The Effects of Remimazolam on Cerebral Blood Flow Following General Anesthesia Induction

This study will enroll 40 subjects aged 18 years or older scheduled for elective surgery under general anesthesia with endotracheal intubation. Basic medical history information will be collected. Subjects will be divided into two groups of 20 each: a remimazolam group and a propofol group. The study period will span from one day before surgery to one day after surgery. The study will assess middle cerebral artery cerebral blood flow following general anesthesia induction and postoperative anesthesia recovery.

Study Overview

• Status: Completed
• Conditions: Cerebral Blood Flow
• Intervention / Treatment: Drug: Propofol (Group P); Drug: Remimazolam

Detailed Description

A significant reduction in cerebral blood flow (CBF) frequently occurs following general anesthesia induction. This decrease in CBF can lead to a reduction in the delivery of oxygen and glucose to brain tissue. If the magnitude or duration of this reduction exceeds the compensatory capacity of cerebral autoregulation, it can result in an imbalance between cerebral oxygen supply and demand, thereby increasing the risk of cerebral ischemia and neurological injury. Patients who are elderly, have hypertension, a history of cerebrovascular disease (e.g., stroke, intracranial arterial stenosis), or pre-existing brain injury are at higher risk for pronounced CBF reduction after induction, making them more susceptible to postoperative cognitive dysfunction, exacerbation of existing deficits, or new ischemic events. This underscores the urgent need to identify effective and safe therapeutic strategies to mitigate this risk.

Remimazolam is a novel benzodiazepine agent, structurally derived from midazolam with the introduction of a metabolically labile methyl propionate side chain. It similarly acts on the GABAA receptor, promoting chloride ion influx and inhibiting neuronal electrical activity. Administered intravenously for sedation and hypnosis, it is characterized by rapid onset, short duration of action, rapid recovery, minimal accumulation, and metabolism independent of hepatic or renal pathways. Previous studies indicate that benzodiazepines generally lack significant cardiovascular depressant effects and are associated with a lower incidence of hemodynamic instability during anesthesia induction. However, the specific impact of remimazolam on CBF following general anesthesia induction remains unclear.

Therefore, to further elucidate the effects of this novel benzodiazepine, remimazolam-which reportedly lacks significant cardiovascular depression-on CBF post-induction, we propose the following strategies for our clinical study: (1) compare remimazolam with the commonly used agent propofol for anesthesia induction; (2) administer remimazolam as an intravenous bolus of 0.3 mg/kg and propofol at 2 mg/kg for induction; (3) implement goal-directed fluid management during the peri-induction period; (4) utilize ultrasound to monitor blood flow in the middle cerebral artery; and (5) assess postoperative recovery parameters. Through this comprehensive approach, we aim to determine whether remimazolam offers a protective or optimizing effect on CBF during general anesthesia induction, thereby providing an empirical foundation for its routine clinical use in this context.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have signed the informed consent form and are willing to comply with the study protoco
• Age greater than 18 years
• ASA physical status classification I to II
• Scheduled for elective surgery
• Undergoing general anesthesia with endotracheal intubation
• No history of cerebrovascular disease, carotid artery stenosis, or traumatic brain injury.

Exclusion Criteria:

