Pharmacokinetic model-driven infusion of fentanyl in children

• Published in: Anesthesiology (Philadelphia) Vol. 85; no. 6; pp. 1268 - 1275
• Main Authors: GINSBERG, B, HOWELL, S, GLASS, P. S. A, MARGOLIS, J. O, ROSS, A. K, DE L. DEAR, G, SHAFER, S. L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01-12-1996
• Subjects: Anesthetics, Intravenous - administration & dosage; Anesthetics, Intravenous - blood; Anesthetics, Intravenous - pharmacokinetics; Anesthetics. Neuromuscular blocking agents; Biological and medical sciences; Child; Child, Preschool; Computers; Fentanyl - administration & dosage; Fentanyl - blood; Fentanyl - pharmacokinetics; Humans; Medical sciences; Models, Biological; Neuropharmacology; Pharmacology. Drug treatments; Human; Intravenous administration; Continuous; Perfusion; Fentanyl; General anesthesia; Opiates; Narcotic analgesic; Pharmacokinetics; Child; Computer aid
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199612000-00007

This study determined the accuracy of previously defined adult fentanyl pharmacokinetics in children having surgery; from this population, the pharmacokinetics of fentanyl were characterized in children when administered via a computerized assisted continuous-infusion device.
Twenty children between the ages of 2.7 and 11 y scheduled to undergo elective noncardiac surgery were studied. After induction, anesthesia was maintained with 60% nitrous oxide in oxygen supplemented with fentanyl (n = 10) or fentanyl plus isoflurane (n = 10). Fentanyl was administered via computerized assisted continuous-infusion to target concentrations determined by clinical requirements. Plasma fentanyl concentrations were measured and used to evaluate the performance of the fentanyl pharmacokinetics and then to determine a new set of pharmacokinetic parameters and the variance in the context-sensitive half-times simulated for these patients.
The original adult fentanyl pharmacokinetics resulted in a positive bias (10.4%), indicating that measured concentrations were mostly greater than predicted. A two-compartment model with age and weight as covariates provided the optimal pharmacokinetic parameters. These resulted in a residual performance error of -1.1% and a median absolute performance error of 17.4%. The context-sensitive times determined from this pediatric population were considerably shorter than the context-sensitive times previously published for adults.
The pharmacokinetics of fentanyl administered by computerized assisted continuous-infusion differ between adults and children. The newly derived parameters are probably more suitable to determine infusion schemes of up to 4 h in children between the ages of 2 and 11 y.