低剂量抑肽酶在冠状动脉搭桥手术中的安全性：德国2436例患者的单中心研究

Safety of low-dose aprotinin in coronary artery bypass graft surgery: a single-centre investigation in 2,436 patients in Germany.

作者信息

Kluth Mario, Lueth Jan U, Zittermann Armin, Lanzenstiel Markus, Koerfer Reiner, Inoue Kazuo

机构信息

Institute for Anaesthesiology, Heart Center North-Rhine Westfalia, Ruhr University Bochum, Bad Oeynhausen, Germany.

出版信息

Drug Saf. 2008;31(7):617-26. doi: 10.2165/00002018-200831070-00007.

DOI:10.2165/00002018-200831070-00007

PMID:18558795

Abstract

BACKGROUND

The antifibrinolytic agent aprotinin is used to limit blood loss in cardiac surgery. In a recently performed multicentre observational study, the use of aprotinin was dose-dependently associated with a higher risk of renal failure and cardiovascular events.

OBJECTIVE

Therefore, the aim of this study was to evaluate the impact of low-dose aprotinin (2 million kallikrein-inhibitor units) on safety variables in a large single-centre investigation in patients who underwent coronary artery bypass graft (CABG) surgery.

METHODS

Clinical outcome variables such as renal failure, myocardial infarction, gastrointestinal failure, neurological complications and in-hospital mortality were assessed in 2,436 CABG surgery patients, whereof 1,162 patients received low-dose aprotinin perioperatively and 1,274 patients did not receive aprotinin. Statistical analysis was performed using multivariable logistic regression.

RESULTS

In patients receiving aprotinin, the odds ratios of experiencing one of the aforementioned adverse events were not significantly different from the patients who did not receive aprotinin (p = 0.136-0.288). Moreover, the need for rethoracotomy did not differ between the two groups (p = 0.129). However, the use of low-dose aprotinin reduced the risk of peri- and postoperative use of packed red blood cells by 39% and was associated with a mean reduction in postoperative blood loss of 201 mL compared with patients who did not receive aprotinin (p < 0.001). Mean total blood loss in the aprotinin group and the control group was 875 mL (standard deviation [SD]: 757 mL) and 1,105 mL (SD: 867 mL), respectively (p < 0.001). In a sub-analysis in 2,049 patients undergoing their first cardiac surgery and undergoing CABG using the internal mammary artery, efficacy and safety data of aprotinin were similar to the results of the entire study cohort of 2,436 patients.

CONCLUSIONS

Our data indicate that low-dose aprotinin efficiently reduces blood loss and does not adversely affect relevant safety variables in CABG surgery.

摘要

背景

抗纤溶药物抑肽酶用于限制心脏手术中的失血。在最近进行的一项多中心观察性研究中，抑肽酶的使用与肾衰竭和心血管事件的较高风险呈剂量依赖性相关。

目的

因此，本研究的目的是在一项针对接受冠状动脉旁路移植术（CABG）的患者的大型单中心调查中，评估低剂量抑肽酶（200万激肽释放酶抑制单位）对安全变量的影响。

方法

对2436例CABG手术患者的临床结局变量进行评估，如肾衰竭、心肌梗死、胃肠功能衰竭、神经系统并发症和住院死亡率，其中1162例患者围手术期接受低剂量抑肽酶治疗，1274例患者未接受抑肽酶治疗。使用多变量逻辑回归进行统计分析。

结果

接受抑肽酶治疗的患者发生上述不良事件之一的比值比与未接受抑肽酶治疗的患者无显著差异（p = 0.136 - 0.288）。此外，两组再次开胸手术的需求无差异（p = 0.129）。然而，与未接受抑肽酶治疗的患者相比，低剂量抑肽酶的使用使围手术期和术后使用浓缩红细胞的风险降低了39%，且术后失血量平均减少201 mL（p < 0.001）。抑肽酶组和对照组的平均总失血量分别为875 mL（标准差[SD]：757 mL）和1105 mL（SD：867 mL）（p < 0.001）。在对2049例首次接受心脏手术并使用乳内动脉进行CABG的患者进行的亚分析中，抑肽酶的疗效和安全性数据与2436例患者的整个研究队列的结果相似。