Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective: A Propensity Score Analysis

Bardiya Zangbar, Mazhar Khalil, Angelika C Gruessner, Bellal A Joseph, Randall S Friese, Narong Kulvatunyou, Julie Wynne, Rifat - Latifi, Peter M Rhee, Terence S Okeeffe

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Abstract

Introduction: Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 %. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures. Methods: All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug. Results: 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 % (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3–5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 % (36/1795) vs. 0.08 % (3/3756); OR 25.6; 95 % CI 7.8–83.2; p <0.0001]. Of the patients who had seizures after severe TBI, 25 % (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 %, p = 0.50). Conclusions: In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 % in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalWorld Journal of Surgery
DOIs
StateAccepted/In press - Jun 15 2016

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etiracetam
Propensity Score
Seizures
Anticonvulsants
Phenytoin
Traumatic Brain Injury
Post-Traumatic Epilepsy
Databases

ASJC Scopus subject areas

  • Surgery

Cite this

@article{ad777a7241c64f6289f63c483355818b,
title = "Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective: A Propensity Score Analysis",
abstract = "Introduction: Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 {\%}. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures. Methods: All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug. Results: 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 {\%} (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3–5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 {\%} (36/1795) vs. 0.08 {\%} (3/3756); OR 25.6; 95 {\%} CI 7.8–83.2; p <0.0001]. Of the patients who had seizures after severe TBI, 25 {\%} (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 {\%}, p = 0.50). Conclusions: In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 {\%} in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.",
author = "Bardiya Zangbar and Mazhar Khalil and Gruessner, {Angelika C} and Joseph, {Bellal A} and Friese, {Randall S} and Narong Kulvatunyou and Julie Wynne and Latifi, {Rifat -} and Rhee, {Peter M} and Okeeffe, {Terence S}",
year = "2016",
month = "6",
day = "15",
doi = "10.1007/s00268-016-3606-y",
language = "English (US)",
pages = "1--6",
journal = "World Journal of Surgery",
issn = "0364-2313",
publisher = "Springer New York",

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TY - JOUR

T1 - Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective

T2 - A Propensity Score Analysis

AU - Zangbar, Bardiya

AU - Khalil, Mazhar

AU - Gruessner, Angelika C

AU - Joseph, Bellal A

AU - Friese, Randall S

AU - Kulvatunyou, Narong

AU - Wynne, Julie

AU - Latifi, Rifat -

AU - Rhee, Peter M

AU - Okeeffe, Terence S

PY - 2016/6/15

Y1 - 2016/6/15

N2 - Introduction: Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 %. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures. Methods: All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug. Results: 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 % (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3–5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 % (36/1795) vs. 0.08 % (3/3756); OR 25.6; 95 % CI 7.8–83.2; p <0.0001]. Of the patients who had seizures after severe TBI, 25 % (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 %, p = 0.50). Conclusions: In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 % in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.

AB - Introduction: Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 %. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures. Methods: All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug. Results: 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 % (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3–5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 % (36/1795) vs. 0.08 % (3/3756); OR 25.6; 95 % CI 7.8–83.2; p <0.0001]. Of the patients who had seizures after severe TBI, 25 % (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 %, p = 0.50). Conclusions: In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 % in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.

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