ASSOCIATION OF INTRAVENOUS PHENYTOIN TOXICITY WITH DEMOGRAPHIC, CLINICAL, AND DOSING PARAMETERS

Previous studies investigating intravenous phenytoin toxicity have bee n largely anecdotal, and have inferred an association with older patie nts, cardiovascular disease, and higher doses, concentrations, and inf usion rates of phenytoin. This investigation sought to elucidate bath the incidence and nature of acute intravenous phenytoin toxicity in em ergency department patients, and to identify any demographic, clinical , or dosing associations with toxicity, by analyzing a retrospective c ase series over 3 years in a municipal teaching hospital. A consecutiv e series of 164 patients who received intravenous phenytoin loading in the emergency department following acute seizure presentation was ide ntified. Demographic, clinical, and dosing data were collected, and th e nature of toxicity was noted. Data were then analyzed statistically for potential associations with toxicity, Eight cases of hypotension a nd no apnea or arrhythmias were noted in the 164 patients (4.9% incide nce). Analysis of demographic, clinical, and dosing data found statist ically significant associations between hypotension and both a lower p henytoin dose administered (537 mg in hypotensive patients v 787 mg in normotensive patients, P =.00046) and the presence of abnormal neurol ogical signs at initial presentation (20% incidence when abnormal sign s present v 3.5% incidence when absent, P =.026). No other association s were found between toxicity and other variables, This sample size co uld detect differences ranging from 4% to 11% in complication rate (hy potension) for the various demographic, clinical, and dosing parameter s with a statistical power of 80%. It was concluded that the incidence of hypotension from intravenous phenytoin administration in this stud y population was approximately 5%, and the incidence of apnea and card iac arrhythmia in this series was 0%. No associations with age, comorb idities, or infusion rates were found, in contrast to other studies, A ssociation of intravenous phenytoin toxicity with lower phenytoin dose is likely related to prompt cessation of the drug once signs of toxic ity occur. The possible association of toxicity with abnormal initial neurological signs has not previously been reported and may possibly d efine a population at risk if validated by prospective research in add itional populations. Copyright (C) 1996 by W.B. Saunders Company.