The Effect of Esketamine on Postoperative Cognitive Function in Elderly Patients Undergoing Oral and Maxillofacial Surgery

Effect of Esketamine on Postoperative Cognitive Function in Elderly Patients Undergoing Oral and Maxillofacial Surgery: A Prospective, Randomized, Double-Blind, Placebo-Controlled Parallel Clinical Trial

Esketamine is a common anesthetic adjuvant. Previous studies have shown that it may have protective effects on the brain. This study aims to investigate whether esketamine can improve cognitive function recovery in elderly patients (aged 60 years and older) undergoing oral and maxillofacial surgery.

Participants will be randomly assigned to receive either esketamine or a placebo (normal saline) during anesthesia. Neither the participants nor the researchers will know which treatment is given.

Cognitive function will be assessed using standardized tests before surgery and at 1, 3, 7, and 15 days after surgery. Sleep quality, pain scores, emotional status, and adverse events will also be recorded. Blood samples will be collected to explore potential mechanisms.

The study is expected to enroll approximately 98 participants at the Third Affiliated Hospital of Air Force Medical University in Xi'an, China. Participation will last about 16 days from the day before surgery to the final follow-up on day 15 after surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Perioperative Neurocognitive Disorders
• Intervention / Treatment: Drug: esketamine; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Haopeng Zhang; Phone Number: +86 17791305967; Email: haopeng.zhang@foxmail.com
• Study Contact Backup: Name: Guanghui Hao; Phone Number: +8615291285018; Email: 15291285018@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • The Third Affiliated Hospital of Air Force Medical University
      • Contact: Guanghui Hao, Master's Candidate; Phone Number: +86 15291285018; Email: 15291285018@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age ≥ 60 years, either sex; Scheduled for elective oral and maxillofacial surgery under general anesthesia (including oral and maxillofacial tumor surgery, orthognathic surgery, and maxillofacial trauma repair surgery); American Society of Anesthesiologists (ASA) physical status I-III; Expected duration of anesthesia ≥ 2 hours; Willing and able to provide written informed consent.

Exclusion Criteria:

