The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes et al. We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes et al reported a smaller effect and lower precision, but did not account for matched data of crossover trials (11/12 included trials) and added a risk-of-bias criterion (sample size). When re-analysed to account for crossover data, opioids decreased breathlessness (standardised mean differences −0.32; −0.18 to −0.47; I2=44.8%) representing a clinically meaningful reduction of 0.8 points (0–10 numerical rating scale), consistent across meta-analyses.
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Contributors Concept and design: ME, DCC, JMB, MJJ, JH; first draft: ME, SB; statistical analysis: JMB; interpretation, revision and acceptance of the final version to be published: ME, SB, DCC, JMB, JH, MJJ.
Funding ME was supported by unrestricted grants from The Swedish Society of Medicine, the Swedish Respiratory Society, the Swedish Heart-Lung Foundation, the Scientific Committee of Blekinge County Council and the Wera and Emil Cornell Foundation.
Competing interests DCC has received intellectual property payments and advisory board payments. MJJ has been a clinical consultant for Mayne Pharma. Authors of this paper have longstanding interest in the research of breathlessness and have published several opioid-related trials and meta-analyses (including ME and DCC6). MJJ was an external clinical academic (not statistical) peer reviewer for the original Barnes et al protocol submitted to Cochrane.
Provenance and peer review Not commissioned; externally peer reviewed.
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