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Benzodiazepines were as safe as and more effective than placebo for out-of-hospital status epilepticus

Samuel Wiebe, MD, MSc
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*See Glossary.

†Information provided by author.

Source of funding: National Institutes of Health.

For correspondence: Dr. D.H. Lowenstein, Harvard Medical School, Boston, MA, USA. E-mail daniel_lowenstein@hms.harvard.edu.

Ann Intern Med. 2002;136(3):86. doi:10.7326/ACPJC-2002-136-3-086
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Question: In patients with out-of-hospital status epilepticus, are benzodiazepines safer and more effective than placebo when given by paramedics for terminating the condition?

Design: Randomized {allocation concealed*}†, blinded {patients, clinicians, data collectors, and outcome assessors}†,* placebo-controlled trial with follow-up to time of arrival at the emergency department.

Setting: San Francisco, California, USA.

Patients: 205 patients (258 enrollments) who were ≥ 18 years of age (mean age 51 y, 63% men, 50% white) and had an out-of-hospital diagnosis of status epilepticus. Exclusion criteria included pulse < 60 beats/min, systolic blood pressure < 100 mm Hg, and a history of long-term use of or sensitivity to benzodiazepines. Only data from the first enrollment of each patient was reported. {Follow-up was 100%.}†

Intervention: Patients were allocated to intravenous injection of lorazepam, 2 mg (n = 66); diazepam, 5 mg (n = 68); or placebo (n = 71), given over a 1- to 2-minute period and only during generalized tonic-clonic seizure activity. If seizures recurred or continued ≥ 4 minutes after the first injection, an identical second injection was given. Open-label diazepam was immediately available for a difficult or unsafe extrication of a patient or if a patient was at high risk for a life-threatening complication.

Main outcome measures: Termination of status epilepticus and out-of-hospital complications.

Main results: {Analysis was by intention to treat.}† Lorazepam and diazepam groups did not differ, but each were more effective than placebo for terminating status epilepticus (diazepam vs placebo comparison was of borderline statistical significance) (Table). An out-of-hospital complication occurred in 11%, 10%, and 23% of patients who received lorazepam, diazepam, and placebo (P = 0.08), respectively.

Conclusion: In patients with status epilepticus, both lorazepam and diazepam were as safe as and more effective than placebo when given by paramedics for terminating the condition.

Lorazepam (Lor) vs diazepam (Dia) vs placebo (Plac) for out-of-hospital status epilepticus until arrival at the emergency department‡

OutcomeComparisonsEvent ratesRBI (95% CI)NNT (CI)
Termination of<br/>status epilepticusLor vs Dia59% vs 43%37% (−13 to 80)Not<br/>significant
Lor vs Plac59% vs 21%166% (60 to 268)3 (2 to 8)
Dia vs Plac43% vs 21%80% (0 to 190)Borderline significance

‡Abbreviations defined in Glossary; RBI, NNT, and CI calculated from adjusted data in article.





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