Neurotoxicity of common peripheral nerve block adjuvants.
Neurotoxicity of common peripheral nerve block adjuvants.
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DOI：
10.1097/aco.0000000000000222
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Williams BA
中科院分区：
文献类型：
--
作者：
Knight JB;Schott NJ;Kentor ML;Williams BA
概述神经周佐剂在局部麻醉剂神经阻滞注射中的镇痛作用，并评估有关佐剂是否调节局部麻醉剂的神经细胞学特性的现有知识。右美托咪定、可乐定、丁丙诺啡、地塞米松和咪达唑仑等神经周围辅助药物具有独特的镇痛作用。这些药物预防神经毒性的给药在各种细胞和体内模型中进行了表征。这种缓解的大部分可能是通过减少局部麻醉剂的剂量，同时实现相等或上级镇痛。剂量-浓度动物模型未显示有害作用的证据。关于布比卡因-可乐定-丁丙诺啡-地塞米松联合阻滞的临床观察显示，对阻滞持续时间和反跳痛有有益作用，无长期神经毒性证据。神经周围可乐定和右美托咪定的体外和体内研究显示，局部麻醉剂产生的神经周围炎症反应减弱。添加右美托咪定作为外周神经阻滞佐剂可延长阻滞持续时间，且无神经毒性。联合使用可乐定、丁丙诺啡和地塞米松似乎不会改变局部麻醉剂的神经毒性。咪达唑仑在体外可显著增加局麻药的神经毒性，但与可乐定-丁丙诺啡-地塞米松（无局麻药）联合使用时，在体外或体内均不产生神经毒性。需要进一步的大物种动物试验和人体试验来加强这些发现的临床适用性。
Outline the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluate current knowledge regarding whether adjuvants modulate the neurocytologic properties of local anesthetics. Perineural adjuvant medications such as dexmedetomidine, clonidine, buprenorphine, dexamethasone, and midazolam play unique analgesic roles. The dosing of these medications to prevent neurotoxicity is characterized in various cellular and in vivo models. Much of this mitigation may be via reducing the dose of local anesthetic used while achieving equal or superior analgesia. Dose-concentration animal models have shown no evidence of deleterious effects. Clinical observations regarding blocks with combined bupivacaine-clonidine-buprenorphine-dexamethasone have shown beneficial effects on block duration and rebound pain without long-term evidence of neurotoxicity. In vitro and in vivo studies of perineural clonidine and dexmedetomidine show attenuation of perineural inflammatory responses generated by local anesthetics. Dexmedetomidine added as a peripheral nerve blockade adjuvant improves block duration without neurotoxic properties. The combined adjuvants clonidine, buprenorphine, and dexamethasone do not appear to alter local anesthetic neurotoxicity. Midazolam significantly increases local anesthetic neurotoxicity in vitro, but when combined with clonidine-buprenorphine-dexamethasone (sans local anesthetic) produces no in vitro or in vivo neurotoxicity. Further larger-species animal testing and human trials will be required to reinforce the clinical applicability of these findings.