Acute Severe Asthma In Children Research Articles

Safety and Effectiveness of Magnesium Sulphate for Severe Acute Asthma Management Among Under-five Children: Systematic Review and Meta-analysis.

Asthma is the common chronic inflammatory disease affecting children. It is usually associated with airway hyper-responsiveness. Globally, the prevalence of asthma among pediatrics population varies from 10% to 30%. Its symptoms range from chronic cough to life-threatening bronchospasm. At emergency department, all patients with acute severe asthma should initially receive oxygen, nebulized β2-agonists, nebulized anticholinergic agent, and corticosteroids. Though bronchodilators act within minutes, corticosteroids may require hours. Magnesium sulphate (MgSO4) was first considered for treating asthma about 60 years ago. Several case reports were published on its usefulness in decreasing admission and endotracheal intubation. So far, evidence is conflicting to fully employ MgSO4 for asthma management in children under five. This systematic review was aimed to evaluate the effectiveness and safety of MgSO4 in the treatment of severe acute asthmatic attacks in children. A systematic and comprehensive search of literature was performed to identify controlled clinical trials conducted on IV and nebulized MgSO4 in pediatric patients with acute asthma. Data generated from three randomized clinical trials were included in the final analysis. In this analysis, intravenous MgSO4 did not improve respiratory function (RR=1.09, 95%CI: 0.81-1.45) and not safer than conventional treatment (RR=0.38, 95%CI: 0.08-1.67). Similarly, use of nebulized MgSO4 showed no significant effect on respiratory function (RR=1.05, 95%CI: 0.68-1.64) and more tolerable (RR=0.31, 95%CI: 0.14-0.68). Intravenous MgSO4 may not be superior to conventional treatment in moderate to severe acute asthma among children and neither have significant adverse effects. Similarly, nebulized MgSO4 showed no significant effect on respiratory function in moderate to severe acute asthma in children under five but it seems a safer alternative.

Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

RationaleSevere acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only.ObjectivesTo identify the use and type of...

Humidified and standard oxygen therapy in acute severe asthma in children (HUMOX): A pilot randomised controlled trial.

Oxygen (O2) is a mainstay of treatment in acute severe asthma but how it is administered varies widely. The objectives were to examine whether a trial comparing humidified O2 to standard O2 in children is feasible, and specifically to obtain data on recruitment, tolerability and outcome measure stability. Heated humidified, cold humidified and standard O2 treatments were compared for children (2-16 years) with acute severe asthma in a multi-centre, open, parallel, pilot randomised controlled trial (RCT). Multiple outcomes were assessed. Of 258 children screened, 66 were randomised (heated humidified O2 n = 25; cold humidified O2 n = 21; standard O2 n = 20). Median (IQR) length of stay (hours) in hospital was 37.9 (29.1), 52 (35.4) and 49.1 (29.7) for standard, heated humidified and cold humidified respectively and time (hours) on O2 was 15.9 (9.4), 13.6 (14.9) and 13.1 (14.9) for the three groups respectively. The mean (standard deviation) time (hours) taken to step down nebulised to inhaled treatment was 5.6 (14.3), 35.1 (28.2) and 32.7 (20.1). Asthma Severity Score decreased in all three groups similarly, although missing data prevented complete analysis. Humidified O2 was least well tolerated with eight participants discontinuing their randomised treatment early. An important barrier to recruitment was research nurse availability. Although, the results of this pilot study should not be extrapolated beyond the study sample and inferential conclusions should not be drawn from the results, this is the first RCT to compare humidified and standard O2 therapy in acute severe asthmatics of any age. These findings and accompanying screening data show that a large RCT of O2 therapy is feasible. However, challenges associated with randomisation and data collection should be addressed in any future trial design.

