A pharmacokinetic model of antiseizure medication load to guide care in the epilepsy monitoring unit.

Abstract

Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering antiseizure medications (ASMs) in the epilepsy monitoring unit (EMU). The relationship between ASM taper strategy, seizure timing, and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU. We studied 80 patients who underwent intracranial electroencephalographic recording for epilepsy surgery planning. We developed a first order pharmacokinetic model of the ASMs administered in the EMU to generate a continuous metric of overall ASM load. We then related modeled ASM load to seizure likelihood and severity. We determined the association between the rate of ASM load reduction, the length of hospital stay, and the probability of having a severe seizure. Finally, we used modeled ASM load to predict oncoming seizures. Seizures occurred in the bottom 50th percentile of sampled ASM loads across the cohort (p< .0001, Wilcoxon signed-rank test), and seizures requiring rescue therapy occurred at lower ASM loads than seizures that did not require rescue therapy (logistic regression mixed effects model, odds ratio=.27, p= .01). Greater ASM decrease early in the EMU was not associated with an increased likelihood of having a severe seizure, nor with a shorter length of stay. A pharmacokinetic model can accurately estimate ASM levels for patients in the EMU. Lower modeled ASM levels are associated with increased seizure likelihood and seizure severity. We show that ASM load, rather than ASM taper speed, is associated with severe seizures. ASM modeling has the potential to help optimize taper strategy to minimize severe seizures while maximizing diagnostic yield.