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

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.