Pharmacokinetics of levobupivacaine with epinephrine in transversus abdominis plane block for postoperative analgesia after Caesarean section.

Abstract

Transversus abdominis plane block is increasingly used for post-Caesarean section analgesia. Cases of toxicity and the limited pharmacokinetic information during pregnancy motivated this study. The objective of the study was to characterise and compare the pharmacokinetics of levobupivacaine with epinephrine in tranversus abdominis plane block, in post-Caesarean section patients and healthy volunteers. After approval by the Ethics Committee, we collected data from 12 healthy parturients after elective Caesarean section (Study 1) and data from 11 healthy male volunteers from a previous study (Study 2). Transversus abdominus plane block was performed under ultrasound guidance. The following injectates were used: levobupivacaine 0.25%, 20 ml with epinephrine 5 μg ml^-1 (Study 1) per side; 20 ml of the same solution (unilateral block) (study 2). The plasma venous concentration of levobupivacaine was measured serially for 90 min. Pharmacokinetic parameters (volume of distribution, clearance, and absorption half-life) were estimated using a non-linear mixed effects model (NONMEM). Simulation in 1000 patients estimated the maximum concentration and the time to reach it after bilateral transversus abdominis plane block. Venous concentrations were below toxic levels (2.62 mg L^-1). Levobupivacaine volume of distribution after Caesarean section was higher than in healthy volunteers [172 L (70 kg)^-1 (95% confidence interval: 137-207) vs 94.3 L (70 kg)^-1 (95% CI: 62-128); P<0.01]. Clearance and absorption half-life were similar. The simulation showed that maximum levobupivacaine concentration is lower and occurs later in postpartum patients (P<0.01). Postoperative analgesia was effective. Postpartum women reached relatively low plasma concentrations of levobupivacaine after transversus abdominal plane block given a volume of distribution 80% higher than volunteers, which could confer a greater margin of safety. NCT02852720.