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Meta-Analysis
. 2016 Feb 22;2(2):CD006405.
doi: 10.1002/14651858.CD006405.pub3.

High flow nasal cannula for respiratory support in preterm infants

Dominic Wilkinson  1 , Chad Andersen, Colm P F O'Donnell, Antonio G De Paoli, Brett J Manley
Affiliations
Meta-Analysis

High flow nasal cannula for respiratory support in preterm infants

Dominic Wilkinson et al. Cochrane Database Syst Rev. .

Update in

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Brett Manley was the first author of one of the trials included in this review. Analysis of that paper was performed by other review authors.

Figures

1
1
Forest plot of comparison: 1 HFNC versus CPAP soon after birth for treatment or prophylaxis of RDS, outcome: 1.4 Treatment failure within 7 days of trial entry.
2
2
Forest plot of comparison: 3 HFNC versus CPAP to prevent extubation failure, outcome: 3.3 Death.
3
3
Forest plot of comparison: 3 HFNC versus CPAP to prevent extubation failure, outcome: 3.2 CLD.
4
4
Forest plot of comparison: 3 High Flow Nasal Cannula versus CPAP to prevent extubation failure, outcome: Treatment failure.
5
5
Forest plot of comparison: 3 HFNC versus CPAP to prevent extubation failure within 7 days, outcome: 3.5 Reintubation within 7 days of trial entry.
6
6
Forest plot of comparison: 3 HFNC versus CPAP to prevent extubation failure, outcome: Nasal trauma.
7
7
Forest plot of comparison: 3 HFNC versus CPAP to prevent extubation failure, outcome: Pneumothorax.
1.1
1.1. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 1 Death or CLD.
1.2
1.2. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 2 CLD.
1.3
1.3. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 3 Death.
1.4
1.4. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 4 Treatment failure within 7 days of trial entry.
1.5
1.5. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 5 Intubation within 7 days of trial entry.
1.6
1.6. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 6 Intubation at any time point after trial entry.
1.7
1.7. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 7 Duration of any respiratory support (days).
1.8
1.8. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 8 Duration of supplemental oxygen (days).
1.9
1.9. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 9 Duration of hospitalisation (days).
1.10
1.10. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 10 Pneumothorax.
1.11
1.11. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 11 Nosocomial sepsis.
1.12
1.12. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 12 Gastrointestinal perforation or severe NEC.
1.13
1.13. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 13 Days to full feeds.
1.14
1.14. Analysis
Comparison 1 HFNC versus CPAP for primary respiratory support after birth, Outcome 14 Nasal trauma.
2.1
2.1. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 1 Death or CLD.
2.2
2.2. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 2 CLD.
2.3
2.3. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 3 Death.
2.4
2.4. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 4 Treatment failure within 7 days of trial entry.
2.5
2.5. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 5 Intubation at any time point after trial entry.
2.6
2.6. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 6 Duration of mechanical ventilation via an endotracheal tube (days).
2.8
2.8. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 8 Duration of hospitalisation (days).
2.9
2.9. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 9 Pneumothorax.
2.10
2.10. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 10 Nosocomial Sepsis.
2.11
2.11. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 11 Gastrointestinal perforation or severe NEC.
2.12
2.12. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 12 Days to full feeds.
2.13
2.13. Analysis
Comparison 2 HFNC versus NIPPV for primary respiratory support after birth, Outcome 13 Nasal trauma.
3.1
3.1. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 1 Death or CLD.
3.2
3.2. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 2 CLD.
3.3
3.3. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 3 Death.
3.4
3.4. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 4 Treatment failure within 7 days of trial entry.
3.5
3.5. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 5 Reintubation within 7 days of trial entry.
3.6
3.6. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 6 Reintubation at any time point after trial entry.
3.7
3.7. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 7 Duration of mechanical ventilation via an endotracheal tube (days).
3.8
3.8. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 8 Duration of any respiratory support (days after randomisation).
3.9
3.9. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 9 Duration of any respiratory support (postmenstrual age at end).
3.10
3.10. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 10 Duration of supplemental oxygen (days after randomisation).
3.11
3.11. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 11 Duration of supplemental oxygen (postmenstrual age at end).
3.12
3.12. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 12 Duration of hospitalisation (days).
3.13
3.13. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 13 Pneumothorax.
3.14
3.14. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 14 Nosocomial Sepsis.
3.15
3.15. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 15 ROP (any stage).
3.16
3.16. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 16 Gastrointestinal perforation or severe NEC.
3.17
3.17. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 17 Days to full feeds.
3.18
3.18. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 18 Weight gain prior to discharge from hospital (grams).
3.19
3.19. Analysis
Comparison 3 HFNC versus CPAP to prevent extubation failure, Outcome 19 Nasal trauma.
4.1
4.1. Analysis
Comparison 4 Humidified HFNC versus non‐humidified HFNC to prevent extubation failure, Outcome 1 Reintubation within 7 days of trial entry.
5.1
5.1. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 1 Death or CLD.
5.2
5.2. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 2 CLD.
5.3
5.3. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 3 Death.
5.4
5.4. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 4 Treatment failure within 7 days of trial entry.
5.5
5.5. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 5 Reintubation within 7 days of trial entry.
5.6
5.6. Analysis
Comparison 5 Alternative HFNC models to prevent extubation failure, Outcome 6 Necrotising Enterocolitis.
6.1
6.1. Analysis
Comparison 6 Alternative HFNC humidification devices, Outcome 1 Death or CLD.
6.2
6.2. Analysis
Comparison 6 Alternative HFNC humidification devices, Outcome 2 CLD.
6.3
6.3. Analysis
Comparison 6 Alternative HFNC humidification devices, Outcome 3 Treatment failure.
6.4
6.4. Analysis
Comparison 6 Alternative HFNC humidification devices, Outcome 4 Intubation at any time point after trial entry.
6.5
6.5. Analysis
Comparison 6 Alternative HFNC humidification devices, Outcome 5 Nasal trauma.
7.1
7.1. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 1 Death or CLD.
7.2
7.2. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 2 CLD.
7.3
7.3. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 3 Death.
7.4
7.4. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 4 Treatment failure.
7.5
7.5. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 5 Intubation at any time point after trial entry.
7.8
7.8. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 8 Duration of hospitalisation (days).
7.9
7.9. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 9 Pneumothorax.
7.10
7.10. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 10 Necrotising enterocolitis.
7.11
7.11. Analysis
Comparison 7 HFNC for weaning from CPAP, Outcome 11 Nosocomial sepsis.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Abdel Hady 2011 {published and unpublished data}
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Kugelman 2015 {published and unpublished data}
    1. Kugelman A, Riskin A, Said W, Shoris I, Mor F, Bader D. A randomized pilot study comparing heated humidified high‐flow nasal cannulae with NIPPV for RDS. Pediatric Pulmonology 2015;50(6):576‐83. [PUBMED: 24619945] - PubMed
Liu 2014 {published and unpublished data}
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Miller 2010 {published data only}
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Mostafa‐Gharehbaghi 2014 {published and unpublished data}
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Nair 2005 {unpublished data only}
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Sadeghnia 2014 {published data only}
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Woodhead 2006 {published data only}
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Yoder 2013 {published and unpublished data}
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References to studies excluded from this review

