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


Therapeutics

Lorazepam reduced recurrent alcohol-related seizures in chronic alcohol abuse

ACP J Club. 1999 Nov-Dec;131:63. doi:10.7326/ACPJC-1999-131-3-063


Source Citation

D'Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999 Mar 25;340:915-9.


Abstract

Question

In patients with alcohol abuse who present with a seizure, does lorazepam prevent recurrent alcohol-related seizures?

Design

Randomized, double-blind, placebo-controlled trial with follow-up for 6 hours.

Setting

2 hospital emergency departments in Boston, Massachusetts, USA.

Patients

229 patients were enrolled, but 43 met the initial exclusion criteria, including another possible cause of the seizure, current receipt of drugs that caused or protected against recurrent seizures, or a requirement for treatment for symptoms of moderate-to-severe alcohol withdrawal other than seizures. 186 patients who were ≥ 21 years of age (mean age 45 y, 96% men); had chronic alcohol abuse; presented after a witnessed, generalized seizure; and had had ≥ 1 drinks within the previous 72 hours were included in the intention-to-treat analysis.

Intervention

100 patients were allocated to receive lorazepam, 2 mg, in 2 mL normal saline intravenously, and 86 were allocated to receive 4 mL normal saline intravenously.

Main outcome measures

The primary end point was the occurrence of a second seizure during the 6-hour observation period. Secondary end points included admission to the hospital.

Main results

In an intention-to-treat analysis, fewer patients in the lorazepam group had a second seizure within 6 hours than did those in the control group (P < 0.001) (Table). Hospital admission rates were not higher in the placebo group than in the lorazepam group {odds ratio 1.76, 95% CI 0.96 to 3.23}*. Of the 50 patients in the control group who were discharged from the emergency department after the study, 7 (14%) were transported to an emergency department in Boston within 48 hours because of a second seizure; the number in the lorazepam group was 1 of 67 {1.5%, absolute difference 13%, CI 4% to 25%}.†

Conclusion

Intravenous lorazepam reduced recurrent seizures in patients with chronic alcohol abuse who presented after a witnessed, generalized, alcohol-related seizure.

Source of funding: In part, Boston Department of Health and Hospitals.

For correspondence: Dr G. D'Onofrio, Yale University, Department of Emergency Medicine, 464 Congress Avenue, New Haven, Connecticut 06519, USA. FAX 203-785-4580.

*Numbers calculated from data in article by using the intention-to-treat sample (n = 186).

†Numbers calculated from data supplied by author.


Table. Intravenous lorazepam vs placebo in patients with chronic alcohol abuse presenting after a witnessed, generalized, alcohol-related seizure†

Outcome at 6 hr Lorazepam Placebo RRR (95% CI) NNT (CI)
Second seizure 3% 24% 88% (63 to 96) 5 (4 to 9)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Excessive consumption of alcohol, both acute and chronic, is one of the everyday reasons for admission to emergency medical services. Seizures are a clinical manifestation of alcohol withdrawal, but can occur outside withdrawal periods and for many reasons. 50% of seizures seen in emergency services are associated with excessive alcohol consumption (1), but almost all other causes of seizures can be aggravated by alcohol consumption > 50 g/d.

The study by D'Onofrio and colleagues used rigorous methods, but only included patients whose seizures were directly related to alcohol. Alcoholic patients with other causes of seizures (e.g., hypoglycemia, hypomagnesemia, cranial trauma, pre-delirium tremens) were excluded, although these are substantial clinical problems.

A key clinical message of this study is that secondary prevention of recurrent seizures by lorazepam is useful for these patients and should be used in emergency services. The reduced rate of readmission for recurrent seizures within 48 hours of treatment underlines the importance of the findings. It is hoped that these results will help change negative attitudes related to people having difficulty with alcohol and the skepticism about the effectiveness of treatment that is often encountered with emergency service teams. At present, some emergency service teams receive training from alcohol specialists, but the effectiveness of this support remains to be proved.

Raymund Schwan, MD, PhD
Michel Reynaud, MD, PhDCentre Hospitalier UniversitaireClermont-Ferrand, France


Reference

1. Bouget J, David C, Saussey E. Accident de sevrage alcoolique. Le probléme des crises convulsives. Alcoologie. 1999;21:178-83.