Question 5: Magnesium Sulphate for Acute Asthma in children.

Most children who present to the emergency department with acute asthma, respond well to inhaled ß2-agonists (spacer or nebuliser), oxygen (if required) and systemic steroids. Guidelines across the world agree on this simple, straight forward evidenced based approach. In children with more severe asthma attacks and those who do not respond to initial treatment, the evidence base for the secondary level treatment is less clear. Many regimens exist for the next step. Intravenous Magnesium Sulphate (MgSO4) is now used frequently in these situations and some centres are starting to use nebulized MgSO4 as part of the initial maximal inhaled therapy options. This paper examines the role of MgSO4 in acute asthma in children. It focusses on how MgSO4 might work, what are the current recommendations for use and then what is the current evidence base to support its use. We have presented the evidence for the use of both nebulized and intravenous MgSO4. At the end of the paper we have suggested future directions for research in this area. Our aim is to present a synthesis of the current role of MgSO4 in the management of an acute asthma attack.

Which intravenous bronchodilators are being administered to children presenting with acute severe wheeze in the UK and Ireland?

During a prospective 10-week assessment period, 3238 children aged 1-16 years presented with acute wheeze to Paediatric Emergency Research in the UK and Ireland centres. 110 (3.3%) received intravenous bronchodilators. Intravenous magnesium sulfate (MgSO4) was used in 67 (60.9%), salbutamol in 61 (55.5%) and aminophylline in 52 (47.3%) of cases. In 35 cases (31.8%), two drugs were used together, and in 18 cases (16.4%), all three drugs were administered. When used sequentially the most common order was salbutamol, then MgSO4, then aminophylline. Overall, 30 different intravenous treatment regimens were used varying in drugs, dose, rate and duration.

Treating acute severe asthma attacks in children: using aminophylline.

Aminophylline does have a role in treating severe asthma attacks in children with asthma. Clinicians just need to be aware of the toxic side-effects of the drug and manage the drug carefully. https://bit.ly/3o7IJV1.

Cohort study to test the predictability of the NHS Institute for Innovation and Improvement Paediatric Early Warning System.

OBJECTIVE: To test the predictability of the National Health Service Institute for Innovation and Improvement (NHSIII) Paediatric Early Warning System (PEWS) score to identify children at risk of developing critical illness. DESIGN: Cohort study. SETTING: Admissions to all paediatric wards at the University Hospital of Wales between 1 December 2005 and 30 November 2006. OUTCOME MEASURES: Unscheduled paediatric high dependency unit (PHDU) admission, paediatric intensive care unit (PICU) admission and death. RESULTS: There were 9075 clinical observations from 1000 children. An NHSIII PEWS score of 2 or more, which triggers review, has a sensitivity of 73.2% (95% CI 62.2% to 82.4%), specificity of 75.2% (95% CI 74.3% to 76.1%), positive predictive value (PPV) of 2.6% (95% CI 2.0% to 3.4%), negative predictive value of 99.7% (95% CI 99.5% to 99.8%) and positive likelihood ratio of 3.0 (95% CI 2.6 to 3.4) for predicting PHDU admission, PICU admission or death. Six (37.5%) of the 16 children with an adverse outcome did not have an abnormal NHSIII PEWS score. The area under the receiver operating characteristic curve for the NHSIII PEWS score was 0.83 (95% CI 0.77 to 0.88). CONCLUSIONS: The NHSIII PEWS has a low PPV and its full implementation would result in a large number of false positive triggers. The issue with PEWS scores or triggers is neither their sensitivity nor children with high scores which require clinical interventions who are not 'false positives'; but their low specificity and low PPV arising from the large number of children with low but raised scores.

Treatment of childhood asthma. Options and rationale for inhaled therapy.

