Feldman H S, Dvoskin S, Halldin M H, Ask A L, Doucette A M
Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Boston, MA 02115, USA.
Reg Anesth. 1997 Sep-Oct;22(5):451-60. doi: 10.1016/s1098-7339(97)80033-8.
Ropivacaine is the S(-) propyl homolog of bupivacaine and mepivacaine. Studies in humans have confirmed the results of studies in laboratory animals that ropivacaine is a long-acting local anesthetic with an anesthetic profile similar to bupivacaine. Acute, intravenous systemic toxicity studies have been conducted in sheep and dogs. Local anesthetic efficacy has been studied after epidural administration in the dog. This study was initiated to determine the local anesthetic efficacy and pharmacokinetics of ropivacaine and bupivacaine after epidural administration in an experimental sheep model and to evaluate the sheep model as a model of experimental epidural anesthesia.
Twelve adult nonpregnant ewes were prepared with chronically implanted lumbar epidural catheters and arterial lines. Each sheep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% and 0.75%) in a blinded, random, cross-over fashion. Onset and duration of sensory and motor blockade were evaluated. Arterial blood samples were drawn for serum drug concentration determinations and pharmacokinetic analysis.
Onset and duration of motor blockade were similar for comparable concentrations of both drugs. Both concentrations of ropivacaine and bupivacaine 0.5% demonstrated differential neural blockade. The peak serum concentrations generally occurred within 8 minutes after administration. The terminal elimination half-life in serum was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, respectively. No signs of systemic toxicity were observed. Results of sensory and motor blockade were consistent with previous studies in laboratory animals and humans.
Ropivacaine produces sensory and motor blockade which is similar to that produced by equal concentrations of bupivacaine after epidural administration in the sheep. Peak serum concentrations produced no signs of systemic toxicity. The results of this study are consistent with previously published data from studies in laboratory animals and humans. The sheep model of experimental epidural anesthesia appears to be a clinically relevant method to evaluate experimental local anesthetics.
罗哌卡因是布比卡因和甲哌卡因的S(-)丙基同系物。人体研究证实了实验动物研究的结果，即罗哌卡因是一种长效局部麻醉药，其麻醉特性与布比卡因相似。已在绵羊和犬身上进行了急性静脉全身毒性研究。在犬身上研究了硬膜外给药后的局部麻醉效果。开展本研究以确定罗哌卡因和布比卡因在实验性绵羊模型中硬膜外给药后的局部麻醉效果和药代动力学，并评估绵羊模型作为实验性硬膜外麻醉模型的情况。
对12只成年未孕母羊进行慢性腰段硬膜外导管和动脉导管植入。每只羊以盲法、随机、交叉方式接受5.0 mL罗哌卡因和布比卡因（0.5%和0.75%）注射。评估感觉和运动阻滞的起效时间和持续时间。采集动脉血样用于血清药物浓度测定和药代动力学分析。
两种药物相同浓度时，运动阻滞的起效时间和持续时间相似。罗哌卡因的两种浓度和0.5%布比卡因均表现出不同的神经阻滞。血清峰值浓度一般在给药后8分钟内出现。罗哌卡因和布比卡因在血清中的终末消除半衰期分别约为3.5 - 4.0小时和6小时。未观察到全身毒性迹象。感觉和运动阻滞结果与先前在实验动物和人体中的研究一致。
在绵羊中，罗哌卡因硬膜外给药后产生的感觉和运动阻滞与相同浓度布比卡因产生的相似。血清峰值浓度未出现全身毒性迹象。本研究结果与先前发表的实验动物和人体研究数据一致。实验性硬膜外麻醉的绵羊模型似乎是评估实验性局部麻醉药的一种临床相关方法。
