Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial | Emergency Medicine | JAMA Pediatrics | JAMA Network
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1.
Hall  CB, Weinberg  GA, Iwane  MK,  et al.  The burden of respiratory syncytial virus infection in young children.  N Engl J Med. 2009;360(6):588-598.PubMedGoogle ScholarCrossref
2.
Johnson  LW, Robles  J, Hudgins  A, Osburn  S, Martin  D, Thompson  A.  Management of bronchiolitis in the emergency department: impact of evidence-based guidelines?  Pediatrics. 2013;131(suppl 1):S103-S109.PubMedGoogle ScholarCrossref
3.
Hasegawa  K, Tsugawa  Y, Brown  DF, Mansbach  JM, Camargo  CA  Jr.  Temporal trends in emergency department visits for bronchiolitis in the United States, 2006 to 2010.  Pediatr Infect Dis J. 2014;33(1):11-18.PubMedGoogle ScholarCrossref
4.
Hasegawa  K, Tsugawa  Y, Brown  DF, Mansbach  JM, Camargo  CA  Jr.  Trends in bronchiolitis hospitalizations in the United States, 2000-2009.  Pediatrics. 2013;132(1):28-36.PubMedGoogle ScholarCrossref
5.
Pelletier  AJ, Mansbach  JM, Camargo  CA  Jr.  Direct medical costs of bronchiolitis hospitalizations in the United States.  Pediatrics. 2006;118(6):2418-2423.PubMedGoogle ScholarCrossref
6.
Meissner  HC.  Viral bronchiolitis in children.  N Engl J Med. 2016;374(1):62-72.PubMedGoogle ScholarCrossref
7.
Ralston  SL, Lieberthal  AS, Meissner  HC,  et al; American Academy of Pediatrics.  Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis.  Pediatrics. 2014;134(5):e1474-e1502.PubMedGoogle ScholarCrossref
8.
Gajdos  V, Katsahian  S, Beydon  N,  et al.  Effectiveness of chest physiotherapy in infants hospitalized with acute bronchiolitis: a multicenter, randomized, controlled trial.  PLoS Med. 2010;7(9):e1000345.PubMedGoogle ScholarCrossref
9.
Farley  R, Spurling  GK, Eriksson  L, Del Mar  CB.  Antibiotics for bronchiolitis in children under two years of age.  Cochrane Database Syst Rev. 2014;(10):CD005189.PubMedGoogle Scholar
10.
Zhang  L, Mendoza-Sassi  RA, Klassen  TP, Wainwright  C.  Nebulized hypertonic saline for acute bronchiolitis: a systematic review.  Pediatrics. 2015;136(4):687-701.PubMedGoogle ScholarCrossref
11.
Zhang  L, Mendoza-Sassi  RA, Wainwright  C, Klassen  TP.  Nebulised hypertonic saline solution for acute bronchiolitis in infants.  Cochrane Database Syst Rev. 2013;(7):CD006458.PubMedGoogle Scholar
12.
Mandelberg  A, Amirav  I.  Hypertonic saline or high volume normal saline for viral bronchiolitis: mechanisms and rationale.  Pediatr Pulmonol. 2010;45(1):36-40.PubMedGoogle ScholarCrossref
13.
Brooks  CG, Harrison  WN, Ralston  SL.  Association between hypertonic saline and hospital length of stay in acute viral bronchiolitis: a reanalysis of 2 meta-analyses.  JAMA Pediatr. 2016;170(6):577-584.PubMedGoogle ScholarCrossref
14.
Zhang  L.  Hypertonic saline for bronchiolitis: a meta-analysis reanalysis.  J Pediatr. 2016;176:221-224.PubMedGoogle ScholarCrossref
15.
Wu  S, Baker  C, Lang  ME,  et al.  Nebulized hypertonic saline for bronchiolitis: a randomized clinical trial.  JAMA Pediatr. 2014;168(7):657-663.PubMedGoogle ScholarCrossref
16.
Ralston  S, Hill  V, Martinez  M.  Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis.  Pediatrics. 2010;126(3):e520-e525.PubMedGoogle ScholarCrossref
17.
Grewal  S, Ali  S, McConnell  DW, Vandermeer  B, Klassen  TP.  A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department.  Arch Pediatr Adolesc Med. 2009;163(11):1007-1012.PubMedGoogle ScholarCrossref
18.
Lowell  DI, Lister  G, Von Koss  H, McCarthy  P.  Wheezing in infants: the response to epinephrine.  Pediatrics. 1987;79(6):939-945.PubMedGoogle Scholar
19.
Jacobs  JD, Foster  M, Wan  J, Pershad  J.  7% Hypertonic saline in acute bronchiolitis: a randomized controlled trial.  Pediatrics. 2014;133(1):e8-e13.PubMedGoogle ScholarCrossref
20.
Laird  NM, Ware  JH.  Random-effects models for longitudinal data.  Biometrics. 1982;38(4):963-974.PubMedGoogle ScholarCrossref
21.
Anil  AB, Anil  M, Saglam  AB, Cetin  N, Bal  A, Aksu  N.  High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis.  Pediatr Pulmonol. 2010;45(1):41-47.PubMedGoogle ScholarCrossref
22.
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. 2014;168(7):664-670.PubMedGoogle ScholarCrossref
23.
Ipek  IO, Yalcin  EU, Sezer  RG, Bozaykut  A.  The efficacy of nebulized salbutamol, hypertonic saline and salbutamol/hypertonic saline combination in moderate bronchiolitis.  Pulm Pharmacol Ther. 2011;24(6):633-637.PubMedGoogle ScholarCrossref
24.
Sarrell  EM, Tal  G, Witzling  M,  et al.  Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms.  Chest. 2002;122(6):2015-2020.PubMedGoogle ScholarCrossref
25.
Fernandes  RM, Plint  AC, Terwee  CB,  et al.  Validity of bronchiolitis outcome measures.  Pediatrics. 2015;135(6):e1399-e1408.PubMedGoogle ScholarCrossref
Original Investigation
August 7, 2017

