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

Differential Effects of Remimazolam and Propofol on Dynamic Cerebral

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.

Study Overview

• Status: Recruiting
• Conditions: General Anesthesia; Laparoscopic Cholecystectomy; Propofol; Remimazolam; Dynamic Cerebral Autoregulation
• Intervention / Treatment: Drug: Remimazolam; Drug: Propofol

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xing Liu, Dr.; Phone Number: +8618379804346; Email: liuxingmed@163.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • the Second Affiliated Hospital of Nanchang University, Nanchang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-60 years, gender not limited
2. Patients proposed to undergo elective laparoscopic cholecystectomy under general anesthesia, with an expected operative length of approximately 1h~2h
3. Good penetration of the temporal window.
4. ASA anesthesia classification grade I to II.
5. can communicate effectively with the physician.
6. Patients were aware of and voluntarily signed the informed consent form.

Exclusion Criteria:

1. Relative contraindications to general anesthesia: patients with severe heart and lung function diseases.
2. History of syncope, and dizziness.
3. Patients with a history of psychiatric disorders, neurological disorders, drug abuse, or drug addiction
4. Patients with cerebrovascular or carotid artery lesions;
5. Those who are unable to cooperate in completing the test
6. Persons who have taken benzodiazepines intermittently in the last three months.
7. Those with known allergies or allergies to the test drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam group; 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; The experimental group was sedated with remimazolam.; Other Names: sufentanil; cisatracurium besylate
Active Comparator: Propofol group; 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; The control group was sedated with propofol.; Other Names: sufentanil; cisatracurium besylate

What is the study measuring?

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
Complication	All the perioperative complications are recorded.	During the perioperative period
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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Nanchang University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Propofol; Laparoscopic Cholecystectomy; General Anesthesia; Remimazolam; dynamic cerebral autoregulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Neuromuscular Agents; Nicotinic Antagonists; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Propofol; Sufentanil; Dsuvia; Cisatracurium; Atracurium
• Other Study ID Numbers: 2022-TCD-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No