Myocardial and Cerebral Drug Concentrations and the Mechanisms of Death after Fatal Intravenous Doses of Lidocaine, Bupivacaine, and Ropivacaine in the Sheep
Myocardial and Cerebral Drug Concentrations and the Mechanisms of Death after Fatal Intravenous Doses of Lidocaine, Bupivacaine, and Ropivacaine in the Sheep
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绵羊静脉注射致命剂量利多卡因、布比卡因和罗哌卡因后心肌和脑部药物浓度及死亡机制
DOI：
10.1213/00000539-198909000-00002
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发表时间：
1989
影响因子：
5.7
通讯作者：
S. Hipkins
中科院分区：
文献类型：
--
作者：
C. Nancarrow;A. J. Rutten;W. Runciman;L. Mather;R. Carapetis;C. McLean;S. Hipkins
本文报道了静脉注射利多卡因、布比卡因和罗哌卡因的心血管效应和死亡机制。利多卡因、布比卡因和罗哌卡因的致死剂量在每种药物连续每日剂量递增处理的绵羊中确立。利多卡因的平均致死剂量（± SD）为1450 ± 191 mg（30.8 ± 5.8 mg/kg），布比卡因为156 ± 31 mg（3.7 ± 1.1 mg/kg），罗哌卡因为325 ± 108 mg（7.3 ± 1.0 mg/kg）;因此致死剂量比约为9：1：2。在利多卡因治疗的4只动物中，呼吸抑制伴心动过缓和低血压（无心律失常）是死亡原因。四分之三的布比卡因治疗动物在室性心动过速/纤颤突然发作后死亡，无缺氧或酸中毒;第四只动物以与利多卡因治疗动物相似的方式死亡。给予罗哌卡因的五只动物中有三只以类似于利多卡因治疗动物的致命作用的方式死亡，但与利多卡因治疗动物不同的是，所有三只绵羊中也有室性心律失常的时期。其余2只罗哌卡因给药绵羊因室性心动过速/纤颤突然发作而死亡。利多卡因给药动物心肌中发现的致死剂量的平均百分比为2.8 ± 0.7，布比卡因给药动物为3.3 ± 0.9，罗哌卡因给药动物为2.2 ± 1.4;全脑中的相应百分比分别为0.71 ± 0.01、0.71 ± 0.21和0.89 ± 0.27。
This paper reports the cardiovascular effects of intentionally toxic intravenous doses of lidocaine, bupivacaine, and ropivacaine and the mechanisms of death. Fatal doses of lidocaine, bupivacaine, and ropivacaine were established in sheep treated with successive daily dose increments of each drug. The mean fatal dose of lidocaine (± SD) was 1450 ± 191 mg (30.8 ± 5.8 mg/kg), that of bupivacaine was 156 ± 31 mg (3.7 ± 1.1 mg/kg), and that of ropivacaine was 325 ± 108 mg (7.3 ± 1.0 mg/kg); thus the ratio of fatal doses was approximately 9:1:2. In four out of four lidocaine-treated animals, respiratory depression with bradycardia and hypotension without arrhythmias were the causes of death. Three out of four bupivacaine-treated animals died after the sudden onset of ventricular tachycardia/fibrillation without hypoxia or acidosis; the fourth died in a similar manner to the lidocaine-treated animals. Three out of five animals given ropivacaine died in a manner resembling the fatal effects of lidocaine-treated animals, but unlike the lidocaine-treated animals, in all three sheep there were also periods of ventricular arrhythmias. The remaining two ropivacaine-treated sheep died as a result of the sudden onset of ventricular tachycardia/fibrillation. The mean percentages of the fatal dose found in the myocardium was 2.8 ± 0.7 for lidocaine-treated animals, 3.3 ± 0.9 for bupivacaine-treated animals, and 2.2 ± 1.4 for ropivacaine-treated animals; the corresponding percentages in whole brain were, respectively, 0.71 ± 0.01, 0.71 ± 0.21, and 0.89 ± 0.27.