When should administration of Magnesium sulfate be considered in a child with asthma Quizlet

Med Princ Pract. 2020 May; 29(3): 292–298.

Abstract

Objective

Systemic administration of magnesium sulfate (MgSO₄) has been proposed as a treatment for pediatric patients with acute asthma. However, previous trials show mixed results and uncertain evidence of benefit. The aim of the study was to ascertain whether intravenous (IV) MgSO₄ improves lung function parameters in children with acute asthma.

Methods

This was a prospective clinical trial. All patients with acute asthma received 40–50 mg/kg or maximum 1,500 mg (>30 kg) of single dose IV MgSO₄, administered over 60 min. Spirometry was conducted before and 15 min after MgSO₄ infusion.

Results

One hundred and fifteen children aged 6 to 17 years presenting with acute asthma and FEV₁ between 40% and 75% of predicted were included. Then, the patients were classified into 2 groups; mild asthma attack (FEV₁ ranged from 60% to 75%; n = 50) or moderate asthma attack (FEV₁ ranged from 40% to 59%; n = 65). The baseline characteristics were similar in both groups. The mean percent predicted pre and post values for FEV₁/FVC ratio (mild group: 82.59 ± 9.46 vs. 85.06 ± 8.95; moderate group: 77.31 ± 11.17 vs. 79.99 ± 11.77), FEV₁ (mild group: 67.14 ± 4.99 vs. 72.29 ± 8.05; moderate group: 48.50 ± 6.81 vs. 53.78 ± 9.81), PEF (mild group: 65.49 ± 12.32 vs. 71.37 ± 12.96; moderate group: 47.56 ± 11.78 vs. 51.97 ± 13.98), and FEF_25–75 (mild group: 58.20 ± 12.24 vs. 66.57 ± 16.95; moderate group: 37.77 ± 11.37 vs. 43.41 ± 14.19) showed a statistically significant (p < 0.05 for all) bronchodilator effect after MgSO₄ infusion in both groups with few side effects.

Conclusion

Administration of IV MgSO₄ was associated with improved pulmonary function in children with acute asthma.

Keywords: Asthma, Children, Magnesium sulfate, Spirometry

Significance of the Study

• This study investigates the efficacy of systemic magnesium sulfate treatment in asthmatic children with a considerable number of patients.

• It appears to have a beneficial bronchodilator response by providing sufficient bronchodilator effect on pulmonary function parameters in children with acute asthma.

• Systemic magnesium sulfate may be considered for patients with acute asthma attack.

Introduction

Asthma is the most common chronic lung disease occurring in all age groups frequently beginning in childhood. The prevalence of asthma has increased in developed countries over the last 4 decades. The disease is associated with airway inflammation and characterized by hyper-responsiveness of the airways with reversible airway obstruction. Asthma symptoms can be triggered by respiratory viruses, allergens, tobacco smoking, air pollutants, and cold or dry air. In spite of the availability of good preventive treatment, respiratory symptoms and acute attacks related to asthma in children still occur and are responsible for a considerable number of clinic or emergency visits, hospital admissions, and missed school days [1].

The main goal of treatment in acute asthma attack is to relax airway smooth muscles, decrease vascular permeability, increase mucociliary clearance, decrease mucus secretion, and most importantly, downregulate airway inflammation. The most indispensable initial treatment for asthma attack is short-acting β2 agonists such as salbutamol/albuterol or terbutaline to relieve airway obstruction. Safe and effective inhalation of these drugs leads to bronchodilatation. Alternative additive therapies in the treatment of acute asthma attack may include inhaled ipratropium bromide, subcutaneous or inhaled epinephrine/adrenaline, intravenous (IV) or inhaled magnesium sulfate (MgSO4), and IV aminophylline [2].

Among these additive therapies, MgSO4 may offer a clinically useful option in treating acute asthma exacerbations in children. Although the precise mechanism by which MgSO4 produces bronchodilatation of smooth muscles is not well understood, it is thought to act by enhancing calcium uptake in the sarcoplasmic reticulum and/or as a calcium antagonist. Additionally, 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. Other potential beneficial mechanisms in asthma include inhibition of acetylcholine release from cholinergic nerves and reduction in the release of histamine release from mast cells [3]. About 40% of magnesium is bound to plasma proteins and requires distribution into smooth muscle tissue for activity. A retrospective study using covariate analysis investigated serum magnesium disposition by clearance and volume distribution in pediatric population, and stated that only body weight was significantly correlated with serum magnesium concentrations. The authors also reported that magnesium had a short half-life of 2.7 h serum concentration in children [4].

