Are Prophylactic Barbiturates Effective After Perinatal Asphyxia?
An updated Cochrane review found low or very low quality evidence regarding the use of prophylactic barbiturates in infants with perinatal asphyxia.
Barbiturates have been administered to infants with perinatal asphyxia in order to prevent seizures, which may worsen secondary neuronal injury. Leslie Young, MD, of the University of Vermont Medical Center, Burlington, VT, and colleagues searched the Cochrane Central Register of Controlled Trials and other databases to determine the effect of prophylactic barbiturate therapy on mortality or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia.
The review included randomized and quasi-randomized controlled trials of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures vs. controls after perinatal asphyxia. Study authors calculated risk ratios (RR), risk differences (RD), mean difference for continuous data as well as the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH).
Dr. Young and coauthors found 9 randomized controlled trials that met the inclusion criteria; 8 of which compared prophylactic barbiturate vs. conventional treatment (n=439) and 1 trial that compared barbiturates vs. phenytoin (n=17).
One study found a lower risk of death or severe neurodevelopmental disability with phenobarbital vs. conventional therapy (RR 0.33, 95% CI: 0.14 to 0.78; RD -0.55, 95% CI: -0.84 to -0.25) but was established as very low quality evidence. Eight other trials found no significant impact on mortality risk (typical RR 0.88, 95% CI: 0.55 to 1.42; typical RD -0.02, 95% CI: -0.08 to 0.05); this was deemed as low quality evidence.
Data from a meta-analysis of 6 studies reporting neonatal seizures found a statistically significant reduction in seizures in the prophylactic barbiturate group vs. conventional treatment (typical RR 0.62, 95% CI: 0.48 to 0.81; typical RD -0.18, 95% CI: -0.27 to -0.09), which was established as low quality evidence.
In the study comparing prophylactic barbiturate vs. phenytoin, study authors found no significant difference in seizure activity during the neonatal period between the 2 study arms (RR 0.89, 95% CI: 0.07 to 12.00).
Dr. Young concluded that though prophylactic barbiturates following perinatal asphyxia did lower the risk of seizures, "there was no reduction seen in mortality and there were few data addressing long-term outcomes." Thus, the use of prophylactic barbiturates for late preterm and term infants immediately following perinatal asphyxia cannot be recommended for routine practice at this time. Future studies should have sufficient sample size and duration to identify clinically significant reductions in mortality and disability, she added.
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