Characterizing Fentanyl Variability Using Population Pharmacokinetics in Pediatric Burn Patients

Abstract

Abstract Opioids are essential first line analgesics for pain management after burn injury. Opioid dosing remains challenging in burn patients, particularly in children, due to the immense variability in efficacy between patients. Opioid pharmacokinetics are altered in burned children, increasing variability and obviating dosing regimens extrapolated from adult-data. The present study aimed to characterize variability in fentanyl pharmacokinetics and identify significant contributors to variability in children with ≥10% total body surface area burn requiring fentanyl during routine wound care. We recorded patient demographics and clinical data. Blood samples were collected following fentanyl administration for pharmacokinetics at time 0, 30, 60, 120, and 240 minutes on day of admission and repeated on days 3 and 7. Serum fentanyl concentrations were quantified using tandem liquid chromatography mass spectrometry. Population analysis was used to estimate pharmacokinetics parameters. Fourteen patients, 1.2–17 years, with burns from 10–50.5% were included in analysis. A two-compartment model with body weight as a covariate best described fentanyl pharmacokinetics for the overall population. The population clearance and intercompartmental clearance were 7.19 and 2.16 L/hour, respectively, and the volume of distribution for the central and peripheral compartments was 4.01 and 25.1 L, respectively. Individual patient parameter estimates had extensive variability. This study confirmed the high variability in pediatric burn patient fentanyl pharmacokinetics and demonstrates similarities and differences to other populations reported in literature. Further research is needed with a larger number of patients to extensively investigate the impact of burns, genetic polymorphisms, and other factors on fentanyl efficacy and patient outcomes.