Though systemic MgSO4 treatment in children with acute asthma may be helpful, results of published trials are conflicting regarding the impact of the treatment on respiratory distress. [5, 6]. Therefore, we hypothesized that MgSO4 infusion would result in significant improvement in spirometric measures of lung function in children with acute exacerbations for asthma.

Material and Methods

This was an open intervention study conducted in the Pediatric Pulmonology Section, Mersin City Training and Research Hospital between February and June 2019. Our hospital is a tertiary pediatric hospital with the only pediatric pulmonology clinic in the region serving a population of 1,793,000. The study included a convenience sample of (1) children aged 6–17 years with MD-diagnosed asthma; (2) presenting with respiratory complaints due to asthma; (3) no history of using short-acting β2 agonist in the past 3 h (in order to examine only systemic MgSO4 response); (4) no history of oral/IV steroid use in the past 12 h; (5) respiratory stable outpatient with an oxygen saturation (SpO2) >92% on room air; (6) spirometry with a forced expiratory volume in 1 s (FEV1) 40% to 75% of predicted measured at the time of the clinic visit. Children who were unable to perform spirometry or who showed unstable clinical status during the study period were excluded.

Patients were given one dose of MgSO4 ranging from 40 to 50 mg/kg or a maximum 1,500 mg for patients >30 kg in 100 mL of normal saline, administered over approximately 60 min at the discretion of the nurse caring for the patient. Spirometry (MIR® Spirolab model 2014, Rome, Italy) was performed before and 15 min after completion of MgSO4 infusion by an experienced technician. The spirometry procedure was conducted with the children seated upright with at least 3 appropriate expiratory maneuvers. In order to examine the degree of airway obstruction, forced vital capacity (FVC), FEV1, peak expiratory flow (PEF), and forced expiratory flow between 25 and 75% of the FVC (FEF25–75) were included as spirometric values, and expressed as percent of predicted based on height and gender of the child. Normal values were defined using the data of the European Respiratory Society Global Lung Function Initiative [7].

All patients were continually monitored (B40® monitore, model 2016, Freiburg, Germany) for blood pressure, SpO2, respiratory depression, and arrhythmia for the safety of magnesium infusion. Then, the patients immediately received standard care for asthma with inhalation of short-acting β2 agonist and systemic steroid if needed as part of their management. Patients showing clinical or laboratory signs of deterioration were excluded from the study. Efficacy of MgSO4 treatment was assessed as the change of FEV1/FVC, FEV1, PEF, and FEF25–75 parameters before and after MgSO4 infusion.

The study protocol was approved by the University of Cukurova and written informed consent was obtained from parents of the study participants. Additionally, all children were verbally informed about the study procedure.

Statistical Analysis

Statistical analyses were performed using an IBM SPSS Statistics Version 20.0 software package. Categorical variables were expressed as numbers and percentages, whereas continuous variables were summarized as mean and standard deviation when the data was equally distributed or as median and minimum-maximum when non-equally distributed. The chi-square test was used to analyze categorical variables. For comparison of continuous variables between two groups, the Student's t test was used. For comparison of two related (paired) continuous variables, paired samples t test was used. A p value <0.05 was considered statistically significant.

Results

One hundred thirty-six children with asthma exacerbation were enrolled in this study. A total of 21 were excluded for insufficiently performed pulmonary function test (n = 12), nausea/vomiting (n = 4), decrease in SpO2 level (n = 4), and hypotension (n = 1) during MgSO4 infusion, resulting in a final sample size of 115 patients. Then, the patients were categorized into 2 groups according to their initial FEV1 results (Fig. ​1).

