The prospective, randomized, double-blind, controlled trial was conducted at the First Affiliated Hospital of Wenzhou Medical University. The study enrolled 133 patients with gastric cancer who were treated by laparoscopic surgery between January 2023 and April 2023 (the diagnostic criteria for gastric cancer are defined in the “Health Industry Standards of the People’s Republic of China: Diagnostic Criteria for Gastric Cancer (WS 316–2010)”), with no gender restriction, age ≥ 18 years old, and ASA grade I to II. The following exclusion criteria were applied: (1) History of radiotherapy and chemotherapy for gastric cancer; (2) Mental disorders; (3) Severe hypertension, coronary heart disease, cardiac insufficiency, pulmonary hypertension, cranial or ocular hypertension, hyperthyroidism, etc.; (4) patients with severe liver and kidney dysfunction; (5) patients with a history of allergic reactions to the drugs used in this study; (6) It is expected that the operation is expected to take more than 10 h, there is the possibility of large blood loss, or conversion to open laparotomy.

This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (approval number: KY2022-201). Additionally, all patients provided written informed consent. The trial was registered at the Chinese Clinical Trial Registry, for the record Numbers for ChiCTR2300072167.

Our research statistician generated random numbers using a computer (simple randomization). The day before the procedure, a study nurse sealed the random numbers in sequentially numbered envelopes and transmitted them to the anesthesiologist. The random numbers then determined the patient’s study group.

Either the esketamine group (Group E) or the control group (Group C) was randomly assigned. Preoperative interviews, eligibility assessments, obtaining written informed consent, the inclusion of participants, and postoperative follow-up were conducted by investigators who had not been involved in perioperative patient care prior to the study and had received training in the assessment of the Visitation scale (all trained and certified by Xinru Lin). Patients and investigators were blinded to study group assignments.

Prior to surgery, all patients were routinely prohibited from drinking and fasting, and no preoperative medications were administered. Following the entry into the operating room, a central vein catheterization was performed(internal jugular vein, Catheter: Bioptimal, cv-501-20yt, size: 5Fr (1.6 mm), Single cavity,20 cm,16Ga), followed by a radial artery puncture catheterization, in order to monitor invasive blood pressure. Patients in both groups receive inhalational and intravenous anesthesia. Under controlled breathing, the Group C was given sufentanil (0.3–0.6 ug/kg), propofol (2 mg/kg), and cisatracurium besylate (0.2 mg/kg) in sequential order during the induction period of anesthesia. The Group E was additionally given 0.5 mg/kg esketamine. During the operation, (0.8-1.0 MAC) sevoflurane was inhaled. Additionally, sufentanil 0.15–0.7ug/kg was intravenously administered at intervals of 30 min. The use of muscle relaxants and vasoactive medications was as required at the discretion of the attending anesthesiologist. The rate of sevoflurane was adjusted intraoperatively to maintain a BIS value of 40–60. Discontinue cisatracurium besylate 30 min before the end of surgery, at the end of the suture, Anesthesia drugs administered inhaled were stopped, and 3 ml of 0.75% ropivacaine was injected into skin wounds to provide anesthesia locally.

After surgery, patients received patient-controlled intravenous analgesia (PCIA). Analgesic pumps in the Group E received sufentanil 2 µg/kg combined with esketamine 1 mg/kg. Group Cs received sufentanil 2 µg/kg, and the total volume of both groups was 100 ml. It was administered continuously to all patients (at a basal rate of 2 mL/h) and on demand as a 2 mL bolus with a lockout interval of 10 min. Immediately after suturing the skin, the infusion began and lasted 48 h. If the VAS score is greater than 3, press the control button, and if the pain does not subside after 30 min, tramadol sustained-release tablets 50–100 mg are used as a remedial analgesic.

The main objective of this study was to assess the variation in postoperative fatigue syndrome (POFS) as measured by the Christensen score three days after surgery. The Christensen fatigue scale, widely employed in clinical settings [23], was utilized to evaluate fatigue levels, with a score of ≥ 6 indicating the presence of postoperative fatigue [24]. The Christensen fatigue scale was administered at four time points: one day before surgery, as well as one, three, and seven days after the surgical procedure.

Secondary outcome measures encompass the evaluation of fatigue levels using the 10-item short form of the Identity-Consequence Fatigue Scale (ICFS-10), assessment of pain severity through the VAS pain score, utilization of postoperative relief analgesics, analysis of sleep quality, determination of the first time out of bed, calculation of the duration of hospitalization, and monitoring of adverse events (such as nausea and vomiting, dizziness, intestinal obstruction, hyperthermia, hypertension, delirium, and palpitations) during the PCIA Rate.

The ICFS, a multidimensional measurement tool, is employed in evaluating the fatigue levels and resumption of regular activities among surgical patients [25, 26]. The ICFS-10, a modified version of the original 31-item ICSF scale, effectively captures 98% of the overall fatigue changes from preoperative to postoperative states, thereby serving as a reliable fatigue indicator subsequent to surgery. Additionally, the survey comprises a concise set of 10 questions, facilitating patient completion and enhancing compliance [27]. In the event of hospital discharge within 7 days post-surgery, patients will be contacted either via phone or WeChat.

No similar research has been conducted on patients who have undergone laparoscopic radical gastrectomy, making it challenging to establish an appropriate foundation for determining the sample size. Based on preliminary findings, Christensen scores on day 3 in the Group C was 5.61 ± 1.63(n = 6), and that in the Group E was 4.79 ± 1.89 (n = 6). Determine the detection level α as 0.05, the detection level β as 0.20, and the degree of certainty (1-β) as 0.80. According to the PASS 15 software, the sample size for the Group E (N1) should be 48 cases, and the sample size for the Group C (N2) should be 48 cases. Considering the 20% loss of follow-up rate, 116 patients, with 58 in each group, were required for this study.

Statistical analysis was performed using SPSS20.0 (IBM, Armonk, NY, USA). Data with a normal distribution were expressed as means ± standard deviations, but data with a skew distribution were expressed as median (25th,75th percentiles). The categorical variable was represented by the number of patients (%). Continuous variables such as Analgesic Dosags were tested for normality using the Kolmogorov-Smirnov test, then Mann-Whitney U or independent sample t tests were used to compare them. Repeated measurement data such as Christensen Score and ICFS-10 score were compared using Repeated ANOVA. The chi-square test or Fisher’s exact test is used to compare categorical variables such as preoperative ASA grading, TNM staging, postoperative fatigue incidence, adverse events, etc., and the results are presented as a percentage. The Hodges-Lehman approach was used to evaluate the differences between the medians and 95% CI. Statistics were deemed significant at P<0.05.