Source: Kew KM, Kirtchuk L, Michell CI. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database of Systematic Reviews 2014.
Study Population: 11 studies with 1769 primarily adult patients with asthma exacerbation
Efficacy Endpoints: Hospitalization
Harm Endpoints: Adverse events (flushing, fatigue, nausea, headache, hypotension)
Narrative: Asthma is a common chronic respiratory disease with acute exacerbations recognized clinically by the signs and symptoms of dyspnea, cough, chest tightness, and wheezing. In the United States approximately 25 million individuals currently have asthma and in 2017, asthma exacerbations accounted for approximately 1.8 million emergency department (ED) visits and 3,500 deaths.1 Acute asthma exacerbations range in severity from mild to deadly. The first line medications for the treatment of asthma exacerbations in the emergency department are oxygen (as needed to maintain arterial oxygen saturation of 93-95%), short-acting beta2-agonists, and systemic corticosteroids, with ipratropium bromide being recommended for severe exacerbations. In cases of treatment failure or severe exacerbations, some studies have recommended intravenous magnesium sulfate.2 Magnesium is believed to treat asthma exacerbations through numerous mechanisms including direct smooth muscle relaxation, an anti-inflammatory effect, and by blocking calcium ion influx into bronchial smooth muscle.3, 4 The goal of the systematic review summarized here is to provide an updated review of the safety and efficacy of intravenous magnesium sulfate in the treatment of moderate to severe asthma exacerbations in the ED.5
The systematic review discussed here included fourteen randomized controlled trials composed of 2313 primarily adult patients who presented to the ED for acute asthma exacerbations of at least moderate severity.6 Patients were excluded if they had diabetes, congestive cardiac disease, hypertension, chronic renal failure, temperature > 38 °C , pneumonia, pregnancy, or required ventilation. Eleven studies with 1769 patients contributed to the primary outcome analysis. The trials compared the efficacy of intravenous magnesium sulfate in any dose (typically 1.2 g - 2 g) to placebo. In both the magnesium sulfate and placebo groups, patients were treated with standard medications for acute asthma. The primary outcome was hospitalization. Secondary outcomes included adverse medication effects, ED treatment duration, intensive care unit admissions, vital signs, forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF), and symptom scale scores. These secondary outcomes were mostly of low to moderate quality of evidence and, with the exception of adverse medication effects, FEV1, and PEF are omitted from this summary as they do not provide additional patient-centric information.5
According to the results of the Cochrane meta-analysis, intravenous magnesium sulfate therapy was associated with a reduced risk of hospitalization (Odds ratio [OR]: 0.75; 95% confidence interval [CI]: 0.60 to 0.92; absolute risk difference [ARD]: 7.1%; number needed to treat [NNT]: 14), an increased FEV1 % predicted (Mean difference [MD]: 4.41%; 95% CI: 1.75 to 7.06; 4 studies, 523 patients, highquality evidence), and an increased PEF % predicted (MD: 4.78%; 95% CI: 2.14 to 7.43; 3 studies, 1129 patients, high-quality evidence).5
Adverse events were inconsistently reported and could not be aggregated. Commonly cited adverse events were mild and included flushing, fatigue, nausea, headache, and hypotension. Most of the serious adverse events that occurred (death, intubation, arrhythmia), were believed to be due to the asthma exacerbation rather than the intravenous magnesium sulfate. In the largest trial included in this meta-analysis, intravenous magnesium sulfate was associated with a slightly increased risk of any adverse events (OR: 1.68; 95% CI: 1.07 to 2.63; ARD: 3.3%; Number Needed to Harm [NNH]: 30). The study was not powered to determine differences between serious adverse events.7
There is however good data from the obstetrics literature to support the safety of intravenous magnesium sulfate. In obstetrics, magnesium sulfate is used for the treatment of pre-eclampsia and eclampsia as well as for fetal neuroprotection before anticipated early preterm delivery. Typical dosing in obstetrics is a 4-6 gram bolus along with maintenance infusions of 1-2 g/hr, which is far higher than the dosing used in the treatment of asthma. In the most comprehensive systematic review of the maternal safety of antenatal magnesium sulfate to date, compared with placebo or no treatment, treatment with magnesium sulfate did not increase the risk of maternal death, cardiac arrest, or respiratory arrest (4 trials, 13,977 women). It did however increase the risk of ‘any side effects’ (e.g. warmth, flushing, itching, hypotension, fatigue, nausea/vomiting), which were generally mild (RR: 4.62; 95% CI: 2.42 to 8.83; ARD: 29.5%; NNH: 3; 4 trials, 13,322 women).8
Caveats: The systematic review reported the quality of evidence to be high, the risk of bias low, and no evidence of significant heterogeneity. However, there are several limitations. First, this metaanalysis was not able to determine the ideal dose of magnesium, and there was some variation in each of these among the trials. The most common dose administered in the trials was 1 to 2 grams slow intravenous infusion over 15-30 minutes. Second, the criteria for hospital admission was not standardized and varied between trials, limiting the generalizability of the findings. Third, although there is high quality data showing an improvement in spirometric values, which may help explain the improved primary outcome, the improvement is minor (less than 5%), and the clinical significance of these changes is questionable. Fourth, in some studies evaluating the safety and efficacy of magnesium therapy, patients with life threatening asthma were excluded. This is important to keep in mind because outside of clinical trials, these patients are the ones who are most often considered for magnesium therapy. However, as they are often excluded from studies, there is limited direct evidence to support magnesium therapy for these patients. Lastly, the data was not conducive to determine the specific subgroup of patients most likely to benefit from this treatment. Future large trials are needed to allow analysis of treatment benefits in subgroups classified based on disease severity.
Current guidelines do not recommend intravenous magnesium sulfate for routine mild to moderate asthma exacerbations. They instead recommend considering it only for patients with severe exacerbations or those who have failed initial treatment.2
In summary, for adults presenting to the ED with moderate to severe asthma exacerbations, intravenous magnesium sulfate therapy used as an adjunct to routine treatment (oxygen, short acting beta agonists and systemic corticosteroids) or when these treatments fail, reduces the need for hospitalization and likely has minimal adverse events. Therefore, we have assigned a color recommendation of Green (benefits > harm) to this treatment.
The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.
See theNNT.com's previous reviews of this topic:
Intravenous Magnesium Sulfate Given During an Asthma Attack, January 10, 2010
Author: John Conway, MD; Benajmin Friedman, MD
Supervising Editor: Shahriar Zehtabchi, MD
Published/Updated: July 1, 2020
The title bar is color-coded with our overall recommendation.