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Pharmacokinetics of continuous infusions of fentanyl in critically ill children
Insights
Fentanyl pharmacokinetics in critically ill children showed a prolonged half-life and high variability in clearance. Dosing should be individualized to achieve effective sedation in pediatric intensive care units.
Area of Science:
- Pediatric Critical Care Medicine
- Clinical Pharmacology
- Pharmacokinetics
Background:
- Continuous infusions of fentanyl are used for sedation and analgesia in mechanically ventilated pediatric patients.
- Understanding fentanyl pharmacokinetics is crucial for optimizing its use in this vulnerable population.
Purpose of the Study:
- To determine the pharmacokinetics of fentanyl during long-term continuous infusion in mechanically ventilated infants and children.
- To assess factors influencing fentanyl clearance and half-life in pediatric intensive care unit (ICU) patients.
Main Methods:
- A prospective case series was conducted in a university hospital pediatric ICU.
- Nineteen mechanically ventilated children (0.05 to 14 years) received continuous fentanyl infusions for over 24 hours.
- Plasma fentanyl concentrations were measured, and pharmacokinetic variables including clearance, volume of distribution, and half-life were calculated.
Main Results:
- The volume of distribution at steady state was significantly increased (15.2 L/kg) and the terminal elimination half-life was prolonged (21.1 hours) compared to previous studies.
- Fentanyl clearance was rapid but showed significant interpatient variability, which was age-dependent.
- Clearance did not appear to increase over the duration of the infusion.
Conclusions:
- Total body clearance of fentanyl in pediatric ICU patients is highly variable.
- Fentanyl dosing requires individualization based on patient response to achieve therapeutic sedation.
- A ten-fold variability in fentanyl infusion rates may be necessary to achieve consistent sedation levels.
Objective:
To determine the pharmacokinetics of fentanyl when used as a long-term continuous infusion for sedation/analgesia in mechanically ventilated critically ill infants and children.
Design:
Prospective, case series.
Setting:
A university hospital pediatric intensive care unit (ICU).
Patients:
Nineteen mechanically ventilated infants and children (0.05 to 14 yrs of age) who received continuous infusions of fentanyl for > 24 hrs.
Interventions:
None.
Measurements:
Plasma concentrations of fentanyl were measured 1 hr after a loading dose and at various intervals during and after the infusions were discontinued. Noncompartmental pharmacokinetic variables, total body clearance, volume of distribution at steady state, and terminal elimination half-life were calculated. Clinical sedation scores, ventilatory settings, pupillary size and reactivity, and patient demographics were recorded.
Results:
After the use of fentanyl by long-term infusion, the volume of distribution at steady state was increased 15.2 L/kg (range 5.1 to 30.5) and the terminal elimination half-life was prolonged 21.1 hrs (range 11.2 to 36.0) compared with previous studies. Clearance was rapid and consistent with other studies. There was a large interpatient variability in clearance that was age dependent. Clearance did not appear to increase over time.
Conclusions:
Total body clearance of fentanyl is highly variable and it should be dosed to effect. Patients seen in a pediatric ICU may require a ten-fold variability in fentanyl infusion rates to achieve similar levels of sedation.