Pharmacokinetics of continuous infusions of fentanyl in critically ill children

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Abstract
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. Prospective, case series. A university hospital pediatric intensive care unit (ICU). Nineteen mechanically ventilated infants and children (0.05 to 14 yrs of age) who received continuous infusions of fentanyl for > 24 hrs. None. 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. 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. 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.

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