Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical
trial.
Author(s): Chamberlain JM(1), Okada P(2), Holsti M(3), Mahajan P(4), Brown KM(1), Vance
C(5), Gonzalez V(6), Lichenstein R(7), Stanley R(8), Brousseau DC(9), Grubenhoff
J(10), Zemek R(11), Johnson DW(12), Clemons TE(13), Baren J(14); Pediatric
Emergency Care Applied Research Network (PECARN).
Collaborators: King D, Kim C, Martz K, Zhao J, Walson P, Weise K, Das A, Venzon
D, Wiedermann B, Koren G, Vocke C, Thompson A, Harris N, Riddle M, Brown L,
Swerdlow P, Zajicek A, Nigrovic L, Lillis K, Mahajan P, Sonnett M, Shaw K, Powell
E, Brown K, Ruddy R, Hoyle J, Borgialli D, Atherly-John Y, Gorelick M, Andrada E,
Stanley R, Conners G, Pruitt C, Jaffe D, Lichenstein R, Dayan P, Alpern E, Bajaj
L, Brown K, Borgialli D, Chamberlain J, Dean J, Gorelick M, Jaffe D, Kuppermann
N, Kwok M, Lichenstein R, Lillis K, Mahajan P, Monroe D, Nigrovic L, Powell E,
Rogers A, Ruddy R, Stanley R, Tunik M, Kavanaugh D, Park H, Dean J, Gramse H,
Holubkov R, Donaldson A, Olson C, Zuspan S, Enriquez R, Brown K, Goldfarb S,
Crain E, Kim E, Krug S, Monroe D, Nelson D, Berlyant M, Zuspan S, Gorelick M,
Alpern L, Anders J, Borgialli D, Cimpello L, Donaldson A, Foltin G, Moler F,
Shreve K, Nigrovic L, Chamberlain J, Dayan P, Dean JM, Holubkov R, Jaffe D,
Powell E, Shaw K, Stanley R, Tunik M, Lillis K, Alessandrini E, Blumberg S,
Enriquez R, Lichenstein R, Mahajan P, McDuffie R, Ruddy R, Thomas B, Wade J,
Schalick W, Hoyle J, Atabaki S, Call K, Gramse H, Kwok M, Rogers A, Schnadower D,
Kuppermann N.
Affiliation(s): Author information:
(1)Division of Emergency Medicine, Children's National Medical Center, Washington,
DC2The Pediatric Emergency Care Applied Research Network (PECARN).
(2)University of Texas, Southwestern, Dallas.
(3)The Pediatric Emergency Care Applied Research Network (PECARN)4Department of
Pediatrics, University of Utah, Salt Lake City.
(4)The Pediatric Emergency Care Applied Research Network (PECARN)5Department of
Pediatrics, Children's Hospital of Michigan, Detroit.
(5)The Pediatric Emergency Care Applied Research Network (PECARN)6University of
California, Davis, Sacramento.
(6)The Pediatric Emergency Care Applied Research Network (PECARN)7Baylor College of
Medicine, Houston, Texas.
(7)Department of Pediatrics, University of Maryland, Baltimore.
(8)The Pediatric Emergency Care Applied Research Network (PECARN)9University of
Michigan, Ann Arbor.
(9)The Pediatric Emergency Care Applied Research Network (PECARN)10Department of
Pediatrics, Medical College of Wisconsin, Milwaukee.
(10)The Pediatric Emergency Care Applied Research Network (PECARN)11Children's
Hospital of Colorado, Denver.
(11)Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa,
Ontario, Canada.
(12)Alberta Children's Hospital, Calgary, Alberta, Canada.
(13)The EMMES Corp, Rockville, Maryland.
(14)The Pediatric Emergency Care Applied Research Network (PECARN)15Department of
Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Publication date & source: 2014, JAMA. , 311(16):1652-60
IMPORTANCE: Benzodiazepines are considered first-line therapy for pediatric
status epilepticus. Some studies suggest that lorazepam may be more effective or
safer than diazepam, but lorazepam is not Food and Drug Administration approved
for this indication.
OBJECTIVE: To test the hypothesis that lorazepam has better efficacy and safety
than diazepam for treating pediatric status epilepticus.
DESIGN, SETTING, AND PARTICIPANTS: This double-blind, randomized clinical trial
was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to
younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US
academic pediatric emergency departments were eligible. There were 273 patients;
140 randomized to diazepam and 133 to lorazepam.
INTERVENTIONS: Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of
lorazepam intravenously, with half this dose repeated at 5 minutes if necessary.
If status epilepticus continued at 12 minutes, fosphenytoin was administered.
MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was cessation of status
epilepticus by 10 minutes without recurrence within 30 minutes. The primary
safety outcome was the performance of assisted ventilation. Secondary outcomes
included rates of seizure recurrence and sedation and times to cessation of
status epilepticus and return to baseline mental status. Outcomes were measured 4
hours after study medication administration.
RESULTS: Cessation of status epilepticus for 10 minutes without recurrence within
30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133
(72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95%
CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted
ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk
difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant
differences in secondary outcomes except that lorazepam patients were more likely
to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95%
CI, 6.1% to 27.7%).
CONCLUSIONS AND RELEVANCE: Among pediatric patients with convulsive status
epilepticus, treatment with lorazepam did not result in improved efficacy or
safety compared with diazepam. These findings do not support the preferential use
of lorazepam for this condition.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621478.
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