Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty
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Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty. / Gromov, Kirill; Grassin-Delyle, Stanislas; Foss, Nicolai B.; Pedersen, Lars Møller; Nielsen, Christian S.; Lamy, Elodie; Troelsen, Anders; Urien, Saik; Husted, Henrik.
In: British Journal of Anaesthesia, Vol. 126, No. 4, 2021, p. 872-880.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty
AU - Gromov, Kirill
AU - Grassin-Delyle, Stanislas
AU - Foss, Nicolai B.
AU - Pedersen, Lars Møller
AU - Nielsen, Christian S.
AU - Lamy, Elodie
AU - Troelsen, Anders
AU - Urien, Saik
AU - Husted, Henrik
N1 - Publisher Copyright: © 2020 British Journal of Anaesthesia
PY - 2021
Y1 - 2021
N2 - 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−1 vs 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
AB - 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−1 vs 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
KW - fast-track surgery
KW - knee arthroplasty
KW - local infiltration anaesthesia
KW - multimodal analgesia
KW - postoperative pain
KW - ropicacaine
U2 - 10.1016/j.bja.2020.11.038
DO - 10.1016/j.bja.2020.11.038
M3 - Journal article
C2 - 33455802
AN - SCOPUS:85099280964
VL - 126
SP - 872
EP - 880
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
SN - 0007-0912
IS - 4
ER -
ID: 285446140