Lorazepam Prevents Recurrent, Alcohol-Related Seizures
Lorazepam Prevents Recurrent, Alcohol-Related Seizures
ABSTRACT & COMMENTARY
Source: D’Onofrio G, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 1999; 340:915-919.
The chronic use of alcohol creates a setup for the development of adult-onset seizures. Alcoholics may have an underlying primary seizure focus that may be stimulated by alcohol use or withdrawal. Head injury with subsequent structural abnormalities is common in alcoholics. In addition, metabolic derangements common to alcohol abusers (e.g., hyponatremia, hypernatremia, hypomagnesemia, and hypoglycemia) may represent primary or exacerbating factors for the development of seizures in this population of patients. D’Onofrio and colleagues sought to investigate the utility of intravenous lorazepam in preventing recurrent alcohol-related seizures in patients presenting to the ED with a single seizure.
The investigators enrolled all adult chronic alcohol abusers during the 21-month study period who presented with a witnessed generalized seizure and at least one drink in the prior 72 hours. Exclusion criteria included abnormal serum lab values that could account for the seizure, the prior use of epileptigenic or antiepileptic drugs (except phenytoin), refusal to provide informed consent, or subsequent development of signs/symptoms suggestive of moderate-to-severe alcohol withdrawal. CT scans and EEGs were performed at the discretion of the treating physicians. Patients were randomly assigned to receive either 2 mg of lorazepam or 2 mL of normal saline, and were then observed for six hours.
One hundred eighty-six patients met inclusion criteria; 16 patients were excluded after entry but included in the intention-to-treat analysis. There was no difference between study groups with regard to age, gender, length of alcohol abuse, amount of alcohol consumed, time from last drink to onset of seizure, time to study drug administration, serum lab values (including ethanol and phenytoin levels when present), and percent positive CTs and EEGs. Twenty-one of 86 placebo patients (24%) and three of 100 lorazepam patients (3%) developed second seizures (P < 0.001). Data analysis revealed no independent predictors of recurrent seizures except for treatment group assignment. The authors conclude that intravenous lorazepam significantly reduces the risk of recurrent seizures in patients with chronic alcohol use who present with a single alcohol-related seizure.
Comment by Frederic Kauffman, MD, FACEP
It is well known that phenytoin is ineffective in preventing recurrent alcohol-related seizures in the absence of an underlying organic cause.1 Preventing alcohol-related seizures in chronic alcohol abusers is a worthy cause, if for no other reason than to prevent associated head trauma and the added costs of subsequent medical evaluation and treatment. For the emergency physician, I see the major challenge as one of not missing any one of myriad associated medical conditions seen in alcoholics that may predispose to subsequent seizures. For instance, in this study, not all patients received head CTs, but of those 153 who did, 30 (15 in each study group) were positive (19.2%). Once the diagnosis of an "uncomplicated" alcohol-related seizure is made, it is reassuring that intravenous lorazepam has been demonstrated to prevent recurrent seizures.
Reference
1. Goldfrank LR, et al. Substance withdrawal. In: Goldfrank LR, et al (eds). Goldfrank’s Toxicologic Emergencies, 4th ed. Norwalk: Appleton and Lange; 1994: 905-918.
Treatment strategies documented in the literature to be effective in the management of seizures in the alcoholic include:
a. phenytoin for uncomplicated alcohol-related seizure prophylaxis.
b. phenobarbital for alcohol-related seizure prophylaxis.
c. initial evaluation, with discharge if head CT scan is negative.
d. intravenous lorazepam for prevention of recurrent alcohol-related seizures.
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