title: Saline in acute bronchiolitis RCT and economic evaluation: hypertonic saline in acute bronchiolitis - randomised controlled trial and systematic review.
abstract: BACKGROUND
  Acute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation.
  
  
  OBJECTIVE
  To test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%.
  
  
  METHODS
  Parallel-group, pragmatic randomised controlled trial, cost-utility analysis and systematic review.
  
  
  METHODS
  Ten UK hospitals.
  
  
  METHODS
  Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission.
  
  
  METHODS
  Supportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours.
  
  
  METHODS
  The trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial.
  
  
  METHODS
  We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searched Chest, Paediatrics and Journal of Paediatrics to January 2015.
  
  
  METHODS
  We included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using the I (2) statistic.
  
  
  RESULTS
  The trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was no difference in adverse events. One infant developed bradycardia with desaturation associated with HS. Mean hospital costs were £2595 and £2727 for the control and intervention groups, respectively (p = 0.657). Incremental QALYs were 0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of £7.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by -0.36 days (95% CI -0.50 to -0.22 days). High levels of heterogeneity (I (2) = 78%) indicate that the result should be treated cautiously.
  
  
  CONCLUSIONS
  In this trial, HS had no clinical benefit on LoS or readiness for discharge and was not a cost-effective treatment for acute bronchiolitis. Claims that HS achieves small reductions in LoS must be treated with scepticism.
  
  
  CONCLUSIONS
  Well-powered randomised controlled trials of high-flow oxygen are needed.
  
  
  BACKGROUND
  This study is registered as NCT01469845 and CRD42014007569.
  This project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 19, No. 66. See the HTA programme website for further project information.
authors: School of Paediatrics and Child Health (SPACH), University of Western Australia, Perth, WA, Australia.
authors: Mark L
authors: ML
authors: Everard
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Daniel
authors: D
authors: Hind
authors: Department of Respiratory Medicine, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors: Kelechi
authors: K
authors: Ugonna
authors: Division of Epidemiology & Biostatistics, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
authors: Jennifer
authors: J
authors: Freeman
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Mike
authors: M
authors: Bradburn
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Simon
authors: S
authors: Dixon
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Chin
authors: C
authors: Maguire
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Hannah
authors: H
authors: Cantrill
authors: Children's Centre, Hospital of North Staffordshire NHS Trust, Stoke-on-Trent, UK.
authors: John
authors: J
authors: Alexander
authors: Institute for Science & Technology in Medicine, Keele University, Stoke-on-Trent, UK.
authors: Warren
authors: W
authors: Lenney
authors: Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
authors: Paul
authors: P
authors: McNamara
authors: Department of Respiratory Medicine, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors: Heather
authors: H
authors: Elphick
authors: Children's Respiratory Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Philip Aj
authors: PA
authors: Chetcuti
authors: Department of Paediatrics, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
authors: Eduardo F
authors: EF
authors: Moya
authors: Department of Child Health, University Hospital of Wales, Cardiff, UK.
authors: Colin
authors: C
authors: Powell
authors: Children's Outpatients, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, UK.
authors: Jonathan P
authors: JP
authors: Garside
authors: Paediatrics, Doncaster and Bassetlaw Hospitals NHS Foundation Trust, Doncaster, UK.
authors: Lavleen Kumar
authors: LK
authors: Chadha
authors: Paediatrics, Doncaster and Bassetlaw Hospitals NHS Foundation Trust, Doncaster, UK.
authors: Matthew
authors: M
authors: Kurian
authors: Paediatric Endocrinology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors: Ravinderjit S
authors: RS
authors: Lehal
authors: Child Health, Rotherham NHS Foundation Trust, Rotherham, UK.
authors: Peter I
authors: PI
authors: MacFarlane
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Cindy L
authors: CL
authors: Cooper
authors: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
authors: Elizabeth
authors: E
authors: Cross
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D000208:Acute Disease; D000280:Administration, Inhalation; D000420:Albuterol / Q000627:therapeutic use; D001988:Bronchiolitis / Q000188:drug therapy / Q000628:therapy; D001993:Bronchodilator Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D007902:Length of Stay; D009330:Nebulizers and Vaporizers; D010102:Oxygen Inhalation Therapy / Q000379:methods; D010359:Patient Readmission; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D012720:Severity of Illness Index; D006113:United Kingdom
chemical_list: D000420:Albuterol; D001993:Bronchodilator Agents; D012462:Saline Solution, Hypertonic