Effect of Subanesthetic Dose of Esketamine on Perioperative Neurocognitive Disorders in Elderly Undergoing Gastrointestinal Surgery: A Randomized Controlled Trial

Background: Perioperative neurocognitive disorders (PND), including delayed neurocognitive recovery (dNCR) and postoperative cognitive dysfunction (POCD), are common postoperative complications in elderly patients and adversely affect their prognosis. The study was designed to explore the effects of esketamine on postoperative cognitive function in elderly patients who underwent gastrointestinal surgery under general anesthesia and its potential mechanism. Methods: Eighty-four patients aged 65 and above undergoing gastrointestinal surgery were randomly divided into 2 groups: the esketamine group (group S) and the control group (group C). Group S received intravenous sub-anesthetic doses of esketamine (0.15 mg/kg) 5 minutes before the initiation of surgery, while group C received the same volume of saline. A battery of neuropsychological tests was used to assess cognitive function before surgery, 7 days, and 3 months after surgery. The primary outcome was the incidence of dNCR at 7 days postoperatively and POCD at 3 months postoperatively in both groups. The secondary outcome measures included changes in the levels of serum interleukin-6 (IL-6) and calcium-binding protein β (S100β) before and 1 day after surgery. Results: The incidence of dNCR in group S was lower than that of group C (18.15% vs 38.24% P=0.033). Contrarily, there was no difference in both groups regarding POCD 3 months postoperatively (6.06% vs 14.37% P=0.247). Plasma IL-6 and S100β levels were significantly elevated in both groups on postoperative day 1 (p< 0.05), but esketamine pretreatment reduced these levels to some extent compared with group C (p< 0.05). Conclusion: Sub-anesthetic doses of esketamine might reduce the incidence of dNCR and improve early postoperative cognitive function in elderly patients undergoing gastrointestinal surgery, which might be related to the anti-neuroinflammation effects of esketamine. Keywords: esketamine, perioperative neurocognitive disorders, gastrointestinal surgery, elderly, neuroinflammatory