A rational basis for the measurement of free phenytoin concentration in critically ill trauma patients.

Phenytoin binding to serum proteins and factors influencing protein binding were investigated in 38 critically ill trauma patients. In 24% of these patients, the free fraction of phenytoin was < or = 10%, whereas in 76%, the free phenytoin fraction was increased > 10%--up to 24%. Nonantiepileptic comedication, sex, or age had no influence on phenytoin binding in any of the 38 patients. Elevated free phenytoin fraction was found in those with hypoalbuminemia and hepatic and renal impairments. In these patients, the free phenytoin fraction should be measured routinely.