Rescue therapy with high‐dose oral phenobarbitone loading for refractory status epilepticus

Abstract

Parenteral phenobarbitone was unavailable in South Africa from 2005 to 2006. This study aimed to establish the effectiveness of enteral phenobarbitone in the management of childhood status epilepticus. Patients in status epilepticus (December 2005-June 2006) received 20 mg/kg phenobarbitone via nasogastric tube in addition to standard status interventions (benzodiazepine boluses, phenytoin infusion). Phenobarbitone concentrations were taken post loading. Phenobarbitone population pharmacokinetics was analysed using non-linear mixed effects modelling. Sixteen patients (7 female, 9 male) were assessed, median age 5 months (range 9 days-168 months). Nine patients received 20 mg/kg; the maximum total dosage administered was 80 mg/kg with a concentration of 283 micromol/L. The typical population value of the volume of distribution was 1.2 (95% confidence interval (CI): 0.8-1.6) L/kg with interindividual variability (as coefficient of variation) of 53% (95% CI, 9-74%). Seizure control was documented within 1 h (n= 8), 1(1)/(2) h (n= 1), 3 h (n= 1) and 4 h (n= 5) following enteral phenobarbitone loading. No adverse effects were apparent from the enteral phenobarbitone administration. Patients tolerated enteral loading with phenobarbitone. A single enteral loading dose resulted in adequate phenobarbitone exposure. This practice was a safe intervention for centres lacking parenteral phenobarbitone. Therapeutic concentrations and seizure control after enteral loading suggested a role for enteral phenobarbitone in the management of acute status epilepticus as well as prophylaxis against seizure recurrence.