下肢手术中加入肾上腺素的和未加入肾上腺素的 450mg 罗哌卡因的药代动力学：一项初步研究。

Pharmacokinetics of 450 mg ropivacaine with and without epinephrine for combined femoral and sciatic nerve block in lower extremity surgery. A pilot study.

机构信息

Department of Anesthesiology, Sint Maartenskliniek, Hengstdal 3, 6574 NA, Nijmegen, The Netherlands.

出版信息

Br J Clin Pharmacol. 2013 May;75(5):1321-7. doi: 10.1111/j.1365-2125.2012.04470.x.

DOI:10.1111/j.1365-2125.2012.04470.x

PMID:23013208

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3635602/

Abstract

AIMS

No pharmacokinetic data exist on doses of ropivacaine larger than 300 mg for peripheral nerve block in man, although in clinical practice higher doses are frequently used. The purpose of the present study was to describe the pharmacokinetic profile in serum of 450 mg ropivacaine with and without epinephrine in patients undergoing anterior cruciate ligament reconstruction.

METHODS

Twelve patients were randomly allocated to receive a single shot combined sciatic/femoral nerve block with 60 ml of either ropivacaine 0.75% alone (group R, n = 6) or ropivacaine 0.75% plus epinephrine 5 μg ml(-1) (group RE, n = 6). Venous blood samples for total and free ropivacaine serum concentrations were obtained during 48 h following block placement. Pharmacokinetic parameters were calculated using a non-compartmental approach.

RESULTS

Results are given as mean (SD) for group R vs. group RE (95% CI of the difference). Total Cmax was 2.81 (0.94) μg ml(-1) vs. 2.16 (0.21) μg ml(-1) (95% CI -0.23, 1.53). tmax was 1.17 (0.30) h vs. 1.67 (0.94) h (95% CI -1.40, 0.40). The highest free ropivacaine concentration per patient was 0.16 (0.08) μg ml(-1) vs. 0.12 (0.04) μg ml(-1) (95% CI -0.04, 0.12). t(1/2) was 6.82 (2.26) h vs. 5.48 (1.69) h (95% CI -1.23, 3.91). AUC was 28.35 (5.92) μg ml(-1) h vs. 29.12 (7.34) μg ml(-1) h (95% CI -9.35, 7.81).

CONCLUSIONS

Free serum concentrations of ropivacaine with and without epinephrine remained well below the assumed threshold of 0.56 μg ml(-1) for systemic toxicity. Changes in pharmacokinetics with epinephrine co-administration did not reach statistical significance.

摘要

目的

尽管在临床实践中经常使用更高剂量，但目前尚无关于人体外周神经阻滞中罗哌卡因剂量超过 300mg 的药代动力学数据。本研究的目的是描述接受前交叉韧带重建术的患者单次使用 60ml 罗哌卡因（单独使用 0.75%罗哌卡因[组 R，n=6]或 0.75%罗哌卡因加肾上腺素 5μg/ml[组 RE，n=6]）时血清中罗哌卡因的药代动力学特征。

方法

静脉血样用于在阻滞放置后 48 小时内获得总游离罗哌卡因血清浓度。使用非房室模型方法计算药代动力学参数。

结果

结果以组 R 与组 RE（差异的 95%置信区间）的平均值（SD）表示。总 Cmax 为 2.81（0.94）μg/ml 与 2.16（0.21）μg/ml（95%CI-0.23，1.53）。tmax 为 1.17（0.30）h 与 1.67（0.94）h（95%CI-1.40，0.40）。每位患者的最高游离罗哌卡因浓度为 0.16（0.08）μg/ml 与 0.12（0.04）μg/ml（95%CI-0.04，0.12）。t1/2 为 6.82（2.26）h 与 5.48（1.69）h（95%CI-1.23，3.91）。AUC 为 28.35（5.92）μg/ml·h 与 29.12（7.34）μg/ml·h（95%CI-9.35，7.81）。