Pharmacokinetics and Analgesic Effect of Ropivacaine during Continuous Epidural Infusion for Postoperative Pain Relief
Pharmacokinetics and Analgesic Effect of Ropivacaine during Continuous Epidural Infusion for Postoperative Pain Relief
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罗哌卡因连续硬膜外输注缓解术后疼痛的药代动力学和镇痛效果
DOI：
10.1097/00000542-199604000-00010
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发表时间：
1996
期刊：
影响因子：
8.8
通讯作者：
T. Arvidsson
中科院分区：
文献类型：
--
作者：
C. Erichsen;J. Sjovall;H. Kehlet;C. Hedlund;T. Arvidsson
采用开放标签、剂量递增设计，对20例拟行腹式子宫切除术的患者进行24小时连续硬膜外输注罗哌卡因（2.5 mg/ml）缓解术后疼痛的药代动力学和临床疗效进行了研究。方法通过T10-T12插入硬膜外导管，在推注42.5 mg罗哌卡因前3 min给予试验剂量7.5 mg，然后立即以10或20 mg/h持续硬膜外输注24 h。在输注后48 h内采集外周静脉血浆样本，并随访尿排泄直至输注结束。在手术结束后2、4、6、8、12和24 h，通过视觉模拟量表评估静息、咳嗽和活动时的术后疼痛。以相同的时间间隔评估感觉（针刺）和运动阻滞（改良Bromage量表）。结果罗哌卡因的总血药浓度在24小时硬膜外输注过程中显著增加，与稳定的游离浓度相反。输注结束时的总血药浓度和未结合血药浓度均与总剂量成比例，但仅后者与输注速率成比例。总血浆清除率和未结合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 ml/min至418+/-138 ml/min，表明时间依赖性动力学。未结合清除率在输注8小时后和治疗结束时的估计值之间也存在差异，即，从10.4+/-5.3 l/min下降5.3%至9.5+/-3.9 l/min（P < 0.05）。治疗期间血浆中罗哌卡因的游离分数降低，这与α 1-酸性糖蛋白浓度的增加有关。疼痛通常得到良好控制，接受20 mg/h罗哌卡因的患者在活动期间的中位视觉模拟量表评分小于30 mm。结论罗哌卡因的药代动力学与剂量无关，但总清除率随时间延长而降低。术后硬膜外输注期间总血浆浓度的一致增加与罗哌卡因未结合血浆浓度的变化小得多形成对比。
Background 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. Methods 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. Results 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. Conclusions 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.