Effects of Intraoperative Low-Dose Esketamine on Postoperative Inflammatory Response and Clinical Recovery in Elderly Patients Undergoing Colorectal Cancer Resection: A Randomized, Double-Blind, Placebo-Controlled Trial 

<title>Abstract</title> <p> Surgical trauma in elderly patients undergoing colorectal cancer resection often triggers a robust systemic inflammatory response leading to delayed recovery. Esketamine, a noncompetitive NMDA receptor antagonist, may possess anti-inflammatory properties. This study aimed to evaluate the effects of intraoperative low-dose esketamine on serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels, and clinical recovery outcomes in this population. <bold/> This was a single-center, prospective, randomized, double-blind, placebo-controlled trial. Sixty elderly patients (60–85 years, ASA grade I–II) scheduled for elective laparoscopic radical resection of colorectal cancer were randomized (1:1) to receive either low-dose esketamine (0.2 mg/kg/h) or normal saline (control) during anesthesia maintenance. The primary outcome was the concentration of serum TNF-α at preoperative, 0.5h, and 16h postoperative time points. Secondary outcomes included IL-6 levels, intraoperative propofol consumption, anesthesia recovery and extubation times, postoperative Visual Analogue Scale scores, the frequency of patient-controlled analgesia compressions, and the incidence of adverse events. Forty-six patients (n=26 in the esketamine group; n=20 in the control group) were finally included in the statistical analysis. Compared to the control group, the esketamine group exhibited significantly lower TNF-α concentrations at 0.5h and 16h postoperatively (P &lt; 0.05). After adjusting for baseline imbalance, no statistically significant differences were observed in postoperative IL-6 levels between the two groups (P &gt; 0.05). The esketamine group showed significantly lower intraoperative propofol consumption (P &lt; 0.001), shorter anesthesia recovery and extubation times (P &lt; 0.05), and reduced VAS scores at 6h-48h post-surgery (P &lt; 0.05). Furthermore, hospitalization duration was shorter in the esketamine group (P &lt; 0.001). There was no significant increase in adverse events such as hallucinations or nausea. <bold/> Intraoperative low-dose esketamine (0.2 mg/kg/h) effectively suppresses the postoperative release of TNF-α, reduces propofol requirements, and enhances postoperative analgesia and clinical recovery in elderly patients undergoing colorectal surgery. <bold>Trial Registration:</bold> The study was retrospectively registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2500101206) on April 22, 2025. </p>