The Dose Range of Remimazolam Besylate in Different Age Groups

Study Overview
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Brief Summary
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This is a multicenter, randomized, parallel, controlled clinical study of patients at different ages underwent elective non-cardiac surgery under general anesthesia. The aim of this study is to explore the dose range of remimazolam besylate for patients at different ages, to provide guidance for anesthesia induction and maintenance of remimazolam besylate. And to investigate the incidence of perioperative hypotension and postoperative related organ dysfunction in patients received total intravenous anesthesia with remimazolam besylate, compared with propofol.

Detailed Description
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Surgery is an effective method to treat surgical diseases, prolong survival time and improve the quality of life, but patients often face the risk of postoperative complications. In general surgery patients, complications occur in more than 30% of patients. Several observational studies have shown that the severity and duration of intraoperative hypotension are significantly related to the risk of postoperative adverse events such as myocardial injury, renal injury, stroke, delirium, prolonged hospitalization, and death. Hypotension, defined as a systolic blood pressure of less than 90 mmHg, a diastolic blood pressure of less than 50 mmHg, or a 20% reduction in systolic blood pressure from baseline, is common during anesthesia and surgery. More than a third of patients receiving propofol sedation experience intraoperative hypotension events, and their duration and degree are associated with harm during surgery. Remimazolam is a new ultra-short-acting sedative drug developed in recent years, which has a similar structure to midazolam. However, compared with midazolam, remimazolam has the advantages of faster onset, faster recovery, and higher safety. Compared with propofol, remimazolam is noninferior in the success rate of sedation, while the incidence of adverse events such as hypotension is lower. At present, remimazolam has completed phase III clinical studies in many fields, such as colonoscopy, fiberoptic bronchoscopy, and general anesthesia induction and maintenance, which have shown its safety and effectiveness. However, there may be differences in hemodynamics and drug sensitivity among patients of different ages. Compared with young patients, elderly patients have a higher risk of hypotension after anesthesia induction. At present, there is a lack of clinical studies with large samples to clarify the recommended dose of remimazolam for anesthesia induction and maintenance in patients of all ages. The updated instructions for remimazolam besylate for injection on March 28, 2022 also mention that remimazolam besylate is used as a sedative drug for general anesthesia induction and maintenance, and the relevant dose reference is given. However, the safety and effectiveness of patients over 65 years have not been confirmed. The precise regulation of clinical use for patients of different ages and the optimization of drug dosage during anesthesia induction and maintenance are the basis for ensuring the safety of clinical medication at present., in order to maintain the stability of perioperative hemodynamics, and prevent or reduce the occurrence of adverse cardiovascular events. This study aims to investigate the effect of remimazolam total intravenous anesthesia on intraoperative hemodynamics and the drug requirement for patients of different ages, with propofol as the control, and intraoperative hemodynamics as the main evaluation index, so as to provide evidence for clinical application of remimazolam for elderly patients in anesthesia induction and maintenance.

Official Title
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The Investigation of the Dose Range of Remimazolam Besylate in Different Age Groups of Adults and Its Effects on Hemodynamics

Conditions
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Remimazolam, Anesthesia

Intervention / Treatment
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* Drug: Remimazolam besylate
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age above 45 years old; American Society of Anesthesiologists grade Ⅰ-II; patients undergoing tracheal intubation or laryngeal mask airway surgery under general anesthesia (intravenous anesthesia); Informed consent: patients voluntarily participated in the trial and signed the informed consent form. Exclusion Criteria: patients with cardiac function grade 3 or above; difficult to observe the pupil size of head or neck surgery patients; patients with multimodal anesthesia such as nerve block or spinal anesthesia compounded; patients known to be allergic to remimazolam besylate or benzodiazepines; major vascular surgery and the type of surgery that directly affects hemodynamics; patients with coagulation dysfunction, endocrine diseases or other hemodynamic conditions; minor surgery (operation duration <1 hour); surgery lasting more than 4 hours; emergency surgery; patients with a history of drug or alcohol dependence; Subjects deemed unsuitable for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Age 45-64<br>Patients aged 45 to 64 years | Drug: Remimazolam besylate<br>* Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need). Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).<br>Drug: Propofol<br>* Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance. Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance<br>|
| Experimental: Age 65-74<br>Patients aged 65 to 74 years | Drug: Remimazolam besylate<br>* Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need). Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).<br>Drug: Propofol<br>* Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance. Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance<br>|
| Experimental: Age 75-84<br>Patients aged 75 to 84 years | Drug: Remimazolam besylate<br>* Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need). Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).<br>Drug: Propofol<br>* Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance. Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance<br>|
| Experimental: Age over 75<br>Patients aged over 85 years | Drug: Remimazolam besylate<br>* Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need). Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).<br>Drug: Propofol<br>* Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance. Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of intraoperative hypotension | Occurrence of intraoperative hypotension | Operation 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative dosage of vasoactive drugs | Intraoperative dosage of vasoactive drugs | Operation 1 day | 
| Anesthesia recovery | Anesthesia recovery | Operation 1 day | 
| Cognitive function assessment | Cognitive function assessment in the anesthesia recovery room | Operation 1 day | 
| Major organ complications | The occurrence of major organ complications within 30 days after surgery | Within 30 days after surgery | 
| Hospital stay of patients | Hospital stay of patients | With 30 days after surgery | 
| 30-day mortality after surgery | 30-day mortality after surgery | 30-day after surgery |