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial

Author Affiliations
  • 1Service d'accueil des urgences pédiatriques, Necker-Enfants Malades University Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
  • 2Epidémiologie Clinique et Évaluation Économique Appliquées aux Populations Vulnérables, INSERM, Unité Mixte de Recherche 1123, Paris, France
  • 3Service d'accueil des urgences pédiatriques, Robert Debré University Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
  • 4Service de Pédiatrie, Antoine Béclère University Hospital, Assistance Publique–Hôpitaux de Paris, Clamart, France
  • 5Centre for Research in Epidemiology and Population Health, INSERM U1018, Villejuif, France
  • 6Service d'accueil des urgences pédiatriques, Toulouse University Hospital, Toulouse, France
  • 7Service d'accueil des urgences pédiatriques, Nantes University Hospital, Nantes, France
  • 8Service de Pédiatrie, Jean Verdier University Hospital, Assistance Publique–Hôpitaux de Paris, Bondy, France
  • 9Service d'accueil des urgences pédiatriques, Marseille Nord University Hospital, Assistance Publique–Hôpitaux de Marseille, Marseille, France
  • 10Service d'accueil des urgences pédiatriques, Lille University Hospital, Lille, France
  • 11Service de Pédiatrie, Caen University Hospital, Caen, France
  • 12Service de Pédiatrie, Ambroise Paré University Hospital, Assistance Publique–Hôpitaux de Paris, Boulogne-Billancourt, France
  • 13Service de Pédiatrie, Sud-Francilien Hospital, Corbeil-Essonnes, France
  • 14Service de médecine infantile, Nancy University Hospital, Vandoeuvre-Lès-Nancy, France
  • 15Service d'accueil des urgences pédiatriques, Creteil Intercommunal Hospital, Creteil, France
  • 16Service d'accueil des urgences pédiatriques, Rennes University Hospital, Rennes, France
  • 17Service de Pédiatrie, Brest University Hospital, Brest, France
  • 18Service d'accueil des urgences pédiatriques, Tours University Hospital, Tours, France
  • 19Service d'accueil des urgences pédiatriques, Rouen University Hospital, Rouen, France
  • 20Service de Pédiatrie, Fontainebleau Hospital, Fontainebleau, France
  • 21Service d'accueil des urgences pédiatriques, Lenval University Hospital, Nice, France
  • 22Service d'accueil des urgences pédiatriques, Limoges University Hospital, Limoges, France
  • 23Service d'accueil des urgences pédiatriques, Bicêtre University Hospital, Assistance Publique–Hôpitaux de Paris, Kremlin-Bicêtre, France
  • 24Service de Pédiatrie, André Mignot Hospital, Le Chesnay, France
  • 25Service de Pédiatrie, Laennec Hospital, Quimper, France
  • 26Service d'accueil des urgences pédiatriques, Mother Child University Hospital, Bron, France
  • 27Epidémiologie, Pharmacologie, Investigation Clinique, Information médicale, Mère-Enfant (EPICIME), Clinical Investigation Center, INSERM Clinical Investigation Center 1407, Bron, France
JAMA Pediatr. 2017;171(8):e171333. doi:10.1001/jamapediatrics.2017.1333
Key Points

Question  What is the effect of treatment with nebulized hypertonic saline, 3%, vs normal saline, 0.9%, on the admission rate among infants with acute moderate to severe bronchiolitis in the emergency department?

Findings  In this randomized clinical trial of 777 healthy infants, the hospital admission rate in the hypertonic saline group was 48.1% compared with 52.2% in the normal saline group. Mild adverse events, such as worsening of cough, occurred more frequently among children in the hypertonic saline group.

Meaning  Nebulized hypertonic saline treatment did not significantly reduce the hospital admission rate among infants with a first episode of acute bronchiolitis admitted to the pediatric emergency department.

Abstract

Importance  Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED).

Objective  To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis.

Design, Setting, and Participants  The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included.

Interventions  Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart.

Main Outcomes and Measures  Hospital admission rate in the 24 hours after enrollment.

Results  Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, –3.2%; 95% CI, –8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (–3.1 [3.2]) than in the NS group (–2.4 [3.3]) (adjusted difference, –0.7; 95% CI, –1.2 to –0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events.

Conclusions and Relevance  Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group.

Trial Registration  clinicaltrials.gov Identifier: NCT01777347

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