1.1 General information
Methods from April 2019 to April 2020, 90 patients undergoing laparoscopic hysterectomy in the Affiliated Hospital of Guangdong Medical University were selected as the observation objects. Group A and group C were randomly divided into two groups. All patients had no serious heart, lung, liver, kidney dysfunction and other contraindications, mental state was good, no abnormal fasting blood glucose or postprandial blood glucose was found before operation, and all patients and their families were informed and agreed. There were no significant differences in age, gender, weight and height among the three groups (all P > 0.05), which were comparable, as shown in Table 1.
Inclusion criteria
① Patients with moderate or severe pain who need more than 24 hours of patient-controlled intravenous analgesia pump after elective endotracheal intubation under general anesthesia;
② ASA was classified as grade I to grade II;
③18kg/㎡<BMI<30kg/㎡;
④ Female inpatients over 18 years old and less than 70 years old;
⑤ There was no disturbance of intravenous infusion;
⑥ They voluntarily participated and signed the informed consent.
Exclusion criteria:
① Patients with history of head injury, intracranial surgery or stroke within 4 weeks before operation, or with organic lesions of central nervous system and disturbance of consciousness;
② Patients who need to enter the surgical intensive care unit (SICU) after operation;
③ Patients with high bleeding risk, including patients with congenital bleeding disease (such as hemophilia), patients with thrombocytopenia (platelet count less than 100 × 109 / L) or platelet dysfunction, and patients with coagulation dysfunction (Pt or APTT higher than the upper limit of normal value);
④ Patients with history of cardiovascular and cerebrovascular diseases, liver (ALT or ast > 1.5 times of the upper limit of normal value), abnormal renal function (CR > upper limit of normal value), endocrine system and other serious primary diseases; patients with mental disease or language communication disorders, unable to understand sedation score, VAS score;
⑤ Those who did not control grade 2 or above hypertension (SBP ≥ 160mmhg or DBP ≥ 100mmhg) or took ACEI and diuretics for 30 days or above;
⑥ Patients with pain during the perioperative period of coronary artery bypass grafting (CABG);
⑦ Patients with a history of asthma and heart failure, and patients who have received organ transplantation surgery;
⑧ Patients who had used acetaminophen within 6 hours before surgery or non steroidal anti-inflammatory drugs (NSAIDs) within 12 hours before surgery;
Patients who had used other drugs 24 hours before operation;
⑨ Those who are taking the drug and have interaction with the test drug to increase the toxicity;
⑩ Patients allergic to experimental drugs;
⑪ Patients with dependence on narcotic drugs or tolerance to opioids before enrollment;
⑫ Patients who participated in other clinical studies within 3 months before operation;
⑬ Patients with other conditions considered unsuitable for participation by the researchers.
1.2 Anesthesia method
With the approval of ethics committee of Affiliated Hospital of Guangdong Medical University, 366 patients undergoing elective gynecological laparoscopic surgery were selected according to the inclusion and exclusion criteria, and the American Society of Anesthesiologists classification I or II. All subjects will have two numbers: screening number and random number (drug number). The screening number is determined by the clinical trial unit and consists of 4 digits. The first two digits are the center number and the last two digits are the screening sequence number of the center. For example, the screening number of the sixth subject screened by the third center is 0306.
In this study, block random method was used. The subjects who met the inclusion criteria were randomly assigned from small to large.
Random number (drug number) was given. The random number table is implemented by the plan process of SAS statistical software. Random number table
In duplicate, sealed and handed over to the main research unit and the sponsor for proper storage. Each eligible subject was given a random number at the time of enrollment, which was consistent with the ECRF, the number on the drug supply package and the drug distribution form.
The numbers are the same. The time point of randomization was when the patients met the inclusion criteria and did not meet the exclusion criteria. The patients were followed up by another anesthesiologist, and the pain degree and the number of adverse reactions at 2, 4, 8, 12, 24 and 48 hours after operation were evaluated respectively. The number and dosage of tramadol used as a remedial analgesic were recorded. The pain degree was assessed by visual analogue scale (VAS) The adverse reactions included respiratory depression, nausea and vomiting, drowsiness, restlessness and pruritus.
