Li D F, Bahar M, Cole G, Rosen M
Br J Anaesth. 1985 Apr;57(4):424-9. doi: 10.1093/bja/57.4.424.
Neurotoxicity after subarachnoid infusion of bupivacaine, lignocaine and 2-chloroprocaine was studied in a chronic rat model. Hartmann's solution 100 microliter h-1 was infused as a control, and 0.5% bupivacaine, 1.5% lignocaine and 2.0% 2-chloroprocaine were infused at 100 microliter h-1 for 3, 6 or 24 h, to five rats in each group. No residual paralysis occurred in the control group, but 27 of 45 rats (60%) which received an infusion of local anaesthetic had residual paralysis lasting until sacrifice at 7 days. The incidence of paralysis was dependent on the duration of exposure to the local anaesthetic, but there were no significant differences in incidence between any of the local anaesthetics tested. Abnormal histology, in the form of neuronal vacuolation, was not a sensitive index, being present in control rats, but more intense in those receiving lignocaine and 2-chloroprocaine than in those given bupivacaine; no correlation with clinical findings could be established. The neurotoxic effects of each local anaesthetic tested as a continuous intrathecal infusion were dose related in the rat, which may be a useful model for screening other local anaesthetics.
在慢性大鼠模型中研究了蛛网膜下腔注入布比卡因、利多卡因和2-氯普鲁卡因后的神经毒性。以每小时100微升的速度注入100微升哈特曼氏溶液作为对照，将0.5%布比卡因、1.5%利多卡因和2.0% 2-氯普鲁卡因以每小时100微升的速度分别注入每组的5只大鼠体内，持续3、6或24小时。对照组未出现残留麻痹，但接受局部麻醉药注入的45只大鼠中有27只（60%）出现残留麻痹，持续至7天后处死。麻痹的发生率取决于局部麻醉药的暴露时间，但在所测试的任何一种局部麻醉药之间，发生率没有显著差异。以神经元空泡化形式出现的异常组织学不是一个敏感指标，在对照大鼠中也存在，但接受利多卡因和2-氯普鲁卡因的大鼠比接受布比卡因的大鼠更严重；无法确定与临床结果的相关性。在大鼠中，每种作为连续鞘内注入测试的局部麻醉药的神经毒性作用与剂量相关，这可能是筛选其他局部麻醉药的有用模型。
