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

Sathe, A; Elm, J; Cloyd, JC; Chamberlain, JM; Silbegleit, R; Kapur, J; Cock, HR; Fountain, N; Shinnar, S; Lowenstein, DH; et al. Sathe, A; Elm, J; Cloyd, JC; Chamberlain, JM; Silbegleit, R; Kapur, J; Cock, HR; Fountain, N; Shinnar, S; Lowenstein, DH; Conwit, RA; Bleck, TP; Coles, LD (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. ISSN 0013-9580 https://doi.org/10.1111/epi.16534
SGUL Authors: Cock, Hannah Rutherford

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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.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Sathe, AG, Elm, JJ, Cloyd, JC, et al. The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus. Epilepsia. 2020; 61: e66– e70, which has been published in final form at https://doi.org/10.1111/epi.16534. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords: 1103 Clinical Sciences, 1109 Neurosciences, Neurology & Neurosurgery
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: EPILEPSIA
ISSN: 0013-9580
Dates:
DateEvent
18 June 2020Published
18 May 2020Published Online
21 April 2020Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
U01NS088034National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
U01NS088023National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
U01NS056975National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
U01NS059041National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
R01NS099653National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
URI: https://openaccess.sgul.ac.uk/id/eprint/111893
Publisher's version: https://doi.org/10.1111/epi.16534

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