Opioids for chronic refractory breathlessness: right patient, right route?

Chronic breathlessness at rest or on minimal exertion despite optimal treatment of the underlying chronic cause(s) is termed chronic refractory breathlessness. This is prevalent across the community and is an independent indicator of poor prognosis. This narrative review focuses on the palliation of chronic refractory breathlessness in people predominantly with non-cancer diagnoses. Breathlessness is a complex sensation with at least three dimensions--intensity, distress/unpleasantness and its impact on function. It is the conscious representation of a mismatch between central ventilatory drive (the demand to breathe) and the responding respiratory output (the ability to breathe). Measurement relies on subjective reports by patients using a choice of uni- and multi-variable tools; the minimal clinically important difference is the smallest change conceived as clinically meaningful by the patients. Exogenous and endogenous opioids work centrally to reduce the sensation of breathlessness, with morphine as a mu opioid receptor agonist the most widely studied. Regular, low doses of sustained-release morphine have been shown to safely reduce breathlessness in this setting without evidence of respiratory depression nor obtundation. Patients should be initiated at a dosage of 10 mg/24 h and titrated by 10 mg if there is no benefit once in steady state. The highest dosage in the only dose-ranging study published to date was only 30 mg/24 h. Predictors of response to opioids for chronic refractory breathlessness include younger people with more severe breathlessness at baseline. Future research should address whether upward titration delivers further clinical benefit and whether all underlying aetiologies respond as predictably to opioids.