Beltramo 2008 {published data only}
    1. 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. Pediatric Academic Society Meeting; 2008 May 3‐6; Honolulu (Hawaii); http://www.abstracts2view.com/pas/ (accessed May 2015):E‐PAS2008:63376.
Boumecid 2007 {published data only}
    1. 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. [PUBMED: 17088340] - PMC - PubMed
Capasso 2005 {published data only}
    1. 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. [PUBMED: 15981754] - PubMed
Choi 2011 {published data only}
    1. Choi BM, Lee EH, Park KH, Chung BH, Park HJ, Choi YO, et al. Comparing Usefulness of Humidified High‐Flow Nasal Cannula (HHFNC) and Nasal Continuous Positive Airway Pressure (NCPAP) for Neonatal Respiratory Diseases in Preterm Infants (Poster). Pediatric Research 2011;70:504.
Courtney 2001 {published data only}
    1. 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. [PUBMED: 11158463] - PubMed
de Jongh 2014 {published data only}
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Fernandez‐Alvarez 2013 {published data only}
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Holleman‐Duray 2007 {published data only}
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Klingenberg 2014 {published data only}
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Lavizzari 2014 {published data only}
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Mazmanyan 2013 {published data only}
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Nasef 2015 {published data only}
    1. Nasef N, El‐Gouhary E, Schurr P, Reilly M, Beck J, Dunn M, et al. High‐flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants. Acta Paediatrica 2015;104(8):e337‐43. [PUBMED: 25759095] - PubMed
Phadtare 2009 {published data only}
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Pyon 2008 {published data only}
    1. 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. Proceedings of the Pediatric Academic Societies Annual Meeting; 2008 May 3‐6; Honolulu (HI). 2008:E‐PAS2008:633763.13.
Saslow 2006 {published data only}
    1. 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(8):476‐80. [PUBMED: 16688202] - PubMed
Shoemaker 2007 {published data only}
    1. 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. [PUBMED: 17262040] - PubMed
Sreenan 2001 {published data only}
    1. 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(5):1081‐3. [PUBMED: 11331690] - PubMed
Wilson 1996 {published data only}
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References to studies awaiting assessment

