Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. New Eng J Med 366(7): 591–600, Feb 16, 2012.
Early termination of prolonged seizures with intravenous (IV) administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular (IM) route. Methods—This double-blind randomized trial compared the efficacy of IM midazolam with that of IV 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 IM autoinjector or IV 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.
Results—At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the IM-midazolam group and 282 of 445 (63.4%) in the IV-lorazepam group (P < 0.001). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with IM midazolam and 14.4% with IV 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 IM-midazolam group and 4.8 minutes in the IV-lorazepam group, and median times from active treatment to cessation of convulsions [were] 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups. Conclusions—For subjects in status epilepticus, IM midazolam is at least as safe and effective as IV lorazepam for prehospital seizure cessation.
This important study gives us clear evidence that IM midazolam (Versed) should be the prehospital treatment of choice for status epilepticus. IM midazolam was more effective in terminating seizures than IV lorazepam (Ativan), and patients were less likely to need hospital admission. IM midazolam took a little longer to act after administration; however, because it did not require first starting an IV, the interval from deciding to treat until termination of the seizure trended shorter. For in-hospital (or interfacility transfer) patients, the decision is more complex, as patients may have a pre-existing IV or need an IV for other purposes, and treatment duration is longer. But in the prehospital setting, where the goal is prompt cessation of seizure and contact time is typically short, IM midazolam is superior to IV lorazepam.
The IM midazolam treatment protocol was simplified and used a higher dose than typical in EMS systems. There were only 2 doses—5 mg for patient body weight 13–40 kg and 10 mg for weights greater than 40 kg. Error in pediatric medications is an ongoing challenge, and this may be at least a partial solution. The authors pointed out that the higher dose is in line with the recommendations of epilepsy specialists, and because respiratory depression may be more related to duration of seizure than medications, terminating seizures early may actually decrease the need for intubation/ventilation.
With its superior clinical performance and operational benefits (it does require refrigeration), midazolam appears to be the preferred prehospital medication for the treatment of status epilepticus.
Angelo Salvucci, Jr., MD, FACEP, is medical director for the Santa Barbara County and Ventura County (CA) EMS agencies and a member of the EMS World editorial advisory board.?