title: Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A Paediatric Acute Respiratory Intervention Study (PARIS).
abstract: BACKGROUND
  Bronchiolitis imposes the largest health care burden on non-elective paediatric hospital admissions worldwide, with up to 15 % of cases requiring admission to intensive care. A number of previous studies have failed to show benefit of pharmaceutical treatment in respect to length of stay, reduction in PICU admission rates or intubation frequency. The early use of non-invasive respiratory support devices in less intensive scenarios to facilitate earlier respiratory support may have an impact on outcome by avoiding progression of the disease process. High Flow Nasal Cannula (HFNC) therapy has emerged as a new method to provide humidified air flow to deliver a non-invasive form of positive pressure support with titratable oxygen fraction. There is a lack of high-grade evidence on use of HFNC therapy in bronchiolitis.
  
  
  METHODS
  Prospective multi-centre randomised trial comparing standard treatment (standard subnasal oxygen) and High Flow Nasal Cannula therapy in infants with bronchiolitis admitted to 17 hospitals emergency departments and wards in Australia and New Zealand, including 12 non-tertiary regional/metropolitan and 5 tertiary centres. The primary outcome is treatment failure; defined as meeting three out of four pre-specified failure criteria requiring escalation of treatment or higher level of care; i) heart rate remains unchanged or increased compared to admission/enrolment observations, ii) respiratory rate remains unchanged or increased compared to admission/enrolment observations, iii) oxygen requirement in HFNC therapy arm exceeds FiO2 ≥ 40 % to maintain SpO2 ≥ 92 % (or ≥94 %) or oxygen requirement in standard subnasal oxygen therapy arm exceeds >2L/min to maintain SpO2 ≥ 92 % (or ≥94 %), and iv) hospital internal Early Warning Tool calls for medical review and escalation of care. Secondary outcomes include transfer to tertiary institution, admission to intensive care, length of stay, length of oxygen treatment, need for non-invasive/invasive ventilation, intubation, adverse events, and cost.
  
  
  CONCLUSIONS
  This large multicenter randomised trial will allow the definitive assessment of the efficacy of HFNC therapy as compared to standard subnasal oxygen in the treatment of bronchiolitis.
  
  
  BACKGROUND
  The trial is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12613000388718 (registered on 10 April 2013).
authors.affiliation: Paediatric Critical Care Research Group, Lady Cilento Children's Hospital and The University of Queensland, Brisbane, Australia. d.franklin2@uq.edu.au.|The University of Queensland, School of Medicine, Brisbane, Australia. d.franklin2@uq.edu.au.|Mater Research Institution The University of Queensland, Brisbane, Australia. d.franklin2@uq.edu.au.|Paediatric Intensive Care Unit, Paediatric Critical Care Research Group (PCCRG), Lady Cilento Children's Hospital and The University of Queensland, 501 Stanley St, South, Brisbane, Queensland, 4101, Australia. d.franklin2@uq.edu.au.
authors.forename: Donna
authors.initials: D
authors.lastname: Franklin
authors.affiliation: Starship Children's Hospital, Auckland, New Zealand.|Liggins Institute, University of Auckland, Auckland, New Zealand.|KidzFirst Middlemore Hospital, Auckland, New Zealand.
authors.forename: Stuart
authors.initials: S
authors.lastname: Dalziel
authors.affiliation: Paediatric Critical Care Research Group, Lady Cilento Children's Hospital and The University of Queensland, Brisbane, Australia.|The University of Queensland, School of Medicine, Brisbane, Australia.|Mater Research Institution The University of Queensland, Brisbane, Australia.|Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Luregn J
authors.initials: LJ
authors.lastname: Schlapbach
authors.affiliation: Emergency Department, Royal Children's Hospital, Melbourne, Australia.|Murdoch Children's Research Institute Melbourne, Melbourne, Australia.|University of Melbourne, Melbourne, Australia.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Franz E
authors.initials: FE
authors.lastname: Babl
authors.affiliation: Emergency Department, Royal Children's Hospital, Melbourne, Australia.|Murdoch Children's Research Institute Melbourne, Melbourne, Australia.|University of Melbourne, Melbourne, Australia.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Ed
authors.initials: E
authors.lastname: Oakley
authors.affiliation: Murdoch Children's Research Institute Melbourne, Melbourne, Australia.|Emergency Department, Monash Children's Hospital, Melbourne, Australia.|Monash University, Melbourne, Australia.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Simon S
authors.initials: SS
authors.lastname: Craig
authors.affiliation: Emergency Department, The Townsville Hospital, Townsville, Australia.|James Cook University, Townsville, Australia.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Furyk
authors.affiliation: KidzFirst Middlemore Hospital, Auckland, New Zealand.|University of Auckland, Auckland, New Zealand.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Neutze
authors.affiliation: Emergency Department, The Canberra Hospital, Canberra, Australia.|Australian National University, Canberra, Australia.|Paediatric Research in Emergency Departments International Collaborative (PREDICT), Brisbane, Australia.
authors.forename: Kam
authors.initials: K
authors.lastname: Sinn
authors.affiliation: School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Whitty
authors.affiliation: Paediatric Critical Care Research Group, Lady Cilento Children's Hospital and The University of Queensland, Brisbane, Australia.|Mater Research Institution The University of Queensland, Brisbane, Australia.
authors.forename: Kristen
authors.initials: K
authors.lastname: Gibbons
authors.affiliation: The University of Queensland, School of Medicine, Brisbane, Australia.|Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Fraser
authors.affiliation: Paediatric Critical Care Research Group, Lady Cilento Children's Hospital and The University of Queensland, Brisbane, Australia.|The University of Queensland, School of Medicine, Brisbane, Australia.|Mater Research Institution The University of Queensland, Brisbane, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schibler
mesh_terms: D001988:Bronchiolitis / Q000628:therapy*; D006801:Humans; D007223:Infant; D044623:Nutrition Therapy; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D011446:Prospective Studies; D016896:Treatment Outcome