Effects of Opioids on Breathlessness and Exercise Capacity in Chronic Obstructive Pulmonary Disease: A Systematic Review

Magnus Ekstrom, Fredrik Nilsson, Amy Abernethy, David Currow

    Research output: Contribution to journalReview articlepeer-review

    131 Citations (Scopus)


    Rationale: Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from breathlessness, deconditioning, and reduced health-related quality of life (HRQL) despite best medical management. Opioids may relieve breathlessness at rest and on exertion in COPD. Objectives: We aimed to estimate the efficacy and safety of opioids on refractory breathlessness, exercise capacity, and HRQL in COPD. Methods: This was a systematic review and metaanalysis using Cochrane methodology. We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase up to 8 September, 2014 for randomized, double-blind, placebo-controlled trials of any opioid for breathlessness, exercise capacity, or HRQL that included at least one participant with COPD. Effects were analyzed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random effect models. Measurements and Main Results: A total of 16 studies (15 crossover trials and 1 parallel-group study, 271 participants, 95% with severe COPD) were included. There were no serious adverse effects. Breathlessness was reduced by opioids overall: SMD, 20.35 (95% CI, 20.53 to 20.17; I2, 48.9%), by systemic opioids (eight studies, 118 participants): SMD, 20.34 (95% CI, 20.58 to 20.10; I2, 0%), and less consistently by nebulized opioids (four studies, 82 participants): SMD, 20.39 (95% CI, 20.71 to 20.07; I2, 78.9%). The quality of evidence was moderate for systemic opioids and low for nebulized opioids on breathlessness.Opioids did not affect exercise capacity (13 studies, 149 participants): SMD, 0.06 (95% CI, 20.15 to 0.28; I2, 70.7%). HRQL couldnot be analyzed. Findingswere robust in sensitivity analyses.Risk of study bias was low or unclear. Conclusions: Opioids improved breathlessness but not exercise capacity in severe COPD.

    Original languageEnglish
    Pages (from-to)1079-1092
    Number of pages14
    JournalAmerican Thoracic Society. Annals
    Issue number7
    Publication statusPublished - 1 Jul 2015


    • Breathlessness
    • Chronic obstructive pulmonary disease
    • Exercise capacity
    • Opioids
    • Quality of life


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