Response Surface Modeling of Remimazolam and Sevoflurane

Официальное название

Response Surface Model Between Remimazolam and Sevoflurane; Comparison of the Minto and the Greco Model

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Remimazolam (Byfavo)
  Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software.
• Препарат Sevoflurane (Volatile Anesthetic)
  Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.

Первичные конечные точки

• Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model [Срок оценки: During anesthetic induction]
• Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model [Срок оценки: During anesthetic induction]

Вторичные конечные точки (11)

• BIS response according to hypnotic combinations [Срок оценки: During anesthetic induction]
• Loss of consciousness (LOC) [Срок оценки: During anesthetic induction]
• Recovery of consciousness (ROC) [Срок оценки: During emergence from anesthesia]
• Heart rate [Срок оценки: Intraoperative period]
• Systolic blood pressure [Срок оценки: Intraoperative period]
• Mean blood pressure [Срок оценки: Intraoperative period]
• Cardiac output [Срок оценки: Intraoperative period]
• Cardiac index [Срок оценки: Intraoperative period]
• Stroke volume variation [Срок оценки: Intraoperative period]
• Pulse pressure variation [Срок оценки: Intraoperative period]
• Peripheral oxygen saturation [Срок оценки: Intraoperative period]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

South Korea · 1 центр

• Pusan National University Yangsan Hospital — Yangsan

Публикации

• 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. PMID 27696490
• 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. PMID 27482310
• Byung-Moon Choi: An overview of pharmacodynamic drug interaction with isobole and response surface model in anesthesia. APM 2016; 11: 1-13

Идентификаторы

NCT: NCT07620782 · 05-2023-090

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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