鞘内给予利多卡因和布比卡因后谷氨酸释放和神经功能障碍在大鼠。

Glutamate release and neurologic impairment after intrathecal administration of lidocaine and bupivacaine in the rat.

机构信息

Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan.

出版信息

Reg Anesth Pain Med. 2011 Sep-Oct;36(5):452-6. doi: 10.1097/AAP.0b013e318228cdb0.

DOI:10.1097/AAP.0b013e318228cdb0

PMID:21857271

Abstract

BACKGROUND

Local anesthetic-induced neurotoxicity is one of the potential causes of postspinal anesthesia neurologic injury. Many experimental and clinical studies have demonstrated that lidocaine is more neurotoxic than bupivacaine. The mechanisms of local anesthetic-induced neurotoxicity remain unclear. Glutamate is an excitatory amino acid and widely exists in the central nervous system. Overstimulation of the glutamate receptors may produce neuronal toxic effect. In this study, we used in vivo microdialysis to examine the glutamate release in cerebrospinal fluid (CSF) after intrathecal lidocaine and bupivacaine injection.

METHODS

Male Wistar rats were used. Administration of lidocaine (5 groups: normal saline, 2.5%, 5%, 10%, and 10% + MK-801 intrathecally injected) and bupivacaine (4 groups: normal saline, 0.25%, 0.5%, and 1% intrathecally injected) was performed in both microdialysis and postinjection neurologic sequelae studies. After intrathecal injection of the studied agents, the CSF dialysates were collected in 10-minute intervals for 2 hours. Cerebrospinal fluid glutamate concentrations were measured by high-performance liquid chromatography. In addition, tail-flick latencies were examined daily before and after microdialysis for 4 days.

RESULTS

Intrathecal lidocaine concentration-dependently elevated glutamate release in CSF. Pretreatment with MK-801 significantly inhibited the glutamate release induced by 10% lidocaine. Intrathecal bupivacaine has no influence on glutamate release in CSF. The tail-flick latencies were significantly prolonged for 4 days after intrathecal lidocaine injection, and these effects were in a concentration-dependent manner. Pretreatment with MK-801 significantly reversed the 10% lidocaine-induced prolonged tail-flick latencies. There was no difference of the tail-flick latencies among the bupivacaine-treated groups.

CONCLUSIONS

Intrathecal lidocaine caused a concentration-dependent increase of the CSF glutamate release and postinjection neurologic impairment; these effects can be reversed by MK-801. However, intrathecal bupivacaine shows no influence. We suggest that glutamate may be involved in the pathogenesis of lidocaine-induced spinal neurotoxicity.

摘要

背景

局部麻醉药诱导的神经毒性是脊髓麻醉后神经损伤的潜在原因之一。许多实验和临床研究表明，利多卡因比布比卡因更具神经毒性。局部麻醉药诱导的神经毒性的机制尚不清楚。谷氨酸是一种兴奋性氨基酸，广泛存在于中枢神经系统中。谷氨酸受体的过度刺激可能产生神经元毒性作用。在这项研究中，我们使用体内微透析技术检测鞘内注射利多卡因和布比卡因后脑脊液（CSF）中谷氨酸的释放。

方法

雄性 Wistar 大鼠。在微透析和注射后神经后遗症研究中，分别给予利多卡因（5 组：生理盐水、2.5%、5%、10%和 10%+MK-801 鞘内注射）和布比卡因（4 组：生理盐水、0.25%、0.5%和 1%鞘内注射）。鞘内注射研究药物后，每 10 分钟收集 CSF 透析液 2 小时。采用高效液相色谱法测定脑脊液谷氨酸浓度。此外，在微透析前和微透析后 4 天内，每天检测尾巴闪烁潜伏期。

结果

鞘内利多卡因浓度依赖性地增加 CSF 中的谷氨酸释放。MK-801 预处理显著抑制了 10%利多卡因诱导的谷氨酸释放。鞘内布比卡因对 CSF 中谷氨酸的释放没有影响。鞘内注射利多卡因后，尾巴闪烁潜伏期显著延长 4 天，且呈浓度依赖性。MK-801 预处理显著逆转了 10%利多卡因引起的尾巴闪烁潜伏期延长。布比卡因处理组的尾巴闪烁潜伏期无差异。