Magnesium sulfate (MgSO4) has been proposed as an adjunct therapy for severe and potentially fatal asthma exacerbations. If used correctly, MgSO4 has an excellent safety profile. Several studies were conducted to investigate its role and provided evidence that MgSO may be beneficial in the treatment of adult patients with severe or life-threatening exacerbation. To find the effects of intravenous (IV) or nebulized magnesium sulfate in acute asthma, many randomized and quasi‐randomized trials were conducted. IV MgSO4 as an adjunct to standard treatment was found to be beneficial in the treatment of severe or life-threatening exacerbation; however, the role of nebulized MgSO4 is less evident due to the lack of sufficient evidence.
Acute asthma
Asthma is inflammation and obstruction of the bronchial tubes. Acute asthma is characterized by an increase in symptoms caused by tightening of the muscles surrounding the bronchial tubes, which restricts air flow. It’s also referred to as an asthma attack or an acute asthma exacerbation. Common allergens, air irritants, some health conditions can trigger acute asthma exacerbation.
Acute severe asthma is defined as a severe asthma attack that does not improve after taking asthma medications. This type of asthma is potentially fatal. Severe asthma is unresponsive to repeated courses of beta-agonist therapy.
Magnesium Sulfate & uses of magnesium sulfate
Magnesium sulfate is a magnesium salt with a molecular weight of 120.37 g/mol and the counter ion is sulfate.
It functions as an anticonvulsant, cardiovascular drug, analgesic, calcium channel blocker, anesthetic, anti-arrhythmia drug. It is a metal sulfate and a magnesium salt. Excessive magnesium sulfate use can result in serious, life-threatening side effects.
Magnesium sulfate (MgSO4) has been proposed as an adjunct therapy for severe and potentially fatal asthma exacerbations. In theory, magnesium can inhibit calcium influx into the cytosol, release histamine from mast cells, and release acetylcholine from cholinergic nerve endings and thus induce bronchial smooth muscle relaxation in a dose-dependent manner. It may also enhance the bronchodilator effect of a β2-agonist by increasing receptor affinity.
In the literature in 1936, the clinical use of magnesium for asthma was first reported. Okayama et al. reported rapid bronchodilating effects of IV MgSO4 infusion in 10 asthma patients in 1987. Its effectiveness in preventing endotracheal intubation and mechanical ventilation in an elderly asthma patient with severe exacerbation was also reported in 1989.
Skobeloff et al. conducted the first randomized controlled trial (RCT) to investigate its efficacy in 1989. Several RCTs and meta-analyses have been conducted since then. Simultaneously, the use of nebulized MgSO4 has piqued scientific interest. Current guidelines recommend IV MgSO4 as an adjunct therapy to improve pulmonary functions and reduce hospitalization in certain patients with severe and life-threatening acute exacerbations that have not responded to initial treatments, whereas the evidence for nebulized magnesium is weaker.
Intravenous magnesium sulfate
According to the findings of a Cochrane review conducted by Rowe et al., IV MgSO4 as an adjunct to standard treatment was beneficial in severe acute asthma patients, to improve lung functions and reduce the hospital admission rate.
Rodrigo et al.’s findings were not consistent, but the number of pooled studies and patients was lower than in the Cochrane review.
According to Mohammed et al.’s recent reviews, the efficacy was only marginal on pulmonary function and not significant on hospital admission. Their analyses, however, were not limited to severe exacerbations.
Notably, nebulized ipratropium bromide was used as the standard treatment in two recent RCTs. Even in subgroups of life-threatening exacerbation, Bradshaw et al.’s trial did not show an additional benefit of 1.2 g IV MgSO4. The trials by Singh et al., on the other hand, showed a positive effect on forced expiratory volume in 1 second (FEV1) percent predicted but had limitations due to a smaller number of participants and a single-blind design.
Guidelines currently recommend nebulized ipratropium as an additional bronchodilator for moderate exacerbation, and it is widely used in practice. As a result, the efficacy of IV MgSO4 should be investigated further in the context of current treatment guidelines.
However, because of its low toxicity, MgSO4 should be used in patients with severe life-threatening asthma exacerbations who do not respond to standard treatments.
Nebulizer for asthma
A nebulizer is a small machine that produces a mist from liquid medication, allowing for faster and easier medication absorption into the lungs. A nebulizer cannot be used to deliver every medication. Certain medications, such as steroids, must be administered using an inhaler.
A nebulizer uses pressurized air to deliver liquid medication. While people with asthma typically use both nebulizers and inhalers, a nebulizer may be easier to use on occasion, especially in young children who may not have the proper technique for an inhaler.
Blitz et al. found that nebulized MgSO4 improved pulmonary functions in severe subgroups. The findings, however, were based on only 87 adult asthmatics from two trials. More trials were examined in a recent review by Mohammed et al., who discovered that nebulized MgSO4 had marginal benefits on pulmonary functions and hospital admission rates. They concluded that the evidence is insufficient to draw conclusions because of the heterogeneity in treatment doses, the severity of patients, and the small number of pooled studies.
In Gallegos-Solórzano et al.’s trial, nebulized MgSO4 was found to improve post-bronchodilator lung functions and oxygen saturation. It also decreased admission rates at 90 minutes when added to nebulized albuterol and ipratropium. However, the largest trial failed to demonstrate any benefit of additional MgSO4 therapy. From the trials, it can be concluded that the use of nebulized MgSO4 may be beneficial in treating patients with severe exacerbations; however, larger trials are required for more evidence.
Effects of IV vs. nebulized magnesium sulfate upon respiratory function and hospital admission
According to a postal survey of all adult emergency departments (EDs) in the UK, IV MgSO4 is now used in 93 percent of EDs, and more than 80 percent of severe or life-threatening asthma patients receive the therapy. The agent was used to improve breathlessness (70 percent) or to reduce admissions (51 percent). The main reason for the low use of nebulized MgSO4 (1%) was a lack of evidence.
Mohammed et al. showed the effects (upon respiratory function and hospital admission) of IV vs. nebulized magnesium sulfate.
Mohammad et al’ study showed that intravenous magnesium sulfate should be the standard treatment for children with acute severe asthma who have not responded to initial treatment, while the role of nebulized magnesium sulfate in children and the roles of both nebulized and intravenous magnesium sulfate in adults require further investigation.
Meanwhile, a large randomized trial comparing nebulized and intravenous magnesium sulfate to each other and placebo is needed in adults with acute severe asthma to see if magnesium sulfate can improve symptoms and reduce hospital admissions. More research on nebulized magnesium sulfate in children is currently being conducted.
Adult patients with severe or life-threatening exacerbation may benefit from IV MgSO4 as an adjunct to standard treatment. Due to a lack of evidence, the role of nebulized MgSO4 is less clear.
References:
- https://www.medicalnewstoday.com/articles/acute-asthma#prevention
- https://www.cedars-sinai.org/health-library/diseases-and-conditions/a/acute-severe-asthma.html
- https://pubchem.ncbi.nlm.nih.gov/compound/Magnesium-sulfate#section=Other-Experimental-Properties
- https://www.healthline.com/health/asthma-nebulizer-machine#how-do-nebulizers-work
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269605/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658351/
