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

J Paediatr Child Health. 2010 Jan;46(1-2):17-22. doi: 10.1111/j.1440-1754.2009.01611.x. Epub 2009 Nov 23.

Abstract

Aim: 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.

Method: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug*
  • Enteral Nutrition*
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Phenobarbital / administration & dosage*
  • Phenobarbital / pharmacokinetics
  • Phenobarbital / pharmacology
  • Phenobarbital / therapeutic use

Substances

  • Phenobarbital