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Physiological effects of high-flow nasal cannula therapy in preterm infants
  1. Zheyi Liew1,2,
  2. Alan C Fenton3,4,
  3. Sundeep Harigopal3,4,
  4. Saikiran Gopalakaje1,2,
  5. Malcolm Brodlie1,2,
  6. Christopher J O’Brien1
  1. 1 Paediatric Respiratory Medicine, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  2. 2 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  3. 3 Newcastle Neonatal Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  4. 4 Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Dr Malcolm Brodlie, Paediatric Respiratory Medicine, Great North Children’s Hospital, Newcastle upon Tyne NE1 4LP, UK; m.j.brodlie{at}


Objective High-flow nasal cannula (HFNC) therapy is increasingly used in preterm infants despite a paucity of physiological studies. We aimed to investigate the effects of HFNC on respiratory physiology.

Study design A prospective randomised crossover study was performed enrolling clinically stable preterm infants receiving either HFNC or nasal continuous positive airway pressure (nCPAP). Infants in three current weight groups were studied: <1000 g, 1000–1500 g and >1500 g. Infants were randomised to either first receive HFNC flows 8–2 L/min and then nCPAP 6 cm H2O or nCPAP first and then HFNC flows 8–2 L/min. Nasopharyngeal end-expiratory airway pressure (pEEP), tidal volume, dead space washout by nasopharyngeal end-expiratory CO2 (pEECO2), oxygen saturation and vital signs were measured.

Results A total of 44 preterm infants, birth weights 500–1900 g, were studied. Increasing flows from 2 to 8 L/min significantly increased pEEP (mean 2.3–6.1 cm H2O) and reduced pEECO2 (mean 2.3%–0.9%). Tidal volume and transcutaneous CO2 were unchanged. Significant differences were seen between pEEP generated in open and closed mouth states across all HFNC flows (difference 0.6–2.3 cm H2O). Infants weighing <1000 g received higher pEEP at the same HFNC flow than infants weighing >1000 g. Variability of pEEP generated at HFNC flows of 6–8 L/min was greater than nCPAP (2.4–13.5 vs 3.5–9.9 cm H2O).

Conclusions HFNC therapy produces clinically significant pEEP with large variability at higher flow rates. Highest pressures were observed in infants weighing <1000 g. Flow, weight and mouth position are all important determinants of pressures generated. Reductions in pEECO2 support HFNC’s role in dead space washout.

  • neonatology
  • respiratory
  • high flow nasal cannula oxygen
  • physiology

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  • MB and CJO’B contributed equally.

  • Contributors ZL and SG: enrolled infants, performed measurements, collected and analysed data. ACF, SH, MB and CJO’B: conceived the study, developed the protocol and study design and analysed the data. All authors had intellectual input to the manuscript and approved the final version as submitted and agree to be accountable for all aspects of the work.

  • Funding Funding from Newcastle upon Tyne Hospitals NHS Charity for equipment. MB was supported by a Medical Research Council Clinician Scientist Fellowship (MR/M008797/1). The research was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University.

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests ZL, ACF, SH, SG and CJO’B: none. MB: not related to this work: investigator-led research grants from Pfizer and Roche Diagnostics; speaker fees paid to Newcastle University from Novartis, Roche Diagnostics and TEVA. Travel expenses to educational meeting Boehringer Ingelheim and Vertex Pharmaceuticals.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data available on reasonable request to ORCiD 0000-0003-4591-8299 once study is fully published and analysed subject to approval by full study team.

  • Patient consent for publication Not required.

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