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 (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. 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 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

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.

Heliox for croup in children.

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.