Effects of Esketamine on Postoperative Cognitive Function in Elderly Patients Undergoing Pulmonary Lobectomy: A Randomised, Single-Blind Controlled Clinical Trial.

BACKGROUND: Elderly patients undergoing pulmonary lobectomy with incision are at a high risk for postoperative cognitive dysfunction (POCD). Intraoperative esketamine may offer potential neuroprotective benefits. This study aimed to evaluate the efficacy of intraoperative esketamine in reducing the incidence of POCD in elderly patients undergoing pulmonary lobectomy with incision. METHODS: In this single-blind, controlled clinical trial, patients (aged 65-75 years) undergoing conventional pulmonary lobectomy were randomly allocated to receive esketamine (0.3 mg/kg/h) or remifentanil (0.1-0.2 µg/kg/min) during surgery. Cognitive function was assessed using the mini-mental state examination (MMSE) and negative emotional scores were recorded at baseline and multiple postoperative time points. Intraoperative and postoperative parameters, including heart rate (HR) and mean arterial pressure (MAP), pain scores and adverse events, were recorded. Blood samples were collected to measure amyloid-beta (Aβ) and microtubule-associated protein tau (tau) concentrations. RESULTS: No significant difference was found in the incidence of postoperative delirium between the two groups, but the esketamine group exhibited a significantly lower incidence of POCD on days 1 and 3 postoperatively than the control group. The esketamine group also had significantly higher serum Aβ42/40 levels and significantly lower tau levels on day 1 postoperatively. At the end of surgery, the HR, MAP and pain visual analogue scale score of the control group were significantly higher than those of the esketamine group. No significant differences were observed in terms of adverse events between the two groups. CONCLUSION: Intraoperative administration of esketamine (0.3 mg/kg/h) was associated with a lower incidence of POCD and more stable hemodynamic indicators in elderly patients undergoing thoracic surgery, without increasing adverse events. The application of esketamine indicates a possible benefit with a favourable safety profile in reducing postoperative cognitive decline in this population. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200065266.