Sciatic nerve blockade in infant, adolescent, and adult rats - A comparison of ropivacaine with bupivacaine
Sciatic nerve blockade in infant, adolescent, and adult rats - A comparison of ropivacaine with bupivacaine
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DOI：
10.1097/00000542-199811000-00021
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发表时间：
1998-11-01
期刊：
影响因子：
8.8
通讯作者：
Berde, CB
中科院分区：
文献类型：
--
作者：
Kohane, DS;Sankar, WN;Berde, CB
研究背景：罗哌卡因是一种新型的局部麻醉药。没有关于其在儿童中的安全性、有效性或感觉选择性的数据。布比卡因和罗哌卡因的坐骨神经阻滞持续时间和全身毒性在婴儿，青少年和成年rats.Methods：婴儿，青少年和成年大鼠接受罗哌卡因或布比卡因阻滞。评估伤害性、本体感受性和运动阻滞。量化全身效应（对侧腿部镇痛、癫痫发作、呼吸窘迫、呼吸暂停）。血浆局部麻醉药浓度测定在终端apnea.Results：神经阻滞的绝对剂量持续时间比在老年大鼠的婴儿两种药物。罗哌卡因的阻滞持续时间通常与布比卡因相同或略短于布比卡因。药物之间的感觉选择性没有差异。诱导所有全身毒性指数所需的剂量与年龄呈负相关（例如，罗哌卡因在婴儿中的半数致死剂量[LD 50]为155 mg/kg;在成人中为54 mg/kg）。在所有年龄段，罗哌卡因的所有毒性指数均以高于布比卡因的每公斤剂量发生（例如，布比卡因在婴儿中的LD 50为92 mg/kg;在成人中为30 mg/kg）。在终末呼吸暂停的血浆浓度高于布比卡因在所有年龄段，并在婴儿高于在老年rats.Conclusions：罗哌卡因类似布比卡因在其局部麻醉效果，但有更大的安全边际。对于给定的绝对剂量，幼年大鼠的坐骨神经阻滞持续时间长于青少年或成年大鼠。虽然婴儿中引起毒性的剂量（毫克/千克）比成人高得多，但这可能与更广泛的治疗指数不一致。
Background: Ropivacaine is a newly introduced local anesthetic. No data are available regarding its safety, efficacy, or sensory-selectivity in children. The sciatic block duration and systemic toxicity of bupivacaine and ropivacaine were com pared among infant, adolescent, and adult rats.Methods: Infant, adolescent, and adult rats received blocks with ropivacaine or bupivacaine. Nociceptive, proprioceptive, and motor blockade were assessed. Systemic effects (contralateral leg analgesia, seizures, respiratory distress, apnea) were quantified. Plasma local anesthetic concentrations were measured at terminal apnea.Results: Nerve blockade for a given absolute dose lasted longer in infants than in older rats for both drugs. Block duration from ropivacaine generally was the same as or slightly shorter than bupivacaine. There was no difference in sensory-selectivity between the drugs. Doses required to induce all systemic toxicity indices were inversely related to age (e.g., the lethal dose in 50% of animals [LD50] of ropivacaine in infants is 155 mg/kg; in adults it is 54 mg/kg). All indices of toxicity occurred at higher doses per kilogram for ropivacaine than bupivacaine, at all ages (eg., the LD50 of bupivacaine in infants is 92 mg/kg; in adults it is 30 mg/kg). Plasma concentrations at terminal apnea were higher for ropivacaine than for bupivacaine at all ages, and were higher in infants than in older rats.Conclusions: Ropivacaine resembles bupivacaine in its local anesthetic effects but has a greater margin of safety. For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults. Although the doses (in milligrams per kilogram) causing toxicity were much higher in infants than in adults, this probably does not correspond to a wider therapeutic index.