Breathlessness attacks in individuals with chronic obstructive pulmonary disease (COPD) may be relieved with short-acting opioids, according to systematic review and meta-analysis findings published in Palliative Medicine.

Despite lack of consensus, several guidelines suggest opioid treatment for refractory dyspnea in COPD. Adverse events with opioid treatment (primary reason for not prescribing opioids) for dyspnea in COPD have not been systematically evaluated.

Investigators therefore sought to comprehensively assess opioids’ effect on dyspnea in COPD, including the effect of opioids on breathlessness and exercise endurance as well as adverse effects.

The investigators conducted a systematic review and meta-analysis for parallel or crossover randomized controlled trials (RCTs) that reported on patients with COPD treated with opioids compared with placebo. The researchers searched the EMBASE, CENTRAL, and PubMed databases without language restriction from inception through November 2022. Overall, 24 studies (4 parallel control, 20 cross-over) were included (N=975).

Short-acting opioids appeared to be safe, have potential to lessen dyspnea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnea.

The researchers defined COPD as having a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of less than 70%. Low risk of bias was noted in 5 studies, concerns about the randomization process were noted in 16 studies, and concerns over the selection of reported results were logged in 17 studies. Crossover studies all had low or very low quality of evidence, with additional concerns about imprecision and inconsistency. The 4 parallel control studies were rated as having moderate quality of evidence for pooled results for dyspnea and exercise endurance.

Sustained-release opioids were administered in all parallel control studies; short-acting opioids were administered in 11 of the crossover studies.

In the pooled results of the parallel control studies administering opioids for more than 1 week, the investigators found the sustained-release opioids did not improve dyspnea (standardized mean difference [SMD], -0.02; 95% CI, -0.22 to 0.19; I2=39%) or exercise endurance (SMD, 0.00; 95% CI, -0.27 to 0.27; I2=0%). However, short-acting opioids improved breathlessness (SMD, -0.43; 95% CI, -0.55 to -0.30; I2=18%), and improved exercise endurance (SMD, 0.22; 95% CI 0.02-0.41; I2=70%) in pooled results of cross-over studies. Further meta-analysis for short-acting opioids in 11 cross-over studies showed dyspnea similarly improved.

Subgroup analysis of the cross-over studies concerning breathlessness showed no significant differences for type of opioids, administration route, duration of action, or history. Subgroup analysis of crossover studies concerning exercise endurance showed a significant difference only in analysis of history (interaction P =.04).

In most of the cross-over studies, patients treated with short-acting opioids had minor side effects (vomiting, constipation, nausea, and dizziness), and short-acting opioids were infrequently associated with serious adverse effects.

Systematic review and meta-analysis limitations include underpowered sample sizes in many of the included crossover studies and significant heterogeneity in the pooled outcome of exercise endurance.

“Dyspnea and exercise endurance did not improve with the use of sustained-release opioids in patients with COPD,” the investigators concluded. “Short-acting opioids appeared to be safe, have potential to lessen dyspnea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnea,” they added.

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