Effects of combined therapy with nebulized β₂-agonist and anticholinergics in severe exacerbation of chronic obstructive pulmonary disease. A randomized controlled trial

The aim of the study was to compare the efficacy of nebulized salbutamol and ipratropium with nebulized salbutamol alone in patients with severe exacerbation of COPD. The study was designed as prospective, randomized, single blind. Inclusion criteria were severe exacerbation of COPD (worsening of dyspnea, FEV₁ at admission < 1 L or < 35 %pred. ; SpO₂ < 92 %; respiratory rate > 24 min–1 ); age > 45 yrs; smoking history > 10 packs/yrs; no need for invasive respiratory support. Fifty patients with COPD (M: F = 41: 9; mean age, 68 yrs; mean FEV₁ , 0.72 L, mean PaO₂, 46 mm Hg) were included in the study and randomized to receive either nebilized salbutamol 2.5 mg and ipratropium bromide 500 mg q4h for 7 days (n = 26) or nebilized salbutamol 2.5 mg alone q4h for 7 days (n = 24). All patients also received oral corticosteroids, antibiotics, oxygen and nonin vasive ventilation if necessary. There were no differences between the groups in demographic, functional or gasometric parameters. Both groups showed significant improvements in FEV₁, FVC and IC, but treatment with combined therapy rather than salbutamol alone resulted in more rapid improvement in FVC (in 1 day: 1.90 ± 0.51 L vs 1.61 ± 0.50 L, р = 0.048; in 3 days: 2.00 ± 0.51 L vs 1.67 ± 0.49 L, р = 0.024) and in IC (in 1 day: 1.67 ± 0.39 L vs 1.38 ± 0.37 L, р = 0.010; in 3 days: 21.77 ± 0.51 L vs 1.44 ± 0.40 L, р = 0.015). Dyspnea (Visual Analog Score) also improved more rapidly in patients received salbutamol and ipratropium (in 1 day: 32 ± 13 mm vs 42 ± 15 mm, р = 0.019; in 3 days: 26 ± 11 mm vs 33 ± 13 mm, р = 0.045). The need for additional salbutamol inhalations was significantly higher in patients received salbutamol alone (5.6 ± 3.5 vs 1.3 ± 1.5 inhalations per 1 patient during 7 days, p < 0.01). There was no difference between two groups with regards to other parameters including respiratory rate, pulse, PaCO₂ , pH, and other parameters excepting more marked increase in the PaO₂ in the 1st group after 1 day of the therapy (р = 0.019). The incidence of adverse events was similar in both the groups. Therefore, in severe exacerbations of COPD, the combined therapy with nebulized salbutamol and ipratropium is more effective than nebulized salbutamol alone.

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