Clinical Outcomes of Magnesium Sulphate and Aminophylline in Adult Acute Asthma: A Systematic Review and Network Meta-analysis
Main Article Content
Magnesium sulfate (MgSO?) and aminophylline are commonly used as adjunctive therapies in adults with acute asthma exacerbations who do not adequately respond to standard treatment. However, their comparative effectiveness remains uncertain. This network meta-analysis (NMA) aimed to evaluate the clinical outcomes of MgSO? and aminophylline in adults with acute asthma. A systematic review and meta-analysis were conducted following PRISMA guidelines, identifying articles from PubMed, SpringerLink, and Taylor & Francis. Random-effects models generated standardized mean differences (SMD) with 95% confidence intervals (CI). A league rank table was also generated to estimate the most effective agent in treating acute asthma. Overall heterogeneity was evaluated using the I² test. The NMA demonstrated no statistically significant difference between MgSO? and aminophylline in improving FEV? (SMD = 0.68; 95% CI: ?1.59 to 2.95; p = 0.5573). Ranking analysis suggested that, besides placebo, nebulized MgSO? had the highest probability of being the most effective intervention for FEV? improvement, although this finding did not reach statistical significance (nebulized MgSO?: MD = 1.11; 95% CI: 0.20–3.38; p = 0.6641). Qualitative synthesis indicated that MgSO? was associated with improvements in PEFR. In addition, aminophylline showed a potential reduction in hospital admission rates, whereas results for MgSO? were inconsistent across studies. MgSO? and aminophylline showed comparable effects on FEV? improvement in adults with acute asthma. MgSO? demonstrated favorable results in PEFR improvement, while aminophylline may offer potential benefits in reducing hospital admissions. Given the heterogeneity and limited sample sizes of available trials, further high-quality head-to-head studies are warranted to clarify their relative clinical effectiveness.
Keywords:
Magnesium sulphate, Aminophylline, Acute Asthma
Abu-Sultaneh, S., Miller, A. G., Basnet, S., Craven, H. J., Dalabih, A., & Irazuzta, J. E. (2025). Intravenous Bronchodilators in Pediatric Critical Asthma: A Systematic Review and Network Meta-Analysis. Pediatric Pulmonology. https://doi.org/10.1002/ppul.71192
Al-Shamrani, A., Al-Harbi, A. S., Bagais, K., Alenazi, A., & Alqwaiee, M. (2019). Management of asthma exacerbation in the emergency departments. International Journal of Pediatrics and Adolescent Medicine, 61–67. https://doi.org/10.1016/j.ijpam.2019.02.001
Ambro?ej, D., Adamiec, A., Forno, E., Orzo?ek, I., Feleszko, W., & Castro-Rodriguez, J. A. (2024). Intravenous magnesium sulfate for asthma exacerbations in children: Systematic review with meta-analysis. Paediatric Respiratory Reviews, 23–30. https://doi.org/10.1016/j.prrv.2024.01.003
Aralihond, A., Shanta, Z., Pullattayil, A., & Powell, C. V. E. (2020). Treating acute severe asthma attacks in children: Using aminophylline. Breathe, 16(4), 1–9. https://doi.org/10.1183/20734735.0081-2020
Bessmertny, O., DiGregorio, R. V, Cohen, H., Becker, E., Looney, D., & Golden, J. (2002). A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults. Annals of Emergency Medicine, 39(6), 585–591. https://doi.org/10.1067/mem.2002.123300
Bloch, H., Silverman, R., Mancherje, N., Grant, S., Jagminas, L., & Scharf, S. M. (1995). Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma. Chest, 107(6), 1576–1581. https://doi.org/10.1378/chest.107.6.1576
Chen, X., Ma, D., Li, H., Liu, Y., Xu, G., & Deng, X. (2025). Temporal trends and future projections of incidence rate and mortality for asthma in China: an analysis of the Global Burden of Disease Study 2021. Frontiers in Medicine, 12. https://doi.org/10.3389/fmed.2025.1529636
Dabbs, W., Bradley, M. H., & Chamberlin, M. (2024). Acute Asthma Exacerbations: Management Strategies. American Family Physician. https://www.aafp.org/afp
Elsakaya, M. S., Ismail, M. T., Hamed, M. N., Hendawy, H. A., & Omera, M. A. (2018). Nebulized magnesium sulfate in acute asthma. Medicine Science | International Medical Journal, 391. https://doi.org/10.5455/medscience.2018.07.8796
Gandia, F., Guénard, H., Sriha, B., Tabka, Z., & Rouatbi, S. (2012). Inhaled magnesium sulphate in the treatment of bronchial hyperresponsiveness. Magnesium Research, 25(4), 168–176. https://doi.org/10.1684/mrh.2012.0323
Gayen, S., Dachert, S., Lashari, B. H., Gordon, M., Desai, P., & Criner, G. J. (2024). Critical Care Management of Severe Asthma Exacerbations. Journal of Clinical Medicine. https://doi.org/10.3390/jcm13030859
Healthcare Improvement Scotland. (2019). British guideline on the management of asthma: a national clinical guideline. Healthcare Improvement Scotland.
