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Pharmacokinetic model-driven infusion of fentanyl in children
B Ginsberg1, S Howell, P S Glass
1Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Insights
Adult fentanyl pharmacokinetics do not accurately predict levels in children undergoing surgery. New pharmacokinetic parameters for fentanyl administered via computerized infusion were determined, showing shorter context-sensitive half-times in pediatric patients.
Area of Science:
- Pharmacology
- Anesthesiology
- Pediatric Medicine
Background:
- Adult fentanyl pharmacokinetics were assessed for accuracy in pediatric surgical patients.
- Fentanyl pharmacokinetics were characterized in children receiving computerized continuous infusion.
Purpose of the Study:
- To determine the accuracy of adult fentanyl pharmacokinetics in children undergoing surgery.
- To characterize fentanyl pharmacokinetics in pediatric patients receiving computerized assisted continuous infusion.
Main Methods:
- Twenty children (2.7-11 years) undergoing elective noncardiac surgery were studied.
- Anesthesia was maintained with nitrous oxide and fentanyl, with or without isoflurane, via computerized infusion.
- Plasma fentanyl concentrations were measured to evaluate and refine pharmacokinetic models.
Main Results:
- Adult pharmacokinetic models showed a positive bias (10.4%) in children.
- A two-compartment model incorporating age and weight provided optimal pediatric pharmacokinetic parameters.
- Derived pediatric context-sensitive half-times were significantly shorter than adult values.
Conclusions:
- Fentanyl pharmacokinetics differ between adults and children when administered via computerized continuous infusion.
- Newly derived pediatric pharmacokinetic parameters are likely more accurate for infusion schemes up to 4 hours in children aged 2-11 years.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.