Inhaled Fentanyl Citrate & Dyspnea

Effects of Inhaled Fentanyl Citrate on Perceived Respiratory Discomfort (Dyspnea) During Exercise in the Presence of External Thoracic Restriction

"Dyspnea" refers to the awareness of breathing discomfort that is typically experienced during exercise in health and disease. In various participant populations, dyspnea is a predictor of disability and death; and contributes to exercise intolerance and an adverse health-related quality-of-life. It follows that alleviating dyspnea and improving exercise tolerance are among the principal goals of disease management. Nevertheless, the effective management of dyspnea and activity-limitation remains an elusive goal for many healthcare providers and current strategies aimed at reversing the underlying chronic disease are only partially successful in this regard. Thus, research aimed at identifying dyspnea-specific medications to complement existing therapies for the management of exertional symptoms is timely and clinically relevant. The purpose of this study is to test the hypothesis that single-dose inhalation of fentanyl citrate (a mu-opioid receptor antagonist) will improve the perception of dyspnea during strenuous exercise in healthy, young men in the presence of an external thoracic restriction. To this end, the investigators plan compare the effects of inhaled 0.9% saline placebo and inhaled fentanyl citrate (250 mcg) on detailed assessments of neural respiratory drive (diaphragm EMG), ventilation, breathing pattern, dynamic operating lung volumes, contractile respiratory muscle function, cardio-metabolic function and dyspnea (sensory intensity and affective responses) during symptom-limited, high-intensity, constant-work-rate cycle exercise testing with and without external thoracic restriction in healthy, men aged 20-40 years.

Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of nebulized fentanyl citrate (250 mcg)

Chest wall strapping to reduce vital capacity by 20% of its baseline value + single-dose inhalation of 0.9% saline placebo

No chest wall strapping (unloaded control) + single-dose inhalation of nebulized fentanyl citrate (250 mcg)

Inclusion Criteria: Male Aged 20-40 years FEV1 ≥80% predicted FEV1/FVC >70% Exclusion Criteria: Current or ex-smoker Body Mass Index <18.5 or >30 kg/m2 History of cardiovascular, vascular, respiratory, renal, liver, musculoskeletal, endocrine, neuromuscular and/or metabolic disease/dysfunction Taking doctor prescribed medications History of using pain-relieving (opioid) and/or anti-depressant medications in the previous 6 weeks Allergy to latex Allergy to lidocaine or its "caine" derivatives

Kotrach HG, Bourbeau J, Jensen D. Does nebulized fentanyl relieve dyspnea during exercise in healthy man? J Appl Physiol (1985). 2015 Jun 1;118(11):1406-14. doi: 10.1152/japplphysiol.01091.2014. Epub 2015 Mar 12.