Intensive Care Medicine

, Volume 43, Issue 2, pp 209–216 | Cite as

High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (TRAMONTANE study)

  • Christophe Milési
  • Sandrine Essouri
  • Robin Pouyau
  • Jean-Michel Liet
  • Mickael Afanetti
  • Aurélie Portefaix
  • Julien Baleine
  • Sabine Durand
  • Clémentine Combes
  • Aymeric Douillard
  • Gilles CambonieEmail author
  • Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP)



Nasal continuous positive airway pressure (nCPAP) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (AVB). Although oxygen delivery via high flow nasal cannula (HFNC) is increasingly used, evidence of its efficacy and safety is lacking in infants.


A randomized controlled trial was performed in five pediatric intensive care units (PICUs) to compare 7 cmH2O nCPAP with 2 L/kg/min oxygen therapy administered with HFNC in infants up to 6 months old with moderate to severe AVB. The primary endpoint was the percentage of failure within 24 h of randomization using prespecified criteria. To satisfy noninferiority, the failure rate of HFNC had to lie within 15% of the failure rate of nCPAP. Secondary outcomes included success rate after crossover, intubation rate, length of stay, and serious adverse events.


From November 2014 to March 2015, 142 infants were included and equally distributed into groups. The risk difference of −19% (95% CI −35 to −3%) did not allow the conclusion of HFNC noninferiority (p = 0.707). Superiority analysis suggested a relative risk of success 1.63 (95% CI 1.02–2.63) higher with nCPAP. The success rate with the alternative respiratory support, intubation rate, durations of noninvasive and invasive ventilation, skin lesions, and length of PICU stay were comparable between groups. No patient had air leak syndrome or died.


In young infants with moderate to severe AVB, initial management with HFNC did not have a failure rate similar to that of nCPAP. This clinical trial was recorded in the National Library of Medicine registry (NCT 02457013).


Bronchiolitis Continuous positive airway pressure High flow nasal cannula Infant Noninvasive ventilation Oxygen inhalation therapy Randomized controlled trial Respiratory syncytial virus infections Respiratory therapy 



Members of the Respiratory GFRUP Study Group substantially contributed to study conception, data interpretation, manuscript revision, and final approval. It includes, in addition to the authors of the manuscript, the following members: Guillaume Emeriaud, MD, PhD (Division of Pediatric Critical Care, Department of Pediatrics, Sainte-Justine University Hospital, University of Montréal, Montréal, QC, Canada); Philippe Jouvet, MD, PhD (Division of Pediatric Critical Care, Department of Pediatrics, Sainte-Justine University Hospital, University of Montréal, QC, Canada); Julie Guichoux, MD (Pediatric Intensive Care Unit, Pellegrin University Hospital, Bordeaux, France); Fabrice Michel, MD, PhD (Department of Pediatric Anesthesia, La Timone University Hospital, Marseille, France); Marti Pons Odena, MD, PhD (Pediatric Intensive Care Unit, Hospital Universitario Sant Joan de Deu University Hospital, Barcelona, Spain); Florent Baudin, MD (Pediatric Intensive Care Unit, Women-Mothers & Children’s University Hospital, Lyon, France); Chloe Genier, GN (Pediatric Intensive Care Unit, Women & Children’s University Hospital, Nantes, France); Ingrid Nissen, MD (Pediatric Intensive Care Unit, St Olavs University Hospital, Trondheim, Norway); Olivier Brissaud, MD (Pediatric Intensive Care Unit, Pellegrin University Hospital, Bordeaux, France); Stéphane Dauger MD, PhD (Pediatric Intensive Care Unit, Robert-Debré University Hospital, Paris, France).

Compliance with ethical standards

Funding source

All phases of this study were supported by Montpellier University Hospital (Grant: research contract 2012–2015). This study has also been supported by Fisher and Paykel Healthcare with the provision of 30 HFNC circuits. Fisher and Paykel was not involved in the study design and had no role in data management, data analysis and data interpretation, nor in the writing of the report and the decision to submit it for publication.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

134_2016_4617_MOESM1_ESM.doc (224 kb)
Supplementary material 1 (DOC 224 kb)
134_2016_4617_MOESM2_ESM.docx (14 kb)
Supplementary material 2 (DOCX 15 kb)


