Intramuscular midazolam safe and effective for pre-hospital status epilepticus

The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) trial results published in the NEJM suggest that IM midazolam is at least as safe and effective as IV lorazepam for prehospital termination of seizures in status epilepticus.

This double-blind, randomised, phase 3, noninferiority trial designed and conducted by the Neurological Emergencies Treatment Trials (NETT) network, a multidisciplinary clinical trials infrastructure funded by the National Institute of Neurological Disorders and Stroke (NINDS), compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics.

Subjects with seizures lasting for more than 5 minutes and continuing to convulsive on arrival of the paramedics were given either i.m midazolam via autoinjector or i.v lorazepam. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy and Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures.

At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P 0.001 for both noninferiority and superiority). Besides, there was no difference between the treatment groups with respect to need for intubation or seizure recurrence or incidence of adverse effects.

All adults and those children with an estimated body weight of more than 40 kg received either 10 mg of intramuscular midazolam followed by intravenous placebo or intramuscular placebo followed by 4 mg of intravenous lorazepam. In children with an estimated weight of 13 to 40 kg, the active treatment was 5 mg of intramuscular midazolam or 2 mg of intravenous lorazepam.

It is possible that this might mean some subjects were administered lorazepam doses below the recommended standard of 0.1mg/kg/dose. The study also did not compare the effects of autoinjector versus conventional IM treatments nor the efficacy of IM/IV lorazepam/midazolam.

However the study results seem to support the use of intramuscular midazolam by emergency medical personnel in the pre hospital setting for status epileptics. In addition midazolam has the advantage of better stability when not refrigerated, compared to lorazepam.

Citation: Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600. PubMed PMID: 22335736; PubMed Central PMCID: PMC3307101.