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High flow nasal cannula for respiratory support in preterm infants

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Authors

Dominic Wilkinson1, Chad Andersen2, Colm PF O'Donnell3, Antonio G De Paoli4

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs


1Discipline of Obstetrics and Gynecology, Women's and Children's Hospital, University of Adelaide, North Adelaide, Australia [top]
2Department of Perinatal Medicine, Children's Youth and Women's Health Service, North Adelaide, Australia [top]
3The National Maternity Hospital, Dublin 2, Ireland [top]
4Department of Paediatrics, Royal Hobart Hospital, Hobart, Australia [top]

Citation example: Wilkinson D, Andersen C, O'Donnell CPF, De Paoli AG. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD006405. DOI: 10.1002/14651858.CD006405.pub2.

Contact person

Dominic Wilkinson

Discipline of Obstetrics and Gynecology
Women's and Children's Hospital, University of Adelaide
72 King William Road
North Adelaide
SA
5006
Australia

E-mail: dominic.wilkinson@adelaide.edu.au

Dates

Assessed as Up-to-date: 14 December 2010
Date of Search: 23 July 2010
Next Stage Expected: 14 September 2012
Protocol First Published: Issue 1, 2007
Review First Published: Issue 5, 2011
Last Citation Issue: Issue 5, 2011

Abstract

Background

High flow nasal cannulae (HFNC) are small, thin, tapered cannulae used to deliver oxygen or blended oxygen and air at flow rates of > 1 L/min. HFNC can be used to provide high concentrations of oxygen and may deliver positive end-expiratory pressure.

Objectives

To compare the safety and efficacy of HFNC with other forms of non-invasive respiratory support in preterm infants.

Search methods

The strategy included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010), MEDLINE, CINAHL, EMBASE and abstracts from conference proceedings.

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

Data were extracted and analysed by the authors. Relative risk, risk difference and number needed to treat were calculated.

Results

Four studies were identified for inclusion in the review. The studies differed in the interventions compared (nasal continuous positive airway pressure (CPAP), humidified HFNC, non-humidified HFNC), the flow rates provided and the indications for respiratory support. Meta-analysis and subgroup analysis were not possible. When used as primary respiratory support after birth, one trial found similar rates of treatment failure in infants treated with HFNC and nasal CPAP. Following extubation, one trial found that infants treated with HFNC had a significantly higher rate of reintubation than those treated with nasal CPAP. Another trial found similar rates of reintubation for humidified and non-humidified HFNC, and the fourth trial found no difference between two different models of equipment used to deliver humidified HFNC.

Authors' conclusions

There is insufficient evidence to establish the safety or effectiveness of HFNC as a form of respiratory support in preterm infants. When used following extubation, HFNC may be associated with a higher rate of reintubation than nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with nasal CPAP and with other means of respiratory support; or of support following extubation. These trials should measure clinically important outcomes.

Plain language summary

Nasal cannulae for breathing support in premature babies

A high flow nasal cannula (HFNC) delivers oxygen or a mixture of oxygen and air via small, thin tubes that sit just inside the nostrils. This is used to provide help to preterm babies with breathing problems. The review found only four randomised studies that compared HFNC with other non-invasive ways of supporting babies' breathing. There is not enough evidence to tell if HFNC is safe or effective compared to other ways of supporting premature babies with breathing difficulties.

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Background

There are a variety of non-invasive ways in which respiratory support can be provided to preterm infants with apnoea or parenchymal lung disease. These include oxygen via a head box or nasal cannula, nasal continuous positive airways pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV).

Nasal cannulae are a means of administration of oxygen or blended oxygen and air via two small, thin, tapered tubes (usually less than 1 cm in length) that sit just inside the nostrils without occluding them (Frey 2003). Oxygen delivered by 'low flow' nasal cannulae (LFNC) typically refers to the use of flow rates of less than or equal to 1 L/minute. Usually the gas used is unblended (that is 100% oxygen), unheated and non-humidified. LFNC are commonly used in convalescing preterm infants, often with chronic lung disease (Walsh 2005), though traditionally the cannula has not been thought to provide significant support to the infant's pulmonary function (apart from the provision of oxygen).

In contrast, 'high flow' nasal cannulae (HFNC) have been used to refer to the administration of oxygen or blended oxygen and air to newborn infants via nasal cannulae at higher flow rates than with LFNC. For the purposes of this review, HFNC will be defined as the use of flow rates of greater than 1 L/minute. The use of high flow rates in preterm infants may provide positive end-expiratory pressure (PEEP) (Locke 1993; Frey 2001; Sreenan 2001). In HFNC systems, circuit flow is adjusted according to clinical effect and, although a pressure relief valve is often used, the circuit pressure is not routinely measured. Oxygen administered via HFNC is usually blended with air, heated and humidified (Waugh 2004). HFNC have been suggested as an alternative form of respiratory support for preterm infants with apnoea, respiratory distress syndrome or chronic lung disease. They appear to be easy to apply and care for (Saslow 2006).

Nasal continuous positive airway pressure (CPAP) is widely used in premature and term newborns and provides an effective, safe alternative to endotracheal intubation (Morley 2004). It has been shown to reduce extubation failure, treat apnoea and respiratory distress syndrome and, by minimising duration of mechanical ventilation, may reduce chronic lung disease (De Paoli 2003). The most effective and popular means of administering CPAP is by using short binasal prongs (Morley 2004). These prongs are designed to fit snugly into the infant's nostrils with minimal leakage. By contrast, nasal cannulae do not usually occlude the nostrils and have the potential for a large leak around them. Other methods of delivering CPAP to the nose that are in common use include single nasal prongs and nasal masks (De Paoli 2008). Oxygen administered by nasal CPAP is usually blended, humidified and heated. As opposed to HFNC, the pressure delivered by the circuit for nasal CPAP is measured and regulated directly.

