Esketamine has promising anti-inflammatory effects in orthopedic surgery and plays a protective role in postoperative cognitive function and pain management.

Am J Transl Res 2025;17(1):277-285 www.ajtr.org /ISSN:1943-8141/AJTR0160298 Original Article Esketamine has promising anti-inflammatory effects in orthopedic surgery and plays a protective role in postoperative cognitive function and pain management Lichun Han1,2, Bozhen Tian2, Siyuan Li3 The Key Laboratory of Biomedical Information Engineering of The Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, Shaanxi, China; 2Department of Anesthesiology, Xi’an Daxing Hospital, Xi’an 710000, Shaanxi, China; 3Anesthesia and Comfort Health Center, Xi’an International Medical Center Hospital, Xi’an 710004, Shaanxi, China 1 Received September 3, 2024; Accepted December 10, 2024; Epub January 15, 2025; Published January 30, 2025 Abstract: Objective: To investigate the effects of subanesthetic doses of esketamine on serum inflammatory cytokine levels and its impact on postoperative cognition and pain in patients undergoing elective orthopedic surgery. Methods: From November 2023 to March 2024, patients scheduled for elective orthopedic surgery were randomly divided into an observation group or a control group, with 100 patients in each group (ChiCTR2300079156). The observation group received an intravenous injection of 0.25 mg/kg esketamine before the induction of general anesthesia, while the control group was administered an equivalent volume of normal saline. Postoperative measurements included serum levels of interleukin-6 (IL-6), interleukin-1 (IL-1), and interleukin-10 (IL-10), as well as immunoglobulin levels (IgM and IgG), complete blood count (including white blood cell count, hemoglobin, and platelet count), intraoperative blood loss, cognitive function scores (assessed using the Mini-Mental State Examination [MMSE]), postoperative pain scores, and the incidence of adverse reactions (including nausea, vomiting, headache, dizziness, hallucinations, agitation, allergic reactions, and cardiovascular and respiratory responses). Results: Postoperatively, serum levels of IL-6 and IL-1 in the observation group were significantly lower than those in the control group (P<0.05), while IL-10 levels were significantly higher (P<0.05). The control group showed a significant decrease in immunoglobulin levels (IgM and IgG) after surgery, whereas the observation group exhibited higher postoperative immunoglobulin levels compared to control group. In terms of complete blood count, the observation group had significantly better white blood cell and platelet counts compared to the control group (P<0.05), with no significant difference in hemoglobin levels. Intraoperative blood loss was significantly lower in the observation group (P<0.05). Cognitive function, as measured by the MMSE scores, was significantly better in the observation group compared to the control group at 6 and 24 hours postoperatively (P<0.05). Additionally, the observation group had significantly lower pain scores at 6 and 24 hours postoperatively and a lower incidence of adverse reactions. Conclusion: Subanesthetic doses of esketamine in elective orthopedic surgery can effectively reduce postoperative inflammatory cytokine levels, improve immunoglobulin levels, reduce intraoperative blood loss, protect postoperative cognitive function, and significantly decrease the incidence of postoperative pain and adverse reactions. These findings suggest that subanesthetic dosing of esketamine has a high level of safety and efficacy in this clinical setting. Keywords: Esketamine, inflammatory cytokines, orthopedic surgery, cognitive function, adverse reactions, complete blood count Introduction Elective orthopedic surgery plays a crucial role in the field of surgery, with postoperative recovery and prognosis directly impacting the patient’s quality of life. However, the surgical procedure itself is inherently traumatic and often triggers the activation of the body’s inflamma- tory response. This inflammatory reaction not only increases the risk of postoperative complications but also negatively affects immune function and cognitive abilities. Recent studies have highlighted the importance of controlling postoperative inflammation to improve patient outcomes [1]. Esketamine, a commonly used anesthetic with both analgesic and anti-inflamhttps://doi.org/10.62347/VTKD5295 Esketamine’s effects in orthopedic surgery matory properties, has garnered increasing attention for its potential benefits when administered at subanesthetic doses. Previous studies have demonstrated that low dose esketamine can modulate immune responses and reduce inflammatory cytokine levels, thereby decreasing the incidence of postoperative complications [2, 3]. However, there is a lack of systematic research on the effects of subanesthetic doses of esketamine on serum inflammatory cytokine levels and other related physiological indicators in patients undergoing elective orthopedic surgery [4, 5]. Therefore, this study aims to investigate the impact of subanesthetic doses of esketamine on postoperative serum inflammatory cytokine levels, immunoglobulin levels, complete blood count parameters, intraoperative blood loss, cognitive function, and the incidence of adverse reactions in patients undergoing elective orthopedic surgery. Materials and methods General information A prospective study design was employed, enrolling 200 patients scheduled for elective orthopedic surgery at Xi’an International Medical Center Hospital from November 2023 to March 2024. Patients were randomly assigned to either the observation group (esketamine) or the control group (placebo) using a random number table, with 100 patients in each group (clinical trial registration number: ChiCTR2300079156). This study was approved by the Medical Ethics Committee of Xi’an International Medical Center Hospital. All patients in the study signed informed consent forms. Inclusion Criteria: (1) Patients undergoing elective orthopedic surgery under general anesthesia; (2) Age between 18 and 89 years, regardless of gender; (3) American Society of Anesthesiologists (ASA) physical status classification of I-III. Exclusion Criteria: (1) Patients with cardiac, pulmonary, hepatic, or renal insufficiency; (2) Patients with hematological disorders; (3) History of medication use within 1 month prior to surgery, including opioid analgesics, nonsteroidal anti-inflammatory drugs, antibiotics, or antidepressants; (4) History of alcohol abuse; (5) Patients with psychiatric disorders; (6) Patients 278 with endocrine-related diseases such as thyroid disease, diabetes, or hypothalamic-pituitary-adrenal axis disorders; (7) Use of sedatives, antiemetics, or antipruritic medications within 24 hours before surgery; (8) Pregnant or lactating women; (9) Individuals unable to understand verbal instructions; (10) Any other factors that may influence the outcome of the trial. Study methods Preoperative preparation: Intravenous access was established, and blood oxygen satura (...truncated)