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感染性休克的早期目标导向治疗——一项患者水平的荟萃分析
Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis


The PRISM Investigators* 其他 • 2017.06.08
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急诊科早期脓毒症休克患者实施早期目标导向治疗并不优于常规治疗

 

周飞虎†,康红军†,Naomi R. George‡,Peter C. Hou‡*

†中国人民解放军总医院重症医学科;‡ Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

*通讯作者

 

2001年,Emanuel Rivers在《新英格兰医学杂志》上发表了关于脓毒症休克早期目标导向治疗(EGDT)的临床研究1。这是一项被誉为具有里程碑意义的单中心随机对照试验(RCT),共计纳入了263例患者。研究结果显示EGDT显著改善了患者的死亡率,研究结论被全球多家学术机构采纳并用于制定重症脓毒症和脓毒症休克的国际指南2。此后,《新英格兰医学杂志》又发表了三项相关临床研究(后文统称“三项研究”)来比较EGDT与常规治疗(UC)的优劣,每一项研究均为多中心、纳入病例超过1,000例的RCT研究(ProCESS 2014、ARISE 2015和ProMISe 2015)。没有一项研究证实EGDT在脓毒症休克早期治疗中优于常规治疗3-5

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摘要


背景

一项单中心试验和观察性研究表明,早期目标导向治疗(early,goal-directed therapy,EGDT)能够降低感染性休克的死亡率;之后,三项多中心试验(ProCESS、ARISE以及ProMISe)的结果显示,EGDT没有益处。我们设计了一项前瞻性的荟萃分析,通过对近期三项试验的个体患者的资料进行荟萃分析,试图提高统计学功效并探讨EGDT治疗效果的异质性。

 

方法

我们协调统一了三项试验的入组标准、干预方案、结局、资源利用的指标以及数据收集方法,并且在揭盲前详细规定了所有的分析方案。在试验完成之后,我们将数据加以汇集,将ProCESS试验中基于试验方案的标准治疗组排除在外,并解决了残留差异的问题。主要结局是90日死亡率。次要结局包括1年生存率、器官支持以及住院花费。针对16种患者特征以及6种诊疗特征,我们对不同亚组与治疗方案的交互作用进行了检验。

 

结果

我们对7个国家138家医院中的3,723例患者进行了研究。EGDT组(1,852例患者中有462例死亡,24.9%)和常规治疗组(1,871例患者中有475例死亡,25.4%)的90日死亡率相似;调整后的比值比为0.97(95%置信区间[CI],0.82~1.14;P=0.68)。与常规治疗组相比,EGDT组与下列结局相关:重症监护的平均时间(±SD)较长(5.3日±7.1日对4.9日±7.0天,P=0.04)以及心血管支持的平均时间(±SD)较长(1.9日±3.7日对1.6日±2.9日,P=0.01);尽管EGDT组的平均花费较高,但其他结局没有显著差异。亚组分析显示,对于休克较为严重(血清乳酸水平较高、低血压合并高乳酸血症或者预测死亡风险较高)的患者,或在常规复苏期间使用血管加压药或液体的倾向性较低的医院,EGDT并未显示出治疗获益。

 

结论

对个体患者数据进行的荟萃分析表明,与常规治疗相比,EGDT未引起结局的改善,而且对于各种不同的患者和医院特征,EGDT均与住院花费较高相关(由美国国立综合医学研究所[National Institute of General Medical Sciences]和其他单位资助;PRISM在ClinicalTrials.gov注册号为NCT02030158)。





作者信息

The PRISM Investigators*
The members of the writing committee (Kathryn M. Rowan, Ph.D., Derek C. Angus, M.D., M.P.H., Michael Bailey, Ph.D., Amber E. Barnato, M.D., Rinaldo Bellomo, M.D., Ruth R. Canter, M.Sc., Timothy J. Coats, M.D., Anthony Delaney, M.D., Ph.D., Elizabeth Gimbel, R.N., B.S., Richard D. Grieve, Ph.D., David A. Harrison, Ph.D., Alisa M. Higgins, M.P.H., Belinda Howe, M.P.H., David T. Huang, M.D., M.P.H., John A. Kellum, M.D., Paul R. Mouncey, M.Sc., Edvin Music, M.S.I.S., Sandra L. Peake, M.D., Ph.D., Francis Pike, Ph.D., Michael C. Reade, M.B., B.S., D.Phil., M. Zia Sadique, Ph.D., Mervyn Singer, M.D., and Donald M. Yealy, M.D.) assume responsibility for the overall content and integrity of this article. The affiliations of the writing committee members are listed in the Appendix. Address reprint requests to Dr. Rowan at the Intensive Care National Audit and Research Centre, Napier House, 24 High Holborn, London WC1V 6AZ, United Kingdom, or at kathy.rowan@icnarc.org. *The Protocolized Resuscitation in Sepsis Meta-Analysis (PRISM) study is a collaboration of the Protocolized Care for Early Septic Shock (ProCESS) Investigators, based in the United States; the Australasian Resuscitation in Sepsis Evaluation (ARISE) Investigators, based in Australia and New Zealand; the Protocolised Management in Sepsis (ProMISe) Investigators, based in the United Kingdom; and the International Forum for Acute Care Trialists. A complete list of the investigator groups is provided in the Supplementary Appendix, available at NEJM.org.

 

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