Efficacy and safety of short-acting anticholinergics in patients with acute exacerbation of chronic obstructive pulmonary disease receiving maintenance therapy with tiotropium

Abstract

The aim of the study was to assess efficacy and safety of ipratropium and ipratropium/fenoterol in patients with acute exacerbation of COPD receiving maintenance therapy with tiotropium. Design: prospective, randomized, controlled cross-over study. Patients and methods. Thirty six patients with COPD exacerbation (mean age 66 yrs; mean FEV 1 26 %) were included in the study. Patients were randomized to receive either ipratropium or ipratropium/fenoterol on two different test days. The study consisted of two different protocols. In the 1st protocol, the patients received either nebulized solution of ipratropium 500 μg or ipratropium/fenoterol 500/1000 μg. In the 2nd protocol, patients received either ipratropium 80 μg via metered dose inhaler (MDI) and spacer or ipratropium/fenoterol 80/200 μg. Spirometry, clinical and hemodynamic measurements were performed immediately before and at 1 and 4 hours after inhalation of ipratropium or ipratropium/fenoterol. Nebulized therapy with ipratropium or ipratropium/fenoterol resulted in statistically and clinically significant improvement in FEV1 , FVC and IC at 1 and 4 hours after inhalation ( р < 0.01). In terms of the bronchodilator effect, add-on therapy with ipratropium/fenoterol was nonsignificantly superior to add-on ipratropium. There were no serious adverse events after inhaled therapy including hemodynamic parameters (BP, ECG, QTc). Only ipratropium/fenoterol resulted in increase of heart rate, approximately by 3.8 beats per minute (bpm) at 1 hour after inhalation ( p < 0.001). Inhaled therapy with ipratropium or ipratropium/fenoterol via MDI and spacer led to similar results as nebulized therapy. Heart rate was increased at 1 hour after inhalation of ipratropium/fenoterol via MDI and spacer by 3.7 bpm ( p < 0.001). In patients with acute exacerbation of COPD receiving maintenance therapy with tiotropium, the addition of ipratropium or ipratropium / fenoterol provides significant bronchodilator effect without any serious adverse events.