IntroductionMillions of persons with chronic pain across North America and Europe use opioids. While the immunosuppressive properties of opioids are associated with risks of infections, these outcomes could be mitigated through careful patient selection and monitoring practices when appropriate. It is important to recognise that some patients do benefit from a carefully tailored opioid therapy. Enough primary studies have been published to date regarding the role of opioids in potential immunosuppression presenting as an increased rate of infection acquisition, infectious complications and mortality. There is thus a critical need for a consensus in this area.Methods and analysisThe methodology is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies and the Cochrane Handbook for Systematic Reviews of Interventions. We plan to systematically search Ovid MEDLINE, CINAHL, PsycINFO, EMB Review, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Google Scholar databases from their inception date to December 2023. Full-text primary studies that report measurable outcomes in adults with chronic pain, all routes of opioid use, all types of infections and all settings will be included. We will identify a scope of reported infections and the evidence on the association of opioid use (including specific opioid, dosage, formulation and duration of use) with the risk of negative infectious outcomes. Opioid use-associated outcomes, comparing opioid use with another opioid or a non-opioid medication, will be reported. The meta-analysis will incorporate individual risk factors. If data are insufficient, the results will be synthesised narratively. Publication bias and confounding evaluation will be performed. The Grading of Recommendations Assessment, Development and Evaluation framework will be used.Ethics and disseminationApproval for the use of published data is not required. The results will be published, presented at conferences and discussed in deliberative dialogue groups.PROSPERO registration numberCRD42023402812.
