This prospective, randomized, double-blinded study was approved by the Medical Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (No. LCKY2019-07). This study is in accordance with the CONSORT 2010 statement [14]. We would go to the ward the day before the operation and give informed consent to the patient in a separate room. After obtained the written informed consent, 64 patients, ASA II or III, aged 18 to 65 years old, scheduled for elective thoracoscopic radical pneumonectomy were enrolled, and randomly divided into two groups using a computer-generated digit-number program (SAS PLAN; SAS Institute Inc.): normal saline group (control group) and lidocaine group, 32 patients in each group. The exclusion criteria included mental disorders or no cooperation; serious respiratory or cardiovascular disease; local anesthetic drug allergy; a previous history of chest surgery; experiencing hyperalgesia or refractory cancer pain; used of analgesics within 3 months; acute or chronic pain of any cause; planning a second operation or the conversion to thoracotomy.
This study was a double-blind design. The sequential numbers from 1 to 64 for participants were marked outside of each individual envelopes. Based on a computer-generated sequence, 32 paper slips marked with #1 [normal saline group (control group)] and 32 slips marked with #2 (lidocaine group) were sealed inside of envelopes. On the day of study, an investigator who was not involved in the administration and observation was opened an envelope with the smallest sequential number and prepared the solutions of medicines based on the number appeared on the paper slip, either #1 or #2. Then, the unlabeled syringes of solutions were handed over to an anesthesiologist who was administrating the medicines and performing general anesthesia. Patients, the anesthesiologist who performed anesthesia and another anesthesiologist who observed and recorded the data were all blinded to the medication patient had received. All anesthesia operations and monitoring were expected to be completed by two fixed anesthesiologists.
After arrival in the operating room, all patients were continuously monitored pulse oxygen saturation, heart rate, electrocardiogram, and non-invasive blood pressure (invasive arterial blood pressure monitoring if necessary). After pre-oxygenation via face mask, anesthesia was induced with intravenous 2 mg/kg propofol, 0.3 μg/kg sufentanil, 0.2 mg/kg cisatracurium and 1.5 mg/kg lidocaine (Sinopharm Group Rongsheng Pharmaceutical Co., Ltd., Henan Wuzhi, batch number: H20043676) over 10 s (lidocaine group) or same volume of normal saline (control group), followed by 2 mg·kg−1·h−1 continuous lidocaine (lidocaine group) or normal saline (control group) until the end of the surgery. Tracheal intubation was performed, and anesthesia was maintained with 0.1 μg·kg−1·min−1 remifentanil continuous intravenous infusion. By adjusting the concentration of sevoflurane, bispectral index was maintained between 40—60. If necessary, added cisatracurium 2 mg to ensure the muscle relaxation required for surgery. When the heart rate was greater than 100 beats/minute or the mean arterial pressure increases by 15%, added sufentanil 5 μg. When the operation completed, a mixture of 2 μg/kg sufentanil and 10 mg/kg lidocaine (lidocaine group)or 2 μg/kg sufentanil (control group) was continuously intravenous infused by postoperative patient-controlled intravenous analgesia pump (100 ml). An initial loading dose consisted of 5 ml of the pump. The background dosing rate was 2 ml/h, and lasted for 48 h. The patient-controlled dosing was 0.5 ml for every successful trigger with a lockout interval of 15 min.
At the end of surgery, the tracheal tube was removed and the patient was sent to the post anesthesia care unit (PACU). All patients had previously received guidance on intravenous PCA and numerical rating scales (NRS), ranging from grade 0 (no pain) to grade 10 (most severe pain). Stable vital signs and Numerical Rating Scale (NRS) < 4 were the criteria for discharge from the PACU. If NRS ≥ 4, 5 mg dezocine (a potent opioid analgesic like morphine) was used as a rescue medication.
Gender, age, body mass index, duration of operation (from the beginning of the skin incision to the end of the suture), and the use of anesthetics were recorded. The primary outcome of the study was the incidence of CPSP in the two groups of patients after surgery at 3 months. The secondary outcome was the incidence of CPSP in the two groups of patients after surgery at 6 months; the effect of perioperative intravenous infusion lidocaine on postoperative pain within the first 24 and 48 h; total amount of sufentanil (including intraoperative dosage and information automatically provided by the intravenous PCA pumps); the number of PCA triggers within 48 h after surgery. Patients were followed by a research assistant who did not know the treatment plan at 3 and 6 months after the operation. The research assistant by asking for medical history, physical examination, and questionnaire. After excluded other potential causes of pain, such as psychological factors, recurrence or metastasis of lung cancer, etc., asked whether the patient had experienced persistent pain or chronic onset due to surgery. If his/her answer was yes, then it was marked as suffering from CPSP. Further questions were as follows: Can you rate your pain from 0 to 10? Where was the painful part? How did the pain occur, caused by stretching, coughing or spontaneous? Was your pain intermittent or continuous? What medicine did you take to relieve the pain? If taken, was the medicine over the counter medicine or prescription drugs?
Our preliminary study showed that the incidence of CPSP at 3 months was 11% in lidocaine group and 44% in control group. Considering alpha of 0.05 and power of 80, and 10% shedding rate, so at least 56 cases were needed as the initial sample size. In order to increase the sample size as much as possible and avoid the loss of follow-up patients, 64 patients were finally included. Statistical analysis was performed using SPSS23 statistical software program (SPSS Inc., Chicago, IL). Shapiro–Wilk test was used to examine the normality of distribution of data. All continuous data were presented as the mean with standard deviation or as median. Categorical data are expressed as count and percentage (%). Continuous variables were compared using the Student t-test or Mann–Whitney U test if the data were not distributed normally. Categorical variables were compared using the chi-square or Fisher exact test, as appropriate. p < 0.05 was considered to be statistically significant.