Lidocaine Infusion Population Pharmacokinetics Study (LIPPS): determining pharmacokinetics of lidocaine in those undergoing breast reconstructive surgery

We aim to develop a population pharmacokinetic model for lidocaine administration by intravenous infusion and identify clinically important covariates by conducting a prospective, single-centre, exploratory interventional study. It is anticipated that this project will provide data to inform a model which will facilitate accurate and potentially safer dosing of intravenous lidocaine. We plan to recruit 40 female adult patients undergoing breast reconstruction surgery. Patients will receive a bolus dose of lidocaine followed by an intravenous infusion. Dosing will be calculated using lean body weight and based on the dosing protocol approved and used in the LOLIPOP Pilot Trial (1) which has proven it to be safe and feasible. As an additional safety feature, we will be using half the dose of that used in LOLIPOP. This is because, unlike the LOLIPOP Trial, pain is not one of our outcome measures. Our primary aim of examining serial serum lidocaine concentrations and the potential formulation of a pharmacokinetic model is achievable at these lower doses. Lidocaine samples will be taken at hourly intervals throughout the duration of the infusion, and twice postoperatively between 8 and 26 hours of ceasing the infusion Current research (including the LOLIPOP Trial) is focussed on the analgesic properties of intravenous lidocaine. Several studies have already demonstrated a reduction in pain scores and a decrease in peri-operative opioid consumption. The goal of intravenous infusion is to establish and maintain therapeutic plasma concentrations of 0.5-5 mcg/mL, whilst avoiding higher doses that may result in toxicity. Lidocaine has complex pharmacokinetics and demonstrates non-linear (time-dependent) pharmacokinetics with prolonged infusion, including increasing plasma concentrations and prolonging elimination half-life. Establishing a population-based pharmacokinetic model will facilitate a dosing regimen that maintains plasma lidocaine concentrations within a safe therapeutic window. This will improve the safety of intravenous lidocaine infusion by decreasing the risks of systemic toxicity, and potentially improve its efficacy by maintaining effective therapeutic plasma levels. [1] Toner A.J. BMA, Schug S.A., Corcoran T.B. A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Anaesthesia. 2021. ClinicalTrials.gov registration ID: NCT05072314