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Triple Inhaled Drug Protocol for the Treatment of Acute Severe Asthma^*

^* From the Departamento de Emergencia (Dr. G. J. Rodrigo), Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay; and Unidad de Cuidado Intensivo (Dr. C. Rodrigo), Asociación Española 1a de Socorros Mutuos, Montevideo, Uruguay.

Correspondence to: Gustavo J. Rodrigo, MD, Departamento de Emergencia, Hospital Central de Las Fuerzas Armadas, Av 8 de Octubre 3020, Montevideo 11600, Uruguay; e-mail: gurodrig{at}adinet.com.uy

Study objective: This study tests the hypothesis that the administration of multiple doses of inhaled albuterol (A), ipratropium bromide (IB), and flunisolide (F) provides an additional benefit to adults with acute severe asthma compared with the administration of A plus IB (A/IB) or A plus F (A/F).

Design: Randomized, double-blind, prospective trial.

Patients and interventions: One hundred seventy-two patients who presented to an emergency department were assigned to receive A, IB, and F (ie, triple drug treatment [TDG]; 56 patients), A/IB (60 patients), or A/F (56 patients). All drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h.

Results: Patients who received TDG had an overall 64% greater improvement (95% confidence interval [CI], 24 to 103%; p = 0.002) in FEV₁ (mean [± SD], 2.1 ± 0.6 L) than those who received A/F (mean, 1.7 ± 0.6 L), and a 41% greater improvement (95% CI, 1 to 80%; p = 0.04) than those who received A/IB (mean, 1.8 ± 0.6 L). Differences between groups increased with time (p = 0.001). At 3 h, there was a trend toward a reduction in hospital admission rates (A/IB group, 25%; A/F group, 20%; and TDG group, 11%). The patients who were the most likely to benefit (ie, those with a greater improvement in pulmonary function and a significant reduction in the hospitalization rate) from TDG were those with more severe obstruction (ie, FEV₁, < 30% of predicted). The benefit of TDG was equally evident independent of the patient’s previous use of corticosteroids.

Conclusions: The data suggest that there was a therapeutic benefit from the addition of IB and F to A administered in high doses, particularly in those patients in whom the FEV₁ was < 30% of the predicted value.

Key Words: acute severe asthma • albuterol • emergency department treatment • flunisolide • ipratropium bromide

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