Postoperative pain and pain management and neurocognitive outcomes after non-cardiac surgery: a protocol for a series of systematic reviews

Background: Postoperative delirium (POD) is common after non-cardiac surgery in older adults and can result in increased risk of adverse outcomes including postoperative cognitive dysfunction (POCD). Pain after surgery is also frequent and can persist as chronic postsurgical pain (CPSP). Evidence is inconsistent and controversial on whether acute and chronic postsurgical pain, and different postoperative pain management strategies (including opioid versus opioid-sparing strategies), is associated with the occurrence of POD and POCD. In this protocol, we propose a series of systematic reviews to answer the following research questions: In adults undergoing non-cardiac surgery, (1) is acute postsurgical pain associated with POD and/or POCD? (2) Are opioid-sparing/avoidance strategies of acute postoperative pain management associated with lower incidence and/or severity of POD and POCD, compared to predominantly opioid-based strategies? (3) Is CPSP associated with POCD? (4) Are opioid-sparing management strategies of CPSP associated with lower incidence and/or severity of POCD compared to standard of care or strategies not aiming at reduced opioid use? Methods: We will search MEDLINE, EMBASE, Cochrane (CENTRAL), CINAHL, and PSYCHINFO. According to the research question, we will include cohort and case-control studies (questions 1 and 3) or randomized controlled trials and non-randomized studies (questions 2 and 4). The risk of bias will be assessed independently and in duplicate using the revised Cochrane risk-of-bias tool, the Newcastle-Ottawa Scale, and the Joanna-Briggs Institute critical appraisal checklist. Disagreements will be resolved by a third reviewer. Findings will be reported narratively, and where possible and appropriate, meta-analyses will be performed. Certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We will conduct the reviews in accordance with the guideline of the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols. Discussion: Our systematic reviews will summarize available evidence to date on the association of postoperative pain and its management strategies with the incidence of POD and POCD in non-cardiac surgery. We will evaluate the existing evidence and its limitations and inform the design of future interventional studies comparing the effects of different pain management strategies on postoperative neurocognitive outcomes. Systematic review registration: PROSPERO CRD42021192105.