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A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2)

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Abstract

Purpose

High-flow nasal cannula (HFNC) therapy is increasingly proposed as first-line respiratory support for infants with acute viral bronchiolitis (AVB). Most teams use 2 L/kg/min, but no study compared different flow rates in this setting. We hypothesized that 3 L/kg/min would be more efficient for the initial management of these patients.

Methods

A randomized controlled trial was performed in 16 pediatric intensive care units (PICUs) to compare these two flow rates in infants up to 6 months old with moderate to severe AVB and treated with HFNC. The primary endpoint was the percentage of failure within 48 h of randomization, using prespecified criteria of worsening respiratory distress and discomfort.

Results

From November 2016 to March 2017, 142 infants were allocated to the 2-L/kg/min (2L) flow rate and 144 to the 3-L/kg/min (3L) flow rate. Failure rate was comparable between groups: 38.7% (2L) vs. 38.9% (3L; p = 0.98). Worsening respiratory distress was the most common cause of failure in both groups: 49% (2L) vs. 39% (3L; p = 0.45). In the 3L group, discomfort was more frequent (43% vs. 16%, p = 0.002) and PICU stays were longer (6.4 vs. 5.3 days, p = 0.048). The intubation rates [2.8% (2L) vs. 6.9% (3L), p = 0.17] and durations of invasive [0.2 (2L) vs. 0.5 (3L) days, p = 0.10] and noninvasive [1.4 (2L) vs. 1.6 (3L) days, p = 0.97] ventilation were comparable. No patient had air leak syndrome or died.

Conclusion

In young infants with AVB supported with HFNC, 3 L/kg/min did not reduce the risk of failure compared with 2 L/kg/min. This clinical trial was recorded on the National Library of Medicine registry (NCT02824744).

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References

  1. Meissner HC (2016) Viral bronchiolitis in children. N Engl J Med 374:62–72

    Article  CAS  Google Scholar 

  2. Franklin D, Babl FE, Schlapbach LJ et al (2018) A randomized trial of high-flow oxygen therapy in infants with bronchiolitis. N Engl J Med 378:1121–1131

    Article  CAS  Google Scholar 

  3. Thia LP, McKenzie SA, Blyth TP, Minasian CC, Kozlowska WJ, Carr SB (2008) Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis. Arch Dis Child 93:45–47

    Article  Google Scholar 

  4. 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 34:1865–1872

    Article  Google Scholar 

  5. Essouri S, Durand P, Chevret L et al (2011) Optimal level of nasal continuous positive airway pressure in severe viral bronchiolitis. Intensive Care Med 37:2002–2007

    Article  Google Scholar 

  6. 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 48:45–51

    Article  Google Scholar 

  7. 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 39:1088–1094

    Article  Google Scholar 

  8. Hough JL, Pham TM, Schibler A (2014) Physiologic effect of high-flow nasal cannula in infants with bronchiolitis. Pediatr Crit Care Med 15:e214–e219

    Article  Google Scholar 

  9. 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 50:713–720

    Article  Google Scholar 

  10. Sinha IP, McBride AKS, Smith R, Fernandes RM (2015) CPAP and high-flow nasal cannula oxygen in bronchiolitis. Chest 148:810–823

    Article  Google Scholar 

  11. Milési C, Essouri S, Pouyau R et al (2017) 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). Intensive Care Med 43:209–216

    Article  Google Scholar 

  12. Milési C, Boubal M, Jacquot A et al (2014) High-flow nasal cannula: recommendations for daily practice in pediatrics. Ann Intensive Care 4:29

    Article  Google Scholar 

  13. 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 40:84–91

    Article  Google Scholar 

  14. Ralston SL, Lieberthal AS, Meissner HC et al (2014) Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 134:e1474–e1502

    Article  Google Scholar 

  15. Hollman G, Shen G, Zeng L et al (1998) Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis. Crit Care Med 26:1731–1736

    Article  CAS  Google Scholar 

  16. 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–F41

    Article  CAS  Google Scholar 

  17. Black J, Baharestani MM, Cuddigan J et al (2007) National Pressure Ulcer Advisory Panel’s updated pressure ulcer staging system. Adv Skin Wound Care 20:269–274

    Article  Google Scholar 

  18. O’Driscoll BR, Howard LS, Davison AG, British Thoracic Society (2008) BTS guideline for emergency oxygen use in adult patients. Thorax 63(Suppl 6):vi1–vi68. https://doi.org/10.1136/thx.2008.102947

    Article  PubMed  Google Scholar 

  19. te Pas AB, Wong C, Kamlin CO, Dawson JA, Morley CJ, Davis PG (2009) Breathing patterns in preterm and term infants immediately after birth. Pediatr Res 65:352–356

    Article  Google Scholar 

  20. Schmalisch G, Wilitzki S, Wauer RR (2005) Differences in tidal breathing between infants with chronic lung diseases and healthy controls. BMC Pediatr 5:36

    Article  CAS  Google Scholar 

  21. Ramnarayan P, Schibler A (2017) Glass half empty or half full? The story of high-flow nasal cannula therapy in critically ill children. Intensive Care Med 43:246–249

    Article  Google Scholar 

  22. 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–e349

    Article  Google Scholar 

  23. ten Brink F, Duke T, Evans J (2013) High-flow nasal prong oxygen therapy or nasopharyngeal continuous positive airway pressure for children with moderate-to-severe respiratory distress? Pediatr Crit Care Med 14:e326–e331

    Article  Google Scholar 

  24. Bressan S, Balzani M, Krauss B, Pettenazzo A, Zanconato S, Baraldi E (2013) High-flow nasal cannula oxygen for bronchiolitis in a pediatric ward: a pilot study. Eur J Pediatr 172:1649–1656

