Intravenous magnesium sulfate may reduce hospital admission rates for adults treated for acute asthma in emergency departments

Resident Focus - Volume 11, Issue 4

Reference: Cochrane Database Syst Rev. 2014 May 28;(5):CD010909 (level 2 [mid-level] evidence)

Asthma is a chronic respiratory illness involving difficulty breathing due to periodic inflammation and constriction of bronchial smooth muscles, and is estimated to affect nearly 25 million people in the United States with a prevalence of 8.2%. Adults with asthma may experience life-threatening exacerbations of their symptoms, leading to multiple emergency department visits each year. Standard treatment of asthma exacerbations includes oxygen, inhaled albuterol and ipratropium, and often IV or oral steroids. Patients with inadequate response to these treatments typically get admitted to the hospital. Although the mechanism is not completely understood, magnesium sulfate is thought to relax bronchial smooth muscle and reduce inflammation, and is currently recommended by several guidelines for acute refractory asthma despite mixed evidence regarding its efficacy (BTS/SIGN – Grade B, NHLBI – Evidence B). As our healthcare system continues to work to reduce unnecessary hospitalizations, could earlier inclusion of IV magnesium sulfate into standard care help reduce the need for hospital admission for adult patients with asthma exacerbations?

To investigate this question, a recent Cochrane review identified 14 randomized placebo- controlled trials evaluating IV magnesium sulfate for the treatment of 2,313 adult patients presenting to emergency departments with acute asthma exacerbations. All studies included in the meta-analysis evaluated 1.2 g or 2 g of IV magnesium sulfate infused over 15-30 minutes, and most study durations ranged from 45 minutes to 4 hours. The analysis was limited by clinical heterogeneity in administered regimens, patient populations, and time of magnesium sulfate initiation. Patients received standard therapies including oxygen, nebulized short-acting beta-2 agonist, and steroids, although the exact regimens varied. In addition, 4 studies included administration of nebulized ipratropium bromide to all patients, and 3 studies included administration of theophylline. Heterogeneity in patient populations included one high-quality trial with relatively older and sicker patients and patients with a history of chronic obstructive pulmonary disorder (COPD), while 4 other studies excluded patients with COPD. Time between presentation of patients to the emergency department and IV magnesium sulfate initiation also varied, with some studies giving patients IV magnesium with standard treatment and others waiting for several hours of no response to standard treatment (up to 6 hours in 1 high-quality trial) before administration.

In the primary meta-analysis of 11 trials with 1,769 adult patients, IV magnesium sulfate was associated with a significant reduction in hospital admission rates compared to placebo (OR 0.75, 95% CI 0.60 - 0.92, NNT 8-49 with hospital admission in 56.5% of the placebo group). Three high-quality trials included in the meta-analysis had inconsistent results: one trial found no significant difference in the hospitalization rate, another found IV magnesium associated with a non-significant reduction, and a third found a significant reduction in admission rates with magnesium, but it was based on outcomes at four hours after intervention. Analyses of secondary outcomes showed that patients receiving IV magnesium also demonstrated significant improvement in forced expiratory volume in 1 second (4 studies with 523 patients), percentage predicted expiratory flow (3 studies with 1,129 patients) and peak expiratory flow (8 studies with 1,460 patients). No significant differences were observed in duration of treatment in the emergency department, hospital length of stay, intensive care admission, respiratory rate, or systolic blood pressure. Although there was inconsistent reporting of adverse events, headache, hypotension, flushing, fatigue, and nausea were associated with the administration of IV magnesium in some of the trials.

This systematic review supports the current guideline recommendations for treatment of acute refractory asthma with IV magnesium, but importantly also suggests that routine administration of IV magnesium sulfate concurrently with standard treatments may reduce hospitalization rates in patients presenting with an acute asthma exacerbation. However, given the variable definitions of refractory asthma among studies, inconsistency in reporting adverse events, and absence of evaluation of the safety profile of IV magnesium, its use should be considered on a patient-by-patient basis at this time.

For more information, see Magnesium sulfate for acute asthma in adults and adolescents in Dynamed Plus. DynaMed users click here.