Unfortunately both systems may have adverse effects. The use of binasal prongs to deliver CPAP is associated with trauma to the nasal septum and distortion of the nares (Robertson 1996; Sreenan 2001). It has been thought that HFNC may cause less nasal injury (Saslow 2006), however the use of humidified, unheated HFNC has been associated with mucosal irritation, nasal obstruction or bleeding as well as a possible increase in the risk of nosocomial infection (Kopelman 2003a; Kopelman 2003b). There have been concerns about contamination of the units used for administering HFNC with gram negative organisms including Ralstonia (MMWR 2005). One case has been reported associating HFNC with pneumocephalus, pneumo-orbitis and scalp emphysema (Jasin 2008).

There has also been concern about the possibility of lung overdistension and trauma from unmeasured and variable PEEP with high flow nasal cannulae (Finer 2005). Other possible risks associated with HFNC include gastric distension or perforation.

The purpose of this review is to compare HFNC with other methods of providing non-invasive respiratory support in newborn infants.

Objectives

The objectives were as follows.

In preterm infants, to compare the efficacy and safety of high flow nasal cannulae (HFNC) with other non-invasive methods of respiratory support including:

  • head box oxygen;
  • low flow nasal cannulae (LFNC);
  • nasal continuous positive airways pressure (CPAP);
  • non-invasive positive pressure ventilation (NIPPV);
  • alternative forms of HFNC.

Subgroup analysis was planned to determine the efficacy of HFNC in infants with different underlying illnesses and of different gestational ages:

  • parenchymal lung disease (requiring supplemental oxygen);
  • apnoea of prematurity;
  • corrected gestational age greater than/or equal to 30 weeks;
  • corrected gestational age < 30 weeks.

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Methods

Criteria for considering studies for this review

Types of studies

All randomised and quasi-randomised studies (including crossover trials). Studies reported in abstract form were included in the 'Studies awaiting assessment' category. Data from one unpublished study (published only in abstract form) were obtained from the authors to enable its inclusion in the review.

Types of participants

  1. Preterm infants (< 37 weeks gestational age) receiving respiratory support after birth, either prophylactically or for respiratory distress syndrome without a prior period of intermittent positive pressure ventilation (IPPV).
  2. Preterm infants (< 37 weeks gestational age) requiring respiratory support following a period of intermittent positive pressure ventilation (IPPV).

Types of interventions

High flow nasal cannula oxygen was defined for the purposes of this review as the delivery of oxygen or blended oxygen and air via a nasal cannula at flow rates of greater than 1 litre per minute (L/minute).

Alternative interventions included:

  • head box oxygen;
  • low flow nasal cannulae (flow rate less than or equal to 1 L/minute);
  • nasal CPAP;
  • NIPPV;
  • HFNC using an alternative technique (e.g. humidified versus non-humidified, or different models for delivering HFNC)*.

Comparisons that were not in the original review protocol that we have included after review of the available data are marked by an asterix (*).

Types of outcome measures

Primary outcomes
  • Death (before hospital discharge)
  • Chronic lung disease (the need for supplemental oxygen at or greater than 36 weeks postmenstrual age for infants born before 32 weeks gestation; or the need for supplemental oxygen at 28 days of life)
  • Death or chronic lung disease (as defined above)
  • Failure of treatment as indicated by the need for reintubation
Secondary outcomes
Respiratory support:
  • duration in days of any form of respiratory support (mechanical ventilation, CPAP, high flow nasal cannula, oxygen*);
  • length of stay (days).
Complications:
  • air leak syndromes (pneumothorax, pneumomediastinum, pneumopericardium or pulmonary interstitial emphysema (PIE)) reported either individually or as a composite outcome;
  • nasal trauma (defined as erythema or erosion of the nasal mucosa, nares or septum as assessed by a blinded observer);
  • nosocomial sepsis (defined as positive blood or cerebrospinal fluid (CSF) cultures taken after five days of age);
  • gastrointestinal perforation or severe necrotizing enterocolitis (stage II or more according to Bell's criteria (Bell 1978));
  • growth (weight gain prior to discharge from hospital);
  • days to full feeds *.
Neurosensory outcomes:
  • retinopathy of prematurity (any and severe stage 3 or greater);
  • long term neurodevelopmental outcome (rates of cerebral palsy on physician assessment, developmental delay i.e. IQ 2 standard deviations less than the mean on validated assessment tools such as Bayley's Mental Developmental Index), blindness, hearing impairment requiring amplification.

Outcome measures that were not in the original protocol that were included after review of the available data are marked by an asterisk (*).

Search methods for identification of studies

See the Cochrane Neonatal Group methods used in reviews.

The standard search strategy of the Cochrane Neonatal Group was used. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), PubMed (January 1966 to July 2010), CINAHL (January 1982 to July 2010), and EMBASE (January 1980 to July 2010) were searched for clinical trials (publication type "clinical trial" or "randomised controlled trial") using the MeSH headings: infant, newborn AND oxygen inhalation therapy OR positive pressure respiration AND the text words "nasal cannula*" OR "nasal prong*". A second search looked for the MeSH heading "infant, newborn" in combination with the textword "high flow nasal"(**). In addition, the published abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched (2000 to 2010).

Clinical trial registries were also searched for ongoing or recently completed trials (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp).

There were no language restrictions.

An additional search string added after review of the search results is indicated by a double asterisk (**).

Data collection and analysis

The standard methods of the Cochrane Neonatal Review Group were employed.

Selection of studies

All randomised and quasi-randomised controlled trials fulfilling the selection criteria described in the previous section were included. The authors reviewed the results of the search and separately selected the studies for inclusion. The review authors resolved any disagreement by discussion.

Data extraction and management

Trial searches, assessments of methodology and extraction of data were performed independently by each review author, with comparison and resolution of any differences found at each stage. For each trial, information was collected regarding blinding of randomisation, the intervention and outcome measurements as well as completeness of follow up. For crossover trials, data from the first period only were used.

Where any queries arose or where additional data were required, the study authors were contacted.

