Clinical Question

Is magnesium sulfate an effective addition to usual care for adults with chronic obstructive pulmonary disease (COPD) exacerbations?

Evidence-Based Answer

Adding intravenous magnesium to standard care for adults with COPD exacerbations may decrease hospital admissions and the length of hospitalization. Seven people with COPD exacerbations would need to be treated with intravenous magnesium to prevent one admission. Patients treated with intravenous magnesium who require hospitalization have a decreased length of stay (mean difference = 2.7 days). There is insufficient evidence about the frequency and severity of adverse events.¹ (Strength of Recommendation: A, consistent, good-quality patient-oriented evidence.)

Practice Pointers

Acute exacerbations of COPD are common, with 7% to 33% of patients being hospitalized for severe exacerbations per year, depending on their baseline severity of illness.² The authors of the Cochrane review sought to determine the effectiveness and safety of nebulized and intravenous magnesium sulfate in treating COPD exacerbations in terms of hospitalization rate and other factors.

This Cochrane review included 762 patients in 11 randomized controlled trials conducted in Iran, New Zealand, Nepal, Turkey, the United Kingdom, Tunisia, and the United States.¹ The trials investigated magnesium, administered via intravenous or nebulized routes, in addition to standard therapies in adults 35 years and older with acute COPD exacerbations in emergency department settings.

Seven studies investigated intravenous magnesium sulfate plus standard care vs. placebo plus standard care. Three studies examined nebulized magnesium sulfate plus standard care vs. placebo plus standard care. One study investigated nebulized magnesium sulfate plus intravenous magnesium sulfate vs. nebulized ipratropium bromide plus intravenous saline. The trials described weight-based magnesium sulfate dosing of 40 mg per kg of body weight, up to a maximum dose of 2 g administered by infusion over 20 minutes.

The primary outcomes were hospital admission, the need for noninvasive ventilation or assisted ventilation, intensive care unit admission, and serious adverse events. Secondary outcomes included the length of hospital stay, mortality, other adverse events, lung function, blood gas measurements, and dyspnea score, as measured by the dyspnea severity score and the Borg dyspnea scale. Lower scores on the dyspnea severity and Borg scales indicate less severe dyspnea. Although it is unclear what a minimal clinically significant difference on the dyspnea severity scale would be, a minimal clinically significant difference on the Borg scale is only a one-unit difference.³

This review showed that fewer patients receiving intravenous magnesium sulfate plus standard treatment vs. standard treatment alone were hospitalized (number needed to treat [NNT] = 7; 95% CI, 3 to 32) and that their length of hospital stay was shorter (mean difference = −2.7 days; 95% CI, −0.66 to −4.73). Patients receiving intravenous magnesium sulfate had a slightly lower dyspnea score (standardized mean difference = −1.4; 95% CI, −1.83 to −0.96). There was no significant difference in the need for noninvasive ventilation; no serious adverse events were reported in either group. Patients who received nebulized magnesium sulfate plus standard treatment experienced no improvement in hospitalization or intensive care unit admission rates, compared with standard treatment alone, and there was no difference in the use of noninvasive ventilation, length of hospital stay, or dyspnea score. Serious adverse events were not assessed in those studies.

Patients who received nebulized plus intravenous magnesium sulfate compared with nebulized ipratropium bromide, both in addition to standard treatment, experienced no difference in length of hospital stay or rates of hospitalization, endotracheal intubation, or serious adverse events.

International guidelines recognize the effectiveness of intravenous magnesium sulfate as a second- or third-line agent for treating severe asthma exacerbations.⁴ However, U.S. and international guidelines do not include intravenous magnesium sulfate for the management of severe COPD exacerbations.^5,6

The findings of this Cochrane review suggest that family physicians should be prepared to discuss the role of intravenous magnesium sulfate as an adjunctive therapy for severe COPD exacerbations that do not respond to initial treatments.

The practice recommendations in this activity are available at https://www.cochrane.org/CD013506.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army, the U.S. Department of Defense, or the U.S. government.