NIHR DC Discover

Infant being given oxygen

NIHR Signal High-flow oxygen therapy may have a role in treating infants with more severe bronchiolitis

Published on 18 September 2018

doi: 10.3310/signal-000646

A randomised controlled trial of 1,472 infants with bronchiolitis found that more children improved when started on high-flow oxygen therapy than with standard oxygen therapy. 

Those who failed to improve on standard therapy were switched to high flow oxygen. Most then improved - overall, similar numbers were transferred to intensive care. There was also no difference between the groups in the proportion of infants needing intubation, length of time on oxygen therapy or days spent in hospital.

The place in the pathway for high-flow oxygen remains to be clarified. For example, it isn’t clear from this study whether high flow oxygen is best used as first-line treatment or as "rescue" treatment in infants with bronchiolitis. Further research including cost-effectiveness will be needed before advocating high-flow oxygen for all infants hospitalised with bronchiolitis.

Share your views on the research.

Why was this study needed?

Bronchiolitis is inflammation of small airways in the lungs. It is most commonly caused by respiratory syncytial virus, and usually affects infants. The first symptoms are similar to a cold, then cough, wheeze and fever develop.

Respiratory syncytial virus usually affects children under two years of age, and about half of them develop bronchiolitis. Most recover within two to three weeks, but some have severe symptoms needing hospital treatment. This amounted to 44,304 children aged less than one year in 2016-17.

A 2014 Cochrane review found only one small study of high flow oxygen therapy in 19 infants with bronchiolitis. There were slight early improvements in oxygen levels but no difference at 24 hours. Duration of oxygen therapy and time in hospital were the same in each group. The authors concluded that there was insufficient evidence to determine the effectiveness of high flow oxygen therapy. This study aimed to fill this research gap.

What did this study do?

This randomised controlled trial included 1,472 infants aged less than 12 months with bronchiolitis needing oxygen supplementation. It took place in 17 emergency departments and paediatric wards in Australia and New Zealand. Infants were assigned to heated and humidified high-flow 2 litres/kg/min oxygen or standard 2 litres/min oxygen. The target blood oxygen levels were 92%/94% to 98%, depending on the hospital.

The primary outcome was escalation of the level of treatment if the infant’s condition was not improving (according to specified criteria). In the high-flow oxygen group, this meant intubation or admission to an intensive care unit (ICU). In the standard oxygen group, high-flow oxygen therapy was an option followed by ICU and other interventions.

Children in each group who failed to improve were managed differently. Outcomes such as admission to intensive care and length of stay were included.

What did it find?

  • Escalation of treatment occurred in 12% (87/739) of infants on high-flow oxygen compared with 23% (167/733) on standard oxygen (relative risk [RR] 0.52, 95% confidence interval [CI] 0.40 to 0.66). However, 102 infants starting on standard oxygen responded to simple escalation of switching to high-flow oxygen.
  • A similar proportion required transfer to ICU; 9% (65/739) in the standard oxygen group compared with 12% (87/739) in the high-flow oxygen group (odds ratio 1.37, 95% CI 0.96 to 1.95). Intubation rates were rare, 1% in each group (OR 1.99, 95% CI 0.60 to 6.65).
  • There was no difference in the time until escalation of care between the two treatments; 0.72 days for high-flow oxygen and 0.67 days for standard oxygen (mean difference 0.05, 95% CI −0.17 to 0.26). The effects were similar when categorised by age, the infant being born prematurely, or detection of respiratory syncytial virus.
  • Compared with standard oxygen, high-flow oxygen therapy did not affect length of stay in hospital (mean difference [MD] 0.18 days, 95% CI −0.09 to 0.44), length of stay in the ICU (MD −0.09 days, 95% CI −0.74 to 0.55) or the duration of oxygen therapy (MD −0.06 days, 95% CI −0.28 to 0.16).
  • No serious adverse events were seen in either treatment group. One case of collapsed lung and three cases of apnoea were seen in each group.

What does current guidance say on this issue?

NICE’s 2015 guideline on bronchiolitis in children recommends oxygen supplementation for children with bronchiolitis if their oxygen saturation is persistently less than 92%. Continuous positive airway pressure may be considered in children with bronchiolitis who have impending respiratory failure.

The guideline committee could not identify the best method to deliver oxygen to a child with bronchiolitis. They recommended further research into high-flow oxygen therapy such as described here.

