Tuesday, January 31, 2017

Underdosing of lorazepam in children is associated with increased seizure duration

The first dose of lorazepam, when administered as a first-line antiepileptic drug (AED) for pediatric refractory status epilepticus, frequently is underdosed, and doses lower than 0.1 mg/kg are associated with increased seizure duration, according to research presented at the 70th Annual Meeting of the American Epilepsy Society (AES).

The results emphasize the importance of following AES status epilepticus guidelines, which call for lorazepam dosing of 0.1 mg/kg, said Dmitry Tchapyjnikov, MD, of Duke University School of Medicine in Durham, North Carolina, and colleagues.

“There is high variability in lorazepam dosing when used in the treatment of status epilepticus, but little is known about how this dosing variability affects seizure duration,” the researchers said. The investigators analyzed data from a multicenter prospective observational cohort of pediatric patients admitted with refractory status epilepticus (ie, status epilepticus did not resolve after two or more AEDs) between 2011 and 2016. The data were compiled by the Pediatric Status Epilepticus Research Group.

Researchers grouped patients by those who received a lower dose ( < 0.05 mg/kg), medium dose (0.05 mg/kg to < 0.1 mg/kg), and higher dose ( ≥ 0.1 mg/kg) of lorazepam. They used Cox proportional hazards models to assess the association between lorazepam dose and time to seizure resolution, adjusting for age, sex, presumed seizure cause, seizure duration prior to lorazepam administration, home AED use, prior neurologic conditions, and study site.

A total of 103 patients were included in the analysis. Patients had a median age of 4.5, and 48% were female. Lorazepam was administered at a median of 20 minutes after seizure onset. Twenty-eight percent of patients received a lower dose, 43% a medium dose, and 29% a higher dose. Individuals in the higher dose group were significantly more likely to experience seizure resolution sooner than patients in the medium and lower dose groups, with hazard ratios of 1.62 and 2.49, respectively. Median time to total seizure resolution following lorazepam administration was 93 minutes in the higher dose group, 160 minutes in the medium dose group, and 350 minutes in the lower dose group.
Among patients who had convulsive seizures, those in the higher dose group were more likely to experience convulsive seizure resolution sooner than those in the lower dose group (hazard ratio, 1.89). Median time to convulsive seizure resolution was 67 minutes in the higher dose group and 120 minutes in the lower dose group.


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