Assessment of risk of bias in included studies

The methodological quality of the studies was assessed using the following key criteria: allocation concealment (blinding of randomisation), blinding of intervention, completeness of follow up, and blinding of outcome measurement or assessment. For each criterion, the assessment was: yes, no, can't tell. The review authors separately assessed each study. Any disagreement was resolved by discussion. This information was added to the 'Characteristics of Included Studies' table.

The following issues were evaluated and entered into the 'Risk of bias' table.

  1. Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated? For each included study, we categorized the method used to generate the allocation sequence as:
    1. adequate (any truly random process e.g. random number table; computerised random number generator);
    2. inadequate (any non-random process e.g. odd or even date of birth; hospital or clinic record number);
    3. unclear.
  2. Allocation concealment (checking for possible selection bias). Was allocation adequately concealed?For each included study, we categorized the method used to conceal the allocation sequence as:
    1. adequate (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
    2. inadequate (open random allocation; unsealed or non-opaque envelopes; alternation; date of birth);
    3. unclear.
  3. Blinding (checking for possible performance bias). Was knowledge of the allocated intervention adequately prevented during the study? At study entry? At the time of outcome assessment?For each included study, we categorized the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding was assessed separately for different outcomes or classes of outcomes. In some situations there may be partial blinding, for example where outcomes are self-reported by unblinded 'participants' but they are recorded by blinded personnel without knowledge of group assignment. Where needed, 'partial' was added to the list of options for assessing quality of blinding. We categorized the methods as:
    1. adequate, inadequate or unclear for participants;
    2. adequate, inadequate or unclear for personnel;
    3. adequate, inadequate or unclear for outcome assessors.
  4. Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed?For each included study and for each outcome, we described the completeness of data including attrition and exclusions from the analysis. We noted whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total number of randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes.Where sufficient information was reported or supplied by the trial authors, we re-included missing data in the analyses. We categorized the methods as:
    1. adequate (< 20% missing data);
    2. inadequate (greater than/or equal to 20% missing data):
    3. unclear.
  5. Selective reporting bias. Are reports of the study free of any suggestion of selective outcome reporting?For each included study, we described how we investigated the possibility of selective outcome reporting bias and what we found. We assessed the methods as:
    1. adequate (where it was clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review have been reported);
    2. inadequate (where not all the study’s pre-specified outcomes were reported; one or more of the reported primary outcomes were not pre-specified; outcomes of interest were reported incompletely and so could not be used; study failed to include results of a key outcome that would have been expected to have been reported);
    3. unclear.
  6. Other sources of bias. Was the study apparently free of other problems that could put it at a high risk of bias?
    1. For each included study, we described any important concerns we had about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data-dependent process). We assessed whether each study was free of other problems that could put it at risk of bias, as:
    2. yes;no;or unclear.

If needed, we planned to explore the impact of the level of bias through undertaking sensitivity analyses.

Measures of treatment effect

Categorical data (for example number dying or with chronic lung disease) were extracted for each intervention group, and relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) were calculated. Means and standard deviations were obtained for continuous data (for example number of days of respiratory support, or duration of oxygen dependency). For each measure of effect the 95% confidence interval (CI) was calculated.

Assessment of heterogeneity

Heterogeneity was estimated using the I2 statistic, to determine the suitability of pooling results.

Data synthesis

The fixed-effect model was to be applied for meta-analysis. Means and standard deviations were obtained for continuous data (for example number of days of respiratory support, or duration of oxygen dependency) and analysis performed using the weighted mean difference (WMD). For each measure of effect the 95% CI was calculated.

Subgroup analysis and investigation of heterogeneity

We planned to perform subgroup analysis by underlying illness and by gestational age:

  • apnoea of prematurity (preterm infants receiving respiratory support for apnoea without evidence of parenchymal lung disease i.e. not requiring supplemental oxygen);
  • parenchymal lung disease (e.g. hyaline membrane disease or chronic lung disease, defined as preterm infants requiring respiratory support including supplemental oxygen);
  • postmenstrual age greater than/or equal to 30 weeks (at the time of study);
  • postmenstrual age < 30 weeks (at the time of study).

Sensitivity analysis

A sensitivity analysis was to be performed by quality of methods used.

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Results

Description of studies

See Characteristics of Included Studies, Characteristics of excluded studies

Four studies in total were identified for inclusion. The studies by Campbell 2006 (40 infants), Woodhead 2006 (30 infants) and Miller 2010 (40 infants) were available as full journal publications. The study by Nair 2005 (67 infants) was published as an abstract. Additional unpublished data were generously provided by Nair et al enabling its inclusion in this review. Five randomised controlled trials of HFNC versus nasal CPAP or nasal intermittent mandatory ventilation are currently under way (Yoder 2007; Collins 2008; Kugelman 2010; Manley 2010; Weintraub 2010).

  1. HFNC versus nasal CPAP for preterm infants soon after birth for treatment or prophylaxis of respiratory distress syndrome (RDS)
    Nair 2005 studied preterm infants with respiratory distress in the first six hours after birth. Infants in this study had a mean gestational age of 32 weeks. The authors compared humidified HFNC (mean flow rate 5 to 6 L/min) with constant flow (bubble) CPAP at 5 to 6 cm H2O. Infants who developed respiratory failure (defined by pH less than/or equal to 7.25 with CO2 greater than/or equal to 60, fraction of inspired oxygen (FiO2) greater than/or equal to 70%, or severe or frequent apnoea) were intubated. This trial was stopped early because of the temporary recall of VapothermTM devices related to reports external to this trial of Ralstonia infections.
  2. HFNC versus nasal CPAP for preterm infants after extubation following mechanical ventilation for RDS
    Campbell 2006 studied intubated infants (mean 27 weeks gestation) at the time of extubation. The authors compared humidified, unheated HFNC (mean flow rate 1.8 L/min) with variable flow CPAP (infant-flow) at 5 to 6 cm H2O. The primary outcome was need for reintubation, with decisions to reintubate based upon meeting one or more of several criteria (uncompensated respiratory acidosis with pH less than/or equal to 7.25, FiO2 greater than/or equal to 60%, severe or frequent apnoea).
  3. Warmed, humidified HFNC versus 'standard' HFNC for preterm infants after extubation following mechanical ventilation for RDS
    Woodhead 2006 studied infants with a mean gestational age of 32 weeks following extubation. The authors compared humidified HFNC (VapothermTM) (mean flow rate 3.1 L/min) with non-humidified HFNC (mean flow 1.8 L/min) following extubation.

