肝素在中重度脓毒症诱导性凝血功能障碍患者中的疗效：一项观察性研究。

Efficacy of unfractionated heparin in patients with moderate sepsis-induced coagulopathy: An observational study.

机构信息

Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.

Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.

出版信息

Thromb Res. 2024 Sep;241:109095. doi: 10.1016/j.thromres.2024.109095. Epub 2024 Jul 6.

DOI:10.1016/j.thromres.2024.109095

PMID:39024902

Abstract

INTRODUCTION

The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin.

MATERIALS AND METHODS

In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups.

RESULTS

Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596-0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926-1.391, 0.853-1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265-0.751, 0.410-0.940, respectively).

CONCLUSIONS

Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.

摘要

介绍

2021 年《拯救脓毒症运动指南》建议对脓毒症患者使用低分子肝素预防静脉血栓栓塞症。然而，观察性研究表明，抗凝剂整体上可能对合并凝血功能障碍的重症脓毒症患者有益，但普通肝素的最佳目标仍不清楚。本研究旨在探究哪些脓毒症患者最能从普通肝素治疗中获益。

材料和方法

本回顾性观察性研究使用大型日本医疗数据库，于 2006 年至 2019 年期间确定需要紧急住院的成年脓毒症患者。将患者分为两组：入院 72 小时内接受普通肝素治疗组和未接受普通肝素治疗组。使用多变量逻辑回归模型，根据患者和治疗变量进行调整，比较两组患者的住院死亡率、主要出血并发症和血栓栓塞事件。此外，我们评估了肝素给药与不同亚组患者住院死亡率之间的相关性。

结果

在 30342 例脓毒症患者中，2520 例患者早期接受肝素治疗，27822 例患者未接受肝素治疗。多变量逻辑回归显示，肝素与降低住院死亡率显著相关（调整后的比值比：0.735，95%可信区间：0.596-0.903），但与主要出血和血栓栓塞风险无显著相关（调整后的比值比：1.137，1.243；95%可信区间：0.926-1.391，0.853-1.788）。亚组分析表明，肝素仅在中重度脓毒症合并凝血功能障碍评分 3 或 4 分的患者中具有显著的生存获益（调整后的比值比：0.452，0.625；95%可信区间：0.265-0.751，0.410-0.940）。