Simulated bupivacaine pharmacokinetics after labor epidural analgesia followed by transversus abdominis plane block with liposomal bupivacaine for intrapartum cesarean delivery

Study Objective

To simulate bupivacaine pharmacokinetics in scenarios of labor epidural analgesia (LEA) extended for intrapartum cesarean delivery (CD) with epidural or intrathecal boluses, followed by transversus abdominis plane (TAP) block with liposomal bupivacaine (LB) for postcesarean analgesia.

Design

Bupivacaine plasma concentrations were simulated using a 2-compartment distribution model fit to previous study data.

Setting

Virtual pharmacokinetic simulations.

Patients

Virtual individuals (1000, each scenario) had uniform weight (80 kg) but varying absorption parameters.

Interventions

The 6 scenarios varied in LEA infusion duration (6 or 24 h), local anesthetic used for bolus to extend LEA (epidural lidocaine or intrathecal bupivacaine), TAP block regimen, and time between bolus and TAP block.

Measurements

Scenario outcomes included geometric mean (GM) peak bupivacaine plasma concentration (C_max) with 95% prediction interval (PI), median (range) C_max, and number of virtual individuals (per 1000) with C_max reaching estimated toxicity thresholds (neurotoxicity: 2000 μg/L; cardiotoxicity: 4000 μg/L).

Main Results

In simulated scenarios of LEA infusion for 24 h with an epidural bolus of lidocaine 400 mg for CD followed 1 h later by TAP block, the GM C_max for the scenarios with TAP blocks including either LB 266 mg plus bupivacaine hydrochloride 52 mg or bupivacaine hydrochloride 104 mg was 1860 (95% PI, 1107–3124) and 1851 (95% PI, 1085–3157) μg/L, respectively. Among 1000 virtual individuals for each scenario, 404 and 401 had C_max reaching 2000 μg/L, respectively; 1 and 0 had C_max reaching 4000 μg/L, respectively. For other scenarios, GM C_max remained <1000 μg/L.

Conclusions

Across 6 different simulations of TAP blocks for intrapartum CD analgesia, LEA with bupivacaine (with or without boluses for extension and including a conservative modeling of lidocaine without epinephrine), followed by TAP block with LB and/or bupivacaine hydrochloride 0, 1, or 2 h after CD, is unlikely to result in bupivacaine plasma concentrations reaching local anesthetic systemic toxicity thresholds in healthy patients.