Abstract

PR1-153

Population Pharmacokinetics of Intraperitoneal Bupivacaine Using Atomization versus Nebulization and Opioid Requirements in Young Children

Meier P, Pereira L, Zurakowski D, Houck C
Boston Children's Hospital, Boston, MA, USA

Introduction: Intraperitoneal (IP) administration of local anesthetics is used in adults for perioperative analgesia during elective laparoscopic surgery. The population pharmacokinetics (PK) of IP bupivacaine has not been characterized in children. The objectives were (1) to develop a population PK model to compare the PK of bupivacaine and (2) assess opioid requirements following IP manual bolus atomization versus micropump nebulization.1
Method: In a prospective study, after IRB approval and written informed parental consent, 67 children (44 males, 23 females) ages 6 months to 6 years (median 30 months), undergoing robot-assisted laparoscopic urologic surgery received IP bupivacaine after creation of the pressurized pneumoperitoneum. Group 1 received 1.25 mg/kg bupivacaine in 30mL NS via mucosal atomization as a bolus over 30sec. Group 2 received 1.25mg/kg of undiluted bupivacaine 0.5% via a micropump nebulizer into the CO2 insufflation tubing over 15-30min. Venous blood samples were obtained at 4 time intervals between 1-120min. Nonlinear regression modeling was used to estimate PK parameters for each technique with 95% confidence intervals.
Results: Baseline characteristics of the 2 groups were comparable. No clinical signs of neuro-or cardio-toxicity were observed. Highest plasma concentration was 2.44μg/mL for the atomizer vs 0.97μg/mL for the nebulizer technique (Fig.1). IP bupivacaine PK was described as 1-compartment model with significant group differences in all PK parameters except half-life and mean residence time (Table 1). The nebulizer had a significantly lower Cmax and shorter Tmax (p<0.001). Lower plasma concentrations with less variability (95% CI) were observed and predicted by the PK model (Fig.2) for the nebulizer than the atomizer (p<0.001). Adjusting for age as a covariate, Cmax and AUC were significantly lower with the nebulizer (p<0.001, Wald test). There were no differences in cumulative postop IV/oral morphine requirements through 24h between atomizer vs nebulizer group (0.14 vs 0.17mg/kg, p=0.85).
Discussion/Conclusion: This is the first population PK study of IP bupivacaine administration in children. Delivery by micropump nebulization results in lower plasma concentrations along with less patient variability, reduced toxicity risk, and efficacy comparable to manual bolus atomization.
Ref: Meier PM et al SPA 2013