First-Line Therapy for Adult Patients with Acute Asthma Receiving a Multiple-Dose Protocol of Ipratropium Bromide Plus Albuterol in the Emergency Department

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Abstract
We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and beta(2)-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given beta(2)-agonists alone. One hundred eighty patients (mean age +/- SD, 34.3 +/- 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV(1) < 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n = 92) or albuterol and IB (n = 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 microg of albuterol and 504 microg of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV(1) or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p < 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p = 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p = 0.001) greater improvement in FEV(1) from the control group. At the end of protocol (3 h), 39% (n = 36) of patients in the control group and 20% (n = 18) in the IB group were admitted (p = 0.01). The use of high doses of IB reduced the risk of hospital admission 49% (relative risk = 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test = 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV(1) /= 24 h). On the contrary, previous use of inhaled beta(2)-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV(1) less than 30%, and with long duration of symptoms before the ED presentation (>/= 24 h).