Pulmonary Arterial Hypertension Clinical Trial
Official title:
Effect of Morphine on Dyspnea and 6-Minute Walk Distance in Pulmonary Arterial Hypertension
Despite advances in treatment and corresponding improvements in survival, patients with pulmonary arterial hypertension (PAH) remain highly symptomatic. In one survey of 315 patients with PAH, sixty-eight percent had moderate or severe dyspnea on exertion and 40% had a profound and clinically significant deficit in quality of life. Palliative care is being increasingly investigated in life-limiting cardiovascular diseases to alleviate symptoms. In PAH, its implementation is frequently delayed until end-of-life. Opioids are a common palliative care intervention, however the efficacy and safety of opioids for symptom relief in PAH has not been evaluated.
There is biologic plausibility for opioids in the treatment of dyspnea in PAH. Opioids have
widespread effects including venodilation, vasodilation, reducing sympathetic outflow,
blunting hypercapnic and hypoxic ventilatory responses, and altering the central perception
of dyspnea. Although the origins of dyspnea in PAH are incompletely understood and
multifactorial, right ventricular dysfunction reduces exercise capacity and likely also plays
a role in the development of dyspnea. Mechanoreceptors situated in the right atrium and right
ventricle sense elevated pressures and via sympathetic afferents may lead to an augmentation
of ventilatory response and hence dyspnea. Morphine may specifically antagonize this feedback
loop by causing venodilation and blunting sympathetics. Morphine also reduces central
chemosensitivity and perceptions of dyspnea. Therefore, the drug may antagonize both
peripheral and central drivers of dyspnea in PAH.
Investigators will conduct a single-center feasibility study of morphine for treatment of
dyspnea and exercise intolerance in PAH. Participants will complete two 6-minute walk tests
(6MWT) within one week. Participants will be randomly assigned to receive morphine prior to
either the first or second 6MWT. Symptoms and 6-minute walk distance (6MWD) will be compared
between the two tests.
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