Pharmacological treatment of refractory breathlessness

Abstract

Refractory breathlessness is one of the most common and devastating symptoms of advanced cardiorespiratory disease, both malignant and nonmalignant. In spite of increased interest in research in the last 20 years, there have been few significant advances in the palliation of this distressing condition. The most successful palliative regimens for breathlessness always include pharmacological and nonpharmacological interventions used concurrently. When patients are active, nonpharmacological treatments (e.g., exercise) are the most effective. As the patient becomes more breathless, eventually becoming breathless at rest, pharmacological treatments become more important. Opioids have the most extensive evidence base to guide their use. Other pharmacological interventions may act partly by helping breathlessness (by mechanisms still uncertain) or by treating concomitant precipitating and exacerbating conditions, such as depression and anxiety. A specific treatment to palliate breathlessness remains elusive. The neurophysiological substrate of breathlessness perception is still relatively poorly understood and not well reproduced in animal models. Research using functional MRI and other imaging, with more precise clinical trial methods, may help to bring significant advances. In the next 5 years, novel approaches to delivering opioids may be developed, the effective use of inhaled furosemide may be elucidated and the place of antidepressants and anxiolytics will become clearer. A role for cannabinoids may emerge. New drugs may be developed as our understanding of neurophysiology grows.

Keywords::

• antidepressant
• anxiolytic
• breathlessness
• clinical trial
• inhaled Furosemide
• opioid
• palliation
• refractory

Acknowledgements

S Booth would like to acknowledge the support of a SuPaC grant, which made the research underpinning this article possible and Cicely Saunders International, which has supported her in work on breathlessness. The authors are very grateful to Mrs Jacquie Adie for her work on this manuscript.

Sources on which this work was drawn

S Booth, S Moosavi and I Higginson carried out a short systematic review of pharmacological therapies in advanced disease and advanced cancer and are actively involved in breathlessness research. S Moosavi has been involved in some research on inhaled furosemide and the pathophysiology of breathlessness. All are members of the National Cancer Research Institute breathlessness subgroup of the clinical studies group in palliative care.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.