Intervention Review

You have free access to this content

Nebulized epinephrine for croup in children

  1. Candice Bjornson1,*,
  2. Kelly Russell2,
  3. Ben Vandermeer3,
  4. Terry P Klassen4,
  5. David W Johnson1

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 10 OCT 2013

Assessed as up-to-date: 3 JUL 2013

DOI: 10.1002/14651858.CD006619.pub3

How to Cite

Bjornson C, Russell K, Vandermeer B, Klassen TP, Johnson DW. Nebulized epinephrine for croup in children. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD006619. DOI: 10.1002/14651858.CD006619.pub3.

Author Information

  1. 1

    Faculty of Medicine, University of Calgary, Alberta Children's Hospital, Department of Pediatrics, Calgary, Alberta, Canada

  2. 2

    University of Manitoba, Department of Pediatrics and Child Health, Winnipeg, Manitoba, Canada

  3. 3

    University of Alberta, Department of Pediatrics, Edmonton, Alberta, Canada

  4. 4

    Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada

*Candice Bjornson, Department of Pediatrics, Faculty of Medicine, University of Calgary, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 10 OCT 2013



References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Corkey 1981 {published data only}
  • Corkey C, Barker G, Edmonds J, Mok P, Newth C. Radiographic tracheal diameter measurements in acute infectious croup: an objective scoring system. Critical Care Medicine 1981;9:587-90.
Fernandez 1993 {published data only}
  • Fernandez MA, Gonzalez SE, Etxefarria RI, Urcelay EI, Diez AM, Ciriza WM, et al. Randomized double-blind study of treatment of croup with adrenaline and/or dexamethasone in children. Anales Espandoles de Pediatria 1993;38(1):29-32.
Fogel 1982 {published data only}
  • Fogel JM, Berg IJ, Gerber MA, Sherter CB. Racemic epinephrine in the treatment of croup: nebulization alone versus nebulization with intermittent positive pressure breathing. Journal of Pediatrics 1982;101(6):1028-31.
Gardner 1973 {published data only}
  • Gardner HG, Powell KR, Roden VJ, Cherry JD. The evaluation of racemic epinephrine in the treatment of infectious croup. Pediatrics 1973;52(1):52-5.
Kristjansson 1994 {published data only}
  • Kristjansson S, Berg-Kelly K, Winso E. Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects. Acta Paediatrica 1994;83(11):1156-60.
Kuusela 1988 {published data only}
Waisman 1992 {published data only}
  • Waisman Y, Klein BL, Boenning DA, Young GM, Chamberlain JM, O'Donnel R, et al. Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatrics 1992;89(2):302-6.
Westley 1978 {published data only}
  • Westley C, Ross C, Brooks J. Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study. American Journal of Diseases of Children 1978;132:484-7.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Anonymous 1996 {published data only}
  • Anonymous. Inhaled budesonide and adrenaline for croup. Drug and Therapeutics Bulletin 1996;34(3):22-4.
Banac 2005 {published data only}
  • Banac S, Palcieevski G, Roziemanici V, Ahel V. Administration of nebulized L-epinephrine in children with croup. Medicina 2005;41(3):242-5.
Bass 1978 {published data only}
Bass 1980 {published data only}
Beaudry 1983 {published data only}
Brown 2002 {published data only}
  • Brown J. The management of croup. British Medical Bulletin 2002;61:189-202.
Celis 1978 {published data only}
  • Celis PA, Frias VJ, Aragon JG, Eternod GJ, Serafin FJ. Evaluation of racemic epinephrine with intermittent positive pressure in the treatment of acute infections laryngotracheitis. Boletin Medico del Hospital Infantile de Mexico 1978;35(4):59-67.
Cherry 1974 {published data only}
Choi 1999 {published data only}
  • Choi B, Song K, Shim J, Hong S. Prospective randomized study comparing L-epinephrine and budesonide aerosols in the treatment of moderate to severe croup. Journal of the Korean Pediatric Society 1999;42(1):40-6.
Cressman 1994 {published data only}
Cristaldi 2001 {published data only}
  • Cristaldi A, Villani A, Bifano M, Cavaliere GF, Cristaldi S, Turbacci M, et al. [Osturzione acuta delle alte vie respiratorie]. Rivista Italiana Di Pediatria 2001;27(4):462-5.
Cronin 1996 {published data only}
  • Cronin M, Diedericks R. Steroids in the management of croup - nebulized adrenaline is also useful. BMJ 1996;312(7029):510.
Danen 2011 {published data only}
  • Danen R, Van Der Wouden H, Bindels P. Role of corticosteroids in pseudo-croup. Huisarts en Wetenschap 2011;54(4):204-8.
Dardick 1974 {published data only}
  • Dardick KR. Racemic epinephrine in croup. Pediatrics 1974;53(2):290.
da Silva 2012 {published data only}
