Tsuchida Takumi, Makino Yuto, Wada Takeshi, Ushio Noritaka, Totoki Takaaki, Fujie Naoki, Yasuo Shunsuke, Matsuoka Tadashi, Koami Hiroyuki, Yamakawa Kazuma, Iba Toshiaki
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine Hokkaido University Faculty of Medicine Sapporo Japan.
Department of Preventive Services Kyoto University Graduate School of Medicine Kyoto Japan.
Acute Med Surg. 2024 Apr 17;11(1):e950. doi: 10.1002/ams2.950. eCollection 2024 Jan-Dec.
There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage.
We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases.
Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality.
A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.
关于抗凝血酶对脓毒症的影响，报告结果并不一致；此外，关于剂量如何影响治疗效果的报告有限。因此，我们旨在对抗凝血酶用于脓毒症的情况进行系统评价和荟萃分析，并对抗凝血酶剂量进行荟萃回归分析。
我们纳入了接受抗凝血酶治疗的成年脓毒症患者的随机对照试验（RCT）和观察性研究。结局包括全因死亡率和严重出血并发症。使用随机效应模型进行统计分析和数据合成；此外，采用荟萃回归和漏斗图来探讨异质性和偏倚。
纳入了7项RCT和6项观察性研究。RCT和观察性研究中的大多数患者分别患有严重脓毒症和脓毒性弥散性血管内凝血（DIC）。使用RCT进行的荟萃分析显示，抗凝血酶组和对照组之间的死亡率无显著差异。然而，观察性研究的荟萃分析表明，使用抗凝血酶后死亡率有下降趋势（优势比[OR]，0.79；95%置信区间[CI]，0.68 - 0.92；P = 0.002）。在两种研究类型中，抗凝血酶组的出血并发症均显著高于对照组（OR，1.90；95% CI，1.52 - 2.37；P < 0.01）。荟萃回归分析显示抗凝血酶剂量与死亡率之间无相关性。
RCT的荟萃分析证实抗凝血酶无生存获益，而主要关注脓毒性DIC的观察性研究的荟萃分析显示其对改善结局有显著有益作用。应根据抗凝血酶的利弊来考虑其适应证。
