Effect of phenobarbital on free radicals in neonates with hypoxic ischemic encephalopathy--a randomized controlled trial.

Background: Phenobarbital is one of the oldest, cheapest and easily available cerebroprotective drugs for the hypoxic brain. However, its potential and various actions have not been fully explored.

Aim: To evaluate the effects of Phenobarbital on levels of oxidants and anti-oxidants in term and near term neonates with hypoxic ischemic encephalopathy.

Methods: Design--randomized controlled trial. Setting--tertiary care referral perinatal centre. Procedure--asphyxiated neonates (gestation > or = 34 weeks) with HIE were randomized to receive Phenobarbital 20 mg/kg i.v. within first six hours of life or to control group. CSF levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and blood levels of vitamins A and E were estimated at 10-12 hours of age.

Results: CSF levels of MDA, SOD, GPx and blood levels of vitamins A and E were significantly lower in the Phenobarbital group (p<0.001). There was a trend towards lower levels of CSF MDA, SOD, GPx and blood vitamins A and E in babies with normal outcome as compared to babies with adverse outcome (death or neurologically abnormal at discharge).

Conclusion: Phenobarbital in the dose of 20 mg/kg i.v. given within 6 hours of life in term and near-term neonates with HIE, was associated with a decrease in lipid peroxides, anti-oxidant enzymes and anti-oxidant vitamins.