Search tips
Search criteria 


Logo of thoraxThoraxVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Thorax. 2005 September; 60(9): 740–746.
Published online 2005 July 29. doi:  10.1136/thx.2005.040444
PMCID: PMC1747524

Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis


Background: Current guidelines recommend the use of a combination of inhaled ß2 agonists and anticholinergics, particularly for patients with acute severe or life threatening asthma in the emergency setting. However, this statement is based on a relatively small number of randomised controlled trials and related systematic reviews. A review was undertaken to incorporate the more recent evidence available about the effectiveness of treatment with a combination of ß2 agonists and anticholinergics compared with ß2 agonists alone in the treatment of acute asthma.

Methods: A search was conducted of all randomised controlled trials published before April 2005.

Results: Data from 32 randomised controlled trials (n = 3611 subjects) showed significant reductions in hospital admissions in both children (RR = 0.73; 95% CI 0.63 to 0.85, p = 0.0001) and adults (RR = 0.68; 95% CI 0.53 to 0.86, p = 0.002) treated with inhaled anticholinergic agents. Combined treatment also produced a significant increase in spirometric parameters 60–120 minutes after the last treatment in both children (SMD = –0.54; 95% CI –0.28 to –0.81, p = 0.0001) and adults (SMD = –0.36; 95% CI –0.23 to –0.49, p = 0.00001).

Conclusions: This review strongly suggests that the addition of multiple doses of inhaled ipratropium bromide to ß2 agonists is indicated as the standard treatment in children, adolescents, and adults with moderate to severe exacerbations of asthma in the emergency setting.

Full Text

The Full Text of this article is available as a PDF (198K).

