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在抑肽酶时代结束后,重新评估赖氨酸类似物在心脏手术中抗纤维蛋白溶解治疗的作用。

Re-evaluation of the role of antifibrinolytic therapy with lysine analogs during cardiac surgery in the post aprotinin era.

机构信息

Institute of Anesthesiology, Heart and Diabetes Center Nordrheinwestfalen, Bad Oeynhausen, Ruhr University of Bochum, Bochum, Germany.

出版信息

Curr Opin Anaesthesiol. 2011 Feb;24(1):92-7. doi: 10.1097/ACO.0b013e32833ff3eb.

Abstract

PURPOSE OF REVIEW

Hemorrhage, transfusions and the need for re-exploration can have a detrimental effect on patient outcome in cardiac surgery. With the suspension of aprotinin from the market, only the antifibrinolytics tranexamic acid and epsilon-aminocaproic acid (EACA) are left as pharmacological options to reduce hemostatic activation and associated bleeding complications. In light of the aprotinin story, the need for large independent safety studies has become evident. The current review will focus on the question of how far the quality of available data allows for judging these agents with regard to safety and efficacy, as well as whether or not new trails are warranted.

RECENT FINDINGS

Both, tranexamic acid and EACA are effective in reducing blood loss and transfusion requirements in cardiac surgery. Analysis of data is complicated as the dosing scheme, especially for tranexamic acid, varies extremely and the agents are highly overdosed in most relevant trials. Newer data indicates that in a dose-dependent fashion, tranexamic acid is associated with an increase of adverse events, particularly the observation of seizures. In these studies, however, tranexamic acid has also been highly overdosed.

SUMMARY

The lysine analogs are unspecific enzyme inhibitors. Therefore, it is conceivable that an overdosing might reveal severe clinical side-effects beyond the inhibition of plasmin. Further studies re-evaluating the drug safety of tranexamic acid and EACA using the recommended and approved doses are necessary.

摘要

目的综述

出血、输血和再次探查的需要可能对心脏手术患者的预后产生不利影响。随着抑肽酶从市场上撤出,只有抗纤维蛋白溶解药氨甲环酸和氨基己酸(EACA)作为减少止血激活和相关出血并发症的药物选择。鉴于抑肽酶的故事,显然需要进行大型独立安全性研究。本综述将重点讨论现有数据的质量在多大程度上允许我们判断这些药物的安全性和有效性,以及是否需要新的试验。

最近的发现

氨甲环酸和 EACA 均可有效减少心脏手术中的失血和输血需求。由于剂量方案(尤其是氨甲环酸)差异极大,并且在大多数相关试验中药物剂量过高,因此分析数据变得复杂。新的数据表明,氨甲环酸与不良事件的增加有关,特别是癫痫发作的观察,呈剂量依赖性。然而,在这些研究中,氨甲环酸也被高度过量使用。

总结

赖氨酸类似物是非特异性酶抑制剂。因此,可以想象,过量使用可能会导致除纤溶酶抑制以外的严重临床副作用。有必要使用推荐和批准的剂量对氨甲环酸和 EACA 的药物安全性进行重新评估。

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