Tips on Managing Status Epilepticus

By Sally Beattie, MS, RN, CS, GNP

Summary—Generalized convulsive status epilepticus (GCSE) threatens the lives of 65,000-150,000 U.S. citizens annually and is most common in children and adults over age 60. Clinicians must provide prompt and effective treatment to ensure the best outcome. Several intravenous drug protocols exist; however, experts are uncertain about the best initial drug treatment. Investigators conducted a five-year multicenter, double-blind randomized trial of four regimens to determine the most efficacious. Results highlight the need for better therapies because the protocol recommended by the investigators proved successful in only 55% of patients. Practitioners should prepare with an established treatment plan, the availability of appropriate drugs in the appropriate doses, and the skills to deal with potential side effects.

GCSE is a dangerous life-threatening emergency affecting 65,000-150,000 people in the United States each year.1 About half of the cases occur in young children; however, adults over age 60 may be particularly susceptible. GCSE is defined as more than 30 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between seizures. It may occur after an acute cerebral insult in persons with previously established epilepsy, especially if they have stopped taking their medications, or as a first unprovoked seizure. It also might be associated with an acute or progressive neurological insult or systemic metabolic dysfunction, or it might occur without identifiable cause.2 Untreated or ineffectively treated, GCSE may result in potentially dire consequences including circulatory collapse, acidosis, renal failure from myoglobinuria, or epileptic encephalopathy.3

Although several drug treatment protocols exist for treating GCSE, the best initial treatment was unknown. Data from controlled trials was sparse and did not directly compare available regimens. The need to identify and document the most efficacious strategy was paramount. To address the issue, a five-year randomized, double-blind trial was conducted at 16 Veteran’s Administration and six affiliated university hospitals.

Current Treatment Regimens

Investigators decided to compare four existing intravenous (IV) regimens:
1. diazepam (0.15mg/kg) followed by phenytoin (18mg/kg);
2. lorazepam (0.1mg/kg);
3. phenobarbitol (15mg/kg);
4. phenytoin (18mg/kg).

Researchers recruited 518 study subjects. Of these, 30% were nonveterans and 18% were female,4 thus contributing to generalizable study results. An additional 52 patients were included in an intention-to-treat analysis. Eligible patients were classified as having:

• overt GSCE (easily visible), N=384;

• or subtle GSCE (indicated by coma and ictal discharges on an electroencephalogram, with or without visible convulsive movements such as rhythmic muscle twitches or tonic eye deviation), N=134.

In randomized blind fashion, one of the aforementioned treatments were administered to study subjects. Successful outcome was indicated by cessation of all motion and EEG seizure activity within 20 minutes after giving the initial drug infusion and without recurrence during the next 40 minutes. Patients were given a second blind drug infusion if needed to stop the seizure activity. The study/observation period lasted 12 hours.

Results: Better Methods Still Needed

The results revealed that the first treatment regimen was successful in just 55.5% of patients with verified overt GCSE but in only 14.9% of those with subtle GCSE. Among the overt GCSE group, lorazepam was significantly more effective than the phenytoin group, but no more so than the diazepam or phenobarbital groups. There were no differences in efficacy among treatments in the subtle GCSE group. Finally, there were no significant differences among the four treatments in either group regarding the frequency of the commonly reported drug-related side effects (hypoventilation, hypotension, and cardiac rhythm disturbance), recurrence during the 12-hour study period, or outcome at 30 days after the episode of GCSE.

In the intention-to-treat analysis, the differences among treatment groups with overt and subtle status epilepticus were not significant.

It is widely acknowledged that prompt administration of appropriate treatment is associated with favorable outcomes in treating GCSE. In this study, treatments that included phenytoin required the most time to administer. Lorazepam required the least time and was the easiest to use and the most effective drug in the paired comparisons. As a result, investigators recommend using lorazepam for initial IV treatment of GCSE until new therapies become available.

Data from much earlier studies5,6,7 have reported better efficacy rates but included other classes of status epilepticus and less stringent definitions of treatment success. The investigators in this trial thought the use of a period >20 minutes in the definition of treatment success would expose patients to unnecessary risk including further neurological abnormalities and death.

Practice Implications

This study highlights the need for practitioners, regardless of practice setting, to be aware of the possible need to manage a patient experiencing an episode of generalized convulsive status epilepticus. Several universal aspects of treating this life-threatening emergency need to be in place:
• a clear plan of immediate treatment;
• prompt administration of effective drugs in adequate doses;
• and ability to deal with the possibility of apnea or hypoventilation.2

A neurologist should be consulted if treatment is unsuccessful and to help establish a long-term treatment plan pending the episode’s etiology. Reinforcing the need for patients with established epilepsy or other seizure disorders to take their medication religiously is mandatory. Although the results of this study cannot be generalized to the pediatric population, the need for a plan, availability of appropriate medications, and the ability to deal with adverse side effects is no less indicated.

References

1. Delorenzo RJ, Pellock JM, Towne AR, et al. Epidem iology of status epilepticus. J Clin Neurophys 1995;12:316-325.

2. Working Group on Status Epilepticus. Treatment of convulsive status epilepticus; recommendations of the Epilepsy Foundation of America’s Working Group on Status Epilepticus. JAMA 1993;270:854-859.

3. Adams RD, Victor M, Ropper AH, et al. Epilepsy and disorders of consciousness. In: Principles of Neurology. 6th ed. McGraw-Hill; New York; 1997:339.

4. Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. NEJM 1998;339:792-798.

5. Waltregny A, Dargent J. Preliminary study of parenteral lorazepam in status epilepticus. Acta Neurol Belg 1975;75:219-229.

6. Sorel L, Mechler L, Harmant J. Comparative trial of intravenous lorazepam and clonazepam in status epilepticus. Clin Ther 1981;4:326-336.

7. Levy RJ, Krall RL. Treatment of status epilepticus with lorazepam. Arch Neurol 1984;41:605-611.