Phenytoin Serum Concentrations in Patients With Left Ventricular Support Devices: A Case Series

Achieving therapeutic levels of phenytoin is critical to its efficacy and safety. Free serum levels represent pharmacologically active phenytoin due to the high protein binding of the drug. Predicting free serum levels in patients with left ventricular support devices can be challenging, as the pharmacokinetics (PK) can be significantly altered, and equations to correct total levels have not been validated in this population. The aim of this case series was to describe serum phenytoin concentrations in critically ill patients requiring left ventricular support devices.

A retrospective chart review was performed including patients who received phenytoin therapy and had at least 1 set of simultaneously measured free and total serum phenytoin levels during left ventricular support with a mechanical device. Corrected total phenytoin levels were calculated using Sheiner-Tozer equations.

Three patients were included in this case series. Patients 1 and 2 required venoarterial extracorporeal membrane oxygenation (ECMO) during phenytoin therapy, and patient 3 had a durable left ventricular assist device (LVAD). Measured phenytoin levels ranged from 4.1 to 11.4 µg/mL, and calculated corrected levels were 6.8 to 18.4. Measured free phenytoin levels ranged from 1.2 to 3.6 µg/mL, which correlated with free fractions of 15.8% to 37.9%.

This case series demonstrates a higher percentage of free phenytoin compared to the total serum level than would be predicted and an inability to rely on corrected total phenytoin level to predict whether it is within therapeutic range. Monitoring of free serum phenytoin concentrations should be strongly considered in critically ill patients requiring LVAD or ECMO support.