Camille Riff1,2, Aurélie Bourgoin3, Amelie Marsot4,5, Laurent Allanioux4, Marc Leone3, Olivier Blin4,5, Romain Guilhaumou4. 1. Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, AP-HM, 13385, Marseille, France. camille.riff@gmail.com. 2. Pharmacologie Intégrée et Interface Clinique Industrielle, Institut des Neurosciences Timone - AMU-CNRS 7289, Aix-Marseille Université, 13385, Marseille, France. camille.riff@gmail.com. 3. Aix Marseille Université, Service d'Anesthésie-Réanimation, Hôpital Nord, Assistance Publique des Hôpitaux de Marseille, APHM, Marseille, France. 4. Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, AP-HM, 13385, Marseille, France. 5. Pharmacologie Intégrée et Interface Clinique Industrielle, Institut des Neurosciences Timone - AMU-CNRS 7289, Aix-Marseille Université, 13385, Marseille, France.
Abstract
PURPOSE: Tumescent lidocaine anesthesia (TLA) is an opportunity to perform mastectomy for breast cancer without general anesthesia in elderly women. Few reports are available on the pharmacokinetics of lidocaine in a context of TLA during a unilateral mastectomy. The aim of this study was to describe lidocaine pharmacokinetics in elderly women undergoing breast cancer surgery after TLA and to explore the risk of the toxicity of this technique. METHODS: A prospective study was conducted to examine the pharmacokinetics of lidocaine in women undergoing TLA. TLA consists of an intradermal lidocaine instillation (20 mL, 1% [200 mg]) followed by a tumescent lidocaine infiltration (100 mL of 1% lidocaine [1000 mg] and 0.5 mg epinephrine to 1 L Ringer's lactate) via an infusion pump. A population pharmacokinetic (popPK) analysis was performed using the nonlinear mixed effects model (NONMEM). RESULTS: The analysis included 116 observations from 17 women with a median (range) age of 83.4 (60.5-90.0). The median tumescent lidocaine dose was 800 mg (range 375-1000 mg) infused over 48.0 ± 11.0 min. A one-compartment disposition model with first order absorption, two input compartments, and a central elimination best described the pharmacokinetics of lidocaine. The estimates (between subject variability; relative standard error, %) of apparent volume, apparent clearance, tumescent absorption rate, and instillation absorption rate were 195.0 (46.3; 14.5%) L, 24.7 (48.9; 13.3%) L h-1, 0.28 (39.6; 13.8%) h-1, and 2.56 (135.3; 44.9%) h-1, respectively. CONCLUSIONS: This is the first popPK model developed to describe kinetic profiles of TLA. These findings confirm the slow diffusion of lidocaine from the tumescent deposit.
PURPOSE: Tumescent lidocaine anesthesia (TLA) is an opportunity to perform mastectomy for breast cancer without general anesthesia in elderly women. Few reports are available on the pharmacokinetics of lidocaine in a context of TLA during a unilateral mastectomy. The aim of this study was to describe lidocaine pharmacokinetics in elderly women undergoing breast cancer surgery after TLA and to explore the risk of the toxicity of this technique. METHODS: A prospective study was conducted to examine the pharmacokinetics of lidocaine in women undergoing TLA. TLA consists of an intradermal lidocaine instillation (20 mL, 1% [200 mg]) followed by a tumescent lidocaine infiltration (100 mL of 1% lidocaine [1000 mg] and 0.5 mg epinephrine to 1 L Ringer's lactate) via an infusion pump. A population pharmacokinetic (popPK) analysis was performed using the nonlinear mixed effects model (NONMEM). RESULTS: The analysis included 116 observations from 17 women with a median (range) age of 83.4 (60.5-90.0). The median tumescent lidocaine dose was 800 mg (range 375-1000 mg) infused over 48.0 ± 11.0 min. A one-compartment disposition model with first order absorption, two input compartments, and a central elimination best described the pharmacokinetics of lidocaine. The estimates (between subject variability; relative standard error, %) of apparent volume, apparent clearance, tumescent absorption rate, and instillation absorption rate were 195.0 (46.3; 14.5%) L, 24.7 (48.9; 13.3%) L h-1, 0.28 (39.6; 13.8%) h-1, and 2.56 (135.3; 44.9%) h-1, respectively. CONCLUSIONS: This is the first popPK model developed to describe kinetic profiles of TLA. These findings confirm the slow diffusion of lidocaine from the tumescent deposit.
Authors: P D Thomson; K L Melmon; J A Richardson; K Cohn; W Steinbrunn; R Cudihee; M Rowland Journal: Ann Intern Med Date: 1973-04 Impact factor: 25.391