Abstract: 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. 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.

Plain-language summary: We did not include any new trials in this update. We included three randomised controlled trials (studies in which participants are allocated by chance to receive a treatment) involving a total of 91 children with croup aged from 6 months to 4 years. Studies ran for between 7 and 16 months; two were conducted in the USA and one in Spain. In one study children with mild croup received either heliox with 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. 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 to severe croup. None of the studies reported adverse events. The quality of the evidence was low as the trials included few children, and in one trial children, their families, and the physicians knew which treatment was given.