A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks

doi:10.1016/j.pupt.2005.03.003

Pulmonary Pharmacology & Therapeutics

Volume 18, Issue 6, December 2005, Pages 416-421

https://doi.org/10.1016/j.pupt.2005.03.003 Get rights and content

Abstract

Although it is well known that intravenous administration of MgSO₄ as an adjunct to conventional therapy is effective in treating asthma attacks, the effect of nebulized MgSO₄ as a vehicle for salbutamol has been less evaluated. The aim of this study was to compare the effects of nebulized salbutamol administrated through either MgSO₄ or isotonic saline solution on the ‘peak expiratory flow rate’ (PEFR), other respiratory and clinical parameters, and hospitalization rate of patients suffering from moderate to severe asthma attacks.

Twenty-six patients with asthma attack were enrolled in the study in a randomized single blind fashion. After obtaining initial peak expiratory flow measurements (PEFR) and clinical evaluation, all patients received 1 mg/kg corticosteroids and oxygen therapy and then either isotonic MgSO₄ (2.5 ml, 6.3%)+salbutamol (2.5 ml) or saline (2.5 ml)+salbutamol (2.5 ml) through a jet nebulizer (group 1 (n=14) vs group 2 (n=12), respectively). The nebulizations were repeated every 20 min for the first hour and every hour for the rest of 4 h. The PEFR measurements and clinical assessment were performed after nebulization at 20th, 60th, 120th, 180th and 240th minutes. Patients were discharged when PEFR reached the target level of 70% of predicted.

The baseline PEFRs and clinical parameters were similar between groups 1 and 2 (50.2±18.5 vs 44.1±13.9, respectively, p>0.05). The mean% increase in PEFR at different measurement levels was similar between the groups. When the treatment response was evaluated within the groups, group 2 showed statistically significant increase in PEFR (% of predicted) 1 h earlier than group 1 (60th vs 120th minute, p=0.003 vs p=0.007). The mean duration of achieving target-PEFRs was 105.7±72.1 min for group 1 and 118.3±96.7 min for group 2 (p>0.05).

This study suggested that the additional usage of MgSO₄ to nebulized salbutamol has no beneficial effect on the treatment of asthma attacks.

Introduction

Asthma attacks are serious respiratory problems that can be lethal when not treated appropriately [1]. The mainstay treatments of asthma attacks include oxygen supplementation, inhaled beta-2 agonists and systemic corticosteroids [2]. Magnesium is an intracellular cation that acts as a physiological antagonist to calcium. It has also an essential role in the activation of more than 300 enzymes including adenyl cyclase [3], [4].

The use of intravenous magnesium sulphate (MgSO₄) in treating asthma attacks has been shown to improve pulmonary function as an adjunct therapy [1], [2], [5], [6], [7].

In contrast to intravenous MgSO₄, data on nebulized MgSO₄ have been scant. There are limited numbers of studies that were designed slightly different and that provided varied results. The effect of nebulized MgSO₄ as a vehicle for salbutamol has been less evaluated. The aim of this study was to compare the effects of nebulized salbutamol administrated through either MgSO₄ or isotonic saline solution on the ‘peak expiratory flow rate’ (PEFR), other respiratory parameters, duration of observation in emergency department (ED), and admission rate to hospital of patients suffering from moderate to severe asthma attacks.

Section snippets

Participants

A total of 26 patients (18–60 years old) who were admitted to ED with moderate to severe asthma attacks, were included in the study. The attack severity was evaluated on the basis of the Global Initiative for Asthma (GINA) 2002 criteria (Table 1) [2]. Patients with febrile disease, diabetes, congestive heart failure, atherosclerotic heart disease, intractable hypertension, chronic obstructive lung disease, renal and hepatic failure and, arrhythmia were excluded from the study. Pregnant and

Results

Out of 40 patients screened over a period of 6 months, a total of 26 patients including 14 (10 females and 4 males) patients in group 1 and 12 (9 females and 3 males) patients in group 2 were enrolled in the study. Premedication prior to admission was the most common exclusion criteria. Two excluded patients were febrile and diagnosed with pneumonia. One patient was later excluded because the final diagnosis was COPD. Four patients were excluded because of the severe hypertension. Only single

Discussion

Our study showed that in moderate to severe asthma attacks, salbutamol nebulization through MgSO₄ did not result in additional bronchodilation when compared to salbutamol administrated through saline. The improvement in PEFR and clinical scores were similar between the groups. Both deliveries were well tolerated. Two patients in saline group, one patient in MgSO₄ group underwent admission.

