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

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−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. 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