All patients did not use any preoperative medication. They were fasting for 4-6 hours before operation. After entering the room, nasal catheter continued to inhale oxygen for 3 L / min. ECG, BP, HR, SpO2 were detected, peripheral vein and infusion were opened, and rescue equipment and drugs such as tracheal intubation were prepared. Intravenous infusion of lactate Ringer's solution 8-10 ml / kg was performed by a fixed skilled anesthesiologist. After 3 min of nitrogen and oxygen removal, induction was started. Midazolam 0.03 mg / kg, etomidate 0.3 mg / kg, atracurium CIS besylate 0.2 mg / kg, sufentanil 0.5 UG / kg, At the same time, the fresh oxygen flow rate of mask inhalation was set to 3L / min. after the patient's consciousness disappeared, the laryngoscope was used to intubate through the mouth under the light vision. The endotracheal tube should be "id = 7.0", the surface should be fully lubricated, and the intubation should be successful at one time. After intubation, mechanical ventilation should be set: VT 8ml:kg-1, rr12 times / min. Anesthesia was maintained with propofol 4-6mg / kg / h, atracurium CIS benzenesulfonate 0.2-0.3mg/kg/h, sufentanil 0.2-0.4ug/kg/h, BIS value was controlled between 40-60, PetCO2 was maintained at 35-45mmhg, CO2 pneumoperitoneum pressure was automatically controlled at 12mmhg, sufentanil and cisatracurium sulfonate were stopped 30 minutes before the end of operation, and propofol was stopped 5 minutes before the end of operation.
Laparoscopic surgery was performed in all four groups, and the operation was performed by the same group of doctors. There was no significant difference in operation site, operation time, intraoperative blood loss, intraoperative fluid infusion volume and operation method (P > 0.05), which was comparable, as shown in Table 1. After operation, they were randomly divided into four groups: group A: sufentanil 3 μ g / kg; group B: low-dose nalbuphine group: 0.1 mg / kg + 3 μ g / kg sufentanil group; group C: medium dose of nabufen group: 1 mg / kg of nabufen + 2 μ g / kg of sufentanil; group D: large dose of nabufen group: 2 mg / kg of nabufen + 1 μ g / kg of sufentanil; 30 cases in each group. In addition to different intervention measures, the perioperative nursing care of the four groups were the same and were performed according to the conventional methods.
1.3 Observation indicators
Main outcome measures: the number and total amount of tramadol administered within 24 hours after operation.
Secondary evaluation index:
Visual analogue scale was used to evaluate the degree of postoperative pain and discomfort at 2, 4, 8, 12, 24 and 48 hours after operation, the total amount of analgesic pump used, the total number of times of pressing and effective times of pressing. The incidence of adverse reactions included respiratory depression, nausea and vomiting, drowsiness, restlessness, pruritus and satisfaction with analgesia.
The postoperative 48 hours were recorded The highest Ramsay Sedation score within H (restlessness: 1 point; awake, quiet cooperation: 2 points; drowsiness, quick response to instructions: 3 points; light sleep, wake-up: 4 points; sleep, slow response to call: 5 points; deep sleep, call should not be 6 points); rescue analgesia, PCIA invalid pressing times and total pressing times, postoperative nausea and vomiting, skin itching, drowsiness were recorded Situation.
Visual analogue scale (VAS) was used to measure the patient's analgesia. A 10 cm horizontal line was drawn on a piece of paper. The range was 0-10. 0 indicated no pain, 10 was the strongest pain. The closer to 10, the more painful the subjective feeling was. Ask the patient to make a mark on the horizontal line according to the self feeling on the paper, and then measure the distance from the starting point with a ruler, which is the score value.
1.4 Statistical methods
SPSS18.0 software was used for analysis. The measurement data were expressed as mean ± standard deviation (). The one-way ANOVA, Q-test and t-test were used. Chi square test was used for counting data. The difference was statistically significant with P < 0.05.