张素 II 治疗。

Angiotensin II for the Treatment of Vasodilatory Shock.

机构信息

From Anesthesiology Institute, Center for Critical Care and Department of Outcomes Research, Cleveland Clinic, Cleveland (A.K.); the Department of Medicine (Critical Care), University of Ottawa, and the Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa (S.W.E.); Division of Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC (X.S.W.); Regions Hospital, St. Paul, MN (K.H.); University of Tennessee College of Medicine, Chattanooga (J.T.); the Division of Nephrology, Baylor University Medical Center, Dallas (H.S.); the Department of Medicine, Emory University School of Medicine, Atlanta (L.W.B.); Inova Medical Center, Falls Church, VA (L.A.); the Department of Internal Medicine, University of California Davis School of Medicine, Sacramento (T.E.A.), the Division of Critical Care, Department of Anesthesiology, University of California Los Angeles, Los Angeles (D.W.B.), and La Jolla Pharmaceutical Company, San Diego (J.J., S.K., L.S.C., G.F.T.) - all in California; the Department of Pulmonary and Critical Care Medicine, Riverside Methodist Hospital, Columbus, OH (C.M.); the Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore (M.T.M.); the Department of Surgery, Sunrise Hospital, Las Vegas (S.C.); Intensive Care Unit, Wellington Hospital, and Medical Research Institute of New Zealand, Wellington, New Zealand (P.J.Y.); the Division of Critical Care, Department of Medicine, Eastern Idaho Regional Medical Center, Idaho Falls (K.K.); the Department of Medicine, Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago (R.G.W.); the Department of Critical Care and Nephrology, King's College London, Guy's and St. Thomas' Hospital, London (M.O.); the Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh (R.M.); the Department of Medicine, Albert Einstein College of Medicine, and the Division of Critical Care Medicine, Montefiore Medical Center, Bronx, NY (M.N.G.); John Hunter Hospital, New Lambton Heights, and School of Medicine and Public Health, University of Newcastle, Callaghan, NSW (R.P.), the Department of Intensive Care, Wesley Hospital and Princess Alexandra Hospital, University of Queensland, St Lucia (B.V.), and School of Medicine, University of Melbourne, Parkville (R.B.), and the Intensive Care Unit, the Royal Melbourne Hospital, University of Melbourne (A.M.D.), Melbourne, VIC - all in Australia; the Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki (J.H.); INSERM UMR 995 LIRIC (Lille Inflammation Research Center), Centre Hospitalier Universitaire Lille, Critical Care Center and University of Lille School of Medicine, Lille, France (R.F.); and the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (B.T.T.).

出版信息

N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.

DOI:10.1056/NEJMoa1704154

PMID:28528561

Abstract

BACKGROUND

Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition.

METHODS

We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors.

RESULTS

A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12).

CONCLUSIONS

Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).

摘要

背景

对大剂量血管加压素无反应的血管扩张性休克与高死亡率相关。我们研究了血管紧张素 II 治疗这种情况的疗效。

方法

我们将接受超过 0.2μg/kg/分钟去甲肾上腺素或等效剂量的另一种血管加压剂的血管扩张性休克患者随机分为血管紧张素 II 组或安慰剂组。主要终点为输注开始后 3 小时的平均动脉压反应，定义为从基线至少增加 10mmHg 或增加至至少 75mmHg，同时不增加背景血管加压剂的剂量。

结果

共 344 名患者被分配到两种方案之一；321 名患者接受了研究干预（163 名接受血管紧张素 II，158 名接受安慰剂），并纳入分析。血管紧张素 II 组达到主要终点的患者多于安慰剂组（163 名患者中有 114 名，69.9%）（比值比，7.95；95%置信区间 [CI]，4.76 至 13.3；P<0.001）。48 小时时，血管紧张素 II 组心血管序贯器官衰竭评估（SOFA）评分的平均改善（评分范围为 0 至 4，评分越高表示功能障碍越严重）大于安慰剂组（-1.75 对 -1.28，P=0.01）。血管紧张素 II 组有 60.7%的患者和安慰剂组有 67.1%的患者报告了严重不良事件。血管紧张素 II 组有 75 名（46%）患者和安慰剂组有 85 名（54%）患者在 28 天内死亡（风险比，0.78；95%CI，0.57 至 1.07；P=0.12）。