THE EFFECT OF ADDING IPRATROPIUM BROMIDE TO SALBUTAMOL IN THE TREATMENT OF ACUTE ASTHMA - A POOLED ANALYSIS OF 3 TRIALS

Objective: To assess the effect on FEV1 and clinical outcomes of addin g ipratropium bromide to salbutamol in the treatment of acute asthma. Methods: We conducted a pooled analysis of three randomized double-bli nded clinical trials conducted in the United States, Canada, and New Z ealand. The studies enrolled 1,064 patients aged 18 to 55 years who pr esented at the emergency department with acute asthma. Patients were r andomized to treatment with a combination of nebulized 2.5 mg salbutam ol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medica tions were administered at baseline and; in the US at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up f or 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization. Results: Treatment groups were comparable at bas eline. Of the 1,064 patients randomized , 1,015 patients (95%) remaine d in the study for measurement at 45 min, and 961 patients (90%) compl eted the final measurement at 90 min. Comparison of overall improvemen t in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval [ CI] = -20, 107). The distribution of change in FEV1 was skewed by a sm all number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these out liers produced a larger and more precise estimate of effect (mean difl ference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value = 0.03). In addition, 4.9% (95% CI= -1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving comb ination therapy had lower risk for each of three clinical outcomes: th e need for additional treatment (relative risk [RR]=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and r isk of hospitalization (RR=0.80, 95% CI=0.61, 1.06). Conclusion: Addin g ipratropium bromide to salbutamol in the treatment of acute asthma p roduces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, an d hospitalizations. These apparent benefits of adding ipratropium brom ide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respirat ory tract infection. Confirmatory studies are needed, especially for c linical outcomes.