Several reports have shown that intravenous administration of MgSO₄ undoubtedly improves pulmonary function

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Cited by (27)

Limitations of the results from randomized clinical trials involving intravenous and nebulised magnesium sulphate in adults with severe acute asthma
2019, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
The most commonly reported ARs were dry and bitter mouth, but no other ARs were associated with the treatment [23]. The Gaur et al. [24] (Table 3) and several other RCTs [25–30] lack at least one optimal treatment option. As expected they report contradictory results [24] (Table 4) [25–30].
The role of intravenous (IV) or nebulised magnesium sulphate (MgSO₄) in the treatment of severe acute asthma in adults is unclear. A controversy exists regarding its efficacy. In children MgSO₄ has a more evident clinical effect, but the child population has not been considered in this work. The applicability of the results from randomized clinical trials (RCTs) involving MgSO₄ in adult population is questioned in the optimal treatment of asthma exacerbations. According to the newest guidelines from the Global Initiative for Asthma (GINA), optimal treatment in the emergency department (ED) is based on short-acting beta₂-agonists (SABA), oral or IV corticosteroids (CS), short acting muscarinic antagonists (SAMA) and the controlled oxygen therapy. Further improvements with IV or nebulised MgSO₄ were assessed in a recent large multicentre, double-blind, placebo-controlled randomized 3 Mg trial, which failed to demonstrate clinical benefit. Several other RCTs found some benefit with MgSO₄, although the majority lacked some treatment options that are used in the optimal treatment of asthma exacerbations. Therefore, we reviewed the limitations of RCTs of IV or nebulised MgSO₄ in adults with acute asthma, with the aim to answer in which subpopulation MgSO₄ could be beneficial.
Monitoring peak expiratory flow could predict COPD exacerbations: A prospective observational study
2019, Respiratory Medicine
Exacerbation of chronic obstructive pulmonary disease (ECOPD) is an important event during the course of the disease. It causes a more rapid decline in lung function, which is associated with hospitalization and the risk of death. Therefore, it is essential to discover approaches to early detection and prevention of ECOPD. Peak expiratory flow (PEF) can be safely used instead of spirometry which can assess the severity of COPD as a standard tool. We hypothesized that monitoring PEF could possibly be used to predict the ECOPD.
To verify this hypothesis, daily morning PEF was monitored for 6 months in 53 patients with moderate to severe COPD (mean FEV1 31.53%predicted) who were enrolled in Ningbo, China.
A total of 69 exacerbations of COPD (63 of gradual onset, six of sudden onset) were recorded in this study. Thirty cases (43.5%) of gradual onset exacerbations needed to be hospitalized, and the mean PEF significantly decreased (vs baseline) during the 5 days that preceded those exacerbations (from 161.9 ± 39.4 L/min to 137.9 ± 36.1 L/min, P < 0.05, statistical power = 0.92). However, this was not the case with non-hospitalized exacerbations (from 175.4 ± 42.5 L/min to 161.5 ± 39.3 L/min, P = 0.172, statistical power = 0.63). The ROC analysis demonstrated that 24 h before hospitalized exacerbation, the optimal cutoff value of ΔPEF for its prediction was 28 L/min (17% from baseline), with a sensitivity and specificity of 76.7% and 72.7%, respectively (area under the curve [AUC] = 0.84, P < 0.05, statistical power = 0.78). While 48 h before hospitalized exacerbation, the optimal cutoff value of ΔPEF for its prediction was 14 L/min (9% from baseline), with a sensitivity and specificity of 86.7% and 66.7%, respectively (AUC = 0.863, P < 0.05, statistical power = 0.87).
As a rapid, inexpensive method, PEF could be used for the prediction and early detection of hospitalized exacerbation of COPD. This may provide opportunity for early intervention of ECOPD.
The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment
2017, Allergologia et Immunopathologia
After the bronchodilator effect of magnesium was shown, the use of magnesium in treatment of asthma exacerbations became common. With the results of recent studies, the use of intravenous magnesium in severe asthma exacerbations took its place. We aimed to examine the effects of adding isotonic magnesium sulphate instead of isotonic saline into nebulised salbutamol on the Modified Pulmonary Index Score (MPIS) and the hospitalisation rate in moderate asthma exacerbations.
Our study population included 100 children age between 3 and 15 years with asthma admitted to emergency department due to moderate asthma exacerbations. The patients were randomised to placebo or magnesium, with 50 patients in each arm. All patients received 1 mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15 mg/kg/dose) and 1 ml magnesium sulphate (15%) + 1.5 ml isotonic saline on three occasions at roughly 20 min intervals (Magnesium group) or nebulised salbutamol (0.15 mg/kg/dose) and 2.5 ml isotonic saline mixture on three occasions at roughly 20 min intervals (Placebo group). The MPIS of patients on 0th min, 20th min, 40th and 120th min were calculated and compared. The primary outcome was to compare MPIS values at the end of 120th min.
Both groups have similar demographic, allergic characteristics and baseline MPIS scores. When the MPIS scores in the 120th min and admission rates in the 200th min, there was no significant difference between the two groups.
The use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study.
Lack of efficacy of nebulized magnesium sulfate in treating adult asthma: A meta-analysis of randomized controlled trials
