Nebulized Magnesium Sulfate Research Articles

Systematic Review on Efficacy of Magnesium (Intravenous or Nebulized) for Acute Asthma Episodes in Children: Evidence-based Medicine Viewpoint.

This systematic review and meta-analysis aimed to evaluate the efficacy of intravenous (IV) and nebulized magnesium sulfate for acute asthma in children. Ten randomized and quasi-randomized trials (6 IV, 4 nebulized) were identified through search of databases (PubMed, Cochrane Library, and EMBASE). Intavenous magnesium sulfate treatment was associated with significant effects on respiratory function (standardized mean difference 1.94; 95% CI 0.80,3.08; P=0.0008) and hospital admission (RR 0.55; 95% CI 0.31,0.95; P=0.03). But nebulized magnesium sulfate treatment showed no significant effect on respiratory function (standardized mean difference 0.19; 95% CI–0.01, 0.40; P=0.07) or hospital admission (RR 1.11; 95% CI 0.86,1.44; P=0.42). Authors concluded that IV magnesium sulfate is an effective treatment in children, with significant improvement in pulmonary function and decrease in hospitalization and need for further treatment, but nebulized magnesium sulfate treatment showed no significant effect on respiratory function or hospital admission and further treatment.

Comparison Efficacy of Randomized Nebulized Magnesium Sulfate and Ipratropium Bromide/Fenoterol in Children with Severe Asthma Exacerbation

Comparison Efficacy of Randomized Nebulized Magnesium Sulfate and Ipratropium Bromide/Fenoterol in Children with Severe Asthma Exacerbation

The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment

BackgroundAfter 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. MethodsOur 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 1mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15mg/kg/dose) and 1ml magnesium sulphate (15%)+1.5ml isotonic saline on three occasions at roughly 20min intervals (Magnesium group) or nebulised salbutamol (0.15mg/kg/dose) and 2.5ml isotonic saline mixture on three occasions at roughly 20min 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. ResultsBoth 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. ConclusionsThe use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study.

Nebulised magnesium sulphate in the management of asthma.

While the use of intravenous magnesium sulphate (MgSO4) is an accepted part of the pharmacological management of patients with asthma, there is conflicting information about whether it is beneficial in its nebulised form.

The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma.

ObjectiveEvaluation of the efficacy of nebulized magnesium sulfate (MgSO4) alone and in combination with salbutamol in acute asthma.MethodsA double-blind randomized controlled study was conducted in Chest and Emergency Departments. Thirty patients of acute attack of bronchial asthma were randomized into three groups: MgSO4 nebulization (group A), salbutamol nebulization (group B), and their combination (group C). All patients were monitored before and after nebulization (each 20 minutes) for peak expiratory flow rate (PEFR), respiratory rate (RR), heart rate (HR), blood pressure, pulsus paradoxus, oxygen saturation, clinical examination, and Fischl index.ResultsA highly significant improvement in PEFR, PEFR percentage, and Fischl index and significant decrease in RR and HR was observed in all groups. A similar improvement in PEFR was observed in group A and group B (P=0.389). The difference in peak expiratory flow (PEF) improvement was insignificant between group B and group C (P=0.101), while there was a significant difference between group A and group C (P=0.014) in favor of group C.ConclusionNebulized MgSO4 alone or combined with salbutamol has a clinically significant bronchodilator effect in acute asthma and leads to clinical improvement, increase in PEFR, reduction in HR, and reduction in RR. The response to nebulized MgSO4 alone (PEFR improvement 54±35.6 L/min, P=0.001) is comparable (P=0.389) to that of nebulized salbutamol (PEFR improvement 67.0±41.9 L/min, P=0.001) and is significantly less than (P=0.014) that of nebulized combination (PEFR improvement 92.0±26.9 L/min, P=0.000).

Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study.

