PHARMACOKINETICS OF CONTINUOUS INFUSIONS OF FENTANYL IN CRITICALLY ILL CHILDREN

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 u nit (ICU). Patients: Nineteen mechanically ventilated infants and chil dren (0.05 to 14 yrs of age) who received continuous infusions of fent anyl for >24 hrs. Interventions: None. Measurements: Plasma concentrat ions of fentanyl were measured 1 hr after a loading dose and at variou s intervals during and after the infusions were discontinued. Noncompa rtmental pharmacokinetic variables, total body clearance, volume of di stribution at steady state, and terminal elimination half-life were ca lculated. Clinical sedation scores, ventilatory settings, pupillary si ze and reactivity, and patient demographics were recorded. Results: Af ter the use of fentanyl by long-term infusion, the volume of distribut ion at steady state was increased 15.2 L/kg (range 5.1 to 30.5) and th e terminal elimination half-life was prolonged 21.1 hrs (range 11.2 to 36.0) compared with previous studies. Clearance was rapid and consist ent 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 va riable and it should be dosed to effect. Patients seen in a pediatric ICU may require a ten-fold variability in fentanyl infusion rates to a chieve similar levels of sedation.