Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1862-1868

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

GUSTAVO J. RODRIGO and CARLOS RODRIGO

Departamento de Emergencia, Hospital Central de las FF.AA, and Unidad de Cuidado Intensivo, Asociación Española 1^a de Socorros Mutuos, Montevideo, Uruguay

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 ₂-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given 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 FEV₁ < 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 µg of albuterol and 504 µg of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV₁ 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 FEV₁ 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 (FEV₁  30% of predicted) and long duration of symptoms before the ED presentation ( 24 h). On the contrary, previous use of inhaled 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 FEV₁ less than 30%, and with long duration of symptoms before the ED presentation ( 24 h).

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