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N Engl J Med. 2012 Feb 16;366(7):591-600. doi: 10.1056/NEJMoa1107494.

Intramuscular versus intravenous therapy for prehospital status epilepticus.

Collaborators (168)

Silbergleit R, Lowenstein D, Barsan W, Pancioli A, Stevenson V, Zaleski E, Harney D, Harsh D, Pinkerton J, Kade A, Siewert N, Pinawin A, Ring C, Brenne P, Vonderschmidt K, Durkalski V, Palesch Y, Dillon C, Pauls K, Wu Q, Zhao W, Conwit R, Janis S, Jett D, Fureman B, Welch RD, Mango L, Mika VH, Atas J, Dunne R, Wheaton D, Levy P, Velilla MA, Sherwin R, O'Neil B, Groves A, Rosenthal M, Pancioli A, Ewing I, Waymeyer P, McMullan J, Vonderschmidt M, Schwartz H, Stettler B, Knight W, Adeoye O, Cadena R, Bonomo J, Grise E, Heitsch L, Gagai N, Schmit P, Stark S, Doellman T, Hemphill J 3rd, Meeker M, Rosborough K, Duncan J, Sporer K, Gelb A, Smith W, Ramanujam P, Nakagawa K, Moheet A, Kamel H, Naravetla B, Mercer M, Wong C, Jones E, Milling TJ, Ottman M, King B, LaChance L, Brockman J, Didonato P, Hinchey P, Wright DW, Bitner MD, Beltran GW, Howlett-Smith H, McDougal AG, Linzer JF Sr, Merck LH, Espinoza T, Lewandowski CA, Vohra TT, Crouse PL, Baker AE, Creech DR, Russman AN, Quinn JV, Casal S, Hebig A, Liao M, D'Souza P, Denninghoff KR, Spaite DW, Barnhart B, Haro W, Bobrow BJ, Ornato JP, Noe SL, Payne AD, Towne AR, Kurz MC, Carmack JT, Biros M, Mahoney B, Sargent C, Hildebrandt D, Kummer C, Gesme D, Aufderheide TP, Brandt JT Jr, Colella M, Pirrallo R, Bialkowski W, Hermanson B, Sandoval C, Morrow K, McCormick K, Burpee K, Price G, Kawa D, Humphries RL, Dechtenberg L, Sweat C, Pettigrew LC, Baren JM, Bledsoe R, Stahlman B, Lamond K, Nathanson PG, Kasner SE, Le Roux PD, Warden CR, Lowe RA, Stone RN, Mayer S, Flomenbaum N, Falo M, Magitbay LV, Surti C, Cordi H, Ribaudo D, Rosengart A, Vibbert M, Ortega-Gutierrez S, Choi H, Gilmore E, Malhotra R, Berger L, Gentile NT, Wang A, Vates C, Usatch B, Freeman BB, Cleary SL, Stern B, Ting T, Krauss G, Ganley V, Rice S, Ronald J, Stevens M, Browne B, Rosenthal R, Hill P.

Author information

Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48105, USA.



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; number, NCT00809146.).

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