Group 1 consisted of children with a mild attack (FEV1 between 60 and 75% of predicted) and group 2 of children with moderate attack (FEV1 between 40 and 59% of predicted). The demographic characteristics of children are detailed in Table ​1. Baseline characteristics were similar for age at participation, sex, history of parental asthma, age of first asthma symptom, atopic status (allergic rhinitis, atopic dermatitis, allergy skin test positivity, and IgE levels), indoor smoking exposure, and current asthma medication among the 2 groups (p > 0.05). Additionally, there were no statistically significant differences in SpO2, heart rate, and systolic and diastolic blood pressure changes during pre and post MgSO4 infusion in either group (Table ​2).

Table 1

Demographic characteristics of children with acute asthma

Table 2

Oxygen saturation, heart rate, and blood pressure of children with acute asthma

When the mean pre and post FEV1/FVC ratio (82.59 ± 9.46 vs. 85.06 ± 8.95), FEV1 (67.14 ± 4.99 vs. 72.29 ± 8.05), PEF (65.49 ± 12.32 vs. 71.37 ± 12.96), and FEF25–75 (58.20 ± 12.24 vs. 66.57 ± 16.95) percent predicted values were compared, all lung function parameters showed significant improvement with MgSO4 infusion in children with acute asthma in the mild group (Fig. ​2). Similarly, when the mean pre and post FEV1/FVC ratio (77.31 ± 11.17 vs. 79.99 ± 11.77), FEV1 (48.50 ± 6.81 vs. 53.78 ± 9.81), PEF (47.56 ± 11.78 vs. 51.97 ± 13.98), and FEF25–75 (37.77 ± 11.37 vs. 43.41 ± 14.19) percent predicted values were compared, all parameters again improved significantly with MgSO4 treatment in children with acute asthma in the moderate group (Fig. ​3).

Lung function parameters in children with acute asthma in the mild group.

Lung function parameters in children with acute asthma in the moderate group.

The mean change in FEV1 and FEF25–75 with MgSO4 infusion was 7.7 and 14.2% in the mild group, and 10.9 and 14.9% in the moderate group.

Discussion

Several studies have reported that systemic administration of MgSO4 in adults with moderate to severe acute asthma resulted in significantly improved short-term pulmonary function [8, 9]. Although most studies examining the potential clinical role of MgSO4 treatment in children with acute asthma have shown beneficial effect, its precise role has still not been fully elucidated [10, 11, 12, 13, 14, 15]. In this regard, two meta-analyses examined the role of IV MgSO4 for acute severe asthma as part of the co-therapies with inhaled β2 agonists and systemic steroids mainly conducted in the pediatric emergency department [16, 17]. After pooling the results, IV MgSO4 was found to be effective as an adjunctive therapy in avoiding hospitalization (odds ratio: 0.290, 95% confidence interval: 0.143 to 0.589). In addition, the pooled result on asthma symptom scores showed consistent improvement in the analysis. The use of IV MgSO4 in the emergency room was well tolerated with only minor side effects. Both meta-analyses concluded that IV magnesium sulfate is an effective additional treatment for children with acute severe asthma who had not responded to initial standard treatment. Moreover, a recent study reported IV infusion of MgSO4 during the first hour of hospitalization in patients with acute severe asthma was associated with significantly reduced percentage of children who required mechanical ventilation support [18].

In a study conducted by Singhi et al. [19] comparing the efficacy of IV MgSO4, terbutaline, and aminophylline for children with acute, severe asthma poorly responsive to standard initial treatment, adding a single dose of IV MgSO4 to inhaled β2 agonists and corticosteroids was found to be more effective, and safer than using terbutaline or aminophylline when treating children with acute severe asthma poorly responsive to initial treatment.

A few studies have investigated the effect of MgSO4 treatment on pulmonary function. Children treated with IV magnesium infusion in addition to nebulized salbutamol for acute asthma had significantly greater immediate improvement in PEFR compared to placebo group [10, 12]. Additionally, this effect was sustained for hours in the treatment group. A single double-blind placebo-controlled trial conducted on a limited number of children with acute asthma examined the effect of MgSO4 infusion on detailed pulmonary function; the treatment group showed greater percentage of improvement in FVC, FEV1, and PEFR measurements, and were more likely to be discharged to their homes than the placebo group [11].

