Knight Joshua B, Schott Nicholas J, Kentor Michael L, Williams Brian A
aDepartment of Anesthesiology, University of Pittsburgh Medical Center bVA Pittsburgh Health System, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Curr Opin Anaesthesiol. 2015 Oct;28(5):598-604. doi: 10.1097/ACO.0000000000000222.
This review outlines the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluates 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.
本综述概述了神经周围佐剂在局部麻醉神经阻滞注射中的镇痛作用,并评估了关于佐剂是否调节局部麻醉药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佐剂发挥着独特的镇痛作用。这些药物预防神经毒性的给药方式在各种细胞和体内模型中得到了表征。这种减轻作用很大程度上可能是通过减少局部麻醉药的使用剂量,同时实现同等或更好的镇痛效果。剂量 - 浓度动物模型未显示有害影响的证据。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表明,对阻滞持续时间和反弹痛有有益影响,且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表明,可减轻局部麻醉药产生的神经周围炎症反应。
作为外周神经阻滞佐剂添加的右美托咪定可改善阻滞持续时间且无神经毒性。可乐定、丁丙诺啡和地塞米松联合佐剂似乎不会改变局部麻醉药的神经毒性。咪达唑仑在体外显著增加局部麻醉药的神经毒性,但与可乐定 - 丁丙诺啡 - 地塞米松联合使用(不含局部麻醉药)时,在体外和体内均未产生神经毒性。需要进一步进行更大动物物种的测试和人体试验,以加强这些发现的临床适用性。