JAMA Pediatrics Journal Club Slides: Nebulized Hypertonic Saline for Bronchiolitis

1. JAMA Pediatrics Journal Club Slides:Nebulized Hypertonic Saline for Bronchiolitis Florin TA, Shaw KN, Kittick M, Yakscoe S, Zorc JJ. Nebulized hypertonic saline for bronchiolitis in the emergency department: a randomized clinical trial. JAMA Pediatr. Published online May 26, 2014. doi:10.1001/jamapediatrics.2013.5306.

2. Introduction • Background • Acute bronchiolitis is the most frequent lower respiratory infection and most frequent cause for hospitalization in infants. • There are no proven effective therapies for bronchiolitis; nebulized hypertonic saline (HS) has been proposed as a potential therapy. • HS is thought to increase mucociliary clearance by lowering the viscosity of mucus secretions, stimulating cilial beat, and reducing airway edema. • There is conflicting evidence about the role of HS for the treatment of acute bronchiolitis. • Study Objective • To determine whether nebulized 3% HS compared with normal saline (NS) improves respiratory distress in infants with bronchiolitis not responding to a trial of nasal suctioning and nebulized albuterol sulfate in the emergency department (ED).

3. Methods • Study Design • Randomized clinical trial with blinding of investigators, health care providers, and parents. • Setting • A single urban tertiary care pediatric ED during 2 bronchiolitis seasons, from November 1 to April 30 of 2010 and 2011. • Patients • Inclusion:(1) Aged 2 to <24 months, (2) first episode of bronchiolitis (wheezing with signs and symptoms of respiratory distress and upper respiratory infection), (3) Respiratory Distress Assessment Instrument (RDAI) score of 4-15 after albuterol treatment. • Exclusion: (1) History of wheezing or asthma, or bronchodilator therapy before current illness, (2) chronic lung or heart disease, (3) critical illness, (4) inability to receive nebulized medications, (5) non–English-speaking guardians.

4. Methods • Interventions • 4 mL of 3% HS vs 4 mL of NS. • Outcomes • Primary: Respiratory Assessment Change Score (RACS) at 1 hour after study intervention (RACS = change in RDAI score + standardized change in respiratory rate; decrease in RACS signifies clinical improvement). • Secondary: Vital signs, oxygen saturation, hospitalization, physician clinical impression, parental perception of improvement, adverse events. Respiratory Distress Assessment Instrument (adapted from Lowell et al22)

5. Results Consolidated Standards for Reporting of Trials Study Flow Diagram

6. Results Baseline Characteristics

7. Results RACS Values 1 Hour After HS and NS Administration Using a RACS of −3 as a clinically significant improvement, the NS group demonstrated improvement in respiratory status 1 hour after treatment, and the HS group did not substantially improve.

8. Results Outcomes 1 Hour After Saline Administration • Difference in RACS at 1 hour after treatment demonstrated significantly less improvement in HS group compared with NS group. • No significant difference in RDAI score. • Greater decrease in respiratory rate from baseline to 1 hour in NS group compared with HS group. • No significant differences in secondary outcomes.

9. Results • No significant difference in RACS at 2 hours after study intervention between the 2 groups. • During patient follow-up, there were no significant differences between the HS and NS groups in: • Parental perception of study treatment improving their child’s symptoms. • Unscheduled pediatrician visits. • Hospitalization after initially being discharged from the ED. • No adverse events occurred during the study.

10. Comment • This randomized clinical trial demonstrated that infants with bronchiolitis with persistent distress after nasal suctioning and a trial of albuterol who received a single dose of nebulized 3% HS in the ED had less improvement in respiratory distress compared with those receiving NS. • Lack of benefit of HS compared with NS in the ED is consistent with findings of prior studies. • These results are in contrast to those of studies examining the use of HS repeatedly over time, which generally show a decreased length of stay in hospitalized infants or improved clinical severity in outpatients.

11. Comment • Limitations • Single-center study—results may not be generalizable. • Single dose of 3% HS—relatively low concentration of HS. Results may differ with increasing concentrations or repeated doses. • Intended to separate delivery of albuterol and HS, so primary outcome was measured after peak effect of albuterol; however, it is possible there were residual effects of albuterol at time of assessment. • RACS as short-term outcome; however, ED and primary care providers make disposition and treatment decisions based on short-term outcomes, making this a relevant choice given the practice environment. • Conclusions • HS results in less improvement 1 hour after treatment in the ED compared with NS in infants with bronchiolitis who had persistent distress after albuterol and nasal suctioning. • Administration of a single dose of HS in the acute care setting does not appear to be more effective than NS in improving short-term respiratory distress in bronchiolitis.

12. Contact Information • If you have questions, please contact the corresponding author: • Todd A. Florin, MD, MSCE, Division of Pediatric Emergency Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, ML 2008, Cincinnati, OH 45229 (todd.florin@cchmc.org). Funding/Support • This study was supported by a Young Investigator Award from the Academic Pediatric Association. Conflict of Interest Disclosures • None reported.