Magnesium sulfate for severe acute asthma in children

Magnesium is an abundant intracellular cation that has been used for years in the treatment of hyper-tension and seizures associated with eclampsia of pregnancy as well as used as a tocolytic agent.(1) Over sixty years ago, Haury showed that magnesium sulfate (MgSO(4)) could produce bronchodilation in asthmatics.(2) However, interest in magnesium sulfate as a potential therapy for acute asthma surfaced in the late 1980s following a series of studies demonstrating that magnesium produced dose-dependent bronchodilation. The precise mechanism by which magnesium produces smooth muscle relaxation is not known, but it is thought to act by enhancing calcium uptake in the sarcoplasmic reticulum(3) and/or as a calcium antagonist.(4) In addition, magnesium is a cofactor regulating a number of enzymatic and cellular activities in the body, including adenyl cyclase and sodium-potassium ATP-ase, potentially enhancing the effects of β2-agonists.(5) Other potential beneficial mechanisms in asthma include inhibition of acetylcholine release from cholinergic nerves(6) and reduction of histamine release from mast cells.(7)It is not clear whether magnesium acts as a functional antagonist to bronchoconstriction like the β2-agonists and theophylline or a specific antagonist like anticholinergics and antihistamines. Studies showing attenuation of the bronchoconstriction from histamine and methacholine would suggest functional antagonism.(8,9) Some suggest that the response to intravenous magnesium sulfate is dependent upon achieving serum magnesium concentrations of 4-6 mg/dL (1.6-2.4 mmol/L).(10) These values are similar to those that are employed to achieve tocolysis (4-8 mg/dL) and about one half those associated with severe toxicity of respiratory failure, cardiac arrhythmias and death (12-15 mg/ dL).(1) It should be pointed out that studies have not reported lower magnesium concentrations in asthmatics than controls although one study reported correlation with bronchial hyperresponsiveness and intracellular magnesium concentrations in asthmatics. (11-13) Thus, it is unlikely that the bronchodilator response to magnesium is a result of restoring normal homeostasis but most likely a function of its direct antagonistic effects on intracellular calcium activity.