Anticonvulsants for neonates with seizures

Abstract

At present there is little evidence from randomised controlled trials to support the use of any of the anticonvulsants currently used in the neonatal period. In the literature, there remains a body of opinion that seizures should be treated because of the concern that seizures in themselves may be harmful, although this is only supported by relatively low grade evidence (Levene 2002; Massingale 1993). Development of safe and effective treatment strategies relies on future studies of high quality (randomised controlled trials with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden.

The bumetanide-sensitive Na-K-2Cl cotransporter NKCC1 as a potential target of a novel mechanism-based treatment strategy for neonatal seizures

“…6,28,41 Barbiturates and benzodiazepines, which are GABA A receptor agonists that are efficacious for treating adult seizures, are currently among the first-line drugs for neonatal seizures; however, they are often ineffective, and have been shown to actually potentiate seizure activity in the immature brain. 19,67 Phenytoin has been used with a similar amount of success.…”

“…19,67 Phenytoin has been used with a similar amount of success. 6,50 Barbiturates and benzodiazepines have also been known to produce a phenomenon termed "electroclinical dissociation" in neonates, whereby the overt clinical manifestations of seizures (convulsions) are inhibited, but electroencephalographydocumented cortical seizure activity is either unaffected or exacerbated. 16,62 This insidious effect of the GABA agonists has the potential for great harm, because it provides physicians with a false sense of security that seizures are under control, while cortical seizure activity-and its associated detrimental effects-continues.…”

“…6,12,60 To date, the only randomized trial of antiepileptic drugs for the treatment of neonatal seizures compared the current first-line drugs (phenobarbital and phenytoin). 50 In this study, the majority of neonates had asphyxia, infarction, or hemorrhage as the origin of their seizures.…”

“…8,10,50 A recent Cochrane Review concluded that there is little evidence to endorse the use of any of the anticonvulsants currently used in the neonatal period. 6 The distinct clinical phenotype and treatment response of neonatal seizures, compared with adult seizures, is probably due to the different mechanisms of seizure generation, propagation, and termination in these 2 age groups. It is likely that an improved understanding of the molecular pathophysiology underlying neonatal seizures would lead to improved treatment by defining targets for novel mechanism-based therapeutics.…”

Preventing deaths from complications of labour and delivery

“…Repeated seizures increase the extent of neuronal injury as well as the risk of subsequent epilepsy [54][55][56]. Phenobarbitone and phenytoin are the commonly used anticonvulsants [57]. The drugs given together are effective in suppressing only just more than 50% of the seizures.…”