Assessing the relative efficacy of components of opioid-free anaesthesia in adult surgical patients: protocol for a systematic review and component network meta-analysis

Introduction The rise of opioid-free anaesthesia (OFA) aims to reduce postoperative pain while reducing opioid-related side effects during surgery. However, the various adjuvant agents used in OFA complicate the evaluation of their effectiveness and risks. Recent reviews question the clinical benefits of OFA, highlighting the need for thorough evaluation. This protocol describes a network meta-analysis to compare the effectiveness of OFA with opioid-based anaesthesia and will identify key components for optimal postoperative outcomes. Methods and analysis We will perform a systematic search of literature published in English without time restriction in Embase, The Cochrane Library, MEDLINE (via PubMed) and CINAHL, along with Google Scholar for grey literature. The final search will be performed on 1 October 2024. We will include randomised controlled trials with adult patients undergoing surgery with general anaesthesia, excluding preclinical, observational, regional anaesthesia-only and prolonged anaesthesia outside the operating room studies. The primary outcome is postsurgical pain scores, with secondary outcomes including quality of recovery, opioid consumption, adverse effects and long-term events. We will assess bias using the Cochrane risk of bias 2 tool and conduct Bayesian network meta-analyses for pooled estimates. We will report effect estimates as ORs and standardised mean differences with 95% credible intervals and assess certainty using GRADE methodology. Ethics and dissemination Ethics approval is not required for this systematic review. Results will be published in a peer-reviewed journal and presented at national and international anaesthesia and pain management conferences. PROSPERO registration number CRD42024505853.