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布比卡因、罗哌卡因(含肾上腺素)及其与利多卡因等体积混合液用于股神经和坐骨神经阻滞的药效学和药代动力学比较:一项双盲随机研究。

A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study.

作者信息

Cuvillon Philippe, Nouvellon Emmanuel, Ripart Jacques, Boyer Jean-Christophe, Dehour Laurence, Mahamat Aba, L'hermite Joel, Boisson Christophe, Vialles Nathalie, Lefrant Jean Yves, de La Coussaye Jean Emmanuel

机构信息

Division of the Department of Anesthesiology and Pain Management, University Groupe Caremeau Hospital, France.

出版信息

Anesth Analg. 2009 Feb;108(2):641-9. doi: 10.1213/ane.0b013e31819237f8.

Abstract

BACKGROUND

Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time.

METHODS

In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block.

RESULTS

Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 +/- 9 min versus 28 +/- 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 +/- 12 min versus 23 +/- 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine-lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine-lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine-lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01).

CONCLUSION

Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.

摘要

背景

利多卡因与长效局部麻醉剂的混合剂常用于外周神经阻滞。关于局部麻醉剂混合剂的安全性、有效性或药代动力学的数据较少。在本研究中,我们比较了0.5%布比卡因或0.75%罗哌卡因单独使用,以及等量的0.5%布比卡因与2%利多卡因混合溶液或0.75%罗哌卡因与2%利多卡因混合溶液用于股-坐骨外周神经阻滞后手术的效果。主要终点是起效时间。

方法

在一项双盲、随机研究中,82例计划进行下肢手术的成年人接受了坐骨神经(20 mL)和股神经(20 mL)外周神经阻滞,分别使用0.5%布比卡因(200 mg)、0.5%布比卡因20 mL(100 mg)与2%利多卡因(400 mg)的混合剂、0.75%罗哌卡因(300 mg)或0.75%罗哌卡因20 mL(150 mg)与2%利多卡因(400 mg)的混合剂。每种溶液均含有1:200,000的肾上腺素。比较了进行阻滞的时间、起效时间(注射结束至感觉和运动阻滞完全)、感觉和运动阻滞的持续时间以及通过静脉自控镇痛使用吗啡的情况。在阻滞放置后0、5、15、30、45、60和90分钟采集5 mL静脉血样以测定药物浓度。

结果

所有四组患者的人口统计学特征和手术时间相似。将利多卡因与长效局部麻醉剂联合使用可缩短坐骨神经的起效时间(感觉和运动阻滞)。布比卡因-利多卡因混合剂的起效时间为16±9分钟,而单独使用布比卡因为28±12分钟。罗哌卡因-利多卡因混合剂的起效时间为16±12分钟,而单独使用罗哌卡因为23±12分钟。接受布比卡因-利多卡因混合剂的患者在40分钟内所有患者的感觉阻滞均完成,而接受单独布比卡因的患者为60分钟,接受罗哌卡因-利多卡因混合剂的患者为30分钟,接受单独罗哌卡因的患者为40分钟(P<0.05)。混合剂组的感觉和运动阻滞持续时间明显更短。术后48小时内,除单独使用布比卡因(中位数:9 mg)与布比卡因-利多卡因混合剂(15 mg)相比(P<0.01)外,各组间视觉模拟评分法疼痛评分和吗啡用量无差异。各组间不良事件发生率无差异。与接受长效局部麻醉剂与利多卡因混合剂的患者相比,仅接受长效局部麻醉剂的患者血浆中布比卡因和罗哌卡因的浓度更高,且升高持续时间更长(P<0.01)。

结论

长效局部麻醉剂与利多卡因的混合剂可诱导起效更快、持续时间更短的阻滞。由于长效局部麻醉剂浓度降低的益处可能被血浆中显著浓度的利多卡因抵消,因此是否有安全益处尚不清楚。

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