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Meta-Analysis
. 2015 Sep 18;2015(9):CD006915.
doi: 10.1002/14651858.CD006915.pub3.

Heliox inhalation therapy for bronchiolitis in infants

Jean-Michel Liet  1 , Thierry Ducruet, Vineet Gupta, Gilles Cambonie
Affiliations
Meta-Analysis

Heliox inhalation therapy for bronchiolitis in infants

Jean-Michel Liet et al. Cochrane Database Syst Rev. .

Abstract

Background: Bronchiolitis is the leading cause of hospitalisation among infants in high-income countries. Acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. Heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high-resistance airways and decrease the work of breathing. In this review, we selected trials that objectively assessed the effect of the addition of heliox to standard medical care for acute bronchiolitis.

Objectives: To assess heliox inhalation therapy in addition to standard medical care for acute bronchiolitis in infants with respiratory distress, as measured by clinical endpoints (in particular the rate of endotracheal intubation, the rate of emergency department discharge, the length of treatment for respiratory distress) and pulmonary function testing (mainly clinical respiratory scores).

Search methods: We searched CENTRAL (2015, Issue 2), MEDLINE (1966 to March week 3, 2015), EMBASE (1974 to March 2015), LILACS (1982 to March 2015) and the National Institutes of Health (NIH) website (May 2009).

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs of heliox in infants with acute bronchiolitis.

Data collection and analysis: Two review authors independently extracted data and assessed trial quality.

Main results: We included seven trials involving 447 infants younger than two years with respiratory distress secondary to viral bronchiolitis. All children were recruited from a paediatric intensive care unit (PICU; 378 infants), except in one trial (emergency department; 69 infants). All children were younger than two (under nine months in two trials and under three months in one trial). Positive tests for respiratory syncytial virus (RSV) were required for inclusion in five trials. The two other trials were carried out in the bronchiolitis seasons. Seven different protocols were used for inhalation therapy with heliox.When heliox was used in the PICU, we observed no significant reduction in the rate of intubation: risk ratio (RR) 2.73 (95% confidence interval (CI) 0.96 to 7.75, four trials, 408 infants, low quality evidence). When heliox inhalation was used in the emergency department, we observed no increase in the rate of discharge: RR 0.51 (95% CI 0.17 to 1.55, one trial, 69 infants, moderate quality evidence).There was no decrease in the length of treatment for respiratory distress: mean difference (MD) -0.19 days (95% CI -0.56 to 0.19, two trials, 320 infants, moderate quality evidence). However, in the subgroup of infants who were started on nasal continuous positive airway pressure (nCPAP) right from the start, because of severe respiratory distress, heliox therapy reduced the length of treatment: MD -0.76 days (95% CI -1.45 to -0.08, one trial, 21 infants, low quality evidence). No adverse events related to heliox inhalation were reported.We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation: MD -1.04 (95% CI -1.60 to -0.48, four trials, 138 infants, moderate quality evidence). This outcome had statistical heterogeneity, which remained even after removing the study using a standard high-concentration reservoir mask. Several factors may explain this heterogeneity, including first the limited number of patients in each trial, and the wide differences in the baseline severity of disease between studies, with the modified Wood Clinical Asthma Score (m-WCAS) in infants treated with heliox ranging from less than two to more than seven.

Authors' conclusions: Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. We noticed this beneficial effect regardless of which heliox inhalation protocol was used. Nevertheless, there was no reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress. Heliox could reduce the length of treatment in infants requiring CPAP for severe respiratory distress. Further studies with homogeneous logistics in their heliox application are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid inclusion of children with mild bronchiolitis who may not benefit from heliox inhalation. Such studies would provide the necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis.

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Conflict of interest statement

Jean‐Michel Liet: I was investigator in one trial, supported by Air Liquide Santé International. Air Liquide provided the heliox and air tanks, set up the study equipment and was involved in the study design. Air Liquide Santé had no role in data management, data analysis or data interpretation, or writing of the report and decision to submit it for publication. I had no financial relationship with Air Liquide Santé. Currently I am a local investigator in a multicentre observational study promoted by Air Liquide Healthcare. My institution receives money when a child is included.

Gilles Cambonie et al performed a study with heliox referenced as Cambonie G, Milési C, Fournier‐Favre S, Counil F, Jaber S, Picaud J‐C, Matecki S. Clinical effects of heliox administration for acute bronchiolitis in young infants. Chest 2006; 129: 676‐82. As indicated in the published article, for this study Air Liquide Santé provided the heliox and air tanks, set up the study equipment, and was involved in the study design; it had no role in data management, data analysis or data interpretation, or in the writing of the report and the decision to submit it for publication. The review author has no financial relationship with Air Liquide Santé. Thierry Ducruet: none known.

Vineet Gupta: none known.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Forest plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.2 Need for mechanical ventilation (invasive or not).
3
3
Forest plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.3 Rate of endotracheal intubation.
4
4
Forest plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.4 Rate of emergency department discharge.
5
5
Forest plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.5 Length of treatment for respiratory distress.
6
6
Forest plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.10 Change in clinical respiratory scores in the first hour after starting heliox.
7
7
Funnel plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.2 Need for mechanical ventilation (invasive or not).
8
8
Funnel plot of comparison: 1 Heliox inhalation versus air or oxygen inhalation, outcome: 1.10 Change in clinical respiratory scores in the first hour after starting heliox.
1.1
1.1. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 2 Need for mechanical ventilation (invasive or not).
1.3
1.3. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 3 Rate of endotracheal intubation.
1.4
1.4. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 4 Rate of emergency department discharge.
1.5
1.5. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 5 Length of treatment for respiratory distress.
1.6
1.6. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 6 Length of PICU stay.
1.7
1.7. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 7 Change in O2 needs after 1 hour of heliox treatment.
1.8
1.8. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 8 Change in SpO2 in the first hour after starting heliox treatment.
1.9
1.9. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 9 Change in CO2 in the 1st hour after starting treatment.
1.10
1.10. Analysis
Comparison 1 Heliox inhalation versus air or oxygen inhalation, Outcome 10 Change in clinical respiratory scores in the first hour after starting heliox.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Cambonie 2006 {published data only}
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