    This was a randomised crossover trial; results from only the first study period were used for analysis. The authors defined failure of extubation either by the need for reintubation (at the discretion of treating physicians) or a switch to the alternative modality of HFNC.
  4. Alternative models for delivery of humidified HFNC to preterm infants after extubation following mechanical ventilation for RDS
    Miller 2010 studied preterm infants of 26 to 29 weeks gestation who had been intubated in the first 72 hours of life. The study compared two different brands of equipment (Fischer and PaykelTM versus VapothermTM) for delivery of humidified HFNC at 6 L/min. The primary outcome was the need for reintubation within 72 hours of extubation. Infants were reintubated if they had FiO2 greater than/or equal to 70%, pH less than/or equal to 7.25 with CO2 greater than/or equal to 65, or severe or frequent apnoea.

Risk of bias in included studies

Blinding was not attempted for clinical management in any of the studies. Woodhead 2006 blinded assessment of nasal mucosa by keeping a Vapotherm unit at the bedside for all infants during examination. There were preset criteria for respiratory failure in Campbell 2006; Nair 2005 and Miller 2010, though frequency of blood gas testing and recording of apnoea were potentially open to bias. In the study by Woodhead 2006 intubation decisions as well as alterations to flow rates were left to the discretion of treating physicians and respiratory therapists. This may have contributed to a difference in flow rates between the two arms of the study. Secondary outcomes were retrieved from medical records in all three studies and were potentially open to bias. One patient in the study by Miller 2010 was excluded from the analysis after developing sepsis and dying during the study, though this patient should have been included as requiring reintubation. There was also an imbalance in the numbers of infants randomised to each arm in that study, which may reflect lack of allocation concealment.

Allocation concealment was not clear in the studies by Woodhead 2006 and Miller 2010.

Effects of interventions

Comparison 1. HFNC versus nasal CPAP for preterm infants soon after birth for treatment or prophylaxis of RDS

One study was available for this comparison (Nair 2005). Rates of respiratory failure (and consequent need for intubation) were similar between humidified HFNC and nasal CPAP (4/33 HFNC, 4/34 CPAP) (Figure 1). There were no deaths in either group; one infant in the CPAP group developed chronic lung disease. Secondary outcomes (including duration of respiratory support, nasal trauma, pneumothorax, sepsis and length of hospitalisation) were similar between groups.

Comparison 2. HFNC versus nasal CPAP for preterm infants after extubation following mechanical ventilation for RDS

One study was available for this comparison (Campbell 2006). There was a higher rate of reintubation (12/20 infants treated with humidified, unheated HFNC compared to 3/20 infants treated with nasal CPAP; RR 4.00, 95% CI 1.33 to 12.05) (Figure 4). Nasal mucosal damage was not observed in either group. There was no significant difference in the incidence of necrotizing enterocolitis, intraventricular haemorrhage, chronic lung disease, sepsis or retinopathy of prematurity between groups.

Comparison 3. Warmed, humidified HFNC versus 'standard' HFNC for preterm infants after extubation following mechanical ventilation for RDS

One study was available for this comparison (Woodhead 2006). There was no significant difference in need for intubation during the first 24 hours of the study (that is prior to crossover) (0/15 infants treated with humidified HFNC compared to 2/15 infants treated with non-humidified HFNC) (Figure 2). Nasal mucosal scores were not available for the first study period, however the authors noted a significantly more normal appearance in infants treated with humidified HFNC.

Comparison 4. Alternative models for delivery of humidified HFNC to preterm infants after extubation following mechanical ventilation for RDS

One study compared different models for delivery of HFNC (Miller 2010). There was no significant difference in the need for reintubation within 72 hours of extubation (3/17 infants treated with Fischer and Paykel, 3/22 infants treated with Vapotherm) (Figure 3). There was one death in the Vapotherm group, and one infant in the Fischer and Paykel group developed necrotising enterocolitis. Rates of chronic lung disease were similar between the two groups. Side effects (pneumothorax, pulmonary haemorrhage, lung hyperinflation, feeding intolerance) were not observed in either group.

Discussion

This review identified four small randomised trials including a total of 177 premature infants that compared HFNC with other forms of non-invasive respiratory support in preterm infants. The studies were not adequately powered to exclude clinically meaningful differences between the interventions. Meta-analysis was not performed due to differences in the comparisons between studies. Sensitivity analysis and subgroup analysis were not possible. Data were not available for important primary and secondary outcomes relevant to this review in two of the four studies. There were no studies comparing HFNC with low flow nasal cannulae, head box oxygen or with NIPPV.

The four studies were methodologically sound, however allocation concealment was not possible and bias may have occurred, particularly where there were no established criteria for reintubation (Woodhead 2006).

HFNC versus nasal CPAP

For infants needing primary respiratory support after birth, HFNC was not more effective than nasal CPAP in one small study (Nair 2005). For infants extubated following mechanical ventilation, one study (Campbell 2006) found a significantly higher rate of reintubation in infants treated with HFNC.

This contrasts with Nair 2005 and with two retrospective studies that have found similar or reduced rates of extubation failure in infants treated with HFNC compared to nasal CPAP (Holleman-Duray 2007; Shoemaker 2007). The different findings may relate to the study design (randomised rather than historical comparison), but may also relate to the type of gas conditioning (unheated, bubble humidifier), or to the relatively low flow rates used in Campbell 2006 (mean flow 1.8 L/min). Although two earlier studies found significant elevations in pharyngeal pressure at flow rates of 1 to 2 L/min (Locke 1993; Sreenan 2001), more recent studies in premature infants receiving HFNC therapy have found elevated pharyngeal pressure only at flow rates greater than/or equal to 4 L/min (Saslow 2006; Spence 2007; Wilkinson 2008; Lampland 2009).

