Metabolic and cardiovascular changes during prolonged ritodrine infusion in fetal lambs
Bassett, J.M.; Hanson, C.; Weeding, C.M.
Obstetrics and Gynecology 73(1): 117-122
1989
ISSN/ISBN: 0029-7844 PMID: 2642323 Document Number: 343176
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 micrograms/minute (1-3 micrograms/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 short-term experiments, but differences from the effects of long-term 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 alpha-amino 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, ritodrine's effects on oxygenation and lactacidemia could jeopardize fetal survival.