Reduction in incidence of periventricular, intraventricular hemorrhages in hypertensive newborn beagles pretreated with phenobarbital

Abstract

Periventricular and intraventricular intracerebral hemorrhages occur frequently in premature newborns and are markers for, or contribute significantly to, neurologic morbidity in survivors. Hemorrhages are hypothesized to result from rapid fluctuations in cerebral perfusion pressure and/or cerebral blood flow. Phenobarbital sodium has been given to premature infants in anticonvulsant dosages in attempts to prevent hemorrhages, but its efficacy in clinical studies has been disputed. In this study, in the 24 to 72-hour-old newborn beagle, an animal model for periventricular and intraventricular intracerebral hemorrhage, phenobarbital sodium was administered to obtain anticonvulsant serum levels prior to phenylephrine-induced hypertensive insult. None of the animals was hypoxic or hypercarbic. Resulting hypertensive systemic mean arterial BPs were 99 +/- 8 mm Hg in the 15 control pups and 93 +/- 15 mm Hg in the 15 phenobarbital sodium-treated pups (not statistically significantly different). The duration of the hypertension was the same in both groups. Phenobarbital caused a significant decrease in mean arterial BP in the treated group just after its administration (P less than .05). Six of the 15 control pups (40%) and one of the 15 treated pups (7%) demonstrated macroscopic and microscopic periventricular and intraventricular hemorrhage (P less than .05, chi 2, Yates correction). Thus, in nonasphyxiated newborn beagles, phenobarbital sodium significantly reduced the incidence of hemorrhage after hypertensive insult.