Heliox for croup in children
Abstract
Background
Croup is thought to be triggered by a viral infection and is characterised by respiratory distress due to upper airway inflammation and swelling of the subglottic mucosa in children. Mostly it is mild and transient and resolves with supportive care. In moderate to severe cases, treatment with corticosteroids and nebulised epinephrine (adrenaline) is required. Corticosteroids improve symptoms but it takes time for a full effect to be achieved. In the interim, the child is at risk of further deterioration. This may rarely result in respiratory failure necessitating emergency intubation and ventilation. Nebulised epinephrine may result in dose‐related adverse effects including tachycardia, arrhythmias and hypertension and its benefit may be short‐lived. Helium‐oxygen (heliox) inhalation has shown therapeutic benefit in initial treatment of acute respiratory syncytial virus (RSV) bronchiolitis and may prevent morbidity and mortality in ventilated neonates. Heliox has been used during emergency transport of children with severe croup and anecdotal evidence suggests that heliox relieves respiratory distress.
Objectives
To examine the effect of heliox on relieving symptoms and signs of croup, as determined by a croup score (a tool for measuring the severity of croup).
To examine the effect of croup on rates of admission or intubation (or both), through comparisons of heliox with placebo or any active intervention(s) in children with croup.
Search methods
We searched CENTRAL 2013, Issue 10, MEDLINE (1950 to October week 5, 2013), EMBASE (1974 to November 2013), CINAHL (1982 to November 2013), Web of Science (1955 to November 2013) and LILACS (1982 to November 2013). In addition, we searched two clinical trials registries: the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and clinicaltrials.gov (searched 12 November 2013).
Selection criteria
Randomised controlled trials (RCTs) and quasi‐RCTs comparing the effect of helium‐oxygen mixtures with placebo or any active intervention(s) in children with croup.
Data collection and analysis
Two review authors independently identified and assessed citations for inclusion. A third review author resolved disagreements. We assessed included trials for allocation concealment, blinding of intervention, completeness of outcome data, selective outcome reporting and other potential sources of bias. We reported mean differences for continuous data and odds ratios for dichotomous data. We descriptively reported data not suitable for statistical analysis.
Main results
We included three RCTs with a total of 91 participants. One study compared heliox 70%/30% with 30% humidified oxygen administered for 20 minutes in children with mild croup and found no statistically significant differences in the overall change in croup scores between heliox and the comparator. In another study, children with moderate to severe croup were administered intramuscular dexamethasone 0.6 mg/kg and either heliox 70%/30% with one to two doses of nebulised saline, or 100% oxygen with one to two doses of nebulised racaemic epinephrine for three hours. In this study, the heliox group's croup scores improved significantly more at all time points from 90 minutes onwards. However, overall there were no significant differences in croup scores between the groups after four hours using repeated measures analysis. In a third study, children with moderate croup all received one dose of oral dexamethasone 0.3 mg/kg with heliox 70%/30% for 60 minutes in the intervention group and no treatment in the comparator. There was a statistically significant difference in croup scores at 60 minutes in favour of heliox but no significant difference after 120 minutes. It was not possible to pool outcomes because the included studies compared different interventions and reported different outcomes. No adverse events were reported.
Authors' conclusions
There is some evidence to suggest a short‐term benefit of heliox inhalation in children with moderate to severe croup who have been administered oral or intramuscular dexamethasone. In one study, the benefit appeared to be similar to a combination of 100% oxygen with nebulised epinephrine. In another study there was a slight change in croup scores between heliox and controls, with unclear clinical significance. In another study in mild croup, the benefit of humidified heliox was equivalent to that of 30% humidified oxygen, suggesting that heliox is not indicated in this group of patients provided that 30% oxygen is available. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in children with moderate to severe croup.
PICOs
Plain language summary
Helium‐oxygen (heliox) treatment for croup in children
Croup is an acute illness commonly seen in children up to six years of age but mostly by the age of two. It is triggered by viral infections causing upper airway obstruction with varying degrees of respiratory distress. Mostly, it is mild and transient and resolves with supportive care. Croup is characterised by a barking cough, hoarseness, varying degrees of inspiratory stridor (abnormal breathing sound) and chest wall retractions and is usually preceded by one to three days of upper respiratory tract infection symptoms. The peak croup seasons are autumn and winter but can occur at any time.
Corticosteroids are an accepted treatment for moderate to severe croup, supplemented in more severe cases by nebulised epinephrine and oxygen. Epinephrine is often effective and safe but can have undesired effects (such as increased heart rate and anxiety). Corticosteroids improve croup symptoms but it takes time for their full effect to be achieved. In the meantime the child remains at risk of deterioration. This may rarely result in the development of respiratory failure, which may require emergency intubation and ventilation. Therefore, finding a safe and effective treatment to bridge the gap between the administration and effectiveness of the corticosteroids is important for clinical practice.
Some studies have shown a benefit of using heliox in children with croup. Heliox, a gas with lower density than air or oxygen, is believed to reduce the resistance to gas flow in narrowed upper airways, potentially improving symptoms and signs of respiratory distress. This review found three randomised controlled trials (RCTs) assessing the effect of heliox in 91 children with croup. Heliox did not appear to be more effective than administration of 30% oxygen in children with mild croup. In children with moderate to severe croup who had been administered oral or intramuscular corticosteroids, heliox appeared to be at least as effective as continuous 100% oxygen with one to two doses of nebulised racaemic epinephrine (adrenaline as a fine spray) in one study. It was slightly more effective than no treatment in another study. There were no adverse effects or outcomes reported. The included trials were small and had a number of methodological limitations. Further methodologically well‐designed RCTs with more participants are needed to further assess the role of heliox in managing children with moderate to severe croup. The evidence is current to November 2013.