Eficácia do uso do sulfato de magnésio intravenoso no tratamento da asma aguda em crianças e adolescentes: uma revisão integrativa

The objective of this study was to analyze the main effects of intravenous magnesium sulfate for the treatment of severe acute asthma in children and adolescents. An integrative review was carried out using the descriptors “magnesium sulfate”, “severe asthma”, “children”, and “adolescents” in English, Portuguese, and Spanish. The inclusion criteria were full articles that portrayed the topic of intravenos use of magnesium sulphate in the treatment of severe acute asthma in children and adolescents, published between 2010 and 2018. The study was completed with 6 articles and the main effects observed were efficacy and decrease in the hospitalization rate of the pediatric patients, causing greater benefit to the patients studied in the last 7 years.

Efficacy of Nebulized Magnesium Sulphate in the Treatment of Acute Bronchial Asthma Compared to Nebulized Salbutamol: A Randomized Control Trial

Background: Nebulized salbutamol is commonly used in treatment of asthma in children. The use of nebulized MgSO4 is one of the different treatment options available during acute exacerbation.
 Objective: To compare the efficacy of nebulized MgSO4 with nebulized salbutamol in the treatment of acute asthma in children.
 Materials and method: This randomized controlled study was conducted in Dhaka Medical College Hospital between January to December 2016. Children of 7-12 years with acute exacerbation of asthma were randomized into study group-A (MgSO4 group, n=30) and control group-B (Salbutamol group, n=30). Children of both groups were treated with serial nebulization thrice at 20 minute intervals by either 2.4 ml (4% MgSO4, 96 mg) or salbutamol (0.15 mg/kg minimum 2.5 mg) with 2.5 ml of isotonic normal saline.
 Results: The mean final PEFR were not different between the two groups (275.0±41.42 L/min in MgS04 group and 263±36.17 L/min in salbutamol group). The increase in PEF was statistically significant and comparable in both groups (by 35.1% in the MgS04 group and by 42.1% in the salbutamol group). Fischl score improvement was comparable and significant in both groups (4.31 to 0.43 in MgS04 group and 4.29 to 0.76 in salbutamol group). Statistically significant increase in oxygen saturation and reduction of heart rate was found in MgS04 group without any side effects. Nebulized MgSO4 was found having significant bronchodilator effect which is comparable to salbutamol.
 Conclusion: Nebulized MgS04 was found equally effective as nebulized salbutamol in the treatment of severe acute asthma in children.
 Bangladesh J Child Health 2020; VOL 44 (1) :24-29

Extracorporeal and advanced therapies for progressive refractory near-fatal acute severe asthma in children.

Asthma is the most common chronic illness and is one of the most common medical emergencies in children. Progressive refractory near-fatal asthmarequiring intubation and mechanical ventilation can lead to death. Extracorporeal membrane oxygenation (ECMO) can provide adequate gas exchange during acute respiratory failure although data on outcomes in children requiring ECMO support for status asthmaticus is sparse with one study reporting survival rates of nearly 85% with asthma being one of the best outcome subsets for patients with refractory respiratory failure requiring ECMO support. We describe the current literature on the use of ECMO and other advanced extracorporeal therapies available for children with acute severe asthma. We also review other advanced invasive and noninvasive therapies in acute severe asthma both before and while on ECMO support.

A clinical study of risk factors for acute severe asthma in children

Background: Asthma is one of the most prevalent diseases worldwide with an estimated 300 million affected children. Acute severe asthma in children is one of the common causes of emergency admissions. There is no much study regarding the risk factors for acute severe asthma in children in India. Hence the present study was conducted to know the risk factors for acute severe asthma in children.Methods: A prospective observational study of 100 children between the age group of 5 and 18 years who presented with symptoms and signs of acute severe asthma admitted to the pediatric intensive care unit (PICU) of Indira Gandhi Institute of Child Health (IGICH) for a period of 12 months between January 2015 to December 2015 formed the study group. These children were evaluated for the risk factors responsible for acute severe asthma.Results: A total of 100 children with acute severe asthma were enrolled in the study. The predominant age group was between 5-10 years (68%), the risk factors responsible for acute severe asthma were poor drug compliance (68%), which was statistically significant (p-value <0.0001), exposure to house dust (61%) and smoke (42%) (p <0.0001). There was also marked rise in absolute eosinophil count (62%).Conclusions: Acute severe asthma in children is one of the common causes of emergency admissions. The present study has shown that poor drug compliance, exposure to house dust and smoke were significant risk factors for acute severe asthma.

