Administration of Levetiracetam in Traumatic Brain Injury: Is it Warranted?

D'John, Jason; Ibrahim, Ramzi; Patel, Prasanna; DeHoff, Kaitlyn; Kolbe, Nina

doi:10.7759/cureus.9117

Cited by 5 publications

(14 citation statements)

References 10 publications

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“…We found an ARR of 0.6% for populations of both composite mild and moderate TBI as well as in cohorts with exclusively mild TBI. Our study showed a modest but clear trend toward the benefits of seizure prophylaxis in 8 studies, which included a total of 5637 patients. Nonsevere TBI is very common; mild TBI alone affects over 1 million people yearly in North America yearly .…”

Section: Discussionmentioning

confidence: 69%

“…Pease et al and Faropoulos et al only included mild and moderate TBI, respectively. DJohn et al grouped mild and moderate TBI into 1 category called nonsevere, and thus, we could not determine the distribution of mild vs moderate TBI. Candy et al dichotomized TBI into mild and nonmild, and we similarly could not include any moderate TBI in this study.…”

Section: Resultsmentioning

confidence: 99%

“…Most patients were given levetiracetam, phenytoin, or valproic acid, depending on the study. Three studies only used levetiracetam for prophylaxis …”

Section: Resultsmentioning

confidence: 99%

“…However, newer antiseizure medications such as levetiracetam may pose less risks. Up to one-quarter of patients are inappropriately discharged with antiseizure medications after failure to stop prophylactic medications after 7 days . Prolonged and unnecessary antiseizure medication usage may also inhibit recovery from TBI, especially in moderate and severe TBI .…”

Section: Discussionmentioning

confidence: 99%

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Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury

Pease,

Mittal,

Merkaj

et al. 2024

JAMA Neurol

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ImportanceGuidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial.ObjectiveTo determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI.Data SourcesPubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched.Study SelectionObservational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction.Main Outcome MeasuresThe main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI.ResultsA total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients.Conclusion and RelevanceSeizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

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Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

“…Most patients were given levetiracetam, phenytoin, or valproic acid, depending on the study. Three studies only used levetiracetam for prophylaxis …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury

Pease,

Mittal,

Merkaj

et al. 2024

JAMA Neurol

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“…In critical care, levetiracetam has been studied for the treatment of status epilepticus, tumor-related seizures, and seizures following subarachnoid or intracerebral hemorrhage, trauma, and stroke [2][3][4][5][6][7]. The pharmacokinetic and pharmacodynamic properties of this antiepileptic drug make it an advantageous option in the care of patients in the ICU.…”

Section: Introductionmentioning

confidence: 99%

The Pharmacokinetics of Levetiracetam in Critically Ill Adult Patients: An Intensive Care Unit Clinical Study

et al. 2022

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The aim of this study was to investigate levetiracetam pharmacokinetics in critically ill adult intensive care patients and to identify pathophysiological factors affecting its kinetics. Fourteen critically ill patients in an intensive care unit were enrolled in the study and received intravenous levetiracetam. Blood samples were collected at specific time points to determine the levetiracetam pharmacokinetics. Patient characteristics such as renal function, demographics, disease severity, organ dysfunction, and biochemical laboratory tests were evaluated for their influence on the kinetics of levetiracetam. Estimated glomerular filtration rate (eGFR) had a statistically significant (p = 0.001) effect on levetiracetam clearance. None of the other patient characteristics had a statistically significant effect on the pharmacokinetics. Simulations of dosing regimens revealed that even typically administered doses of levetiracetam may result in significantly increased concentrations and risk of drug toxicity in patients with impaired renal function. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score differed significantly among the three groups with different epileptic activity (p = 0.034). The same groups also differed in terms of renal function (p = 0.031). Renal dysfunction should be considered when designing levetiracetam dosage. Patients with a low APACHE II score had the lowest risk of experiencing epileptic seizures.

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