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Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate–Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society

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Abstract

Background

There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate–severe traumatic brain injury (TBI).

Methods

We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate–severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate–severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations.

Results

The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use.

Conclusions

Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate–severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

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Acknowledgements

We would like to acknowledge the work of our independent medical librarian, Thomasin Adams-Webber, MLS, MA, Information Specialist, Health Search Library and Information Services University Health Network. The American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care affirms the educational benefit of this document. The American Epilepsy Society (AES) Board of Directors approved Affirmation of Value for this guideline on October 24, 2023.

Funding

Support for Distiller software and medical librarian assistance was provided by the Neurocritical Care Society.

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Author notes

  1. Contributed equally as coauthors: Jennifer A. Frontera and Emily J. Gilmore

Authors and Affiliations

  1. Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA

    Jennifer A. Frontera

  2. Department of Neurology, Yale School of Medicine, New Haven, CT, USA

    Emily J. Gilmore

  3. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Emily L. Johnson

  4. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    DaiWai Olson

  5. Department of Neurology, Charleston Area Medical Center, Charleston, WV, USA

    Appaji Rayi

  6. Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA

    Eljim Tesoro

  7. Department of Neurosurgery, Northwell Health, Great Neck, NY, USA

    Jamie Ullman

  8. Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, ON, Canada

    Yuhong Yuan

  9. Department of Neurology, Harvard Medical School, Boston, MA, USA

    Sahar F. Zafar

  10. Department of Clinical Pharmacology, University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA

    Shaun Rowe

  11. Department of Neurology, NYU, 150 55th St., Brooklyn, NY, USA

    Jennifer A. Frontera

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Contributions

Drafting, analysis, and revision of the manuscript: JAF, EJG; data analysis and revision of the manuscript: ELJ, DO, AR, ET, JU, SFZ, and SR; data analyses, statistical analyses, and data interpretation: YY.

Corresponding author

Correspondence to Jennifer A. Frontera.

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Conflicts of interest

The panel was required to be free of content-related commercial conflicts of interest for participation in this committee. Disclosures unrelated to the content of this article are listed as follows: JAF receives grant funding for COVID-related research from the NIH National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), and National Heart, Lung, and Blood Institute. JAF has received consulting feeds from BrainCool, FirstKind Medical, Lumosa, and PER-Physician Education Resource. JAF has been compensated travel expenses by Alexion and receives publication royalties from Thieme. EJG receives grant funding for TBI-related research from the NIH/NINDS. EJG has received consulting fees from UCB and AAN. EJG has been compensated travel expenses by American Academy of Neurology (AAN). ELJ has received consulting fees from EpiWatch and receives grant funding from the NIH/NIA. DO receives funding as the editor for the Journal of Neuroscience Nursing and has received research funding from the NIH/NINDS and the Agnes Marshall Walker Foundation. ET has received consulting fees from Medical Insights Group. SFZ receives grant funding from the NIH/NINDS. SFZ is a clinical neurophysiologist for CortiCare. AR, JU, YY, and SR report no disclosures.

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This study did not involve human subjects and was exempt from institutional review board review according to the New York University Institutional Review Board.

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Frontera, J.A., Gilmore, E.J., Johnson, E.L. et al. Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate–Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society. Neurocrit Care (2024). https://doi.org/10.1007/s12028-023-01907-x

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