Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

4 anticonvulsant drug regimens had similar efficacies for generalized convulsive status epilepticus

ACP J Club. 1999 Mar-April;130:39. doi:10.7326/ACPJC-1999-130-2-039


Source Citation

Treiman DM, Meyers PD, Walton NY, et al., for the Veterans Affairs Status Epilepticus Cooperative Study Group. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med. 1998 Sep 17;339:792-8.


Abstract

Question

What is the comparative efficacy of 4 intravenous drug therapies (lorazepam, phenobarbital, phenytoin, and diazepam followed by phenytoin) for generalized convulsive status epilepticus?

Design

Randomized, double-blind, controlled trial with 12-hour follow-up.

Setting

16 Veterans Affairs medical centers and 6 affiliated university hospitals in the United States.

Patients

570 patients with generalized convulsive status epilepticus. 395 patients had overt status epilepticus defined as ≥ 2 generalized convulsions without full recovery of consciousness between seizures or continuous convulsive activity for > 10 minutes. 175 patients had subtle status epilepticus, defined as coma and ictal discharges on electroencephalography, with or without subtle convulsive movements. Exclusion criteria were age < 18 years, pregnancy, neurosurgical emergencies, or contraindications to study drugs. 518 patients (mean age 59.5 y, 83% men) had confirmed diagnoses.

Intervention

Patients were allocated to intravenous lorazepam, 0.1 mg/kg of body weight (n = 146); phenobarbital, 15 mg/kg (n = 133); phenytoin, 18 mg/kg (n = 145); or diazepam, 0.15 mg/kg, followed by phenytoin, 18 mg/kg (n = 146).

Main outcome measures

Treatment success, defined as resolution of all clinical and electrical evidence of seizures within 20 minutes of initiation of treatment without recurrence within 20 to 60 minutes; recurrence within 12 hours; and adverse effects.

Main results

Intention-to-treat analyses showed no differences in the success rates of the 4 treatments for overt status epilepticus (P = 0.12) or subtle status epilepticus (P = 0.91) (Table). Analysis of 384 patients with confirmed overt status epilepticus showed that lorazepam had a higher success rate than phenytoin alone (P = 0.002). Analysis of 134 patients with confirmed subtle status epilepticus found no overall differences among treatments. The groups did not differ for recurrence among successfully treated patients at 12 hours or for adverse effects.

Conclusion

Among patients with generalized convulsive status epilepticus, initial intravenous treatment with lorazepam, phenobarbital, phenytoin, or diazepam followed by phenytoin had similar efficacies, recurrence rates, and adverse effects.

Sources of funding: Department of Veterans Affairs Medical Research Service Cooperative Studies Program; lorazepam and dummy lorazepam Tubexes donated by Wyeth-Ayerst Laboratories.

For correspondence: Dr. D.M. Treiman, Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 97 Paterson Street, New Brunswick, NJ 08901-0019, USA. FAX 732-235-7041.


Table. Treatment success of 4 drug therapies for status epilepticus at 12 hours

Drug therapies Success rates
Overt status epilepticus Subtle status epilepticus
Lorazepam 67.0% 26.1%
Phenobarbital 63.0% 24.4%
Phenytoin 51.0% 19.5%
Diazepam and phenytoin 59.6% 23.4%

Commentary

Generalized convulsive status epilepticus requires prompt treatment to prevent death or serious brain injury. Because hypoxia and hypotension often complicate treatment of status epilepticus, careful monitoring is indicated. Accurate diagnosis and rapid treatment are more important than the initial choice of anticonvulsant; lorazepam, phenobarbital, or diazepam plus phenytoin are all reasonable choices. Lorazepam may have clinically important advantages over the alternatives. It has low toxicity, rapidly diffuses across the blood-brain barrier, lasts longer than diazepam or short-acting barbiturates, and can be given rectally (1). The study by Treiman and colleagues suggests that lorazepam is at least as good as, and possibly better than, the alternatives.

The high rate of treatment failure in the study was probably caused by a reasonable but rigid definition of treatment efficacy: cessation of all clinical and electrical seizure activity within 20 minutes without recurrence during the next 40 minutes. In addition, previous studies probably included patients who did not have generalized convulsive status epilepticus according to the inclusion criteria used by Treiman and colleagues.

Even the best treatments in this study were effective for only two thirds of patients with overt status epilepticus and one quarter of patients with subtle status epilepticus. Future clinical studies should investigate whether higher doses of lorazepam have greater efficacy (2). Epilepsy remains a disease of unknown cause lacking effective, safe therapy. Further research is needed to advance understanding of the underlying abnormality.

Steven M. Belknap, MD
University of Illinois College of Medicine at PeoriaPeoria, Illinois, USA


References

1. Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol. 1995;37:682-8.

2. Labar DR, Ali A, Root J. High-dose intravenous lorazepam for the treatment of refractory status epilepticus. Neurology. 1994;44:1400-3.