Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

Aerosol furosemide for dyspnea: High-dose controlled delivery does not improve effectiveness.

Published studies have shown great variability in response when aerosolized furosemide has been tested as a palliative treatment for dyspnea. We hypothesized that a higher furosemide dose with controlled aerosol administration would produce consistent dyspnea relief. We optimized deposition by controlling inspiratory flow (300-500mL/s) and tidal volume (15% predicted vital capacity) while delivering 3.4µm aerosol from either saline or 80mg of furosemide. We induced dyspnea in healthy subjects by varying inspired PCO2 while restricting minute ventilation. Subjects rated "Breathing Discomfort" on a Visual Analog Scale (BDVAS, 100% Full Scale≡intolerable). At the PETCO2 producing 60% BDVAS pre-treatment, furosemide produced a clinically meaningful reduction of BDVAS (i.e., >20% FS) in 5/11 subjects; saline reduced dyspnea in 3/11 subjects; neither treatment worsened dyspnea in any subject. Furosemide and saline treatment effects were not statistically different. There were no significant adverse events. Higher furosemide dose and controlled delivery did not improve consistency of treatment effect compared with prior studies.