Different forms of HFNC

There was no evidence from one small study (Woodhead 2006) of any benefit from humidification of HFNC. During the second half of the crossover trial infants treated with non-humidified HFNC had a higher rate of being switched to humidified HFNC because of perceived treatment failure. This may have related to the higher flow rates used in infants receiving humidified HFNC. There were higher (more abnormal) scores for nasal mucosal injury in infants treated with non-humidified HFNC.

There was no difference in effectiveness between two different models of equipment used to deliver HFNC in another small study (Miller 2010). None of the included studies examined the effect of different flow rates or cannula sizes.

Authors' conclusions

Implications for practice

Based on the results of this review there is insufficient evidence to determine whether or not HFNC is safe or effective as a form of respiratory support in preterm infants. When used following extubation, HFNC may be associated with a higher rate of reintubation than nasal CPAP.

Implications for research

Further adequately powered randomised controlled trials should be undertaken in preterm infants that compare HFNC with nasal CPAP and with other means of primary respiratory support; or of support following extubation. These trials should measure clinically important outcomes, including death, chronic lung disease, need for mechanical ventilation and duration of respiratory support. If HFNC is shown to be effective, further research should aim to establish which patient subgroups benefit from HFNC, and compare different strategies for delivering HFNC (for example nasal cannula size, flow rates, temperature/humidity settings).

Acknowledgements

Yolanda Montagne provided invaluable assistance with literature searches.

Contributions of authors

The authors Wilkinson, Andersen and O'Donnell developed the protocol; all authors performed the literature search, data collection and analysis and collaborated in the writing of the review.

Declarations of interest

  • None noted.

Differences between protocol and review

Comparisons not in the original protocol that were included after review of the available data included:

  • comparison of HFNC with HFNC of alternative technique (e.g. humidified versus non-humidified).

Outcome measures that were not in the original protocol that were included after review of the available data included:

  • days to full feeds, and duration of oxygen therapy.

One additional search string was added.

Additional tables

  • None noted.

Potential conflict of interest

  • None noted.

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Characteristics of studies

Characteristics of Included Studies

Campbell 2006

Methods

Randomised controlled trial

Participants

40 intubated preterm infants < 1250g, (mean 27 weeks gestation, median 39/24 hours old at extubation)

Interventions

Humidified, non-heated HFNC (mean flow rate 1.6L/min, n=20)

CPAP - variable flow, short binasal prongs, 5-6cm H2O pressure; n=20

Outcomes

Need for reintubation in first 7 days after extubation (criteria for intubation included uncompensated respiratory acidosis, FiO2 >60%, severe or frequent apnoea)

Nasal damage

NEC, CLD, IVH, ROP, sepsis, change in oxygen use post-extubation, episodes of apnoea or bradycardia, rate of weight gain

Notes

Higher caffeine use in HFNC group (14/20 compared to 9/20).

Study funded by Physicians Services incorporated Foundation, Toronto.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Permuted block randomisation with random number table

Allocation concealment (selection bias) Low risk

Opaque envelopes

Blinding (performance bias and detection bias)
Need for intubation
High risk

Standardised criteria for reintubation (but not reported whether infants met these criteria equally in each group)

Blinding (performance bias and detection bias)
Nasal damage
Unclear risk

Miller 2010

Methods

Randomised controlled trial

Participants

40 preterm infants, 26-29 weeks gestation, intubated in the first 72 hours of life, mean 28.2 weeks gestation, birth weight 1100g

Interventions

HFNC - VapothermTM 6L/min; n=20

HFNC - Fischer and PaykelTM 6L/min; n=20

Weaned by no more than 1L/min per day

Outcomes

Extubation failure within 72 hours (reintubated if oxygen requirement persistently >70%, CO2 on arterial blood gas of >65 with pH of < 7.25, >3 apnoea episodes requiring moderate stimulation in 12 h or two apnoea episodes requiring vigorous stimulation in an 8h period

Reintubation less than/or equal to 7 days

Duration of mechanical ventilation after initial extubation

Incidence of CLD (oxygen requirement at 36 weeks corrected age)

Pneumothorax

Hyperinflated on CXR

Pulmonary haemorrhage

Feeding intolerance (>50% residuals)

Notes

One infant randomised to HFNC (Vapotherm) was reintubated but then died during the study (blood culture indicated Pseudomonas sepsis) and was excluded from analysis.

Study was jointly funded by the two manufacturers of HFNC equipment.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk
Allocation concealment (selection bias) Unclear risk
Blinding (performance bias and detection bias)
Need for intubation
High risk
Blinding (performance bias and detection bias)
Nasal damage
Unclear risk

Not assessed

Nair 2005

Methods

Randomised controlled trial

Participants

67 preterm infants with respiratory distress requiring CPAP in 1st 6 hours, 27-34 weeks gestation (mean 32 weeks)

Interventions

HFNC - VapothermTM 5-6L/min; n=33

CPAP - bubble CPAP, Hudson prongs, 5-6cm H2O; n=34

Outcomes

Respiratory failure (leading to intubation) (pHless than/or equal to7.25 and CO2 greater than/or equal to60 (arterial), or FiO2 >70%, or severe or frequent apnoeas)

Nasal injury

BPD, mortality, length of hospitalisation, sepsis, pneumothorax

Notes

Study finished prior to achieving target sample size due to recall of Vapotherm units. A full study manuscript including results was obtained from the authors.

Vapotherm provided equipment for the study.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Stratified into 27-30 weeks gestation and 31-34 weeks. Permuted block randomisation

Allocation concealment (selection bias) Low risk

Sealed envelopes

Blinding (performance bias and detection bias)
Need for intubation
High risk

Standardised criteria for respiratory failure, though frequency of blood gases and recording of apnoeas not blinded

Blinding (performance bias and detection bias)
Nasal damage
High risk

Woodhead 2006

Methods

Randomised crossover trial

Participants

30 infants admitted to neonatal intensive care unit, intubated, planned to extubate to HFNC

Interventions

Randomised to one modality for 24 hours after extubation then switched to other modality

Humidified HFNC - VapothermTM (mean 3.1L/min); n=15

Non-humidified HFNC (mean 1.8L/min); n=13

Outcomes

Need for intubation (no pre-specified criteria)

Nasal mucosa examination

Pneumothorax or pneumomediastinum

Notes

Data from the first crossover period only were included in the review.

