Metabolic and Cardiovascular Changes During Prolonged Ritodrine Infusion in Fetal Lambs

Prophylaxis of threatened premature labor with ritodrine may lead to prolonged fetal exposure to the drug. To investigate the direct consequences of this, 11 fetal lambs were given ritodrine hydrochloride for periods of 2-4 days by continuous intravenous infusion at 5 or 10/tig/minute (1- 3/ug/minute/kg estimated fetal weight). These dosages had no measurable effects on the ewes. In the fetus, measurements confirmed and extended the results of earlier shortterm experiments, but differences from the effects of longterm maternal ritodrine infusion imply little placental transfer of the drug in sheep. Ritodrine had little or no effect on mean arterial pressure, blood pH, pCO2, plasma alphaamino acid nitrogen, or growth hormone, but resulted in marked hypoxemia, tachycardia, hyperlactacidemia, hyperglycemia, and hyperinsulinemia during the first 24-48 hours of infusion. Despite continued ritodrine infusion, heart rate and the metabolic parameters returned toward normal within 72 hours. Hypoxemia persisted longer, but tended to lessen after 2 days of infusion. The results indicate that tachyphylaxis to ritodrine develops in the fetal lamb during prolonged administration, but that when fetal well-being is already compromised, ritodrineʼs effects on oxygenation and Iactacidemia could jeopardize fetal survival