Impact of perioperative esketamine on the perioperative neurocognitive dysfunction: a systematic review and meta-analysis of randomised controlled studies

Objectives: The effect of esketamine on perioperative neurocognitive dysfunction (PND) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of perioperative esketamine administration on PND. Design: Systematic review and meta-analysis. Data sources: PubMed, EMBASE, Web of Science and Cochrane Library were searched from their inception to 25 April 2024. Eligibility criteria for selecting studies: We included the randomised controlled trials (RCTs) that compared single or continuous intravenous infusion of esketamine to saline among adult surgical patients without pre-existing neurocognitive disorders. Data extraction and synthesis: Two reviewers independently extracted pertinent information from the included studies. Risk of bias was assessed using Cochrane's risk of bias criteria. Risk ratios (RRs) and their corresponding 95% CIs were synthesised using a random-effects model. The overall evidence quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework. Results: 10 RCTs were included in our meta-analysis, involving 854 surgical patients. Perioperative esketamine was associated with a reduced risk of postoperative delirium (POD) (relative risk (RR): 0.46, 95% CI: 0.30 to 0.71, p<0.001) and delayed neurocognitive recovery (dNCR) (RR: 0.41, 95% CI: 0.21 to 0.78, p<0.001). However, no statistically significant difference was found in the risk of postoperative neurocognitive disorder (post-NCD) at 3 months postsurgery between the esketamine and control groups (RR: 0.57, 95% CI: 0.19 to 1.73, p=0.40). Additionally, pain severity was reduced on postoperative day 1, with no difference in the risk of adverse events or length of hospital stay. Conclusion: Perioperative esketamine reduces the risk of short-term PND, including POD and dNCR, without significantly affecting the incidence of adverse events or length of hospital stay. However, no significant differences were observed in the risk of post-NCD at 3 months following surgery. This systematic review and meta-analysis offers valuable data for PND research and clinical drug intervention strategies.