A comparison of four treatments for generalized convulsive status epilepticus

David M. Treiman, Patti D. Meyers, Nancy Y. Walton, Joseph F. Collins, Cindy Colling, A. James Rowan, Adrian Handforth, Edward Faught, Vincent P. Calabrese, Basim M. Uthman, R. Eugene Ramsay, Meenal B. Mamdani, Pratap Yagnik, John C. Jones, Elizabeth Barry, Jane G. Boggs, Andres M Kanner

Research output: Contribution to journalArticle

924 Citations (Scopus)

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 difference 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.

Original languageEnglish (US)
Pages (from-to)792-798
Number of pages7
JournalNew England Journal of Medicine
Volume339
Issue number12
DOIs
StatePublished - Sep 17 1998
Externally publishedYes

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Status Epilepticus
Phenytoin
Lorazepam
Phenobarbital
Diazepam
Seizures
Therapeutics
Intention to Treat Analysis
Coma
Pharmaceutical Preparations
Multicenter Studies
Electroencephalography
Emergencies
Cohort Studies
Stroke
Body Weight
Recurrence
Muscles

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Treiman, D. M., Meyers, P. D., Walton, N. Y., Collins, J. F., Colling, C., Rowan, A. J., ... Kanner, A. M. (1998). A comparison of four treatments for generalized convulsive status epilepticus. New England Journal of Medicine, 339(12), 792-798. https://doi.org/10.1056/NEJM199809173391202

A comparison of four treatments for generalized convulsive status epilepticus. / Treiman, David M.; Meyers, Patti D.; Walton, Nancy Y.; Collins, Joseph F.; Colling, Cindy; Rowan, A. James; Handforth, Adrian; Faught, Edward; Calabrese, Vincent P.; Uthman, Basim M.; Ramsay, R. Eugene; Mamdani, Meenal B.; Yagnik, Pratap; Jones, John C.; Barry, Elizabeth; Boggs, Jane G.; Kanner, Andres M.

In: New England Journal of Medicine, Vol. 339, No. 12, 17.09.1998, p. 792-798.

Research output: Contribution to journalArticle

Treiman, DM, Meyers, PD, Walton, NY, Collins, JF, Colling, C, Rowan, AJ, Handforth, A, Faught, E, Calabrese, VP, Uthman, BM, Ramsay, RE, Mamdani, MB, Yagnik, P, Jones, JC, Barry, E, Boggs, JG & Kanner, AM 1998, 'A comparison of four treatments for generalized convulsive status epilepticus', New England Journal of Medicine, vol. 339, no. 12, pp. 792-798. https://doi.org/10.1056/NEJM199809173391202
Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ et al. A comparison of four treatments for generalized convulsive status epilepticus. New England Journal of Medicine. 1998 Sep 17;339(12):792-798. https://doi.org/10.1056/NEJM199809173391202
Treiman, David M. ; Meyers, Patti D. ; Walton, Nancy Y. ; Collins, Joseph F. ; Colling, Cindy ; Rowan, A. James ; Handforth, Adrian ; Faught, Edward ; Calabrese, Vincent P. ; Uthman, Basim M. ; Ramsay, R. Eugene ; Mamdani, Meenal B. ; Yagnik, Pratap ; Jones, John C. ; Barry, Elizabeth ; Boggs, Jane G. ; Kanner, Andres M. / A comparison of four treatments for generalized convulsive status epilepticus. In: New England Journal of Medicine. 1998 ; Vol. 339, No. 12. pp. 792-798.
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T1 - A comparison of four treatments for generalized convulsive status epilepticus

AU - Treiman, David M.

AU - Meyers, Patti D.

AU - Walton, Nancy Y.

AU - Collins, Joseph F.

AU - Colling, Cindy

AU - Rowan, A. James

AU - Handforth, Adrian

AU - Faught, Edward

AU - Calabrese, Vincent P.

AU - Uthman, Basim M.

AU - Ramsay, R. Eugene

AU - Mamdani, Meenal B.

AU - Yagnik, Pratap

AU - Jones, John C.

AU - Barry, Elizabeth

AU - Boggs, Jane G.

AU - Kanner, Andres M

PY - 1998/9/17

Y1 - 1998/9/17

N2 - 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 difference 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.

AB - 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 difference 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.

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