NIHR DC Discover

NIHR Signal High-flow oxygen therapy may be a useful alternative to other forms of breathing support for preterm babies

Published on 17 May 2016

doi: 10.3310/signal-000240

This systematic review found high-flow oxygen delivered by nose was as effective and safe as other non-invasive methods of breathing support for preterm babies. The numbers of treatment failures, deaths and rates of chronic lung disease were similar.

Most studies were of high-flow oxygen for babies after tubes used for ventilation had been removed. For these babies use of high-flow techniques were less likely to cause nasal damage or a collapsed lung than other non-invasive methods.

High-flow oxygen therapy delivers gas through thin tubes that sit just inside each nostril, whereas the most common non-invasive alternative - continuous positive airway pressure –usually delivers gas through tight fitting nasal prongs. Both carry risk of damaging the nose.

The review analysed 15 trials that were open to bias due to potential selective reporting of outcomes.

It was not possible to say which non-invasive option was best, so the benefits and limitations of different approaches should be weighed up on a case by case basis.

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Why was this study needed?

About eight out of every 100 babies born in the UK are born prematurely and many need help to breathe because of underdeveloped lungs.

Mechanical ventilation has traditionally been used to support the baby’s breathing by blowing air directly into the lungs via a tube in the airway. It is available in hospitals where babies are delivered, but even with great care, it risks damaging the baby’s lungs or airway.

So efforts are made either to avoid mechanical ventilation, or to shorten the time it is needed by using other less-invasive methods, once mechanical ventilation tubes are removed.

Nasal continuous positive airway pressure is a common and effective non-invasive breathing support option. High-flow nasal cannula therapy has been adopted in recent years with the perceived advantage of being less risky or invasive and simpler to administer. The efficacy and safety evidence for high-flow therapy is still uncertain, despite its widespread use in neonatal practice and this study set out to try clarify the issue.

This review aimed to find out how high-flow therapy compared with other non-invasive forms of breathing support in preterm babies by combining the results of several trials. It updates a similar 2011 systematic review that concluded there was insufficient evidence to establish the effectiveness or safety of high flow therapy, having identified just four relevant trials.

A previous 2015 NIHR Signal looked at heated, humidified high-flow oxygen to support breathing in preterm babies, one way of delivering this therapy. The review underlying this identified nine trials.

What did this study do?

This Cochrane review found 15 randomised trials comparing high flow therapy with other non-invasive breathing support methods in 1,730 preterm babies (before 37 weeks of pregnancy).

It mainly compared high-flow therapy with nasal continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation. Researchers identified one trial of humidified versus non-humidified high flow therapy.

Breathing support occurred immediately after birth, or following the removal of a breathing tube (extubation) already in place as part of mechanical breathing support.

Trials were rarely registered and so were open to bias due to potential selective reporting of outcomes. This lessens the chance high-flow therapy will be shown to be worse than alternatives.

What did it find?

  • Deaths were rare, but after high flow nasal oxygen use, the rate was similar to the death rate using CPAP. For example, in six trials including 934 babies treated with high flow oxygen, the risk of deaths in babies that were intubated first and then given oxygen after extubation was statistically no different whichever method was used, the typical RR was 0.77, (95% CI 0.43 to 1.36).
  • There were also no significant differences in rates chronic lung disease, treatment failure (see Definitions) or re-intubation between high flow therapy and the other non-invasive techniques tested (six trials, 934 babies).
  • Only one trial (75 babies) compared high flow therapy with nasal intermittent positive pressure ventilation shortly after birth, and also found no difference.
  • For babies who were stable on CPAP, two trials (149 babies) found those who switched to high flow therapy spent around three days less time in hospital compared with those who remained on CPAP. The effect of high flow therapy on duration of breathing in this scenario was not clear; one trial showed high flow therapy increased the duration of breathing support, the other trial showed the opposite.
  • Compared with nasal CPAP, babies using high flow therapy had less damage to their nose (four trials, 645 babies).

What does current guidance say on this issue?

NICE guidance on Preterm labour and birth (2015) does not give specific recommendations on breathing support in newborns.

What are the implications?

The newer high-flow therapy was similar in efficacy and safety compared with more established non-invasive alternatives for breathing support in the preterm babies, with a lower chance of nasal injury.

The trials were small and many were likely to be affected by bias; meaning we don’t know if some of the lack of differences observed were real, or due to study biases.

The effectiveness of high-flow therapy in very preterm (less than 28 weeks gestational age) or late preterm infants (more than 32 weeks) was not addressed, due to trials in these groups.

Citation and Funding

Wilkinson D, Andersen C, O'Donnell CPF et al. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2016;(2):CD006405.

This review was funded by the University of Oxford, Adelaide and Melbourne, as well as NHMRC (Australia) and US Department of Health and Human Services.

Bibliography

NHS Choices. Premature labour and birth. Signs of premature labour. London: Department of Health; last reviewed 2015.

