Review Of: Silbergleit R., Durkalski V., Lowenstein D., et al. Intramuscular versus Intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591–600.
This study compares the effectiveness of two commonly used benzodiazepines for the treatment of seizures. Investigators compared the midazolam (Versed) intramuscular (IM) to lorazepam (Ativan) IV. This was a randomized and double-blinded study. A total of 893 patients were enrolled; 448 received midazolam and 445 received lorazepam. Both medications were effective in stopping seizures, and investigators concluded that IM midazolam is at least as safe as IV lorazepam.
Doc Wesley: What a wonderful study to address one of the most challenging patient-care scenarios. I remember the frustration I experienced with attempting to insert IVs multiple times on thrashing seizure patients before intraosseous was readily available, wishing the seizure would stop so I could get the line in during their post-ictal period. It never failed that the patient would be in status epilepticus, and I’d have to give up and transport the patient as best I could.
Treatment of seizures has been studied extensively, but the prehospital challenges haven’t. Most medical directors have opted for IV or intranasal (IN) administration of lorazepam based on the literature I’ve read. We have avoided the use of midazolam and diazepam primarily out of fear of respiratory suppression.
This study has clearly demonstrated that IM injections of midazolam are just as effective and in some ways superior to IVs of lorazepam. First, we must be clear that differences exist between midazolam and lorazepam. Midazolam has an amnestic effect, which in the case of seizure control, probably has no effect. The dose of midazolam, 10mg IM, used in this study, is in all likelihood greater than that used by most EMS physicians, as is the dose of lorazepm, 2mg IV.
But these doses are consistent with the treatment recommendations of the neurology organizations.
With that said, the time to administer IM midazolam was half that of IV lorazepam, but the time to effect was the same. However, in situations in which IV access is delayed or fails, IM midazolam prevails.
Finally, lorazepam requires refrigeration or decreasing effective storage life to 60–90 days. Use of IM midazolam would remove one more medication that requires careful stocking. I’m going to be seriously considering making the transition to midazolam in the near future.
Medic Marshall: I’m going to echo Dr. Wesley’s comments: This really is a wonderful study. The investigators were able to demonstrate IM midazolam was just as safe as IV lorazepam. From a street perspective, I’m grateful for a study like this. One of the most difficult things to watch, at least in my opinion, is a patient thrashing and seizing. All I want to do is make it stop.
I like to think I’m pretty decent with my IV sticks, but attempting vascular access on these patients is definitely not easy—not to mention potentially dangerous, and putting you or others around at risk for an accidental needle stick. Not to say attempting an IM injection isn’t as dangerous, but generally you need only one stick as compared with multiple sticks for vascular access.
Having the pleasure of working as a paramedic for the Doc here, I really hope he makes the decision to make midazolam IM the primary means of treating active seizures. I know I’d really appreciate it and so would my colleagues.
Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.
This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion.
The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.
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). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.
For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, NCT00809146.)