Department of Orthopaedic Surgery, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Université Paris-Saclay, UVSQ, INSERM, Infection et Inflammation, Département de Biotechnologie de la Santé, Montigny le Bretonneux, France; Hôpital Foch, Département des Maladies des Voies Respiratoires, Suresnes, France.
Br J Anaesth. 2021 Apr;126(4):872-880. doi: 10.1016/j.bja.2020.11.038. Epub 2021 Jan 15.
Ropivacaine is commonly used in local infiltration anaesthesia (LIA) as pain management after total knee arthroplasty (TKA). Although considered safe, no studies evaluated the pharmacokinetics of high-dose ropivacaine infiltration in simultaneous bilateral TKA.
We studied 13 patients undergoing unilateral and 15 undergoing bilateral TKA. Standard LIA technique was used with ropivacaine 0.2%, 200 ml (400 mg) injected peri-articularly in each knee. Free and total plasma concentrations of ropivacaine were measured within 24 h using liquid chromatography-mass spectrometry. A population pharmacokinetic model was built using non-linear mixed-effects models.
Peak free ropivacaine concentration was 0.030 (0.017-0.071) μg ml (mean [99% confidence interval]) vs 0.095 (0.047-0.208) μg ml, and peak total ropivacaine concentration was 0.756 (0.065-1.222) μg mlvs 1.695 (0.077-3.005) μg ml for unilateral and bilateral TKA, respectively. The pharmacokinetics was ascribed a one-compartment model with first-order absorption. The main identified covariates were protein binding, allometrically scaled body weight on clearance and volume, and unilateral or bilateral surgery on volume.
This is the first study to investigate the pharmacokinetics of free and total ropivacaine after unilateral and bilateral TKA. A population model was successfully built and peak free ropivacaine concentration stayed below previously proposed toxic thresholds in patients undergoing unilateral and bilateral TKA receiving LIA with high-dose ropivacaine.
ClinicalTrials.gov Identifier: NCT04702282.
罗哌卡因常用于全膝关节置换术后（TKA）的局部浸润麻醉（LIA）以缓解疼痛。尽管被认为是安全的，但没有研究评估在同时进行双侧 TKA 时高剂量罗哌卡因浸润的药代动力学。
我们研究了 13 例单侧 TKA 患者和 15 例双侧 TKA 患者。在每个膝关节周围关节内注射 0.2%罗哌卡因 200ml（400mg），采用标准 LIA 技术。在 24 小时内使用液相色谱-质谱法测量游离和总血浆罗哌卡因浓度。使用非线性混合效应模型建立群体药代动力学模型。
游离罗哌卡因的峰浓度分别为 0.030（0.017-0.071）μg/ml（均值[99%置信区间]）与 0.095（0.047-0.208）μg/ml，总罗哌卡因的峰浓度分别为 0.756（0.065-1.222）μg/ml 与 1.695（0.077-3.005）μg/ml，分别用于单侧和双侧 TKA。药代动力学被归为一个一室模型，具有一级吸收。主要的识别变量包括蛋白结合、清除率和体积的比例尺度体重、单侧或双侧手术对体积的影响。
这是第一项研究单侧和双侧 TKA 后游离和总罗哌卡因药代动力学的研究。成功建立了群体模型，接受单侧和双侧 TKA 并接受高剂量罗哌卡因 LIA 的患者的游离罗哌卡因峰浓度保持在先前提出的毒性阈值以下。
ClinicalTrials.gov 标识符：NCT04702282。
