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Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus

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Abstract

Most seizures in critically ill patients are nonconvulsive. A significant number of neurological and medical conditions can be complicated by nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE), with brain infections, hemorrhages, global hypoxia, sepsis, and recent neurosurgery being the most prominent etiologies. Prolonged NCSs and NCSE can lead to adverse neurological outcomes. Early recognition requires a high degree of suspicion and rapid and appropriate duration of continuous electroencephalogram (cEEG) monitoring. Although high quality research evaluating treatment with antiseizure medications and long-term outcome is still lacking, it is probable that expeditious pharmacological management of NCSs and NCSE may prevent refractoriness and further neurological injury. There is limited evidence on pharmacotherapy for NCSs and NCSE, although a few clinical trials encompassing both convulsive and NCSE have demonstrated similar efficacy of different intravenous (IV) antiseizure medications (ASMs), including levetiracetam, valproate, lacosamide and fosphenytoin. The choice of specific ASMs lies on tolerability and safety since critically ill patients frequently have impaired renal and/or hepatic function as well as hematological/hemodynamic lability. Treatment frequently requires more than one ASM and occasionally escalation to IV anesthetic drugs. When multiple ASMs are required, combining different mechanisms of action should be considered. There are several enteral ASMs that could be used when IV ASM options have been exhausted. Refractory NCSE is not uncommon, and its treatment requires a very judicious selection of ASMs aiming at reducing seizure burden along with management of the underlying condition.

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Authors and Affiliations

  1. Comprehensive Epilepsy Center, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Pablo Bravo, Aparna Vaddiparti & Lawrence J. Hirsch

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  2. Aparna Vaddiparti
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Correspondence to Lawrence J. Hirsch.

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Dr. Bravo and Dr. Vaddiparti have no conflicts of interest/competing interests. Dr. Hirsch has received consultation fees for advising from Accure, Aquestive, Ceribell, Marinus, Medtronic, Neuropace and UCB; royalties from Wolters-Kluwer for authoring chapters for UpToDate-Neurology, and from Wiley for co-authoring the book “Atlas of EEG in Critical Care”, by Hirsch and Brenner; and honoraria for speaking from Neuropace and Natus.

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Dr. PB contributed to the draft of the entire manuscript and design of all figures; Dr. AV contributed to the draft of Sect. 4.1 (Evidence on pharmacotherapy for NCSs and NCSE) including Table 1 and design of Fig. 3; Dr. LJH contributed to the draft and revision of the entire manuscript as well as design of all figures and tables. All authors have reviewed and read the final version of this manuscript.

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Bravo, P., Vaddiparti, A. & Hirsch, L.J. Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus. Drugs 81, 749–770 (2021). https://doi.org/10.1007/s40265-021-01502-4

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