Effect of perioperative esketamine administration on the incidence of postoperative delirium: a systematic review and meta-analysis

Postoperative delirium (POD) is a common neurocognitive complication following surgery, particularly in older adults. Esketamine has been investigated for potential neuroprotective effects in the perioperative setting. This systematic review and meta-analysis aimed to evaluate the effect of perioperative esketamine on the incidence of POD. A comprehensive literature search was conducted across multiple electronic databases (PubMed, Cochrane Library, EMBASE, and Google Scholar) to identify randomized controlled trials (RCTs) evaluating the association between perioperative esketamine administration and POD. The primary outcome was the incidence of POD. Secondary outcomes included postoperative cognitive dysfunction (POCD), delayed neurocognitive recovery (dNCR), postoperative nausea and vomiting (PONV), length of hospital stay, length of post-anesthesia care unit (PACU) stay, and postoperative pain in the first 24 h after surgery. PROSPERO registration: CRD42024587392. 25 RCTs involving 3,669 participants were included (esketamine: 17 trials; ketamine: 8 trials). Esketamine was associated with a lower incidence of POD (risk ratio [RR]: 0.55, 95% confidence interval [CI]: 0.46–0.67, P < 0.00001), whereas ketamine showed no significant effect (RR: 0.64, 95% CI: 0.32–1.29, P = 0.21). Results were consistent in studies enrolling elderly patients (≥ 65 years) (RR: 0.57, 95% CI: 0.41–0.80, P = 0.001). Esketamine was also associated with a lower risk of PONV and reduced pain within 24 h after surgery. No significant differences were observed in hospital or PACU length of stay. Perioperative administration of esketamine was associated with significantly lower incidence of POD, without concomitant increases in length of hospital or PACU stay. 1. Perioperative administration of esketamine was associated with significantly reduced incidence of postoperative delirium. 2. Secondary analysis demonstrated that ketamine administration was not associated with a significant reduction in the incidence of postoperative delirium. 3. Our study revealed no significant increase in hospital or post-anesthesia care unit stay associated with esketamine use.