  • da Silva PSL, Fonseca MCM, Iglesias SBO, Junior EL, de Aguiar VE, do Carvalho WB. Nebulized 0.5, 2.5 and 5 ml L-epinephrine for post-extubation stridor in children: a prospective, randomized, double-blind clinical trial. Intensive Care Medicine 2012;38(2):286-93.
de Benedictis 2012 {published data only}
Dunman 2005 {published data only}
Ellis 1974 {published data only}
  • Ellis EF, Taylor JC, Lefkowit MS. Racemic epinephrine in croup (continued). Pediatrics 1974;53(2):291-2.
Fitzgerald 1996 {published data only}
  • Fitzgerald D, Mellis C, Johnson M, Allen H, Cooper P, Asperen P. Nebulized budesonide is as effective as adrenaline in moderately severe croup. Pediatrics 1996;97(5):722-5.
Fogel 1983 {published data only}
  • Fogel JM, Berg IJ, Gerber MA, Sherter CB. Efficacy in racemic epinephrine in croup - reply. Journal of Pediatrics 1983;103(4):662.
Frazier 2010 {published data only}
Ghosh 2001 {published data only}
  • Ghosh A, Morton R. Nebulized epinephrine or corticosteroids in croup. Emergency Medicine Journal 2001;18(2):119.
Gilligan 2005 {published data only}
  • Gilligan P, Shepherd M, Lumsden G, Law H, Brenchley J, Kitching G, et al. SOCRATES 4 (synopsis of Cochrane reviews applicable to emergency services). Emergency Medicine Journal 2005;22(2):126-7.
Gonzalez 1984 {published data only}
Heisinge 1974 {published data only}
  • Heisinge DH. Epinephrine in croup. Pediatrics 1974;53(2):290.
Jones 1996 {published data only}
Klassen 1997 {published data only}
Kline-Krammes 2012 {published data only}
  • Kline-Krammes S, Reed C, Giuliano JS Jr, Schwartz HP,  Forbes M,  Pope J, et al. Heliox in children with croup: a strategy to hasten improvement. Air Medical Journal 2012;31(3):131-7.
Koren 1983 {published data only}
  • Koren G. Efficacy of racemic epinephrine in croup. Journal of Pediatrics 1983;103(4):661.
Kunkel 1996 {published data only}
  • Kunkle NC, Baker MD. Use of racemic epinephrine, dexamethasone, and mist in the outpatient management of croup. Pediatric Emergency Care 1996;12(3):156-9.
Ledwith 1995 {published data only}
  • Ledwith CA, Shea LM, Mauro RD. Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. Annals of Emergency Medicine 1995;25(3):331-7.
Lenney 1978 {published data only}
  • Lenney W, Milner AD. Treatment of acute viral croup. Archives of Disease in Childhood 1978;53(9):704-6.
Loriette 1997 {published data only}
  • Loriette Y, Poirier V, Labbel A. Acute laryngitis [Laryngites aiguës]. Revue Internationale de Pediatrie 1997;278:10-2.
Niggermann 1995 {published data only}
  • Niggerman B, Wahn U. Micronephrin, adrenaline medihaler aerosol and the use of nebulized steroids for laryngitis. Monatsschrift Kinderheilkunde 1995;143(12):1259-60.
Osmond 2002 {published data only}
  • Osmond M. Croup. Clinical Evidence 2002;8:319-29.
Pitluk 2011 {published data only}
Preutthipan 2005 {published data only}
  • Preutthipan A, Poomthavorn P, Sumanapisan A, Chinrat B, Thasuntia S, Plitponkarnpim A, et al. A prospective, randomized double-blind study in children comparing two doses of nebulized L-epinephrine in postintubation croup. Journal of the Medical Association of Thailand 2005;88(4):508-12.
Remington 1986 {published data only}
Rygnestad 2001 {published data only}
  • Rygnestad T, Skogvoll E. Treatment of pseudocroup with racemic adrenaline. Tidsskrift For Den Norske Laegeforening 2001;12(10):1263-4.
Singer 1976 {published data only}
  • Singer OP, Wilson WJ. Laryngotracheobronchitis - 2 years experience with racemic epinephrine. Canadian Medical Association Journal 1976;115(2):132-4.
Skolnik 1989 {published data only}
  • Skolnik NS. Treatment of croup. A critical review. American Journal of Disease of Children 1989;143(9):1045-9.
Steele 1998 {published data only}
  • Steele DW, Santucci KA, Wright RO, Natarajan R, McQuillen KK, Jay GD. Pulsus paradoxus: an objective measure of severity in croup. American Journal of Respiratory and Critical Care Medicine 1998;157:331-4.
Taussig 1975 {published data only}
  • Taussig L, Castro O, Beaudry P, Fox W, Bureau M. Treatment of laryngotracheobronchitis (croup): use of intermittent positive-pressure breathing and racemic epinephrine. American Journal of Diseases of Children 1975;129:790-3.
Taussig 1976 {published data only}
Thomas 1998 {published data only}
Thompson 1974 {published data only}
Vorwerk 2010 {published data only}
Weber 2001 {published data only}
  • Weber JE, Chudnofsky CR, Younger JG, Larkin GL, Boczar M, Wilkerson MD, et al. A randomized comparison of helium-oxygen mixture (Heliox) and racemic epinephrine for the treatment of moderate to severe croup. Pediatrics 2001;107(6):E96.
Zach 1981 {published data only}
  • Zach M. Simple nebulization of racemic epinephrine in the treatment of acute laryngitis (croup). Monatsschrift Kinderheilkunde 1981;129(3):168-70.
Zoorob 2011 {published data only}

