Association of intravenous phenytoin toxicity with demographic, clinical, and dosing parameters

Previous studies investigating intravenous phenytoin toxicity have been largely anecdotal, and have inferred an association with older patients, cardiovascular disease, and higher doses, concentrations, and infusion rates of phenytoin. This investigation sought to elucidate both the incidence and nature of acute intravenous phenytoin toxicity in emergency department patients, and to identify any demographic, clinical, or dosing associations with toxicity, by analyzing a retrospective case series over 3 years in a municipal teaching hospital. A consecutive series of 164 patients who received intravenous phenytoin loading in the emergency department following acute seizure presentation was identified. Demographic, clinical, and dosing data were collected, and the nature of toxicity was noted. Data were then analyzed statistically for potential associations with toxicity. Eight cases of hypotension and no apnea or arrhythmias were noted in the 164 patients (4.9% incidence). Analysis of demographic, clinical, and dosing data found statistically significant associations between hypotension and both a lower phenytoin dose administered (537 mg in hypotensive patients v 787 mg in normotensive patients, P = .00046) and the presence of abnormal neurological signs at initial presentation (20% incidence when abnormal signs present v 3.5% incidence when absent, P = .026). No other associations were found between toxicity and other variables. This sample size could detect differences ranging from 4% to 11% in complication rate (hypotension) for the various demographic, clinical, and dosing parameters with a statistical power of 80%. It was concluded that the incidence of hypotension from intravenous phenytoin administration in this study population was approximately 5%, and the incidence of apnea and cardiac arrhythmia in this series was 0%. No associations with age, comorbidities, or infusion rates were found, in contrast to other studies. Association of intravenous phenytoin toxicity with lower phenytoin dose is likely related to prompt cessation of the drug once signs of toxicity occur. The possible association of toxicity with abnormal initial neurological signs has not previously been reported and may possibly define a population at risk if validated by prospective research in additional populations.