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Jun 20, 2023

What are the benefits and risks of hypertonic saline solution via nebuliser for treating infants with acute bronchiolitis, compared to normal saline solution?

Key messages Compared to nebulised normal saline, nebulised hypertonic saline

Key messages

Compared to nebulised normal saline, nebulised hypertonic saline may reduce hospital stay by almost 10 hours for infants admitted with acute bronchiolitis; may improve 'clinical severity scores', which are used by doctors to assess disease severity; and may reduce the risk of hospitalisation by 13% amongst children treated as outpatients or in the emergency department.

We found only minor and spontaneously resolved adverse events (such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea) from the use of nebulised hypertonic saline when given with treatment to relax airways (bronchodilators).

Our confidence in the evidence is low to very low; future large studies are needed to confirm the benefits of nebulised hypertonic saline for children with acute bronchiolitis.

What is acute bronchiolitis?

Acute bronchiolitis is the most common lower respiratory tract infection in children aged up to two years. Bronchiolitis occurs when small structures (bronchioles) leading to the lungs become infected, causing inflammation, swelling, and mucus production. This makes breathing difficult, especially in very young children, who develop coughs and wheezing.

Because bronchiolitis is usually caused by a virus, drug treatment is generally not effective. Hypertonic saline (a strong, or highly concentrated, sterile salt water solution) breathed in as a fine mist using a nebuliser may help relieve wheezing and breathing difficulty.

What did we want to find out?

We wanted to find out if hypertonic saline solution via nebuliser is more effective and safe for the treatment of infants with acute bronchiolitis compared to normal saline solution.

What did we do?

We searched for studies that compared nebulised hypertonic (≥ 3%) saline solution alone or combined with bronchodilators versus nebulised normal (0.9%) saline or standard treatment for infants with acute bronchiolitis. We combined the results across the included studies.

What did we find?

We included 34 trials involving 5205 infants with acute bronchiolitis. Eleven trials await assessment. Nine trials had no funding, and five trials were funded by government sources or academic agencies. The remaining 20 trials did not provide funding sources. Nebulised hypertonic saline may reduce hospital stay by 9.6 hours in comparison to normal saline or standard treatment for infants admitted with acute bronchiolitis. Clinical severity scores of infants improved slightly when administered nebulised hypertonic saline compared to normal saline. It remains unclear whether nebulised hypertonic saline can reduce the number of days to resolution of symptoms. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation by 13% amongst children treated as outpatients or in the emergency department. However, hypertonic saline may not reduce the risk of readmission to hospital after discharge. We found only minor and spontaneously resolved adverse events (such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea) from the use of nebulised hypertonic saline when given with bronchodilators.

What are the limitations of the evidence?

Our confidence in the evidence is low to very low, and further research is likely to change the results of this review. Two main factors reduced our confidence in the evidence. Firstly, in some trials children were not randomly placed into different treatment groups, which means that any differences between groups could be due to differences between people rather than treatments. Secondly, there were inconsistencies in results across trials.

How up-to-date is the evidence?

The evidence is current to 13 January 2022.

Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.

Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017.

To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022.

We included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation.

Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics.

We included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources.

Hospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) −0.40 days, 95% confidence interval (CI) −0.69 to −0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD −0.64, 95% CI −1.08 to −0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD −1.07, 95% CI −1.60 to −0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD −0.89, 95% CI −1.44 to −0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD −1.16 days, 95% CI −1.43 to −0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD −0.87 days, 95% CI −1.31 to −0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD −1.30 days, 95% CI −2.28 to −0.32; 2 trials, 205 infants; very low-certainty evidence).

Twenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence).