Magnesium has bronchodilating properties attributed to its role as a powerful relaxant of smooth muscle. It has not been widely developed as a therapeutic agent because of problems with excessive systemic vasodilation, hypotension, and unpleasant symptoms. In addition, studies have not demonstrated benefit in stable asthma, and studies in acute exacerbations have shown conflicting results. Hughes and colleagues conducted a randomized, placebo-controlled trial of nebulized isotonic magnesium sulfate as an adjunct to albuterol in the emergency treatment of acute asthma.
They studied patients 16 to 65 years of age who presented to two emergency departments in New Zealand because of severe asthma during one year. For inclusion, patients had to be diagnosed with asthma and have a forced expiratory volume in one second (FEV1) of less than 50 percent of predicted value. Patients with pneumonia, hypotension, fixed airway obstruction, cardiac or renal disease, or pregnancy, and those requiring immediate intubation were excluded from the study. After assessment, all patients were given 2.5 mg of albuterol by jet nebulization plus 100 mg of intravenous hydrocortisone.
If the FEV1 remained below 50 percent of predicted after 30 minutes, the patients were randomized to receive 2.5 mg of albuterol mixed with either 2.5 mL of isotonic magnesium sulfate or 2.5 mL of isotonic saline on three occasions at 30-minute intervals. Patients and staff were blinded to treatment allocation. Vital signs and FEV1 were recorded before and 30 minutes after each nebulization treatment. Patients whose FEV1 remained below 50 per-cent of predicted value after the final treatment were recommended for hospital admission.
|Baseline FEV1< 30% predicted||Baseline FEV1,> 30% predicted|
|FEV1measurements||Magnesium, n = 12||Saline, n = 12||Magnesium, n = 16||Saline,n = 12|
|At baseline (L)||0.90 (0.35)||0.82 (0.17)||1.50 (0.30)||1.58 (0.30)|
|At 90 minutes (L)||1.73 (0.70)||1.01 (0.22)||2.14 (0.71)||2.09 (0.68)|
The 28 eligible patients assigned to receive magnesium were comparable to the 24 patients who received saline in all significant respects. Thirty minutes after the third nebulizer treatment, the mean FEV1 in patients treated with magnesium was 1.96 L compared with 1.55 L in the control group. As a percentage of the predicted value, the FEV1 results were 51.2 percent in those treated with magnesium compared with 41.3 percent in the control group. Compared with baseline measurements, the FEV1 improved by 0.72 L in the magnesium-treated group and by 0.35 L in the control group. Twelve patients treated with magnesium and 17 treated with saline were admitted to the hospital following treatment in the emergency department. The differences in FEV1 improvement between the two treatments was greatest in patients with life-threatening asthma (FEV1 less than 30 percent of predicted value). The two groups did not differ in changes in blood pressure or heart rate, and no clinically significant adverse reactions were noted (see accompanying table).
The authors conclude that isotonic magnesium sulfate enhances salbutamol nebulizer treatment of severe acute asthma and produces about twice the increase in FEV1 of albuterol alone. They stress the importance of using isotonic solutions (formulated to 250 mmol per L), the route of administration, and the careful selection and monitoring of patients. These results, plus those of previous studies, indicate that magnesium is effective in the treatment of severe exacerbations of asthma (peak expiratory flow 38 percent of predicted value) but not in situations where the FEV1 is 60 percent or more of predicted value. This selectivity could explain the apparently conflicting results of previous studies. The article and an accompanying editorial call for more research into the role of magnesium in acute severe asthma and chronic obstructive pulmonary disease.