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.

Ascorbic acid concentrations in umbilical cord veins and arteries of preterm and term newborns.

Ascorbic acid (AA) is a powerful antioxidant required for the defense against oxidative stress. At present it is not known whether AA may play a role in the developmental process of the fetus. We therefore determined the relationship of AA levels between the umbilical cord vein (UCV) and umbilical cord artery (UCA) of preterm ( < 37 weeks of gestation) and term ( > or = 37 weeks of gestation) infants and compared those levels to matched maternal venous AA levels. We also assessed the association between UCV plasma AA levels with birth weight and gestational age by measuring AA in 88 UCV plasma samples and 58 UCA plasma samples obtained from newborn infants ranging in gestational age from 24 to 42 weeks and birth weight from 675 to 5,020 g, by high pressure liquid chromatography. Maternal venous samples were collected at the time of delivery. The mean UCV plasma AA levels (mg/dl) were significantly lower in the preterm group than in the term group (0.43 +/- 0.59 and 1.16 +/- 0.97, respectively; p < 0.002); however, the mean UCA plasma AA levels did not differ between the groups. In contrast, mean maternal venous plasma AA levels of the preterm group (1.33 +/- 0.62) were significantly higher than those of the mothers in the term group (0.72 +/- 0.69; p < 0.01). A direct correlation was found between UCV levels and birth weight (r = 0.23, p < 0.05), and UCV levels and gestational age (r = 0.23, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)