Efficacy of nebulized magnesium sulfate in moderate bronchiolitis

N Guruprasad; C A Gopalakrishna Mithra; Vinod H Ratageri

doi:10.4103/jpcc.jpcc_11_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 3 | Page : 90-94

Efficacy of nebulized magnesium sulfate in moderate bronchiolitis

N Guruprasad, C A Gopalakrishna Mithra, Vinod H Ratageri
Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India

Date of Submission	20-Jan-2022
Date of Decision	12-Apr-2022
Date of Acceptance	13-Apr-2022
Date of Web Publication	12-May-2022

Correspondence Address:
Dr. Vinod H Ratageri
Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli - 580 021, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_11_22

Abstract

Background: Bronchiolitis is a common cause of illness and hospitalization in infants and young children. The effectiveness of various bronchodilators remains unclear. This study was conducted to assess the efficacy of nebulized magnesium sulfate in hospitalized children with moderate bronchiolitis in the age group of 1–24 months.
Subjects and Methods: This was a prospective observational study done from December 2018 to June 2020. All children with moderate bronchiolitis (clinical severity score [CSS]-4–8) meeting inclusion/exclusion criteria were enrolled. A detailed history, demographic profile, CSS and oxygen saturation in room air, and heart rate were recorded. They were given two doses of magnesium sulfate in the form of nebulization for 10 min each, at 30 min apart. The children were assessed for CSS at 0 h, 1 h, and 4 h after nebulization. The children were considered improved if CSS <4 at the end of 4 h. The children were monitored for adverse reactions of magnesium sulfate.
Results: Sixty children were enrolled. The mean age was 7.5 ± 6.47 months. Most children (51.7%) were in 1–6 months. The mean CSS scores at 0 h, 1 h, and 4 h were 6 ± 1.008, 2.95 ± 1.395, and 2.40 ± 1.564, respectively (P = < 0.001). Fifty-three (88.3%) children improved and seven (11.7%) children did not improve. In nonimproved group, subanalysis was done and found hypoxia (odds ratio − 12.6) as a significant risk factor. Flushing was the most common adverse effect noticed in eight (13.3%) children.
Conclusions: Children with moderate bronchiolitis were improved with nebulized magnesium sulfate.

Keywords: Bronchiolitis, clinical severity score, hypoxia, magnesium sulfate, nebulization

How to cite this article:
Guruprasad N, Mithra C A, Ratageri VH. Efficacy of nebulized magnesium sulfate in moderate bronchiolitis. J Pediatr Crit Care 2022;9:90-4

How to cite this URL:
Guruprasad N, Mithra C A, Ratageri VH. Efficacy of nebulized magnesium sulfate in moderate bronchiolitis. J Pediatr Crit Care [serial online] 2022 [cited 2023 Mar 24];9:90-4. Available from: http://www.jpcc.org.in/text.asp?2022/9/3/90/345090

Introduction

Bronchiolitis is the most common disease of the lower respiratory tract during the first year of life. The symptoms are usually mild and may only last for a few days, but in some cases, the disease can cause severe illness.^[1] Bronchiolitis typically affects children younger than 2 years with a peak incidence between 2 and 6 months of age.^[2] No specific treatment is currently available and supportive care remains the mainstay of treatment which includes adequate hydration and humidified oxygen supplementation. Various treatment options have been proposed, of which only nebulized epinephrine and hypertonic saline have been shown to some extent useful.^[3],[4] There are no recommendations on magnesium sulfate so far for bronchiolitis.

Among chronic respiratory illnesses of childhood, asthma is the most common life-threatening disease. Treating asthma with magnesium sulfate is effective,^[5] and clinical presentation of bronchiolitis is similar to asthma, both involve narrowing of distal airways. Magnesium act on bronchioles, resulting in improvement of the airways.^[6] A study by Kose et al.^[7] showed improvement with the use of magnesium sulfate; however, Pruikkonen et al.^[8] did not find the benefit. Hence, there was a paucity of literature and lack of clarity about the effectiveness of the use of magnesium sulfate in bronchiolitis. Hence, we studied the efficacy of nebulized magnesium sulfate in bronchiolitis (moderate).

