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

Ekström, Magnus; Nilsson, Fredrik; Abernethy, A. P.; Currow, David C.

doi:10.1513/annalsats.201501-034oc

Cited by 189 publications

(193 citation statements)

References 37 publications

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“…A recent prospective observational study of individuals with advanced COPD found that receipt of opioids, among selected patients with careful dose titration and close monitoring for side effects, significantly improved respiratory questionnaire scores and dyspnea ratings at 4-6 months compared with baseline [18]. A more recent systematic review [19] on opioids for refractory dyspnea and exercise intolerance in advanced COPD drew similar conclusions as the earlier one by Jennings et al [16].…”

Section: Editorialsupporting

confidence: 55%

“…First, these trials were all characterized by small numbers of subjects [10,[16][17][18][19] and some studies included individuals without COPD [16,17]. The efficacy and safety of opioids may understandably differ between individuals with COPD versus individuals with lung cancer or congestive heart failure.…”

Section: Editorialmentioning

confidence: 99%

“…The efficacy and safety of opioids may understandably differ between individuals with COPD versus individuals with lung cancer or congestive heart failure. Second, several of the trials excluded individuals with comorbidities that frequently occur in COPD [16][17][18][19] or individuals with previous adverse reaction to opioids [10], thereby potentially impacting the generalizability of the study results. Third, assessments of breathlessness and exercise performance, which were the primary outcome measures, were not standardized and arguably crude and difficult to interpret [16,19].…”

Section: Editorialmentioning

confidence: 99%

“…Second, several of the trials excluded individuals with comorbidities that frequently occur in COPD [16][17][18][19] or individuals with previous adverse reaction to opioids [10], thereby potentially impacting the generalizability of the study results. Third, assessments of breathlessness and exercise performance, which were the primary outcome measures, were not standardized and arguably crude and difficult to interpret [16,19]. Fourth, most of the trials involved low or single opioid dosing levels [10,16,19] and therefore, efficacy and safety findings may not apply to 'realword', suboptimal patterns of opioid use that have been observed to occur in the COPD population [1,2].…”

Section: Editorialmentioning

confidence: 99%

“…Third, assessments of breathlessness and exercise performance, which were the primary outcome measures, were not standardized and arguably crude and difficult to interpret [16,19]. Fourth, most of the trials involved low or single opioid dosing levels [10,16,19] and therefore, efficacy and safety findings may not apply to 'realword', suboptimal patterns of opioid use that have been observed to occur in the COPD population [1,2]. Fifth, few of the published studies evaluated opioids over 'longer-term' follow-up periods [17,18].…”

Section: Editorialmentioning

confidence: 99%

See 4 more Smart Citations

The need to address increasing opioid use in elderly COPD patients

Vozoris

O’Donnell

2016

Expert Review of Respiratory Medicine

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Section: Editorialsupporting

confidence: 55%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

Section: Editorialmentioning

confidence: 99%

See 3 more Smart Citations

The need to address increasing opioid use in elderly COPD patients

Vozoris

O’Donnell

2016

Expert Review of Respiratory Medicine

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Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease

Ekström

Chang

Louw

et al. 2022

JAMA

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ImportanceChronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed.ObjectiveTo determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.Design, Setting, and ParticipantsMulticenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019.InterventionsPeople were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week’s dose, or placebo.Main Outcomes and MeasuresThe primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days −3 to −1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day −1) to the mean step count from week 3 (from days 19 to 21).ResultsAmong the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −0.3 [95% CI, −0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, −0.3 [95%, CI, −1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −1453 [95% CI, −3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, −1312 [95% CI, −3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, −692 [95% CI, −2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, −1924 [95% CI, −47 699 to 921]).Conclusions and RelevanceAmong people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness.Trial RegistrationClinicalTrials.gov Identifier: NCT02720822

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The Role of Opioids in Patients With Chronic Obstructive Pulmonary Disease and Chronic Breathlessness

Widera

2020

JAMA Intern Med

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

Abstract: Opioids improved breathlessness but not exercise capacity in severe COPD.

Cited by 189 publications

References 37 publications

The need to address increasing opioid use in elderly COPD patients

The need to address increasing opioid use in elderly COPD patients

Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease

The Role of Opioids in Patients With Chronic Obstructive Pulmonary Disease and Chronic Breathlessness

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