多中心重症监护试验中的死亡率：具有显著效果的干预措施分析。

Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect.

机构信息

1Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2Cardiac and Vascular Department, Mauriziano Hospital, Turin, Italy. 3Department of Anesthesia and Intensive Care, Maria Cecilia Hospital - GVM Care & Research, Cotignola (RA), Italy. 4Department of Medical Sciences "M. Aresu," University of Cagliari, Cagliari, Italy. 5Cardiovascular Anesthesia and Intensive Care, San Carlo Hospital, Potenza, Italy. 6Division of Cardiac Anesthesia and Intensive Care, Azienda Ospedaliera Dei Colli, V Monaldi, Naples, Italy. 7A.O. Mater Domini Germaneto, Catanzaro, Italy. 8Cardioanesthesia and Intensive Care, IRCCS University Hospital San Martino Ist, Genova, Italy. 9Department of Anesthesia and Intensive Care, S. Maria dei Battuti Hospital ULSS 9, Treviso, Italy. 10Cardiothoracic and Vascular Anesthesia and Intensive Care, S. Orsola-Malpighi University Hospital, Bologna, Italy. 11FTGM-"G. Pasquinucci" Heart Hospital, Massa, Italy. 12Department of Pharmacology and Anesthesiology, University Hospital of Padova, Padova, Italy. 13Department of Anesthesia and Intensive Care, "S. Maria di Ca' Foncello," Treviso, Italy. 14Department of Anaesthesia and Critical Care Medicine, University Hospital of Pisa, Pisa, Italy. 15Anesthesia and Critical Care Medicine, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy. 16Department of Anesthesia and Intensive Care, University of Cagliari, Cagliari, Italy. 17Cardioanesthesia and Intensive Care, Civil Hospital "SS Annunziata," Sassari, Italy. 18Cardiac and Vascular Department, Casa di Cura Villa Verde, Taranto, Italy. 19Department of Anesthesia, Intensive Care Medicine, Cardinal Massaia Hospital, Asti, Italy. 20Division of Cardiac Surgery, University of Genova Medical School, Genova, Italy. 21Department of Anesthesiology and Intensive Care, Semmelweis University, Budapest, Hungary. 22Anesthesia and Resuscitation, United Company Hospital Papardo-Piemonte, Messina, Italy. 23Depa

出版信息

Crit Care Med. 2015 Aug;43(8):1559-68. doi: 10.1097/CCM.0000000000000974.

DOI:10.1097/CCM.0000000000000974

PMID:25821918

Abstract

OBJECTIVES

We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions.

DATA SOURCES

MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references.

STUDY SELECTION

We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility.

DATA EXTRACTION

For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up.

DATA SYNTHESIS

We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions.

CONCLUSIONS

We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

摘要

目的

我们旨在确定多中心随机对照试验中影响成年危重症患者死亡率的所有治疗方法。我们还评估了这些研究的方法学方面，并调查了临床医生对选定干预措施的意见和常规做法。

资料来源

检索了 MEDLINE/PubMed、Scopus 和 Embase。还建议专家纳入进一步的文章，并交叉检查参考文献。

研究选择

我们选择了符合以下标准的文章：发表在同行评议的期刊上；多中心随机对照试验设计；涉及成年危重症患者的非手术干预；以及未经调整的里程碑死亡率有统计学意义的效果。共识会议评估了所有干预措施，并排除了那些缺乏可重复性、缺乏普遍性、高 I 型错误概率、干预组和对照组之间存在重大基线不平衡、重大设计缺陷、随后更大规模高质量试验的矛盾、修改后的意向治疗分析、仅在调整后发现效果、以及缺乏生物学合理性的干预措施。

资料提取

对于所有选定的研究，我们记录了干预措施及其对照、设置、样本量、是否完成或中断招募、是否存在盲法、效应大小以及随访时间。

资料综合

我们发现了 15 种干预措施，这些干预措施在 24 项多中心随机对照试验中影响了死亡率。中位数样本量较小（199 例），中位数中心数量也较少（10 个）。盲法试验招募的患者显著更多，涉及的中心也更多。显示危害的多中心随机对照试验还涉及更多的中心和更多的患者（p = 0.016 和 p = 0.04，分别）。来自 61 个国家的 555 名临床医生对这些干预措施的有效性的看法存在差异。