Intramuscular versus intravenous therapy for prehospital status epilepticus.
Author(s): Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan
W; NETT Investigators.
Collaborators: 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.
Affiliation(s): Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48105,
USA. robert.silbergleit@umich.edu
Publication date & source: 2012, N Engl J Med. , 366(7):591-600
BACKGROUND: Early termination of prolonged seizures with intravenous
administration of benzodiazepines improves outcomes. For faster and more reliable
administration, paramedics increasingly use an intramuscular route.
METHODS: 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.
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
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.
CONCLUSIONS: 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, ClinicalTrials.gov NCT00809146.).
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