[Skip to Content]
[Skip to Content Landing]

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency DepartmentA Randomized Clinical Trial

Educational Objective
To learn about the treatment of children with acute moderate to severe asthma.
1 Credit CME
Key Points

Question  What is the effectiveness of nebulized magnesium in children and adolescents with acute asthma in the emergency department who remain in moderate or severe respiratory distress after evidence-based standardized initial therapy?

Findings  In this randomized clinical trial that included 816 patients, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the rate of hospitalization for asthma within 24 hours (43.5% vs 47.7%, respectively).

Meaning  The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.


Importance  While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.

Objective  To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.

Design, Setting, and Participants  A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.

Interventions  Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).

Main Outcomes and Measures  The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.

Results  Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, −4.2%; absolute risk difference 95% [exact] CI, −11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, −0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, −1.32 to 1.67]; P = .82); oxygen saturation (−0.04% [95% CI, −0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, −1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).

Conclusions and Relevance  Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.

Trial Registration  ClinicalTrials.gov Identifier: NCT01429415

Sign in to take quiz and track your certificates

Buy This Activity
Our websites may be periodically unavailable between 7:00pm CT February 4, 2023 and 1:00am CT February 5, 2023 for regularly scheduled maintenance.

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

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.

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
National Asthma Education and Prevention Program.  Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma: summary report 2007.   J Allergy Clin Immunol. 2007;120(5)(suppl):S94-S138. doi:10.1016/j.jaci.2007.09.029 PubMedGoogle ScholarCrossref
Global Initiative for Asthma. Global Initiative for Asthma (GINA). Accessed April 5, 2020. http://www.ginasthma.org
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
Tse  SM , Tantisira  K , Weiss  ST .  The pharmacogenetics and pharmacogenomics of asthma therapy.   Pharmacogenomics J. 2011;11(6):383-392. doi:10.1038/tpj.2011.46 PubMedGoogle ScholarCrossref
Cheuk  DK , Chau  TC , Lee  SL .  A meta-analysis on intravenous magnesium sulphate for treating acute asthma.   Arch Dis Child. 2005;90(1):74-77. doi:10.1136/adc.2004.050005 PubMedGoogle ScholarCrossref
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
Su  Z , Li  R , Gai  Z .  Intravenous and nebulized magnesium sulfate for treating acute asthma in children: a systematic review and meta-analysis.   Pediatr Emerg Care. 2018;34(6):390-395. doi:10.1097/PEC.0000000000000909 PubMedGoogle ScholarCrossref
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
Schuh  S , Macias  C , Freedman  SB ,  et al.  North American practice patterns of intravenous magnesium therapy in severe acute asthma in children.   Acad Emerg Med. 2010;17(11):1189-1196. doi:10.1111/j.1553-2712.2010.00913.x PubMedGoogle ScholarCrossref
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
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
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
Powell  C , Kolamunnage-Dona  R , Lowe  J ,  et al; MAGNETIC study group.  Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.   Lancet Respir Med. 2013;1(4):301-308. doi:10.1016/S2213-2600(13)70037-7 PubMedGoogle ScholarCrossref
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
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
Ducharme  FM , Chalut  D , Plotnick  L ,  et al.  The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers.   J Pediatr. 2008;152(4):476-480, 480.e1. doi:10.1016/j.jpeds.2007.08.034PubMedGoogle ScholarCrossref
US Committee on Extension to the Standard Atmosphere.  US Standard Atmosphere, 1976. US Government Printing Office; 1976.
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
Chalut  DS , Ducharme  FM , Davis  GM .  The Preschool Respiratory Assessment Measure (PRAM): a responsive index of acute asthma severity.   J Pediatr. 2000;137(6):762-768. doi:10.1067/mpd.2000.110121 PubMedGoogle ScholarCrossref
Birken  CS , Parkin  PC , Macarthur  C .  Asthma severity scores for preschoolers displayed weaknesses in reliability, validity, and responsiveness.   J Clin Epidemiol. 2004;57(11):1177-1181. doi:10.1016/j.jclinepi.2004.02.016 PubMedGoogle ScholarCrossref
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
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
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
Coates  AL , Leung  K , Vecellio  L , Schuh  S .  Testing of nebulizers for delivering magnesium sulfate to pediatric asthma patients in the emergency department.   Respir Care. 2011;56(3):314-318. doi:10.4187/respcare.00826 PubMedGoogle ScholarCrossref
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
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
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
Holm  S .  A simple sequentially rejective multiple test procedure.   Scand J Stat. 1979:65-70.Google Scholar
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
Bjerg  A , Sandström  T , Lundbäck  B , Rönmark  E .  Time trends in asthma and wheeze in Swedish children 1996-2006: prevalence and risk factors by sex.   Allergy. 2010;65(1):48-55. doi:10.1111/j.1398-9995.2009.02105.xPubMedGoogle ScholarCrossref
Castro-Rodríguez  JA , Holberg  CJ , Wright  AL , Martinez  FD .  A clinical index to define risk of asthma in young children with recurrent wheezing.   Am J Respir Crit Care Med. 2000;162(4, pt 1):1403-1406. doi:10.1164/ajrccm.162.4.9912111 PubMedGoogle ScholarCrossref
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
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
Lima  JJ .  Do genetic polymorphisms alter patient response to inhaled bronchodilators?   Expert Opin Drug Metab Toxicol. 2014;10(9):1231-1240. doi:10.1517/17425255.2014.939956 PubMedGoogle ScholarCrossref
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
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
Knightly  R , Milan  SJ , Hughes  R ,  et al.  Inhaled magnesium sulfate in the treatment of acute asthma.   Cochrane Database Syst Rev. 2017;11:CD003898. doi:10.1002/14651858.CD003898.pub6 PubMedGoogle Scholar
British Thoracic Society; Scottish Intercollegiate Guidelines Network.  British guideline on the management of asthma.   Thorax. 2014;69(suppl 1):1-192.PubMedGoogle ScholarCrossref
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.