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脂质乳剂预处理对离体鼠心模型中甲哌卡因和布比卡因心脏毒性的影响不同。

Lipid emulsion pretreatment has different effects on mepivacaine and bupivacaine cardiac toxicity in an isolated rat heart model.

机构信息

Department of Anaesthesiology, University of Regensburg, Regensburg, Germany.

出版信息

Br J Anaesth. 2014 Apr;112(4):735-41. doi: 10.1093/bja/aet353. Epub 2013 Oct 29.

Abstract

BACKGROUND

The use of lipid emulsions to reduce cardiac toxicity of local anaesthetics (LAs) has shown success in experimental studies and some clinical cases, and thus has been implemented in clinical practice. However, lipid treatment is usually given after the occurrence of neurological or cardiovascular symptoms of systemic intoxication. The aim of this study was to determine if pretreatment with lipid emulsion reduces cardiac toxicity produced by bupivacaine or mepivacaine.

METHODS

Isolated rat hearts were perfused with or without lipid emulsion (0.25 ml kg(-1) min(-1)) before administration of equipotent doses of bupivacaine (250 µM) or mepivacaine (1000 µM). Haemodynamic parameters and times from start of perfusion LA to a 1 min period of asystole and recovery were determined.

RESULTS

Pretreatment with lipid emulsion extended the time until occurrence of asystole and decreased times to recovery in bupivacaine-induced cardiac toxicity but not in mepivacaine-induced cardiac toxicity compared with control. Lipid pretreatment impaired rate-pressure product recovery in mepivacaine-intoxicated hearts.

CONCLUSIONS

This study confirms that pretreatment with a lipid emulsion reduces cardiac toxicity of LAs. The efficacy of pretreatment with lipid emulsion was LA-dependent, so pharmacokinetic properties, such as lipophilicity, might influence the effects of lipid emulsion pretreatment.

摘要

背景

在实验研究和一些临床病例中,使用脂肪乳剂来降低局部麻醉剂(LA)的心脏毒性已取得成功,因此已在临床实践中实施。然而,脂肪治疗通常在发生全身中毒的神经或心血管症状后进行。本研究的目的是确定脂质乳剂预处理是否可以减轻布比卡因或甲哌卡因引起的心脏毒性。

方法

在给予等效力的布比卡因(250 µM)或甲哌卡因(1000 µM)之前,用或不用脂肪乳剂(0.25 ml kg(-1) min(-1))对分离的大鼠心脏进行预处理。测定血流动力学参数和从开始灌注 LA 到停搏 1 分钟和恢复的时间。

结果

与对照组相比,脂质乳剂预处理可延长布比卡因引起的心脏毒性发作时间,并减少心脏毒性发作至恢复的时间,但对甲哌卡因引起的心脏毒性无影响。脂质预处理会损害甲哌卡因中毒心脏的速率-压力产物的恢复。

结论

本研究证实,脂质乳剂预处理可降低 LA 的心脏毒性。脂质乳剂预处理的疗效取决于 LA,因此亲脂性等药代动力学特性可能会影响脂质乳剂预处理的效果。

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