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.
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.