What are the implications?

This large well-conducted trial indicates that high-flow oxygen therapy has a place in the care pathway of infants with bronchiolitis. However, it remains unclear whether it should be used first, for all infants, or only used if standard oxygen therapy has not improved their condition.

Standard oxygen therapy worked well for 566 infants, indicating that high flow oxygen may not be necessary in the majority of cases. Indeed high-flow oxygen from admission did not prevent admissions to the ICU.

Additionally, there was no difference in the outcomes of need for intubation, or length of stay in hospital. These outcomes were identified as most important in NICE’s guideline on bronchiolitis in children. Therefore, it remains to be seen if this study would influence current recommendations.

Citation and Funding

Franklin D, Babl FE, Schlapbach LJ, et al. A randomized trial of high-flow oxygen therapy in infants with bronchiolitis. N Engl J Med. 2018;378(12):1121-31.

This study was supported by a project grant (GNT1081736) from the National Health and Medical Research Council (NHMRC) and by the Queensland Emergency Medical Research Fund. Sites participating in the study were supported by a range of government grants to institutions and individuals.

Bibliography

Beggs S, Wong ZH, Kaul S,  et al. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev. 2014;(1):CD009609.

British Lung Foundation. Support for you: bronchiolitis. London: British Lung Foundation; last reviewed 2016.

NHS Digital. Hospital Admitted Patient Care Activity, 2016-17. London: NHS Digital; 2017.

NHS website. Bronchiolitis. London: Department of Health; updated 2015.

NICE. Bronchiolitis in children: diagnosis and management. NG9. London: National Institute for Health and Care Excellence; 2015.

Why was this study needed?

Bronchiolitis is inflammation of small airways in the lungs. It is most commonly caused by respiratory syncytial virus, and usually affects infants. The first symptoms are similar to a cold, then cough, wheeze and fever develop.

Respiratory syncytial virus usually affects children under two years of age, and about half of them develop bronchiolitis. Most recover within two to three weeks, but some have severe symptoms needing hospital treatment. This amounted to 44,304 children aged less than one year in 2016-17.

A 2014 Cochrane review found only one small study of high flow oxygen therapy in 19 infants with bronchiolitis. There were slight early improvements in oxygen levels but no difference at 24 hours. Duration of oxygen therapy and time in hospital were the same in each group. The authors concluded that there was insufficient evidence to determine the effectiveness of high flow oxygen therapy. This study aimed to fill this research gap.

What did this study do?

This randomised controlled trial included 1,472 infants aged less than 12 months with bronchiolitis needing oxygen supplementation. It took place in 17 emergency departments and paediatric wards in Australia and New Zealand. Infants were assigned to heated and humidified high-flow 2 litres/kg/min oxygen or standard 2 litres/min oxygen. The target blood oxygen levels were 92%/94% to 98%, depending on the hospital.

The primary outcome was escalation of the level of treatment if the infant’s condition was not improving (according to specified criteria). In the high-flow oxygen group, this meant intubation or admission to an intensive care unit (ICU). In the standard oxygen group, high-flow oxygen therapy was an option followed by ICU and other interventions.

Children in each group who failed to improve were managed differently. Outcomes such as admission to intensive care and length of stay were included.

What did it find?

  • Escalation of treatment occurred in 12% (87/739) of infants on high-flow oxygen compared with 23% (167/733) on standard oxygen (relative risk [RR] 0.52, 95% confidence interval [CI] 0.40 to 0.66). However, 102 infants starting on standard oxygen responded to simple escalation of switching to high-flow oxygen.
  • A similar proportion required transfer to ICU; 9% (65/739) in the standard oxygen group compared with 12% (87/739) in the high-flow oxygen group (odds ratio 1.37, 95% CI 0.96 to 1.95). Intubation rates were rare, 1% in each group (OR 1.99, 95% CI 0.60 to 6.65).
  • There was no difference in the time until escalation of care between the two treatments; 0.72 days for high-flow oxygen and 0.67 days for standard oxygen (mean difference 0.05, 95% CI −0.17 to 0.26). The effects were similar when categorised by age, the infant being born prematurely, or detection of respiratory syncytial virus.
  • Compared with standard oxygen, high-flow oxygen therapy did not affect length of stay in hospital (mean difference [MD] 0.18 days, 95% CI −0.09 to 0.44), length of stay in the ICU (MD −0.09 days, 95% CI −0.74 to 0.55) or the duration of oxygen therapy (MD −0.06 days, 95% CI −0.28 to 0.16).
  • No serious adverse events were seen in either treatment group. One case of collapsed lung and three cases of apnoea were seen in each group.