Materials and Methods

This was a hospital-based, prospective observational study done at a tertiary care hospital in a medical college in North Karnataka, between December 1, 2018, and June 30, 2020. Institutional Ethical Committee approval was taken (no.KIMS/EC/S11/2018–19, date November 16, 2018). Informed consent was obtained from the parents of all the enrolled children.

Inclusion criteria

All children in the age group of 1–24 months with clinically diagnosed bronchiolitis, with clinical severity score 4–8.^[7]

Exclusion criteria

(i) Previous history of wheezing, (ii) steroids usage within 24 h of presentation, (iii) children with immunodeficiency, (iv) known hypersensitivity to magnesium sulfate, (v) chronic lung disease, and (vi) congenital heart disease were excluded from the study.

Methods of collection of data

Bronchiolitis was defined as “first episode of wheezing preceded by a constellation of clinical symptoms and signs, suggestive of a viral upper respiratory prodrome followed by increased respiratory effort in children <2 years of age.”^[9] Moderate bronchiolitis was defined as clinical severity score (CSS) of 4–8.^[7]

All enrolled children in the study were taken detailed history including demographic details, CSS (RR, wheeze, retractions, and general condition of child), oxygen saturation (SaO2) in room air (determined by Nellcor pulse oximetry), and heart rate. Complete hemogram and chest X-ray was done after taking consent from the parents/guardians to rule out other causes for respiratory illness, mainly pneumonia. All eligible children with moderate bronchiolitis (score 4–8) were nebulized with magnesium sulfate (magnesium sulfate 150 mg diluted with 4 cc of 0.9% saline solution). Each milliliter of 50% magnesium sulfate contains 500-mg magnesium sulfate (0.1 ml of magnesium sulfate constitutes 50 mg), so 0.3 ml gives 150 mg of magnesium sulfate. Through an insulin syringe, 12 units (0.3 ml) of 50% magnesium sulfate was taken and diluted with 4 ml of normal saline (0.9%). This solution was used for nebulization. All children with moderate bronchiolitis were given two doses of magnesium sulfate in the form of nebulization for 10 min each, at 30 min apart. The child was assessed for CSS at 0 h (baseline), 1 h, and 4 h after starting the first dose of nebulization. SaO₂ was noted at 0 h and 4 h. SaO₂ of ≥92% in room air was considered normal.^[1] The patients were considered improved if CSS <4 at the end of 4 h. The patients with CSS ≥4 at the end of 4 h were considered nonimproved. Any worsening (CSS score >8) of the condition of the child during the study was considered treatment failure, and treatment was changed to standard protocol for the management of bronchiolitis. The patients were monitored for adverse reactions of magnesium sulfate, mainly hypotension, arrhythmias, loss of deep tendon reflexes, nausea, feeling of warmth, flushing, somnolence, double vision, slurring of speech, oliguria, weakness, muscular paralysis, respiratory arrest, and cardiac arrest after each dose of magnesium sulfate nebulization, till 4 h from the start of nebulization. Children who are given only breast milk for the first 6 months of life were taken as exclusively breastfed, and the rest were taken as nonexclusively breastfed. Socioeconomic status was taken according to modified Kuppuswamy classification 2020.^[11] Children immunized as per age were considered completely immunized, immunized but not complete for age were considered partially immunized, and not given any vaccine were considered nonimmunized.

Sample size was calculated based on data from previous literature,^[7] and the mean CSS score before treatment was 6.1 (1.11) and 4 h after treatment was 4.7 (2.0). Standard deviation of paired difference was 1.74 (assuming the correlation coefficient (r) between the two as 0.5). To reject the null hypothesis, that the difference between the two is zero with probability (power) of 0.99 and Type I error probability of 0.01, we require a minimum of 41 subjects. Statistical analysis was done using Microsoft Excel datasheet and analyzed using SPSS 22 version software (IBM SPSS Statistics, Somers, NY, USA). Categorical data were represented in the form of frequencies and proportions. Continuous data were represented as mean and standard deviation. Paired t-test was used to see the significance of paired data, that is before and after giving nebulized magnesium sulfate. P value (probability that the result is true) of <0.05 was considered statistically significant after assuming all the rules of statistical tests.