BackgroundClinical trials with longitudinally measured outcomes are often plagued by missing data due to patients withdrawing or dropping out from the trial before completing the measurement schedule. The reasons for dropout are sometimes clearly known and recorded during the trial, but in many instances these reasons are unknown or unclear. Often such reasons for dropout are non-ignorable. However, the standard methods for analysing longitudinal outcome data assume that missingness is non-informative and ignore the reasons for dropout, which could result in a biased comparison between the treatment groups.MethodsIn this article, as a post hoc analysis, we explore the impact of informative dropout due to competing reasons on the evaluation of treatment effect in the MAGNETIC trial, the largest randomised placebo-controlled study to date comparing the addition of nebulised magnesium sulphate to standard treatment in acute severe asthma in children. We jointly model longitudinal outcome and informative dropout process to incorporate the information regarding the reasons for dropout by treatment group.ResultsThe effect of nebulised magnesium sulphate compared with standard treatment is evaluated more accurately using a joint longitudinal-competing risk model by taking account of such complexities. The corresponding estimates indicate that the rate of dropout due to good prognosis is about twice as high in the magnesium group compared with standard treatment.ConclusionsWe emphasise the importance of identifying reasons for dropout and undertaking an appropriate statistical analysis accounting for such dropout. The joint modelling approach accounting for competing reasons for dropout is proposed as a general approach for evaluating the sensitivity of conclusions to assumptions regarding missing data in clinical trials with longitudinal outcomes.Trial registrationEudraCT number 2007-006227-12. Registration date 18 Mar 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1342-0) contains supplementary material, which is available to authorized users.

Efficiency of nebulised magnesium sulphate in infective exacerbations of chronic obstructive pulmonary disease

Conflicting results has been achieved in a small number of clinical studies evaluating the efficiency of magnesium sulphate (MS) in COPD exacerbations. We aimed to investigate the efficiency of nebulised MS in COPD exacerbations. Twenty patients who met the study criteria were randomized into two groups. All patients were treated with O2, antibiotics and oral corticosteroids. Additionally one group received ipratropium bromide (IB) 500 µg together with MS 151 mg/dose, while the other group received IB together with placebo. The patients were followed-up with forced expiratory volume in 1 second (FEV1) and visual analogue scale dyspnea scores for 48 hours. Peak expiratory flow rates (PEFRs) were measured before and 10, 30, 60 and 120 minutes after each nebule treatment. The baseline characteristics of the patients in both groups were similar. The FEV1 values measured at 24 and 48 hours did not show significant changes compared to baseline in both groups. Dyspnea scores in both groups decreased significantly in the first day, and in only MS group in the second day. The % change in the dyspnea score at the end of first day was significantly more in the MS group [-23.8% (13.6)] compared with the placebo group [-9.4% (12.9)] (p= 0.002). The % changes in PEFRs at 10 minutes [4.7 (7.5) and -3.5 (6.0), p= 0.005] and 30 minutes [8.2 (6.7) and 1.3 (5.5), p= 0.03] were significantly greater in the MS group compared with the placebo group on the first day. No side effects developed due to MS. Nebulised MS is a cheap, feasible and safe drug that can be added to the standart bronchodilator treatment since it provides additional relief of dyspnea in patients with COPD exacerbations. This needs to be evaluated in future clinical studies including greater number of patients.

The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: a randomized clinical trial

ObjectiveThirty percent of people with asthma do not respond to standard treatment, and complementary therapies are needed. The objective of this study was to investigate the impact of inhaled magnesium sulfate on the treatment response in emergency department (ED) patients with moderate to severe attacks of asthma. MethodsThis study is a randomized controlled trial, enrolling patients with moderate to severe asthma in the ED. Subjects allocated to the study group were treated with the standard, plus 3ml of 260mmol/L solution of magnesium sulfate every 20 to 60minutes. The control group was treated with nebulized saline as a placebo in addition to standard protocol. The study results included admission rate and changes in peak expiratory flow rate (PEFR) (primary outcomes) as well as dyspnea severity score, respiratory rate and peripheral oxygen saturation. ResultsA total of 50 patients were enrolled (25 allocated to the study group and 25 to the control group). The study group as compared to the control group had significantly more improvement in the intensity of dyspnea, PEFR and Spo2 20, 40 and 60minutes after intervention. In the control group, 11 patients (44%) required admission as compared to 18 (72%) in the control group (P=.02). ConclusionAdding nebulized magnesium sulfate to standard therapy in patients with moderate to severe asthma attacks leads to greater and faster improvement in PEFR, respiratory rate, oxygen saturation and respiratory rate. It also reduces hospitalization rates in this patient population.

