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)
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.
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.
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.
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).
KeywordsBronchiolitis High-flow nasal cannula Infant Noninvasive ventilation Oxygen inhalation therapy Randomized controlled trial Respiratory syncytial virus Respiratory therapy
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).
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.
All phases of this study were supported by the University Hospital Center of Montpellier (Grant: research contract 2012–2015).
Compliance with ethical standards
Conflicts of interest
The authors have no financial relationships and no potential conflicts of interest relevant to this article to disclose.
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