Hossein, S., Pegah, A., Davood, F., Said, A., Babak, M., & Mani, M. (2016). The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: A randomized clinical trial. American Journal of Emergency Medicine, 34(5), 883–886. https://doi.org/10.1016/j.ajem.2016.01.024
Huang, D., O’Brien, R. G., Harman, E., Aull, L., Reents, S., & Visser, J. (1993). Does Aminophylline Benefit Adults Admitted to the Hospital for an Acute Exacerbation of Asthma? Annals of Internal Medicine, 119. http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19787/
Hughes, R. (2003). Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in treatment of severe asthma in adults: randomised placebo-controlled trial. The Lancet, 361(9375), 2114–2117.
Mangat, H. S., D’Souza, G. A., & Jacob, M. S. (1998). Nebulized magnesium sulphate versus nebulized salbutamol in acute bronchial asthma: A clinical trial. European Respiratory Journal, 12(2), 341–344. https://doi.org/10.1183/09031936.98.12020341
Mansour, G. K., & Yousif, A. (2025). Magnesium Sulfate in Pediatric Emergency Medicine: Pharmacology, Evidence, and Clinical Applications. Cureus. https://doi.org/10.7759/cureus.91672
Mao, Z., Zhu, X., Zheng, P., Wang, L., Zhang, F., & Chen, L. (2025). Global, regional, and national burden of asthma from 1990 to 2021: A systematic analysis of the global burden of disease study 2021. Chinese Medical Journal Pulmonary and Critical Care Medicine, 3(1), 50–59. https://doi.org/10.1016/j.pccm.2025.02.005
Mohammed, S., & Goodacre, S. (2007). Intravenous and nebulised magnesium sulphate for acute asthma: Systematic review and meta-analysis. Emergency Medicine Journal, 823–830. https://doi.org/10.1136/emj.2007.052050
Montserrat, J. M. (1995). Gas exchange response to intravenous aminophylline in patients with a severe exacerbation of asthma. European Respiratory Journal, 8(1), 28–33.
Nair, P., Milan, S. J., & Rowe, B. H. (2012). Addition of intravenous aminophylline to inhaled beta2-agonists in adults with acute asthma. Cochrane Database of Systematic Reviews, 2012(12). https://doi.org/10.1002/14651858.CD002742.pub2
Ohta, K., Nakagome, K., Akiyama, K., Matsumura, Y., Kudo, S., & Mano, J. (1996). Aminophylline is effective on acute exacerbations of asthma in adults - objective improvements in peak flow, spirogram, arterial blood gas measurements and lung sounds. Clinical and Experimental Allergy.
Pérez, V. H. E., Mosquera, F. E. C., de la Rosa Caldas, M., Rodríguez, O. A. P., & Liscano, Y. (2025). Effectiveness of Intravenous and Nebulized MgSO4 in Children with Asthma Exacerbation: A Systematic Review and Meta-Analysis of Clinical Trials. Children. https://doi.org/10.3390/children12081064
Sarhan, H. A., El-Garhy, O. H., Ali, M. A., & Youssef, N. A. (2016). The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma. Drug Design, Development and Therapy, 10, 1927–1933. https://doi.org/10.2147/DDDT.S103147
Schenk, P., Vonbank, K., Schnack, B., Haber, P., Lehr, S., & Smetana, R. (2001). Intravenous magnesium sulfate for bronchial hyperreactivity: A randomized, controlled, double-blind study. Clinical Pharmacology & Therapeutics, 69(5), 365–371. https://doi.org/10.1067/mcp.2001.114926
Self, T. H., Abou-Shala, N., Burns, R., Stewart, C. F., Ellis, R. F., & Tsiu, S. J. (1990). Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics: Does aminophylline add any benefit? Chest, 98(6), 1317–1321. https://doi.org/10.1378/chest.98.6.1317
Sharma, S. K., Bhargava, A., & Pande, J. N. (1994). Intravenous magnesium sulphate in acute severe asthma. Pulmonary Immunology and Molecular Biology.
