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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Hee Young Kim, MD, PhD
- Número de teléfono: 82-55-360-2129
- Correo electrónico: anekhy@gmail.com
Ubicaciones de estudio
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Yangsan, Corea del Sur, 50612
- Reclutamiento
- Pusan National University Yangsan Hospital
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Contacto:
- Hee Young Kim, MD, PhD
- Número de teléfono: 82-55-360-2129
- Correo electrónico: anekhy@gmail.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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BIS response according to hypnotic combinations
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Hee Young Kim, MD, PhD, Pusan National University Yangsan Hospital, Yangsan, South Korea
Publicaciones y enlaces útiles
Publicaciones Generales
- 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
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 05-2023-090
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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