• Angela R Tognolini, Xin Liu, Saurabh Pandey, Jason A Roberts, Steven C Wallis, Dwane Jackson, and Victoria A Eley.
• Department of Anaesthesia and Perioperative Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Australia.
• Anaesthesia. 2025 Jan 2.

IntroductionEvidence to support intra-operative lidocaine infusion regimens in patients with obesity is lacking, risking underdosing or toxicity. We aimed to measure the plasma concentrations of lidocaine and its active metabolites to develop a pharmacokinetic model and optimised dosing regimen in patients with obesity.MethodsA standardised weight-based intravenous lidocaine regimen was administered to patients with a BMI ≥ 30 kg.m-2 undergoing elective laparoscopic abdominal surgery. Using lean body weight, a 1.5 mg.kg-1 loading dose over 10 min and infusion of 1.5 mg.kg-1.h-1 was administered intra-operatively. Arterial blood was sampled during and after the infusion. The total and unbound plasma concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide were measured using liquid chromatography-mass spectrometry. Monolix was used for population pharmacokinetic analysis. Dosing simulations were performed using Simulx to develop a regimen that best targeted a therapeutic plasma concentration between 2.5 and 5 μg.ml-1.ResultsThirty patients provided 221 plasma samples (median (IQR [range]) age 51 (44-61 [32-76]) y and 21 female). Median (IQR [range]) total body weight was 107.0 (91.8-132.5 [80.0-189.0]) kg and BMI was 37.7 (33.6-46.5 [30.2-58.4]) kg.m-2. Using total and unbound plasma concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide, a four-compartment model was developed. Unbound lidocaine volume of distribution was 2.1 l.kg-1 and clearance 1.7 l.kg-1.h-1. Simulations showed that doses used currently had a low probability of target attainment of 0%. A loading dose of 2 mg.kg-1 over 20 min followed by an infusion of 3 mg.kg-1.h-1 based on lean body weight improved probability of target attainment to 18.6%. The infusion should be reduced to 2 mg.kg-1.h-1 after 80 min.DiscussionOur simulated dosing regimen achieved therapeutic concentrations more successfully in patients with obesity. Further studies should evaluate the clinical safety and efficacy of this dosing regimen.© 2025 Association of Anaesthetists.

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