    Article  CAS  Google Scholar 

  25. 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 50:373–378

    Article  Google Scholar 

  26. Kepreotes E, Whitehead B, Attia J et al (2017) High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): an open, phase 4, randomised controlled trial. Lancet 389:930–939

    Article  Google Scholar 

  27. Collins CL, Holberton JR, Barfield C, Davis PG (2013) A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr 162(949–954):e1

    Google Scholar 

  28. Manley BJ, Owen LS, Doyle LW et al (2013) High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med 369:1425–1433

    Article  CAS  Google Scholar 

  29. Mauri T, Alban L, Turrini C et al (2017) Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med 43:1453–1463

    Article  CAS  Google Scholar 

  30. Hammer J, Numa A, Newth CJ (1997) Acute respiratory distress syndrome caused by respiratory syncytial virus. Pediatr Pulmonol 23:176–183

    Article  CAS  Google Scholar 

  31. 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 39:247–257

    Article  Google Scholar 

  32. Frizzola M, Miller TL, Rodriguez ME et al (2011) High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol 46:67–74

    Article  Google Scholar 

  33. Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S (2013) Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics 131:e1482–e1490

    Article  Google Scholar 

  34. Kugelman A, Riskin A, Said W, Shoris I, Mor F, Bader D (2015) A randomized pilot study comparing heated humidified high-flow nasal cannulae with NIPPV for RDS. Pediatr Pulmonol 50:576–583

    Article  Google Scholar 

  35. Betters KA, Hebbar KB, McCracken C, Heitz D, Sparacino S, Petrillo T (2017) A novel weaning protocol for high-flow nasal cannula in the PICU. Pediatr Crit Care Med 18:e274–e280

    Article  Google Scholar 

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Acknowledgements

Members of the GFRUP Respiratory Study Group contributed substantially to the study design, data interpretation, manuscript revision, and final approval. The Group 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); 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); and Ingrid Nissen, MD (Pediatric Intensive Care Unit, St. Olav's University Hospital, Trondheim, Norway).

Funding

All phases of this study were supported by the University Hospital Center of Montpellier (Grant: research contract 2012–2015).

Author information

Authors and Affiliations

  1. Department of Neonatal Medicine and Pediatric Intensive Care, Arnaud de Villeneuve University Hospital, 371 Avenue Doyen G Giraud, 34295, Montpellier Cedex 5, France

    Christophe Milési, Julien Baleine, Sabine Durand & Gilles Cambonie

  2. Pediatric Intensive Care Unit, Kremlin Bicêtre University Hospital, Paris, France

    Anne-Florence Pierre & Philippe Durand

  3. Pediatric Intensive Care Unit, Robert Debré University Hospital, Paris, France

    Anna Deho & Stéphane Dauger

  4. Pediatric Intensive Care Unit, Women-Mother-Child University Hospital, Lyon, France

    Robin Pouyau & Etienne Javouhey

  5. Pediatric Intensive Care Unit, Women-Child University Hospital, Nantes, France

    Jean-Michel Liet

  6. Pediatric Intensive Care Unit, Jeanne de Flandre University Hospital, Lille, France

    Camille Guillot & Stéphane Leteurtre

  7. Pediatric Intensive Care Unit, Hautepierre University Hospital, Strasbourg, France

    Anne-Sophie Guilbert

  8. Pediatric Intensive Care Unit, Armand Trousseau University Hospital, Paris, France

    Jérôme Rambaud

  9. Pediatric Intensive Care Unit, La Tronche University Hospital, Grenoble, France

    Astrid Millet

  10. Pediatric Intensive Care Unit, Lenval University Hospital, Nice, France

    Mickael Afanetti

  11. Pediatric Intensive Care Unit, Children’s University Hospital, Bordeaux, France

    Julie Guichoux & Olivier Brissaud

  12. Pediatric Intensive Care Unit, Necker-Sick Children University Hospital, Paris, France

    Mathieu Genuini & Sylvain Renolleau

  13. Pediatric Intensive Care Unit, General Hospital of Pau, Pau, France

    Thierry Mansir

  14. Pediatric Intensive Care Unit, Raymond Poincaré University Hospital, Garches, France

    Jean Bergounioux

  15. Pediatric Intensive Care Unit, La Timone University Hospital, Marseille, France

    Fabrice Michel

  16. Pediatric Intensive Care Unit, Children’s University Hospital, Toulouse, France

    Marie-Odile Marcoux

  17. INSERM, CIC1407, 69500, Bron, France

    Aurélie Portefaix

  18. Department of Medical Information, Arnaud de Villeneuve University Hospital, Montpellier, France

    Aymeric Douillard

Authors
  1. Christophe Milési
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  2. Anne-Florence Pierre
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  3. Anna Deho
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  15. Fabrice Michel
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  26. Aymeric Douillard
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  27. Gilles Cambonie
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Consortia

for the GFRUP Respiratory Study Group

Contributions

CM, JB, SD, and GC conceptualized and designed the study, coordinated and supervised the data collection at their respective investigation sites, drafted the initial manuscript, and approved the final manuscript as submitted. AD carried out the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. AFP, AD, RP, JML, CG, ASG, JR, AM, MA, JG, MG, TM, JB, FM, MOM, PD, SD, EJ, AP, SL, OB, and SR coordinated and supervised the data collection at their respective investigation sites, critically reviewed the manuscript, and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Gilles Cambonie.

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Conflicts of interest

The authors have no financial relationships and no potential conflicts of interest relevant to this article to disclose.

Additional information

The members of the GFRUP Respiratory Study Group are listed in the Acknowledgements.

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Milési, C., Pierre, AF., Deho, A. et al. A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2). Intensive Care Med 44, 1870–1878 (2018). https://doi.org/10.1007/s00134-018-5343-1

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