Cardiovascular and Hematologic Effects of Diphenylhydantoin in Maternal and Fetal Sheep

Abstract

Anticonvulsant therapy often includes diphenylhydantoin (Dilantin) and is usually advocated during the pregnancy of an epileptic woman. The cardiovascular and hematologic effects of diphenylhydantoin (5 mg/kg body weight/ 5 min) were studied in 12 experiments on 5 ewes and their fetuses in which catheters were chronically implanted and an electromagnetic flow probe was continually around the uterine artery. Slight but significant transient decreases in fetal blood pressure (P <.001), oxygen percent saturation (O₂%,P <.02), and O₂content (P <.01) were observed. These parameters recovered to baseline values within 75 minutes after infusion was begun, and no other fetal changes were noted. Maternal metabolic alkalosis was evidenced by significant increases in pH (P < .001) bicarbonate (P <.05), and base excess (P <.02). A slight decrease in the percent hemoglobin was observed at 15, 60, and 90 minutes (P <.02,P <.05, andP <.01, respectively). No changes were observed in maternal heart rate or uterine blood flow, though an increase in blood pressure was observed at 30 minutes (P<.05). From these observations, it is concluded that the administration of diphenylhydantoin intravenously causes transient fetal hypotension, reduction of O₂%, maternal metabolic alkalosis, and transient hypertension without any changes in fetal pH, PCO₂, or uterine blood flow. Therefore, it can be considered a relatively safe drug to be used during pregnancy.