title: Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma.
abstract: BACKGROUND
  Inhaled beta-agonist therapy is central to the management of acute asthma. This review evaluates the benefit of an additional use of intravenous beta(2)-agonist agents.
  
  
  OBJECTIVE
  To determine the benefit of adding intravenous (IV) beta(2)-agonists to inhaled beta(2)-agonist therapy for acute asthma treated in the emergency department.
  
  
  METHODS
  Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register which is a compilation of systematic searches of MEDLINE, EMBASE, CINAHL, and CENTRAL as well as handsearching of 20 respiratory journals. Bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. The search was performed in September 2012.
  
  
  METHODS
  Only RCTs were considered for inclusion. Studies were included if patients presented to the emergency department with acute asthma and were treated with IV beta(2)-agonists with inhaled beta(2)-agonist therapy and existing standard treatments versus inhaled beta(2)-agonists and existing standard treatments.
  
  
  METHODS
  Two review authors independently extracted data and confirmed their findings with corresponding authors of trials. We obtained missing data from authors or calculated from data present in the papers. We used fixed-effect model for odds ratios (OR) and for mean differences (MD) we used both fixed-effect and random-effects models and reported 95% confidence intervals (CI).
  
  
  RESULTS
  From 109 potentially relevant studies only three (104 patients) met our inclusion criteria: Bogie 2007 (46 children), Browne 1997 (29 children) and Nowak 2010 (29 adults). Bogie 2007 investigated the addition of intravenous terbutaline to high dose nebulised albuterol in children with acute severe asthma, requiring intensive care unit (ICU) admission. Browne 1997 investigated the benefit of adding intravenous salbutamol to inhaled salbutamol in children with acute severe asthma in the emergency department. Nowak 2010 investigated addition of IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) among adults, and was reported as a conference abstract only.There was no significant advantage (OR 0.29; 95%CI 0.06 to 1.38, one trial, 29 adults) for adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) with regard to hospitalisation rates.Various outcome indicators for the length of stay were reported among the trials. Browne 1997 reported a significantly shorter recovery time (in terms of cessation of 30 minute salbutamol) for children in the IV salbutamol with inhaled salbutamol group (four hours) versus the 11.1 hours for the inhaled salbutamol group (P = 0.03). Time to cessation of hourly nebuliser was also significantly shorter (P = 0.02) for the IV plus inhaled salbutamol group (11.5 hours versus 21.2 hours), and they were ready for emergency patient discharge on average 9.7 hours earlier than the inhaled salbutamol group (P < 0.05). In a paediatric ICU study Bogie 2007 reported no significant advantage in length of paediatric ICU admission (hours) for adding IV terbutaline to nebulised albuterol (MD -12.95, 95% CI: -38.74, 12.84).Browne 1997 reported there were only six out of 14 children with a pulmonary index score above six in the IV plus inhaled salbutamol group at two hours compared with 14 of the 15 in the inhaled salbutamol group (P = 0.02)In Browne 1997 there was a higher proportion of tremor in the IV plus inhaled salbutamol group than in the inhaled salbutamol group (P < 0.02). Nowak 2010 did not report any statistically significant adverse effects associated with adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids). Troponin levels were elevated in three children in the IV terbutaline + nebulised albuterol group at 12 and 24 hours in Bogie 2007
  
  
  CONCLUSIONS
  There is very limited evidence from one study (Browne 1997) to support the use of IV beta(2)-agonists in children with severe acute asthma with respect to shorter recovery time, and similarly there is limited evidence (again from one study Browne 1997) suggesting benefit with regard to pulmonary index scores; however this advantage needs to be considered carefully in relation to the increased side effects associated with IV beta(2)-agonists. We identified no significant benefits for adults with severe acute asthma. Until more, adequately powered, high quality clinical trials in this area are conducted it is not possible to form a robust evaluation of the addition of IV beta(2)-agonists in children or adults with severe acute asthma.
authors.affiliation: Department of Emergency Medicine and Community Health and Epidemiology, Emergency Health Services, Nova Scotia, Canada. Andrew.Travers@gov.ns.ca.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Travers
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Milan
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Jones
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.forename: Brian H
authors.initials: BH
authors.lastname: Rowe
mesh_terms: D000081:Acetamides / Q000008:administration & dosage; D000208:Acute Disease; D000280:Administration, Inhalation; D061605:Administration, Intravenous; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D004359:Drug Therapy, Combination / Q000379:methods; D004630:Emergencies; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage; D009281:Naphthalenes / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013726:Terbutaline / Q000008:administration & dosage
chemical_list: D000081:Acetamides; D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D009281:Naphthalenes; C425888:bedoradrine; D009241:Ipratropium; D013726:Terbutaline; D000420:Albuterol