Pharmacokinetics and Pharmacodynamics, Remimazolam
Conditions
Keywords
Remimazolam, general anesthesia, pharmacokinetics and pharmacodynamics
Brief summary
The goal of this randomized, controlled clinical trial is to evaluate the efficacy, safety, and recovery profile of an individualized, Eleveld pharmacokinetic/pharmacodynamic model-guided dosing strategy for remimazolam in adult patients undergoing elective non-cardiac surgery under general anesthesia. The main questions it aims to answer are: Does Eleveld model-guided customized dosing significantly reduce the eye-opening time at the end of surgery compared to standard weight-based dosing? Can the Eleveld model-guided approach prevent relative drug accumulation and delayed emergence while maintaining an adequate depth of anesthesia and comparable hemodynamic stability? Researchers will compare the Experimental Group (Eleveld model-guided dosing) to the Control Group (Standard weight-based label dosing) to see if preemptive dose optimization based on individual patient covariates effectively reduces the total drug consumption, frequency of rescue flumazenil administration, and emergence time. Participants will: * Be randomly assigned to receive remimazolam for the induction and maintenance of general anesthesia according to either the Eleveld model-guided customized regimen or the standard weight-based regimen. * Have their depth of anesthesia continuously monitored using a Bispectral Index (BIS) sensor. * Be assessed for the primary outcome (time to eye-opening upon verbal command after discontinuation of anesthetics) and secondary outcomes, including total drug consumption, hemodynamic stability, and postoperative complications (e.g., re-sedation, delirium, PONV).
Interventions
DRUGEleveld model-guided dosing
Eleveld PK/PD model-guided dosing via a web-based calculator
DRUGStandard weight-based label dosing
Induction at 9 mg/kg/h and maintenance at 1-2 mg/kg/h
Sponsors
Seoul National University Hospital
Hana Pharm Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 19 to 79 years undergoing elective non-cardiac surgery expected to last 60 minutes or longer under general anesthesia with endotracheal intubation
Exclusion criteria
* Emergency surgery * Surgery requiring evoked potential (EP) monitoring * Chronic benzodiazepine users * Body Mass Index (BMI) ≥ 35 kg/㎡ * Chronic kidney disease * Hepatic dysfunction or chronic liver disease * Contraindication or history of hypersensitivity to remimazolam * American Society of Anesthesiologists (ASA) physical status ≥ IV * Pregnant women * Contraindication or history of hypersensitivity to flumazenil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Eye-Opening Time, EOT | Time from the discontinuation of remimazolam to eye-opening upon verbal command (min), up to 1h |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to loss of consciousness (LOC) | Time from the start of remimazolam administration to loss of consciousness (min), up to 1h | — |
| Intraoperative Bispectral Index (BIS) values | Perioperative/Periprocedural | — |
| Incidence of intraoperative bradycardia (heart rate < 45 bpm) | Perioperative/Periprocedural | — |
| Incidence of intraoperative tachycardia (heart rate > 110) | Perioperative/Periprocedural | — |
| Incidence of intraoperative hypotension (mean blood pressure < 65 mmHg) | Perioperative/Periprocedural | — |
| Incidence of intraoperative hypertension (SBP > 140 mmHg) | Perioperative/Periprocedural | — |
| Total dose of intraoperative remimazolam (mg) | Perioperative/Periprocedural | — |
| Total dose of intraoperative remifentanil (㎍) | Perioperative/Periprocedural | — |
| Total dose(s) of intraoperative vasopressor(s) | Perioperative/Periprocedural | Ephedrine (mg) |
| Extubation time (min) | Time from the discontinuation of remimazolam to the removal of the endotracheal tube, up to 1h | — |
| Incidence of flumazenil administration | From discontinuation of remimazolam to patient discharge from the operating room, up to 1h | — |
| Incidence of rescue sevoflurane use | Perioperative/Periprocedural | — |
| Incidence of oxygen supplementation in the Post-Anesthesia Care Unit (PACU) | Perioperative/Periprocedural, on the day of surgery | — |
| Incidence of postoperative delirium | Perioperative/Periprocedural, up to 1 week | — |
| Incidence of postoperative nausea and vomiting (PONV) | Perioperative/Periprocedural, up to 1 week | — |
| Length of stay in the PACU (min) | Perioperative/Periprocedural, on the day of surgery | — |
| Incidence of re-sedation | Perioperative/Periprocedural, on the day of surgery | Drop in the Modified Observer's Assessment of Alertness/Sedation \[MOAA/S\] score to 3 or lower during the PACU stay |
| Incidence of intraoperative awareness | Perioperative/Periprocedural | assessed using the Modified Brice Questionnaire |
Countries
South Korea
Contacts
CONTACTHansol Kim, M.D.
Outcome results
None listed