Sodium Bisulfite: Scapegoat for Chloroprocaine Neurotoxicity?
Sodium Bisulfite: Scapegoat for Chloroprocaine Neurotoxicity?
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DOI：
10.1097/00000542-200401000-00016
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发表时间：
2004-01
期刊：
影响因子：
8.8
通讯作者：
M. Taniguchi;A. Bollen;K. Drasner
中科院分区：
文献类型：
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作者：
M. Taniguchi;A. Bollen;K. Drasner
鞘内注射3%奈萨卡因-CE用于硬膜外给药后出现神经损伤，引起了人们对氯普鲁卡因和防腐剂亚硫酸氢钠潜在毒性的担忧。尽管不含亚硫酸氢盐的氯普鲁卡因制剂随后被引入临床实践，但这种麻醉剂和防腐剂的相对毒性从未明确确定。目前的研究使用相关的功能和组织学模型来研究这两种化合物的鞘内神经毒性。方法在第一个实验中，植入鞘内导管的大鼠被给予两种市售氯普鲁卡因溶液中的一种，其中一种含有亚硫酸氢钠；对照组给予生理盐水。给药7天后，用甩尾试验评估动物的感觉损害，并处死动物以获取组织学标本以量化神经损伤。在第二个实验中，采用相同的方法考察了新配制的氯普鲁卡因溶液、氯普鲁卡因与亚硫酸氢钠、亚硫酸氢钠和生理盐水的作用。结果两种实验结果基本一致。在实验1中，单纯氯普鲁卡因组大鼠甩尾潜伏期和神经损伤评分显著高于亚硫酸氢氯普鲁卡因组。与注射生理盐水的动物相比，接受亚硫酸氢氯普鲁卡因注射的动物的损伤评分更高。在实验2中，接受普通氯普鲁卡因的动物的甩尾潜伏期和神经损伤评分显著高于所有其他组。含有亚硫酸氢氯普鲁卡因的神经损伤评分高于生理盐水或单独使用亚硫酸氢氯普鲁卡因。单独使用亚硫酸氢盐的甩尾潜伏期和神经损伤评分与使用生理盐水的相似。结论意外鞘内注射氯普鲁卡因引起的临床缺陷可能是麻醉剂的直接作用，而不是防腐剂。数据还表明，亚硫酸氢钠可以减轻鞘内局部麻醉剂引起的神经毒性损害。
BackgroundNeurologic deficits after apparent intrathecal injection of 3% Nesacaine-CE intended for epidural administration created concern about the potential toxicity of chloroprocaine and the preservative sodium bisulfite. Although bisulfite-free formulations of chloroprocaine were subsequently introduced into clinical practice, the relative toxicities of this anesthetic and preservative were never clearly established. The current studies used a relevant functional and histologic model to investigate the intrathecal neurotoxicity of these two compounds. MethodsIn the first experiment, rats implanted with intrathecal catheters were given one of two commercially available solutions of chloroprocaine, one of which contained sodium bisulfite; control animals received saline. Animals were assessed for sensory impairment 7 days after administration using the tail-flick test and were killed to obtain histologic specimens to quantify nerve injury. In the second experiment, identical methodology was used to investigate the effects of freshly prepared solutions of chloroprocaine, chloroprocaine with sodium bisulfite, sodium bisulfite, and saline. ResultsThe two experiments yielded similar results. In experiment 1, tail-flick latencies and nerve injury scores after administration of plain chloroprocaine were significantly greater than those of chloroprocaine containing bisulfite. Injury scores for animals receiving chloroprocaine with bisulfite were elevated compared with those for animals given saline. In experiment 2, animals receiving plain chloroprocaine developed elevations in tail-flick latencies and nerve injury scores that were significantly greater than those for all other groups. Nerve injury scores with chloroprocaine containing bisulfite were greater than with saline or bisulfite alone. Tail-flick latencies and nerve injury scores with bisulfite alone were similar to those with saline. ConclusionsClinical deficits associated with unintentional intrathecal injection of chloroprocaine likely resulted from a direct effect of the anesthetic, not the preservative. The data also suggest that bisulfite can reduce neurotoxic damage induced by intrathecal local anesthetic.