FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 339:792-798 September 17, 1998 Number 12 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background and Methods Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled.

Results Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam and phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days.

Conclusions As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam and phenytoin, it is easier to use.

Source Information

From the Neurology Services of the Veterans Affairs Medical Centers in West Los Angeles, Calif. (D.M.T., P.D.M., N.Y.W., A.H.), Bronx, N.Y. (A.J.R.), Birmingham, Ala. (E.F.), Richmond, Va. (V.P.C.), Gainesville, Fla. (B.M.U.), and Miami (R.E.R.), and the Hines Veterans Affairs Medical Center, Chicago (M.B.M.); the Departments of Neurology of the University of California at Los Angeles School of Medicine, Los Angeles (D.M.T., N.Y.W.), Mount Sinai College of Medicine, New York (A.J.R.), the University of Alabama School of Medicine, Birmingham (E.F.), the Medical College of Virginia, Richmond (V.P.C.), the University of Florida School of Medicine, Gainesville (B.M.U.), the University of Miami School of Medicine, Miami (R.E.R.), and the Loyola University School of Medicine, Chicago (M.B.M.); the Veterans Affairs Cooperative Studies Program Coordinating Center, Perry Point, Md. (J.F.C.); and the Veterans Affairs Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, N.M. (C.C.). Other authors were Pratap Yagnik, M.D. (Neurology Service, Veterans Affairs Medical Center, and Department of Neurology, Medical College of Pennsylvania — both in Philadelphia); John C. Jones, M.D. (Neurology Service, Veterans Affairs Medical Center, and Department of Neurology, University of Wisconsin School of Medicine — both in Madison); Elizabeth Barry, M.D. (Neurology Service, Veterans Affairs Medical Center, and Department of Neurology, University of Maryland School of Medicine — both in Baltimore); Jane G. Boggs, M.D. (Neurology Service, Veterans Affairs Medical Center, and Department of Neurology, Medical College of Virginia — both in Richmond); and Andres M. Kanner, M.D. (Neurology Service, Veterans Affairs Medical Center, and Department of Neurology, University of Wisconsin School of Medicine — both in Madison).

Address reprint requests to Dr. Treiman at the Department of Neurology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, 97 Paterson St., New Brunswick, NJ 08901-0019.

Full Text of this Article

This article has been cited by other articles:

