Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness

Barnes, Hayley; McDonald, Julie; Smallwood, Natasha; Manser, Renée

doi:10.1002/14651858.cd011008.pub2

Cited by 133 publications

(117 citation statements)

References 81 publications

(1 reference statement)

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“…Characteristics are for trials included in each published meta-analysis 3 6 7

*Negative estimate indicates reduction in breathlessness by opioids compared with placebo.

†Included both trials of systemic and nebulised opioids which were not reported separately.

CHF, congestive heart failure; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; I 2 , proportion of the total variance in effect estimates that are between studies; MD, mean difference; RCT, randomised controlled trial; SMD, standardised mean difference.

…”

Section: Resultsmentioning

confidence: 99%

“…The meta-analysis of Barnes et al 7 re-analysed using random effects model and accounting for matched data of crossover trials. In the pooled analysis compared with placebo, systemic opioids reduced breathlessness by a mean 0.32 (95% CI 0.18 to 0.47; p<0.001) SDs.…”

Section: Resultsmentioning

confidence: 99%

“…Data were extracted from the published meta-analyses by Jennings et al ,3 4 Ekström et al 6 and Barnes et al 7 (by ME), and cross-validated (DCC and MJJ) regarding study populations, designs, interventions and methods, for the whole study population and in participants with COPD, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…A new Cochrane meta-analysis by Barnes et al ,7 drawing from a similar evidence base, reported a smaller benefit of opioids than the other reviews, and wider 95% CIs which nearly crossed zero. The risk of bias was rated as ‘high’ for all studies; previous ratings were mainly ‘unclear’ or ‘low’ 3 4 6.…”

Section: Introductionmentioning

confidence: 93%

“…The risk of bias was rated as ‘high’ for all studies; previous ratings were mainly ‘unclear’ or ‘low’ 3 4 6. Barnes et al 7 rated the quality of evidence for opioids for breathlessness as ‘very low’.…”

Section: Introductionmentioning

confidence: 99%

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One evidence base; three stories: do opioids relieve chronic breathlessness?

Ekström

Bland

Currow

et al. 2017

Thorax

103

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The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes 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; I=44.8%) representing a clinically meaningful reduction of 0.8 points (0-10 numerical rating scale), consistent across meta-analyses.

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“…Characteristics are for trials included in each published meta-analysis 3 6 7

*Negative estimate indicates reduction in breathlessness by opioids compared with placebo.

†Included both trials of systemic and nebulised opioids which were not reported separately.

…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

One evidence base; three stories: do opioids relieve chronic breathlessness?

Ekström

Bland

Currow

et al. 2017

Thorax

103

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Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status

et al. 2020

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IMPORTANCE Morphine is used as palliative treatment of chronic breathlessness in patients with advanced chronic obstructive pulmonary disease (COPD). Evidence on respiratory adverse effects and health status is scarce and conflicting.OBJECTIVE To assess the effects of regular, low-dose, oral sustained-release morphine on disease-specific health status (COPD Assessment Test; CAT), respiratory outcomes, and breathlessness in patients with COPD.INTERVENTIONS Participants were randomly assigned to 10 mg of regular, oral sustained-release morphine or placebo twice daily for 4 weeks, with the possibility to increase to 3 times daily after 1 or 2 weeks. DESIGN, SETTING, AND PARTICIPANTSThe Morphine for Treatment of Dyspnea in Patients With COPD (MORDYC) study was a randomized, double-blind, and placebo-controlled study of a 4-week intervention. Patients were enrolled between November 1, 2016, and January 24, 2019. Participants were recruited in a pulmonary rehabilitation center and 2 general hospitals after completion of a pulmonary rehabilitation program. Outpatients with COPD and moderate to very severe chronic breathlessness (modified Medical Research Council [mMRC] breathlessness grades 2-4) despite optimal pharmacological and nonpharmacological treatment were included. A total of 1380 patients were screened, 916 were ineligible, and 340 declined to participate. MAIN OUTCOMES AND MEASURESPrimary outcomes were CAT score (higher scores represent worse health status) and arterial partial pressure of carbon dioxide (PaCO 2 ). Secondary outcome was breathlessness in the previous 24 hours (numeric rating scale). Data were analyzed by intention to treat. Subgroup analyses in participants with mMRC grades 3 to 4 were performed.RESULTS A total of 111 of 124 included participants were analyzed (mean [SD] age, 65.4 [8.0] years; 60 men [54%]). Difference in CAT score was 2.18 points lower in the morphine group (95% CI, -4.14 to -0.22 points; P = .03). Difference in PaCO 2 was 1.19 mm Hg higher in the morphine group (95% CI, -2.70 to 5.07 mm Hg; P = .55). Breathlessness remained unchanged. Worst breathlessness improved in participants with mMRC grades 3 to 4 (1.33 points lower in the morphine group; 95% CI, -2.50 to -0.16 points; P = .03). Five participants of 54 in the morphine group (9%) and 1 participant of 57 in the placebo group (2%) withdrew because of adverse effects. No morphine-related hospital admissions or deaths occurred. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, regular, low-dose, oral sustained-release morphine for 4 weeks improved disease-specific health status in patients with COPD without affecting PaCO 2 or causing serious adverse effects. The worst breathlessness improved in participants with mMRC grades 3 to 4. A larger randomized clinical trial with longer follow-up in patients with mMRC grades 3 to 4 is warranted.

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Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer

et al. 2021

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Key Points Question What are the benefits and harms associated with pharmacologic interventions for managing breathlessness in adults with advanced cancer? Findings This systematic review and meta-analysis of 19 studies (17 randomized clinical trials and 2 retrospective studies) found that opioids and anxiolytics were not associated with improved breathlessness in patients with advanced cancer within the limits of the identified studies, which mainly focused on exertional breathlessness for opioids. Data on harms were too limited to draw conclusions. Meaning Although the existing data on opioids and pharmacologic interventions do not show an association with improved breathlessness in advanced cancer, they may be considered in selected patients in the context of potential harms and the evidence of an association of nonpharmacologic interventions with improved breathlessness.

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Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness

Cited by 133 publications

References 81 publications

One evidence base; three stories: do opioids relieve chronic breathlessness?

One evidence base; three stories: do opioids relieve chronic breathlessness?

Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer

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