What does current guidance say on this issue?

NICE’s 2015 guideline on bronchiolitis in children recommends oxygen supplementation for children with bronchiolitis if their oxygen saturation is persistently less than 92%. Continuous positive airway pressure may be considered in children with bronchiolitis who have impending respiratory failure.

The guideline committee could not identify the best method to deliver oxygen to a child with bronchiolitis. They recommended further research into high-flow oxygen therapy such as described here.

What are the implications?

This large well-conducted trial indicates that high-flow oxygen therapy has a place in the care pathway of infants with bronchiolitis. However, it remains unclear whether it should be used first, for all infants, or only used if standard oxygen therapy has not improved their condition.

Standard oxygen therapy worked well for 566 infants, indicating that high flow oxygen may not be necessary in the majority of cases. Indeed high-flow oxygen from admission did not prevent admissions to the ICU.

Additionally, there was no difference in the outcomes of need for intubation, or length of stay in hospital. These outcomes were identified as most important in NICE’s guideline on bronchiolitis in children. Therefore, it remains to be seen if this study would influence current recommendations.

Citation and Funding

Franklin D, Babl FE, Schlapbach LJ, et al. A randomized trial of high-flow oxygen therapy in infants with bronchiolitis. N Engl J Med. 2018;378(12):1121-31.

This study was supported by a project grant (GNT1081736) from the National Health and Medical Research Council (NHMRC) and by the Queensland Emergency Medical Research Fund. Sites participating in the study were supported by a range of government grants to institutions and individuals.

Bibliography

Beggs S, Wong ZH, Kaul S,  et al. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev. 2014;(1):CD009609.

British Lung Foundation. Support for you: bronchiolitis. London: British Lung Foundation; last reviewed 2016.

NHS Digital. Hospital Admitted Patient Care Activity, 2016-17. London: NHS Digital; 2017.

NHS website. Bronchiolitis. London: Department of Health; updated 2015.

NICE. Bronchiolitis in children: diagnosis and management. NG9. London: National Institute for Health and Care Excellence; 2015.

A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis

Published on 22 March 2018

Franklin, D.,Babl, F. E.,Schlapbach, L. J.,Oakley, E.,Craig, S.,Neutze, J.,Furyk, J.,Fraser, J. F.,Jones, M.,Whitty, J. A.,Dalziel, S. R.,Schibler, A.

N Engl J Med Volume 378 , 2018

BACKGROUND: High-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting >/=3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTS: The analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, -11 percentage points; 95% confidence interval, -15 to -7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. CONCLUSIONS: Among infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. (Funded by the National Health and Medical Research Council and others; Australian and New Zealand Clinical Trials Registry number, ACTRN12613000388718 .).

Expert commentary

Children receiving high flow therapy triggered fewer of the trial specified clinical markers of concern, but this did not result in a shorter duration of oxygen therapy, or faster discharge from hospital, or fewer admissions to critical care.

The trial results do not support the routine use of high flow oxygen therapy on admission to hospital. Low flow oxygen should remain the standard of care for children with acute bronchiolitis, with CPAP (a type of positive airway pressure ventilator) support for those with developing respiratory failure.

High flow oxygen therapy may have a role in acute bronchiolitis, and its clinical value should be further explored.

Steve Cunningham, Professor of Paediatric Respiratory Medicine, University of Edinburgh

Expert commentary

Use of high flow oxygen for children has crept into UK practice often without much evidence base, and without people really knowing how it works. The treatment of acute bronchiolitis is largely supportive, with no specific therapies. Many have relatively trivial illnesses, but the strength of this study was that the investigators studied large numbers at the sicker end of the spectrum (less than a year old, needing oxygen treatment).

High flow oxygen was more effective in preventing deterioration than standard oxygen treatment and salvaged some infants who were deteriorating on standard oxygen treatment. 

High flow oxygen should thus become standard therapy in infants with bronchiolitis who are deteriorating on standard therapy including conventional flow oxygen.

Professor Andrew Bush, Imperial College and Royal Brompton Hospital