LAKE BUENA VISTA, FLA. – The median length of stay and rate of readmission did not differ between infants with bronchiolitis who were treated with nebulized 3% hypertonic saline and those treated with normal saline in the first U.S. prospective, double-blind, randomized controlled trial comparing the two treatments.*

The median length of stay was 2.0 days in 93 infants younger than age 12 months who were admitted to an urban tertiary care children’s hospital with a diagnosis of bronchiolitis and who were randomized to receive the hypertonic saline treatments without concomitant bronchodilators, and 2.0 days in 97 such infants who received normal saline without bronchodilators, Dr. Alyssa Silver reported at the Pediatric Hospital Medicine 2014 meeting.

The mean length of stay also did not differ significantly between the groups, nor did the rate of readmission and rate of adverse event, Dr. Silver, a pediatric hospitalist and director of pediatric inpatient physician assistant services at the Children’s Hospital at Montefiore, Bronx, N.Y., reported at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Infants offered enrollment were those admitted with bronchiolitis to an urban tertiary care children’s hospital in a population with a high endemic prevalence of asthma. Those with status asthmaticus, certain chronic diseases, and prior exposure to hypertonic saline were among those excluded.

The infants included in the study were enrolled within 12 hours of admission between 2011 and 2014, received 4 mL of hypertonic or normal saline every 4 hours via standard hospital wall nebulizer until discharge and were assessed daily by study personnel who made follow-up calls at 1 week and 1 month after discharge to document readmissions.

To address the theoretical concern of bronchospasm with hypertonic saline, patients were evaluated using the Respiratory Distress Assessment Instrument prior to first study treatment and at 30 minutes after the treatment as a safety measure and were withdrawn if the measure increased by four or more points, Dr. Silver said.

The treatment and control groups were similar with respect to demographic factors.

Subgroup analyses showed no differences in length of stay between infants in the treatment and control groups who were respiratory syncytial virus positive, had a history of wheezing, or had a history of prematurity, Dr. Silver noted.

Enrollment in the study was halted at the time of an interim analysis because of the demonstrated lack of difference in length of stay between the groups.

Bronchiolitis is the leading cause of hospitalization for children under 12 months of age – at a cost of about $500 million each year. The national average length of stay for infants with bronchiolitis is 3.3 days.

"Despite the high incidence of bronchiolitis, there is a lack of a unified inpatient treatment plan beyond supportive care of oxygen and intravenous hydration. Many different approaches have been used, but none have proven useful," Dr. Silver said, adding that interest in the use of nebulized hypertonic saline has been on the rise.

Based on literature from its use in patients with cystic fibrosis, the proposed mechanism of action is hydration of the airway surface liquid, which decreases airway wall edema and improves ciliary function, thereby assisting with the clearance of secretions, she explained.

A Cochrane review suggested benefit, but there are a number of concerns about generalizing the findings. For example, all of the included studies were performed outside of the United States, included varying dosing regimens, and excluded patients with a history of wheeze, and most allowed the use of adjunctive bronchodilators and were performed in areas with a much longer length of stay than occurs in the United States.

More recent studies in the United States questioned the utility of hypertonic saline, but also allowed the use of bronchodilators and excluded patients with a history of wheezing.

The findings of the current study suggest that although 3% hypertonic saline is safe in infants with bronchiolitis – including those with a history of wheeze, and even in a population with high endemic prevalence of asthma – there is no utility for the routine use of 3% hypertonic saline vs. normal saline without adjunctive bronchodilators in this population, she said.

However, the study is limited by the single-center design, and lack of complete coverage for recruiting of admitted patients (the study was unfunded and relied on voluntary study personnel), although more than 75% of patients admitted for bronchiolitis were offered enrollment.

Future studies might benefit by enrolling patients earlier than within 12 hours of admission with a minimum severity score to enter, assessing similar outcomes using higher concentrations of nebulized sodium chloride, studying on demand vs. scheduled saline treatments for bronchiolitis, and/or by comparing either intervention to supportive care alone, Dr. Silver said.

Dr. Silver reported having no disclosures.

*An earlier version of this article misstated the city name in the dateline.

RCT: 3% hypertonic saline fails to improve bronchiolitis outcomes