Pharmacokinetics of magnesium sulfate in the sheep model.

The pharmacokinetic parameters of MgSO4 were followed in the pregnant sheep model following intravenous dosages of MgSO4 comparable to those used in the therapy of the preeclamptic woman. Hemodynamic parameters, including maternal arterial pressure, central venous pressure, systemic vascular resistance, pulmonary artery pressure, heart rate, cardiac output, cardiac index, rate pressure product, stroke volume, stroke index, blood gases, fetal arterial pressure, heart rate, and blood gases, all remain stable during the infusion of MgSO4. Biochemical changes accompanying MgSO4 infusion in these doses were evaluated. It was found that the fetal serum levels of MgSO4 were approximately 70% of those in the mother. The MgSO4 was rapidly excreted into the maternal urine and 8.9% of the MgSO4 infused was cleared by 2 hr after the termination of the infusion. MgSO4 was also excreted by the fetus into amniotic fluid. It was found that a minimum dosage of 1 mg/kg/hr of magnesium was required to achieve a magnesium level in maternal serum at the lower limit of the therapeutic range of 4 mEq/L.

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

Since the demonstration of opiate receptors in the spinal cord in the mid-1970s, investigators have been looking for the most effective epidural narcotic. With the use of the chronically catheterized maternal sheep model, we injected two different doses of preservative-free fentanyl (50 and 100 micrograms) into the epidural space. No statistically significant changes were observed, either in maternal or fetal arterial pressure and acid-base status or in maternal central venous pressure, systemic and pulmonary vascular resistance, cardiac output, and intrauterine pressure (p greater than 0.05). With a dose of 50 micrograms of fentanyl, maternal levels of fentanyl peaked at 60 minutes (50 pg/ml) and the fetal levels of fentanyl peaked at 45 minutes (20 pg/ml). With the 100 micrograms dose of fentanyl, maternal levels of fentanyl peaked at 45 minutes (230 pg/ml) and the fetal levels peaked at 15 minutes (110 pg/ml). We conclude that the injection of 50 and 100 micrograms of fentanyl into the maternal epidural space has no adverse effects on mother or fetus in the sheep model.

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.