{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:22:30Z","timestamp":1792074150370,"version":"4.4.0"},"reference-count":153,"publisher":"National Institute for Health and Care Research","issue":"66","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["09\/91\/22"],"award-info":[{"award-number":["09\/91\/22"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>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 &gt;\u200992% for 6 hours, by 25%.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>Parallel-group, pragmatic randomised controlled trial, cost\u2013utility analysis and systematic review.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>Ten UK hospitals.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Supportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every \u00b1\u20096 hours.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Data sources<\/jats:title><jats:p>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<jats:italic>Chest<\/jats:italic>,<jats:italic>Paediatrics<\/jats:italic>and<jats:italic>Journal of Paediatrics<\/jats:italic>to January 2015.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Review methods<\/jats:title><jats:p>We included randomised\/quasi-randomised trials which compared HS versus saline (\u00b1\u2009adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using the<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>statistic.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Results<\/jats:title><jats:p>The trial randomised 158 infants to HS (<jats:italic>n<\/jats:italic>\u2009=\u2009141 analysed) and 159 to standard care (<jats:italic>n<\/jats:italic>\u2009=\u2009149 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 \u00a32595 and \u00a32727 for the control and intervention groups, respectively (<jats:italic>p<\/jats:italic>\u2009=\u20090.657). Incremental QALYs were 0.0000175 (<jats:italic>p<\/jats:italic>\u2009=\u20090.757). An incremental cost-effectiveness ratio of \u00a37.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (<jats:italic>n<\/jats:italic>\u2009=\u20091922) including our own. HS reduced the mean LoS by \u20130.36 days (95% CI \u20130.50 to \u20130.22 days). High levels of heterogeneity (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200978%) indicate that the result should be treated cautiously.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-12\"><jats:title>Future work<\/jats:title><jats:p>Well-powered randomised controlled trials of high-flow oxygen are needed.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-13\"><jats:title>Study registration<\/jats:title><jats:p>This study is registered as NCT01469845 and CRD42014007569.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-14\"><jats:title>Funding details<\/jats:title><jats:p>This project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 19, No. 66. See the HTA programme website for further project information.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta19660","type":"journal-article","created":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T08:21:15Z","timestamp":1440490875000},"page":"1-130","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Saline in Acute Bronchiolitis RCT and Economic evaluation: hypertonic saline in acute bronchiolitis \u2013 randomised controlled trial and systematic review"],"prefix":"10.3310","volume":"19","clinical-trial-number":[{"clinical-trial-number":"nct01469845","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"given":"Mark L","family":"Everard","sequence":"first","affiliation":[{"name":"School of Paediatrics and Child Health (SPACH), University of Western Australia, Perth, WA, 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