  1. 1.
    Hall CB, Simőes EA, Anderson LJ (2013) Clinical and epidemiologic features of respiratory syncytial virus. Curr Top Microbiol Immunol 372:39–57PubMedGoogle Scholar
  2. 2.
    Pierce HC, Mansbach JM, Fisher ES et al (2015) Variability of intensive care management for children with bronchiolitis. Hosp Pediatr 5:175–184CrossRefPubMedGoogle Scholar
  3. 3.
    Hammer J, Numa A, Newth CJ (1997) Acute respiratory distress syndrome caused by respiratory syncytial virus. Pediatr Pulmonol 23:176–183CrossRefPubMedGoogle Scholar
  4. 4.
    Stokes GM, Milner AD, Groggins RC (1981) Work of breathing, intra-thoracic pressure and clinical findings in a group of babies with bronchiolitis. Acta Paediatr Scand 70:689–694CrossRefPubMedGoogle Scholar
  5. 5.
    Cambonie G, Milési C, Jaber S et al (2008) Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis. Intensive Care Med 34:1865–1872CrossRefPubMedGoogle Scholar
  6. 6.
    Essouri S, Durand P, Chevret L et al (2011) Optimal level of nasal continuous positive airway pressure in severe viral bronchiolitis. Intensive Care Med 37:2002–2007CrossRefPubMedGoogle Scholar
  7. 7.
    Pham TM, O’Malley L, Mayfield S, Martin S, Schibler A (2015) The effect of high flow nasal cannula therapy on the work of breathing in infants with bronchiolitis. Pediatr Pulmonol 50:713–720CrossRefPubMedGoogle Scholar
  8. 8.
    Milési C, Matecki S, Jaber S et al (2013) 6 cmH2O continuous positive airway pressure versus conventional oxygen therapy in severe viral bronchiolitis: a randomized trial. Pediatr Pulmonol 48:45–51CrossRefPubMedGoogle Scholar
  9. 9.
    Borckink I, Essouri S, Laurent M et al (2014) Infants with severe respiratory syncytial virus needed less ventilator time with nasal continuous airways pressure then invasive mechanical ventilation. Acta Paediatr 103:81–85CrossRefPubMedGoogle Scholar
  10. 10.
    Essouri S, Laurent M, Chevret L et al (2014) Improved clinical and economic outcomes in severe bronchiolitis with pre-emptive nCPAP ventilatory strategy. Intensive Care Med 40:84–91CrossRefPubMedGoogle Scholar
  11. 11.
    Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA (2013) Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med 39:247–257CrossRefPubMedGoogle Scholar
  12. 12.
    Schlapbach LJ, Schaefer J, Brady AM, Mayfield S, Schibler A (2014) High-flow nasal cannula (HFNC) support in interhospital transport of critically ill children. Intensive Care Med 40:592–599CrossRefPubMedGoogle Scholar
  13. 13.
    Milési C, Baleine J, Matecki S et al (2013) Is treatment with a high flow nasal cannula effective in acute viral bronchiolitis? A physiologic study. Intensive Care Med 39:1088–1094CrossRefPubMedGoogle Scholar
  14. 14.
    McKiernan C, Chua LC, Visintainer PF, Allen H (2010) High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr 156:634–638CrossRefPubMedGoogle Scholar
  15. 15.
    Schibler A, Pham TM, Dunster KR et al (2011) Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery. Intensive Care Med 37:847–852CrossRefPubMedGoogle Scholar
  16. 16.
    Abboud PA, Roth PJ, Skiles CL, Stolfi A, Rowin ME (2012) Predictors of failure in infants with viral bronchiolitis treated with high-flow, high-humidity nasal cannula therapy. Pediatr Crit Care Med 13:e343–e349CrossRefPubMedGoogle Scholar
  17. 17.
    Metge P, Grimaldi C, Hassid S et al (2014) Comparison of a high-flow humidified nasal cannula to nasal continuous positive airway pressure in children with acute bronchiolitis: experience in a pediatric intensive care unit. Eur J Pediatr 173:953–958CrossRefPubMedGoogle Scholar
  18. 18.
    Mayfield S, Bogossian F, O’Malley L, Schibler A (2014) High-flow nasal cannula oxygen therapy for infants with bronchiolitis: pilot study. J Paediatr Child Health 50:373–378CrossRefPubMedGoogle Scholar
  19. 19.
    Bueno Campaña M, Olivares Ortiz J, Notario Muñoz C et al (2014) High flow therapy versus hypertonic saline in bronchiolitis: randomised controlled trial. Arch Dis Child 99:511–515CrossRefPubMedGoogle Scholar
  20. 20.
    Hilliard TN, Archer N, Laura H et al (2012) Pilot study of vapotherm oxygen delivery in moderately severe bronchiolitis. Arch Dis Child 97:182–183CrossRefPubMedGoogle Scholar
  21. 21.
    Sinha IP, McBride AK, Smith R, Fernandes RM (2015) CPAP and high-flow nasal cannula oxygen in bronchiolitis. Chest 148:810–823CrossRefPubMedGoogle Scholar
  22. 22.
    Hough JL, Pham TM, Schibler A (2014) Physiologic effect of high-flow nasal cannula in infants with bronchiolitis. Pediatr Crit Care Med 15:e214–e219CrossRefPubMedGoogle Scholar
