Eisenach J C, Castro M I
Department of Anesthesia, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.
Anesthesiology. 1989 Nov;71(5):718-22. doi: 10.1097/00000542-198911000-00015.
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.
尽管艾司洛尔可能是产科及产科麻醉中一种有用的治疗药物，但对胎儿安全性的担忧限制了其应用。为评估母体给予艾司洛尔对胎儿急性血流动力学的影响，将生理盐水或艾司洛尔（以逐步递增方式，剂量为4 - 200微克·千克⁻¹·分钟⁻¹）注入9只慢性制备的怀孕母羊的母体静脉导管中，并通过异丙肾上腺素激发试验评估β-肾上腺素能阻滞程度。在对照实验中，尽管母体给予异丙肾上腺素（0.1微克）会使子宫血流量短暂减少20±5%（平均值±标准误；P<0.05），但生理盐水输注及重复的异丙肾上腺素激发试验并未改变所测参数。艾司洛尔使母体血压和胎儿心率呈剂量依赖性下降（给予200微克·千克⁻¹·分钟⁻¹的艾司洛尔后，母体血压下降22±8%，胎儿心率下降27±7%；P<0.05）。给予200微克·千克⁻¹·分钟⁻¹的艾司洛尔后，胎儿动脉血氧分压从给药前的18.2±1.2毫米汞柱降至14.1±1.5毫米汞柱（P<0.05）。母体给予艾司洛尔在母羊和胎儿中均产生了类似的剂量依赖性β-肾上腺素能阻滞，在80和200微克·千克⁻¹·分钟⁻¹剂量后出现完全阻滞。停止输注艾司洛尔30分钟后，胎儿静息心率以及母体和胎儿经异丙肾上腺素刺激后的心率仍低于对照值。这些结果表明，母体给予艾司洛尔可能会对胎儿产生不良影响，限制了其在产科环境中的应用。