Epidemiological studies suggest the prevalence of asthma is increasing, though some remain sceptical as to the magnitude or indeed the presence of an increase. However, despite improved diagnosis and the availability of the potent drugs now available there remains considerable respiratory morbidity associated with asthma. It is clear from a number of studies that failure to deliver drugs to the lungs when using inhaler devices is a factor contributing to this high level of morbidity. Failure of drug delivery may result from the prescribing of inappropriate devices, failure to use devices appropriately or failure to comply with a treatment regimen. For most of the currently available forms of asthma therapy there are significant advantages to be gained from administering them in aerosol form. The benefits to be derived from administering these drugs as an aerosol include a rapid onset of action for drugs such as beta-agonists and a low incidence of systemic effects from drugs such as beta-agonists and corticosteroids. Over the past 25 years our understanding of the nature of asthma has changed. Though this has been reflected in the emphasis on inhaled corticosteroid therapy in recent guidelines, it has not been reflected in the range of inhaler devices available. Manufacturers continue to place drugs such as corticosteroids in the same devices as short acting beta-agonists even though the requirements for these different drug classes are very different. It is likely that this contributes to suboptimal therapeutic responses with inhaled corticosteroids. However, the variability associated with current delivery systems is relatively small compared with the variability introduced by poor compliance. There is no work currently available to indicate how the use of cheap disposable devises which do not incorporate any form of positive feedback influence compliance with inhaled steroids. Optimising aerosolised drug delivery in childhood involves consideration of the class of drugs, the particular drug within a class but more importantly, the age and abilities of the child. Devices must be selected to suit a particular child's needs and abilities. Devices utilising tidal breathing are generally used such as spacing chambers or, less commonly these days, nebulisers. A screaming or struggling child, or failure to use a closely fitting mask, reduces drug delivery to the lungs enormously. Failure to respond to inhaled therapy in early childhood may be attributable to failure of drug delivery. Drug delivery in early childhood using current devices remains more an art than a science.

Antioxidant status in asthma.

Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. This study examines the antioxidant status in children with asthma compared with a control group in a cross-sectional analysis. Red blood cell GSH-Px, superoxide dismutase (SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol were measured in 37 subjects (26 males) with stable controlled asthma. Thirty-five subjects (20 males) without eczema, hayfever, or recurrent respiratory symptoms were used as a control group. Children with asthma had significantly reduced red blood cell GSH-Px activity compared with controls [median (inter-quartile range) for asthma group, 10.25 (9.25-11.91); for control group, 11.75 (10.34-12.26) IU/g Hb; P = 0.006]. There were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma. The effects of disease activity and treatment on antioxidant status needs for further study.

Ultrastructural diversity in the pore canal systems of amphipod crustaceans.

Transmission electron microscopy was used to analyze the structure and organization of the intracuticular pore canal system in 34 species of amphipod crustaceans. Pore canals were detectable in all species, including those that, from scanning electron microscopy, had been considered to lack them. Canal structure ranges from simple transcuticular passages of uniform diameter to more elaborate systems with distal canal dilatations variously equipped with electron dense collars, tubular filaments, single or multiple channels leading to the surface and transverse partitions separating canal contents of different electron densities. Considerable branching between tubular elements of the canal system is evident in many species. In most species the canals communicate with the outsidevia epicuticular channels. Even in those species in which this communication was not established, their epicuticle generally contains abundant cavities with external pores. Although some consistency in structure and organization is present among a few groups of taxonomically related species, pore canal characteristics generally could not be correlated with habitat or life style. It is suggested that the structural and organizational variety present reflects a considerable array of functions among amphipod pore canal systems.

Updating asthma management: the process of change.

A strategic approach to changing clinical practice that is managed by a multidisciplinary team is an effective way of implementing new treatment methods or approaches to patient care. The Royal Children's Hospital, Melbourne, Australia, a tertiary pediatric hospital, instituted new Asthma Delivery Device Guidelines in recognition of current evidence that described the benefits of treating acute pediatric asthma with pressurized metered dose inhalers and spacer devices. The working group that coordinated the project attributes the successful change in practice to a multifaceted, multidisciplinary approach, a significant planning stage, initial and ongoing intensive staff and patient/parent education, and accessibility of information.