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Care Excellence; 2015.

NIHR DC. Heated, humidified high-flow oxygen therapy may be a useful alternative to other forms of respiratory support for preterm babies. Southampton: National Institute for Health Research Dissemination Centre; 2015.

Why was this study needed?

About eight out of every 100 babies born in the UK are born prematurely and many need help to breathe because of underdeveloped lungs.

Mechanical ventilation has traditionally been used to support the baby’s breathing by blowing air directly into the lungs via a tube in the airway. It is available in hospitals where babies are delivered, but even with great care, it risks damaging the baby’s lungs or airway.

So efforts are made either to avoid mechanical ventilation, or to shorten the time it is needed by using other less-invasive methods, once mechanical ventilation tubes are removed.

Nasal continuous positive airway pressure is a common and effective non-invasive breathing support option. High-flow nasal cannula therapy has been adopted in recent years with the perceived advantage of being less risky or invasive and simpler to administer. The efficacy and safety evidence for high-flow therapy is still uncertain, despite its widespread use in neonatal practice and this study set out to try clarify the issue.

This review aimed to find out how high-flow therapy compared with other non-invasive forms of breathing support in preterm babies by combining the results of several trials. It updates a similar 2011 systematic review that concluded there was insufficient evidence to establish the effectiveness or safety of high flow therapy, having identified just four relevant trials.

A previous 2015 NIHR Signal looked at heated, humidified high-flow oxygen to support breathing in preterm babies, one way of delivering this therapy. The review underlying this identified nine trials.

What did this study do?

This Cochrane review found 15 randomised trials comparing high flow therapy with other non-invasive breathing support methods in 1,730 preterm babies (before 37 weeks of pregnancy).

It mainly compared high-flow therapy with nasal continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation. Researchers identified one trial of humidified versus non-humidified high flow therapy.

Breathing support occurred immediately after birth, or following the removal of a breathing tube (extubation) already in place as part of mechanical breathing support.

Trials were rarely registered and so were open to bias due to potential selective reporting of outcomes. This lessens the chance high-flow therapy will be shown to be worse than alternatives.

What did it find?

  • Deaths were rare, but after high flow nasal oxygen use, the rate was similar to the death rate using CPAP. For example, in six trials including 934 babies treated with high flow oxygen, the risk of deaths in babies that were intubated first and then given oxygen after extubation was statistically no different whichever method was used, the typical RR was 0.77, (95% CI 0.43 to 1.36).
  • There were also no significant differences in rates chronic lung disease, treatment failure (see Definitions) or re-intubation between high flow therapy and the other non-invasive techniques tested (six trials, 934 babies).
  • Only one trial (75 babies) compared high flow therapy with nasal intermittent positive pressure ventilation shortly after birth, and also found no difference.
  • For babies who were stable on CPAP, two trials (149 babies) found those who switched to high flow therapy spent around three days less time in hospital compared with those who remained on CPAP. The effect of high flow therapy on duration of breathing in this scenario was not clear; one trial showed high flow therapy increased the duration of breathing support, the other trial showed the opposite.
  • Compared with nasal CPAP, babies using high flow therapy had less damage to their nose (four trials, 645 babies).

What does current guidance say on this issue?

NICE guidance on Preterm labour and birth (2015) does not give specific recommendations on breathing support in newborns.

What are the implications?

The newer high-flow therapy was similar in efficacy and safety compared with more established non-invasive alternatives for breathing support in the preterm babies, with a lower chance of nasal injury.

The trials were small and many were likely to be affected by bias; meaning we don’t know if some of the lack of differences observed were real, or due to study biases.

The effectiveness of high-flow therapy in very preterm (less than 28 weeks gestational age) or late preterm infants (more than 32 weeks) was not addressed, due to trials in these groups.

Citation and Funding

Wilkinson D, Andersen C, O'Donnell CPF et al. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2016;(2):CD006405.

This review was funded by the University of Oxford, Adelaide and Melbourne, as well as NHMRC (Australia) and US Department of Health and Human Services.

Bibliography

NHS Choices. Premature labour and birth. Signs of premature labour. London: Department of Health; last reviewed 2015.

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Care Excellence; 2015.

NIHR DC. Heated, humidified high-flow oxygen therapy may be a useful alternative to other forms of respiratory support for preterm babies. Southampton: National Institute for Health Research Dissemination Centre; 2015.

High flow nasal cannula for respiratory support in preterm infants

Published on 24 February 2016

Wilkinson, D.,Andersen, C.,O'Donnell, C. P.,De Paoli, A. G.,Manley, B. J.

