Critical appraisal of “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”

Abstract

<h2>Abstract</h2><h3>Background</h3> Intravenous benzodiazepines have been shown to be effective in management of status epilepticus, but due to ease of administration intramuscular route is being frequently used in prehospital care without documented evidence. <h3>Methods</h3> A double-blinded randomised clinical trial aiming to demonstrate that intramuscular midazolam is at least as effective as intravenous lorazepam (non-inferiority design). The non-inferiority margin was set at 10 percentage points below that of intravenous lorazepam's effect. Children and adults found in status epilepticus were included in the study and the interventions given serially by an intramuscular autoinjector followed by intravenous infusion. Double dummy strategy was followed so that each subject received either intramuscular midazolam or intravenous lorazepam along with a placebo. These subjects were followed thereafter for cessation of seizures on arrival to hospital (primary outcome) without the need for rescue therapy. Secondary outcomes included requirement of endotracheal intubation, recurrence of seizures, and timing of treatment relative to the cessation of convulsions. <h3>Results</h3> After screening and exclusion 893 subjects were assigned to interventions, 448 in the intramuscular midazolam group and 445 in the intravenous lorazepam group. Of the 448 of the former group 443 actually received the intervention while the intervention could be given in only 297 in the later group, 329 of 448 subjects (73.4%) in the intramuscular midazolam group and 282 of 445 (63.4%) in the intravenous lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0–16.1; <i>P</i> < 0.001 for both non-inferiority and superiority) had no seizures on arrival to the emergency without the need for rescue therapy. There was no difference between the two intervention groups with regards to the need of endotracheal intubation or recurrence of seizures. the median times to administration of active treatment in the intramuscular midazolam group were 1.2 and 4.8 min in the intravenous lorazepam group, with median times from active treatment to cessation of convulsions of 3.3 min and 1.6 min in the two groups respectively. <h3>Conclusions</h3> In the management of status epilepticus, intramuscular midazolam was at least as safe and effective as intravenous lorazepam for prehospital control of seizure with lesser time required for its administration.