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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Singh
Daljit
D
Neonatal Unit, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh, India.
Kumar
Praveen
P
Narang
Anil
A
D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005609:Free Radicals; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000401:mortality; D007231:Infant, Newborn; D008297:Male; D009422:Nervous System Diseases / Q000517:prevention & control; D009460:Neurologic Examination; D010634:Phenobarbital / Q000008:administration & dosage / Q000627:therapeutic use*; D012640:Seizures / Q000517:prevention & control; D015996:Survival Rate; D016896:Treatment Outcome
D000927:Anticonvulsants; D005609:Free Radicals; D010634:Phenobarbital