Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD

Abstract

Background: This study examined the effects of inhaled furosemide on the ventilatory and perceptual response to high-intensity constant-load cycle exercise in chronic obstructive pulmonary disease (COPD). Methods: In a randomised, double-blind, placebocontrolled, crossover study, 20 patients with COPD (mean (SD) forced expiratory volume in 1 s 45 (15)% predicted) received either nebulised furosemide 40 mg or placebo on two separate days. Thirty minutes after each treatment, patients performed pulmonary function tests and a symptom-limited cycle exercise test at 75% of their maximum incremental work rate. Changes in spirometry, plethysmographic lung volumes, dynamic operating lung volumes, ventilation, breathing pattern, cardiovascular function, dyspnoea intensity and exercise endurance time were compared between treatments. Results: Compared with placebo, treatment with furosemide resulted in a mean (SD) decrease in dyspnoea intensity at the highest equivalent exercise time (ie, isotime for each patient) of 0.9 (1.0) Borg units (p,0.01) and an increase in exercise endurance time of 1.65 (0.63) min (p,0.05). These improvements were associated with increases in dynamic inspiratory capacity, tidal volume and mean tidal expiratory flow rates at isotime (p,0.01). The eight patients whose exercise endurance time improved by .1 min had greater changes in operating lung volumes (p,0.05), submaximal oxygen pulse (p,0.05) and oxygen uptake (p = 0.05) than those in whom exercise endurance time did not improve. Conclusion: Alleviation of exertional dyspnoea after single-dose furosemide inhalation in COPD is multifactorial but improvements in dynamic ventilatory mechanics are contributory in some individuals.Perceived respiratory difficulty (dyspnoea) and activity limitation are the dominant symptoms of chronic obstructive pulmonary disease (COPD) and contribute importantly to perceived poor health-related quality of life in this population.

The Adjunctive Effect of Nebulized Furosemide in COPD Exacerbation: A Randomized Controlled Clinical Trial

“…25 Although the effect of nebulized furosemide on dyspnea is likely to be independent of its systemic diuretic effect, 18,26 the systemic effect of nebulized furosemide has not been ruled out. 17 Both heart rate and blood pressure decreased in the furosemide group, by about 4 beats/min and 9 mm Hg, respectively, which is consistent with the results in the study by Rodriguez Vazquez et al 13 ; however, these changes were not clinically important. The change in heart rate and blood pressure could explain functional cardiac effects related to this medication; however, considering multiple contributing factors, including patient anxiety and potential diuretic effects of furosemide, it may preclude a direct correlation between these findings.…”

“…The mean change of P aO 2 contributed by furosemide was about 4 mm Hg, and for pH it was approximately 0.03. These findings can be attributed to a reduction in breathing frequency, improved ventilation, and increased dynamic inspiratory capacity, as was proposed in a study by Jensen et al 17 ␤-adrenergic agents transiently decrease P aO 2 as a result of their pulmonary vasodilator effects. While patients with severe COPD have a limited ability to sustain a bronchodilation, increasing blood flow to poorly ventilated lung regions causes a ventilation-perfusion mismatch.…”

“…Our findings are contrary to the findings by Jensen et al, who reported that furosemide had no effect in stable COPD subjects. 17 However, our subjects were different from those in the Jensen study; our subjects were patients with COPD and an acute exacerbation who presented to the emergency department. Since exacerbation is often associated with hypoxia, hypercarbia, and acidosis, it is expected that these patients show physiologically different responses.…”

“…[6][7][8][9] Some studies have found that inhaled furosemide, a common diuretic, alleviates dyspnea by modulating vagal afferent activity in animal lung models, 10 reduces induced dyspnea in healthy subjects, 11,12 and might be effective against dyspnea in patients with asthma 13 and lung cancer. 14, 15 Ong et al 16 and Jenson et al 17 evaluated the efficacy of inhaled furosemide in COPD patients, and supported its use as a therapy in patients with COPD exacerbation. 3,5,17,18 Studies of inhaled furosemide in COPD were mainly conducted in stable patients with induced dyspnea; therefore, the short-term effect of nebulized furosemide in COPD exacerbation has not been investigated.…”

“…14, 15 Ong et al 16 and Jenson et al 17 evaluated the efficacy of inhaled furosemide in COPD patients, and supported its use as a therapy in patients with COPD exacerbation. 3,5,17,18 Studies of inhaled furosemide in COPD were mainly conducted in stable patients with induced dyspnea; therefore, the short-term effect of nebulized furosemide in COPD exacerbation has not been investigated. We evaluated nebulized furosemide as an adjunct to conventional therapy in the management of patients with COPD exacerbations in an emergency department.…”