The Effect of Sustained-Release Morphine on Breathlessness and Quality of Life in Severe Chronic Obstructive Pulmonary Disease

Abstract

Morphine has been proposed as a treatment for breathlessness in patients with severe chronic obstructive pulmonary disease (COPD), but there is uncertainty as to whether or not it is effective. Orally administered sustained-release morphine was compared with placebo in a randomized, double-blind, crossover trial with two 6-wk treatment periods separated by a 2-wk washout period. The primary end point was quality of life measured using the Chronic Respiratory Disease Questionnaire (CRQ). Secondary end points included 6-min walk (6MW), distance, and breathlessness scores. Sixteen subjects with a mean age 70.7 yr, FEV1 of 0.6 L, and VC of 1.90 L were studied. There was no change in the total CRQ score with either treatment, but the score on the Mastery subscale was significantly worse with morphine (p = 0.02). The 6MW distance increased by 21 m from the beginning to the end of the placebo treatment period, but it decreased by 35 m with morphine (p = 0.04). There were no differences between treatments in breathlessness scored on daily diary cards or on the Dyspnea subscale of the CRQ. Almost all the subjects experienced adverse effects related to morphine. Sustained-release morphine was not a useful treatment for breathlessness in these patients with severe COPD.

An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea

“…Short-term administration reduces breathlessness in patients with a variety of conditions, including advanced COPD (236,237), interstitial lung disease (238), cancer (239), and chronic heart failure (240). However, evidence of long-term efficacy is limited and conflicting (241,242). Opioids are associated with frequent side effects (241,243), particularly constipation, but clinically significant respiratory depression is uncommon with the doses used to treat dyspnea, even in elderly patients (244,245).…”

“…However, evidence of long-term efficacy is limited and conflicting (241,242). Opioids are associated with frequent side effects (241,243), particularly constipation, but clinically significant respiratory depression is uncommon with the doses used to treat dyspnea, even in elderly patients (244,245). Randomized controlled trials have not found nebulized opioids to be associated with fewer side effects than oral or parenteral opioids (246).…”

Once-Daily Opioids for Chronic Dyspnea: A Dose Increment and Pharmacovigilance Study

“…Dose titration stopped at 30mg per 24 hours given the levels of toxicity reported in a earlier study that used higher doses of opioids in the chronic setting. [21] These results may under-represent the net clinical benefit. As with pain, people may increase activity as the symptom is better controlled but report only marginal improvement in the symptom itself.…”

Dyspnea in Pulmonary Arterial Hypertension

“…Recent neuroimaging studies suggest that neural pathways involved in pain and dyspnea sensation may be shared and, therefore, similar neurophysiological and psychological approaches used to understand and manage pain can be applied to dyspnea (Nishino, 2011). Previous randomised controlled trials have reported the effectiveness of sustained-release morphine in patients with refractory dyspnea, including those with severe COPD (Abernethy et al, 2003;Poole et al, 1998) and chronic heart failure (Johnson et al, 2002). Currently there is no data on use of opioids to relieve dyspnea in patients with progressive advanced PAH and clinical trials are on-going.…”