Singh, A. K., Gaur, S., & Kumar, R. (2008). A Randomized Controlled Trial of Intravenous Magnesium Sulphate as an Adjunct to Standard Therapy in Acute Severe Asthma. Iranian Journal of Allergy, Asthma and Immunology.
Tiffany, B. R., Berk, W. A., Todd, I. K., & White, S. R. (1993). Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations. Chest, 104(3), 831–834. https://doi.org/10.1378/chest.104.3.831
Wrenn, K., Slovis, C. M., Murphy, F., Greenberg, R. S., & Emory, F. (1991). Aminophylline Therapy for Acute Bronchospastic Disease in the Emergency Room. Annals of Internal Medicine. http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19732/
Wu, M. (2026). Global Epidemiology of Asthma: An Ecological Study of GBD 2021 Results and Forecasts to 2040. Journal of Preventive Medicine and Healthcare, 8(1), 1043. https://doi.org/10.31981/GBD.2021.0
Al-Shamrani, A., Al-Harbi, A. S., Bagais, K., Alenazi, A., & Alqwaiee, M. (2019). Management of asthma exacerbation in the emergency departments. International Journal of Pediatrics and Adolescent Medicine, 61–67. https://doi.org/10.1016/j.ijpam.2019.02.001
Ambro?ej, D., Adamiec, A., Forno, E., Orzo?ek, I., Feleszko, W., & Castro-Rodriguez, J. A. (2024). Intravenous magnesium sulfate for asthma exacerbations in children: Systematic review with meta-analysis. Paediatric Respiratory Reviews, 23–30. https://doi.org/10.1016/j.prrv.2024.01.003
Aralihond, A., Shanta, Z., Pullattayil, A., & Powell, C. V. E. (2020). Treating acute severe asthma attacks in children: Using aminophylline. Breathe, 16(4), 1–9. https://doi.org/10.1183/20734735.0081-2020
Bessmertny, O., DiGregorio, R. V, Cohen, H., Becker, E., Looney, D., & Golden, J. (2002). A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults. Annals of Emergency Medicine, 39(6), 585–591. https://doi.org/10.1067/mem.2002.123300
Bloch, H., Silverman, R., Mancherje, N., Grant, S., Jagminas, L., & Scharf, S. M. (1995). Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma. Chest, 107(6), 1576–1581. https://doi.org/10.1378/chest.107.6.1576
Chen, X., Ma, D., Li, H., Liu, Y., Xu, G., & Deng, X. (2025). Temporal trends and future projections of incidence rate and mortality for asthma in China: an analysis of the Global Burden of Disease Study 2021. Frontiers in Medicine, 12. https://doi.org/10.3389/fmed.2025.1529636
Dabbs, W., Bradley, M. H., & Chamberlin, M. (2024). Acute Asthma Exacerbations: Management Strategies. American Family Physician. https://www.aafp.org/afp
Elsakaya, M. S., Ismail, M. T., Hamed, M. N., Hendawy, H. A., & Omera, M. A. (2018). Nebulized magnesium sulfate in acute asthma. Medicine Science | International Medical Journal, 391. https://doi.org/10.5455/medscience.2018.07.8796
Gandia, F., Guénard, H., Sriha, B., Tabka, Z., & Rouatbi, S. (2012). Inhaled magnesium sulphate in the treatment of bronchial hyperresponsiveness. Magnesium Research, 25(4), 168–176. https://doi.org/10.1684/mrh.2012.0323
Gayen, S., Dachert, S., Lashari, B. H., Gordon, M., Desai, P., & Criner, G. J. (2024). Critical Care Management of Severe Asthma Exacerbations. Journal of Clinical Medicine. https://doi.org/10.3390/jcm13030859
Healthcare Improvement Scotland. (2019). British guideline on the management of asthma: a national clinical guideline. Healthcare Improvement Scotland.
Hossein, S., Pegah, A., Davood, F., Said, A., Babak, M., & Mani, M. (2016). The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: A randomized clinical trial. American Journal of Emergency Medicine, 34(5), 883–886. https://doi.org/10.1016/j.ajem.2016.01.024
Huang, D., O’Brien, R. G., Harman, E., Aull, L., Reents, S., & Visser, J. (1993). Does Aminophylline Benefit Adults Admitted to the Hospital for an Acute Exacerbation of Asthma? Annals of Internal Medicine, 119. http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19787/
Hughes, R. (2003). Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in treatment of severe asthma in adults: randomised placebo-controlled trial. The Lancet, 361(9375), 2114–2117.