Changing hospital management of croup. What does this mean for general practice?

BACKGROUND: The hospital management of croup has altered significantly over the last decade, with current data suggesting that all children with croup who demonstrate an increase in difficulty breathing should be treated with corticosteroids, and children with more severe croup should be treated with nebulised adrenaline. OBJECTIVE: To discuss the assessment of croup severity, the recent changes in treatment and to make suggestions for the management of croup in general practice. DISCUSSION: Children with mild croup require reassurance. There is no evidence that steroids have a place in management in this group. A single dose of prednisolone is appropriate for children with stridor at rest, but no recession and they can be managed in the general practice setting provided they can be reviewed within 2-4 hours. Failure to improve after treatment with steroids means hospital referral. Children with more severe croup require hospital assessment and possible admission.

Non-specific cough in children: diagnosis and treatment.

Cough is a common reason for parents to seek medical attention. When the history, examination, chest X-ray and, if possible, spirometry are normal, the cough can be classified as non-specific, which is often found. This article focuses on non-specific cough, addresses common questions and gives a simple approach to evaluating the child with a cough.

Use of paediatric early warning systems in Great Britain: has there been a change of practice in the last 7 years?

OBJECTIVE: To determine the use of paediatric early warning systems (PEWS) and rapid response teams (RRTs) in paediatric units in Great Britain. DESIGN: Cross sectional survey. SETTING: All hospitals with inpatient paediatric services in Great Britain. OUTCOME MEASURES: Proportion of units using PEWS, origin of PEWS used, criterion included in PEWS, proportion of units with an RRT and membership of RRT. RESULTS: The response rate was 95% (149/157). 85% of units were using PEWS and 18% had an RRT in place. Tertiary units were more likely than district general hospital to have implemented PEWS, 90% versus 83%, and an RRT, 52% versus 10%. A large number of PEWS were in use, the majority of which were unpublished and unvalidated systems. CONCLUSIONS: Despite the inconclusive evidence of effectiveness, the use of PEWS has increased since 2005. The implementation has been inconsistent with large variation in the PEWS used, the activation criteria used, availability of an RRT and the membership of the RRT. There must be a coordinated national evaluation of the implementation, impact and effectiveness of a standardised PEWS programme in the various environments where acutely sick children are managed.

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

BACKGROUND: 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 £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). 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. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81456894. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Toddler diarrhoea: is it a useful diagnostic label?

Toddler diarrhoea is a term coined many years ago to describe a young child who passes several loose stools a day but who is otherwise healthy with excellent growth and normal examination. It could be argued that it is not an appropriate diagnostic term as it potentially stops the clinician from thinking about the possible causes of loose stools in this clinical situation. This article, which follows a debate between the authors on the topic at the 2010 Royal College of Paediatrics and Child Health Annual meeting, discusses the differential diagnoses of a young child presenting with the so-called toddler diarrhoea.

Cohort study to test the predictability of the Melbourne criteria for activation of the medical emergency team.

OBJECTIVE: To test the predictability of the Melbourne criteria for activation of the medical emergency team (MET) to identify children at risk of developing critical illness. DESIGN: Cohort study. SETTING: Admissions to all paediatric wards at the University Hospital of Wales. OUTCOME MEASURES: Paediatric high dependency unit admission, paediatric intensive care unit admission and death. RESULTS: Data were collected on 1000 patients. A single abnormal observation determined by the Melbourne Activation Criteria (MAC) had a sensitivity of 68.3% (95% CI 57.7 to 77.3), specificity 83.2% (95% CI 83.1 to 83.2), positive predictive value (PPV) 3.6% (95% CI 3.0 to 4.0) and negative predictive value 99.7% (95% CI 99.5 to 99.8) for an adverse outcome. Seven of the 16 children (43.8%) would not have transgressed the MAC prior to the adverse outcomes. Four hundred and sixty-nine of the 984 children (47.7%) who did not have an adverse outcome would have transgressed the MAC at least once during the admission. CONCLUSION: The MAC has a low PPV and its full implementation would result in a large number of false positive triggers. Further research is required to determine the relative contribution of the components of this complex intervention (Paediatric Early Warning System, education and MET) on patient outcome.

