1. Research design: This is a 1:1 parallel, double-blind (participants, investigators, and outcomes assessors) randomized controlled trial. Intravenous lidocaine or saline will be assigned to patients with lung cancer undergoing minimally invasive (thoracoscopic or robotic) surgery.
2. Research Methods:
2.1. Intervention: 2% lidocaine hydrochloride or placebo (0.9% sodium chloride).
2.2. Dose planning: The intervention initiates within 30 minutes before anesthesia induction with an intravenous loading dose of 1.5 mg/kg (ideal body weight, IBW) administered over 10-20 minutes. This is followed by a continuous maintenance infusion of 1-1.5 mg/kg/h during surgery, terminating 1 hour after skin closure. The maximum infusion rate is capped at 120 mg/h. IBW is used to calculate dosage to prevent toxicity in overweight patients; however, for patients weighing less than their IBW, actual body weight is used. Patients in the placebo group receive the same volume and rate as the treatment group.
Dose Guidelines Based on IBW (Broca Index): Males: height (cm) - 100; Females: height (cm) - 105.
2.3. Dose adjustment: No dosage changes are permitted. If systemic local anesthetic toxicity is suspected, the infusion must be stopped immediately and not resumed. Supportive care and lipid emulsion therapy will be provided. If infusion is interrupted due to mechanical issues (e.g., pump malfunction), it may be restarted at the original rate.
2.4. Additional care and procedures: To minimize confounding, general anesthesia will be maintained using a balanced technique. Postoperative care follows the unit's standard Enhanced Recovery After Surgery (ERAS) protocol. Concurrent continuous infusion of other local anesthetics (e.g., epidural or wound catheters) is prohibited during the IMP infusion period.
2.5. Postoperative analgesia management: After surgery, all patients will receive intravenous patient-controlled analgesia (or continuous infusion) with sufentanil (2 µg/kg diluted to 100 ml) at a background rate of 2 ml/h.
2.6. Sample size calculation: Based on a median recurrence-free survival (RFS) of 18 months in the control group and an expected extension to 24 months in the treatment group, the estimated Hazard Ratio (HR) is 0.75 (representing a 25% risk reduction). With a two-sided alpha of 0.05 and 90% power, 635 patients per group are required. Adjusting for a 10% dropout rate, the total sample size is set at 1400 patients (700 per group).
2.7. Randomization: Participants will be randomly assigned (1:1) using a minimization algorithm. Stratification factors include age (\<45, 45-65, 65-80 years), gender, trial center, and pathological type of lung cancer.
3. Efficacy evaluation criteria: The primary efficacy endpoint is Disease-Free Survival (DFS) within 36 months post-surgery. Chest CT scans will be performed at 6, 12, 18, 24, and 36 months to assess recurrence or metastasis. Additionally, the FACT-L questionnaire will be used to assess cancer-specific quality of life.
4. Adverse events: The lidocaine dose and duration in this study align with international consensus statements on safety. The infusion is limited to the intraoperative period and ends 1 hour post-skin closure, minimizing accumulation risks. Safety monitoring will be conducted throughout the infusion. In the event of toxicity, lipid emulsion (20%) is available for immediate rescue following AAGBI guidelines.
5. Quality control and quality assurance: SOPs will be strictly followed. Since the IMP infusion ends 1 hour after skin closure, monitoring will primarily occur in the operating room and PACU. Data will be recorded using EDC software. The investigators aim to collect outcome data for all randomized participants according to the intention-to-treat principle.
6. Statistical analysis: Data will be analyzed using SPSS 21 based on the intention-to-treat (ITT) principle.
Primary Analysis: The primary outcome (DFS at 36 months) will be analyzed using a multivariate Cox regression model to estimate the Hazard Ratio (HR) between the lidocaine and placebo groups, adjusting for covariates.
Covariates: Age, gender, comorbidities, ASA classification, cancer stage, and neoadjuvant therapies.
Survival Analysis: Kaplan-Meier curves and Log-rank tests will be used to compare survival distributions.
Missing Data: Missing data will be handled using multiple imputation to ensure robustness.
7. Ethics: The study adheres to the Declaration of Helsinki and local regulations. Ethics committee approval is required prior to initiation. Written informed consent will be obtained from all participants, ensuring they understand the risks and their right to withdraw. Privacy and data confidentiality will be strictly maintained.
