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

Background: People living with serious respiratory illness (SRI) 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 SRI. EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to 11th July 2022. Reports of randomised controlled trials (RCTs) administering opioids to treat symptoms in people with SRI were included. Key exclusion criteria included <80% of participants have a non-malignant 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: Of 17 included trials, 6 were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and 1 (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 (odds ratio (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.