CME Practice parameter : Antiepileptic drug prophylaxis in severe traumatic brain injury Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: To review the evidence regarding antiepileptic drug (AED) prophylaxis in patients with severe traumatic brain injury (TBI) in order to make practice recommendations. Methods: The authors identified relevant studies by searching multiple databases and reviewing reference lists of other sources. They included studies that prospectively compared post-traumatic seizure rates in patients given AED prophylaxis vs controls. Each study was graded (class I to IV) according to a standard classification-of-evidence scheme and results were analyzed and pooled. Results: Pooled class I studies demonstrated a significantly lower risk of early post-traumatic seizures (those occurring within 7 days after injury) in patients given phenytoin prophylaxis compared to controls (relative risk 0.37, 95% CI 0.18 to 0.74). Pooled class I and class II studies demonstrated no significant difference in the risk of late post-traumatic seizures (those occurring beyond 7 days after injury) in patients given AED prophylaxis compared to controls (relative risk 1.05, 95% CI 0.82 to 1.35). Serum AED levels were suboptimal in these studies and adverse effects were mild but frequent. Conclusions: For adult patients with severe TBI, prophylaxis with phenytoin is effective in decreasing the risk of early post-traumatic seizures. AED prophylaxis is probably not effective in decreasing the risk of late post-traumatic seizures. Further studies addressing milder forms of TBI, the use of newer AEDs, the utility of EEG, and the applicability of these findings to children are recommended. NEUROLOGY 2003;60:10–16 The Quality Standards Subcommittee (QSS) of the American Academy of Neurology (AAN) is charged with developing practice parameters for neurologists for diagnostic procedures, treatment modalities, and clinical disorders. Practice parameters are strategies for patient management that assist physicians in clinical decision-making. They comprise one or more recommendations based on analysis of evidence on a specific clinical problem. This report addresses the prophylactic use of antiepileptic drugs (AEDs) in patients with severe traumatic brain injury (TBI). TBI is a common neurologic disorder, accounting for about 1.1 million emergency department visits and one hospitalization per 1,000 people each year in the United States.1,2 Among all patients with head trauma who seek medical attention, about 2% develop post-traumatic seizures, although the number varies widely depending primarily on injury severity. About 12% of patients with severe TBI develop posttraumatic seizures, and the rate may be more than 50% for those with penetrating missile injuries.3-5 The use of AEDs to treat patients who have developed post-traumatic epilepsy is standard. However, the important question of whether to use AEDs prophylactically after TBI to prevent the development of post-traumatic seizures is unanswered. The development of seizures is both physically and psychologically debilitating, complicates acute management QSS Educational Statement: The Quality Standards Subcommittee (QSS) of the American Academy of Neurology seeks to develop scientifically sound, clinically relevant practice parameters for neurologists for diagnostic procedures, treatment modalities, and clinical disorders. Practice parameters are strategies for patient management that might include diagnosis, symptom, treatment, or procedure evaluation. They consist of one or more specific recommendations based on analysis of evidence. From the Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. D.H. L. is currently affiliated with the Department of Neurology, University of California, San Francisco. Approved by the Quality Standards Subcommittee on March 2, 2002. Approved by the Practice Committee on August 13, 2002. Approved by the AAN Board of Directors on October 19, 2002. Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116. 10 Copyright © 2003 by AAN Enterprises, Inc. and subsequent rehabilitation, and contributes to the substantial cost associated with the care of the head-injured patient. However, the prophylactic use of AEDs carries with it the risk of adverse effects that may be especially disabling in this population. There is substantial variability among clinicians in the practice of post-traumatic seizure prophylaxis. Two surveys of neurosurgeons reported that a majority prescribed AEDs for seizure prophylaxis at least some of the time, although the indications, choice of drug, and duration of treatment varied widely.6,7 Similar variability was seen in the care of headinjured patients referred to a rehabilitation center.8 Published studies have addressed the issue of posttraumatic seizure prophylaxis, although they differ both in their methods and findings. We performed a systematic review and analysis of the literature on this topic and propose recommendations for the use of AED prophylaxis after severe TBI, based on the standard classification schemes of the AAN QSS. Methods. We searched Medline, Science Citation Index, the Cochrane Database, and Current