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Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty

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BACKGROUND: 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.

METHODS: 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.

RESULTS: Peak free ropivacaine concentration was 0.030 (0.017-0.071) μg ml-1 (mean [99% confidence interval]) vs 0.095 (0.047-0.208) μg ml-1, and peak total ropivacaine concentration was 0.756 (0.065-1.222) μg ml-1vs 1.695 (0.077-3.005) μg ml-1 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.

CONCLUSIONS: 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.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04702282.

Original languageEnglish
JournalBritish Journal of Anaesthesia
Volume126
Issue number4
Pages (from-to)872-880
Number of pages9
ISSN0007-0912
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2020 British Journal of Anaesthesia

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • fast-track surgery, knee arthroplasty, local infiltration anaesthesia, multimodal analgesia, postoperative pain, ropicacaine, Anesthetics, Local/administration & dosage, Arthroplasty, Replacement, Knee/adverse effects, Prospective Studies, Pain Management/methods, Pain, Postoperative/metabolism, Humans, Middle Aged, Male, Ropivacaine/administration & dosage, Female, Aged, Anesthesia, Local/methods, Cohort Studies

ID: 61845175