Abstracts

Rationale: To assess the effect of body mass index (BMI) on outcome measures in patients receiving a single intravenous fosphenytoin loading dose.Methods: A 5-year retrospective review was conducted on patients who received an intravenous loading dose of fosphenytoin at Mayo Clinic, Rochester, MN. Patients were included if they had received an intravenous fosphenytoin dose of at least 10 mg/kg of actual body weight, had a serum fosphenytoin level at 24 hours, were older than 17 years of age and had consented to research. Patients were divided into three groups based on their BMI: normal (<26 kg/m2), overweight (26-29.9 kg/m2) and obese (≥30 kg/m2). Serum fosphenytoin levels were recorded from 1-24 hours after the medication was administered. Information pertaining to adverse events, hospital length of stay, mortality and drug efficacy were collected. Administration of a second antiepileptic medication was considered a surrogate marker for efficacy. A fosphenytoin total level of 10-20 mcg/mL or free drug level of 1-2 mcg/mL was considered therapeutic.Results: 410 consecutive patients were included in the study. The mean BMI for the cohort was 28 (range 14.9-57.8). 42% of the patients had a normal BMI; while 26.3% were overweight and 31.7% were obese. The mean fosphenytoin loading dose was 19 mg/kg (range 10-32 mg/kg). At 24 hours, the obese group was more likely than the non-obese groups to have a therapeutic fosphenytoin level of 10-20 mcg/mL (75.4% vs. 68.5% vs. 61.6%, p=0.04). Patients with a BMI < 30 were more likely to have a supratherapeutic drug level. This finding did not change after adjusting for the dose, time of the level, renal function or albumin level. Obese patients were statistically more likely to receive a second antiepileptic agent compared to the non-obese groups (38.8% vs. 28.7% vs. 18.6%, p=0.03). Nystagmus was more common in the non-obese groups (11.1% vs. 4.6%, p=0.03). The incidence of bradycardia, hypotension and ataxia was not statistically different between the groups. Hypotension was the most commonly reported adverse event in all of the groups, which occurred in 39% of patients. Hospital length of stay ranged from 0-138 days (0 days indicated those patients who received fosphenytoin while in the emergency department). The median (IQR) length of stay in the obese and non-obese groups was 8 (4-24) and 7 (4-15) days, respectively (p=0.02). 48 patients died during their hospitalization.Conclusions: This study found significant differences in the fosphenytoin drug levels after receiving a single loading dose based on BMI. Adverse reactions were similar in the two groups, although non-obese patients were more likely to develop nystagmus after the dose. Obese patients received a second antiepileptic medication more often, suggesting a lack of drug efficacy.