Abstracts

Rationale: Status epilepticus is the most common neurological emergency in childhood and is associated with an overall mortality rate of 8%. Terminating seizures is crucial since the risk of cerebral damage increases with continuous seizing. Fosphenytoin is an intravenous medication used in the management of status epilepticus and is dosed on a milligram per kilogram basis. In the United States, 17% of children and adolescents are obese. Data is lacking regarding whether or not medication dose adjustments are needed in the obese population, especially those medications used in emergent situations. Fosphenytoin, a pro-drug of phenytoin, is highly protein bound and water soluble. Due to the fact that it is water soluble, it is possible that weight-based dosing using actual body weight, may lead to supra-therapeutic levels in obese patients. This may increase the likelihood of adverse effects including cardiovascular collapse, central nervous system depression, and paradoxical seizures. No studies exist regarding the effect of obesity on the pharmacokinetics of fosphenytoin and therefore it is unknown whether dose adjustments are warranted in obese pediatric patients. The primary objective of this study is to determine if obesity has an effect on phenytoin levels in pediatric patients. The secondary objective is to determine if obese pediatric patients experience more adverse effects than non-obese pediatric patients. Methods: A retrospective, matched-cohort study was performed in all patients aged 2-18 years who received fosphenytoin at Texas Children's Hospital from March 2007 - March 2013. Patients were included if their body mass index was greater or equal to the 95^th percentile and had at least one phenytoin level drawn approximately 2 hours following a fosphenytoin loading dose. Patients were excluded if receiving chronic phenytoin therapy. Obese pediatric patients who met study criteria were matched to non-obese pediatric patients based on age and sex. Data collected included baseline demographics, phenytoin levels (total and free if available), albumin, adverse events (arrhythmia, hypotension, altered mental status), and seizure alleviation. Results: Approximately 1000 charts were queried with a total of 58 obese patients meeting study criteria. The majority of patients were male children (7 ± 5 years of age). Mean total phenytoin levels were 21.2 (±7.8) mcg/mL in the obese patients compared to 20.2 (±7.1) mcg/mL in the non-obese patients (p=0.68) following a mean loading dose of 19.9 (±7.8) mg PE/kg and 22.1 (±6.4) mg PE/kg (p=0.39), respectively. Results for the secondary objective are still in progress. Conclusions: Obesity does not appear to have an effect on phenytoin levels in pediatric patients.