Acute Asthma in Adults: Do Anticholinergics Add Anything?
ABSTRACT & COMMENTARY
Synopsis: In initial management of acute severe asthma in adults, adding nebulized ipratropium bromide to an intensive treatment protocol including albuterol had no effect on short-term physiologic improvement or rates of hospital admission.
Source: McFadden ER, et al. Am J Med 1997;102:7-13.
A previous report by mcfadden et al (Am J Med 1995;99:651-661) documented the clinical effectiveness of an aggressive protocol for assessing and treating acute severe asthma in the ED. This study sought to determine whether adding ipratropium bromide to nebulized albuterol in the same protocol would further improve either airway function or hospital admission rate in similar patients. In addition to peak flow monitoring, the protocol includes initial treatment with 2.5 mg of nebulized albuterol every 20 minutes for the first hour. Intravenous aminophylline and cortico-steroids are added during the second hour if needed, and decisions to admit or discharge the patient are made according to fixed criteria after two hours of therapy.
In the present study, 123 patients (mean age, 34; mainly African-American females) presenting to the ED with acute asthma were treated according to the protocol as described above over a three-month period. Ipratropium bromide, 0.5 mg, was then added to the albuterol solution for the first and third doses in treating 131 patients (mean age, 38; similar demographics) during the next three months; nothing else was changed. Although the age difference in the patient groups was statistically significant (P < 0.01), their asthma attacks were of comparable severity as indicated by peak flow rate (mean, 205 L/min; 43% of predicted) and findings on physical examination.
There were no differences in rate of improvement in peak flow rate, length of stay in the ED, or rate of admission to the hospital (28% and 25% in ipratropium and no-ipratropium groups, respectively). Among patients requiring hospitalization, there was no difference in peak flow rate measured about seven hours after admission in the two groups. The authors conclude that anticholinergic agents such as ipratropium are not first-line treatments for acute asthma, and add no clinical benefit to an aggressive initial treatment regimen based on nebulized albuterol.
COMMENT BY DAVID J. PIERSON, MD
Clinicians who try to keep up with the literature on bronchodilator therapy used acutely for asthma or COPD are sometimes frustrated by the seemingly contradictory results of different studies. It seems clear that beta-agonist sympathomimetic drugs such as albuterol are the most effective bronchodilators for treating acute severe asthma. The confusion comes from studies examining the value of adding a second agent such as aminophylline or ipratropium to beta-agonist therapy. For both aminophylline and ipratropium, some studies conclude that they help, and others conclude that they do not help. Among the many variables in study design that may affect the results in all such studies, perhaps the greatest is the dosage regimen of beta-agonist used in treating the patients. A number of studies reporting additional benefit from a second drug have used suboptimal doses of the primary agent, and it remains to be seen whether such benefit would have occurred if appropriately aggressive therapy with the beta-agonist were employed.
This study does a good job of eliminating this last variable. As discussed in these pages when the previous report of this group’s ED asthma protocol was published (Crit Care Alert 1996;3:82-83), the dose and frequency of albuterol administration is appropriately aggressive and in keeping with the results of other studies. It may be that ipratropium would have shown some benefit if a more modest albuterol dose had been used. However, although no comment about adverse effects is made in the article, the higher albuterol doses employed have been shown numerous times to be safe and well-tolerated.
This study’s results may not be of much help, however, with respect to the management of acute severe asthma once patients are admitted to the ICU. McFadden et al assessed the effects of one or two doses of ipratropium given during a one-hour period. However, the onset of bronchodilator effect is much slower with ipratropium (60-90 minutes for peak effect vs 10-20 minutes with albuterol), and it may last longer after a given dose. Thus, the brief observation period used in this study may have precluded detection of a positive effect from ipra-tropium.
Another unknown in managing acute asthma is whether adult patients respond differently from children. The literature suggests that ipratropium may be more effective in pediatric asthma than in adult patients. My own clinical experience in managing adult asthmatics in the outpatient setting is that only a minority of patients benefit clinically from ipratropium (in contrast to the situation in COPD). Data on the efficacy of anticholinergic agents in the ICU management of status asthmaticus are generally lacking. It is common practice to add ipratropium to beta-agonist therapy when patients are sufficiently ill with acute asthma to be treated in an ICU, and the drug’s adverse effects in this setting are very few, but such practice cannot currently be backed up by much solid data.
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