Effect of magnesium sulfate nebulization on the incidence of postoperative sore throat.

Background and Aims:Postoperative sore throat (POST) is a well-recognized complication after general anesthesia (GA). Numerous nonpharmacological and pharmacological measures have been used for attenuating POST with variable success. The present study was conducted to compare the efficiency of preoperative nebulization of normal saline and magnesium sulfate in reducing the incidence of POST following GA.Materials and Methods:Following institutional ethical committee approval and written informed consent, a prospective randomized double-blinded study was conducted in 100 cases divided into two equal groups. Patients included in the study were of either gender belonging to American Society of Anesthesiologist (ASA) status 1 or 2 undergoing elective surgery of approximately 2 h or more duration requiring tracheal intubation. Patients in Group A are nebulized with 3 ml of normal saline and the patients in Group B are nebulized with 3 ml of 225 mg isotonic nebulized magnesium sulfate for 15 min, 5 min before induction of anesthesia. The incidence of POST at rest and on swallowing and any undue complaints at 0, 2, 4, and 24 h in the postoperative period are evaluated.Results:There is no significant difference in POST at rest during 0th, 2nd and 4th h between normal saline and MgSO4. Significant difference is seen at 24th h, where MgSO4 lessens POST. There is no significant difference in POST on swallowing during 0th and 2nd h between normal saline and MgSO4. Significant difference is seen at 4th h, where MgSO4 has been shown to lessen POST.Conclusions:MgSO4 significantly reduces the incidence of POST compared to normal saline.

Nebulized Magnesium Sulfate in Acute Bronchiolitis: A Randomized Controlled Trial.

To assess the efficacy of nebulized magnesium sulfate as a bronchodilator in infants hospitalized with acute bronchiolitis. This three-center double masked randomized clinical trial comprised 120 children with moderate to severe bronchiolitis. They were randomly assigned into two groups: the first group was treated with nebulized magnesium sulfate (40 mg/kg) and nebulized epinephrine (0.1 ml/kg) and the second group (control) was treated with nebulized epinephrine (0.1 ml/kg). The primary outcome was the length of hospital stay. The use of oxygen, temperature, oxygen saturation (SPO2), pulse rate (PR), respiratory rate (RR) and respiratory distress assessment instrument (RDAI) score were measured in the beginning of the study and during hospitalization. The mean (SD) age of 120 infants was 5.1(± 2.6) mo and 60% were boys. The length of hospital stay was not different between the two groups (P > 0.01). Use of oxygen supplementation, SPO2 and vital signs were similar in the two groups. Improvement in RDAI score was significantly better in infants treated with nebulized magnesium sulfate than in the other group (P 0.01). Thus, in infants with acute bronchiolitis, the effect of nebulized magnesium sulfate is comparable to nebulized epinephrine. However nebulized magnesium sulfate can improve the clinical score so it may have additive effect to reduce symptoms during hospitalization.

Advances in acute asthma.

