Maternally administered esmolol produces fetal beta-adrenergic blockade and hypoxemia in sheep

Although esmolol may be a useful therapeutic agent in obstetrics and obstetric anesthesia, concerns about fetal safety have limited its use. To assess acute fetal hemodynamic effects of maternally administered esmolol, saline or esmolol (4-200 micrograms.kg-1.min-1 in a stepped manner) was infused into maternal venous catheters in nine chronically prepared pregnant ewes, and the degree of beta-adrenergic blockade was assessed by isoproterenol challenge. In control experiments saline infusion and repeated isoproterenol challenges did not alter measured parameters, although maternally administered isoproterenol (0.1 micrograms) transiently decreased uterine blood flow by 20 +/- 5% (mean +/- SEM; P less than 0.05). Esmolol produced a dose-dependent decrease in maternal blood pressure and fetal heart rate (maternal blood pressure decreased by 22 +/- 8% and fetal heart rate decreased by 27 +/- 7% following esmolol, 200 micrograms.kg-1.min-1; P less than 0.05). Fetal arterial PO2 decreased from 18.2 +/- 1.2 mmHg before to 14.1 +/- 1.5 mmHg following esmolol, 200 micrograms.kg-1.min-1 (P less than 0.05). Maternally administered esmolol produced similar dose-dependent beta-adrenergic blockade in both ewe and fetus, with complete blockade following the 80 and 200 micrograms.kg-1.min-1 doses. Thirty minutes following cessation of esmolol infusion, fetal resting heart rate and maternal and fetal isoproterenol-stimulated heart rate remained below control values. These results suggest that maternally administered esmolol may produce adverse fetal effects, limiting its usefulness in the obstetric setting.