Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review

Mark Everard, D. Hind, K. Ugonna, J. Freeman, M. Bradburn, S. Dixon, C. Maguire, H. Cantrill, J. Alexander, W. Lenney, P. Mcnamara, H. Elphick, P.A.J. Chetcuti, E.F. Moya, C. Powell, J.P. Garside, L.K. Chadha, M. Kurian, R.S. Lehal, P.I. Macfarlane & 2 others C.L. Cooper, E. Cross

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    Abstract

    © Queen's Printer and Controller of HMSO 2015. 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%. Design: Parallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review. Setting: Ten UK hospitals. Participants: Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. Interventions: 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. Main outcome measures: 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. Data sources: 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. Review 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 I2 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 (I2 = 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.
    Original languageEnglish
    Pages (from-to)1-130
    JournalHealth Technology Assessment
    Volume19
    Issue number66
    DOIs
    Publication statusPublished - 2015

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    Bronchiolitis
    Cost-Benefit Analysis
    Length of Stay
    Randomized Controlled Trials
    Quality-Adjusted Life Years
    Hospitalization
    Confidence Intervals
    Oxygen
    Pediatrics
    Hospital Costs
    Information Storage and Retrieval
    Bradycardia
    MEDLINE
    Health Care Costs
    Registries
    Arm
    Thorax
    Therapeutics
    Air
    Outcome Assessment (Health Care)

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    Everard, Mark ; Hind, D. ; Ugonna, K. ; Freeman, J. ; Bradburn, M. ; Dixon, S. ; Maguire, C. ; Cantrill, H. ; Alexander, J. ; Lenney, W. ; Mcnamara, P. ; Elphick, H. ; Chetcuti, P.A.J. ; Moya, E.F. ; Powell, C. ; Garside, J.P. ; Chadha, L.K. ; Kurian, M. ; Lehal, R.S. ; Macfarlane, P.I. ; Cooper, C.L. ; Cross, E. / Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review. In: Health Technology Assessment. 2015 ; Vol. 19, No. 66. pp. 1-130.
    @article{64cbca50462a465c97696121d839e723,
    title = "Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review",
    abstract = "{\circledC} Queen's Printer and Controller of HMSO 2015. 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{\%}. Design: Parallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review. Setting: Ten UK hospitals. Participants: Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. Interventions: 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. Main outcome measures: 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. Data sources: 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. Review 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 I2 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 (I2 = 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.",
    author = "Mark Everard and D. Hind and K. Ugonna and J. Freeman and M. Bradburn and S. Dixon and C. Maguire and H. Cantrill and J. Alexander and W. Lenney and P. Mcnamara and H. Elphick and P.A.J. Chetcuti and E.F. Moya and C. Powell and J.P. Garside and L.K. Chadha and M. Kurian and R.S. Lehal and P.I. Macfarlane and C.L. Cooper and E. Cross",
    year = "2015",
    doi = "10.3310/hta19660",
    language = "English",
    volume = "19",
    pages = "1--130",
    journal = "Health Technology Assessment",
    issn = "1366-5278",
    publisher = "National Co-ordinating Centre for HTA",
    number = "66",

    }

    Everard, M, Hind, D, Ugonna, K, Freeman, J, Bradburn, M, Dixon, S, Maguire, C, Cantrill, H, Alexander, J, Lenney, W, Mcnamara, P, Elphick, H, Chetcuti, PAJ, Moya, EF, Powell, C, Garside, JP, Chadha, LK, Kurian, M, Lehal, RS, Macfarlane, PI, Cooper, CL & Cross, E 2015, 'Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review' Health Technology Assessment, vol. 19, no. 66, pp. 1-130. https://doi.org/10.3310/hta19660

    Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review. / Everard, Mark; Hind, D.; Ugonna, K.; Freeman, J.; Bradburn, M.; Dixon, S.; Maguire, C.; Cantrill, H.; Alexander, J.; Lenney, W.; Mcnamara, P.; Elphick, H.; Chetcuti, P.A.J.; Moya, E.F.; Powell, C.; Garside, J.P.; Chadha, L.K.; Kurian, M.; Lehal, R.S.; Macfarlane, P.I.; Cooper, C.L.; Cross, E.

    In: Health Technology Assessment, Vol. 19, No. 66, 2015, p. 1-130.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Saline in acute bronchiolitis RCT and economic evaluation: Hypertonic saline in acute bronchiolitis – Randomised controlled trial and systematic review

    AU - Everard, Mark

    AU - Hind, D.

    AU - Ugonna, K.

    AU - Freeman, J.

    AU - Bradburn, M.

    AU - Dixon, S.

    AU - Maguire, C.

    AU - Cantrill, H.

    AU - Alexander, J.

    AU - Lenney, W.

    AU - Mcnamara, P.

    AU - Elphick, H.

    AU - Chetcuti, P.A.J.

    AU - Moya, E.F.

    AU - Powell, C.

    AU - Garside, J.P.

    AU - Chadha, L.K.

    AU - Kurian, M.

    AU - Lehal, R.S.

    AU - Macfarlane, P.I.

    AU - Cooper, C.L.

    AU - Cross, E.

    PY - 2015

    Y1 - 2015

    N2 - © Queen's Printer and Controller of HMSO 2015. 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%. Design: Parallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review. Setting: Ten UK hospitals. Participants: Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. Interventions: 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. Main outcome measures: 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. Data sources: 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. Review 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 I2 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 (I2 = 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.

    AB - © Queen's Printer and Controller of HMSO 2015. 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%. Design: Parallel-group, pragmatic randomised controlled trial, cost–utility analysis and systematic review. Setting: Ten UK hospitals. Participants: Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. Interventions: 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. Main outcome measures: 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. Data sources: 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. Review 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 I2 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 (I2 = 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.

    U2 - 10.3310/hta19660

    DO - 10.3310/hta19660

    M3 - Article

    VL - 19

    SP - 1

    EP - 130

    JO - Health Technology Assessment

    JF - Health Technology Assessment

    SN - 1366-5278

    IS - 66

    ER -