Corresponding Author: Suzanne Schuh, MD, Pediatric Emergency Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, M5G 1X8, ON, Canada (suzanne.schuh@sickkids.ca).
Accepted for Publication: September 21, 2020.
Author Contributions: Dr Schuh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Schuh, Coates, Willan, Zemek, Plint, Gravel, Ducharme, Johnson, Black, Curtis, Klassen, Nicksy, Freedman.
Acquisition, analysis, or interpretation of data: Sweeney, Rumantir, Willan, Stephens, Atenafu, Finkelstein, Thompson, Zemek, Plint, Gravel, Black, Curtis, Beer, Nicksy, Freedman.
Drafting of the manuscript: Schuh, Stephens, Curtis, Nicksy, Freedman.
Critical revision of the manuscript for important intellectual content: Schuh, Sweeney, Rumantir, Coates, Willan, Stephens, Atenafu, Finkelstein, Thompson, Zemek, Plint, Gravel, Ducharme, Johnson, Black, Curtis, Beer, Klassen, Freedman.
Statistical analysis: Willan, Stephens, Atenafu.
Obtained funding: Schuh, Zemek, Plint, Gravel, Johnson, Curtis, Freedman.
Administrative, technical, or material support: Sweeney, Rumantir, Coates, Finkelstein, Thompson, Gravel, Ducharme, Black, Beer, Nicksy, Freedman.
Supervision: Schuh, Sweeney, Rumantir, Johnson, Beer, Klassen.
Conflict of Interest Disclosures: Dr Schuh reported receiving grants from the Canadian Institutes for Health Research (CIHR), Thrasher Research Fund, Physicians’ Services Incorporated Foundation, and Hospital for Sick Children and nonfinancial support from La Diffusion Technique Francaise during the conduct of the study. Dr Sweeney reported receiving grants from the Hospital for Sick Children during the conduct of the study. Dr Finkelstein reported receiving grants from CIHR during the conduct of the study. Dr Zemek reported holding competitively funded research grants from CIHR, Ontario Neurotrauma Foundation, Physicians’ Services Incorporated Foundation, CHEO Foundation, Ontario Brain Institute, Ontario SPOR Support Unit, National Football League, and Clinical Research Chair in Pediatric Concussion from the University of Ottawa. He has no commercial conflicts of interest to disclose. Dr Gravel reported receiving grants from CIHR during the conduct of the study. Dr Ducharme reported receiving unrestricted research funds from GlaxoSmithKline, AstraZeneca, Novartis, Teva, and Trudell Medical; grants from GlaxoSmithKline, Covis, Thorasys, and CIHR; and personal fees from Thorasys, Covis, and Teva outside the submitted work. No other disclosures were reported.
Funding/Support: This research was supported by grants from CIHR, the Thrasher Research Fund, the Physicians’ Services Incorporated Foundation, and the Hospital for Sick Children. Dr Freedman is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: The Pediatric Emergency Research Canada (PERC) Network members include the following: Suzanne Schuh, MD, Judy Sweeney, RN, BScN, Maggie Rumantir, MD, Allan L. Coates, MDCM, BEng, Andrew R. Willan, PhD, Derek Stephens, MSc, BSc, Yaron Finkelstein, MD, and Darcy Nicksy, BScPhM (The Hospital for Sick Children, Toronto, Ontario, Canada); Graham Thompson, MD, and Stephen B. Freedman, MDCM, MSc (Alberta Children’s Hospital, Calgary, Alberta, Canada); Darcy Beer, MD, and Terry Klassen, MD, MSc (Winnipeg Children’s Hospital, Winnipeg, Manitoba, Canada); Sarah Curtis, MD (Stollery Children’s Hospital, Edmonton, Alberta, Canada); Jocelyn Gravel, MD, MSc, and Francine Ducharme, MD, MSc (Sainte-Justine Pédiatrie, Montreal, Quebec, Canada); Roger Zemek, MD, and Amy Plint, MD, MSc (Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada); and Karen Black, MD, MSc (British Columbia Children’s Hospital, Vancouver, British Columbia, Canada).
Meeting Presentation: This study was accepted for a platform presentation at the annual conference of the Pediatric Academic Societies; May 2020; Philadelphia, Pennsylvania.
Additional Contributions: We thank the participants and their families for trusting us to conduct this trial; the trial investigators and support staff across all sites for their commitment to the successful conduct of the trial; the site coordinators, including Rena Papadimitropoulos (research coordinator, Children’s Hospital of Winnipeg), Arpita Majundar (MSc, Children’s Hospital of Winnipeg), Jianling Xie (MD, MPH, Alberta Children’s Hospital), Dale Dalgleish (RN, BHScN, CHEO), Candice McGahern (BA, CHEO), Ally Slattery (RN, British Columbia Children’s Hospital), Maryse Lagace (RN, BScN, CCRP, CHU Sainte-Justine, Montreal), Manasi Rajagopal (research coordinator, Stollery Children’s Hospital), and Nadia Dow (research coordinator, Stollery Children’s Hospital) for trial coordination; the emergency department physicians, nurses, and ancillary staff at all sites; the staff of the Pediatric Research Academic Initiative at SickKids Emergency (PRAISE) and of the SickKids Emergency Assistants for Research in Child Health (SEARCH) programs for identifying potentially eligible participants; Tanveer H. Collins (MD, The Hospital for Sick Children) for his help with the database; Aya Finkelstein (The Hospital for Sick Children) for her help with the study database; and Lejla Halilovic (BSc, The Hospital for Sick Children) for her administrative assistance with the manuscript preparation. The site coordinators and Dr Collins received financial compensation for their role in the study. The other contributors were not compensated.
Data Sharing Statement: See Supplement 6.
1.Moorman
JE , Rudd
RA , Johnson
CA ,
et al; Centers for Disease Control and Prevention (CDC). National surveillance for asthma: United States, 1980-2004.
MMWR Surveill Summ. 2007;56(8):1-54.
PubMedGoogle Scholar 4.Ortiz-Alvarez
O , Mikrogianakis
A ; Canadian Paediatric Society, Acute Care Committee. Managing the paediatric patient with an acute asthma exacerbation.
Paediatr Child Health. 2012;17(5):251-262. doi:
10.1093/pch/17.5.251
PubMedGoogle ScholarCrossref 7.Griffiths
B , Kew
KM . Intravenous magnesium sulfate for treating children with acute asthma in the emergency department.
Cochrane Database Syst Rev. 2016;4:CD011050.
PubMedGoogle Scholar 9.Liu
X , Yu
T , Rower
JE , Campbell
SC , Sherwin
CM , Johnson
MD . Optimizing the use of intravenous magnesium sulfate for acute asthma treatment in children.
Pediatr Pulmonol. 2016;51(12):1414-1421. doi:
10.1002/ppul.23482
PubMedGoogle ScholarCrossref 11.Johnson
MD , Zorc
JJ , Nelson
DS ,
et al; Pediatric Emergency Care Applied Research Network (PECARN). Intravenous magnesium in asthma pharmacotherapy: variability in use in the PECARN Registry.
J Pediatr. 2020;220:165-174.e2. doi:
10.1016/j.jpeds.2020.01.062
PubMedGoogle ScholarCrossref 12.Mahajan
P , Haritos
D , Rosenberg
N , Thomas
R . Comparison of nebulized magnesium sulfate plus albuterol to nebulized albuterol plus saline in children with acute exacerbations of mild to moderate asthma.
J Emerg Med. 2004;27(1):21-25. doi:
10.1016/j.jemermed.2004.02.006
PubMedGoogle ScholarCrossref 13.Meral
A , Coker
M , Tanaç
R . Inhalation therapy with magnesium sulfate and salbutamol sulfate in bronchial asthma.
Turk J Pediatr. 1996;38(2):169-175.
PubMedGoogle Scholar 15.Alansari
K , Ahmed
W , Davidson
BL , Alamri
M , Zakaria
I , Alrifaai
M . Nebulized magnesium for moderate and severe pediatric asthma: a randomized trial.
Pediatr Pulmonol. 2015;50(12):1191-1199. doi:
10.1002/ppul.23158
PubMedGoogle ScholarCrossref 16.Schuh
S , Sweeney
J , Freedman
SB ,
et al; Pediatric Emergency Research Canada Group. Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial.
Trials. 2016;17(1):261. doi:
10.1186/s13063-015-1151-x
PubMedGoogle ScholarCrossref 18.US Committee on Extension to the Standard Atmosphere. US Standard Atmosphere, 1976. US Government Printing Office; 1976.