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Adair 1971
  • Adair J, Ring W, Jordan W, Elwyn R. Ten-year experience with IPPB in the treatment of acute laryngotracheobronchitis. Anesthesia and Analgesia 1971;50(4):649-55.
Begg 1994
Bourchier 1984
  • Bourchier D, Dawson K, Fergusson D. Humidification in viral croup: a controlled trial. Australian Paediatric Journal 1984;20:289-91.
Butte 1999
Cho 1996
  • Cho MK, Bero LA. The quality of drug studies published in symposium proceedings. Annals of Internal Medicine 1996;124(5):485-9.
Cohen 1988
  • Cohen J. Statistical Power Analysis for the Behavioral Science. 2nd Edition. New York: Academic Press, 1988.
Davis 1993
  • Davis, Cooper D, Mitchell I. The measurement of thoraco-abdominal asynchrony in infants with severe laryngotracheobronchitis. Chest 1993;103:1842-8.
Denny 1983
  • Denny F, Murphy T, Clyde W, Collier A, Henderson F. Croup: an 11-year study in a pediatric practice. Pediatrics 1983;71(6):871-6.
Dobrovoljac 2012
  • Dobrovoljac M, Geelhoed GC. How fast does oral dexamethasone work in mild to moderately severe croup? A randomized double-blinded clinical trial. Emergency Medicine Australasia 2012;24(1):79-85. [10.1111/j.1742-6723.2011.01475.x. Epub 2011 Sep 4]
Downes 1975
  • Downes J, Raphael R. Pediatric intensive care. Anesthesiology 1975;43:238-50.
Egger 1997
  • Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315(7109):629-34.
Fanconi 1990
  • Fanconi S, Burger R, Maurer H, Uehlinger J, Ghelfi D, Muhlemann C. Transcutaneous carbon dioxide pressure for monitoring patients with severe croup. Journal of Pediatrics 1990;117:701-5.
Follman 1992
Geelhoed 1995
  • Geelhoed G, Macdonald W. Oral and inhaled steroids in croup: a randomized placebo-controlled trial. Pediatric Pulmonology 1995;20:355-61.
Godden 1997
  • Godden CW, Campbel MJ, Hussey M, Cogswell JJ. Double-blind placebo controlled trial of nebulised budesonide for croup. Archives of Disease in Childhood 1997;76:155-8.
Higgins 2002
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from 2011.
Husby 1993
  • Husby S, Agertoft L, Mortensen S, Pedersen D. Treatment of croup with nebulised steroid (budesonide): a double blind, placebo-controlled study. Archives of Disease in Childhood 1993;68:352-5.
Johnson 1998
  • Johnson D, Jacobson S, Edney P, Hadfield P, Mundy M, Schuh S. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. New England Journal of Medicine 1998;339(8):498-503.
Johnson 2001
  • Johnson D, Williamson J. Croup: duration of symptoms and impact on family functioning. Poster presentation. Pediatric Research 2001;49:83A.
Johnson 2003
Johnson 2005
  • Johnson D. Croup. Clinical Evidence 2005;14:310-27.
Kaditis 1998
Kairys 1989
  • Kairys S, Olmstead EM, O'Connor G. Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics 1989;83(5):683-93.
Klassen 1994
Klassen 1995
  • Klassen T, Rowe P. The croup score as an evaluative instrument in clinical trials [abstract]. Archives of Pediatrics & Adolescent Medicine 1995;149:60.
Klassen 1999
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Available from Chichester, UK: Wiley-Blackwell, 2011.
Leipzig 1979
Marx 1997
  • Marx A, Torok TJ, Holman RC, Clarke MJ, Anderson LJ. Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. Journal of Infectious Diseases 1997;176(6):1423-7.
Massicotte 1973
  • Massicotte P, Tetreault L. Evaluation of methyl-prednisolone in the treatment of acute laryngitis in children [Evaluation de la methyl-prednisolone dans le traitement des laryngites aigues de l'enfant.]. L'union Medicale du Canada 1973;102:2064-72.
Moore 2007
Neto 2002
Russell 2011
Schulz 1995
  • Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12.
Scolnik 2006
  • Scolnik D, Coates AL, Stephens D, Da Silva Z, Lavine E, Schuh S. Controlled delivery of high vs low humidity vs mist therapy for croup in emergency departments: a randomized controlled trial. JAMA 2006;295(11):1274-80.
Tibballs 1992
  • Tibballs J, Shann F, Landau L. Placebo-controlled trial of prednisolone in children intubated with croup. Lancet 1992;340(8822):745-8.
von Muhlendahl 1982
Westfall 2009
  • Westfall TC, Westfall DP, Brunton LL, Lazo JS, Parker KL. Chapter 10. Adrenergic agonists and antagonists. In: Goodman, Gilman editor(s). The Pharmacological Basis of Therapeutics. McGraw Hill Companies, 2009.

References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Bjornson 2011