A recent Cochrane review analyzed studies on systemic MgSO4 in the treatment of children with acute asthma [20]. The review emphasized that treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio: 0.32, 95% confidence interval: 0.14 to 0.74). But the estimated reduction in true population in admission had a wide confidence interval between 86 and 26%. There was reduced length of hospital admission by 5.3 h with IV MgSO4 treatment. The review also concluded that there was an additive benefit of MgSO4 treatment on other parameters such as reduction in intensive care admissions, vital signs, spirometry, or scores on symptom scales, or the likelihood of returning to the emergency department within 48 h with generally mild and infrequent reported side effects. However, the authors concluded that it was difficult to know whether this was either evidence of safety or was sufficient to recommend such a therapy in the presence of weak effect size and small sample size in the trials in the literature.

The current prospective study has demonstrated that in children aged between 6 and 17 years with mild or moderate acute asthma, systemic infusion of MgSO4 treatment resulted in a beneficial bronchodilator effect as determined by spirometry parameters. Moreover, it could be speculated that MgSO4 treatment would also be beneficial in children with severe asthma based on the study results. Unlike most studies reported in children with acute asthma, the present study on a reasonable sample size has shown beneficial bronchodilator response in the absence of inhaled β2 agonists. It should be noted that although IV MgSO4 provided statistically significant bronchodilator effect in lung function parameters, its benefit appears not as potent as inhaled β2 agonists (i.e., expected change in FEV1 >12% and FEF25–75 >%24) [21]. In contrast, we did not observe any improvement in SpO2 levels with MgSO4 infusion in both treatment groups. This could be related to the initially selected patients with SpO2 levels >92% or SpO2 might not change even in the presence of sufficient bronchodilation [22]. Because the study was aimed only at investigating the effect of MgSO4 infusion on pulmonary function parameters, other outcomes (e.g., improvement in asthma symptom scores, emergency department visit, hospital admission, etc.) were not assessed. Our findings must be supported by additional studies including other parameters mentioned above.

One of the major limitations of this study is the lack of a control group. Therefore, we do not know if the children would have simply improved on their own without the magnesium sulfate treatment. The main reason for not adding a control group was ethical concerns.

Systemic use of MgSO4 appears to be safe; minor side effects such as headache, muscle tightness or contraction, flushing, heart disturbances, confusion, dry mouth, malaise, and hypotension have been reported in the literature [23]. Approximately 7% of children with side effects attributed to MgSO4 infusion were excluded from our study. Another limitation of this study is that magnesium levels of the study participants were not routinely measured prior to and after the treatment in order to determine a therapeutic level. However, the dose of MgSO4 used suggests that it did achieve sufficient beneficial effect in the study population.

Conclusion

Systemic use of MgSO4 appears to have a beneficial effect on bronchodilator response in spirometric parameters in children with acute asthma with few side effects. Thus, it may be considered for the management of children with asthma suffering from acute airway obstruction.

Statement of Ethics

The study protocol was approved by the University of Cukurova and written informed consent was obtained from parents of the study participants. Additionally, all children were verbally informed about the study procedure.

Disclosure Statement

There is no competing interest.

Acknowledgement

The authors thank Prof. Mark A. Brown for his critical review.

References

1. Tesse R, Borrelli G, Mongelli G, Mastrorilli V, Cardinale F. Treating Pediatric Asthma According Guidelines. Front Pediatr. 2018 Aug;6:234. [PMC free article] [PubMed] [Google Scholar]

2. Landau LI, Martinez FD. Asthma: Treatment. In: Taussig LM, Landau LI, Le Souef PN, Morgan WJ, Martinez FD, Sly PD, editors. Pediatric Respiratory Medicine. 2nd ed. Philadelphia: Mosby; 2008. pp. pp.829–44. [Google Scholar]

3. Kelly HW. Magnesium sulfate for severe acute asthma in children. J Pediatr Pharmacol Ther. 2003 Jan;8((1)):40–5. [PMC free article] [PubMed] [Google Scholar]

4. Rower JE, Liu X, Yu T, Mundorff M, Sherwin CM, Johnson MD. Clinical pharmacokinetics of magnesium sulfate in the treatment of children with severe acute asthma. Eur J Clin Pharmacol. 2017 Mar;73((3)):325–31. [PubMed] [Google Scholar]

