Should Levetiracetam or Phenytoin Be Used for Posttraumatic Seizure Prophylaxis? A Systematic Review of the Literature and Meta-analysis

Khan, Nickalus R.; VanLandingham, Matthew; Fierst, Tamara; Hymel, Caroline; Hoes, Kathryn; Evans, Linton T.; Mayer, Rory R.; Barker, Fred G.; Klimo, Paul

doi:10.1227/neu.0000000000001445

Cited by 30 publications

(17 citation statements)

References 23 publications

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“…It has been shown that Phenytoin and Levetiracetam are equally efficacious in preventing early seizures post TBI. This is supported by a body of literature, including well-conducted randomised-controlled trials [5,[12][13][14][15]. A meta-analysis of 1186 patients identified that the rate of early post-traumatic seizures was 5.4% with Levetiracetam and 3.4% with Phenytoin (no significant difference) [12].…”

Section: Discussionmentioning

confidence: 87%

Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients

et al. 2020

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Background Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance). Method A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed. Results The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test). Conclusion In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies.

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Section: Discussionmentioning

confidence: 87%

Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients

et al. 2020

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“…We found some differences between relatively lower versus higher income countries. It was striking that levetiracetam was significantly more frequently reported by higher income countries as an agent of choice for seizure prophylaxis and treatment, while valproate and phenytoin were reported more frequently by lower income countries, although high-level evidence in the literature on the agent of choice is lacking [ 37 ]. However, there were no clear structural differences in management overall, and this could not therefore be considered an explanation for the treatment variation.…”

Section: Discussionmentioning

confidence: 99%

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Huijben¹,

Volovici

Cnossen³

et al. 2018

Crit Care

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BackgroundGeneral supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.MethodsWe performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.ResultsThe survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate).The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).ConclusionsPractice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2000-6) contains supplementary material, which is available to authorized users.

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“…Inaba et al (n = 813) also found no difference in terms of adverse drug reactions or mortality between those on Keppra and phenytoin prophylaxis [ 3 ]. A systematic review of the literature and meta-analysis did find a higher incidence of adverse effects (13% versus 7%) on phenytoin compared to Keppra, including worse neurological status and persistent fever [ 6 ]. No data had previously been reported comparing adverse effects or long-term outcomes for those on early Keppra seizure prophylaxis versus no treatment.…”

Section: Discussionmentioning

confidence: 99%

“…There is less data comparing Keppra to no treatment or placebo. To date, only one retrospective study has directly compared the rate of early PTS in those receiving Keppra prophylaxis versus no treatment, finding a non-significant decrease from 3.4% to 1.9% in the prophylaxis group [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures

Hazama¹,

Ziechmann²,

Arul³

et al. 2018

Cureus

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Objective: Traumatic brain injury (TBI) is a leading cause of long-term disability. Early onset post-traumatic seizures (PTS) after traumatic injury to the brain is a strong predictor of adverse outcomes in these patients. Our study investigates the role of Keppra in early PTS prophylaxis compared to no treatment, taking into account risk factors including injury severity, seizure history, and anti-epileptic drug (AED) use.Methods: This was a retrospective cohort study based on patient chart data from January 2013 to January 2017 at a level one trauma center in the United States. A t-test was performed with P<0.05 as significant; we utilized a 95% confidence interval (CI) for our findings. Subgroup analysis was performed, with respect to the Glasgow Coma Scale (GCS) score (Group A: Mild GCS=13-15, Keppra N=135, Non-Keppra N=122; Group B: Moderate GCS=9-12, Keppra N=23, Non-Keppra N=19; Group C: Severe GCS= <8, Keppra N=69, Non-Keppra=35).Results: Of 403 patients included in the study, 227 were given Keppra. Demographics between treatment groups were similar. Whole cohort analysis confirmed six patients with PTS, and no significant difference between groups (Keppra N=3, Non-Keppra N=3, OR=0.77, P=0.75, 95% CI=(0.154-3.87)). Subgroup analysis revealed reduction in seizure incidence in Keppra groups A (OR=0.18, P=0.27, 95% CI=(0.008-3.80)) and B (OR=0.82, P=0.92, 95% CI=(0.015-43.7)), but this reduction was not statistically significant. Those with the severe TBI in group C accounted for the majority of seizures (n=4, OR=1.52, P=0.71, 95% CI=(0.15-15.4)). Conclusion: Patients with more severe TBI suffered a higher incidence of early-onset post-traumatic seizures. Data of the cohort as a whole revealed a trend towards a lower seizure incidence in patients who were treated with Keppra prophylaxis. Despite this trend, the decrease in seizure incidence did not reach statistical significance.

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Should Levetiracetam or Phenytoin Be Used for Posttraumatic Seizure Prophylaxis? A Systematic Review of the Literature and Meta-analysis

Abstract: ADE, adverse drug eventAED, antiepileptic drugCI, confidence intervalOR, odds ratioPTS, posttraumatic seizureTBI, traumatic brain injury.

Cited by 30 publications

References 23 publications

Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients

Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures

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