A randomized controlled trial of phenobarbital in neonates with hypoxic ischemic encephalopathy

Phenobarbital is one of the oldest, cheapest and most easily available cerebro-protective drugs for the hypoxic brain. It has multiple actions that could be of benefit to the asphyxiated brain. However, its potential has not been fully explored.

To study the effect of phenobarbital given within six hours of life to term and near-term asphyxiated neonates, on mortality, neurological abnormality at discharge and seizures.

This was a randomized controlled trial set in a tertiary care referral perinatal centre. Asphyxiated neonates (gestational age >or= 34 weeks) manifesting with hypoxic ischemic encephalopathy (HIE) in the first six hours of life were randomized to receive either injection of phenobarbital 20 mg/kg IV or to the control group. The primary outcome was death or abnormal neurological examination at discharge while seizures, need for ventilation and multi-organ dysfunction were secondary outcomes.

Twenty-five babies received phenobarbital and 20 were in the control group. The mortality (20% vs. 15%) and abnormal neurological outcome at discharge (30% vs. 53%, p = 0.15) were statistically not different between the two groups. In the phenobarbital group, 8% of neonates developed seizures while 40% of babies in the control group developed seizures (p = 0.01, relative risk (RR) = 0.20 (0.05-0.84)). Phenobarbital was well tolerated and did not increase the need for respiratory support.

Phenobarbital in the dose of 20 mg/kg IV given within six hours of life to term and near-term neonates with HIE, significantly decreased the incidence of neonatal seizures and was well tolerated. However, it did not alter the mortality and neurologic outcome at discharge.