布比卡因、芬太尼和可乐定联合用于腰椎硬膜外术后镇痛：一种新型优化方法。

Combinations of bupivacaine, fentanyl, and clonidine for lumbar epidural postoperative analgesia: a novel optimization procedure.

作者信息

Sveticic Gorazd, Gentilini Andrea, Eichenberger Urs, Zanderigo Eleonora, Sartori Valentina, Luginbühl Martin, Curatolo Michele

机构信息

Division of Pain Therapy, Department of Anesthesiology, Inselspital, Bern, Switzerland.

出版信息

Anesthesiology. 2004 Dec;101(6):1381-93. doi: 10.1097/00000542-200412000-00019.

DOI:10.1097/00000542-200412000-00019

PMID:15564946

Abstract

BACKGROUND

The authors developed and applied a method to optimize the combination of bupivacaine, fentanyl, and clonidine for continuous postoperative lumbar epidural analgesia.

METHODS

One hundred eighteen patients undergoing knee or hip surgery participated in the study. Postoperative epidural analgesia during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of bupivacaine, fentanyl, and clonidine (expressed as drug concentration in the solution administered) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score. For the first time in a clinical investigation, a regression model was applied when the optimization procedure led to combinations associated with unacceptable side effects.

RESULTS

The authors analyzed 12 combinations with an allowed bupivacaine concentration range of 0-2.5 mg/ml, a fentanyl concentration range of 0-5 microg/ml, and a clonidine concentration range of 0-5 microg/ml. The best combinations of bupivacaine, fentanyl, and clonidine concentrations were 1.0 mg/ml-1.4 microg/ml-0.5 microg/ml, 0.9 mg/ml-3.0 microg/ml-0.3 microg/ml, 0.6 mg/ml-2.5 microg/ml-0.8 microg/ml, and 1.0 mg/ml-2.4 microg/ml-1.0 microg/ml, respectively, all producing a similarly low pain score. The incidence of side effects was low. The application of the regression model to combinations associated with high incidence of motor block successfully directed the optimization procedure to combinations within the therapeutic range.

CONCLUSIONS

The results support further study of the combinations of bupivacaine, fentanyl, and clonidine mentioned above for postoperative analgesia after knee and hip surgery. This novel optimization method may be useful in clinical research.

摘要

背景

作者研发并应用了一种方法来优化布比卡因、芬太尼和可乐定用于术后持续腰段硬膜外镇痛的联合用药方案。

方法

118例行膝关节或髋关节手术的患者参与了本研究。术后48小时内的硬膜外镇痛在副作用限制条件下进行优化。最初，凭经验选择并研究了布比卡因、芬太尼和可乐定的8种联合用药方案（以给药溶液中的药物浓度表示）。为确定后续联合用药方案，应用优化模型，直至连续三步疼痛评分未降低。在临床研究中，当优化程序导致出现不可接受的副作用的联合用药方案时，首次应用回归模型。

结果

作者分析了12种联合用药方案，布比卡因浓度范围为0 - 2.5mg/ml，芬太尼浓度范围为0 - 5μg/ml，可乐定浓度范围为0 - 5μg/ml。布比卡因、芬太尼和可乐定浓度的最佳联合用药方案分别为1.0mg/ml - 1.4μg/ml - 0.5μg/ml、0.9mg/ml - 3.0μg/ml - 0.3μg/ml、0.6mg/ml - 2.5μg/ml - 0.8μg/ml和1.0mg/ml - 2.4μg/ml - 1.0μg/ml，所有方案产生的疼痛评分均同样低。副作用发生率低。将回归模型应用于与运动阻滞高发生率相关的联合用药方案，成功地将优化程序导向了治疗范围内的联合用药方案。