  23. 23.
    Milési C, Boubal M, Jacquot A et al (2014) High-flow nasal cannula: recommendations for daily practice in pediatrics. Ann Intensive Care 4:29CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hollman G, Shen G, Zeng L et al (1998) Helium-oxygen improves clinical asthma scores in children with acute bronchiolitis. Crit Care Med 26:1731–1736CrossRefPubMedGoogle Scholar
  25. 25.
    Debillon T, Zupan V, Ravault N, Magny JF, Dehan M (2001) Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed 85:F36–F41CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Khemani RG, Rubin S, Belani S et al (2015) Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. Intensive Care Med 41:94–102CrossRefPubMedGoogle Scholar
  27. 27.
    Ganu SS, Gautam A, Wilkins B, Egan J (2012) Increase in use of non-invasive ventilation for infants with severe bronchiolitis is associated with decline in intubation rates over a decade. Intensive Care Med 38:1177–1183CrossRefPubMedGoogle Scholar
  28. 28.
    Larrar S, Essouri S, Durand P et al (2006) Effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis. Arch Pediatr 13:1397–1403CrossRefPubMedGoogle Scholar
  29. 29.
    Bakalli I, Celaj E, Simaku A, Kola E, Sallabanda S (2015) Predictors of noninvasive ventilation success in children with acute respiratory failure. Intensive Care Med 41:950–951CrossRefPubMedGoogle Scholar
  30. 30.
    Cambonie G, Milési C, Fournier-Favre S et al (2006) Clinical effects of heliox administration for acute bronchiolitis in young infants. Chest 129:676–682CrossRefPubMedGoogle Scholar
  31. 31.
    Black J, Baharestani MM, Cuddigan J et al (2007) National Pressure Ulcer Advisory Panel’s updated pressure ulcer staging system. Adv Skin Wound Care 20:269–274CrossRefPubMedGoogle Scholar
  32. 32.
    Donlan M, Fontela PS, Puligandla PS (2011) Use of continuous positive airway pressure (CPAP) in acute viral bronchiolitis: a systematic review. Pediatr Pulmonol 46:736–746CrossRefPubMedGoogle Scholar
  33. 33.
    Liet JM, Ducruet T, Gupta V, Cambonie G (2015) Heliox inhalation therapy for bronchiolitis in infants. Cochrane Database Syst Rev 9:CD006915Google Scholar
  34. 34.
    Collett PW, Perry C, Engel LA (1985) Pressure-time product, flow, and oxygen cost of resistive breathing in humans. J Appl Physiol 58:1263–1272CrossRefPubMedGoogle Scholar
  35. 35.
    Beasley JM, Jones SE (1981) Continuous positive airway pressure in bronchiolitis. Br Med J (Clin Res Ed) 283:1506–1508CrossRefGoogle Scholar
  36. 36.
    Schiller O, Levy I, Pollak U, Kadmon G, Nahum E, Schonfeld T (2011) Central apnoeas in infants with bronchiolitis admitted to the paediatric intensive care unit. Acta Paediatr 100:216–219CrossRefPubMedGoogle Scholar
  37. 37.
    Ricart S, Rovira N, Garcia-Garcia JJ et al (2014) Frequency of apnea and respiratory viruses in infants with bronchiolitis. Pediatr Infect Dis J 33:988–990CrossRefPubMedGoogle Scholar
  38. 38.
    Alansari K, Toaimah FH, Khalafalla H, El Tatawy LA, Davidson BL, Ahmed W (2016) Caffeine for the treatment of apnea in bronchiolitis: a randomized trial. J Pediatr. doi: 10.1016/j.jpeds.2016.04.060 Google Scholar
  39. 39.
    Javouhey E, Barats A, Richard N et al (2008) Non-invasive ventilation as primary ventilatory support for infants with severe bronchiolitis. Intensive Care Med 34:1608–1614CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Christophe Milési
    • 1
  • Sandrine Essouri
    • 2
  • Robin Pouyau
    • 3
  • Jean-Michel Liet
    • 4
  • Mickael Afanetti
    • 5
  • Aurélie Portefaix
    • 3
    • 6
  • Julien Baleine
    • 1
  • Sabine Durand
    • 1
  • Clémentine Combes
    • 1
  • Aymeric Douillard
    • 7
  • Gilles Cambonie
    • 1
    Email author
  • Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP)
  1. 1.Pediatric Intensive Care Unit, Département de Pédiatrie Néonatale et RéanimationsCHU de Montpellier, Arnaud de Villeneuve University HospitalMontpellier Cedex 5France
  2. 2.Pediatric Intensive Care UnitKremlin Bicêtre University HospitalParisFrance
  3. 3.Pediatric Intensive Care UnitWomen-Mothers and Children’s University HospitalLyonFrance
  4. 4.Pediatric Intensive Care UnitWomen and Children’s University HospitalNantesFrance
  5. 5.Pediatric Intensive Care UnitLenval University HospitalNiceFrance
  6. 6.INSERM, CIC1407BronFrance
  7. 7.Department of Medical InformationArnaud de Villeneuve University HospitalMontpellierFrance

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