The purpose of this study is to highlight some of the recent findings related with the management of acute exacerbations in the context of the emergency department setting. β₂-agonist heliox-driven nebulization significantly increased by 17% [95% confidence interval (CI) 5.2-29.4] peak expiratory flow, and decreased the rate of hospital admissions (risk ratio 0.77, 95% CI 0.62-0.98), compared with oxygen-driven nebulization. Other findings indicate that there is no robust evidence to support the use of intravenous or nebulized magnesium sulphate in adults with severe acute asthma, and that levalbuterol was not superior to albuterol regarding efficacy and safety in individuals with acute asthma. Finally, hyperlactatemia developed during the first hours of acute asthma treatment has a high prevalence, is related with the use of β₂-agonists and had no clinical consequences. After a comprehensive review of the best quality pieces of literature published in the last year, it is possible to conclude that the goals of acute asthma management remain almost unchanged.

O-203a Inhaled Magnesium For Moderate And Severe Paediatric Asthma

Background Intravenous magnesium sulfate, a rescue therapy added to combined bronchodilator and systemic steroid therapy for moderate and severe asthma, is uncommonly administered. We hypothesised that nebulized magnesium sulfate would confer benefit without undue risk. Methods Patients aged 2 to 14 y with moderate and severe status asthmaticus (PRAM severity score >4) admitted to infirmary care were randomised double-blind to 800 mg nebulized magnesium sulfate or normal saline placebo via Aeroneb Pro and Idehaler, after intensive therapy with combined albuterol-ipratropium and intravenous methylprednisolone. Time to medical readiness for discharge was the primary outcome; sample size was chosen to detect a 10% improvement. Improvement over time in PRAM severity score and other secondary outcomes were compared for the overall group and severe asthma subset. Results 191 magnesium sulfate and 174 placebo patients met criteria for analysis. The groups were similar with mean baseline PRAM scores >7. Blinded active therapy significantly increased blood magnesium level 2 h post-treatment 0.85 (SD 0.07) vs 0.82 (SD 0.06) mmol/L, p = 0.001). There were no important adverse effects. However, accelerated failure time analysis showed a non-significantly shortened time to medical readiness for discharge of 14% favouring the magnesium sulfate group, OR=1.14, 95% CI 0.93 to 1.40, p = 0.20. Mean times until readiness for discharge were 14.6 h [SD 9.7] vs 15.6 h [SD 11.3] for the investigational and placebo groups, respectively, p = 0.9. Conclusions Adding nebulized magnesium sulfate to combined nebulized bronchodilator and systemic steroid therapy fails to provide evident benefit for patients with moderate or severe status asthamticus.

Economic evaluation of nebulized magnesium sulphate in acute severe asthma in children.

The aim of this study was to estimate the cost-effectiveness of nebulized magnesium sulphate (MgSO4) in acute asthma in children from the perspective of the UK National Health Service and personal social services. An economic evaluation was conducted based on evidence from a randomized placebo controlled multi-center trial of nebulized MgSO4 in severe acute asthma in children. Participants comprised 508 children aged 2-16 years presenting to an emergency department or a children's assessment unit with severe acute asthma across thirty hospitals in the United Kingdom. Children were randomly allocated to receive nebulized salbutamol and ipratropium bromide mixed with either 2.5 ml of isotonic MgSO4 or 2.5 ml of isotonic saline on three occasions at 20-min intervals. Cost-effectiveness outcomes were constructed around the Yung Asthma Severity Score (ASS) after 60 min of treatment; whilst cost-utility outcomes were constructed around the quality-adjusted life-year (QALY) metric. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative cost-effectiveness thresholds for either: (i) a unit reduction in ASS; or (ii) an additional QALY. MgSO4 had a 75.1 percent probability of being cost-effective at a GBP 1,000 (EUR 1,148) per unit decrement in ASS threshold, an 88.0 percent probability of being more effective (in terms of reducing the ASS) and a 36.6 percent probability of being less costly. MgSO4 also had a 67.6 percent probability of being cost-effective at a GBP 20,000 (EUR 22,957) per QALY gained threshold, an 8.5 percent probability of being more effective (in terms of generating increased QALYs) and a 69.1 percent probability of being less costly. Sensitivity analyses showed that the results of the economic evaluation were particularly sensitive to the methods used for QALY estimation. The probability of cost-effectiveness of nebulized isotonic MgSO4, given as an adjuvant to standard treatment of severe acute asthma in children, is less than 70 percent across accepted cost-effectiveness thresholds for an additional QALY.

