Erichsen C J, Sjövall J, Kehlet H, Hedlund C, Arvidsson T
Department of Anesthesiology, Hvidovre University Hospital, Denmark.
Anesthesiology. 1996 Apr;84(4):834-42. doi: 10.1097/00000542-199604000-00010.
The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design.
Through an epidural catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion was followed up to the end of infusion. Postoperative pain at rest, on coughing, and at mobilization was assessed by means of a visual analog scale 2,4,6,8,12, and 24 h after the end of surgery. Sensory (pinprick) and motor block (modified Bromage scale) were assessed at the same intervals.
The total plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional to the infusion rate. The total and unbound plasma clearance was independent of dose. Total mean clearance decreased on average by 21% (P < 0.001) during the last 12 h of epidural infusion, i.e., from 539 +/- 191 ml/min to 418 +/- 138 ml/min, indicating time-dependent kinetics. The unbound clearance also varied between estimates after 8 h of infusion and the end of treatment, i.e., a 5.3% decrease from 10.4 +/- 5.3 l/min to 9.5 +/- 3.9 l/min (P < 0.05). The unbound fraction of ropivacaine in plasma decreased during treatment, and this was related to the increase in alpha1-acid glycoprotein concentration. Pain was generally well controlled, and median visual analog scale scores during mobilization were less than 30 mm in patients receiving ropivacaine at 20 mg/h.
The pharmacokinetics of ropivacaine were independent of dose, but total clearance decreased with time over 24 h. The consistent increase in total plasma concentration during the postoperative epidural infusion contrasted to much less variation in the unbound plasma concentrations of ropivacaine.
采用开放标签、递增剂量设计，对20例行腹式子宫切除术患者在术后24小时持续硬膜外输注2.5毫克/毫升罗哌卡因以缓解疼痛的药代动力学和临床疗效进行了研究。
通过在T10 - T12置入硬膜外导管，在给予42.5毫克推注剂量前3分钟给予7.5毫克罗哌卡因试验剂量，随后立即以10毫克/小时或20毫克/小时进行24小时持续硬膜外输注。输注后长达48小时采集外周静脉血浆样本，并随访至输注结束时的尿排泄情况。术后静息、咳嗽和活动时的疼痛在手术结束后2、4、6、8、12和24小时通过视觉模拟评分进行评估。在相同时间间隔评估感觉（针刺）和运动阻滞（改良Bromage评分）。
与稳定的游离浓度相反，罗哌卡因的总血浆浓度在24小时硬膜外输注期间显著且持续增加。输注结束时的总血浆浓度和游离血浆浓度均与总剂量成正比，尽管只有后者与输注速率成正比。总血浆清除率和游离血浆清除率与剂量无关。在硬膜外输注的最后12小时内，总平均清除率平均下降21%（P < 0.001），即从539 ± 191毫升/分钟降至418 ± 138毫升/分钟，表明存在时间依赖性动力学。输注8小时后至治疗结束时，游离清除率的估计值之间也存在差异，即从10.4 ± 5.3升/分钟下降5.3%至9.5 ± 3.9升/分钟（P < 0.05）。罗哌卡因在血浆中的游离分数在治疗期间下降，这与α1 - 酸性糖蛋白浓度的增加有关。疼痛总体得到良好控制，接受20毫克/小时罗哌卡因治疗的患者活动时视觉模拟评分中位数小于30毫米。
罗哌卡因的药代动力学与剂量无关，但总清除率在24小时内随时间下降。术后硬膜外输注期间总血浆浓度持续增加，而罗哌卡因游离血浆浓度的变化则小得多。
