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

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.