Respiratory Disorders

MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children.

Posted by

0


There are few data on the role of nebulised magnesium sulphate (MgSO4) in the management of acute asthma in children. Those studies that have been published are underpowered, and use different methods, interventions and comparisons. Thus, no firm conclusions can be drawn.
OBJECTIVES: Does the use of nebulised MgSO4, when given as an adjunct to standard therapy in acute severe asthma in children, result in a clinical improvement when compared with standard treatment alone?
DESIGN: Patients were randomised to receive three doses of MgSO4 or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour. The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation.
SETTING: Emergency departments and children`s assessment units at 30 hospitals in the UK. 
PARTICIPANTS: Children aged 2-15 years with acute severe asthma.
INTERVENTIONS: Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years) or 5 mg (ages >/= 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals. MAIN OUTCOME MEASURES: The primary outcome measure was the ASS after 1 hour of treatment. Secondary measures included `stepping down` of treatment at 1 hour, number and frequency of additional salbutamol administrations, length of stay in hospital, requirement for intravenous bronchodilator treatment, and intubation and/or admission to a paediatric intensive care unit. Data on paediatric quality of life, time off school/nursery, health-care resource usage and time off work were collected 1 month after randomisation.
RESULTS: A total of 508 children were recruited into the study; 252 received MgSO4 and 256 received placebo along with the standard treatment. There were no differences in baseline characteristics. There was a small, but statistically significant difference in ASS at T60 in those children who received nebulised MgSO4 {0.25 [95% confidence interval (CI) 0.02 to 0.48]; p = 0.034} and this difference was sustained for up to 240 minutes [0.20 (95% CI 0.01 to 0.40), p = 0.042]. The clinical significance of this gain is uncertain. Assessing treatment-covariate interactions, there is evidence of a larger effect in those children with more severe asthma exacerbations ( p = 0.034) and those with a shorter duration of symptoms ( p = 0.049). There were no significant differences in the secondary outcomes measured. Adverse events (AEs) were reported in 19% of children in the magnesium group and 20% in the placebo group. There were no clinically significant serious AEs in either group. The results of the base-case economic analyses are accompanied by considerable uncertainty, but suggest that, from an NHS and Personal Social Services perspective, the addition of magnesium to standard treatment may be cost-effective compared with standard treatment only. The results of economic evaluation show that the probability of magnesium being cost-effective is over 60% at cost-effectiveness thresholds of pound1000 per unit decrement in ASS and pound20,000 per quality-adjusted life-year (QALY) gained, respectively; it is noted that for some parameter variations this probability is much lower, reflecting the labile nature of the cost-effectiveness ratio in light of the small differences in benefits and costs shown in the trial and the relation between the main outcome measure (ASS) and preference based measures of quality of life used in cost-utility analysis (European Quality of Life-5 Dimensions; EQ-5D).
CONCLUSIONS: This study supports the use of nebulised isotonic MgSO4 at the dose of 151 mg given three times in the first hour of treatment as an adjuvant to standard treatment when a child presents with an acute episode of severe asthma. No harm is done by adding magnesium to salbutamol and ipratropium bromide, and in some individuals it may be clinically helpful. The response is likely to be more marked in those children with more severe attacks and with a shorter duration of exacerbation. Although the study was not powered to demonstrate this fully, the data certainly support the hypotheses that nebulised magnesium has a greater clinical effect in children who have more severe exacerbation with shorter duration of symptoms.

 

Cooking fuels and prevalence of asthma: a global analysis of phase three of the International Study of Asthma and Allergies in Childhood (ISAAC).

Posted by

0


Background

Indoor air pollution from a range of household cooking fuels has been implicated in the development and exacerbation of respiratory diseases. In both rich and poor countries, the effects of cooking fuels on asthma and allergies in childhood are unclear. We investigated the association between asthma and the use of a range of cooking fuels around the world.

