Phenobarbitone versus Phenytoin for Treatment of Neonatal Seizures: An Open-label Randomized Controlled Trial.

ABSTRACT

Objective: To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and nearterm neonates. Design: Open labeled randomized controlled trial. Setting: Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. Participants: All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Intervention Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Primary outcome variable Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Results: Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Conclusion: Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology.