Zhong Z, Qulian G, Yuan Z, Wangyuan Z, Zhihua S
Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha City, Hunan Province, China.
Anaesth Intensive Care. 2009 Nov;37(6):929-36. doi: 10.1177/0310057X0903700612.
Previous studies suggest that ropivacaine causes the least neurotoxicity among local anaesthetics. Most data derive from a single injection of ropivacaine into the subarachnoid space. The histological changes and behavioural effects of repeated intrathecal administration have yet to be studied. We examined the possible neurotoxicity of multiple doses of intrathecal ropivacaine in rats. Rats received 0.12 ml/kg body weight ropivacaine in normal saline at concentrations of 0.25%, 0.5%, 0.75% and 1.0% at 90-minute intervals via an implanted intrathecal catheter (ID 0.12 mm, OD 0.35 mm) for 48 hours. At L3, the spinal cord and posterior roots were examined by light and electron microscopy. We performed in situ TUNEL assay to evaluate apoptosis in the spinal cord. Sensory threshold to noxious stimulation along with behavioural change were also studied. Both 0.75% and 1.0% ropivacaine induced neuronal injury characterised by infiltration of inflammatory cells, vacuolation of myelin sheaths and axons, abnormal morphology of neurons and apoptosis in the spinal cord, mainly in posterior roots and the adjacent posterior white matter Compared to controls, the percentage of maximum possible effect did not show any significant differences between the rats treated with variable concentrations of ropivacaine or tested with either heat or mechanical stimulation. As expected, the recovery time to normal ambulation was prolonged as the ropivacaine concentration was increased. Ropivacaine can induce neurotoxicity and trigger apoptosis in a dose-dependent manner after repeated intrathecal administration. Although the clinical safety profile of ropivacaine appears favourable compared with other local anaesthetics, it is possible our findings have clinical significance.
先前的研究表明，在局部麻醉剂中，罗哌卡因引起的神经毒性最小。大多数数据来自于将罗哌卡因单次注入蛛网膜下腔。重复鞘内给药的组织学变化和行为影响尚未得到研究。我们研究了大鼠多次鞘内注射罗哌卡因可能产生的神经毒性。大鼠通过植入的鞘内导管（内径0.12毫米，外径0.35毫米），以90分钟的间隔接受浓度为0.25%、0.5%、0.75%和1.0%的罗哌卡因生理盐水溶液，剂量为0.12毫升/千克体重，持续48小时。在L3水平，通过光镜和电镜检查脊髓和后根。我们进行原位TUNEL检测以评估脊髓中的细胞凋亡。还研究了对有害刺激的感觉阈值以及行为变化。0.75%和1.0%的罗哌卡因均诱导了神经元损伤，其特征为炎症细胞浸润、髓鞘和轴突空泡化、神经元形态异常以及脊髓细胞凋亡，主要发生在后根和相邻的后白质。与对照组相比，用不同浓度罗哌卡因处理的大鼠或接受热刺激或机械刺激测试的大鼠，最大可能效应百分比没有显著差异。正如预期的那样，随着罗哌卡因浓度的增加，恢复正常行走的时间延长。重复鞘内给药后，罗哌卡因可诱导神经毒性并以剂量依赖方式触发细胞凋亡。尽管与其他局部麻醉剂相比，罗哌卡因的临床安全性似乎良好，但我们的研究结果可能具有临床意义。