5. DeSanti RL, Agasthya N, Hunter K, Hussain MJ. The effectiveness of magnesium sulfate for status asthmaticus outside the intensive care setting. Pediatr Pulmonol. 2018 Jul;53((7)):866–71. [PubMed] [Google Scholar]

6. Griffiths B, Kew KM, Normansell R. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Paediatr Respir Rev. 2016 Sep;20:45–7. [PubMed] [Google Scholar]

7. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. ERS Global Lung Function Initiative. Multiethnic reference values for spirometry fort he 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40((6)):1324–43. [PMC free article] [PubMed] [Google Scholar]

8. Goodacre S, Cohen J, Bradburn M, Stevens J, Gray A, Benger J, et al.3Mg Research Team The 3Mg trial: a randomised controlled trial of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma. Health Technol Assess. 2014 Apr;18((22)):1–168. [PMC free article] [PubMed] [Google Scholar]

9. Silverman RA, Osborn H, Runge J, Gallagher EJ, Chiang W, Feldman J, et al.Acute Asthma/Magnesium Study Group IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. Chest. 2002 Aug;122((2)):489–97. [PubMed] [Google Scholar]

10. Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial. J Pediatr. 1996 Dec;129((6)):809–14. [PubMed] [Google Scholar]

11. Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Pediatr Adolesc Med. 2000 Oct;154((10)):979–83. [PubMed] [Google Scholar]

12. Devi PR, Kumar L, Singhi SC, Prasad R, Singh M. Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy. Indian Pediatr. 1997 May;34((5)):389–97. [PubMed] [Google Scholar]

13. Gürkan F, Haspolat K, Boşnak M, Dikici B, Derman O, Ece A. Intravenous magnesium sulphate in the management of moderate to severe acute asthmatic children nonresponding to conventional therapy. Eur J Emerg Med. 1999 Sep;6((3)):201–5. [PubMed] [Google Scholar]

14. Powell C, Kolamunnage-Dona R, Lowe J, Boland A, Petrou S, Doull I, et al.MAGNETIC study group Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial. Lancet Respir Med. 2013 Jun;1((4)):301–8. [PubMed] [Google Scholar]

15. Irazuzta JE, Chiriboga N. Magnesium sulfate infusion for acute asthma in the emergency department. J Pediatr (Rio J) 2017 Nov-Dec;93(Suppl 1):19–25. [PubMed] [Google Scholar]

16. Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child. 2005 Jan;90((1)):74–7. [PMC free article] [PubMed] [Google Scholar]

17. Su Z, Li R, Gai Z. Intravenous and Nebulized Magnesium Sulfate for Treating Acute Asthma in Children: A Systematic Review and Meta-Analysis. Pediatr Emerg Care. 2018 Jun;34((6)):390–5. [PubMed] [Google Scholar]

18. Torres S, Sticco N, Bosch JJ, Iolster T, Siaba A, Rocca Rivarola M, et al. Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in children, conducted in a tertiary-level university hospital: a randomized, controlled trial. Arch Argent Pediatr. 2012 Aug;110((4)):291–6. [PubMed] [Google Scholar]

19. Singhi S, Grover S, Bansal A, Chopra K. Randomised comparison of intravenous magnesium sulphate, terbutaline and aminophylline for children with acute severe asthma. Acta Paediatr. 2014 Dec;103((12)):1301–6. [PubMed] [Google Scholar]

20. Griffiths B, Kew KM. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Cochrane Database Syst Rev. 2016 Apr;4:CD011050. [PMC free article] [PubMed] [Google Scholar]

21. Kanchongkittiphon W, Gaffin JM, Kopel L, Petty CR, Bollinger ME, Miller RL, et al. Association of FEF25%-75% and bronchodilator reversibility with asthma control and asthma morbidity in inner-city children with asthma. Ann Allergy Asthma Immunol. 2016 Jul;117((1)):97–9. [PMC free article] [PubMed] [Google Scholar]

22. Tal A, Pasterkamp H, Leahy F. Arterial oxygen desaturation following salbutamol inhalation in acute asthma. Chest Dec. 86((6)):868–869. [PubMed] [Google Scholar]

23. Davalos Bichara M, Goldman RD. Magnesium for treatment of asthma in children. Can Fam Physician. 2009 Sep;55((9)):887–9. [PMC free article] [PubMed] [Google Scholar]

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