Results

Study recruitment is shown in flowchart [Figure 1].

Figure 1: Flowchart for the recruitment of children

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The total number of children enrolled in our study was 60. The male: female ratio was 2:1 (M – 68.3% and F – 31.7%) with a mean age of 7.5 ± 6.47 months. Among the enrolled children, 51.7% were in 1–6 months of age, 33.3% were in 6–12 months of age, and 15% were in 13–24 months of age. The clinical features in order of frequency were cough (91.7%), fever (81.7%), cold (63.3%), hurried breathing (63.3%), chest retractions (48.3%), noisy breathing (46.7%), reduced feeding (40%), and others including vomiting, loose stools, and irritability (13.3%). Majority of the children (51.7%) presented <3 days of illness, 38.3% between 4 and 6 days of illness, and 10% >6 days of illness.

Risk factors for bronchiolitis analysis showed that children who are born at term gestation constitute 86.7%, 11.7% were preterm, and 1.7% were postterm. Among the enrolled children, 85% had normal birth weight, 95% were exclusive breastfed, 76.6% of children were completely immunized, and 23.4% were partially immunized. None of the children had exposure for passive smoking. Lower middle and upper lower class constitute 88%.

Laboratory values revealed that the mean Hb was 10.06 ± 1.75 g%, mean total count was 9643 ± 3364, and mean platelet count was 4.11 ± 1.67 lakhs. Normal counts were seen in 93.3% (56), leukopenia in 5% (3), and leukocytosis in 1.7% (1). Chest X-ray was normal in 48.3% of the children and 38.3% had infiltrations, 6.6% had both hyperinflation and infiltrations, 5% had only hyperinflation, and 1.6% had patchy atelectasis.

[Table 1] shows SaO₂ levels in children before and after nebulization. The mean saturation was 90% ± 7% before giving nebulization and 93% ± 4% after nebulization. Further analysis showed mean SaO₂ before nebulization and after nebulization, it was statistically significant in both hypoxic and nonhypoxic children groups.

Table 1: Effect of nebulization on oxygen saturation

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The mean pulse rate (PR) at baseline was 131 ± 23, at 1 h was 129 ± 23, and at 4 h was 124 ± 23. There was a significant decrease (improvement) in PR score at 1 h and 4 h compared to the baseline score.

The effect of magnesium nebulization on CSS is shown in [Table 2] and [Figure 2]. There was a significant decrease (improvement) in CSS at 1 h and 4 h compared to the baseline score. Among the study population, 88.3% of the children improved and 11.7% of the children did not improve.

Table 2: Clinical severity score at different periods of time

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Figure 2: Bar diagram showing clinical severity score at different periods of time

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There were no adverse effects in 86.6% (52) of children, but 13.3% (8) of children had flushing. None of the children had hypotension, arrhythmias, and loss of Deep Tendon Reflex (DTR). Further analysis for various risk factors and outcomes using univariate and multiple logistic regression [Table 3] and [Table 4] found only hypoxia as significant. Among subjects with hypoxia, 22.7% had no improvement, and among subjects without hypoxia, 5.3% had no improvement. There was no significant association between other risk factors and outcome.

Table 3: Univariate analysis with risk factors associated with outcome

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Table 4: Multiple logistic regression to determine the independent variable for outcome

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Discussion

Bronchiolitis is a common respiratory tract infection in infancy. The most common etiologic agent is the respiratory syncytial virus. The diagnosis of bronchiolitis is mostly clinical, and laboratory investigations have a limited role in diagnosis and management. The current management primarily consists of supportive care which includes mainly maintaining hydration and humidified oxygen.^[9] Currently, there is no specific treatment for bronchiolitis with strong or convincing evidence of effectiveness. Although bronchodilator therapy is a commonly used therapy for bronchiolitis, the evidence of its usage is not very strong and its efficacy is not universally accepted.^[10] Magnesium sulfate is one among the bronchodilators tried in bronchiolitis, but the results are inconclusive^{[7],[8],[12],[13]} to recommend it as a therapy for bronchiolitis.