Optimizing the Dosing of Intravenous Theophylline in Acute Severe Asthma in Children.

Optimizing the management of children presenting with acute severe asthma is of utmost importance to minimize hospital stays, morbidity, and mortality. Intravenous medications, including theophyllines, are used as second-line treatments for children experiencing a life-threatening exacerbation. For intravenous theophylline (aminophylline), guidelines and formularies recommend a target therapeutic range between 10 and 20 mg/l, with the commonest regimen being a loading dose of 5 mg/kg followed by an infusion calculated by age and weight. This review assesses the evidence underpinning these recommendations, highlighting the shortcomings in our understanding of the association between serum concentrations achieved, dose given, and clinical improvement experienced. To close the knowledge gap and improve outcomes for children presenting with acute severe asthma, we propose a series of research strategies to improve the assessment of illness severity, ascertain the optimal dose to maximize benefit and minimize risk, prospectively collect adverse events, and to better understand the inter-individual variation in responses to treatments.

PREDISPOSING FACTORS AND CLINICAL PROFILE OF ACUTE SEVERE ASTHMA

Background: Asthma is a chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. It is also one of the leading causes of morbidity in children and hospital admissions. Current treatments, although helpful, are still unable to prevent childhood asthma exacerbations completely. Objectives: To study the clinical profile and predisposing factors for acute severe asthma in children. Methods: This prospective study was conducted between January 2015 and December 2015 in a tertiary care teaching hospital. Children between the age group of 5 and 18 years admitted with symptoms and signs of acute severe asthma formed the study group. Detailed history and examination were recorded in a systematically designed pro forma, and these patients were evaluated for the predisposing factors. Results: Out of 100 children with acute severe asthma, the predominant age group was between 5 and 10 years (68%). Boys are more commonly affected than girls in the ratio of 1:1.2. The most common predisposing factors were family history of asthma (60%), atopy (32%), and dermatitis (23%). The common risk factors responsible for acute exacerbations were viral infections (83%), poor drug compliance (68%), and exposure to house dust (61%). 55% of the children had acute exacerbation during the winter season. The common comorbid conditions were rhinosinusitis (35%), obesity (23%), and gastroesophageal reflux (9%). Eosinophilia was seen in 62% of the children with acute severe asthma. Conclusion: In the present study, majority of the asthmatics were males and belonged to urban area. Viral infections were the predominant factor for exacerbations and others like family, and previous history of atopy/allergic rhinitis/dermatitis, food allergy, indoor and outdoor pollution, seasonal variations, and comorbid conditions like obesity and rhinosinusitis were the common predisposing risk factors.

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.

Is ketamine a lifesaving agent in childhood acute severe asthma?

Children with acute severe asthma exacerbation are at risk of developing respiratory failure. Moreover, conventional aggressive management might be futile in acute severe asthma requiring intubation and invasive ventilation. The aim of this review is to detail evidence on the use of ketamine in childhood asthma exacerbations. A search of the MEDLINE, EMBASE, and Cochrane databases was performed, using different combinations of the following terms: ketamine, asthma, use, exacerbation, and childhood. In addition, we searched the references of the identified articles for additional articles. We then reviewed titles and included studies that were relevant to the topic of interest. Finally, the search was limited to studies published in English and Spanish from 1918 to June 2015. Due to the scarcity in the literature, we included all published articles. The literature reports conflicting results of ketamine use for acute severe asthma in children. Taking into consideration the relatively good safety profile of the drug, ketamine might be a reasonable option in the management of acute severe asthma in children who fail to respond to standard therapy. Furthermore, pediatricians and pediatric emergency clinicians administering ketamine should be knowledgeable about the unique actions of this drug and its potential side effects.