Mangat, H. S., D’Souza, G. A., & Jacob, M. S. (1998). Nebulized magnesium sulphate versus nebulized salbutamol in acute bronchial asthma: A clinical trial. European Respiratory Journal, 12(2), 341–344. https://doi.org/10.1183/09031936.98.12020341
Mansour, G. K., & Yousif, A. (2025). Magnesium Sulfate in Pediatric Emergency Medicine: Pharmacology, Evidence, and Clinical Applications. Cureus. https://doi.org/10.7759/cureus.91672
Mao, Z., Zhu, X., Zheng, P., Wang, L., Zhang, F., & Chen, L. (2025). Global, regional, and national burden of asthma from 1990 to 2021: A systematic analysis of the global burden of disease study 2021. Chinese Medical Journal Pulmonary and Critical Care Medicine, 3(1), 50–59. https://doi.org/10.1016/j.pccm.2025.02.005
Mohammed, S., & Goodacre, S. (2007). Intravenous and nebulised magnesium sulphate for acute asthma: Systematic review and meta-analysis. Emergency Medicine Journal, 823–830. https://doi.org/10.1136/emj.2007.052050
Montserrat, J. M. (1995). Gas exchange response to intravenous aminophylline in patients with a severe exacerbation of asthma. European Respiratory Journal, 8(1), 28–33.
Nair, P., Milan, S. J., & Rowe, B. H. (2012). Addition of intravenous aminophylline to inhaled beta2-agonists in adults with acute asthma. Cochrane Database of Systematic Reviews, 2012(12). https://doi.org/10.1002/14651858.CD002742.pub2
Ohta, K., Nakagome, K., Akiyama, K., Matsumura, Y., Kudo, S., & Mano, J. (1996). Aminophylline is effective on acute exacerbations of asthma in adults - objective improvements in peak flow, spirogram, arterial blood gas measurements and lung sounds. Clinical and Experimental Allergy.
Pérez, V. H. E., Mosquera, F. E. C., de la Rosa Caldas, M., Rodríguez, O. A. P., & Liscano, Y. (2025). Effectiveness of Intravenous and Nebulized MgSO4 in Children with Asthma Exacerbation: A Systematic Review and Meta-Analysis of Clinical Trials. Children. https://doi.org/10.3390/children12081064
Sarhan, H. A., El-Garhy, O. H., Ali, M. A., & Youssef, N. A. (2016). The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma. Drug Design, Development and Therapy, 10, 1927–1933. https://doi.org/10.2147/DDDT.S103147
Schenk, P., Vonbank, K., Schnack, B., Haber, P., Lehr, S., & Smetana, R. (2001). Intravenous magnesium sulfate for bronchial hyperreactivity: A randomized, controlled, double-blind study. Clinical Pharmacology & Therapeutics, 69(5), 365–371. https://doi.org/10.1067/mcp.2001.114926
Self, T. H., Abou-Shala, N., Burns, R., Stewart, C. F., Ellis, R. F., & Tsiu, S. J. (1990). Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics: Does aminophylline add any benefit? Chest, 98(6), 1317–1321. https://doi.org/10.1378/chest.98.6.1317
Sharma, S. K., Bhargava, A., & Pande, J. N. (1994). Intravenous magnesium sulphate in acute severe asthma. Pulmonary Immunology and Molecular Biology.
Singh, A. K., Gaur, S., & Kumar, R. (2008). A Randomized Controlled Trial of Intravenous Magnesium Sulphate as an Adjunct to Standard Therapy in Acute Severe Asthma. Iranian Journal of Allergy, Asthma and Immunology.
Tiffany, B. R., Berk, W. A., Todd, I. K., & White, S. R. (1993). Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations. Chest, 104(3), 831–834. https://doi.org/10.1378/chest.104.3.831
Wrenn, K., Slovis, C. M., Murphy, F., Greenberg, R. S., & Emory, F. (1991). Aminophylline Therapy for Acute Bronchospastic Disease in the Emergency Room. Annals of Internal Medicine. http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19732/
Wu, M. (2026). Global Epidemiology of Asthma: An Ecological Study of GBD 2021 Results and Forecasts to 2040. Journal of Preventive Medicine and Healthcare, 8(1), 1043. https://doi.org/10.31981/GBD.2021.0
