Presented at the Neonatal Society 2002 Autumn Meeting.
Rennie JM, Boylan GB, Chorley G, Pressler R, Fox GF, Farrer K, Morton M, Binnie C
Departments of Child Health and Neurophysiology, Guy’s King’s St Thomas’ School of Medicine, London UK
Background: There has been tremendous recent progress in the pharmacological treatment of seizures in children and adults, but the advances made have not extended to the newborn period. Little work has been done on the effectiveness of second-line anticonvulsants, and none using video-EEG to quantify the seizure burden.
Aims: We designed an open randomised trial of midazolam and lignocaine as second line anticonvulsant treatments for babies who failed to respond to first line phenobarbitone treatment.
Methods: Babies admitted to the NICUs of King’s College Hospital or Guy’s Hospital, London who were at high risk of seizure were enrolled. The ethics committees of both hospitals approved this study. Seizure diagnosis and response to treatment was measured using continuous video-EEG recording. Babies with seizures were treated with phenobarbitone as first line, up to a dose of 40 mg/kg. Babies who continued to have seizures were then randomly assigned to receive either lignocaine (6mg/kg load, 2mg/kg/hour infusion, increasing to 4mg/kg/hr) or midazolam (60 microgram/kg load, infusion of 150μg/kg/hour increasing to 300μg/kg/hr). Babies whose parents did not wish them to be enrolled into the drug study but who were happy for monitoring to continue received clonazepam.
Results: Eighty-seven babies were monitored; 5 babies were excluded for protocol violations. Twenty two babies had EEG confirmed seizures; 11 babies responded to phenobarbitone alone. Eleven babies were randomized to receive second-line treatment. Three of five babies treated with lignocaine responded, only at the higher dose. Seizures in the remaining babies, who were treated with either midazolam or clonazepam were not controlled.
Conclusions: Our results show that the response to treatment with currently available second line antiepileptic treatments in babies is disappointing. Babies who responded to phenobarbitone alone were more likely to have a normal or mildly abnormal background EEG and a smaller seizure burden than those who required second-line treatment. We believe that the search for an effective anticonvulsant regimen suitable for use in the newborn must continue.