Level 2: Mid-level evidence

Intravenous benzodiazepine, most commonly lorazepam (Ativan), is the preferred first-line treatment for prolonged epileptic seizures in the emergency department, but IV medication can be difficult for first responders to administer. An alternative is for paramedics to give intramuscular midazolam (Versed) , a treatment commonly used due to its speed and relative simplicity of administration.

A randomized trial compared these two options for use by paramedics prior to hospital arrival in 893 children and adults with seizures lasting longer than five minutes and persisting after the arrival of the paramedics (N Engl J Med. 2012;366:591-600).

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Doses were midazolam 10 mg or lorazepam 4 mg for adults and children weighing >40 kg (88 lbs), and midazolam 5 mg or lorazepam 2 mg for smaller children. Blinding was maintained by IV placebo for the midazolam group and by intramuscular placebo for the lorazepam group. Patients were excluded for major trauma, hypoglycemia, cardiac arrest, heart rate <40 beats per minute, pregnancy, known allergy to intervention, or estimated weight <13 kg (28.6 lbs).

The randomized intervention was given to 99% of the midazolam group, but to only 63% of the lorazepam group. Of those not receiving lorazepam, convulsions stopped prior to treatment in 64%, and paramedics failed to start the IV in 28%.

All randomized patients were included in an intention-to-treat analysis. Seizures were terminated without need for rescue medication in 73.4% for intramuscular midazolam vs. 63.4% for IV lorazepam (P<0.001, NNT 10). Intramuscular midazolam was associated with lower rates of hospitalization (57.6% vs. 65.6%, P<0.05, NNT 13) and intensive care admission (28.6% vs. 36.2%, P<0.05, NNT 14).

There were no significant differences in endotracheal intubation within 30 minutes or seizure recurrence within 12 hours of emergency department arrival. Similar results were obtained in per-protocol analyses.

Alan Ehrlich, MD, is a deputy editor for DynaMed, in Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.

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