Effects of perioperative remote ischemic conditioning on postoperative delirium and cognitive outcomes: a systematic review and meta-analysis of randomized controlled trials

Abstract Purpose Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common complications in surgical patients, which contribute to longer hospital stays, poorer functional outcomes and reduced quality of life. As a potential intervention to address this significant burden, remote ischemic conditioning (RIC)—a low cost, non-invasive therapy involving inducing brief cycles of ischemia and reperfusion—has gained interest. The aim of this systematic review and meta-analysis was to synthesise current evidence on the effects of perioperative RIC on neurocognitive outcomes. Methods This systematic review was conducted in accordance with PRISMA guidelines and was registered with PROSPERO (CRD420251041823). A literature search was performed using MEDLINE, Embase, and Web of science from inception to March 16, 2025. Eligible studies included randomized controlled trials (RCTs) assessing the use of perioperative RIC in human adults (≥ 18 years of age) undergoing surgery. Outcomes of interest included incidence of POD and POCD, and performance on global and domain-specific cognitive measures (e.g., Mini Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], and Trail Making Test [TMT]). Study screening, data extraction, and risk of bias assessment using the Cochrane risk of bias tool (ROB-2) were performed by independent reviewers. The DerSimonian-Laird model was used to analyze outcomes, while study heterogeneity was evaluated using Cochran’s Q. Results Out of 4,664 records screened, 16 publications from 15 RCTs (2,912 patients) were included. POD incidence at < 30 days (odds ratio [OR]: 0.77, 95% confidence interval [CI] 0.50 to 1.20, n = 6), POCD incidence at < 30 days (OR: 0.79, 95% CI 0.53 to 1.20, n = 5) and POCD incidence at ≥ 30 days groups (OR: 1.06, 95% CI 0.62 to 1.80, n = 3) were not significantly different between groups. Conversely, patients who received RIC had better MoCA (standardized mean difference [SMD] = 0.48, 95% CI 0.19 to 0.76, n = 2), Stroop test part 1 (SMD = 0.38, 95% CI 0.13 to 0.64, n = 2) and part 2 (SMD = 0.26, 95% CI 0.05 to 0.48, n = 2) scores at < 30 days, and better MMSE (SMD = 1.16, 95% CI 0.81 to 1.50, n = 2) scores at ≥ 30 days. RIC did not significantly improve TMT A and B completion time, Digit Symbol Substitution Test scores, Stroop part 3, Verbal Fluency Test semantic/phonemic, digit span forward/backward, and immediate/delayed verbal memory at any time point. Conclusion We found no support for a preventative effect of perioperative RIC on the incidence of short- and long-term post-operative neurocognitive disorders. Whereas there was no clear benefit of RIC for domain-specific cognitive performance, results indicated the intervention may improve global cognitive function, although there were only a limited number of trials in this regard.