19.Bhogal
SK , McGillivray
D , Bourbeau
J , Benedetti
A , Bartlett
S , Ducharme
FM . Early administration of systemic corticosteroids reduces hospital admission rates for children with moderate and severe asthma exacerbation.
Ann Emerg Med. 2012;60(1):84-91.e3. doi:
10.1016/j.annemergmed.2011.12.027
PubMedGoogle ScholarCrossref 22.Lehr
AR , McKinney
ML , Gouin
S , Blais
JG , Pusic
MV , Ducharme
FM . Development and pretesting of an electronic learning module to train health care professionals on the use of the Pediatric Respiratory Assessment Measure to assess acute asthma severity.
Can Respir J. 2013;20(6):435-441. doi:
10.1155/2013/148645
PubMedGoogle ScholarCrossref 23.Aggarwal
P , Sharad
S , Handa
R , Dwiwedi
SN , Irshad
M . Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study.
Emerg Med J. 2006;23(5):358-362. doi:
10.1136/emj.2005.026203
PubMedGoogle ScholarCrossref 24.Tal
A , Golan
H , Grauer
N , Aviram
M , Albin
D , Quastel
MR . Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction.
J Pediatr. 1996;128(4):479-484. doi:
10.1016/S0022-3476(96)70357-8
PubMedGoogle ScholarCrossref 26.Coates
AL , Leung
K , Chan
J , Ribeiro
N , Charron
M , Schuh
S . Respiratory system deposition with a novel aerosol delivery system in spontaneously breathing healthy adults.
Respir Care. 2013;58(12):2087-2092. doi:
10.4187/respcare.02455
PubMedGoogle ScholarCrossref 27.Ungar
WJ , Coyte
PC ; Pharmacy Medication Monitoring Program Advisory Board. Prospective study of the patient-level cost of asthma care in children.
Pediatr Pulmonol. 2001;32(2):101-108. doi:
10.1002/ppul.1095PubMedGoogle ScholarCrossref 28.Plotnick
LH , Ducharme
FM . Combined inhaled anticholinergic agents and beta-2-agonists for initial treatment of acute asthma in children. [Update in
Cochrane Database Syst Rev. 2000;(4):CD000060].
Cochrane Database Syst Rev. 2000;(2):CD000060. doi:
10.1002/14651858.CD000060PubMedGoogle Scholar 29.Holm
S . A simple sequentially rejective multiple test procedure.
Scand J Stat. 1979:65-70.
Google Scholar 30.Centers for Disease Control and Prevention (CDC). Asthma mortality and hospitalization among children and young adults: United States, 1980-1993.
MMWR Morb Mortal Wkly Rep. 1996;45(17):350-353.
PubMedGoogle Scholar 33.Carroll
CL , Sala
KA , Zucker
AR , Schramm
CM . Beta-adrenergic receptor polymorphisms associated with length of ICU stay in pediatric status asthmaticus.
Pediatr Pulmonol. 2012;47(3):233-239. doi:
10.1002/ppul.21544
PubMedGoogle ScholarCrossref 34.Chun
E , Lee
HS , Bang
BR ,
et al. Dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells could play a role in predicting the response of asthmatics to treatment with corticosteroids.
J Clin Immunol. 2011;31(1):122-127. doi:
10.1007/s10875-010-9463-9
PubMedGoogle ScholarCrossref 36.Moore
PE , Ryckman
KK , Williams
SM , Patel
N , Summar
ML , Sheller
JR . Genetic variants of GSNOR and ADRB2 influence response to albuterol in African-American children with severe asthma.
Pediatr Pulmonol. 2009;44(7):649-654. doi:
10.1002/ppul.21033
PubMedGoogle ScholarCrossref 37.Normansell
R , Knightly
R , Milan
SJ , Knopp-Sihota
JA , Rowe
BH , Powell
C . Inhaled magnesium sulfate in the treatment of acute asthma in children.
Paediatr Respir Rev. 2018;26:31-33. doi:
10.1016/j.prrv.2018.01.001
PubMedGoogle Scholar 39.British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma.
Thorax. 2014;69(suppl 1):1-192.
PubMedGoogle ScholarCrossref