Flow rates differed significantly between interventions.

Funding source unclear.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Random number table, stratified by weight

Allocation concealment (selection bias) Unclear risk
Blinding (performance bias and detection bias)
Need for intubation
High risk

No set criteria for intubation

Blinding (performance bias and detection bias)
Nasal damage
Low risk

'Masking' of intervention. Unclear how effective

BPD: bronchopulmonary dysplasia

CLD: chronic lung disease

CXR: chest x-ray

Characteristics of excluded studies

Beltramo 2008

Reason for exclusion

This study was non-randomised. It compared the need for reintubation in 20 consecutive infants with birth weight < 1750g needing respiratory support post-extubation (the first 8 treated with CPAP, subsequent 12 treated with HRNC).

Boumecid 2007

Reason for exclusion

This crossover trial compared variable flow CPAP with constant flow CPAP and non-humidified nasal cannula at 2L/min. No outcomes of relevance to this review were reported.

Capasso 2005

Reason for exclusion

This study did not examine the use of nasal cannulae for the target indication for this review (resuscitation at birth was studied).

Courtney 2001

Reason for exclusion

This crossover trial compared variable flow CPAP with constant flow CPAP, and a modified nasal cannula attached to a constant flow CPAP circuit. No outcomes of relevance to this review were reported.

Holleman-Duray 2007

Reason for exclusion

This study was non-randomised (it compared HFNC in combination with an early extubation policy in comparison with historical controls).

Lampland 2009

Reason for exclusion

This non-randomised crossover study compared CPAP with HFNC. No outcomes of relevance to this review were reported.

Pyon 2008

Reason for exclusion

This crossover trial compared NCPAP with HFNC. No outcomes of relevance to this review were reported.

Saslow 2006

Reason for exclusion

This crossover trial compared CPAP with high flow nasal cannulae. No outcomes of relevance to this review were reported.

Shoemaker 2007

Reason for exclusion

This non-randomised study compared HFNC with historical controls treated with CPAP.

Sreenan 2001

Reason for exclusion

This crossover trial of CPAP and non-humidified HFNC was non-randomised

Wilson 1996

Reason for exclusion

This study examined nasal cannula compared to nasopharyngeal catheters at flow rates < 1L/min.

Characteristics of studies awaiting classification

Joshi 2008

Methods

Randomised controlled trial of CPAP versus HFNC

Participants

80 preterm infants (BW 1806g), gestational age 32.8 weeks, with respiratory failure not requiring invasive ventilation

Interventions

Conventional CPAP versus high flow device (VapothermTM)

Outcomes

Duration of respiratory support, need for invasive ventilation, pneumonia, pneumothorax, feed intolerance, nasal complications

Notes

Characteristics of ongoing studies

Collins 2008

Study name
Methods

RCT, target sample size 130 infants

Participants

Premature infants < 32 weeks post-extubation

Interventions

HFNC versus CPAP post-extubation

Outcomes

Primary outcome: reintubation rates in first 7 days following primary extubation

Starting date
Contact information

Dr Clare Collins, Mercy Hospital for Women, Melbourne, ccollins@mercy.com.au

Notes

Kugelman 2010

Study name

High Flow Nasal Cannula (HFNC) Versus Nasal Intermittent Mandatory Ventilation (NIMV)for Respiratory Distress Syndrome (RDS): a Randomized, Controlled, Prospective Study

Methods

RCT, estimated enrolment 80 infants

Participants

Premature infants 24-35 weeks needing primary respiratory support or following extubation

Interventions

HFNC versus nasal intermittent mandatory ventilation

Outcomes

Need for intubation and mechanical ventilation, or switching to alternative form of non-invasive support

Starting date

25/8/2010

Contact information

Bnai Zion Medical Center, Neonatal department, Haifa, Israel, tel: 972-4-8359559

Notes

Manley 2010

Study name

The HIPERSPACE Trial: Comparing the failure rate of high-flow nasal cannulae (HFNC) versus nasal continuous positive airway pressure (CPAP) as post-extubation respiratory support in premature infants with gestational age of 24 to 32 weeks

Methods

RCT, target sample size 300 infants

Participants

Premature infants 24-32 weeks being extubated to respiratory support

Interventions

HFNC versus CPAP post-extubation

Outcomes

Failure of treatment defined as acidosis, increasing oxygen requirement, worsening apnoea, emergency need for intubation

Starting date

1/5/2010

Contact information

Dr Brett Manley, Royal Women's Hospital, Melbourne, Australia, brett.manley@thewomens.org.au

Notes

Weintraub 2010

Study name

High Flow Nasal Cannula vs Bubble Nasal CPAP for the Treatment of Transient Tachypnea of the Newborn in Infants >35 Weeks Gestation

Methods

RCT, estimated enrolment 66 infants

Participants

Infants >35 weeks gestation diagnosed with transient tachypnoea and admitted to the NICU within the first 24 hours of life

Interventions

HFNC versus bubble nasal CPAP

Outcomes

Duration of respiratory support

Starting date

July 2010

Contact information

Andrea Weintraub, Mount Sinai School of Medicine, New York, andrea.weintraub@mssm.edu

Notes

Yoder 2007

Study name

Comparison of Humidified High Flow Nasal Cannula to Nasal Continuous Positive Airway Pressure for Non-Invasive Respiratory Support in Neonates

Methods

RCT, non-inferiority, target sample size 420

Participants

Infants >1000g and >27 weeks gestation, either primary respiratory support, or post-extubation

Interventions

HFNC versus nasal CPAP

Outcomes

Extubation success (remaining extubated >72 hours)

Starting date

12/2007

Contact information

Dr B Yoder, Intermountain Medical Center Salt Lake City, Utah, United States, bradley.yoder@hsc.utah.edu

Notes

NICU: neonatal intensive care unit

[top]

References to studies

Included studies

Campbell 2006

Campbell DM, Shah PS, Shah V, Kelly EN. Nasal continuous positive airway pressure from high flow cannula versus infant flow for preterm infants. Journal of Perinatology 2006;26(9):546-9.

