Edouard Ollier1,2, Fabrice Heritier3, Caroline Bonnet3, Sophie Hodin2, Brigitte Beauchesne3, Serge Molliex3,4, Xavier Delavenne2,4. 1. Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France. 2. Laboratoire de Pharmacologie Toxicologie, CHU Saint-Etienne, F-42055, Saint-Etienne, France. 3. Département d'anesthésie Réanimation, CHU de Saint-Etienne, F-42055, Saint-Etienne, France. 4. Université Jean Monnet, Université de Lyon, F-42023, Saint-Etienne, France.
Abstract
AIMS: The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. METHODS: This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. RESULTS: The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. CONCLUSIONS: Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.
RCT Entities:
AIMS: The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. METHODS: This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. RESULTS: The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. CONCLUSIONS: Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.
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