Effects of diphenhydramine in the fetal lamb after maternal or fetal administration.

The effects of diphenhydramine on fetal behavioral states, breathing activity, blood gas status, arterial pressure and heart rate have been investigated in the fetal lamb after maternal or fetal drug administration to steady state in chronically instrumented pregnant sheep. During maternal drug infusion there were declines in the percentage of low voltage electrocorticographic (ECoG) pattern 55-46%), the percentage of low voltage ECoG activity containing rapid eye movements (80-55%), the overall incidence of fetal breathing (42-21%) and in the amount of breathing during low voltage ECoG activity (67-36%). These sedative like effects occurred at fetal plasma drug concentrations (approximately 36 ng/ml) lower than those resulting in discernable central nervous system effects in adults. Drug infusion to fetus achieved higher fetal plasma drug levels (approximately 448 ng/ml) and resulted in a transient decline in arterial Po2 and pH, associated with transient tachycardia and vigorous breathing movements during the initial portion of the infusion. There was also a significant fall in the amount of low voltage ECoG pattern (51-26%) and marked increases in the amount of intermediate voltage pattern (8-46%), and an increase in the occurrence of rapid eye movements during this intermediate voltage pattern (8-63%). In summary, diphenhydramine elicits significant effects in the fetal lamb, the precise nature of which varies with drug concentration.