Response Surface Modeling of Remimazolam and Sevoflurane
Response Surface Model Between Remimazolam and Sevoflurane; Comparison of the Minto and the Greco Model
This prospective randomized open-label study aims to investigate the pharmacodynamic interaction between remimazolam and sevoflurane during general anesthesia using response surface modeling. Although remimazolam has favorable hemodynamic stability compared with propofol, its hypnotic effect may be less predictable and poorly correlated with conventional sedation monitoring indices such as the bispectral index (BIS). In clinical practice, remimazolam and sevoflurane are often combined during induction and maintenance of anesthesia; however, the optimal interaction between these agents remains unclear.
This study will evaluate whether the interaction between remimazolam and sevoflurane is synergistic, additive, or infra-additive using two representative response surface interaction models: the Minto model and the Greco model. BIS values and predicted effect-site concentrations will be analyzed using NONMEM software.
研究概览
详细说明
Remimazolam is a recently developed ultra-short-acting benzodiazepine anesthetic with favorable pharmacokinetic characteristics, including a short context-sensitive decrement time and relatively stable hemodynamics. Despite these advantages, remimazolam may exhibit weaker hypnotic potency and inconsistent correlations with conventional anesthetic depth monitors such as BIS.
In current clinical practice, anesthesiologists frequently combine remimazolam with volatile anesthetics such as sevoflurane during induction or maintenance of anesthesia. However, the pharmacodynamic interaction between remimazolam and sevoflurane has not been fully elucidated.
The present study will investigate the interaction between remimazolam and sevoflurane using response surface modeling. The study will enroll adult patients undergoing elective laparoscopic surgery under general anesthesia. Various combinations of remimazolam infusion rates and end-tidal sevoflurane concentrations will be administered during anesthetic induction. BIS values and predicted effect-site concentrations will be collected and analyzed.
Pharmacodynamic interaction analyses will be performed using NONMEM nonlinear mixed-effects modeling software. Both the Minto interaction model and the Greco interaction model will be applied to determine whether the interaction between remimazolam and sevoflurane is synergistic, additive, or infra-additive.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Hee Young Kim, MD, PhD
- 电话号码：82-55-360-2129
- 邮箱：anekhy@gmail.com
学习地点
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Yangsan、韩国、50612
- 招聘中
- Pusan National University Yangsan Hospital
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接触：
- Hee Young Kim, MD, PhD
- 电话号码：82-55-360-2129
- 邮箱：anekhy@gmail.com
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-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Adults aged 20 to 80 years
- Scheduled for elective surgery under general anesthesia at Pusan National University Yangsan Hospital
- American Society of Anesthesiologists (ASA) physical status I or II
- Able to provide written informed consent
Exclusion Criteria:
- Known allergy to remimazolam or sevoflurane
- Renal, hepatic, neuromuscular, or neurological disease
- Use of medications affecting the central nervous system
- Chronic psychoactive drug use
- Ischemic heart disease
- Pregnant women
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Remimazolam and Sevoflurane Combination During Anesthetic Induction
Participants undergoing elective surgery under general anesthesia will receive varying combinations of remimazolam and sevoflurane during anesthetic induction to evaluate pharmacodynamic interactions using response surface modeling.
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Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software.
Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model
大体时间：During anesthetic induction
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The interaction coefficient (α) describing the pharmacodynamic interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Minto response surface model based on BIS values collected during anesthetic induction.
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During anesthetic induction
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Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model
大体时间：During anesthetic induction
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The pharmacodynamic interaction parameter describing the interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Greco response surface model based on BIS values collected during anesthetic induction.
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During anesthetic induction
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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BIS response according to hypnotic combinations
大体时间：During anesthetic induction
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Bispectral Index (BIS) values will be continuously recorded during anesthetic induction according to predefined combinations of remimazolam effect-site concentration and end-tidal sevoflurane concentration.
The BIS is a processed electroencephalographic monitoring scale ranging from 0 to 100, where lower values indicate deeper levels of hypnosis and higher values indicate lighter levels of sedation or consciousness.
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During anesthetic induction
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Loss of consciousness (LOC)
大体时间：During anesthetic induction
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Time to loss of consciousness during induction
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During anesthetic induction
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Recovery of consciousness (ROC)
大体时间：During emergence from anesthesia
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Time to recovery of consciousness
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During emergence from anesthesia
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Heart rate
大体时间：Intraoperative period
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Heart rate (beats per minute) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Systolic blood pressure
大体时间：Intraoperative period
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Systolic blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Mean blood pressure
大体时间：Intraoperative period
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Mean blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Cardiac output
大体时间：Intraoperative period
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Cardiac output (L/min) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Cardiac index
大体时间：Intraoperative period
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Cardiac index (L/min/m²) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Stroke volume variation
大体时间：Intraoperative period
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Stroke volume variation (%) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Pulse pressure variation
大体时间：Intraoperative period
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Pulse pressure variation (%) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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Peripheral oxygen saturation
大体时间：Intraoperative period
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Peripheral oxygen saturation (%) will be recorded at 5-minute intervals during the intraoperative period.
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Intraoperative period
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合作者和调查者
调查人员
- 首席研究员：Hee Young Kim, MD, PhD、Pusan National University Yangsan Hospital, Yangsan, South Korea
出版物和有用的链接
一般刊物
- Choe S, Choi BM, Lee YH, Lee SH, Lee EK, Kim KS, Noh GJ. Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia. Clin Exp Pharmacol Physiol. 2017 Jan;44(1):30-40. doi: 10.1111/1440-1681.12677.
- Jeon S, Kwon JY, Kim HK, Kim TK. Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models. Korean J Anesthesiol. 2016 Aug;69(4):341-9. doi: 10.4097/kjae.2016.69.4.341. Epub 2016 Jun 22.
- Byung-Moon Choi: An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia. APM 2016; 11: 1-13
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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