Laparoscopic Surgery
Conditions
Keywords
general anesthesia
Brief summary
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.
Detailed description
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.
Interventions
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%.
Sponsors
Pusan National University Yangsan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model | During anesthetic induction | 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. |
| Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model | During anesthetic induction | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BIS response according to hypnotic combinations | During anesthetic induction | 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. |
| Loss of consciousness (LOC) | During anesthetic induction | Time to loss of consciousness during induction |
| Recovery of consciousness (ROC) | During emergence from anesthesia | Time to recovery of consciousness |
| Heart rate | Intraoperative period | Heart rate (beats per minute) will be recorded at 5-minute intervals during the intraoperative period. |
| Systolic blood pressure | Intraoperative period | Systolic blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period. |
| Mean blood pressure | Intraoperative period | Mean blood pressure (mmHg) will be recorded at 5-minute intervals during the intraoperative period. |
| Cardiac output | Intraoperative period | Cardiac output (L/min) will be recorded at 5-minute intervals during the intraoperative period. |
| Cardiac index | Intraoperative period | Cardiac index (L/min/m²) will be recorded at 5-minute intervals during the intraoperative period. |
| Stroke volume variation | Intraoperative period | Stroke volume variation (%) will be recorded at 5-minute intervals during the intraoperative period. |
| Pulse pressure variation | Intraoperative period | Pulse pressure variation (%) will be recorded at 5-minute intervals during the intraoperative period. |
| Peripheral oxygen saturation | Intraoperative period | Peripheral oxygen saturation (%) will be recorded at 5-minute intervals during the intraoperative period. |
Countries
South Korea
Contacts
CONTACTHee Young Kim, MD, PhD
PRINCIPAL_INVESTIGATORHee Young Kim, MD, PhD
Pusan National University Yangsan Hospital, Yangsan, South Korea
Outcome results
None listed