Ipratropium Bromide in Acute Asthma: Small Beneficial Effects?

Abstract

We read with great interest the article by Lanes and colleagues1Lanes SF Garrett JE Wentworth III, CE et al.The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials.Chest. 1998; 114: 365-372Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar regarding the effect of adding ipratropium bromide (IB) to salbutamol in treating acute asthma (August 1998). In this paper, the authors conducted a pooled analysis of three previously published randomized double-blind clinical trials. The studies enrolled 1,064 patients with acute asthma. The authors found that patients receiving IB and salbutamol therapy had greater improvements in FEV1 on average than patients receiving salbutamol alone, but this difference was small (< 10%). Also, they found that the small improvement in lung function was associated with a nonsignificant reduced risk of hospitalization (relative risk [RR], 0.80; 95% confidence interval, 0.61 to 1.06). In an unpublished meta-analysis about IB in acute adult asthma (nine studies, 1,416 subjects [G. Rodrigo, MD, C. Rodrigo, MD; unpublished data; 1998]), we obtained a pooled effect size equivalent to 10.3% (4.3 to 16.3%) greater in pulmonary function in the combined group compared with the control group (effect size, 0.13; range, 0.03 to 0.23). Additionally, this meta-analysis revealed that the addition of IB to β2-agonists significantly reduced the admission rate of 36% (odds ratio = 0.64, 0.45 to 0.92). However, we must emphasize that all of these beneficial effects have been obtained with the utilization of “unrealistic” therapeutic protocols consisting of small doses of IB (eg, in the pooled analysis, a combination of nebulized 2.5 mg salbutamol plus 0.5 mg IB administered only at baseline, and in the US study, at 45 min). Nevertheless, there is substantial evidence that patients with acute asthma respond to increasing doses of bronchodilators,2Rodrigo C Rodrigo G Therapeutic response patterns to high and cumulative doses of salbutamol in acute severe asthma.Chest. 1998; 113: 593-598Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar and that this thought can be applied to IB. In fact, in a preliminary study, we have shown an important additional therapeutic effect (25% increase in peak expiratory flow rate) from adding IB to salbutamol, when both drugs are administered in high and cumulative doses (0.24 mg of IB every 30 min) through metered-dose inhaler and spacer,3Rodrigo C Rodrigo G Treatment of acute asthma: administration of high doses of salbutamol and ipratropium bromide delivered by metered dose inhaler with a spacer (Volumatic) [abstract].Am J Respir Crit Care Med. 1996; 153: A60Google Scholar with minimal adverse effects. Finally, a recently published systematic review4Plotnick LH Ducharme FM Should inhaled anticholinergics be added to β2-agonists for treating acute childhood and adolescent asthma? A systematic review.BMJ. 1998; 317: 971-977Crossref PubMed Scopus (87) Google Scholar about the use of anticholinergics added toβ 2 agonists for treating acute childhood and adolescent asthma indicates that a multiple dose anticholinergic protocol reduces the hospital admission rate by 30% (RR, 0.72; 95% confidence interval 0.53 to 0.99) and improves pulmonary function significantly (effect size, −0.66; range, −0.95 to −0.37). In conclusion, data highlight the need for new and more “realistic” clinical trials examining the effect of higher and cumulative doses of IB.