The maternal and fetal effects of milrinone and dopamine in normotensive pregnant ewes

Abstract

The safety of milrinone, administered during gestation, was evaluated in seven chronically instrumented pregnant ewes and their fetuses. Each of the following six intravenous regimens was administered in random order: milrinone, 75 micrograms.kg-1, over 1 minute, followed by 240-minute infusions of the drug at a rate of 1, 2, or 4 micrograms.kg-1.min-1; dopamine 5 or 10 micrograms.kg-1.min-1 over 60 minutes; or normal saline solution, 0.5 ml.min-1 for 240 minutes. Maternal and fetal acid-base parameters, heart rate, and blood pressure were monitored as were the ewe's venous and intraamniotic pressures and uterine blood flow. Milrinone concentrations determined in maternal arterial blood samples obtained during 1 and 2 micrograms.kg-1.min-1 infusions were found to be within the human therapeutic range. Bolus injection of milrinone, as well as the lowest drug infusion, resulted in no significant changes in uterine blood flow, whereas 2 micrograms.kg-1.min-1 milrinone infusion led to a 14% to 19% increase in uterine blood flow between 120 and 240 minutes. With the highest milrinone infusion, this increase was approximately 20%. In contrast, with both dopamine infusions, a dose-related decrease in uterine blood flow of 15% to 26% occurred between 15 and 60 minutes. No milrinone could be detected in any fetal plasma samples. Fetal arterial pH and blood gas tensions did not change during milrinone infusions. Dopamine 10 micrograms.kg-1.min-1 led to a progressive decrease in fetal arterial pH and an increase in PaCO2, which may have been related to similar changes in the ewe. It is concluded that milrinone has no adverse effects on uterine blood flow and fetal well-being when administered during ovine pregnancy.