Effect of inhaled magnesium sulfate on bronchial hyperresponsiveness.

To determine the response of nebulized magnesium sulfate on the lung function of children with bronchial hyperresponsiveness. Eighty-four children with asthma were divided into three groups randomly: magnesium sulfate (M), albuterol (A), and a combination of magnesium sulfate and albuterol (M + A). All patients were nebulized with acetylcholine, and then treated as designed. Lung function was compared between the three groups. Forced expiratory volume in first second (FEV1) significantly improved in all the three groups but it was better in (A) and (M + A) compared to (M) at 10 min and 20 min [10 min: 1.26 L ± 0.53 (A) vs. 1.10 L ± 0.27 (M), 1.35 L ± 0.59 (M + A) vs. 1.10 L ± 0.27 (M), p < 0.05; 20 min: 1.32 L ± 0.61 (A) vs. 1.17 L ± 0.30 (M), 1.42 L ± 0.59 (M + A) vs. 1.17 L ± 0.30 (M), p < 0.05]. Variation of FEV1, as absolute value at 10 min or 20 min over post-Ach FEV1 was significantly different in (A) or (M + A) compared to (M). Nebulized albuterol and magnesium sulfate + albuterol can more effectively improve FEV1 in children with bronchial hyperresponsiveness than nebulized magnesium sulfate at 10 min and 20 min after inhalation. It is further suggested that addition of magnesium sulfate to albuterol does not result in additional benefit.

The efficacy of nebulized salbutamol, magnesium sulfate, and salbutamol/magnesium sulfate combination in moderate bronchiolitis

The aim of this paper is to compare the effect of nebulized magnesium sulfate to nebulized salbutamol and salbutamol/magnesium sulfate on successful discharge from the emergency department. A total of 56 infants were included in this double-blinded, prospective study. Infants were grouped according to the nebulized treatment they received: group 1-salbutamol/normal saline, group 2-magnesium sulfate and normal saline, and group 3-salbutamol plus magnesium sulfate. Heart beat, bronchiolitis, clinical severity scores (CSS), and oxygen saturation of the patients were determined before and after nebulization (0, 1, 4h). The patients were monitored for adverse reactions. Post-treatment mean CSS results were significantly lower than pre-treatment scores in all groups at 4h with no significant difference within groups. CSS scores were lower in the salbutamol/magnesium sulfate group when compared with the magnesium sulfate and salbutamol groups (3.4 (2.4-4.3), 4.7 (3.8-5.7), 4.0 (3.2-4.3)). CSS were significantly lower than those from the magnesium sulfate group. Nebulized magnesium sulfate plus salbutamol may have additive effects for improving the short-term CSS.

The 3Mg trial: a randomised controlled trial of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma.

