Esketamine and neurocognitive disorders in adult surgical patients: a meta-analysis

Prior meta-analyses have established the potential of intravenous ketamine in safeguarding against neurocognitive impairment, but the efficacy of intravenous esketamine for the prevention of perioperative neurocognitive disorders (PND) remains uncertain. The primary aim of this meta-analysis was to conduct a comprehensive evaluation of the effects of esketamine on PND in adult surgical patients undergoing general anesthesia.

We searched several electronic databases and clinical trial registries to find relevant trials. Randomized controlled trials of perioperative use of esketamine adjuvant were included in the analysis. The main outcome measured was the risk of postoperative delirium(POD) and postoperative cognitive dysfunction (POCD). Secondary outcomes included the assessment of postoperative cognitive status, pain scores (VAS/NRS), remifentanil consumption and the occurrence of postoperative nausea and vomiting (PONV).

Thirteen studies encompassing procedures such as abdominal, thoracoscopic lung, gastrointestinal, laparoscopic gynecological, spinal surgery, and modified radical mastectomy, were included in the analysis. A cohort comprising 1068 adult patients underwent general anesthesia, with 584 patients assigned to the esketamine group and 484 patients designated to the placebo group. The administration of general anesthesia was augmented by intravenous infusion of esketamine, and a comparative analysis was conducted in relation to alternative pharmacological interventions or a placebo. The application of esketamine during the perioperative period was observed to decrease the risk of POD ( RR 0.46; 95% CI: 0.32, 0.66, p < 0.0001, GRADE = High) and exhibited a protective influence on POCD (RR = 0.50; 95%CI: 0.30, 0.84, p = 0.009, I² = 0%, GRADE = Moderate). Significant improvements were observed at 4, 24 and 48 h post-surgery when comparing esketamine to a placebo (4 h: SMD -0.78, 95% CI: -1.24, -0.32, p = 0.0009, I² = 58%, GRADE = Low; 24 h: SMD -0.92, 95% CI: -1.40, -0.44, p = 0.0002, I2 = 86%, GRADE = Low; 48 h: SMD -0.9, 95% CI: -1.68, -0.12, p = 0.02, I² = 89%, GRADE = Low), and intraoperative remifentanil consumption was significantly reduced in the esketamine group (SMD -0.56; 95%CI: - 0.86, - 0.27, p = 0.0002, I² = 62%, GRADE = moderate). A notable reduction in the risk of PONV was observed in the esketamine group(RR = 0.64; 95%CI: 0.49, 0.84, p = 0.001, I² = 0%, GRADE = High).

The use of intravenous esketamine as an adjuvant in general anesthesia may represent a potentially beneficial strategy for reducing susceptibility to PND, with potential benefits for preventing POD and POCD. Furthermore, it can decrease intraoperative opioid consumption and alleviate postoperative pain intensity without increasing the incidence of PONV.

This meta-analysis was registered on PROSPERO (CRD42023453714).