Prospective cohort study to test the predictability of the Cardiff and Vale paediatric early warning system.

OBJECTIVE: To develop and test the predictability of a paediatric early warning score to identify children at risk of developing critical illness. DESIGN: Prospective cohort study. SETTING: Admissions to all paediatric wards at the University Hospital of Wales. OUTCOME MEASURES: Respiratory arrest, cardiac arrest, paediatric high-dependency unit admission, paediatric intensive care unit admission and death. RESULTS: Data were collected on 1000 patients. A single abnormal observation determined by the Cardiff and Vale paediatric early warning system (C&VPEWS) had a 89.0% sensitivity (95% CI 80.5 to 94.1), 63.9% specificity (95% CI 63.8 to 63.9), 2.2% positive predictive value (95% CI 2.0 to 2.3) and a 99.8% negative predictive value (95% CI 99.7 to 99.9) for identifying children who subsequently had an adverse outcome. The area under the receiver operating characteristic curve for the C&VPEWS score was 0.86 (95% CI 0.82 to 0.91). CONCLUSION: Identifying children likely to develop critical illness can be difficult. The assessment tool developed from the advanced paediatric life support guidelines on identifying sick children appears to be sensitive but not specific. If the C&VPEWS was used as a trigger to activate a rapid response team to assess the child, the majority of calls would be unnecessary.

Comparison of complementary and alternative medicine use: reasons and motivations between two tertiary children's hospitals.

AIMS: To compare prevalence, reasons, motivations, initiation, perceived helpfulness, and communication of complementary and alternative medicine (CAM) use between two tertiary children's hospitals. METHODOLOGY: A study, using a face-to-face questionnaire, of 500 children attending the University Hospital of Wales, Cardiff, UK was compared to an identical study of 503 children attending the Royal Children's Hospital, Melbourne, Australia. RESULTS: One year CAM use in Cardiff was lower than Melbourne (41% v 51%; OR = 0.67, 95% CI 0.52-0.85), reflected in non-medicinal use (OR = 0.41, 95% CI 0.29-0.58) and general paediatric outpatients (OR = 0.38, 95% CI 0.21-0.67). Compared to Melbourne, factors associated with lower CAM use in Cardiff included families born locally (father: OR = 0.58, 95% CI 0.44-0.77) or non-tertiary educated parents (mother: OR = 0.54, 95% CI 0.38-0.77). Cardiff participants used less vitamin C (OR = 0.31, 95% CI 0.18-0.51) and herbs (OR = 0.49, 95% CI 0.34-0.71), attended less chiropractors (OR = 0.25, 95% CI 0.06-0.37) and naturopaths (OR = 0.08, 95% CI 0.02-0.33), but saw more reflexologists (OR = 3.33, 95% CI 1.08-10.29). In Cardiff, CAM was more popular for relaxation (OR = 1.92, 95% CI 1.03-3.57) but less for colds/coughs (OR = 0.4, 95% CI 0.27-0.73). Most CAM was self-initiated (by parent) in Cardiff and Melbourne (74% v 70%), but Cardiff CAM users perceived it less helpful (OR = 0.46, 95% CI 0.31-0.68). Non-disclosure of CAM use was high in Cardiff and Melbourne (66% v 63%); likewise few doctors/nurses documented recent medicinal CAM use in inpatient notes (0/21 v 2/22). CONCLUSIONS: The differences in CAM use may reflect variation in sociocultural factors influencing reasons, motivations, attitudes, and availability. The regional variation in use and poor communication highlights the importance of local policy development.

Management of acute asthma in childhood.

In children, acute asthma is one of the most common reasons for admission to hospital. Morbidity and mortality from asthma are unnecessarily high. It is essential that all those caring for asthma patients can accurately assess and treat an acute exacerbation of asthma.

Asthma in childhood.