Supplementary Material


Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Rodrigo G, Rodrigo C, Burschtin O. A meta-analysis of the effects of ipratropium bromide in adults with acute asthma. Am J Med. 1999 Oct;107(4):363–370. [PubMed]
  • Stoodley RG, Aaron SD, Dales RE. The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials. Ann Emerg Med. 1999 Jul;34(1):8–18. [PubMed]
  • Plotnick LH, Ducharme FM. Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev. 2000;(4):CD000060–CD000060. [PubMed]
  • Rodrigo Gustavo J, Rodrigo Carlos. The role of anticholinergics in acute asthma treatment: an evidence-based evaluation. Chest. 2002 Jun;121(6):1977–1987. [PubMed]
  • Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1–12. [PubMed]
  • DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188. [PubMed]
  • Higgins Julian P T, Thompson Simon G, Deeks Jonathan J, Altman Douglas G. Measuring inconsistency in meta-analyses. BMJ. 2003 Sep 6;327(7414):557–560. [PMC free article] [PubMed]
  • Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep 13;315(7109):629–634. [PMC free article] [PubMed]
  • Beck R, Robertson C, Galdès-Sebaldt M, Levison H. Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. J Pediatr. 1985 Oct;107(4):605–608. [PubMed]
  • Cook JJ, Fergusson DM, Dawson KP. Ipratropium and fenoterol in the treatment of acute asthma. Pharmatherapeutica. 1985;4(6):383–386. [PubMed]
  • Reisman J, Galdes-Sebalt M, Kazim F, Canny G, Levison H. Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. J Allergy Clin Immunol. 1988 Jan;81(1):16–20. [PubMed]
  • Watson WT, Becker AB, Simons FE. Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma. J Allergy Clin Immunol. 1988 Dec;82(6):1012–1018. [PubMed]
  • Phanichyakarn P, Kraisarin C, Sasisakulporn C. Comparison of inhaled terbutaline and inhaled terbutaline plus ipratropium bromide in acute asthmatic children. Asian Pac J Allergy Immunol. 1990 Jun;8(1):45–48. [PubMed]
  • Schuh S, Johnson DW, Callahan S, Canny G, Levison H. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. J Pediatr. 1995 Apr;126(4):639–645. [PubMed]
  • Qureshi F, Zaritsky A, Lakkis H. Efficacy of nebulized ipratropium in severely asthmatic children. Ann Emerg Med. 1997 Feb;29(2):205–211. [PubMed]
  • Calvo GM, Calvo AM, Marín HF, Moya GJ. Is it useful to add an anticholinergic treatment to beta 2-adrenergic medication in acute asthma attack? J Investig Allergol Clin Immunol. 1998 Jan-Feb;8(1):30–34. [PubMed]
  • Ducharme FM, Davis GM. Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma. J Pediatr. 1998 Oct;133(4):479–485. [PubMed]
  • Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med. 1998 Oct 8;339(15):1030–1035. [PubMed]
  • Zorc JJ, Pusic MV, Ogborn CJ, Lebet R, Duggan AK. Ipratropium bromide added to asthma treatment in the pediatric emergency department. Pediatrics. 1999 Apr;103(4 Pt 1):748–752. [PubMed]
  • Benito Fernández J, Mintegui Raso S, Sánchez Echaniz J, Vázquez Ronco MA, Pijoan Zubizarreta JI. Eficacia de la administración precoz de bromuro de ipratropio nebulizado en niños con crisis asmática. An Esp Pediatr. 2000 Sep;53(3):217–222. [PubMed]
  • Sienra Monge JJ, Bermejo Guevara MA, del Río Navarro BE, Rosas Vargas MA, Reyes Ruiz NI. Grado y duración de la broncodilatación mediante la administración de un agonista beta 2 solo vs un agonista beta 2 más bromuro de ipratropio en niños con asma aguda. Rev Alerg Mex. 2000 Jan-Feb;47(1):26–29. [PubMed]
  • Timsit S, Sannier N, Bocquet N, Cojocaru B, Wille C, Boursiquot C, Garel D, Marcombes F, Chéron G. Apport du bromure d'ipratropium dans la prise en charge des crises d'asthme aux urgences. Arch Pediatr. 2002 Feb;9(2):117–125. [PubMed]
  • Sharma Anita, Madaan Arvind. Nebulized salbutamol vs salbutamol and ipratropium combination in asthma. Indian J Pediatr. 2004 Feb;71(2):121–124. [PubMed]
  • Bryant DH. Nebulized ipratropium bromide in the treatment of acute asthma. Chest. 1985 Jul;88(1):24–29. [PubMed]
  • Rebuck AS, Chapman KR, Abboud R, Pare PD, Kreisman H, Wolkove N, Vickerson F. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med. 1987 Jan;82(1):59–64. [PubMed]
  • Higgins RM, Stradling JR, Lane DJ. Should ipratropium bromide be added to beta-agonists in treatment of acute severe asthma? Chest. 1988 Oct;94(4):718–722. [PubMed]
  • O'Driscoll BR, Taylor RJ, Horsley MG, Chambers DK, Bernstein A. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet. 1989 Jun 24;1(8652):1418–1420. [PubMed]
  • Lee PC, Helsmoortel CM, Cohn SM, Fink MP. Are low tidal volumes safe? Chest. 1990 Feb;97(2):430–434. [PubMed]
  • Cydulka RK, Emerman CL. Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of asthma. Ann Emerg Med. 1994 Feb;23(2):270–274. [PubMed]
  • Karpel JP, Schacter EN, Fanta C, Levey D, Spiro P, Aldrich T, Menjoge SS, Witek TJ. A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma. Chest. 1996 Sep;110(3):611–616. [PubMed]
  • FitzGerald JM, Grunfeld A, Pare PD, Levy RD, Newhouse MT, Hodder R, Chapman KR. The clinical efficacy of combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma. Canadian Combivent Study Group. Chest. 1997 Feb;111(2):311–315. [PubMed]
  • Garrett JE, Town GI, Rodwell P, Kelly AM. Nebulized salbutamol with and without ipratropium bromide in the treatment of acute asthma. J Allergy Clin Immunol. 1997 Aug;100(2):165–170. [PubMed]
  • Lin RY, Pesola GR, Bakalchuk L, Morgan JP, Heyl GT, Freyberg CW, Cataquet D, Westfal RE. Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: a randomized clinical trial. Ann Emerg Med. 1998 Feb;31(2):208–213. [PubMed]
  • Kamei T, Fujita J, Okada H, Nakamura H, Kishimoto T, Momoi A, Kawaji K, Yoshinouchi T, Ueda N, Takahara J. Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by metered-dose inhaler with InspirEase to relieve acute asthma attack. J Asthma. 1999;36(1):67–75. [PubMed]
  • Weber EJ, Levitt MA, Covington JK, Gambrioli E. Effect of continuously nebulized ipratropium bromide plus albuterol on emergency department length of stay and hospital admission rates in patients with acute bronchospasm. A randomized, controlled trial. Chest. 1999 Apr;115(4):937–944. [PubMed]
  • Nakano Y, Enomoto N, Kawamoto A, Hirai R, Chida K. Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma. J Allergy Clin Immunol. 2000 Sep;106(3):472–478. [PubMed]
  • Rodrigo GJ, Rodrigo C. First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department. Am J Respir Crit Care Med. 2000 Jun;161(6):1862–1868. [PubMed]
  • Rodrigo G, Rodrigo C. Corticosteroids in the emergency department therapy of acute adult asthma: an evidence-based evaluation. Chest. 1999 Aug;116(2):285–295. [PubMed]
  • Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178–CD002178. [PubMed]
  • Santanello NC, Zhang J, Seidenberg B, Reiss TF, Barber BL. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J. 1999 Jul;14(1):23–27. [PubMed]
  • Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet. 1999 Nov 27;354(9193):1896–1900. [PubMed]
  • Que Loretta G, Liu Limin, Yan Yun, Whitehead Gregory S, Gavett Stephen H, Schwartz David A, Stamler Jonathan S. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005 Jun 10;308(5728):1618–1621. [PMC free article] [PubMed]

Articles from Thorax are provided here courtesy of BMJ Group