Placental passage and uterine effects of fentanyl.

Using the chronic maternal-fetal sheep preparation, 27 pregnant ewes were studied to determine the effects of intravenous fentanyl on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Three doses of fentanyl were studied--50, 75, and 100 micrograms. Maternal and fetal arterial blood was collected for determination of fentanyl levels. All blood levels, both maternal and fetal, were normalized to the 50-micrograms dose. The maternal normalized blood levels were found to fit a biexponential equation describing a two-compartment open model. The half-life of the maternal elimination phase was 42 +/- 7.0 min with an overall elimination constant (K) of 0.21 min-1. Maternal plasma fentanyl levels decreased very rapidly in the first 10 min after injection, at which time only 9% of the peak value remained. Fentanyl was detectable in fetal blood as early as 1 min and levels peaked at 5 min. Once equilibrium was established between maternal and fetal blood, the maternal levels remained 2.5 times those of the fetal level from 5 min to 60 min after drug injection. Both maternal and fetal drug levels declined in an approximately parallel fashion. No significant deleterious changes were seen in any maternal or fetal cardiovascular or acid-base parameters, and uterine blood flow and uterine tone were also unaffected (P greater than 0.05).

The maternal and fetal cardiovascular effects of epidural morphine in the sheep model.

Interest in the use of epidural narcotics for analgesia has been widespread since the demonstration of opiate receptors in the spinal cord in the mid nineteen-seventies. Recently, several studies have attempted to evaluate the effectiveness of epidural narcotics for the relief of pain in labor and after cesarean section. Using the chronically catheterized maternal-fetal sheep model, we injected 5 mg of preservative-free morphine into the epidural space. No statistically significant changes were observed, neither in maternal or fetal arterial pressure and acid-base status, nor in maternal central venous pressure, systemic and pulmonary vascular resistance, cardiac output, or intrauterine pressure (p greater than 0.05). There was a significant, although small, decrease in maternal heart rate (8%) and uterine blood flow (9%) at 120 minutes (p less than 0.05), and then a return to control values. The maternal levels of morphine peaked at 15 minutes (29 ng/ml) and the fetal levels of morphine peaked at 90 minutes (3 to 4 ng/ml). We conclude that the injection of 5 mg of morphine into the maternal epidural space has no adverse effect on mother or fetus in the sheep model.

Ketamine, catecholamines, and uterine tone in pregnant ewes.

Blood levels of ketamine, measured in both mother (1,230 ng/ml at 1 minute) and fetus (470 ng/ml at 1 minute) illustrate not only rapidly decreasing levels of the drug after its intravenous administration but also its transplacental passage. Concentrations of norepinephrine, epinephrine, and dopamine did not change in the mother or fetus after ketamine, with the exception of maternal levels of epinephrine, which were significantly higher at 45 minutes than control values (p less than 0.05). Maternal effects of ketamine consisted of increases in mean arterial pressure (7% p less than 0.05), cardiac output (16% p less than 0.01), and respiratory acidosis, all of which were slight and transitory. Although resting uterine tone increased (39% p less than 0.01), the uterine blood flow remained constant. None of the physiologic alterations could be correlated with changes in catecholamine levels. Therefore, the cardiovascular and uterine stimulating properties of ketamine at a dose of 0.7 mg/kg are small and are not the result of increased catecholamine levels in plasma. Further studies are necessary to elucidate the mechanism.