Alteration of ovine fetal respiratory-like activity by diazepam, caffeine, and doxapram

The effects of diazepam, caffeine citrate, and doxapram on fetal respiratory-like activity (RLA) were studied in 10 chronic sheep preparations (90 to 130 days' gestation). We define fetal RLA as regular changes in fetal tracheal pressure occurring with a frequency of at least 1 Hz and an amplitude greater than -5 mm. Hg in the absence of fluctuations in amniotic cavity pressure. In all maternal (8) and fetal (7) intravenous infusions of diazepam (5 to 10 mg.), RLA ceased almost instantaneously. The duration of fetal apnea varied from 29 to 70 minutes with a mean of 57 minutes, and on occasion, a gasping pattern preceded recovery of RLA. Maternal and fetal plasma concentrations of diazepam indicated rapid bidirectional placental transfer. Intravenous infusion of doxapram (3 mg.) to the fetus immediately initiated a transient episode of RLA in 19 of 20 trials. Fetal infusion of caffeine citrate (10 to 20 mg.), especially via the carotid artery, was also associated with the rapid onset of a transient episode of fetal breathing. Saline control infusions were without effect. Fetal blood gases and pH were not altered by the administration of diazepam, caffeine citrate, or doxapram. It is suggested that each drug owes its action on RLA to an effect on fetal central nervous system. The influence of pharmacologic agents on the process and interpretation of fetal monitoring requires continued attention.