Chen 2015 {published data only}
    1. Chen J, Gao WW, Xu F, Du LL, Zhang T, Ling X, Li WT. Comparison of clinical efficacy of heated humidified high flow nasal cannula versus nasal continuous positive airway pressure in treatment of respiratory distress syndrome in very low birth weight infants. Zhongguo Dang Dai Er Ke Za Zhi 2015;17(8):847‐51. [PUBMED: 26287351] - PubMed
Febre 2015 {published data only}
    1. Febre A, Merritt TA, Terry M, Tong C, Goldstein M. Adaptive Dynamic Inspiratory Nasal Apparatus: Comparison to Traditional Nasal Continuous Airway Pressure (NCPAP). Newborn and Infant Nursing Reviews 2015;15(1):17‐20.
Lawrence 2012 {published data only}
    1. Lawrence JR, Martin GC. A Pilot Study To Evaluate the Safety and Efficacy of High Flow Nasal Cannula vs. Conventional NCPAP. Pediatric Academic Society. 2012; Vol. http://www.abstracts2view.com/pas/.
Tang 2015 {published data only}
    1. Lutz TL, Tang J, Osborn DA, Malcolm GA, Reid S, Oliver S. High flow nasal cannula for weaning preterm infants from continuous positive airway pressure. Pediatric Academic Society Meeting; 2013 May 4‐7; Washington, DC; http://www.abstracts2view.com/pas/ (accessed May 2015):E‐PAS2013:3800.38.
    1. Tang J, Reid S, Lutz T, Malcolm G, Oliver S, Osborn DA. Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. BMC Pediatrics 2015;15:147. [PUBMED: 26446072] - PMC - PubMed

References to ongoing studies

ACTRN12610000677000 {published data only}
    1. ACTRN12610000677000. High flow support versus continuous positive airway pressure (cpap) support in non‐acute respiratory support for preterm infants from 30 weeks corrected gestation. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12610000677000.
ACTRN12613000303741 {published data only}
    1. ACTRN12613000303741. A multi‐centre, randomised, controlled, non‐inferiority trial comparing high flow nasal cannulae to nasal continuous positive airway pressure as primary respiratory support, in preterm infants of 28 weeks' gestation and above, with early respiratory distress or apnoea, assessing assigned treatment failure within 72 hours. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12613000303741.
ACTRN12615000077561 {published data only}
    1. ACTRN12615000077561. Weaning preterm infants with a gestational age (GA) of < 30 weeks from respiratory support: a comparison of duration of respiratory support with heated humidified high flow nasal cannula (HHHFNC) and continuous positive airway pressure (CPAP). http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12615000077561.
IRCT2014012716376N1 {published data only}
    1. IRCT2014012716376N1. Comparing two methods of cannula nasal with high flow and conventional FiO2 for successful weaning of preterm infants with respiratory distress from Nasal CPAP in Alzahra and Shahidbeheshti hospitals, Isfahan. http://www.irct.ir/index.php.
ISRCTN66716753 {published data only}
    1. ISRCTN66716753. High Flow Nasal Prongs (HFNP) therapy versus Nasal Continuous Positive Airway Pressure (NCPAP) in establishing full oral feeds in Very Low Birth Weight (VLBW) infants ‐ randomized controlled trial. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN66716753.
JPRN‐UMIN000013906 {published data only}
    1. JPRN‐UMIN000013906. A randomized controlled trial to compare high‐flow nasal cannula with nasal cpap after extubation in preterm infants. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=JPRN‐UMIN000013906.
NCT01270581 {unpublished data only}
    1. High Flow Nasal Cannula vs Bubble Nasal CPAP for the Treatment of Transient Tachypnea of the Newborn in Infants > 35 Weeks Gestation. Ongoing study July 2010.
NCT01939067 {published data only}
    1. NCT01939067. Pulmonary mechanics in preterm infants treated with heated humidified high flow nasal cannula as compared to nasal continuous positive airway Pressure. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT01939067.
NCT02055339 {published data only}
    1. NCT02055339. Comparison of nasal continuous positive airway pressure with low flow oxygen versus heated, humidified high flow nasal cannula for oral feeding of the premature infant (chomp trial): a pilot study. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02055339.

Additional references

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References to other published versions of this review

Wilkinson 2011
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