Hypertonic Saline Effective for Infants With Bronchiolitis

Nicola M. Parry, DVM

September 28, 2015

For infants with acute bronchiolitis, nebulized hypertonic saline (HS) can reduce the risk for hospitalization in outpatients and reduce the length of hospital stay among inpatients, a new study suggests.

Linjie Zhang, MD, PhD, a professor in the Faculty of Medicine, Federal University of Rio Grande, Brazil, and colleagues published the results of their systematic review and meta-analysis online September 28 and in the October issue of Pediatrics.

"[T]his new systematic review shows that nebulized HS is associated with a mean reduction of 0.45 days (∼11 hours) in [length of stay (LOS)] among infants admitted for acute bronchiolitis and a mean reduction of 20% in the risk of hospitalization among outpatients," the authors write. "This review also suggests that nebulized HS is a safe treatment in infants with bronchiolitis, especially when administered in conjunction with a bronchodilator."

Acute bronchiolitis is the most frequent lower respiratory tract infection and the leading cause of hospitalization in children younger than 2 years. It is usually caused by a viral infection, most commonly resulting from respiratory syncytial virus. In the United States, the estimated annual cost of hospitalization for children with acute bronchiolitis is US$500 million. According to the authors, hospital admissions for acute bronchiolitis are also increasing, rising from 21,330 in 2004 and 2005 to 33,472 in 2010 and 2011.

Supportive treatment remains the standard care for children with acute bronchiolitis. HS has been introduced as a treatment for children with acute bronchiolitis because it is thought to decrease airway edema, reduce mucus plugging, and increase mucociliary clearance. In recent decades, an increasing number of randomized clinical trials (RCTs) have therefore been conducted to investigate the use of nebulized HS in children with acute bronchiolitis.

The Cochrane review published in 2013 included 11 RCTs and demonstrated that nebulized 3% saline may significantly reduce LOS in hospitalized infants with acute bronchiolitis and improve the clinical severity score in both outpatient and inpatient settings. However, since then, additional RCTs have reported conflicting results. Dr Zhang and colleagues therefore aimed to provide an updated synthesis of the evidence from all available RCTs in HS in this patient population.

The researchers performed a systematic review of currently available RCTs to assess the effects and safety of nebulized HS in children aged 24 months or younger with acute bronchiolitis. They searched various electronic databases to identify studies for inclusion and excluded those that included patients who had experienced recurrent wheezing or were intubated and ventilated, as well as those that assessed pulmonary function alone.

Among the 24 included studies involving 3209 patients, 1706 children had received HS.

In the inpatient setting, an analysis of 15 studies involving 1956 patients demonstrated that hospitalized children treated with nebulized HS had a significantly shorter LOS compared with those who received 0.9% saline or standard care (mean difference [MD], −0.45 days; 95% confidence interval [CI], −0.82 days to −0.08 days; P = .01). In an analysis of five trials involving 404 children, those who received HS also had significantly improved posttreatment clinical severity scores on day 1 (MD, −0.99 days; 95% CI, −1.48 days to −0.50 days; P < .0001), day 2 (MD, −1.45 days; 95% CI, −2.06 days to −0.85 days; P < .0001), and day 3 (MD, −1.44 days; 95% CI, −1.78 days to −1.11 days; P < .0001) of admission.

In the outpatient setting, an analysis of seven studies involving 951 patients demonstrated that nebulized HS reduced the risk for hospitalization by 20% compared with 0.9% saline (risk ratio [RR], 0.80; 95% CI, 0.67 - 0.96; P = .01).

"The effect size of nebulized HS on reducing LOS in hospitalized patients shown by the present review is only approximately one-third of that shown by the 2013 Cochrane review, which included 6 inpatient trials involving 500 patients (MD, −1.15 days; 95% CI, −1.49 to −0.82 days)," the authors write. "For outpatients, this new review showed a 20% reduction on the risk of hospitalization associated with nebulized HS in contrast with a 37% non–statistically significant reduction shown by the 2013 Cochrane review, which included 4 outpatient trials involving 380 participants (RR, 0.63; 95% CI, 0.37–1.07)."

The authors continue, "Potential adverse effects of intervention with nebulized HS, such as acute bronchospasm, remain a potential concern." However, no significant adverse effects related to HS inhalation were reported in 21 of the 24 trials included in this current study that recorded safety data among 2897 patients, 1557 of whom were treated with HS. Fourteen of these trials involved 828 patients who received nebulized HS, 81.3% of whom received HS in conjunction with a bronchodilator. At least one adverse effect was reported in each of the remaining seven trials involving 729 patients treated with nebulized HS, 74% of whom received HS alone. However, most adverse effects were mild and resolved spontaneously.

"Given the high prevalence of bronchiolitis in infants and huge burden on health care systems throughout the world, benefits of nebulized HS shown by this review, even though smaller than previously estimated, may still be considered clinically relevant," the authors conclude.

The authors have disclosed no relevant financial relationships.

Pediatrics. 2015;136:687-701. Abstract

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