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A5055 - Aerosol Furosemide (80 mg) for the Treatment of Exercise-Induced Dyspnea
Author Block: R. Hallowell1, C. O'Donnell1, A. R. Sheridan2, R. M. Schwartzstein1, R. W. Lansing2, R. B. Banzett1; 1Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, 2Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States.
Rationale: Non-opioid therapies for treating dyspnea are lacking. Evidence suggests that nebulized furosemide may be an effective treatment, though doses, methods of delivery, and outcomes have been variable. We aimed to determine if optimizing the delivery of high-dose nebulized furosemide would reduce variability of dyspnea relief in patients with pulmonary disease.
Methods: 17 patients with chronic exertional dyspnea were recruited. Exclusion criteria included renal insufficiency, heart failure, or pulmonary hypertension. Patients rated recently recalled Breathing Discomfort on a 10-point visual analog scale (BDVAS) and completed a Multidimensional Dyspnea Profile (MDP). They then performed graded exercise using an arm-ergometer until a pre-defined dyspnea threshold was achieved. They completed the BDVAS following each exercise grade, and completed the MDP after excercise. During separate visits, patients received either nebulized saline or 80 mg of nebulized furosemide in a randomized, double-blind, crossover design. The nebulizer system was designed to optimize delivery to small airways. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the BDVAS and MDP. Treatment effect was defined as the difference between pre- and post-treatment BDVAS at end exercise, expressed in absolute terms as % Full Scale. Using paired T-tests, we compared pre- vs post-treatment values, and compared treatment effect with saline vs furosemide. “Responders” were defined as those with a treatment effect ≥ 20% of full scale, our a priori definition of a clinically meaningful change.
Results: The final analysis included 15 patients (8 asthma or COPD, 5 ILD, 1 lung cancer, 1 chronic pulmonary emboli without pulmonary hypertension). Two patients were excluded because they failed to reach the pre-defined dyspnea threshold with exercise prior to treatment. The most frequently chosen descriptor was air hunger (40% of opportunities); there was no difference between responders and non-responders in descriptor choice. Neither treatment produced a statistically significant effect (furosemide -5.3%FS ±4.1SE, p=0.26 vs saline -10%FS ±2.4SE, p=0.71). There was no significant difference between treatments (p=0.45). There were 4 “responders” and one patient that worsened with furosemide; two patients were responders with saline, of which one also responded to furosemide. No adverse events were reported, apart from the expected diuresis with furosemide.
Conclusion: Optimal delivery of high-dose nebulized furosemide was not superior to saline placebo in reducing exercise-induced dyspnea. However, a clinically significant improvement was noted in a few patients. Given its favorable side effect profile, nebulized furosemide might be considered in select patients with refractory dyspnea.