Severe Exacerbations of COPO and Asthma* Incremental Benefit of Adding Ipratropium to Usual Therapy David M. 1btrick, M.D.;t Robert E. Dales, M.D., M.Sc., F.C.C.E;t Rfpn M. Stark, M.Sc.;§ Ginette Laliberte, R.R.7:;1I and Garth Dickinson, M. D. 'If Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the sbort- and longterm management of chronic obstructive lung disease and asthma. We performed a randomized, double-blind trial to assess the incremental bene6t over 24 hours of adding ipratropium vs placebo to a standardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma. Sixty-eight subjects received nebulized salbutamol, intravenous methylprednisolone, intravenous aminophylline, and antibiotics andwere randomized to receive either 80 f.Lg of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment (6 to 8 times per day). Among the 50 patients who completed the study, there were DO signi6cant differences between ipratropium and placebo
groups with respect to baseline FEV., FVC, and PaCO•• The improvement of FEV. from baseliDe to 14 hours was 294(SD = 568) mI in the iprairopium group vs 393(SD 622) ml in placebo group. Adjusting FEV. by age, gender, and smoking did not signi6cantly alter the findings. Those with an admission diagnosis of asthma showed larger !4 hour FEV. responses (487 mIin iprairopium vs SOl mI in placebo) than those with COPD (149 mI ipratropium vs 102 mI in placebo). However, within these two strata, there were DO signi6cant differences in FEV I improvement between ipratropium and placebo groups. 'I1Us study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 14 hours in order to reduce the cost and complexity of (Chat 1990; 98:295-97) therapy.
introduction of ipratropium bromide, a quarT hetenary ammonium atropine analogue with mini-
either concentrated on early response to the first few doses of bronchodilator or did not systematically take into account the use of other active agents. A combination ofa belat-agonist, corticosteroid and aminophylline is often used to treat severe exacerbations of COPD and asthma. The present study was undertaken to assess the incremental benefit ofadding ipratropium to a standardized regimen of this commonly used multidrug therapy: Since prior studies have only examined response to initial doses of ipratropium, and since corticosteroids have no significant immediate effect, we chose to measure FEV1 improvement at 24 hours to determine whether or not there was any benefit outside the very early treatment period.
mal systemic side effects, has brought new life to the centuries-old concept of using anticholinergic agents in the treatment ofrespiratory disease. Evidence from many clinical trials suggests that in stable asthma, a betas-agonist is a better individual drug than ipratropium.v" but there may be additional benefit to using the two drugs in combination. In the treatment of stable COPD (chronic bronchitis or emphysema), ipratropium may be the better individual agent,2.6.7 and again, additional benefit may be seen in combination with a betas-agonist. Indeed, in those with emphysema, all achievable bronchodilation might be achieved with ipratropium alone." In status asthmaticus, ipratropium is generally considered to be inferior to betaj-agonists as an individual agent but is useful in combination with them. 2.8-12 In acute exacerbations of COPD, the addition of ipratropium to beta agonists has not been shown to have any consistent benefit. 11.12 Those studies that examined this question, however,
*From the Ottawa General Hospital, University of Ottawa, Canada. t Resident in Internal Medicine. iAssistant Professor of Medicine and Epidemiology. §Clinical Research Coordinator. IlRespiratoryTechnologist. 'Assistant Professor of Medicine and Family Medicine. Supported by the Ontario Thoracic Society, Canada. Manuscript received May 12, 1989; revision accepted January 17, 1990.
=
METHODS
Eligible subjects were those with all four of the following criteria: (1) presented to the Ottawa General Hospital Emergency Department because of dyspnea, cough, wheeze or chest discomfort; (2) hadair80w obstruction de6ned as maximal forced expiratory volume in one second (FEV J
groups with respect to baseline FEV., FVC, and PaCO•• The improvement of FEV. from baseliDe to 14 hours was 294(SD = 568) mI in the iprairopium group vs 393(SD 622) ml in placebo group. Adjusting FEV. by age, gender, and smoking did not signi6cantly alter the findings. Those with an admission diagnosis of asthma showed larger !4 hour FEV. responses (487 mIin iprairopium vs SOl mI in placebo) than those with COPD (149 mI ipratropium vs 102 mI in placebo). However, within these two strata, there were DO signi6cant differences in FEV I improvement between ipratropium and placebo groups. 'I1Us study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 14 hours in order to reduce the cost and complexity of (Chat 1990; 98:295-97) therapy.
introduction of ipratropium bromide, a quarT hetenary ammonium atropine analogue with mini-
either concentrated on early response to the first few doses of bronchodilator or did not systematically take into account the use of other active agents. A combination ofa belat-agonist, corticosteroid and aminophylline is often used to treat severe exacerbations of COPD and asthma. The present study was undertaken to assess the incremental benefit ofadding ipratropium to a standardized regimen of this commonly used multidrug therapy: Since prior studies have only examined response to initial doses of ipratropium, and since corticosteroids have no significant immediate effect, we chose to measure FEV1 improvement at 24 hours to determine whether or not there was any benefit outside the very early treatment period.
mal systemic side effects, has brought new life to the centuries-old concept of using anticholinergic agents in the treatment ofrespiratory disease. Evidence from many clinical trials suggests that in stable asthma, a betas-agonist is a better individual drug than ipratropium.v" but there may be additional benefit to using the two drugs in combination. In the treatment of stable COPD (chronic bronchitis or emphysema), ipratropium may be the better individual agent,2.6.7 and again, additional benefit may be seen in combination with a betas-agonist. Indeed, in those with emphysema, all achievable bronchodilation might be achieved with ipratropium alone." In status asthmaticus, ipratropium is generally considered to be inferior to betaj-agonists as an individual agent but is useful in combination with them. 2.8-12 In acute exacerbations of COPD, the addition of ipratropium to beta agonists has not been shown to have any consistent benefit. 11.12 Those studies that examined this question, however,
*From the Ottawa General Hospital, University of Ottawa, Canada. t Resident in Internal Medicine. iAssistant Professor of Medicine and Epidemiology. §Clinical Research Coordinator. IlRespiratoryTechnologist. 'Assistant Professor of Medicine and Family Medicine. Supported by the Ontario Thoracic Society, Canada. Manuscript received May 12, 1989; revision accepted January 17, 1990.
=
METHODS
Eligible subjects were those with all four of the following criteria: (1) presented to the Ottawa General Hospital Emergency Department because of dyspnea, cough, wheeze or chest discomfort; (2) hadair80w obstruction de6ned as maximal forced expiratory volume in one second (FEV J
