Abstract & Commentary
Synopsis: Magnesium sulfate, 2 g given IV as a single dose in addition to inhaled beta agonists and systemic steroids, improves airflow (but not symptoms or admission rates) in patients presenting to the emergency department with acute severe asthma.
Source: Silverman RA, et al. IV magnesium sulfate in the treatment of acute severe asthma: A multicenter randomized controlled trial. Chest. 2002;122(2): 489-497.
In a double-blind, multicenter, randomized, controlled trial, patients presenting to 8 hospital emergency departments with acute severe asthma received nebulized albuterol, IV corticosteroids, and either placebo or 2 g of magnesium sulfate intravenously as a single dose 30 minutes after arrival. Silverman and associates included adult patients with asthma (but not COPD or other chronic cardiopulmonary disease) who presented with an acute attack and had no evidence for pneumonia or other complicating condition. Only patients who were able to perform spirometry and had a forced expiratory volume in the first second of 30% or less of the predicted value (FEV1%) were enrolled. A decision whether to admit the patient to the hospital was made using standardized criteria 4 hours after presentation. The primary outcome variable was FEV1% 4 hours after presentation; secondary variables included hospital admission rates, dyspnea as assessed by the Borg 10-point scale, peak expiratory flow, and changes in vital signs.
After exclusion of 6 patients inadvertently enrolled at more than one study hospital, all randomized patients (n = 248) were included using intention-to-treat analysis. At 4 hours, patients who received the dose of magnesium sulfate had slightly but significantly larger mean FEV1% (48.2 vs 43.5; P = 0.045) and peak expiratory flow (272 vs 236 L/min; P < 0.01). When stratification according to initial FEV1% was done, a substantially greater improvement was observed in patients with initial values 25% or less (mean difference, 9.7%; 95% CI, 4.0-15.3%; P = 0.001) than in those with less severe obstruction (mean difference not significant). Patients who received magnesium had significantly lower pulse rates at 4 hours than patients who received placebo, but there were no differences in other clinical variables, Borg dyspnea assessment, or hospital admission rates (32% in each group).
Comment by David J. Pierson, MD
This study shows that 2 g of IV magnesium sulfate administered once as an adjunct to standard therapy improves pulmonary function in adult patients presenting to the emergency department with acute severe asthma. The effect is relatively small, observed primarily in patients with the most severe initial obstruction (FEV1 25% or less of predicted), and unassociated with changes in dyspnea or rates of hospitalization.
The findings of Silverman et al are consistent with an increasing body of data that adding a single dose of IV magnesium is safe and beneficial in the initial treatment of acute severe asthma. This was discussed in a recent systematic review of current data on the emergency department management of this condition by Rowe and colleagues,1 who summarized the results of several randomized controlled trials as shown in the Figure (shown below.)
Although magnesium has been shown to have a detectable effect, beta agonists and systemic corticosteroids are the cornerstones of initial treatment in acute severe asthma. Delivery of beta agonists via nebulizer or metered-dose inhaler with spacer device appears to be similarly efficacious. Recent evidence from studies involving both children and adults indicates that the addition of ipratropium bromide to early beta agonist treatment may reduce airway obstruction and hospital admissions, especially for more severe asthma. Antibiotics, intravenous beta agonists, and intravenous aminophylline have been shown to add little and may increase adverse effects.1
What is the relevance of these findings to the ICU? As far as magnesium is concerned, there are no data. The studies have all been done in the emergency department, generally with a single IV bolus of magnesium at the onset of therapy. There is no evidence that repeated dosing would increase the beneficial effect, or that any relevant outcome would be affected in patients requiring admission to the hospital. Magnesium is inexpensive and essentially without side effects when used as described in the study by Silverman et al, so that, if magnesium has not been given in the emergency department, it would be reasonable to add it as a single dose. The mainstays of therapy for acute severe asthma, however, remain beta-agonist bronchodilators given by aerosol and corticosteroids administered systemically.
Dr. Pierson is Professor of Medicine University of Washington Medical Director Respiratory Care Harborview Medical Center, Seattle, WA.
1. Rowe BH, et al. Evidence-based treatments for acute asthma. Respir Care. 2001;46(12):1380-1390.