Differential Effects of Remimazolam and Propofol on Dynamic Cerebral Autoregulation During General Anesthesia

Study Overview
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Brief Summary
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Cerebral autoregulation (CA) is the property of the cerebral vascular bed to maintain cerebral perfusion in the presence of changes in blood pressure. In the case of anesthesia, altered cerebral autoregulation, including altered carbon dioxide and hemodilution, can impair physiological changes in the body and lead to poor postoperative prognosis. As a novel ultra-short-acting benzodiazepines drugs, remimazolam has been accepted for induction and maintenance of clinical anesthesia. Compared to the traditional benzodiazepines drugs, remimazolam combines the safety of midazolam with the effectiveness of propofol, and also has the advantages of acting quickly, short half-life, no injection pain, slight respiratory depression, independent of liver and kidney metabolism, long-term infusion without accumulation, and has a specific antagonist: flumazenil. Our study aimed to investigate the different effects of remimazolam and propofol on dynamic cerebral blood flow autoregulation function during general anesthesia.

Official Title
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Differential Effects of Remimazolam and Propofol on Dynamic Cerebral

Conditions
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General Anesthesia, Laparoscopic Cholecystectomy, Remimazolam, Propofol, Dynamic Cerebral Autoregulation

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 years, gender not limited Patients proposed to undergo elective laparoscopic cholecystectomy under general anesthesia, with an expected operative length of approximately 1h 2h Good penetration of the temporal window. ASA anesthesia classification grade I to II. can communicate effectively with the physician. Patients were aware of and voluntarily signed the informed consent form. Exclusion Criteria: Relative contraindications to general anesthesia: patients with severe heart and lung function diseases. History of syncope, and dizziness. Patients with a history of psychiatric disorders, neurological disorders, drug abuse, or drug addiction Patients with cerebrovascular or carotid artery lesions; Those who are unable to cooperate in completing the test Persons who have taken benzodiazepines intermittently in the last three months. Those with known allergies or allergies to the test drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam group<br>Induction of anesthesia Slowly injects remimazolam 0.4-0.6 mg/kg (about 1 minute) until loss of consciousness (LoC), if the degree of sedation is insufficient, additional remimazolam (0.05 mg/kg each time) is allowed. After the LoC, intravenous sufentanil 0.3  0.5ug/kg and cisatracurium besylate 0.1 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope. Maintenance of anesthesia remimazolam 0.4 1.2 mg/kg/h and remifentanil 0.1 0.3 ug/kg/min are injected intravenously to maintain sedation and assistant analgesia, and cisatracurium besylate 0.02 mg/kg is allowed to add as appropriate. During the operation, the dose of anesthetic drugs is adjusted so that the fluctuation of heart rate and blood pressure did not exceed 10 %. | Drug: Remimazolam<br>* The experimental group was sedated with remimazolam.<br>* Other names: cisatracurium besylate;|
| Active Comparator: Propofol group<br>Induction of anesthesia Slowly injects propofol 2-4 mg/kg (about 1 min) until loss of consciousness (LoC), allowing additional propofol (0.5 mg/kg each time) if sedation is insufficient. after LoC, intravenous sufentanil 0.3  0.5ug/kg and cisatracurium besylate 0.1 mg/kg. after sufficient muscle relaxation and blood circulation stabilization, the tracheal tube was inserted under the sliding scope. Maintenance of anesthesia propofol 4 10mg/kg/h and remifentanil 0.1 0.3 ug/kg/min are injected intravenously to maintain sedation and assistant analgesia, and cisatracurium besylate 0.02 mg/kg is allowed to add as appropriate. During the operation, the dose of anesthetic drugs is adjusted so that the fluctuation of heart rate and blood pressure did not exceed 10 %. | Drug: Propofol<br>* The control group was sedated with propofol.<br>* Other names: cisatracurium besylate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in dynamic cerebral blood flow autoregulation | Comparison of the consistency, gain and phase of the transfer function parameters in the frequency range of 0.02-0.07 Hz, 0.07-0.2 Hz and 0.2-0.5 Hz for the propofol and rimazolam groups, respectively. | From the time the patient enters the operating room to the time they leave the operating room, one and a half hours on average. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| systolic pressure | Indicators related to perioperative hemodynamics | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| diastolic pressure | Indicators related to perioperative hemodynamics | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| mean pressure | Indicators related to perioperative hemodynamics | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| heart rate | Indicators related to perioperative hemodynamics | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| pulse | Indicators related to perioperative hemodynamics | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| Recovery times | The period from discontinuation of anesthetic drugs to the recovery of the patient's self-consciousness and can respond correctly to external stimuli. All the patients can be allowed to leave the post-anesthesia care unit after Aldrete ≥ 9. Delayed awakening is defined as failure to achieve Aldrete ≥ 9 more than 30 minutes after surgery. | Up to 30 minutes after operation | 
| Complication | All the perioperative complications are recorded. | During the perioperative period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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General Anesthesia, Laparoscopic Cholecystectomy, Remimazolam, Propofol, dynamic cerebral autoregulation