Abstract: We identified 26 new trials in this update, of which 9 await classification due to insufficient data for eligibility assessment, and 17 trials (N = 3105) met the inclusion criteria. We included a total of 28 trials involving 4195 infants with acute bronchiolitis, of whom 2222 infants received hypertonic saline. Hospitalised infants treated with nebulised hypertonic saline had a statistically significant shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -0.41 days, 95% CI -0.75 to -0.07; P = 0.02, I² = 79%; 17 trials; 1867 infants) (GRADE quality of evidence: low). Infants who received hypertonic saline also had statistically significant lower post-inhalation clinical scores than infants who received 0.9% saline in the first three days of treatment (day 1: MD -0.77, 95% CI -1.18 to -0.36, P < 0.001; day 2: MD -1.28, 95% CI -1.91 to -0.65, P < 0.001; day 3: MD -1.43, 95% CI -1.82 to -1.04, P < 0.001) (GRADE quality of evidence: low). Nebulised hypertonic saline reduced the risk of hospitalisation by 14% compared with nebulised 0.9% saline among infants who were outpatients and those treated in the emergency department (RR 0.86, 95% CI 0.76 to 0.98; P = 0.02, I² = 7%; 8 trials; 1723 infants) (GRADE quality of evidence: moderate). Twenty-four trials presented safety data: 13 trials (1363 infants, 703 treated with hypertonic saline) did not report any adverse events, and 11 trials (2360 infants, 1265 treated with hypertonic saline) reported at least one adverse event, most of which were mild and resolved spontaneously. Nebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate.

Plain-language summary: We identified 26 new studies in this update, of which 9 await assessment and 17 trials (N = 3105) were added. We included a total of 28 trials involving 4195 infants with acute bronchiolitis. Nebulised hypertonic saline may reduce hospital stay by 10 hours in comparison to normal saline for infants admitted with acute bronchiolitis. We found that 'clinical severity scores', which are used by doctors to assess patient health, for children treated as outpatients or in hospital improved when administered nebulised hypertonic saline compared to normal saline. Nebulised hypertonic saline may also reduce the risk of hospitalisation by 14% among children treated as outpatients or in the emergency department. We found only minor and spontaneously resolved adverse effects from the use of nebulised hypertonic saline when given with treatment to relax airways (bronchodilators). Reductions in hospital stay were smaller than previously thought. However, an average reduction of 10 hours in the length of hospital stay for infants is significant because bronchiolitis usually has a short duration. Nebulised hypertonic saline appears to be safe and widely available at low cost. The quality of the evidence was low to moderate: there were inconsistencies in results among trials and risk of bias in some trials. Future large trials are therefore needed to confirm the benefits of nebulised hypertonic saline for children with bronchiolitis treated as outpatients and in hospital.