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局部浸润罗哌卡因 400mg 在全膝关节置换术中不使用围手术期止血带的药代动力学。

Pharmacokinetics of 400 mg Locally Infiltrated Ropivacaine After Total Knee Arthroplasty Without Perioperative Tourniquet Use.

机构信息

Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen.

Research Department, Sint Maartenskliniek, Nijmegen, the Netherlands.

出版信息

Reg Anesth Pain Med. 2018 Oct;43(7):699-704. doi: 10.1097/AAP.0000000000000816.

Abstract

BACKGROUND AND OBJECTIVES

Local infiltration analgesia (LIA) with ropivacaine for total knee arthroplasty (TKA) is increasingly used. Despite the high doses of ropivacaine, LIA is considered safe, and this perception is sustained by pharmacokinetic data demonstrating that maximum concentrations of ropivacaine stay well below the toxic threshold in plasma. These pharmacokinetic studies all involve TKA procedures with the use of a tourniquet. Recently, performing TKA without the use of a tourniquet is gaining popularity, but no pharmacokinetic data exist when LIA is administered for TKA without the use of a tourniquet. The purpose of this study was to describe the pharmacokinetic profile of a single-shot ropivacaine (200 mL 0.2%) and 0.75 mg epinephrine (1000 μg/mL) when used for LIA in patients for TKA without a tourniquet.

METHODS

In this prospective cohort study, 20 patients treated with LIA for TKA without a tourniquet were studied. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360, 480, 600, 720, and 1440 minutes after local anesthetic infiltration, in which total and unbound ropivacaine concentrations were determined.

RESULTS

Results are given as median (interquartile range [IQR]). Median peak ropivacaine concentration was 1.16 μg/mL (IQR, 0.46); median peak unbound ropivacaine concentration was 0.05 μg/mL (IQR, 0.02). The corresponding times to reach the maximum concentration for total and unbound ropivacaine were 360 (IQR, 240) and 360 (IQR, 360) minutes, respectively.

CONCLUSIONS

Although great interindividual variability in ropivacaine concentration was found, both total and unbound maximum serum concentrations remained below the assumed systemic toxic thresholds in all samples.

CLINICAL TRIAL REGISTRATION

This study was registered at Netherlands Trial Registry (http://www.trialregister.nl), trial ID NTR6306.

摘要

背景与目的

局部浸润麻醉(LIA)联合罗哌卡因在全膝关节置换术(TKA)中的应用越来越广泛。尽管罗哌卡因的剂量很高,但 LIA 被认为是安全的,这种观念得到了药代动力学数据的支持,这些数据表明罗哌卡因的最高浓度在血浆中仍远低于毒性阈值。这些药代动力学研究都涉及使用止血带的 TKA 手术。最近,不使用止血带进行 TKA 越来越受欢迎,但当不使用止血带时,LIA 用于 TKA 尚无药代动力学数据。本研究旨在描述不使用止血带的情况下,单次注射罗哌卡因(200 mL 0.2%)和 0.75 mg 肾上腺素(1000 μg/mL)用于 LIA 时,患者的药代动力学特征。

方法

在这项前瞻性队列研究中,研究了 20 例不使用止血带接受 LIA 治疗的 TKA 患者。在局部麻醉浸润后 20、40、60、90、120、240、360、480、600、720 和 1440 分钟时采集血浆样本,以确定总罗哌卡因和游离罗哌卡因浓度。

结果

结果以中位数(四分位距[IQR])表示。中位峰罗哌卡因浓度为 1.16 μg/mL(IQR,0.46);中位游离罗哌卡因峰浓度为 0.05 μg/mL(IQR,0.02)。总罗哌卡因和游离罗哌卡因达到最大浓度的相应时间分别为 360(IQR,240)和 360(IQR,360)分钟。

结论

尽管罗哌卡因浓度存在很大的个体间变异性,但在所有样本中,总罗哌卡因和游离罗哌卡因的最大血清浓度均低于假定的全身毒性阈值。

临床试验注册

本研究在荷兰临床试验注册中心(http://www.trialregister.nl)进行,注册号为 NTR6306。

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