COCHRANE COMMENTARIES

Combined anti-cholinergic and short-acting β-agonist therapyreduces hospital admissions for acute asthma

What Is This Review About?

In the emergency department (ED), when treating individualsaged 18 months to 18 years with acute moderate and severeasthma, does the addition of inhaled anticholinergic plus short-acting β-agonists (SABAs) have significant benefits or harmscompared with SABAs alone?

What Are the Findings?

In patients with moderate or severe asthma, groups treated withcombination anticholinergic/SABA therapy had a reduced hos-pital admission rate compared with groups treated with SABAalone (Fig. 1)1. The number needed to treat for additional ben-eficial effect was 16 (95% confidence interval (12 to 29), withan anticipated 27% reduction in the risk of hospital admission.

What Are the Findings Based On?

Fifteen trials (n = 2497) that, through stratifying by asthmaseverity when possible, generated 19 comparisons with no sta-tistical heterogeneity (I2 = 0%) for the primary outcome ofreduction in hospital admission. Nine trials were at a low risk ofbias and the evidence for hospital admission was high quality.The majority of studies were in pre-school- and school-agedchildren. Three studies also included a small proportion ofinfants less than 18 months of age, and there was no evidencethat inclusion of these infants with wheezy episodes affected theresults. Clinical heterogeneity existed with regard to methods ofdelivery (majority used nebulisers rather than inhalationdevice), doses and dosage protocols. The trials’ protocols admin-istered doses of ipratropium between 250 mcg and 500 mcgusually via a nebuliser device, with all but one using two orthree doses over 30 to 90 min. The results of analysis to assessthe effect of intensity of regime were inconclusive. The biggesttreatment effect was realised with children with severe asthma,an intermediate response with moderate asthma and no signifi-cant effect in mild asthma, with effect independent of steroidadministration.

Addition of anticholinergics was also effective for improvinglung function, 120-min clinical score, 60-min oxygen saturationand reducing the need for repeat use of bronchodilators prior todischarge from ED. The combination of anticholinergic andSABAs was also associated with a statistically significant 30%and 39% reduced risk of nausea and tremor, respectively. Therewas no significant difference in relapse rate reported.

Implications for Practice

• Combined ipratropium/SABA therapy is a better first-linetherapy for children with acute moderate and severe asthmaover SABA alone.

• SABA monotherapy is associated with higher risk of hospitaladmissions and adverse events.

• Currently, a multiple fixed dosage protocol over 60 to 90 minis recommended, while further evidence about specific dosageregimens emerges.

Clinical Perspective

The combination of anticholinergics with SABAs has beenthought to yield enhanced and prolonged bronchodilation andprovide more effective treatment for acute asthma exacerba-tions.1,2 Current guidelines recommend the administration ofanticholinergic in poorly responsive acute asthma, and there hasbeen inconsistent use of inhaled anticholinergic/SABA therapyin acute moderate/severe asthma which includes variations forthe age that combined treatment is offered as well as dosage andtimings of drug administration. There has also been an impres-sion that inhaled anticholinergic therapy has a therapeutic rolein all severities of asthma, in light of its safety profile andpotential benefits.

This Cochrane review supports the use of combinedanticholinergic/SABA therapy as a first-line dual therapy in theED and clarifies that there is no proven effectiveness for com-bined therapy in mild asthma. Griffiths et al. state that the needremains for randomised controlled trials to specifically addressthe optimisation of anti-cholinergic/SABA therapy (dosage,intensity and delivery device) and identification of the choicetarget population (severity of asthma, age). Further studiesshould also explore this question in both the primary care andpre-hospital setting.

While details about ideal age and severity of asthma for com-bined therapy as well as dosage, delivery, suitable settingsemerge, the use of combined anticholinergic/SABA therapy inboth acute moderate and severe asthma for individuals aged 18months to 18 years can be recommended as evidence-based bestpractice in treatment protocols and guidelines.

Correspondence: Dr Michael Joseph Barrett, Clinical Fellow in PaediatricEmergency Medicine, Royal Children’s Hospital, Melbourne; ResearchFellow and PhD Candidate, Paediatric Emergency Research Unit, NationalChildren’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland.email: Michael.Barrett@rch.org.au or mjjbarrett@hotmail.com

Edited by Katrina Williams (Katrina.Williams@rch.org.au)Written by Michael Joseph Barrett (Michael.Barrett@rch.org.au)

Conflict of interest: None Declared

Accepted for publication 5 May 2014.

doi:10.1111/jpc.12669

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Journal of Paediatrics and Child Health 50 (2014) 577–578© 2014 The AuthorJournal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

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References

1 Griffiths B, Ducharme FM. Combined inhaled anticholinergics andshort-acting beta2-agonists for initial treatment of acute asthma inchildren. Cochrane Database Syst. Rev. 2013; (8): Art. No.: CD000060,doi: 10.1002/14651858.CD000060.pub2.

2 Griffiths B, Ducharme FM. Combined inhaled anticholinergics andshort-acting beta2-agonists for initial treatment of acute asthmain children. Paediatr. Respir. Rev. 2013; 14: 234–5.Epub 2013/09/28.

Dr Michael Joseph BarrettClinical Fellow in Paediatric Emergency Medicine

Royal Children’s HospitalMelbourne and Research Fellow and Phd Candidate

Paediatric Emergency Research Unit,National Children’s Research Centre,

Our Lady’s Children’s HospitalDublin, Ireland

Fig. 1 Anti-cholinergic and short-acting β-agonists versus short-acting beta2 agonists alone (all protocols) for risk of hospital admission. BI, Boehringer

Ingelheim Pharmaceutical, 2009; CI, confidence interval; df, degrees of freedom; M-H, Mantel Haenszel; SABA, short-acting β-agonist.

MJ BarrettReduction of admissions for acute asthma

Journal of Paediatrics and Child Health 50 (2014) 577–578© 2014 The Author

Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

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