IV magnesium for children with moderate-to-severe asthma exacerbations was associated with increased exacerbation severity and risk for hospitalization without any acceleration in resolution, according to observational study results.
National Heart, Lung, and Blood Institute expert guidelines recommend considering IV magnesium (IV-Mg) for children with moderate-to-severe asthma exacerbations who don’t completely respond to systemic corticosteroid (CCS) and inhaled albuterol, Donald H. Arnold, MD, MPH, professor of pediatrics and director of pediatric emergency medicine research at Monroe Carell Jr. Children’s Hospital at Vanderbilt, and colleagues wrote, adding, however, that a Cochrane systematic review of randomized trials showed varying study results among children treated with IV-Mg
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Donald H. Arnold
“Moreover, recent studies showed that IV-Mg is typically administered late in the ED course, and most children are hospitalized after receiving IV-Mg,” they added. “Yet despite limited evidence for the safety and efficacy of IV-Mg in children, the use of IV-Mg increased in the United States over the past decade.”
Thus, Arnold and colleagues conducted a secondary analysis of a prospective, observational cohort to evaluate whether IV-Mg administered early in the ED decreased exacerbation severity, hospitalizations and time to spacing of inhaled albuterol to 4 hours or more.
The analysis included data from 933 children aged 5 to 17 years with acute moderate or severe asthma exacerbations in an urban tertiary children’s hospital ED between April 2008 and February 2013.
Exacerbations included cough, dyspnea, wheezing and/or chest pain as well as the need for CCS and inhaled albuterol treatments as determined by the clinical team and the Acute Asthma Intensity Research Score (AAIRS), a 0- to 16-point scale, with 16 indicating the most severe cases.
The researchers measured and recorded relevant variables before treatment and 2 and 4 hours after administration of CCS, if the participant was still in the ED. Clinicians considered use of 75 mg/kg IV-Mg if the patient showed insufficient response to CCS and inhaled albuterol after 20 minutes.
A change in AAIRS after 2 hours of ED-administered treatment served as the primary outcome.
According to the study, 301 of the participants (median age, 8.1 years; 57% Black; 67% boys) had an AAIRS of 7 or greater before treatment and were still in the ED 2 hours after treatment began. Of them, 84 (28%) received IV magnesium (IV-Mg) treatment.
IV-Mg treatment appeared associated with a 2-hour increase in AAIRS score based on the study’s propensity score (PS)-adjusted multivariable regression model ( coefficient = 0.98; 95% CI, 0.2-1.77), which denoted increased exacerbations.
Also, patients who received IV-Mg during the first 2 hours of treatment had a 5.8-fold (95% CI, 2.8-11.9) greater odds of hospitalization in the PS-adjusted multivariable regression model. In the inverse probability of treatment weighting multivariable regression model, the odds were 6.8 times greater (95% CI, 3.6-12.9).
There also was no difference in time to albuterol of every 4 hours or more among hospitalized patients (HR = 1.2; 95% CI, 0.8-1.8) in the PS covariate-adjusted Cox proportional hazards model, indicating that IV-Mg did not accelerate exacerbation resolution.
Further, the researchers found an association between IV-Mg treatment and an approximately one-point increase in exacerbation severity on the validated AAIRS. Typically, a decrease of two or more points is clinically meaningful for decisions to deescalate treatment.
The researchers called this one-point increase in clinical severity cause for concern that IV-Mg treatment may be deleterious for children who are experiencing moderate-to-severe asthma exacerbations.
“Although IV-Mg is generally safe and well-tolerated, the results of this observational study of real-world use of IV-Mg indicate that it is associated with increased exacerbation severity and hospitalizations and does not accelerate clinical improvement in hospitalized patients,” they wrote. “In the absence of a randomized controlled trial powered to examine important outcomes, there is insufficient evidence to support the use of IV-Mg for moderate and severe acute asthma exacerbations in children.”
References:
- Antoon JW, et al. Hosp Pediatr. 2021;doi:10.1542/hpeds.2020-004770.
- Pruikkonen H, et al. Eur Respir J. 2018;doi:10.1183/13993003.01579-2017.
PERSPECTIVE
For years, magnesium sulfate has been used in the care of acute asthma exacerbations among both children and adults. As an inexpensive treatment available in most hospitals, it is thought to have minimal adverse effects. It is the recommended treatment for children aged older than 4 years who present with severe asthma exacerbations. In fact, a meta-analysis of five studies found that treatment with magnesium sulfate was effective in preventing hospitalizations in children with acute asthma.
The study by Arnold and colleagues is significant, then, because it suggests further studies should assess the safety and efficacy of this treatment in both adults and children. This therapy did not lead to a reduction in rescue medication and was associated with an increased risk for severe exacerbation. The fact that it did not reduce the need of rescue medication is counterintuitive to why we use magnesium sulfate in the first place, which is because it leads to relaxation of bronchial smooth muscle.
Studies have been conflicting in this area. Another randomized trial comparing magnesium sulfate with placebo in children who were wheezing and unresponsive to bronchodilators found no difference between the two groups in reduction of respiratory distress. I agree with Arnold and colleagues that its relative safety and tolerability should not alone advocate its use.
Further studies are needed to assess its efficacy in reductions of moderate-to-severe asthma exacerbations. A large randomized controlled trial comparing magnesium sulfate with placebo looking at outcomes such as symptom improvement, lung function improvement, exacerbation reduction and hospitalizations is warranted.Jennifer Namazy, MDScripps Clinic Medical Group
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