Nebulized hypertonic saline in infants with acute viral bronchiolitis: a systematic review and meta-analysis of 35 randomized clinical trials

Background Acute bronchiolitis is the leading cause of hospital admission in infants under 2 years. While management is primarily supportive, nebulized hypertonic saline (HS) has been proposed to improve mucociliary clearance, though clinical guidelines remain inconsistent. Objective To evaluate the efficacy of nebulized HS compared with normal saline (NS) in infants with acute bronchiolitis. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in children aged ≤24 months with bronchiolitis. Eligible studies compared nebulized HS with NS and reported hospital admission, clinical symptom severity, or length of hospital stay (LOS). PubMed and the Cochrane Library were searched from inception to February 12, 2025. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses were performed using relative risks (RRs), standardized mean differences (SMDs), and mean differences (MDs), with heterogeneity assessed using the I 2 statistic. Cumulative meta-analyses and sensitivity analyses were also conducted. Results Thirty-five RCTs including 4723 infants were analyzed. Compared with NS, HS reduced hospital admission by 26% (RR 0.74, 95% CI 0.60–0.90), improved symptom severity at 24 h (SMD 0.48), 48 h (0.53), and 72 h (0.42), and shortened LOS (MD −0.44 days, 95% CI −0.68 to −0.21). Heterogeneity was substantial for symptom severity (I 2 =88.9% to 91.7%) and LOS (I 2 =80.3%) warranting cautious interpretation. Cumulative meta-analysis demonstrated early variability followed by stabilization of effect estimates over time. Conclusion Nebulized HS provides consistent clinical benefit compared with NS in infants with bronchiolitis and supports reconsideration of its role in clinical practice.