Stable admission rate for acute asthma in Danish children since 1977.

Childhood asthma is consistently reported to have increased in recent decades in most westernized countries, but it is unknown if this increase is similar across severities. We aimed to study the time-trend of acute hospital admission and readmission for asthma of school-aged children in the recent 35 years in Denmark. We analyzed time-trends in the national incidence rate of hospitalization for acute severe asthma in children aged 5-15 in Denmark during the 35-year period 1977-2012 in the Danish national registry. Only in-patient admissions with a principal diagnosis of asthma (ICD-8: 493** or ICD-10: J45** or J46**) were included. Among children with asthma hospitalizations, we investigated the risk of readmission beyond 1 month of first admission. Admissions were summarized as rates per thousand person years at risk. The overall time-trend is stable with a rate of one admission per year per thousand children at risk and a per-year incidence rate ratio 0.999 [95 % CI 0.997-1.001]. The rate of any readmission decreased from approximately 20 per thousand children in the eighties to less than 10 in the early nineties before stabilizing at around 10 per thousand children from mid-nineties and onwards. During 35 years of nation-wide follow-up, we find a highly stable incidence rate of first hospital admission for acute severe asthma in children. Moreover, rates of readmission halved during the seventies and stabilized in the last twenty years. In conclusion, our data suggest that the reported increase in childhood asthma is mainly due to less severe cases.

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.

Efficacy of Nebulised Budesonide versus Oral Prednisolone in Acute Severe Asthma

To compare the efficacy of nebulised budesonide with that of oral prednisone in the treatment of acute severe asthma in children. Children aged 5-12 y with acute exacerbation of bronchial asthma were included. The study (budesonide) group received budesonide respirator solution (800 μg) at intervals of 20 min and a single dose of placebo tablets. The control (prednisolone) group received placebo solution at intervals of 20 min and a single dose of oral prednisolone (2 mg/kg). Both groups received three doses of nebulised salbutamol (0.15 mg/kg). Heart rate, respiratory rate, oxygen saturation, PEFR (Peak Expiratory Flow Rate) and fitness for discharge were assessed. Both groups showed a progressive decrease in tachycardia with treatment, but it was significantly greater in study group (p = 0.0002). There was significant decrease in tachypnea and improvement in oxygen saturation in both groups, but the difference between the groups (p = 0.334 and p = 0.814 respectively) was not significant. There was significant improvement in PEFR values in budesonide group (p = 0.024). Both groups showed significant improvement in clinical severity scores at the end of 2 h (p < 0.0001). Budesonide group had significantly higher proportion of patients fit for discharge at 2 h (based on clinical severity scores) (p = 0.0278). Nebulised budesonide significantly improves PEFR levels and fitness for discharge at 2 h when compared to oral prednisolone in children between 5 and 12 y with acute severe asthma.

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.

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

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. 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? 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. Emergency departments and children's assessment units at 30 hospitals in the UK. Children aged 2-15 years with acute severe asthma. 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. 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. 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 £1000 per unit decrement in ASS and £20,000 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). 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. Current Controlled Trials ISRCTN81456894. The National Institute for Health Research Health Technology Assessment programme.

Rates of hospitalizations of children with asthma

— Robert W. Wilmott, MD In this issue ofThe Journal, Hasegawa et al, fromHarvardMedical School and theClinical Epidemiology Center of St Luke’s Life Science Institute, have completed a temporal analysis of trends in hospital mortality, mechanical ventilator use, hospital charges, and childhood asthma hospitalizations in the US between 2000 and 2009. These data were generated from the “Kids Inpatient Database,” and the subjects were <18 years of age with asthma. Four years were analyzed: 2000, 2003, 2006 and 2009. The results showed that asthmahospitalizations decreased significantly, andmortality also declined significantly after adjusting for confounders. There was an increase inmechanical ventilation use over this time periodwhichmight reflect amore aggressive approach tomanagement of status asthmaticus in children. Nationwide, hospital charges increased by 26%, which was driven by a rise in the hospital charges per discharge. The results of this study suggest that there has been progress in reducing the impact of severe acute asthma in children in the US. However, mechanical ventilation and hospital charges for asthma hospitalizations have increased markedly. This increase might reflect improved management of sicker patients, yet the large asthma burden presents an ongoing public health and health education challenge. Article page 1127<

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

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO(4)) in acute asthma in children. We assessed the effect of MgSO(4) treatment in children with severe acute asthma. 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 MgSO(4) (250 mmol/L; 151 mg per dose; MgSO(4) 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. Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO(4) and 256 to placebo. Mean ASS at 60 min was lower in the MgSO(4) 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. Overall, nebulised isotonic MgSO(4), 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 (SaO(2)<92%) at presentation and those with preceding symptoms lasting less than 6 h. National Institute for Health Research Health Technology Assessment Programme.

Ketamine for management of acute exacerbations of asthma in children.

Asthma is the most common chronic disease in children, and children with asthma frequently visit the paediatric emergency departments with acute exacerbations. Some of these children fail to respond to standard therapy (aerosol beta(2)-agonist with or without aerosol anticholinergic and oral or parenteral corticosteroids) for acute asthma leading to prolonged emergency department stay, hospitalisation, morbidity (e.g. barotrauma, intubation) and death, albeit rarely. Ketamine may relieve bronchospasm and is a potentially promising therapy for children with acute asthma who fail to respond to standard treatment. To evaluate the efficacy of ketamine compared to placebo, no intervention or standard care for management of severe acute asthma in children who had not responded to standard therapy. We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov. We reviewed reference lists of all primary studies and review articles for additional references. We contacted authors of identified trials and asked them to identify other published and unpublished studies. The latest search was in July 2012. Randomised controlled trials comparing ketamine to placebo or standard care in children (up to 18 years of age) presenting with an acute asthma exacerbation who had not responded to standard therapy. Two review authors independently selected studies. The data were extracted in pre-defined proforma and were analysed independently by two review authors. The data analysis was performed using Review Manager 5.1. A single study enrolling 68 non-intubated children was found eligible for inclusion in review. The study had low or unclear risk of bias. It demonstrated no significant difference in respiratory rate, oxygen saturation, hospital admission rate (odds ratio (OR) 0.77; 95% confidence interval (CI) 0.23 to 2.58) and need for mechanical ventilation between ketamine (0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per hour continuous infusion for two hours) and placebo group. There were no significant side effects of ketamine in the study. There was also no difference in need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40) and in Pulmonary Index Score (mean difference (MD) -0.40; 95% CI -1.21 to 0.41) between the groups. The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showingbenefits of ketamine in both non-ventilated and ventilated children. There were no significant side effects of ketamine. We could not find any trials on ventilated children. To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance. Future trials should also explore different doses of ketamine and its role in children needing ventilation because of severe acute asthma.

Risk Factors for Pediatric Intensive Care Admission in Children With Acute Asthma

Severe acute asthma in children is associated with substantial morbidity and may require pediatric ICU (PICU) admission. The aim of the study was to determine risk factors for PICU admission. The study used a retrospective multicenter case-control design. The cases included children admitted to the PICU because of severe acute asthma and a history of out-patient treatment by pediatricians or pediatric pulmonologists. Controls were children with asthma without a PICU admission for severe acute asthma. The children were matched for sex, age, hospital, and time elapsed since the diagnosis of asthma. Fourteen possible risk factors were analyzed. Sixty-six cases were matched to 164 controls. In univariate analysis, all but one of the analyzed variables were significantly associated with PICU-hospitalization. After multivariate conditional logistic regression analysis, 4 risk factors remained significant. These included active or passive smoking, allergies, earlier hospitalization for asthma, and non-sanitized home. Physicians and parents should be aware of these risk factors, and efforts should be made to counteract them.