Pharmacokinetics of continuous infusion fentanyl in newborns

Although fentanyl administration by continuous infusion in newborns during ventilatory support has increased, pharmacokinetic data are lacking. Our objective was to determine the pharmacokinetics of fentanyl continuous infusions for sedation/analgesia in newborns who had undergone mechanical ventilation. Fentanyl was administered per routine care in seven newborns who had undergone mechanical ventilation and had normal hepatic, renal, and cardiac function. Five blood samples were collected from each newborn's umbilical artery catheter. Sample 1 was obtained at > or = 36 hours after constant fentanyl was infused, and sample 2 was collected 12 hours later. Fentanyl was then discontinued and meperidine given. Additional samples were obtained 6, 12, and 24 hours after fentanyl was discontinued. Decanted plasma was stored at -20 degrees C until gas chromatography analysis was performed. Total body clearance (TBC), elimination half-life, and volume of distribution at steady state were determined. Patient weights were 1.88 +/- 1.12 kg (mean +/- SD) with postnatal age 16 +/- 9 days; the mean gestational age was 32 +/- 4 weeks. Mean final fentanyl dosage was 1.28 +/- 0.58 microgram/kg/hr (range 0.53 to 1.9 micrograms/kg/hr). Mean elimination half-life was 9.5 +/- 2.6 hours (range 5.7 to 12.7 hours), and volume of distribution at steady state was 17 +/- 9 L/kg (range 10.1 to 30.3 L/kg). Mean TBC was 1154 +/- 494 ml/kg/hr (range 565 to 2000 ml/kg/hr). Significant correlation between postnatal age and TBC occurred (r = 0.80; p = 0.03). Newborns were hemodynamically stable during the sampling period. We found an increased volume of distribution at steady state and prolonged elimination half-life compared with single-dose administration in newborns. TBC was similar to reported values for infants and young children but was higher than for older patients.