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Published on: June 21, 2019
A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis
Kenji Inaba1, Jay Menaker, Bernardino C Branco
1Division of Trauma and Surgical Critical Care, University of Southern California, Los Angeles, California 90033, USA. kinaba@surgery.usc.edu
Insights
Levetiracetam (LEV) and phenytoin (PHE) showed similar efficacy in preventing early posttraumatic seizures (PTS) in traumatic brain injury patients. Cost and monitoring needs should guide the choice between LEV and PHE for PTS prophylaxis.
Area of Science:
- Neurology
- Neurosurgery
- Clinical Pharmacology
Background:
- Guidelines recommend seizure prophylaxis to prevent early posttraumatic seizures (PTS).
- Phenytoin (PHE) is a common choice, while levetiracetam (LEV) is a newer, more expensive alternative lacking extensive traumatic brain injury data.
- This study compares the efficacy of PHE and LEV for early PTS prevention.
Purpose of the Study:
- To compare the efficacy of levetiracetam (LEV) versus phenytoin (PHE) for preventing early posttraumatic seizures (PTS).
Main Methods:
- Prospective enrollment of consecutive blunt traumatic brain injury patients at two Level 1 trauma centers.
- Patients received seizure prophylaxis per local protocol and were monitored for clinical seizures within 7 days of admission.
- Primary outcome was clinical early PTS, comparing LEV and PHE groups.
Main Results:
- 813 patients analyzed (406 LEV, 407 PHE) with no significant demographic or injury severity differences.
- Seizure rates were identical (1.5%) between LEV and PHE groups (p = 0.997).
- No significant differences observed in adverse drug reactions or mortality between the two agents.
Conclusions:
- Levetiracetam (LEV) did not demonstrate superior efficacy to phenytoin (PHE) in preventing early posttraumatic seizures (PTS).
- Consideration of cost and the necessity for serum monitoring should inform the selection of prophylactic agents.
- Both agents appear equally effective for early PTS prophylaxis in this patient population.
Background:
Brain Trauma Foundation guidelines recommend seizure prophylaxis for preventing early posttraumatic seizure (PTS). Phenytoin (PHE) is commonly used. Despite a paucity of data in traumatic brain injury, levetiracetam (LEV) has been introduced as a potential replacement, which is more costly but does not require serum monitoring. The purpose of this study was to compare the efficacy of PHE with that of LEV for preventing early PTS.
Methods:
Consecutive blunt traumatic brain injury patients undergoing seizure prophylaxis were prospectively enrolled at two Level 1 trauma centers during a 33-month period. Seizure prophylaxis was administered according to local protocol. Patients were monitored prospectively throughout their hospital stay for clinical evidence of seizure activity. PHE was compared with LEV with clinical early PTS as the primary outcome measure, defined as a seizure diagnosed clinically, occurring within 7 days of admission.
Results:
A total of 1,191 patients were screened for enrollment, after excluding 378 (31.7%) who did not meet inclusion criteria; 813 (68.3%) were analyzed (406 LEV and 407 PHE). There were no significant differences between LEV and PHE in age (51.7 [21.3] vs. 53.6 [22.5], p = 0.205), male (73.9% vs. 68.8%, p = 0.108), Injury Severity Score (ISS) (20.0 [10.0] vs. 21.0 [10.6], p = 0.175), Marshall score of 3 or greater (18.5% vs. 14.7%, p = 0.153), or craniectomy (8.4% vs. 11.8%, p = 0.106). There was no difference in seizure rate (1.5% vs.1.5%, p = 0.997), adverse drug reactions (7.9% vs. 10.3%, p = 0.227), or mortality (5.4% vs. 3.7%, p = 0.236).
Conclusion:
In this prospective evaluation of early PTS prophylaxis, LEV did not outperform PHE. Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent.
Level Of Evidence:
Therapeutic study, level III.
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