• Rossetti, A. O., Logroscino, G., Koubeissi, M. Z., Alshekhlee, A. (2008). IN-HOSPITAL MORTALITY OF GENERALIZED CONVULSIVE STATUS EPILEPTICUS: A LARGE US SAMPLE. Neurology 70: 1939-1940 [Full Text]  
• Knake, S, Gruener, J, Hattemer, K, Klein, K M, Bauer, S, Oertel, W H, Hamer, H M, Rosenow, F (2008). Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J. Neurol. Neurosurg. Psychiatry 79: 588-589 [Abstract] [Full Text]  
• Costello, D. J., Cole, A. J. (2007). Treatment of Acute Seizures and Status Epilepticus. J Intensive Care Med 22: 319-347 [Abstract]  
• Kozak, O. S., Wijdicks, E.F.M., Manno, E. M., Miley, J. T., Rabinstein, A. A. (2007). Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome. Neurology 69: 894-897 [Abstract] [Full Text]  
• O'Hara, K. A. (2007). First Aid for Seizures: The Importance of Education and Appropriate Response. J Child Neurol 22: 30S-37S [Abstract]  
• Glauser, T. A. (2007). Designing Practical Evidence-Based Treatment Plans for Children With Prolonged Seizures and Status Epilepticus. J Child Neurol 22: 38S-46S [Abstract]  
• Cloyd, J. (2007). Pharmacologic Considerations in the Treatment of Repetitive or Prolonged Seizures. J Child Neurol 22: 47S-52S [Abstract]  
• Chung, S. S., Wang, N. C., Treiman, D. M. (2007). Comparative Efficacy and Safety of Antiepileptic Drugs for the Treatment of Status Epilepticus. Journal of Pharmacy Practice 20: 137-146 [Abstract]  
• Rossetti, A. O., Misra, U .K., Kalita, J ., Patel, R . (2007). Sodium valproate vs phenytoin in status epilepticus: A pilot study. Neurology 68: 709-709 [Full Text]  
• Engelhorn, T., Hufnagel, A., Weise, J., Baehr, M., Doerfler, A. (2007). Monitoring of Acute Generalized Status Epilepticus Using Multilocal Diffusion MR Imaging: Early Prediction of Regional Neuronal Damage. Am. J. Neuroradiol. 28: 321-327 [Abstract] [Full Text]  
• de Sevilla, D. F., Garduno, J., Galvan, E., Buno, W. (2006). Calcium-Activated Afterhyperpolarizations Regulate Synchronization and Timing of Epileptiform Bursts in Hippocampal CA3 Pyramidal Neurons. J. Neurophysiol. 96: 3028-3041 [Abstract] [Full Text]  
• Jette, N., Claassen, J., Emerson, R. G., Hirsch, L. J. (2006). Frequency and Predictors of Nonconvulsive Seizures During Continuous Electroencephalographic Monitoring in Critically Ill Children. Arch Neurol 63: 1750-1755 [Abstract] [Full Text]  
• Nandhagopal, R (2006). Generalised convulsive status epilepticus: an overview. Postgrad. Med. J. 82: 723-732 [Abstract] [Full Text]  
• Misra, U. K., Kalita, J., Patel, R. (2006). Sodium valproate vs phenytoin in status epilepticus: a pilot study.. Neurology 67: 340-342 [Abstract] [Full Text]  
• Rossetti, A. O., Logroscino, G., Bromfield, E. B. (2005). Refractory Status Epilepticus: Effect of Treatment Aggressiveness on Prognosis. Arch Neurol 62: 1698-1702 [Abstract] [Full Text]  
• Idrees, U., Londner, M. (2005). Pharmacotherapy Overview of Seizure Management in the Adult Emergency Department. Journal of Pharmacy Practice 18: 394-411 [Abstract]  
• Dubik, M. (2005). Midazolam in the Bum or Between Cheek and Gum?. AAP Grand Rounds 14: 41-42 [Full Text]  
• Walker, M. (2005). Status epilepticus: an evidence based guide. BMJ 331: 673-677 [Full Text]  
• Holtkamp, M., Othman, J., Buchheim, K., Masuhr, F., Schielke, E., Meierkord, H. (2005). A "Malignant" Variant of Status Epilepticus. Arch Neurol 62: 1428-1431 [Abstract] [Full Text]  
• Naylor, D. E., Liu, H., Wasterlain, C. G. (2005). Trafficking of GABAA Receptors, Loss of Inhibition, and a Mechanism for Pharmacoresistance in Status Epilepticus. J. Neurosci. 25: 7724-7733 [Abstract] [Full Text]  
• Goodkin, H. P., Yeh, J.-L., Kapur, J. (2005). Status Epilepticus Increases the Intracellular Accumulation of GABAA Receptors. J. Neurosci. 25: 5511-5520 [Abstract] [Full Text]  
• Engelhorn, T., Doerfler, A., Weise, J., Baehr, M., Forsting, M., Hufnagel, A. (2005). Cerebral Perfusion Alterations during the Acute Phase of Experimental Generalized Status Epilepticus: Prediction of Survival By Using Perfusion-Weighted MR Imaging and Histopathology. Am. J. Neuroradiol. 26: 1563-1570 [Abstract] [Full Text]  
• Brevoord, J. C. D., Joosten, K. F. M., Arts, W. F. M., van Rooij, R. W., de Hoog, M. (2005). Status Epilepticus: Clinical Analysis of a Treatment Protocol Based on Midazolam and Phenytoin. J Child Neurol 20: 476-481 [Abstract]  
• Brevoord, J. C. D., Joosten, K. F. M., Arts, W. F. M., van Rooij, R. W., de Hoog, M. (2005). Status Epilepticus: Clinical Analysis of a Treatment Protocol Based on Midazolam and Phenytoin. J Child Neurol 20: 476-481 [Abstract]  
