Beta‐agonists with or without anti‐cholinergics in the treatment of acute childhood asthma?

Beta‐agonists with or without anti‐cholinergics in the treatment of acute childhood asthma?

Report by Andrew Munro, Specialist Registrar

Checked by Ian Maconochie, Paediatric A&E Consultant

Institution St Mary's Hospital, Paddington, UK

Abstract

A short cut review was carried out to establish whether adding inhaled anti‐cholinergics to beta‐agonists improves outcome in the treatment of acute childhood asthma. 148 papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper is tabulated. It is concluded that anti‐cholinergics reduce time to recovery and discharge and may reduce admissions for moderate to severe groups.

Clinical scenario

A seven year old boy with moderately well controlled asthma since his last admission 10 months ago presents to the emergency department with an acute exacerbation. You ask the nurse to administer salbutamol and ipratropium 5 mg and 0.25 mg as a nebuliser. She questions the value of adding an anti‐cholinergic, despite your theoretical knowledge that the mechanism of action of both drugs should be additive you are left wondering about the clinical evidence to support this.

Three‐part question

In [children with acute asthma who present to the Emergency Department] is [salbutamol and ipratropium better than salbutamol alone] at [producing a clinical improvement and reducing hospital stay]?

Search strategy

OVID Medline 1966 to March Week 4 2006 [(exp asthma/OR asthma mp) AND (exp albutarol/OR salbutamol.mp.) AND (exp atropine derivatives/OR exp ipratropium/).OR [*“Adrenergic beta‐Agonists”/AND *“Cholinergic Antagonists”/AND “Drug Therapy, Combination”/] LIMIT to Humans and English Language and BestBETs paediatric filter. OVID Embase 1980 to 2006 Week 12 [(exp asthma/OR asthma mp) AND (exp Salbutamol/or albutarol.mp.) AND (exp atropine derivative/OR exp ipratropium bromide/) OR [exp Beta Adrenergic Receptor Stimulating Agent/AND exp Cholinergic Receptor Blocking Agent/AND exp Drug Combination/] AND (exp Emergency Ward/). LIMIT to Human and English Language AND (infant <to one year> or child <unspecified age> or preschool child <1 to 6 years> or school child <7 to 12 years> or adolescent <13 to 17 years>). The Cochrane Library 2006 Issue 1 [Ipratropium [MeSH] AND Albutarol [MeSH] AND [Child [MeSH] 40 articles.

Search outcome

Altogether148 articles were found on all three databases of which one presented the best evidence. This is shown in table 1.

Table 1.

Author, date and country	Patient group	Study type	Outcomes	Key results	Study weaknesses
Rodrigo GJ and Castro‐Rodriuez JA, 2005, Uruguay and Chile	16 RCTs	Meta‐analysis	NNT to prevent one admission (1786 children in 10 trials)	13	Significant heterogeneity in spirometric analysis
			SMD of Improvement inpooled spirometric parameters	−0.54 (−0.28–−0.81) p<0.0001

Comment(s)

Other outcomes including pulse, blood pressure, and oxygen saturation showed no significant differences. Reduced admission rates can only be considered a gross measure of combined drug efficacy. Reproducible results may be more likely given the following: 1. An agreed method of assessing the severity of asthma; 2. An increased use of peak flow meters among the background population of known asthmatics; 3. Delineation of clinical pathways for treatment, including admission criteria. Three well designed papers and a Cochrane review showed variably modest benefits in adding inhaled anti‐cholinergics to â2‐agonist in the standard treatment of moderate to severe asthma in children. There is little to suggest that the side effects of adding ipratropium that would preclude its use.

Clinical bottom line

Adding inhaled anti‐cholinergics to beta 2‐agonists in the treatment of acute asthma in children presenting to the Emergency Department reduces time to recovery and discharge and may reduce admissions for moderate to severe groups.