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Meta-Analysis
. 2024 Oct 9;33(174):230265.
doi: 10.1183/16000617.0265-2023. Print 2024 Oct.

Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis

Natasha E Smallwood  1   2 , Amy Pascoe  2 , Marlies Wijsenbeek  3 , Anne-Marie Russell  4   5 , Anne E Holland  2   6   7 , Lorena Romero  8 , Magnus Ekström  9
Affiliations
Meta-Analysis

Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis

Natasha E Smallwood et al. Eur Respir Rev. .

Abstract

Background: People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear.

Methods: We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1.

Results: Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) -0.37, 95% CI -0.67- -0.07), but not breathlessness measured in daily life (SMD -0.10, 95% CI -0.64-0.44). No effects on HRQoL (SMD -0.42, 95% CI -0.98-0.13) or cough (SMD -1.42, 95% CI -3.99-1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70-6.51), constipation (OR 3.08, 95% CI 1.69-5.61) and drowsiness (OR 1.37, 95% CI 1.01-1.86), with serious adverse events including hospitalisation and death identified.

Conclusions: Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits.

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Conflict of interest statement

Conflict of interest: N.E. Smallwood reports grants from NHMRC, MRFF, Cancer Council Australia, Fisher & Paykel Healthcare (FPH), Windermere Foundation, Lung Foundation Australia, Lord Mayor's Foundation Melbourne and Bethlehem Griffiths Foundation, consulting fees from The Limbic and Orchard Consulting, lecture honoraria from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, FPH and Health Ed, travel support from Chiesi and Boehringer Ingelheim, leadership roles as Board Director and past state president of the Thoracic Society of Australia and New Zealand, Board Director of Victorian Doctors’ Program and co-chair of the guidelines committee for European Respiratory Society; and receipt of equipment from FPH, outside the submitted work. M. Wijsenbeek reports grants from The Netherlands Organisation for Health Research and Development, The Dutch Lung Foundation, The Dutch Pulmonary Fibrosis organization, Sarcoidosis.nl, Boehringer Ingelheim, Hoffman la Roche and AstraZeneca-Daiichi, consulting fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Galecto, GSK, Hoffman la Roche, Horizon therapeutics, Kinevant Sciences, Molecure, Nerre Therapeutics, Novartis, PureTech Health, Thyron, Trevi and Vicore, lecture honoraria from Boehringer Ingelheim, CSL Behring, Hoffman la Roche and Novartis, travel support from Boehringer Ingelheim, GSK, Hoffman la Roche and Galapagos, advisory board participation with Galapagos, and leadership roles as Chair of the Idiopathic Interstitial Pneumonia group of the European Respiratory Society, Member of the board of the Netherlands Respiratory Society, Member of the scientific advisory board of the European Idiopathic Pulmonary Fibrosis and related disorders federation, Chair of the educational committee of the European Reference Network for rare Lung Diseases, and membership of the advisory board of the Dutch Lungfibrosis and Sarcoidosis patient associations, outside the submitted work. A-M. Russell reports consulting fees from Boehringer Ingelheim, and lecture honoraria from Boehringer Ingelheim, Hoffman La Roche and the Irish Lung Fibrosis Association, outside the submitted work. A.E. Holland is President of Thoracic Society of Australia and New Zealand, an unpaid position unrelated to the present work. All other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. #: one report described the findings from two separate studies; hence 16 reports describe findings from 17 studies.
FIGURE 2
FIGURE 2
At-home studies reporting breathlessness pragmatically during daily life. SMD: standardised mean difference; IV: inverse variance. #: 10 cm visual analogue scale (VAS) breathlessness intensity (final evening relative to baseline); : 10 cm VAS breathlessness intensity now (days 5–7 average of mean morning/evening scores relative to baseline; +: numerical rating scale (NRS) intensity of breathlessness (16 mg per day dose, days 5–7 average scores relative to days −3 to −1 average score; §: 10 cm VAS breathlessness intensity now (final evening score relative to baseline); ƒ: 10 cm VAS breathlessness (final early evening relative to baseline from alternating weeks’ period; ##: 10 cm VAS breathlessness during last hour (change from baseline to follow-up); ¶¶: Chronic Respiratory Disease Questionnaire (CRQ) dyspnoea subscale (change from baseline to 6 weeks); ++: 10 cm VAS breathlessness during past 24 h (change from baseline to follow-up); §§: NRS over past 24 h (change from baseline to follow-up).
FIGURE 3
FIGURE 3
Laboratory-based exercise studies reporting breathlessness at iso-time or iso-load. SMD: standardised mean difference; IV: inverse variance. #: Borg intensity at iso-time; : 10 cm visual analogue scale breathlessness at iso-load.
FIGURE 4
FIGURE 4
At-home studies reporting health-related quality of life. SMD: standardised mean difference; IV: inverse variance. #: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (change from baseline); : COPD Assessment Test (CAT) (16 mg per day dose, change from baseline); +: King's Brief Interstitial Lung Disease (change from baseline); §: Chronic Respiratory Disease Questionnaire (change from baseline); ƒ: CAT (change from baseline).
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