Heliox for croup in children

Background: 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 (from which benefits are often delayed) and nebulised epinephrine (adrenaline) (which may be short-lived and 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 and 2013. 

Objectives: 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. 

Search methods: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE; Embase; CINAHL; Web of Science; and LILACS in January and February 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 8 February 2018. We contacted British Oxygen Company, a leading supplier of heliox (BOC Australia 2017). 

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo or any active intervention(s) in children with croup. 

Data collection and analysis: We used standard methodological procedures expected by Cochrane. We reported data that could not be pooled for statistical analysis descriptively. 

Main results: We included 3 RCTs with 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months; all studies were conducted in emergency departments in the USA (two studies) and 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 due to an open-label design. We added no new trials for this 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). 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 quality, 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 croup scores 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 -4.86 to 3.46). 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 no difference in hospitalisation rates between groups (OR 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low quality, downgraded due to imprecision and high risk of bias related to open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup received intramuscular dexamethasone (0.6 mg/kg) and either heliox with one to two doses of nebulised saline, or 100% oxygen with one to two doses of adrenaline for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may have little or no difference overall using repeated measures analysis. We assessed the evidence for all outcomes in this comparison as of low quality, 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. 

Authors' conclusions: Due to very limited evidence, uncertainty remains about 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 to severe croup treated with dexamethasone. The effect 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.