A comprehensive review and meta-analysis on the safety and efficacy of esketamine for emerging delirium in elderly patients.

Background: Postoperative delirium (POD), a common complication in older surgical patients, has an incidence between 20 and 50%, highlighting the importance of effective intervention methods. Preventive methods available so far mainly focus on the reduction of well-known perioperative risks to prevent POD onset. Esketamine, a newly added therapeutic agent, has also exhibited the potential for POD incidence reduction and the improvement of patient outcomes. Previous meta-analyses and systematic reviews primarily focused on general adult patient groups; thus, the purpose of the current meta-analysis was specifically to examine the efficacy and safety outcomes of esketamine administration in surgical operations among elderly patients. Methods: This study was registered with PROSPERO (CRD420251151647). A literature search was conducted in the Cochrane Library, PubMed, Embase, Ovid, Scopus, and Web of Science databases until 1 October 2025. Eligible studies were English-language randomized controlled trials (RCTs) involving surgical patients aged ≥60 and reporting esketamine-related POD outcomes. Two reviewers independently selected studies and extracted data. The study quality was assessed using the Cochrane risk of bias (RoB) 2 tool. Data were pooled using fixed- or random-effects models and reported as risk ratios (RRs) or standardized mean differences (SMDs) with 95% CI. Heterogeneity was evaluated using I2 statistics, and publication bias was assessed using funnel plots and Egger's test. Results: A total of 13 RCTs involving 1,581 elderly surgical patients were analyzed. Esketamine significantly reduced the incidence of POD (RR = 0.58, 95% CI: 0.43-0.79), postoperative nausea and vomiting (RR = 0.57, 95% CI: 0.44-0.74), perioperative hypotension (RR = 0.47, 95% CI: 0.27-0.81), and opioid consumption during anesthesia induction (SMD = -0.43, 95% CI: -0.59 to -0.26). However, it increased dizziness (RR = 1.29, 95% CI: 1.03-1.62) and perioperative hypertension (RR = 2.40, 95% CI: 1.16-4.97). No significant differences were found in pain scales [visual analog scale (VAS) and Numerical Rating Scale (NRS)], cognitive function [Mini-Mental State Examination (MMSE)], or psychological events (hallucinations and nightmares). Conclusion: Although perioperative esketamine exhibits benefits across multiple recovery outcomes, particularly in reducing intraoperative opioid consumption during induction, highlighting its potential for optimizing analgesic strategies, caution is warranted regarding the elevated risk of perioperative hypertension in elderly patients. The substantial heterogeneity observed in certain outcomes necessitates further validation. Therefore, current evidence does not yet support its routine clinical application. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251151647, identifier CRD420251151647.