Methods

For phase three of the International Study of Asthma and Allergies in Childhood (ISAAC), written questionnaires were self-completed at school by secondary school students aged 13—14 years, 244 734 (78%) of whom were then shown a video questionnaire on wheezing symptoms. Parents of children aged 6—7 years completed the written questionnaire at home. We investigated the association between types of cooking fuels and symptoms of asthma using logistic regression. Adjustments were made for sex, region of the world, language, gross national income, maternal education, parental smoking, and six other subject-specific covariates. The ISAAC study is now closed, but researchers can continue to use the instruments for further research.

Findings

Data were collected between 1999 and 2004. 512 707 primary and secondary school children from 108 centres in 47 countries were included in the analysis. The use of an open fire for cooking was associated with an increased risk of symptoms of asthma and reported asthma in both children aged 6—7 years (odds ratio [OR] for wheeze in the past year, 1·78, 95% CI 1·51—2·10) and those aged 13—14 years (OR 1·20, 95% CI 1·06—1·37). In the final multivariate analyses, ORs for wheeze in the past year and the use of solely an open fire for cooking were 2·17 (95% CI 1·64—2·87) for children aged 6—7 years and 1·35 (1·11—1·64) for children aged 13—14 years. Odds ratios for wheeze in the past year and the use of open fire in combination with other fuels for cooking were 1·51 (1·25—1·81 for children aged 6—7 years and 1·35 (1·15—1·58) for those aged 13—14 years. In both age groups, we detected no evidence of an association between the use of gas as a cooking fuel and either asthma symptoms or asthma diagnosis.

Interpretation

The use of open fires for cooking is associated with an increased risk of symptoms of asthma and of asthma diagnosis in children. Because a large percentage of the world population uses open fires for cooking, this method of cooking might be an important modifiable risk factor if the association is proven to be causal.

Source: Lancet

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.

Posted by

0


Background

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO4) in acute asthma in children. We assessed the effect of MgSO4 treatment in children with severe acute asthma.

Methods

In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2—16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO4 (250 mmol/L; 151 mg per dose; MgSO4 group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.

Findings

Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO4and 256 to placebo. Mean ASS at 60 min was lower in the MgSO4 group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference −0·25, 95% CI −0·48 to −0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.

Interpretation

Overall, nebulised isotonic MgSO4, given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO2<92%) at presentation and those with preceding symptoms lasting less than 6 h.

Source: lancet

 

“Proning” Benefits Patients with Severe ARDS.

Posted by

0


Acute respiratory distress syndrome–associated 28-day mortality was halved in patients who spent most of the day face down.

 

Patients with acute respiratory distress syndrome (ARDS) commonly develop consolidation of the dependent lung regions. For many years, physicians have transitioned severely hypoxemic patients from supine to prone position to improve aeration of these areas and gas exchange. Small studies of “proning” demonstrated improved oxygenation without affecting more important outcomes; meta-analyses suggested proning could lower ARDS-associated mortality (Intensive Care Med 2010; 36:585).

This large French trial involved 466 patients with moderate-to-severe ARDS (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen [PaO2:FiO2] <150, with FiO2 0.6; positive end-expiratory pressure, 5 cm H2O). All patients received low tidal-volume ventilation and were randomized to daily prone positioning or to supine positioning only. Intervention patients were placed in the prone position within 1 hour of randomization and underwent an average of four sessions of proning (mean duration per daily session, 17.3 hours). At randomization, >80% of patients were receiving neuromuscular blockade, and approximately 40% were receiving glucocorticoids. Mortality at 28 days was 16% in the prone group and 33% in the supine group.

Comment: These results give new life to the practice of proning. Although this intervention is not suitable for all patients with acute respiratory distress syndrome (e.g., those with recent sternotomy or facial trauma), proning should be considered early for most patients with severe disease. Almost all patients in this study received neuromuscular blockade, which reinforces earlier administering of short-term paralytics for severe hypoxemia. Patients in this study were proned for prolonged periods. Delivering care safely to patients in this position for most of the day will require additional training of nurses and other providers.

 

Source: Journal Watch General Medicine