Magnesium sulphate, administered by the intravenous (i.v.) or inhaled (nebulised) route, has been proposed as a treatment for adults with acute severe asthma. Existing trials show mixed results and uncertain evidence of benefit. We aimed to determine whether i.v. or nebulised magnesium sulphate improves symptoms of breathlessness and reduces the need for hospital admission in adults with acute severe asthma. Multicentre, double-blind, placebo-controlled, three-arm, randomised trial. The emergency departments of 34 acute hospitals in the UK. We recruited 1109 adults (age >16 years) with acute severe asthma [peak expiratory flow rate (PEFR) <50% of best/predicted, respiratory rate >25 breaths per minute, heart rate >110 beats per minute or inability to complete sentences in one breath]. Patients with life-threatening features or a contraindication to either nebulised or intravenous magnesium sulphate were excluded. Participants were randomly allocated to i.v. magnesium sulphate (2 g over 20 minutes) or nebulised magnesium sulphate (3 × 500 mg over 1 hour) or standard therapy alone. The primary outcome was the proportion of patients admitted to hospital (either after emergency department treatment or at any time over the subsequent 7 days) and breathlessness measured on a 100-mm visual analogue scale (VAS) over 2 hours after initiation of treatment. We randomised 406 patients to i.v. magnesium sulphate, 339 to nebulised magnesium sulphate and 364 to placebo. Hospital admission was recorded for 394, 332 and 358 patients, respectively, and VAS breathlessness for 357, 296 and 323 patients respectively. Mean age was 36.1 years and 763 out of 1084 (70%) patients were female. Intravenous magnesium sulphate was associated with an odds ratio (OR) of 0.73 [95% confidence interval (CI) 0.51 to 1.04; p=0.083] for hospital admission, an improvement in VAS breathlessness that was 2.6 mm (95% CI -1.6 to 6.8 mm; p=0.231) greater than that associated with placebo and an improvement in PEFR that was 2.4 l/minute (95% CI -8.8 to 13.6 l/minute; p=0.680) greater than that associated with placebo. Nebulised magnesium sulphate was associated with an OR of 0.96 (95% CI 0.65 to 1.40; p=0.819) for hospital admission, an improvement in VAS breathlessness that was 2.6 mm (95% CI -1.8 mm to 7.0 mm; p=0.253) less than that associated with placebo and an improvement in PEFR that was 2.6 l/minute (95% CI -9.2 to 14.5 l/minute; p=0.644) less than that associated with placebo. There were no significant differences between i.v. or nebulised magnesium sulphate and placebo for any other outcomes. The number (%) of patients reporting any side effect was 61 (15.5%) in the i.v. group, 52 (15.7%) in the nebuliser group and 36 (10.1%) in the placebo group. The ORs for suffering any side effect were 1.68 (95% CI 1.07 to 2.63; p=0.025) for i.v. compared with placebo and 1.67 (95% CI 1.05 to 2.66; p=0.031) for nebuliser compared with placebo. We were unable to demonstrate a clinically worthwhile benefit from magnesium sulphate in acute severe asthma. There was some weak evidence of an effect of i.v. magnesium sulphate on hospital admission, but no evidence of an effect on VAS breathlessness or PEFR compared with placebo. We found no evidence that nebulised magnesium sulphate was more effective than placebo. Current Controlled Trials ISRCTN04417063.

The value of magnesium sulfate nebulization in treatment of acute bronchial asthma during pregnancy

Little is known about the effect of inhaled Mg sulfate when added to B2 agonist in acute asthma with pregnancy. Our objectiveTo evaluate the broncho-dilator effect of nebulized magnesium sulfate with B2 agonist in the treatment of acute asthma during pregnancy, and its safety on pregnancy outcome. Material and methodsThe studied patients were randomized into two groups. “Group A” patients received the routine treatment of acute asthma exacerbation plus nebulized salbutamol in dose of 1ml of salbutamol solution dissolved in 9ml of normal saline. “Group B” patients received the same above treatment plus 500mg (1ml) of magnesium sulfate. Two hours after therapy, pulmonary function test and blood gas analysis were done. ResultTotal 60 pregnant women with acute asthma, 30 patients in each group with mean age were 25.9±4.01 and 25.7±3.8. Comparison between both groups in pulse rate, arterial oxygen tension and oxygen saturation was significant (P<0.001). FEV1 was 32.68±7.15 and 56.31±8.25 in groups A and B respectively and % of change was 69% with significant P value<0.001. The frequency of asthma exacerbation till delivery was 3.2±0.98 & 0.4±0.57 in groups A and B respectively (95% CI 2.4–3.1) with significant P value (P<0.001). All patients had either normal delivery (60% and 66.6%) or Cesarian (40% and 33.6%) with smooth neonatal period. In ConclusionAdding Nebulized Mgs for acute asthma during pregnancy is effective and safe. The availability, cheapness of this drug especially for the developing countries added to its advantage.

