Pharmacokinetic modelling and simulation for prolonged infusion of levobupivacaine with or without epinephrine in transversus abdominis plane and erector spinae plane blocks: a randomised controlled trial and analysis of pooled data.

Abstract

BACKGROUND Interfacial blocks often require large volumes of local anaesthetic, raising concerns about systemic absorption and potential toxicity. This study examined the pharmacokinetics of levobupivacaine with and without epinephrine during thoracic erector spinae plane (ESP) or transversus abdominis plane (TAP) blocks, simulating reported 48-h dosing regimens to evaluate safety. METHODS Data from three studies were analysed. Study 1 included 38 patients receiving an ESP block before video-assisted thoracoscopy, whereas Study 2 analysed published data on TAP blocks. Both studies used 20 ml of levobupivacaine 0.25% with or without epinephrine (5 μg ml-1), measuring arterial concentrations over 90 min. Study 3 involved intravenous bupivacaine administration in 10 healthy volunteers. Pharmacokinetic analysis used NONMEM software, with significance set at P<0.05. RESULTS We analysed 258 ESP samples, 150 TAP samples, and 190 bupivacaine i.v. SAMPLES A one-compartment model described the data, with a mean distribution volume of 41.9 L (coefficient of variation, 47%) and clearance rate of 0.288 L min-1 (coefficient of variation, 38%). Epinephrine reduced bioavailability (54.3% vs 32.8%) and prolonged absorption half-life (0.84 min vs 1.55 min; P<0.05). Simulated doses of 50 mg plus 300 mg per 24 h over 48 h remained below toxic thresholds. CONCLUSIONS Similar dosing regimens for ESP and TAP blocks are supported by this pharmacokinetic analysis, with epinephrine effectively reducing systemic drug concentrations by prolonging absorption half-life and lowering bioavailability. The findings suggest that extended 300 mg per 24 h dosing for 48 h is likely to be safe. Further studies in broader patient populations are warranted to evaluate safety. CLINICAL TRIAL REGISTRATION NCT04799184.