Miller 2010

[DOI: 10.1038/jp.2010.38]

* Miller SM, Dowd SA. High-flow nasal cannula and extubation success in the premature infant: a comparison of two modalities. Journal of Perinatology 2010;30(12):805-8.

Nair 2005

Unpublished data only

Nair G, Karna P. Comparison of the effects of Vapotherm and nasal CPAP in respiratory distress. In: PAS. 2005:1.

Woodhead 2006

* Woodhead DD, Lambert DK, Clark JM, Christensen RD. Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial. Journal of Perinatology 2006;26(8):481-5.

Excluded studies

Beltramo 2008

Beltramo F, Romero R, Chandler B, Soliz A. Successful extubation in low birth weight infants: A comparison of continuous positive airway pressure (CPAP) versus Vapotherm. In: PAS. 2008.

Boumecid 2007

* Boumecid H, Rakza T, Abazine A, Klosowski S, Matran R, Storme L. Influence of three nasal continuous positive airway pressure devices on breathing pattern in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2007;92(4):F298-300.

Capasso 2005

* Capasso L, Capasso A, Raimondi F, Vendemmia M, Araimo G, Paludetto R. A randomized trial comparing oxygen delivery on intermittent positive pressure with nasal cannulae versus facial mask in neonatal primary resuscitation. Acta Paediatrica 2005;94(2):197-200.

Courtney 2001

* Courtney SE, Pyon KH, Saslow JG, Arnold GK, Pandit PB, Habib RH. Lung recruitment and breathing pattern during variable versus continuous flow nasal continuous positive airway pressure in premature infants: an evaluation of three devices. Pediatrics 2001;107(2):304-8.

Holleman-Duray 2007

* Holleman-Duray D, Kaupie D, Weiss MG. Heated humidified high-flow nasal cannula: use and a neonatal early extubation protocol. Journal of Perinatology 2007;27(12):776-81.

Lampland 2009

Lampland AL, Plumm B, Meyers PA, Worwa CT, Mammel MC. Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure. The Journal of Pediatrics 2009;154(2):177-82.

Pyon 2008

Pyon KH, Aghai ZH, Nakhla TA, Stahl GE, Saslow JG. High flow nasal cannula in preterm infants: Effects of high flow rates on work of breathing. In: PAS. 2008.

Saslow 2006

* Saslow JG, Aghai ZH, Nakhla TA, Hart JJ, Lawrysh R, Stahl GE, et al. Work of breathing using high-flow nasal cannula in preterm infants. Journal of Perinatology 2006;26:476-80.

Shoemaker 2007

* Shoemaker MT, Pierce MR, Yoder BA, DiGeronimo RJ. High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study. Journal of Perinatology 2007;27(2):85-91.

Sreenan 2001

* Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001;107:1081-3.

Wilson 1996

* Wilson J, Arnold C, Connor R, Cusson R. Evaluation of oxygen delivery with the use of nasopharyngeal catheters and nasal cannulas. Neonatal Network 1996;15(4):15-22.

Studies awaiting classification

Joshi 2008

Joshi R, Rajhans A, Patil S, Dominic S, Phadtare R, Devaskar U. High flow oxygen in neonatal respiratory failure: Is it better than CPAP. In: PAS. 2008.

Ongoing studies

Collins 2008

Unpublished data only

Kugelman 2010

Unpublished data only [ClinicalTrials.gov: NCT01189162]

Manley 2010

Unpublished data only [Other: ACTRN12610000166077]

Weintraub 2010

Unpublished data only [ClinicalTrials.gov: NCT01270581]

Yoder 2007

Unpublished data only [ClinicalTrials.gov: NCT00609882]

Other references

Additional references

Bell 1978

Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of Surgery 1978;187:1-7.

De Paoli 2003

De Paoli AG, Morley C, Davis PG. Nasal CPAP for neonates: what do we know in 2003? Archives of Disease in Childhood. Fetal and Neonatal Edition 2003;88:F168-72.

De Paoli 2008

De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD002977. DOI: 10.1002/14651858.CD002977.pub2.

Finer 2005

Finer NN. Nasal cannula use in the preterm infant: oxygen or pressure? Pediatrics 2005;116(5):1216-7.

Frey 2001

Frey B, McQuillan PJ, Shann F, Freezer N. Nasopharyngeal oxygen therapy produces positive end-expiratory pressure in infants. European Journal of Pediatrics 2001;160:556-60.

Frey 2003

Frey B, Shann F. Oxygen administration in infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2003;88:F84-8.

Jasin 2008

Jasin LR, Kern S, Thompson S, Walter C, Rone JM, Yohannan MD. Subcutaneous scalp emphysema, pneumo-orbitis and pneumocephalus in a neonate on high humidity high flow nasal cannula. Journal of Perinatology 2008;28(11):779-81.

Kopelman 2003a

Kopelman AE. Airway obstruction in two extremely low birthweight infants treated with oxygen cannulas. Journal of Perinatology 2003;23:164-5.

Kopelman 2003b

Kopelman AE, Holbert D. Use of oxygen cannulas in extremely low birthweight infants is associated with mucosal trauma and bleeding, and possibly with coagulase-negative staphylococcal sepsis. Journal of Perinatology 2003;23:94-7.

Locke 1993

Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive end-distending pressure during nasal cannula flow. Pediatrics 1993;91:135-8.

MMWR 2005

MMWR. Ralstonia associated with Vapotherm oxygen delivery device--United States, 2005. MMWR Morbidity and Mortality Weekly Report 2005;54:1052-3.

