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血管紧张素Ⅱ治疗血管扩张性休克的研究
Angiotensin II for the Treatment of Vasodilatory Shock


Ashish Khanna ... 其他 • 2017.08.03
相关阅读
• 一种新型血管升压药

血管扩张性休克:亟须关注的临床问题

 

荆志成

中国医学科学院阜外医院心血管疾病国家重点实验室,心血管内科

 

血管扩张性休克是临床上最常见的一类休克,其主要特征是外周血管扩张,血压下降,而心排血量不变或升高1。主要治疗原则是积极治疗原发病,补充血容量;如果仍然无效,可静脉应用血管收缩药。应用大剂量血管收缩药(如儿茶酚胺类药物或后叶加压素)仍无效时,则定义为儿茶酚胺抵抗的血管扩张性休克,治疗十分棘手,30日死亡率高达50%2

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摘要


背景

对大剂量血管升压药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在此类患者中的疗效。

 

方法

我们将接受超过0.2 μg/(kg·min)去甲肾上腺素或接受等效剂量其他血管升压药的血管扩张性休克患者随机分配到血管紧张素Ⅱ输注组或安慰剂输注组。主要终点是在开始输注药物后3小时平均动脉压的应答。有应答的定义为在没有增加背景血管升压药的情况下,输注药物后平均动脉压比基线升高至少10 mmHg或升高至75 mmHg或以上。

 

结果

共344例患者被分配接受两种治疗方法中的一种。321例患者接受研究干预(其中,163例接受血管紧张素Ⅱ,158例接受安慰剂)并被纳入分析。血管紧张素Ⅱ组(114/163人,69.9%)比安慰剂组(37/158人,23.4%)到达主要终点的患者多(比值比,7.95;95%置信区间[CI],4.76~13.3;P<0.001)。在48小时,血管紧张素Ⅱ组中,心血管序贯器官衰竭评分(Sequential Organ Failure Assessment,SOFA)(评分范围为0~4分,评分较高表示功能障碍程度较重)的平均改善幅度比安慰剂组大(-1.75对-1.28;P=0.01)。血管紧张素Ⅱ组中有60.7%的患者发生严重不良事件,而安慰剂组则为67.1%。血管紧张素Ⅱ组患者28日内死亡率为46%(75/163人),而安慰剂组为54%(85/158人;风险比,0.78;95% CI,0.57~1.07;P=0.12)。

 

结论

血管紧张素Ⅱ能有效提高对大剂量传统血管升压药无应答的血管扩张性休克患者的血压(拉荷亚制药公司[La Jolla Pharmaceutical Company]资助;ATHO-3在ClinicalTrials.gov注册号为NCT02338843)。





作者信息

Ashish Khanna, M.D., Shane W. English, M.D., Xueyuan S. Wang, M.D., Kealy Ham, M.D., James Tumlin, M.D., Harold Szerlip, M.D., Laurence W. Busse, M.D., Laith Altaweel, M.D., Timothy E. Albertson, M.D., M.P.H., Ph.D., Caleb Mackey, M.D., Michael T. McCurdy, M.D., David W. Boldt, M.D., Stefan Chock, M.D., Paul J. Young, M.B., Ch.B., Ph.D., Kenneth Krell, M.D., Richard G. Wunderink, M.D., Marlies Ostermann, M.D., Ph.D., Raghavan Murugan, M.D., Michelle N. Gong, M.D., Rakshit Panwar, M.D., Johanna Hästbacka, M.D., Ph.D., Raphael Favory, M.D., Ph.D., Balasubramanian Venkatesh, M.D., B. Taylor Thompson, M.D., Rinaldo Bellomo, M.D., Jeffrey Jensen, B.S., Stew Kroll, M.A., Lakhmir S. Chawla, M.D., George F. Tidmarsh, M.D., Ph.D., and Adam M. Deane, M.D., for the ATHOS-3 Investigators*
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.). Address reprint requests to Dr. Bellomo at the University of Melbourne, Department of Intensive Care, Austin Hospital and Royal Melbourne Hospital, Melbourne, VIC, Australia, or atrinaldo.bellomo@austin.org.au *A complete list of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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