The Ethics Committee of the Affiliated Anqing Hospital of Anhui Medical University (Ethics Committee reference number: AQ042) approved the present study. This prospective, randomized controlled study was registered at www.clinicaltrial.gov (NCT03788018). The present study was conducted from January 2018 to December 2018 at the Affiliated Anqing Hospital of Anhui Medical University. Patients were required to sign the informed consent at least one day before surgery. 126 patients with American Society of Anesthesiologists (ASA) physical statusⅠand Ⅱ, 40-55 years of age, and scheduled for elective laparoscopic total hysterectomy undergoing general anesthesia were enrolled. The exclusion criteria in the current study included preoperative atrioventricular block and bradycardia, history of allergy to local anesthetics, severe respiratory disease, impaired kidney or liver function. In addition, history of preoperative opioids medication and psychiatric were excluded from this study.
Assigned groups and randomization
Patients were randomized by a nurse of PACU independent of the study who obtained random numbers (random numbers generated by a computer), and patient allocation ratio was 1:1. Assignments were concealed in sealed envelopes. Patients were allocated into two groups, including group LD and group CON. Patients received IV bolus infusion of lidocaine (2%) 1.5 mg/kg and dexmedetomidine 0.5 µg/kg diluted with normal saline to 20 ml in group LD, respectively, over 10 minutes before induction of anesthesia, followed by a continuous IV infusion at rate of lidocaine 1.5 mg/kg  and dexmedetomidine 0.4 µg/kg  made up to 20 mL every hour until 30 min before the end of operation, respectively. Patients received 20 ml normal saline and 20 ml normal saline in group CON, respectively, over 10 minutes before induction of anesthesia, followed by a continuous IV infusion 20 ml normal saline and 20 ml normal saline every hour until 30 min before the end of surgery, respectively. Investigators, clinicians and patients were all fully blinded to treatment allocation. The drug solutions were prepared by an anesthesiologist who was not participated in the administration of the trial.
All surgical procedures for laparoscopic total hysterectomy were implemented by two high-experienced surgeons. All patients received intramuscular phenobarbital (0.1 g) 30 minutes before surgery. Basic non-invasive arterial pressure (NIBP), heart rate (HR), electrocardiogram (ECG), end-tidal CO2 (PetCO2), peripheral pulse oximeter (SPO2), train-of-four (TOF), and Bispectral Index (BIS) monitors were attached to all the subjects for monitoring the vital sign, neuromuscular block, and the depth of anesthesia. Arriving at the operation room, patients were received the ringer’s lactate (1 mL/kg/h) to maintain its patency. All the patients were preoxygenated with 100% oxygen via facemask for 3 to 5 minutes before induction of anesthesia to obtain sufficient oxygenation. Anesthesia was induced with target-controlled infusion (TCI) of propofol and remifentanil. The target predicted plasma concentration of propofol was 3.0 μg/mL . This predicted plasma propofol concentration was kept stable for 3 minutes and then remifentanil TCI begun. The target predicted plasma concentration of remifentanil was 5.0 ng/ml . Cis-atracurium 0.15 mg/kg was injected intravenously when the patients lost consciousness, and an endotracheal tube (ETT) with an internal diameter of 6.5 mm (female) was inserted into the trachea after adequate muscle relaxation. Mechanical ventilation was performed using fabius machine. Tidal volume was set 6-8 mL/kg, and respiratory rate was set 10-13 beat/min (bpm) to keep the PetCO2 between 35 and 45 mmHg during the intraoperative period. A supplemental dose of cis-atracurium was administered intermittently to maintain muscle relaxation during the anesthesia period. The depth of anesthesia was maintained by adjusting predicted propofol and remifentanil TCI according to BIS values and hemodynamic variables within 20% of preoperative values. BIS was kept between 45 and 60 during the anesthesia period. The ringer’s lactate solution was infused at a rate of 6-8 mL/kg/h during the intraoperative period. 30 minutes before the end of surgery, Fentanyl 1μg/kg was administered intravenously, and then patients were connected to an IV patient-controlled analgesic system (IVPCA) with 0.3 µg/kg/h fentanyl and granisetron hydrochloride 6 mg (100 ml of total volume) to deliver a bolus of 0.075 µg/kg of the above analgesics with a lockout time of 15 minutes. Atropine (0.5 mg) and neostigmine (1 mg) was given by intravenously to reverse neuromuscular block when the patients restored spontaneous respiration. Patients were extubated when TOF ratio at least 0.9. The patients were transported to the PACU after their endotracheal tube were extubated in the operating room to continue treatment. All patients were continued to observe for 2 hours during the PACU stay period. The Ramsay sedation score and incidence of bradycardia during the PACU stay period were recorded. The operations were performed by two high-experienced surgeon under a CO2 pneumoperitoneum, and the pressure of pneumoperitoneum was kept between 10 mmHg and 12mmHg for all patients. At the end of surgery, 10 mL of 0.75% ropivacaine was injected the abdominal trocar sites by one surgeon for providing wound infiltration analgesia after surgery.
Our primary outcome was the incidence of nausea, vomiting and PONV during the first 48 hours after surgery. The secondary outcomes included Ramsay sedation score, the incidence of bradycardia, postoperative cumulative fentanyl requirment, and propofol and remifentanil total dose during the anesthesia period. The intensity of pain after the operation was estimated with a 10-cm VAS in the PACU and the ward (0 for no pain, 10 for the most imaginable pain). If the VAS>3, an additional 25 µg of fentanyl was treated intravenously until the VAS<3. Sedation levels of subjects during the PACU stay period were evaluated with the Ramsay sedation scale (1: agitated and uncomfortable, 2: co-operative and orientated, 3: can follow simple directions, 4: asleep but strong response to stimulation, 5: asleep and slow response to stimulation and 6: asleep and no response to stimulation).
Sample size calculation
According to Geng ZY  study, a sample size of 58 patients per group was needed to confirm a 50% reduction in the incidence of PONV with a power of 80% and a significance level of 0.05. Therefore, we enrolled 126 cases to account for drop outs in the present study.
All the statistical analyses in the present study were performed using SPSS statistics v.17 (IBM Corp., Armonk, NY, USA) software. Data are presented as the number (percentage) of subjects or mean±standard deviation. Categorical data were analyzed using the χ2 test or the Fisher’s exact test as appropriate. Continuous data in the two groups were analyzed using the independent t-test. A P value of less than 0.05 was considered statistically significant.