Opioid therapy for refractory dyspnea in patients with advanced chronic obstructive pulmonary disease: patients' experiences and outcomes

Abstract

Background: Dyspnea that is refractory to conventional treatments affects up to 50% of patients with advanced chronic obstructive pulmonary disease (COPD). Although professional societies recommend opioids in this setting, evidence supporting their use over months is limited. We conducted a multicentre mixed-methods study to understand patients' experiences when opioids are added to optimized conventional treatments for advanced COPD.

Methods: A total of 44 patients (median age 74, range 51-89 years) agreed to participate in this 6-month study. After baseline assessments, immediate-release morphine sulfate syrup (initially 0.5 mg twice daily) was slowly titrated upward based on weekly assessments of symptoms. We conducted semistructured interviews and collected contemporaneous measures of health-related quality of life, severity of dyspnea, anxiety, depression, global ratings of opioid "helpfulness" and adverse effects before, at 2 months and at 4-6 months after opioids were started.

Results: Of the 44 patients, 32 (73%) completed the trial; 27 (90%) of 30 patients reported the opioid treatment as very (43%) or somewhat (47%) helpful. Three main themes emerged from the patients' overall positive experiences: small gains have big impact; realign hopes with reality; and "try it." Significant improvements were observed in median (interquartile range) scores between baseline and 4-6 months' assessment for health-related quality of life (Chronic Respiratory Questionnaire: 3.5 [2.8-4.0] v. 4.2 [3.6-4.8]; and Chronic Respiratory Questionnaire-Dyspnea domain: 2.8 [2.3-3.6] v. 3.9 [2.8-4.5]) and decreases in severity of dyspnea (numerical rating scale: 7.0 [5.0-8.0] v. 5.0 [4.0-6.0]). Adverse effects were minimal for most patients.

Interpretation: Opioids were a helpful and acceptable intervention for refractory dyspnea in patients with advanced COPD. Many of the patients experienced sustained benefits over months, which supports recent recommendations to consider opioids in this setting.

Trial registration: ClinicalTrial.gov, no. NCT00982891.

Conflict of interest statement

Competing interests:Graeme Rocker has received support for initiating a COPD outreach program (directed to and managed by Capital District Health Authority) from GlaxoSmithKline and occasional honoraria for sponsored continuing medical education presentations from GlaxoSmithKline, Merck and Pfizer. Paul Hernandez has participated on medical advisory boards for pharmaceutical companies, as a researcher on industry-funded clinical trials, in the development of material or as a speaker for industry-funded continuing medical education for the following companies: Actelion, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, GlaxoSmithKline, Grifols, Merck, Novartis, Pfizer and Takeda. Darcy Marciniuk has undertaken consulting or participated on advisory boards for the Canadian Lung Association, Health Canada, the Public Health Agency of Canada and the Saskatoon Health Region. He has received research support (directed to and managed by the University of Saskatchewan) from AstraZeneca, Boehringer Ingelheim, the Canadian Institute of Health Research, GlaxoSmithKline, Forest Research, the Lung Association of Saskatchewan, Novartis, Pfizer, the Saskatchewan Health Research Foundation, the Saskatchewan Ministry of Health and Schering-Plough. He holds fiduciary positions with the American College of Chest Physicians, the Chest Foundation and the Lung Association of Saskatchewan and is an employee of the University of Saskatchewan. No competing interests declared by Catherine Simpson, Joanne Young, Robert Horton, Tasnim Sinuff, Jillian Demmons or Margaret Donahue.

Figures

Figure 1:

Flow of patients through the trial. Overall, 12 patients did not complete the trial (9 dropped out; 3 died); none of the deaths was unexpected or attributed to the use of opioids. (See Appendix 2 for details of attrition, available at www.cmajopen.ca/content/1/1/E27/suppl/DC1.)

Figure 2:

Global ratings of “helpfulness” of opioids on 5-point Likert scale.