In this NIHR-funded trial babies with a viral chest infection (acute bronchiolitis) were treated either with a strong saline mist (nebulised 3% hypertonic sodium chloride) with standard care or standard care alone. The stronger than usual, hypertonic saline mist had no effect on the time it took for babies to be ready for discharge, nor did the trial demonstrate any other benefit from its use. The treatment itself caused some minor side effects in a few babies, such as excessive coughing and a fall in blood oxygen levels. It was also not cost-effective at usual NHS thresholds. The results of the trial should be directly relevant to the UK context.
The authors also conducted their own systematic review, combining the results of 15 trials including their own trial. These combined results showed a small reduction in length of stay in hospital (just over 8 hours) and was in agreement with a 2013 Cochrane review of 11 trials that concluded hypertonic saline significantly reduced length of stay in hospital by just over a day. However the results of both reviews should be treated with caution.
The results are in line with 2015 NICE guidelines that say hypertonic saline should not be used in these babies.
Why was this study needed?
Bronchiolitis is a common respiratory tract infection affecting about 1 in 3 babies. About 2% to 3% of these babies develop more severe symptoms, such as breathing difficulties, needing hospital treatment. The number of hospital admissions for bronchiolitis has been increasing over the last ten years, from 21,330 admissions in England in 2004 to 30,451 in 2011.
A 2013 Cochrane systematic review of 11 trials found that the use of nebulised hypertonic saline (3% sodium chloride), might significantly reduce the length of time spent in hospital with bronchiolitis compared with using nebulised normal saline (0.9% sodium chloride), but there has been doubt about the conclusion.
The NIHR funded this large randomised controlled trial (called SABRE) to find out whether treatment with nebulised hypertonic saline in addition to standard care would reduce the time babies with bronchiolitis needed to stay in hospital.
What did this study do?
This was a pragmatic randomised controlled trial including 317 babies admitted to ten UK hospitals with bronchiolitis. About half received standard care including treatment with oxygen. The other half received standard care plus treatment with 4ml nebulised 3% hypertonic saline every six hours. The final analysis included 290 children as 26 were ineligible and the notes of one child were lost. The primary outcome was the time until babies were assessed as being fit for discharge.
An economic evaluation and a systematic review of 15 trials including the SABRE trial were also conducted.
What did it find?
- There was no difference between the two groups in the time to being declared fit for discharge (hazard ratio [HR] 0.95, 95% Confidence Interval [CI] 0.75 to 1.20). The average (median) time until a baby in the saline group was fit for discharge was 75.6 hours compared with 75.9 hours in the standard care group.
- There was no difference for the secondary outcome of actual time to discharge (HR 0.97, 95% CI 0.76 to 1.23). The median time for the saline group to be discharged was 88.5 hours compared with 88.7 hours.
- The systematic review found that hypertonic saline reduced the mean length of stay in hospital by about eight hours (difference 0.36 days, 95% CI 0.22 to 0.50 days). However, the results showed a wide variability in treatment effectiveness which means that the pooled estimate of effects should be treated with caution. The authors say that the estimate will not be a useful basis for decision-making.
- The cost utility analysis found that nebulised saline was not cost-effective at usual thresholds. It included underlying costs and benefits that were themselves highly uncertain.
What does current guidance say on this issue?
The 2015 NICE guideline on bronchiolitis recommends that nebulised hypertonic saline should not be used to treat bronchiolitis in children. The guideline recommends giving oxygen supplementation.
What are the implications?
This trial provided strong evidence that using nebulised hypertonic saline added no benefit to standard care for the treatment of bronchiolitis in babies and was not cost-effective. This is in accordance with the 2015 NICE guideline.
The results of the SABRE study should be reliable and generalisable to the UK as it was conducted in ten UK hospitals, including both teaching and district general hospitals, with a typical spectrum of disease and standard treatments.
Everard ML, Hind D, Ugonna K, et al. Saline in Acute Bronchiolitis RCT and Economic evaluation: hypertonic saline in acute bronchiolitis - randomised controlled trial and systematic review. Health Technol Assess. 2015;19(66).
This project was funded by the National Institute for Health Research Health Technology Assessment (HTA) programme (project number 09/91/22).
Chen YJ, Lee WL, Wang CM, et al. Nebulized hypertonic saline treatment reduces both rate and duration of hospitalization for acute bronchiolitis in infants: an updated meta-analysis. Pediatr Neonatol. 2014 Dec;55(6):431-8.
Zhang L, Mendoza-Sassi RA, Wainwright C, et al. Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2013;(7). Art. No.: CD006458.
NHS Choices. Bronchiolitis. London: Department of Health; 2013
NICE. Bronchiolitis in children. NG9. London: National Institute for Health and Care Excellence; 2015.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre