A Temporal Variability Study of Remimazolam for General Anesthesia Induction and Maintenance
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Remimazolam dosage
研究概览
简要总结
The purpose of this study was to observe and compare the differences in plasma concentration, dosage and carboxylesterase 1 activity of remimazolam when remimazolam is used for general anesthesia induction and maintenance at different times of the day, and to explore the effect of time rhythm on the pharmacokinetics and pharmacodynamics of remimazolam, so as to provide new ideas and clinical basis for optimizing medication regimens and anesthesia management.
详细描述
This study is a single-blind, prospective cohort study. It is mainly divided into two parts: 1. Detection of the blood concentration and dosage differences of remimazolam: Patients who were scheduled to undergo laparoscopic cholecystectomy under general anesthesia were included. The patients were divided into the morning group (operation time 8:00-12:00) and the afternoon group (operation time 14:00-18:00) according to the operation time. The blood concentration of remimazolam after anesthesia induction was measured, and the influence of time rhythm on the pharmacokinetics of remimazolam was statistically analyzed. The dosage of remimazolam used during anesthesia maintenance was measured, and statistical analysis was conducted on whether there were dosage differences and the temporal rhythm of drug efficacy of remimazolam during the maintenance process. 2. CES1 Activity detection: Patients who were scheduled to undergo laparoscopic partial hepatectomy under general anesthesia were included. The research subjects were divided into the morning group (8:00-12:00) and the afternoon group (14:00-18:00) based on the liver tissue sampling time. The activity of carboxylate esterase 1 (CES1) in the normal tissues adjacent to liver cancer in patients at different time points was measured. Analyze the influence of time rhythm on the drug metabolism of remimazolam. The effects of time rhythm on the pharmacokinetics and pharmacodynamics of remimazolam were jointly verified from three aspects: blood drug concentration, drug dosage, and CES1 activity.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Experiment 1: Measurement Experiment of Remimazolam Blood Concentration and Dosage
- •Age 18-65 years old, ASAI-II class, BMI18.5-25kg/m^2;
- •Inpatients undergoing laparoscopic cholecystectomy;
- •The estimated time of operation is 1.5~2.5 hours;
- •Voluntary participation and signed informed consent.
- •Experiment 2: Remimazolam metabolic enzyme CES1 activity measurement experiment
- •Age 18-75 years old, ASAI-III class;
- •Inpatients undergoing laparoscopic partial hepatic resection;
- •Voluntary participation and signed informed consent.
排除标准
- •Experiment 1:Measurement Experiment of Remimazolam Blood Concentration and Dosage
- •Pregnant or lactating women;
- •Patients who are allergic to remazolam or contraindicated;
- •Patients who are dependent on or tolerant to opioids or have long-term alcoholism;
- •Serious cardiovascular system, respiratory system, liver and kidney diseases;
- •History of obstructive sleep apnea;
- •Mental disorders or neurological diseases;
- •Patients who participated in clinical trials of other drugs within the last 3 months;
- •The attending physician or researcher considers that there are other circumstances that are not suitable for participation in this study;
- •Refuse to participate in the study
- •Experiment 2: Remimazolam metabolic enzyme CES1 activity measurement experiment
- •Pregnant or lactating women;
- •Patients who are allergic to remazolam or contraindicated;
- •Patients who are dependent on or tolerant to opioids or have long-term alcoholism;
- •Serious cardiovascular system, respiratory system;
- •History of obstructive sleep apnea;
- •Mental disorders or neurological diseases;
- •Patients who participated in clinical trials of other drugs within the last 3 months;
- •The attending physician or researcher considers that there are other circumstances that are not suitable for participation in this study;
- •Refuse to participate in the study
结局指标
主要结局
Remimazolam dosage
时间窗: During the operation
During the maintenance of anesthesia, adjust the infusion rate of remimazolam to maintain the BIS value at 40-60, and record the dosage of remimazolam
Remimazolam blood concentration
时间窗: Within two weeks after the operation
Arterial blood of 2 ml was collected immediately after the end of remimazolam infusion during the anesthesia induction period and 6 minutes after the end of infusion, respectively. After each sample collection, rinse the ductus arteriosus with 1 ml of normal saline. The blood sample was drawn into a plastic tube containing ethylenediaminetetraacetic acid and stored at 4℃. Centrifuge the blood sample within 10 minutes after collection. Transfer the supernatant plasma into a polypropylene tube within 15 minutes after separation and store it immediately at -20℃. Blood samples should be stored at -80℃ within 4 hours after collection. The blood concentration of remimazolam and the concentration of its metabolite CNS7054 were determined by ultra-performance liquid chromatography-tandem mass spectrometry within two weeks after blood collection.
CES1 activity
时间窗: Within two weeks after the operation
When a surgeon removes a liver tumor, 50 mg of normal liver tissue adjacent to the tumor is quickly taken. The liver tissue is rinsed with normal saline, dried with filter paper, and placed in a cryotube. It is then rapidly frozen in liquid nitrogen and stored in a -80 ° C refrigerator for subsequent determination of CES1 enzyme activity by enzyme-linked immunosorbent assay.
次要结局
未报告次要终点
研究者
Jie Chen
Clinical Professor
The Second Affiliated Hospital of Chongqing Medical University