• Holtkamp, M, Othman, J, Buchheim, K, Meierkord, H (2005). Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J. Neurol. Neurosurg. Psychiatry 76: 534-539 [Abstract] [Full Text]  
• Limdi, N. A., Shimpi, A. V., Faught, E., Gomez, C. R., Burneo, J. G. (2005). Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 64: 353-355 [Abstract] [Full Text]  
• Williams, A. J., Tortella, F. C., Lu, X. M., Moreton, J. E., Hartings, J. A. (2004). Antiepileptic Drug Treatment of Nonconvulsive Seizures Induced by Experimental Focal Brain Ischemia. J. Pharmacol. Exp. Ther. 311: 220-227 [Abstract] [Full Text]  
• Marik, P. E., Varon, J. (2004). The Management of Status Epilepticus. Chest 126: 582-591 [Abstract] [Full Text]  
• Pandian, J. D., Cascino, G. D., So, E. L., Manno, E., Fulgham, J. R. (2004). Digital Video-Electroencephalographic Monitoring in the Neurological-Neurosurgical Intensive Care Unit: Clinical Features and Outcome. Arch Neurol 61: 1090-1094 [Abstract] [Full Text]  
• Claassen, J., Mayer, S. A., Kowalski, R. G., Emerson, R. G., Hirsch, L. J. (2004). Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 62: 1743-1748 [Abstract] [Full Text]  
• Gea-Banacloche, J., Johnson, R. T., Bagic, A., Butman, J. A., Murray, P. R., Agrawal, A. G. (2004). West Nile Virus: Pathogenesis and Therapeutic Options. ANN INTERN MED 140: 545-553 [Abstract] [Full Text]  
• Holtkamp, M, Masuhr, F, Harms, L, Einhaupl, K M, Meierkord, H, Buchheim, K (2003). The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists. J. Neurol. Neurosurg. Psychiatry 74: 1095-1099 [Abstract] [Full Text]  
• Parsons, S. J., Tomas, K., Cox, P. (2002). Outcome of Pediatric Status Epilepticus Admitted to Intensive Care. J Intensive Care Med 17: 174-179 [Abstract]  
• Wiebe, S. (2002). Benzodiazepines were as safe as and more effective than placebo for out-of-hospital status epilepticus. Evid. Based Med. 7: 84-84 [Full Text]  
• Cock, H.R., Schapira, A.H.V. (2002). A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus. QJM 95: 225-231 [Abstract] [Full Text]  
• Lockey, A S (2002). Emergency department drug therapy for status epilepticus in adults.. Emerg. Med. J. 19: 96-100 [Abstract] [Full Text]  
• Bleck, T. P. (2002). Refractory Status Epilepticus in 2001. Arch Neurol 59: 188-189 [Full Text]  
• Mayer, S. A., Claassen, J., Lokin, J., Mendelsohn, F., Dennis, L. J., Fitzsimmons, B.-F. (2002). Refractory Status Epilepticus: Frequency, Risk Factors, and Impact on Outcome. Arch Neurol 59: 205-210 [Abstract] [Full Text]  
• Mitchell, W. G. (2002). Status Epilepticus and Acute Serial Seizures in Children. J Child Neurol 17: S36-S43 [Abstract]  
• Claassen, J., Hirsch, L. J., Emerson, R. G., Bates, J. E., Thompson, T. B., Mayer, S. A. (2001). Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 57: 1036-1042 [Abstract] [Full Text]  
• Alldredge, B. K., Gelb, A. M., Isaacs, S. M., Corry, M. D., Allen, F., Ulrich, S., Gottwald, M. D., O'Neil, N., Neuhaus, J. M., Segal, M. R., Lowenstein, D. H. (2001). A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus. NEJM 345: 631-637 [Abstract] [Full Text]  
• Valenzuela, T. D., Copass, M. K. (2001). Clinical Research on Out-of-Hospital Emergency Care. NEJM 345: 689-690 [Full Text]  
• PROVENCIO, J. J., BLECK, T. P., CONNORS, A. F. Jr. (2001). Critical Care Neurology. Am. J. Respir. Crit. Care Med. 164: 341-345 [Full Text]  
• Shorvon, S. (2001). THE MANAGEMENT OF STATUS EPILEPTICUS. J. Neurol. Neurosurg. Psychiatry 70: ii22-ii27 [Full Text]  
• Butler, J., Lewis, M. (2001). Lorazepam or diazepam for generalised convulsions in adults. Emerg. Med. J. 18: 116-a-117 [Full Text]  
• The Status Epilepticus Working Party, , Party, M. o. t. S. E. W., Appleton, R, Choonara, I, Martland, T, Phillips, B, Scott, R, Whitehouse, W (2000). The treatment of convulsive status epilepticus in children. Arch. Dis. Child. 83: 415-419 [Abstract] [Full Text]  
• Sinha, S., Naritoku, D. K. (2000). Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology 55: 722-724 [Abstract] [Full Text]  
• Coplin, W. M., Rhoney, D. H., Lyons, E. A., Murry, K. R., O'Brien, T. J., Cascino, G. D., So, E. L., Hanna Rochester MN, D. R., Browne, T. R. (1999). Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Neurology 53: 1611-1611 [Full Text]  
• (1998). The Best Treatments for Status Epilepticus. JWatch Emergency Med. 1998: 15-15 [Full Text]  
• (1998). Comparing Treatments for Status Epilepticus. JWatch Psychiatry 1998: 15-15 [Full Text]  
• (1998). A Comparison of Treatments for Status Epilepticus. JWatch General 1998: 3-3 [Full Text]