When should nebulized hypertonic saline solution be used in the treatment of bronchiolitis?

Abstract

Bronchiolitis is a common lower respiratory infection that leads to frequent hospitalization at a rate of 31.2 per 1000 infants per year (1). Salbutamol, racemic adrenaline, corticosteroids and nebulized normal saline (NS) are commonly used therapies that all appear to have questionable efficacy in specific settings (2). The present review examines the effectiveness of nebulized 3% hypertonic saline solution (HS) in improving clinical scores, reducing the hospitalization rate and decreasing the length of stay (LOS), and reports adverse events attributed to HS. Part a: EvidEncE-basEd answEr and summary MEDLINE, EMBASE and the Cochrane Library were searched for randomized controlled trials that treated children with nebulized HS for bronchiolitis. One Cochrane meta-analysis published in 2008 (3) concluded that HS improved clinical scores on the first and second but not on the third day of treatment, did not decrease the hospitalization rate in the single small outpatient study, but did reduce LOS. The present review includes the four studies (4-7) from the meta-analysis and three subsequent studies (8-10). The challenge of the review is the heterogeneity of these studies. The mean ages of the children in the studies ranged from 2.6 months (6) to 12.5 months (4). Children were enrolled from outpatient community clinics in Israel (4), paediatric emergency departments (EDs) in Canada (9) and Turkey (10), and inpatient wards in Israel (5,6), China (8), and both the United Arab Emirates and Canada (7). None of the studies enrolled children who required intensive care unit admission. Five studies (4-6,8,10) used the Wang clinical scoring system. The Respiratory Distress Assessment Instrument (7) and the Respiratory Assessment Change Score (9) were used by one study each. All studies randomly assigned children to nebulized treatment groups of either 0.9% NS or 3% HS (4-10). In six studies (4-6,8-10), a protocol-specified bronchodilator was mixed and nebulized along with a saline solution, including terbutaline (4), salbutamol (8) or adrenaline (5,6,9), at variable dosing frequencies and durations. Two of these six studies (5,6) permitted the treating clinicians to provide ‘add-on’ nebulization treatments at their own discretion. The ED study from Turkey (10) had four treatment arms combining salbutamol or adrenaline with 0.9% NS or 3% HS, with a fifth arm receiving only 0.9% NS. In the seventh study (7), clinicians added a bronchodilator to the NS or HS at their discretion, with 37% of the treatments including salbutamol and 23% including adrenaline. Results of clinical scores were inconsistent. The outpatient study and three inpatient studies (4-6,8) demonstrated a statistically significant greater improvement in the HS than in the NS group. These scores improved as the number of HS treatments increased. The remaining inpatient study (7) calculated a clinical score during enrollment, not after saline treatments. Finally, the two studies from the ED (9,10) failed to show any differences in clinical scores between the treatment groups. In the outpatient clinic (4), two children from the NS group (n=32) required hospitalization, compared with three children from the HS group (n=33). In the ED study from Turkey (10), one child from the NS and salbutamol group (n=36), and one child from the HS and adrenaline group (n=39) required hospitalization. The remaining three arms did not have any children requiring hospitalization. In the ED study from Canada (9), 13 children from the NS group (n=23) and eight children from the HS group (n=23) required hospitalization (risk ratio 0.61; 95% CI 0.22 to 1.19). The LOS of hospitalized children was statistically significantly shorter in the HS group in all four studies (5-8). Typically, HS shortened the LOS by approximately one day (typically from approximately four to three days), with the largest decrease being 1.4 days (8). However, the mean LOS was also longest in the latter study (6.0 days in the HS group versus 7.4 days in the NS group) (8). There is concern that HS could precipitate bronchospasm in children with reactive airway disease. No serious adverse events were attributed to HS in the included trials, but because very few children received HS without a bronchodilator, this fact is not totally reassuring. In summary, HS was associated with improved clinical scores in four of seven studies with no obvious pattern. Hospitalization rates were not clearly impacted by therapy, but a trend toward a decreased rate was shown in one ED study (9). However, a shortened LOS was consistently observed in noncritical hospitalized patients.