Magnesium for acute exacerbation of chronic obstructive pulmonary disease: A systematic review of randomised trials.

The efficacy of magnesium sulphate in chronic obstructive pulmonary disease (COPD) was assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on route(s) of administration of magnesium sulphate and medications co-administered. Risk of bias was evaluated and quality of evidence was graded. Four (4) randomized trials were included. All trials had a moderate risk of bias and were of average methodological quality. Magnesium sulphate given intravenously did not seem to have an immediate bronchodilatory effect; however it appears to potentiate the bronchodilatory effect of inhaled beta-2 agonists. Increase in peak expiratory flow rate (PEFR) at 30 and 45 min was greater in those who received magnesium sulphate compared to placebo (P = 0.03), although the mean percentage change in PEFR was just 24%, without significant differences in dyspnoea scores, hospital admission rates, or emergency department readmission rates compared to placebo. Nebulized magnesium sulphate with salbutamol versus nebulized salbutamol with saline placebo showed no significant differences is forced expiratory volume in 1 s (FEV1) measured at 90 min after adjustment for baseline FEV1 (P = 0.34) or differences in the need for hospital admission. Combined inhalational and intravenous magnesium sulphate versus intravenous saline placebo and nebulized ipratropium bromide were comparable in terms of hospital admission, intubation and death, but the ipratropium bromide group showed better bronchodilator effect and improvement in arterial blood gas parameters. Overall, trial evidence for trial evidence for magnesium sulphate in acute exacerbation of COPD is poor, and further well-designed trials are needed.

Effect of Inhaled MgSO4 on FEV1 and PEF in Children with Asthma Induced by Acetylcholine: A Randomized Controlled Clinical Trail of 330 Cases

To determine the response of nebulized magnesium sulfate on the lung function of acetylcholine-induced asthma children. Three hundred and thirty children of asthma with positive bronchial provocation test were randomly divided into three groups: magnesium sulfate, albuterol, and a combination of magnesium sulfate and albuterol. Lung function was compared between the three groups. Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) as percentage over predicted at 10 min and 20 min in albuterol and combination group were significantly improved when compared to magnesium group. The changes in FEV1 and PEF expressed as absolute and percentage over predicted was not statistically significant from baseline to 20 min in magnesium, albuterol, and combination of magnesium sulfate and albuterol. There was no significant adverse effect observed during the present study. Nebulized magnesium sulfate alone has a bronchodilatory effect in Ach-induced asthmatic children. The combination of MgSO4 and albuterol did not has a synergistic effect.

Adjusting for informative missing outcome data in clinical trials with longitudinal study designs

In many clinical trials with longitudinal outcome data, a common situation is where some patients withdraw or dropout from the trial before completing the measurement schedule. In most cases reasons for dropout is related to the subsequent outcome, hence missingess is informative or non-ignorable. Failure to take appropriate account of such missing data can lead to biased estimation of treatment effects. Imputation methods fail for predicting the missing data, as they rely on assumptions that are unverifiable from the observed data. Joint modelling is a novel statistical methodology that can be used to analyse the longitudinal outcome data adjusting for non-ignorable missingness. The methodology combines the information from the longitudinal outcome data and the subsequent dropout patterns over time. In the MAGNETIC trial (a randomised, placebo controlled trial of nebulised Magnesium Sulphate in acute severe asthma in children) the primary outcome, Yung Asthma Severity Score (ASS), was measured at baseline and 20, 40, 60, 120, 180 and 240 minutes following randomisation. The missingness in ASS outcome at various time points was over 5% and reasons for missingness were sometimes clearly related with study withdrawal due to good or poor status of the child, but in many instances these reasons were not known or unclear. Ignoring the informative nature of the missing outcome data in the statistical analysis could result in inaccurate estimation of treatment effect.