This prospective study included a total of 120 patients who were scheduled for elective TKA and were enrolled at the Affiliated Hospital of Nantong University from October 2022 to December 2022. Study approval was obtained from the Institutional Review Board of Ethics Committee of Affiliated Hospital of Nantong University (number: 2022-K023) and the PODCAST trial is registered with clinicaltrials.gov, number NCT05533970 on 09/09/2022. Patients and their family members were informed about the treatment and signed a consent form. The trial was conducted in accordance with the Declaration of Helsinki.

The inclusion criteria for participants in this study were as follows: patients aged between 18 and 65 years, patients with an American Society of Anesthesiology (ASA) score of I, II, or III, and a body mass index (BMI) ranging from 18 to 38 kg/m2. The primary exclusion criteria included the presence of cerebrovascular diseases, coagulopathy, complications related to mental illness, hepatic, renal, or cardiorespiratory failure, allergy to local anesthetics, and pregnancy.

Randomization tables generated by computers randomly assigned patients to three groups (n = 32) to receive 30 mL of plain ropivacaine 0.375% plus 0.25 μg/kg dexmedetomidine (D0 group), 30 mL of plain ropivacaine 0.375% plus 0.5 μg/kg dexmedetomidine (Da group), or 30 mL of plain ropivacaine 0.375% plus 1 μg/kg dexmedetomidine (Db group). The investigator who creates the random sequence is the investigator who logs in and assigns study patients to study groups according to the random list.

Group work was hidden in sealed, numbered, opaque envelopes until the day of surgery. The anesthesiologist’s assistant opened each bag and prepared appropriate study medication. This anesthesiologist is no longer involved in research or patient care. Anesthetists who performed postoperative patient assessments, surgeons, physical therapists, acute pain nurses, and researchers were blinded to treatment group assignment.

All patients were intubated through the peripheral vein of the arm in the anesthesia preparation room, and blood oxygen saturation (SpO2), heart rate (HR), end-tidal carbon dioxide (EtCO2), invasive blood pressure (IBP) and electrocardiogram (ECG) were routinely monitored. The modified high fascia iliaca compartment block was administered 30 minutes prior to surgery. The patient was positioned supine, and the anterior superior iliac spine was identified as a reference point, 5 cm below which the iliac crest was determined. Using ultrasound guidance, the ‘bow-tie sign’ was identified, and the puncture site was disinfected with a skin disinfectant. Various drug concentrations were utilized based on the assigned groups. After entering the operating room, anesthesia was induced with midazolam 0.15 mg/kg, propofol 4 mg/kg, sufentanil 0.25 μg/kg, cisatracurium 0.2 mg/kg Intubation. While propofol and remifentanil were used for the maintenance of anesthesia. Intraoperatively, Lactated Ringer’s solution was administered at a rate of 6 to 8 ml/kg per hour. The consumption of remifentanil and propofol during operation was recorded.

Degree of pain was evaluated by the numerical rating scale at rest (NRS.R) and during movement (NRS.M) at the same time points. The patients were provided with patient-controlled intravenous anesthesia (PCIA) devices contained 100-mg morphine (1 mg/ml) without continuous infusion and set with a lock-out time of 15 min. Patients were instructed to use the device by pushing the button when needed. The devices were set to a maximum dose of 20 mg morphine per day. The post-operative button-push count for PCIA demand and PCIA usage dosage were calculated and recorded at the first 48 h postoperative.

We systematically assess and record the occurrence of adverse events every 8 h was conducted to determine the incidence of adverse events following surgery, including nausea, vomiting, hypotension, bradycardia, arrhythmia, respiratory depression, mechanical ventilation, pruritus, and sedation. Using the three-point scale (1 = mild, 2 = moderate, 3 = severe) above, postoperative nausea, vomiting, and pruritus were assessed.

During the patients’ visits to the pain clinic in the third and sixth months after surgery, an untrained physician unknowingly assessed them. The assessment included evaluating pain intensity, nature, duration, aggravating and mitigating factors, and analgesic medication. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale was used as the assessment tool to evaluate chronic neuropathic pain in this study [19].

Our primary outcome parameter was the difference in NRS scores at movement during the first 48 h postoperatively. According to the preliminary experiment, expected post-treatment the NRS scores at movement during the first 48 h postoperatively was 3.9 ± 1.2 in group D0, 3.5 ± 0.9 in group Da and 2.9 ± 0.5 in group Db. We use PASS 15 software to estimate the sample size required for this study, multiple independent samples one-way ANOVA was used. Power analysis indicated that a minimum sample size of 29 patients in each group was needed, with a significance level of 0.05 and a power of 0.8. To account for patient dropout and protocol violations, the final is derived as at least 32 cases per group, we recruited a total of 96 patients.

The distribution of baseline variables was assessed using the Shapiro-Wilk test. Continuous variables were reported as mean (± SD) and analyzed using one-way ANOVA with post-hoc multiple comparisons. Categorical data were reported as numbers and percentages and analyzed using the chi-squared test or Fisher’s exact test with the Bonferroni correction to calculate adjusted P-values. Nonparametric data were analyzed using the Mann-Whitney U test. Statistical significance was defined as a p-value less than 0.05. All statistical analyses were performed using IBM SPSS Statistics version 26.