Kohane D S, Sankar W N, Shubina M, Hu D, Rifai N, Berde C B
Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Anesthesiology. 1998 Nov;89(5):1199-208; discussion 10A. doi: 10.1097/00000542-199811000-00021.
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 compared among infant, adolescent, and adult rats.
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.
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 (e.g., 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.
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.
罗哌卡因是一种新引入的局部麻醉药。目前尚无关于其在儿童中的安全性、有效性或感觉选择性的数据。比较了布比卡因和罗哌卡因在幼鼠、青春期大鼠和成年大鼠中的坐骨神经阻滞持续时间和全身毒性。
幼鼠、青春期大鼠和成年大鼠接受罗哌卡因或布比卡因阻滞。评估伤害性感受、本体感觉和运动阻滞。对全身效应（对侧腿部镇痛、惊厥、呼吸窘迫、呼吸暂停）进行量化。在终末呼吸暂停时测量血浆局部麻醉药浓度。
对于两种药物，给定绝对剂量的神经阻滞在幼鼠中的持续时间比在年长大鼠中更长。罗哌卡因的阻滞持续时间通常与布比卡因相同或略短。两种药物在感觉选择性上没有差异。诱导所有全身毒性指标所需的剂量与年龄呈负相关（例如，罗哌卡因在幼鼠中的半数致死剂量[LD50]为155mg/kg；在成年大鼠中为54mg/kg）。在所有年龄段，罗哌卡因导致毒性的每千克剂量均高于布比卡因（例如，布比卡因在幼鼠中的LD50为92mg/kg；在成年大鼠中为30mg/kg）。在所有年龄段，终末呼吸暂停时罗哌卡因的血浆浓度均高于布比卡因，且在幼鼠中高于年长大鼠。
罗哌卡因在局部麻醉作用方面与布比卡因相似，但具有更大的安全 margin。对于给定的绝对剂量，幼鼠的坐骨神经阻滞持续时间比青少年或成年大鼠更长。尽管导致毒性的剂量（每千克毫克数）在幼鼠中比成年大鼠高得多，但这可能并不对应于更宽的治疗指数。
