Pharmacodynamic effects and pharmacokinetic profile of continuous infusion fentanyl in newborn piglets

The objective of this study was to determine hemodynamic effects and pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl at 30 microg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10 microg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus and infusion of 5% dextrose. Blood samples were obtained serially from systemic circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion both in the systemic (202.7 +/- 39.1 ng/ml) and sagittal sinus vein (136.7 +/- 20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h. Heart rate was significantly elevated at 30 min and 6 h during infusion but systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased significantly at 30 min (26%, p < 0.01) and remained elevated throughout the infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean clearance was estimated as 56.2 +/- 13.7 ml/kg/h (range 43.5-76.9 ml/kg/h), mean volume of distribution at steady state was 1.29 +/- 0.6 liters/kg (range 0.78-2.15 liters/kg) and the mean half-life was 15.7 +/- 5.7 h (range 9.4-22.5 h). These data suggest that increased systemic oxygen may be necessary to maintain normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.