The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus

Abhishek G. Sathe, Jordan J. Elm, James C. Cloyd, James M. Chamberlain, Robert Silbergleit, Jaideep Kapur, Hannah R. Cock, Nathan B. Fountain, Shlomo Shinnar, Daniel H. Lowenstein, Robin A. Conwit, Thomas P. Bleck, Lisa D. Coles

Research output: Contribution to journalArticle

Abstract

The Established Status Epilepticus Treatment Trial was a blinded, comparative-effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine-refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight-based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight-normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54-1.51) or >90 kg (OR = 0.85, 95% CI = 0.42-1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings.

Original languageEnglish (US)
Pages (from-to)e66-e70
JournalEpilepsia
Volume61
Issue number6
DOIs
StatePublished - Jun 1 2020

Keywords

  • ESETT
  • antiseizure medications
  • dose-response
  • seizure cessation
  • weight-based dosing

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Sathe, A. G., Elm, J. J., Cloyd, J. C., Chamberlain, J. M., Silbergleit, R., Kapur, J., Cock, H. R., Fountain, N. B., Shinnar, S., Lowenstein, D. H., Conwit, R. A., Bleck, T. P., & Coles, L. D. (2020). The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus. Epilepsia, 61(6), e66-e70. https://doi.org/10.1111/epi.16534