Morley 2004

Morley C, Davis P. Continuous positive airway pressure: current controversies. Current Opinion in Pediatrics 2004;16:141-5.

Robertson 1996

Robertson NJ, McCarthy LS, Hamilton PA, Moss AL. Nasal deformities resulting from flow driver continuous positive airway pressure. Archives of Disease in Childhood. Fetal and Neonatal Edition 1996;75:F209-12.

Spence 2007

Spence KL, Murphy D, Kilian C, McGonigle R, Kilani RA. High-flow nasal cannula as a device to provide continuous positive airway pressure in infants. Journal of Perinatology 2007;27:772-5.

Walsh 2005

Walsh M, Engle W, Laptook A, Kazzi SN, Buchter S, Rasmussen M, et al. Oxygen delivery through nasal cannulae to preterm infants: can practice be improved? Pediatrics 2005;116:857-61.

Waugh 2004

Waugh JB, Granger WM. An evaluation of 2 new devices for nasal high-flow gas therapy. Respiratory Care 2004;49:902-6.

Wilkinson 2008

Wilkinson DJ, Andersen CC, Smith K, Holberton J. Pharyngeal pressure with high-flow nasal cannulae in premature infants. Journal of Perinatology 2008;28:42-7.

Other published versions of this review

  • None noted.

[top]

Data and analyses

1 HFNC versus CPAP soon after birth for treatment or prophylaxis of RDS

For graphical representations of the data/results in this table, please use link under "Outcome or Subgroup".

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
1.1 Treatment failure (intubation) 1 67 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.28, 3.78]
1.2 Death 1 67 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
1.3 Chronic lung disease 1 67 Risk Ratio (M-H, Fixed, 95% CI) 0.34 [0.01, 8.13]
1.4 Duration of respiratory support (hours) 1 67 Mean Difference (IV, Fixed, 95% CI) 14.00 [-8.70, 36.70]
1.5 Nasal trauma 1 67 Risk Ratio (M-H, Fixed, 95% CI) 0.15 [0.01, 2.74]
1.6 Proven sepsis 1 67 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.07, 15.80]
1.7 Length of hospitalisation 1 67 Mean Difference (IV, Fixed, 95% CI) -3.00 [-9.47, 3.47]
1.8 Air leak syndromes 1 67 Risk Ratio (M-H, Fixed, 95% CI) 0.21 [0.01, 4.13]

2 High flow nasal cannula versus CPAP to prevent extubation failure

For graphical representations of the data/results in this table, please use link under "Outcome or Subgroup".

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
2.1 Treatment failure (need for intubation) 1 40 Risk Ratio (M-H, Fixed, 95% CI) 4.00 [1.33, 12.05]
2.2 Nasal trauma 1 40 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
2.3 Death 1 80 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
2.4 CLD 1 80 Risk Ratio (M-H, Fixed, 95% CI) 1.40 [0.48, 4.04]
2.5 Necrotising Enterocolitis 1 80 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
2.6 Intraventricular haemorrhage 1 80 Risk Ratio (M-H, Fixed, 95% CI) 3.00 [0.33, 27.63]
2.7 Retinopathy of prematurity 1 80 Risk Ratio (M-H, Fixed, 95% CI) 0.67 [0.12, 3.78]
2.8 Days to full feeds 1 40 Mean Difference (IV, Fixed, 95% CI) -2.00 [-7.11, 3.11]

3 Alternative models for delivery of humidified HFNC to preterm infants after extubation following mechanical ventilation for RDS

For graphical representations of the data/results in this table, please use link under "Outcome or Subgroup".

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
3.1 Treatment failure (need for reintubation within 72 hours) 1 40 Risk Ratio (M-H, Fixed, 95% CI) 1.35 [0.31, 5.90]
3.2 Death 1 40 Risk Ratio (M-H, Fixed, 95% CI) 0.44 [0.02, 10.29]
3.3 CLD 1 39 Risk Ratio (M-H, Fixed, 95% CI) 0.86 [0.29, 2.58]
3.4 Necrotising Enterocolitis 1 40 Risk Ratio (M-H, Fixed, 95% CI) 4.00 [0.17, 92.57]
3.5 Need for reintubation within 1 week 1 40 Risk Ratio (M-H, Fixed, 95% CI) 0.97 [0.37, 2.53]

4 Humidified HFNC versus non-humidified HFNC to prevent extubation failure

For graphical representations of the data/results in this table, please use link under "Outcome or Subgroup".

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
4.1 Endotracheal intubation within 7 days post-extubation 1 28 Risk Ratio (M-H, Fixed, 95% CI) 0.17 [0.01, 3.34]

Figures

Figure 1 (Analysis 1.1)

Refer to caption

Forest plot of comparison: 1 HFNC versus CPAP soon after birth for treatment or prophylaxis of RDS, outcome: 1.1 Treatment failure (intubation) (Figure 1 description).

Figure 2 (Analysis 4.1)

Refer to caption

Forest plot of comparison: 2 Humidified HFNC versus non-humidified HFNC to prevent extubation failure, outcome: 4.1 Endotracheal intubation within 7 days post-extubation (Figure 2 description).

Figure 3 (Analysis 3.1)

Refer to caption

Forest plot of comparison: 3 Alternative models for delivery of humidified HFNC to preterm infants after extubation following mechanical ventilation for RDS, outcome: 3.1 Treatment failure (need for reintubation within 72 hours) (Figure 3 description).

Figure 4 (Analysis 2.1)

Refer to caption

Forest plot of comparison: 3 High Flow Nasal Cannula versus CPAP to prevent extubation failure, outcome: 2.1 Treatment failure (need for intubation) (Figure 4 description).

Sources of support

  • None noted.

Internal sources

  • No sources of support provided.

External sources

  • RACP - Astra Zeneca and Eric Burnard fellowship, Australia
  • DW - Travel support
  • Nuffield Dominions trust, UK
  • DW - salary support

This review is published as a Cochrane review in The Cochrane Library, Issue 5, 2011 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent version of the review.