Methods
The study was approved by the Ethics Committee for Clinical Trials of the First Hospital affiliated of China University of Science and Technology, Hefei, China [approval no. : 2021-ky095]. The research was signed in the Chinese Clinical Trial Registry before patients enrollment (ChiCTR 2000040130). All participants completed written informed consent.
Patients scheduling gynecological laparoscopic operation with American Society of Anesthesiologists (ASA) physical status I or II were enrolled in this research. All patients aged range is between 30 and 65, body mass index (BMI) in between 18.5 and 29.5 kg/m2. They were eliminated if anyone met any of the following standards: poor compliance or non-cooperate; presence of serious disease (cardiovascular disease, bronchial asthma, uncontrolled severe hypertension, fearful blood system dysfunction, liver or kidney dysfunction, obvious electrolyte abnormalities); second degree atrioventricular block, bradycardia (HR< 50 bpm), low blood pressure (SBP< 90 mmHg); history of neurological disease, chronic pain, drug addiction and alcoholism, long-term opioid use; history of allergy to opioids; slow intestinal peristalsis or intestinal obstruction; participant in clinical trials involving other drugs within four weeks; the presence of other conditions. Patients were split into 3 groups according to the effect-site concentration of propofol at in high concentration (3 ug/mL), middle concentration (2.5 ug/mL), low concentration (2 ug/mL) respectively during maintenance.
All participants fasted for 8 h, intravenous access was established after reaching the operating room, and received lactated Ringer’s or colloid solution maintained to expand blood volume. All patients avoided receiving any sedative or analgesic drugs before induction of anesthesia, and measured vital parameters, including invasive arterial blood pressure, cardiac rate, electrocardiography, pulse oxygen saturation, nasopharyngeal temperature and end-tidal carbon dioxide partial pressure. For BIS and PSI monitoring, set different single-use, disposable sensors at the forehead after the skin was cleaned with alcohol swabs. The two sets of EEG recording electrodes were closed to where they were used, in line with the manufacturer’s recommendations, and there was no significant interference between the two monitoring systems. (Fig. 1 ).
Preoxygenated with 100% oxygen before induction. General anesthesia was induced with TCI propofol 4 µg/mL and REM 4 ng/mL[21], after PSI dropped below 50, or the eyelash reflex disappearance, muscle relaxation was performed with rocuronium 0.5mg/kg. Controlled breathing for 5 min, inserted tracheal tube, meanwhile, set mechanical ventilation as target a PETCO2 in the 35 - 45 mmHg and SpO2 > 95%. Kept the patient’s body temperature between 36.0 °C and 37.0 °C. Anesthesia was maintained with propofol and REM, which were adjusted to the target concentration according to the patient’s group.
Sufentanil was administered with 0.15 - 0.7 µg/kg half an hour after the operation began to achieve the long-term analgesia. Propofol and REM were quit by the end of surgery. Patients were organized in a post-anesthesia care unit (PACU), set back to the inpatient ward with a Steward resuscitation score of above 4[22] after surgery. All patients used patient-controlled analgesia for 48 h. The ingredient consisted of 2.5 μg/kg sufentanil and 2 mg granisetron (total volume of 100 ml, including 0.9% normal saline).
The first patient of respective group administrated an effect-site concentration of REM at 3.5 ng/mL, then determined by using a modified up-and-down sequential method[23, 24]. In other words, the reaction of each patient decided the concentration of REM set to the succeeding patient. If the reaction of the previous patient was positive (the PSI value increased by >10 during 2 min after skin incision), the concentration given to the next patient was increased by 0.4 ng/mL. Otherwise, the concentration was decreased by 0.4 ng/mL. Adjusted the concentration of REM according to the group to hold PSI between 25 and 50, if excceed 25% of initial concentration, the patient was eliminated during the period of anesthesia. Infused additional fluids and an intermittent bolus of ephedrine when observed hypotension. Equally, cardiac rate was modulated with atropine of 0.05 mg if lower than 50 beats/min, and esmolol of 20 mg on condition that exceeding 100 beats/min.
Recorded the PSI, BIS, HR and MAP at the following moments: before the induction (T0), induction of anesthesia (T1), 1 min after intubation (T2), pre-incision (T3), 2 min after incision (T4), discontinuation of drugs (T5) and extubation (T6). Additionally, , Incidence of adverse events (including PSI exceed the recommended range, hypertension, hypotension, bradycardia), duration of operation, extubation time, residence time in PACU, hospital day, VAS score in the first day after operation, the occurrence of intraoperative awareness, postoperative delirium were registered. Density spectral array (DSA) was saved at SedLine® Root during the surgery.
According to the sequence method, when each group reached at least seven positive points, the experiment was completed.
SPSS version 27.0 (SPSS Inc., Chicago, IL, USA) was employed for statistical analyses. The modified up-and-down sequential method and probit analysis were used for the EC50 of REM with different concentration of propofol. All data were tested for normality by Shapiro test. The PSI, BIS, HR and MAP at each time were analyzed by using repeated measures ANOVA. Characteristics data of the patients, surgery, anesthesia and postoperative data among groups using one-way analysis of variance (ANOVA) for continuous variables. When a difference in proportions was found among the groups, and a Least Significance Difference or Tamhane T2 was made for multiple comparisons. ROC curve was used to compare the sensitive of PSI and BIS. P < 0.05 was regarded as a statistical difference. Quantitative data were perfomed as the mean (standard deviation) (SD), median [Min, Max], or number (n).