Pre-existing behavioral disorders or psychiatric diseases (e.g., Alzheimer's disease, Parkinson's disease), or current use of antipsychotic medications (e.g., clozapine, risperidone, olanzapine, haloperidol, chlorpromazine); Pre-existing severe organ dysfunction including: severe cardiovascular disease (life-threatening arrhythmias, severe uncontrolled hypertension, coronary artery disease, heart failure), severe respiratory disease (respiratory failure, severe chronic obstructive pulmonary disease), severe hepatic insufficiency (Child-Pugh Class C), or severe renal insufficiency (glomerular filtration rate < 30 mL/min or creatinine > 2.5 mg/dL); Known contraindications to esketamine including: hypersensitivity to the active substance or any excipients; severe risk of elevated blood pressure or intracranial pressure; uncontrolled or untreated hypertension (resting systolic/diastolic blood pressure > 180/100 mmHg); preeclampsia or eclampsia; untreated or inadequately treated hyperthyroidism; conditions requiring uterine relaxation (e.g., uterine rupture, umbilical cord prolapse); use as the sole anesthetic in patients with significant ischemic heart disease; Surgical approach that would interfere with postoperative MoCA assessment; Concurrent participation in another clinical trial; Pre-existing cognitive impairment or Mini-Mental State Examination (MMSE) score < 24, unable to complete questionnaire-based assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine Group; Participants in this arm will receive an intravenous bolus of esketamine 0.3 mg/kg (administered over 1 minute) after anesthesia induction, followed by a continuous infusion of 0.3 mg/kg/h, which will be discontinued 30 minutes before the end of surgery. The drug will be prepared in normal saline to a total volume of 10 mL and administered in a double-blind manner	Drug: esketamine; Esketamine is administered as an intravenous bolus of 0.3 mg/kg (over 1 minute) after anesthesia induction, followed by a continuous intravenous infusion of 0.3 mg/kg/h until 30 minutes before the end of surgery. The drug is diluted with normal saline to a total volume of 10 mL and prepared in identical syringes to ensure blinding. This intervention is used as the experimental treatment to assess its effect on postoperative cognitive recovery in elderly patients undergoing oral and maxillofacial surgery
Placebo Comparator: Normal Saline Group; Participants in this arm will receive an equal volume of normal saline at the same time points as the experimental group: a bolus after anesthesia induction followed by a continuous infusion, which will be discontinued 30 minutes before the end of surgery. The placebo will be prepared in identical syringes to maintain blinding	Drug: Normal Saline; Normal saline is used as the placebo control. It is administered as an intravenous bolus of equal volume after anesthesia induction, followed by a continuous intravenous infusion at an equal rate until 30 minutes before the end of surgery. The saline is prepared in identical syringes to the experimental drug to maintain double-blind conditions. This intervention serves as the comparator to evaluate the specific effect of esketamine on postoperative cognitive recovery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment (MoCA) Score on Postoperative Day 1	Montreal Cognitive Assessment (MoCA) Score on Postoperative Day 1	Day 1 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Telephone-Montreal Cognitive Assessment (T-MoCA) Score at Postoperative Days 3, 7, and 15	The Telephone-Montreal Cognitive Assessment (T-MoCA) is an adapted version of the MoCA designed for telephone administration, removing visual-dependent items. Total scores range from 0 to 22, with higher scores indicating better cognitive function. It will be administered by trained assessors blinded to group allocation at postoperative days 3, 7, and 15 to track cognitive recovery trajectory	Postoperative days 3, 7, and 15
Sleep Quality Assessed by Athens Insomnia Scale (AIS) at Postoperative Days 1 and 3	The Athens Insomnia Scale (AIS) is an 8-item self-report questionnaire assessing sleep quality over the past 24 hours. Total scores range from 0 to 24, with higher scores indicating worse sleep quality: 0-3 = no insomnia; 4-6 = mild insomnia; 7-10 = moderate insomnia; ≥11 = severe insomnia.	Postoperative days 1 and 3
Pain Intensity Measured by Visual Analog Scale (VAS) at Postoperative Hours 6, 12, and 24	The Visual Analog Scale (VAS) is a 10-cm horizontal line anchored by "no pain" at 0 and "worst imaginable pain" at 10. Patients mark their current pain level, and the distance from 0 is measured in millimeters. Scores range from 0 to 10, with higher scores indicating more severe pain.	Postoperative hours 6, 12, and 24
Emotional Status Assessed by Hospital Anxiety and Depression Scale (HADS) at Postoperative Days 1 and 3	The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-report questionnaire with two subscales: anxiety (7 items) and depression (7 items). Each item is scored 0-3, with subscale scores ranging from 0 to 21. Higher scores indicate worse mood disturbance. Scores ≥11 on either subscale indicate clinically significant symptoms.	Postoperative days 1 and 3
Incidence of Rescue Analgesia	Rescue analgesia is defined as the administration of patient-controlled analgesia (PCA) pump when postoperative VAS score reaches ≥4. The incidence will be recorded and compared between groups	During the first 24 hours after surgery
serological indicators	Peripheral venous blood samples (3 mL) will be collected at baseline (1 day before surgery) and at 24 hours after surgery. Serum levels of inflammatory cytokine interleukin-6 (IL-6), neuronal injury marker S100β protein, brain-derived neurotrophic factor (BDNF), and neurofilament light chain (NfL) will be measured using enzyme-linked immunosorbent assay (ELISA). Correlations between biomarker changes and cognitive outcomes will be explored.	Baseline (1 day before surgery) and 24 hours after surgery
incidence of adverse reactions	Adverse events will be monitored from drug administration to 24 hours post-surgery, including: blood pressure fluctuations (MAP change >20% from baseline), heart rate changes (HR >100 bpm or <50 bpm), psychiatric symptoms (hallucinations, dizziness, somnolence), and gastrointestinal reactions (nausea, vomiting with PONV impact scale ≥1). All adverse events will be recorded and compared between groups	From study drug administration to 24 hours after surgery

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Esketamine; Saline Solution
• Other Study ID Numbers: KQ-YJ-2026-193; 82271231 (Other Grant/Funding Number: National Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No