Cochrane Database Syst Rev Volume 2 , 2016

BACKGROUND: High flow nasal cannulae (HFNC) are small, thin, tapered binasal tubes that deliver oxygen or blended oxygen/air at gas flows of more than 1 L/min. HFNC are increasingly being used as a form of non-invasive respiratory support for preterm infants. OBJECTIVES: To compare the safety and efficacy of HFNC with other forms of non-invasive respiratory support in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 1 January 2016), EMBASE (1980 to 1 January 2016), and CINAHL (1982 to 1 January 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing HFNC with other non-invasive forms of respiratory support in preterm infants immediately after birth or following extubation. DATA COLLECTION AND ANALYSIS: The authors extracted and analysed data, and calculated risk ratio, risk difference and number needed to treat for an additional beneficial outcome. MAIN RESULTS: We identified 15 studies for inclusion in the review. The studies differed in the interventions compared (nasal continuous positive airway pressure (CPAP), nasal intermittent positive pressure ventilation (NIPPV), non-humidified HFNC, models for delivering HFNC), the gas flows used and the indications for respiratory support (primary support from soon after birth, post-extubation support, weaning from CPAP support). When used as primary respiratory support after birth compared to CPAP (4 studies, 439 infants), there were no differences in the primary outcomes of death (typical risk ratio (RR) 0.36, 95% CI 0.01 to 8.73; 4 studies, 439 infants) or chronic lung disease (CLD) (typical RR 2.07, 95% CI 0.64 to 6.64; 4 studies, 439 infants). HFNC use resulted in longer duration of respiratory support, but there were no differences in other secondary outcomes. One study (75 infants) showed no differences between HFNC and NIPPV as primary support. Following extubation (total 6 studies, 934 infants), there were no differences between HFNC and CPAP in the primary outcomes of death (typical RR 0.77, 95% CI 0.43 to 1.36; 5 studies, 896 infants) or CLD (typical RR 0.96, 95% CI 0.78 to 1.18; 5 studies, 893 infants). There was no difference in the rate of treatment failure (typical RR 1.21, 95% CI 0.95 to 1.55; 5 studies, 786 infants) or reintubation (typical RR 0.91, 95% CI 0.68 to 1.20; 6 studies, 934 infants). Infants randomised to HFNC had reduced nasal trauma (typical RR 0.64, 95% CI 0.51 to 0.79; typical risk difference (RD) -0.14, 95% CI -0.20 to -0.08; 4 studies, 645 infants). There was a small reduction in the rate of pneumothorax (typical RR 0.35, 95% CI 0.11 to 1.06; typical RD -0.02, 95% CI -0.03 to -0.00; 5 studies 896 infants) in infants treated with HFNC. Subgroup analysis found no difference in the rate of the primary outcomes between HFNC and CPAP in preterm infants in different gestational age subgroups, though there were only small numbers of extremely preterm and late preterm infants. One trial (28 infants) found similar rates of reintubation for humidified and non-humidified HFNC, and two other trials (100 infants) found no difference between different models of equipment used to deliver humidified HFNC. For infants weaning from non-invasive respiratory support (CPAP), two studies (149 infants) found that preterm infants randomised to HFNC had a reduced duration of hospitalisation compared with infants who remained on CPAP. AUTHORS' CONCLUSIONS: HFNC has similar rates of efficacy to other forms of non-invasive respiratory support in preterm infants for preventing treatment failure, death and CLD. Most evidence is available for the use of HFNC as post-extubation support. Following extubation, HFNC is associated with less nasal trauma, and may be associated with reduced pneumothorax compared with nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with other forms of primary non-invasive support after birth and for weaning from non-invasive support. Further evidence is also required for evaluating the safety and efficacy of HFNC in extremely preterm and mildly preterm subgroups, and for comparing different HFNC devices.

Treatment failure was variably defined across the 15 trials but usually included the need to insert a breathing tube into the baby’s windpipe (intubation) based on different medical needs such as:

  • temporary pauses in breathing (apnoea)
  • respiratory distress (rapid, shallow breathing, blue lips and extremities)
  • breathing failure leading to a build-up of carbon dioxide in the blood (respiratory acidosis)
  • sustained need for oxygen (showing high-flow nasal cannula therapy wasn’t working)

Other criteria of treatment failure included the use of rescue treatment following HFNC, such as continuous positive airway pressure or nasal intermittent positive pressure ventilation without subsequent intubation. Some trials didn’t give definitions of treatment failure.

Expert commentary

High flow therapy has crept into neonatal practice without detailed evaluation and comparison with other forms of therapy. While there are some definite advantages to high flow therapy in terms of being a less invasive form of therapy, generally better tolerated by infants and easier perhaps for nursing such babies, one of the potential concerns is whether this increases a preterm infant’s duration of oxygen exposure and/or has any other detrimental effects. This definitely needs further exploration. A large randomised controlled trial may be difficult to organise as some centres have largely stopped using nasal CPAP and there may not be clinical equipoise in such centres. However, further evaluation is still warranted.

Minesh Khashu, Consultant Neonatologist and Professor of Perinatal Health, Poole Hospital