Review question
We wanted to find out whether inhaling heliox is safe and useful in treating children with croup compared with fake treatment (placebo) or other therapies such as 30% humidified oxygen, or 100% oxygen with epinephrine (adrenaline, a drug that helps open airways).
Background
Croup is a short-term illness that causes upper airways to be blocked. It is common in children aged between six months and three years, and is caused by viral infections; it is more frequent in autumn and winter. Symptoms include barking cough, hoarseness, abnormal breathing sounds, and chest wall retractions (inward movement of the skin of the chest wall or the breastbone during inhalation).
Corticosteroid drugs are standard treatment for children with croup, but a limitation of this treatment is that it takes time for the drug to take effect. Children with severe croup may need additional emergency treatments such as a breathing tube or mechanical breathing support. Children with severe croup may need oxygen and adrenaline inhaled as a fine mist (nebulised). Adrenaline is generally safe, but can cause side effects such as fast heart rate and anxiety. Identifying a safe, effective, and fast-acting treatment is important for children and their families.
Heliox (a combination of helium and oxygen) gas may improve airflow and relieve breathing distress. Some studies have shown benefits from heliox for children with croup.
This is an updated review of versions published in 2010, 2013, and 2018.
Search date
15 April 2021.
Study characteristics
We did not include any new trials in this update.
We included 3 randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) involving a total of 91 children with croup aged from 6 months to 4 years. All studies were conducted in emergency departments. Studies took place with a duration of between 7 and 16 months; 2 studies were conducted in the USA, and 1 in Spain. In one study children with mild croup received either heliox or 30% oxygen; in another study children with moderate croup received oral dexamethasone (a type of corticosteroid) and either heliox or no treatment; and in the third study children with moderate to severe croup received injected dexamethasone and either heliox or 100% oxygen with adrenaline.
Key results
Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may be no more effective than 30% oxygen for children with mild croup; as effective as 100% oxygen given with one or two doses of adrenaline; and slightly more effective than no treatment for children with moderate croup. None of the studies reported adverse events (side effects).
Certainty of evidence
The certainty of the evidence was low, as the trials included few children, and in one trial children, their families, and the doctors knew which treatment had been given.
Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.
Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation.
A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress.
This review updates versions published in 2010, 2013, and 2018.
To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation.
We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox.
Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup.
We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively.
We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update.
One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) −0.83, 95% confidence interval (CI) −2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD −0.57, 95% CI −1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI −1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI −8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported.
In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD −1.10, 95% CI −1.96 to −0.24), but there may be no difference between groups at 120 minutes (MD −0.70, 95% CI −1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD −1.11, 95% CI −2.05 to -0.17) but not at 120 minutes (MD −0.71, 95% CI −1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD −4.94, 95% CI −9.66 to −0.22), but there may be no difference at 120 minutes (MD −3.17, 95% CI −7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported.
In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported.
The included studies did not report on adverse events, intensive care admissions, or parental anxiety.
We could not pool the available data because each comparison included data from only one study.