Marko Nemet, I Serhat Karakus, G Cameron Gmehlin, Gabriele Alves Halpern, Kimia Ghafouri, Sergej Abramovich, Roshini Raghu, Mila Pastrak, Nasrin Nikravangolsefid, Gerberi J Dana, Svetlana Herasevich, Yewande Odeyemi, Amos Lal, Ognjen Gajic
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引用次数: 0
摘要
本系统综述检查了在脓毒症-3期进行的多中心随机对照试验(RCTs),这些试验评估了成人脓毒症或脓毒性休克患者的药物和机械干预措施,重点是确定证明降低死亡率的干预措施。在Ovid MEDLINE、Embase、Cochrane Central、ClinicalTrials.gov、WHO ICTRP和Web of Science上对2016年以来发表的试验进行了全面搜索。如果研究纳入了脓毒症或脓毒性休克的成年患者,使用脓毒症-3标准,并报告死亡率为主要或次要结局,则纳入研究。数据由两名独立审稿人提取,包括试验设计特征、资金来源、随机化方法和报告结果。在31项符合条件的多中心随机对照试验中,在550个中心招募了7000多名患者,只有4项试验显示死亡率降低。其中包括来自中国的三项研究——两项评估草药抗炎化合物,一项评估氨茶碱——以及一项评估皮质类固醇治疗血管加压剂依赖性感染性休克的欧洲研究。其余27项试验未报告死亡率获益,并且在患者群体、败血症定义和结果报告中观察到实质性的异质性。对照组的中位死亡率为31.6% (IQR 24.1-45.5),干预组为35.4% (IQR 25.7-49.6)。这些发现表明,尽管进行了广泛的努力,大多数干预措施并没有降低多中心败血症试验中的死亡率。未来的研究应侧重于优化试验设计,改进患者选择,并纳入以患者为中心的死亡率以外的结果。
Mortality in the Sepsis-3 Era: A Systematic Review of Multicenter Randomized Controlled Trials.
This systematic review examined multicenter randomized controlled trials (RCTs) conducted during the Sepsis-3 era that evaluated pharmaceutical and mechanistic interventions in adult patients with sepsis or septic shock, with a focus on identifying interventions that demonstrated mortality benefit. A comprehensive search was performed across Ovid MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, WHO ICTRP, and Web of Science for trials published since 2016. Studies were included if they enrolled adult patients with sepsis or septic shock using Sepsis-3 criteria and reported mortality as either a primary or secondary outcome. Data were extracted by two independent reviewers and included trial design characteristics, funding source, randomization methods, and reported outcomes. Among the 31 eligible multicenter RCTs enrolling over 7,000 patients across 550 centers, only four trials showed a mortality benefit. These included three studies from China-two evaluating herbal anti-inflammatory compounds and one evaluating aminophylline-and one European study assessing corticosteroid therapy in vasopressor-dependent septic shock. The remaining 27 trials reported no mortality benefit, and substantial heterogeneity was observed in patient populations, sepsis definitions, and outcome reporting. Median mortality in control arms was 31.6% (IQR 24.1-45.5), and 35.4% (IQR 25.7-49.6) in intervention arms. These findings suggest that despite extensive efforts, most interventions have not reduced mortality in multicenter sepsis trials. Future research should focus on optimizing trial design, refining patient selection, and incorporating patient-centered outcomes beyond mortality.
期刊介绍:
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.