Magnesium Sulfate for Asthma
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Magnesium Sulfate for Asthma
Rosello reported the first successful use of magnesium sulfate (MgSO4) as a bronchodilating agent for asthma in 1936. In 1940, Haury published his well-known report about two patients who improved significantly with MgSO4 infusion after failure to respond to subcutaneous and intramuscular adrenaline. Since then, many others have used MgSO4 as an adjunct in asthma treatment.
Magnesium (Mg) is a divalent cation that exists in the human body as an essential element. The body has about 21 grams of Mg, mostly in bone, but also intracellularly as the second most common soluble ion. Mg is a cofactor for many enzymes and is involved in neuromuscular function and energy metabolism.
Some of the most common uses of MgSO4 are for the treatment of hypomagnesium, seizures, preeclampsia/eclampsia of pregnancy, cardiac arrhythmias and as a laxative when given orally. Potential side effects with Mg are related to the serum Mg level and include flushing of the skin, somnolence, muscle weakness, hypotension, heart block, depressed central nervous system and respiratory paralysis.
Effects OF Mg
The effects of Mg on the lungs include a modest reduction in airway resistance, an increase in specific conductance and some improvement in maximal expiratory flow rate.
Mg improves pulmonary function by a number of possible mechanisms. At the cellular level, it antagonizes the transfer of calcium across cell membranes. Calcium causes:
- the activation of the contractile mechanism of airway smooth muscles,
- the initiation of the secretory system in the mast and mucus cells and
- the release of neurotransmitter at the parasympathetic nerve endings.
An excess of Mg may lower the depolarizing action of acetylcholine, resulting in a depressed excitability of the bronchial smooth muscle cells.
Inhalation of Mg produces a greater than expected degree of bronchodilation when administered with albuterol. The bronchodilating effects of Mg on the airway are sustained for approximately 30-90 minutes. The use of Mg for chronic obstructive pulmonary disease exacerbation has demonstrated a modest improvement in pulmonary function. Even in the absence of an acute exacerbation, pulmonary function studies have shown to be improved after IV Mg administration.
Clinical Trials Of MgSO4
Surprisingly, the administration of MgSO4 for asthma has actually demonstrated a mixed bag of success with its use. Results of various studies have shown anything from essentially no response in comparison to placebo controls, to profound and rather sudden improvement of life-threatening asthma after failure of conventional methods.
Two recent meta-analyses of clinical trials with MgSO4 for asthma came up with two different conclusions. The most recent meta-analysis by Rodrigo et al. examined five trials, which included 374 adult emergency department (ED) patients with moderate to severe asthma. This group concluded that “the existing evidence of adding MgSO4 to ED patients does not alter treatment outcomes…Nevertheless, the number and size of studies being pooled remain small.”
A second literature review of studies by Rowe et al. came up with a more favorable recommendation. Rowe’s group examined seven trials (five adult, two pediatric), totaling 665 ED patients with acute asthma. They concluded that “current evidence does not support the routine use of IV MgSO4 in all patients with acute asthma presenting to the ED. However, MgSO4 does appear to be safe and beneficial in patients who present with severe acute asthma.”
One possible reason why there’s been a variable response with MgSO4 for asthma may be related to the dose and manner in which it was administered. Additionally, intracellular Mg level varies substantially with age and most studies of Mg has included patients with various ages.
Investigators who gave 1 to 2 grams of MgSO4 IV over a 20-minute period failed consistently to show improvement in pulmonary function and did not reduce overall patient hospital admission rates.
On contrast, Schiermeyer described two asthmatic patients (16 and 22 years old) with impending respiratory failure who obviated the need for intubation shortly after being given a bolus of 2 grams of MgSO4 in 20 mL of normal saline over a two-minute period. Schiermeyer rationalized that a 2-gram bolus of Mg was safe because twice that dose is routinely given at his institution for preterm labor and/or preeclampsia. Other similar reports show asthmatics responded well to bolus MgSO4 infusion after failure to respond to conventional treatment with albuterol and SoluMedrol.
Some studies have shown that a normal Mg level often exists in patients with acute asthma. Serum Mg levels, however, may not reflect actual body stores. Spectrophotometric measurements of intracellular and extracellular Mg levels show a strong correlation for increased bronchial reactivity when intracellular Mg is low. In addition, beta-agonist bronchodilators such as albuterol can decrease Mg levels by 15 percent. Potassium and phosphate levels also decrease significantly with beta-agonist therapy.
The consensus for Mg in asthma is that it may be beneficial in acute severe asthma when treatment with corticosteroids, beta-agonists and other conventional adjuncts fail to improve the patient. This is in accordance with recommendations of the National Asthma Education and Prevention Program’s Guidelines for the Diagnosis and Treatment of Asthma. Further studies with parenteral bolus administration of MgSO4 may demonstrate a common purpose in refractory asthma.
Rodrigo G, Rodrigo C, Burschtin O. Efficacy of magnesium sulfate in acute adult asthma: A meta-analysis of radomized trials. Am J Emerg Med 2000;18:216-221.
Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev 2000;(2):CD001490.
Schiermeyer RP, Finkelstein JA. Rapid infusion of magnesium sulfate obviates need for intubation in status asthmaticus. Am J Emerg Med 1994;12:164-166.
Michael Hahn, a California practitioner, can be reached at email@example.com.