Revisiting infusion rate limitations for continuous lumbar plexus blocks in children and adolescents with 0.2% ropivacaine: a pharmacokinetic analysis

Background: A limitation to widespread use of pediatric lumbar plexus blocks is a scarcity of pharmacokinetic data. Concerns of absorption and consequent toxicity promote low doses resulting in frequent episodes of breakthrough pain. We determined population pharmacokinetics of unbound ropivacaine and its toxic metabolite 2’,6’-pipecoloxylidide (PPX) after a bolus dose and during continuous infusion to simulate current dosing guidelines relative to the toxic threshold of the combined effects of ropivacaine and PPX in the pediatric population. Methods: 20 healthy children, aged 4 - 18 years, undergoing unilateral hip/ femur surgery who received lumbar plexus blocks with 0.2% ropivacaine bolus (2mg/kg) and an infusion (0.4 mg/kg/h) were prospectively enrolled. Blood samples were collected at regular intervals over 26 h to measure total and unbound plasma ropivacaine and PPX concentrations. Results: The concentration vs time plots show an approximately 5-fold range of plateau unbound plasma ropivacaine concentrations and 10-fold range of PPX among the patients, suggesting similar variability in unbound ropivacaine and PPX clearances, respectively. Simulations of ropivacaine and PPX exposure simulating standard infusion rates (0.4 mg/kg/h) with regular bolus dose administration of 0.2mg/kg resulted in the 95 th percentile of sum of unbound ropivacaine + 1/12 PPX concentrations approaching the estimated toxic threshold due to late-occurring approach to high steady-state plasma concentrations of PPX. Discontinuing the continuous infusion and replacing it with larger bolus doses every 6 hours resulted in lower simulated plasma ropivacaine and PPX plasma concentrations. Conclusions: Pharmacokinetic modeling supports a bolus dose of 2mg/kg, continuous infusion rates of ropivacaine at 0.4mg/kg/h and 6hourly boluses of 0.2mg/kg in healthy children for lumbar plexus blockade for the first 24 hours. After that, with currently accepted toxic thresholds for ropivacaine and PPX, consideration should be given to dosing strategies that reduce or eliminate infusions and support timed boluses.