In our study, 53 (88.3%) children improved and 7 (11.7%) children did not improve. There was a significant decrease (improvement) in CSS at 1 h and 4 h compared to baseline score after magnesium sulfate nebulization. Gradually, the CSS reduced, indicating the improvement of the child over a period of 4 h, and it was statistically significant. Similar results were found in a study by Kose et al.^[7] and Modaresi et al.^[13] However, a study by Alansari et al.^[12] showed that IV magnesium sulfate was not useful. However, Kan et al.^[14] showed that magnesium sulfate was safe and effective in treating bronchiolitis below 2 years of age. The bronchodilator effect of magnesium sulfate is responsible for the improvement in clinical scores. The possible mechanism of bronchodilation is (a) inhibition of calcium-mediated smooth muscle contraction, (b) histamine release inhibition from mast cell, (c) inhibition of nicotinic acetylcholine release, and (d) nitric oxide and prostacyclin release, causing vasodilatory action on the pulmonary vasculature.^{[15],[16],[17]}

We observed that baseline saturation before nebulization was normal in 38 (63.3%) children and hypoxia in 22 (36.6%) children. At the end of 4 h, among the hypoxic group, 12 (20%) children had persistent hypoxia, though statistically mean saturation improved in both the groups. None of the children with normal saturation fell into the hypoxia group. The probable mechanism of hypoxia in bronchiolitis is due to airway edema and sloughing of respiratory epithelial cells, causing mismatch of ventilation and perfusion and subsequent reductions in oxygenation.^[9]

Children who did not improve with magnesium sulfate nebulization were analyzed further. The observation of nonimproved group showed that all children were male, five were hypoxic, two were partially immunized, and chest X-ray showed infiltrations and hyperinflation in two children each. After univariate and multivariate analysis using the above parameters, hypoxia was found to be the significant risk factor for nonimprovement. The odds of hypoxia was 12.6, meaning the risk of nonimprovement in hypoxic children is 12.6 times higher compared to children without hypoxia. The probable mechanisms for nonimprovement could be due to (a) unstable nature of MgSO₄ in the respiratory mucosa, (b) a topical irritant effect, (c) site of action inaccessible by the inhalation route, and (d) nebulization route is of low dose compared to the intravenous route.^[18]

Most of the children (86.6%) in our study did not develop any adverse effects. The predominant adverse effect that we came across in our study was transient flushing (13.3%), which is one of the uncommon early side effects of magnesium, probably due to the vasodilator effect of magnesium.^[19] It was predominantly seen in the abdomen, chest, and back. Flushing was transient and resolved without any treatment. Similarly, a study by Kan et al.^[14] showed that magnesium sulfate micro air pump suction was safe and its adverse reaction rate was low (8.2%). One child after nebulization at 4^th h had worsening of CSS, requiring positive pressure ventilation and finally ended up requiring mechanical ventilation probably due to progression of the disease. This child was considered treatment failure and treatment was changed to standard protocol for the management of bronchiolitis. Adverse effects, mainly hypotension, arrhythmias, and loss of deep tendon reflexes noted in the literature during intravenous magnesium sulfate administration,^{[15],[16],[20]} were not observed in our study.

The strength of our study was the adequate sample size. However, the limitations were (i) inclusion of controls would have given more conclusive data regarding the efficacy of nebulized magnesium sulfate, (ii) follow-up of children after 4 h of intervention was not done to know about long-term improvement, and (iii) the CSS mainly depends on subjective complaints rather than objective assessment.

Conclusions

Children with moderate bronchiolitis (CSS 4–8) improved after two doses of nebulized magnesium sulfate with a very low incidence of adverse effects (transient flushing). Hypoxia was the significant risk factor in the nonimproved group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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