Fentanyl citrate (FC) is commonly used for neonatal analgesia and anesthesia. To determine cerebral utilization and clearance of FC, 6 newborn piglets (1-3 days old, mean weight = 1383±204 gms) with postoperative stress, were given a loading dose of FC (30 μg/kg IV) over 15 minutes, immediately followed by a continuous IV infusion of FC (10 μg/kg/hr) for 6 hrs. CSF (0.5 ml) from cisterna magna puncture, and blood samples (1.0 ml) from the sagittal sinus vein and carotid artery were obtained at 0 (pre-MDZ), 1, 2, 3, 4, 5 & 6 hrs during infusion. CSF and plasma FC were assayed by high pressure liquid chromatography sensitive to 0.05 ng/ml. The mean bolus IV dose was 41.5±6.1 μg/kg (range:30-45) and the mean infusion rate was 13.8±2.0 μg/kg/hr (range:10-15). All piglets appeared sedated and were spontaneously breathing. Steady state was assumed when 2-3 consecutive levels fluctuated ≤ 10% during infusion. The data (mean±SD) show that steady state levels were achieved at 0.5 hr after infusion and mean CSF and arterial FC levels were comparable at each time interval. Although mean cerebral utilization (A-V difference) of FC did not vary between 0.5 to 4 hrs, there was a significant rise from 60.7±31.3 ng/ml at 4 hrs to 144.5±41.7 ng/ml (p<0.01) at 6 hrs. The estimated CSF, sagittal sinus and arterial clearance (infusion rate/C55) were 61.2±14.2, 105.3±40.2 & 55.5±17.8 ml/kg/hr. These observations suggest a rapid equilibration between systemic circulation and CSF. In addition, as the time of infusion was prolonged, brain utilization of FC was significantly enhanced. We therefore conclude that the large variation in FC infusion rates required to achieve analgesic effects may be due in part, to the increased utilization of FC by the brain during prolonged infusion.