The prevalence of wheezy illness in children is increasing, along with the number of children diagnosed as having asthma. If physicians are to provide the most effective treatment for these patients, they need to be fully aware of advances in our understanding of the pathophysiology of asthma and of the new and improved treatments that these have brought about.

Childhood asthma as an allergic disease: rationale for the development of future treatment.

UNLABELLED: The fundamental abnormality in asthma is inflammation of the airways. T-helper 2 (Th2) lymphocytes are the key orchestrators of this inflammation, initiating and propagating inflammation through the release of Th2 cytokines. Interleukins(IL)-4, IL-5 and IL-13. IL-4 and IL-13 promote IgE production by B-cells, mast cell growth and differentiation, and upregulate adhesion molecule expression on vascular endothelium. IL-4 also promotes differentiation of uncommitted Th0 lymphocytes into Th2 lymphocytes. IL-5 promotes differentiation and recruitment of eosinophils and activates them to degranulate within tissues, resulting in damage to the respiratory epithelium. Current treatment of childhood asthma relies predominantly on corticosteroids that have nonspecific anti-inflammatory activity and are associated with potential side-effects. Novel therapies that selectively target the underlying immunopathogenesis hold great promise. Disruption of the Th2 lymphocyte induced allergic inflammatory response represents a novel approach to selectively inhibiting allergic inflammation at its origin. Possible therapeutic interventions include inhibition of Th2 response (CpG oligonucleotides, vaccination, CTLA4Ig fusion protein, IL-12, IL-10), inhibition of IgE (the anti-IgE antibody rhuMAb-E25 omalizumab, which is undergoing clinical trials), inhibition of mediator activity (leukotriene modifiers, which are approved for use in childhood asthma), and targeting Th2 cytokines (soluble IL-4 receptors, IL-5 antibody, IL-13). Other therapeutic approaches targeting downstream events in the allergic inflammatory cascade are also currently under investigation (chemokine receptors CCR3, tryptase inhibitors, and inhibitors of cyclic AMP-specific phosphodiesterase 4). CONCLUSION: As we further understand the pathophysiology of asthma, the potential to develop novel treatments increases. This paper addresses current possible new treatments for the future.

Stability of respiratory symptoms in unlabelled wheezy illness and nocturnal cough.

OBJECTIVE: To assess the natural history of respiratory symptoms not labelled as asthma in primary schoolchildren. DESIGN: Repeat questionnaire survey of subgroups identified from a previous questionnaire survey after a two year delay. SUBJECTS: The original population of 5321 Sheffield children aged 8-9 years yielded 4406 completed questionnaires in 1991(82.8%). After excluding children with a label of asthma, there were 370 children with current wheeze, 129 children with frequent nocturnal cough, and a random sample of 222 children with minor cough symptoms and 124 asymptomatic children. RESULTS: Response rates in the four groups were 233 (63.0%), 77 (59.7%), 160 (72.1%), and 90 (72.6%) respectively. Of those who initially wheezed, 114 (48.9%) had stopped wheezing and 42 (18.0%) had been labelled as having asthma. Those with more frequent wheezing episodes (p < 0.02) and a personal history of hay fever (p < 0.01) in 1991 were more likely to retain their wheezy symptoms. In the children with frequent nocturnal cough in 1991, 20.1% had developed wheezing, 42.9% had a reduced frequency of nocturnal coughing, and 14.2% had stopped coughing altogether two years later. One sixth had been labelled as having asthma. Children with nocturnal cough were more likely to develop wheezing if they had a family history of atopy (p = 0.02). Only 3.8% and 3.3% of those with minimal cough and no symptoms respectively in 1991 had developed wheeze by 1993 (1.9% and 1.0% labelled as asthma). CONCLUSIONS: Most unlabelled recurrent respiratory symptoms in 8-10 year olds tend to improve. Unlabelled children who have persistent symptoms have other features such as frequent wheezing attacks and a family or personal history of atopy. If a screening questionnaire were to be used to identify such children, a combination of questions should be employed.