2016, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
Among the remaining 19 full-text articles, 1 was excluded because the data were duplicated with regard to another trial [13], 1 because the patients were children [20], and 1 because the outcomes were incomplete [21]. Ultimately, 16 articles were included in the present analysis (including 10 trials with acute asthma and 6 trials with stable asthma) [7–9,22–34]. The selection process is shown in Fig. 1.
Nebulized magnesium sulfate (MgSO₄) has been used to treat asthma, but the efficacy remains controversial. We aimed to comprehensively review the efficacy of nebulized MgSO₄ in treating adult patients with asthma.
PubMed, Embase, and Cochrane Library were searched for relevant studies published up to July 18, 2016. Randomized controlled trials (RCTs) were included if adult patients with acute or stable asthma had been treated with nebulized MgSO₄ compared with placebo or another bronchodilator. Standardized mean differences (SMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Outcomes included pulmonary function, hospital admission and adverse events.
A total of 1386 patients from sixteen trials (1240 acute asthma patients and 146 stable asthma patients) were subjected to meta-analysis. Compared to placebo as normal saline, whether using in acute or stable adult asthma, nebulized MgSO₄ did not significantly improve the respiratory function: SMD 0.39 (95% CI −0.03–0.82, P = 0.07), and 1.48 (95% CI −0.14–3.11, P = 0.07), respectively. Furthermore, nebulized MgSO₄ did not reduce hospital admission in adult patients with acute asthma (RR, 0.72; 95% CI, 0.52–1.00; P = 0.05), although it was not associated with increased adverse events (RR 1.15; 95% CI, 0.88–1.52; P = 0.31).
Evidence to date suggests that nebulized MgSO₄ has no role in the management of adult patients with acute or stable asthma.
Correlation of CAT Score With Peak Expiratory Flow in Acute Exacerbation of COPD Patients
2016, Journal of the National Medical Association
Citation Excerpt :
Previous studies have indicated that CAT score may be used to assess health conditions of these patients and to determine high-risk patients.7–15 Spirometry is routinely used for clinical assessment of COPD patients, although it has been reported that Peak Expiratory Flow (PEF) can also be safely used instead of spirometry.1,16–19 A literature scan did not yield any reports on the correlation between the CAT score and PEF.
Chronic obstructive pulmonary disease (COPD) leads to physical activity limitation and a significant reduction in quality of life. This study aimed to investigate the correlation between The COPD Assessment Test (CAT) score and peak expiratory flow (PEF), and the factors effecting hospital admission rates of patients with COPD.
This observational study was conducted prospectively. CAT score was calculated and PEF measured at the time of emergency department admission. Descriptive statistics were expressed as number (n), percentage (%), and mean ± standard deviation. Chi-Square and correlation tests were used for statistical analyses. A p value of less than 0.05 was considered statistically significant.
Of 123 patients included in the study, 85 (69.1%) were male and 38 (30.9%) were female. Pulse pressure, pH, blood urea nitrogen, oxygen saturation measured by pulse oximetry (SpO₂), PO₂, PCO_2, and SpO₂ values on arterial blood gas analysis, and PEF value were significantly correlated to CAT score (p < 0.05).
High CAT score and low PEF value can be used to make the decision of hospitalization from emergency department in acute exacerbations of COPD.
Intravenous and nebulized magnesium sulfate for treating acute asthma in adults and children: A systematic review and meta-analysis
2013, Respiratory Medicine
This systematic review and meta-analysis was conducted to estimate the effects of intravenous and nebulized magnesium sulfate on treating adults and children with acute asthma.
Electronic literature search and the manual search of key respiratory journals were performed up to October 18, 2011. Randomized controlled trials were included if patients had been treated with intravenous or nebulized magnesium sulfate in combination with β2-agonists and were compared with the use of β2-agonists. Standardized mean differences (SMDs) and the relative risks (RRs) were calculated for pulmonary functions and hospital admission respectively.
25 trials (16 intravenous, 9 nebulized) involving 1754 patients were included. In adults intravenous treatment was associated with a significant effect upon respiratory function (SMD, 0.30; 95% confidence interval (CI), 0.05 to 0.55; p = 0.02) but weak evidence of effect upon hospital admission (RR 0.86,95% CI 0.73 to 1.01; p = 0.06) in adults, and in children with significant effects upon both respiratory function (SMD, 1.94; 95% CI, 0.80 to 3.08; p = 0.0008) and hospital admission (RR, 0.70; 95% CI, 0.54 to 0.91; p = 0.008). Nebulized treatment was associated with significant effects upon respiratory function (SMD, 0.23; 95% CI, 0.06 to 0.41; p = 0.009) and hospital admission (RR, 0.63; 95% CI, 0.43 to 0.92; p = 0.02) in adults.
The use of intravenous magnesium sulfate, in addition to β2-agonists and systemic steroids, in the treatment of acute asthma appears to produce benefits with respect to improve pulmonary function and reduce the number of hospital admissions for children, and only improve pulmonary function for adults. However, the use of nebulized magnesium sulfate just appears to produce benefits for adults.

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A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks

Abstract

Introduction

Section snippets

Participants

Results

Discussion

Chest

Chest

Ann Emerg Med

Ann Emerg Med

Am J Med

Ann Emerg Med

Lancet

Chest