不同比例利多卡因-布比卡因混合液鞘内注射后大鼠神经行为及脊髓神经结构变化

The behavior and the changes of neurologic and histopathologic structure of rats injected lidocaine-bupivacaine mixtures in different ratio

目的观察不同配比的10%盐酸利多卡因与2.5%盐酸布比卡因混合液的脊髓神经毒性变化。方法将10%盐酸利多卡因与2.5%盐酸布比卡因,按1∶3、1∶2、1∶1、2∶1、3∶1容积比混合鞘内注射,观察其神经行为及脊髓神经结构的变化。选择鞘内置管成功的大鼠48只随机分为6组,每组8只,鞘内分别注射NS（S组）、2.5%盐酸利多卡因＋1.875%盐酸布比卡因（LB13组）、3.33%盐酸利多卡因＋1.67%盐酸布比卡因（LB12组）、5%盐酸利多卡因＋1.25%盐酸布比卡因（LB11组）、6.67%盐酸利多卡因＋0.83%盐酸布比卡因（LB21组）、7.5%盐酸利多卡因＋0.625%盐酸布比卡因（LB31组）。单盲法观察药物注射后1~4 d的TFL、PWT、下肢运动恢复时间,光镜及透射电镜下观察脊髓的病理改变,并对马尾神经进行病理损伤评分。结果 LB31组TFL明显延长（P〈0.05）,后腿运动恢复时间异常延长。光镜观察：LB13组、LB12组、LB11组见马尾神经纤维局灶水肿,而LB21组、LB31组出现了脱髓鞘变性改变。LB31组见脊髓后角白质水肿。病理损伤评分：LB21组和LB31组病理损伤评分高于LB13组、LB12组、LB11组（P〈0.05）。透射电镜：LB13组、LB12组、LB11、LB21组、LB31组见脊髓后角白质间质水肿、有髓神经纤维的板层结构疏松、轴索肿胀等改变,其中LB21组、LB31组损伤较重。结论大鼠鞘内注射不同容积比的10%利多卡因与2.5%布比卡因混合液时,脊髓神经毒性随着混合液中利多卡因的绝对浓度的增加逐渐加重,当二者容积比低于1∶1时脊髓神经毒性较轻。

Objective To observe the behavior and the changes of neurologic and histopathologic structure of rats injected lidocaine-bupivacaine mixtures in different ratio. Methods After successful intrathecal catherization and positive lidocaine test,48 rats were randomly allocated into6 groups with 8 rats in each group. Rats received intrathecally NS（group S）,mixture of 2. 5% lidocaine and 1. 875% bupivacaine（group LB13）,3. 33% lidocaine and 1. 67% bupivacaine（group LB12）,5% lidocaine and 1. 25% bupivacaine（group LB11）,6. 67% lidocaine and 0. 83% bupivacaine（group LB21）,or 7. 5% lidocaine and 0. 625% bupivacaine（group LB31）. TFL and PWT on consecutive 4 days,recovery time of lower limbs and the pathologic changes in the spinal cord by method of microscopy and electron scope were observed by a blind investigator. Results TFL in group LB31 was significantly longer（P〈0. 05） and hind legs motor function and recover time prolonged obviously in group LB31; Edema vacuolar degeneration and interstitial edema in white matter of posterior horn of spinal cord were found in group LB31. The histopathologic score was obviously higher in group LB31 compared with other groups（P〈0. 05）. On transmission electroscope,different levels of ultrastructural changes were found in all groups except in group S. Typical changes included interstitial edema,loosening of the laminae of myelinated fibers,axon swelling and local degeneration with most serious injury in group LB31. Conclusion The spinal injury following intrathecal local anesthetics mixtures was more serious with higher concentration of lidocaine in the mixture. Lidocaine concentration lower than 5% mixed with 1. 25% bupivacaine intrathecally induces no obvious spinal neurotoxicity.