Phenytoin toxicity in patients with traumatic brain injury

Background: We observed that in patients with traumatic brain injury (TBI) who did not improve as expected, serum levels of phenytoin were in the toxic range and that their sensorium improved with modification of the dose. This led us to study the usage of phenytoin in patients with TBI. Aims: To determine the prevalence of phenytoin toxicity in TBI patients and to study the suitability of using ideal body weight (IBW) to guide phenytoin dosing. Setting and Design: Neurotrauma unit of a tertiary care centre in India. Prospective data collection from an already established protocol of drug level monitoring. Materials and Methods: The study cohort included 100 consecutive adult patients with mild or moderate TBI who were administered phenytoin based on IBW. Trough serum phenytoin and albumin levels were measured on day 4 after administration of the loading dose and actual body weight obtained when it was possible. Statistical Analysis: Chi-square was used for comparing categorical variables, student's t-test for continuous variables and multivariate regression analysis to obtain independent risk factors. Results: Clinical toxicity was observed in 15% of patients and biochemical toxicity in 36%, with a significant association between the two (P < 0.01). Using multivariate analysis, abdominal girth <= 75 cm (P = 0.07), neck circumference <= 34 cm (P = 0.025) and IV dose proportion >= 80% (P = 0.003) were independent risk factors for biochemical toxicity. The plot between actual weight and IBW showed that toxicity occurred when IBW was higher than actual weight. Conclusion: The prevalence of biochemical phenytoin toxicity was high, with independent risk factors being a higher proportion of IV administration and overestimation of weight by IBW. Clinical suspicion of phenytoin toxicity was a good predictor of biochemical toxicity.