• History of intracranial lesions, carotid artery stenosis, or traumatic brain injury
• Allergy or contraindications to remimazolam or propofol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Propofol; Propofol is used as the sedative agent during the anesthesia induction period.	Drug: Propofol (Group P); Propofol is used as the sedative agent during the anesthesia induction period (administer propofol at 2 mg/kg for induction).; Other Names: Comparator
Experimental: Remimazolam; Remimazolam is used as the sedative agent during the anesthesia induction period.	Drug: Remimazolam; Remimazolam is used as the sedative agent during the anesthesia induction period (administer remimazolam as an intravenous bolus of 0.3 mg/kg for induction).; Other Names: Experimental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak systolic blood flow velocity (PS)	Peak systolic blood flow velocity (PS) in the middle cerebral artery following general anesthesia induction (at 1, 3, 5, and 10 minutes after endotracheal intubation). Peak systolic blood flow velocity (PS) is the maximum speed of blood flow recorded during the systolic phase of the cardiac cycle, typically measured in centimeters per second (cm/s). Peak systolic blood flow velocity (PS) normal values are vessel-specific and age-dependent. In healthy adults, the commonly cited reference range for the middle cerebral artery (MCA) is approximately 80-120 cm/s. This value decreases with age. For other intracranial arteries, PS is generally lower (e.g., 40-80 cm/s for vertebrobasilar arteries). Physiological factors like hematocrit and gender also cause minor variations. Clinically, PS values above 140-200 cm/s in the MCA often indicate significant pathology such as vasospasm or stenosis.	1, 3, 5, and 10 minutes after endotracheal intubation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The resistance index (RI) of the middle cerebral artery	The resistance index (RI) of the middle cerebral artery (MCA) is a hemodynamic parameter. It reflects downstream cerebrovascular resistance and is defined by the formula: RI = (Peak Systolic Velocity - End-Diastolic Velocity) / Peak Systolic Velocity. A normal RI in the MCA for healthy adults typically ranges from 0.50 to 0.70 (or 50-70%). Values are influenced by age, with neonates and infants having higher normal values (often up to 0.80-0.85) which decrease toward adult levels with maturation. In elderly individuals, a slight increase may be observed due to reduced vascular compliance. An elevated RI (>0.80) generally indicates increased distal vascular resistance, which can be caused by intracranial hypertension, severe microangiopathy, or brain death. A very low RI (<0.50) may suggest a hyperemic state or proximal stenosis.	1, 3, 5, and 10 minutes after endotracheal intubation
Mean blood flow velocity (MV)	Mean blood flow velocity (MV), often referred to as Time-Averaged Maximum Velocity (TAMV), is a key hemodynamic parameter measured by Doppler ultrasound. It represents the average speed of the fastest-moving blood cells within a vessel over one complete cardiac cycle. For the middle cerebral artery (MCA) in healthy adults, the normal MV typically ranges from 40 to 65 cm/s. This value is age-dependent, being higher in children and gradually decreasing with advancing age. A sustained MV outside this range, particularly when asymmetric compared to the contralateral side, can indicate pathological conditions such as stenosis, hyperemia, or impaired autoregulation. Its calculation integrates both systolic and diastolic flow, making it a stable indicator of overall cerebral perfusion.	1, 3, 5, and 10 minutes after endotracheal intubation
Pulsatility index (PI)	The Pulsatility Index (PI) is a dimensionless hemodynamic parameter derived from Transcranial Doppler (TCD) ultrasound. It quantifies the pulsatility of the blood flow waveform, reflecting downstream cerebrovascular resistance. It is calculated using the formula: PI = (Peak Systolic Velocity - End-Diastolic Velocity) / Mean Velocity. For the middle cerebral artery (MCA) in healthy adults, the normal PI typically ranges from 0.70 to 1.10. Age significantly influences this value; neonates have a much higher normal PI (often >1.50), which decreases to adult levels during childhood. An elevated PI (>1.20) generally indicates increased distal resistance, which can be caused by intracranial hypertension or small vessel disease. Conversely, a very low PI (<0.60) may suggest a hyperdynamic state or proximal stenosis.	1, 3, 5, and 10 minutes after endotracheal intubation
Postoperative recovery time	post-anesthesia care unit (PACU) length of stay. There is no single universal "normal value" for Post-Anesthesia Care Unit (PACU) length of stay, as it is highly dependent on the type of surgery, anesthesia technique, institutional protocols, and patient-specific factors. For straightforward, outpatient, or minor inpatient surgeries, a typical stay often ranges from 30 minutes to 2 hours. The primary discharge criteria are based on standardized scoring systems, most commonly the Aldrete score or its modifications. Patients must achieve a predetermined score (usually ≥9 out of 10) indicating stable vital signs, adequate oxygenation, intact consciousness, and controlled pain and nausea before discharge to a ward or home. Prolonged stays beyond expected benchmarks are used as a quality indicator to identify and address potential complications like postoperative nausea and vomiting, pain, or hemodynamic instability.	During the post-anesthesia care unit (PACU)
Postoperative cognitive score	Postoperative cognitive score was assessed by the Mini-Mental State Examination, MMSE). MMSE is a standardized, 30-point questionnaire used to screen for cognitive impairment. It assesses five key domains: orientation (to time and place), registration and recall of words, attention and calculation (e.g., serial sevens), language abilities (naming, repetition, comprehension, reading, writing), and visual construction (copying a pentagon). Administration involves a trained examiner asking the patient specific questions in a quiet setting, typically taking 5-10 minutes. One point is awarded for each correct task, with a maximum total score of 30. Results are interpreted based on the total score: 27-30 suggests normal cognition, 24-26 indicates mild cognitive impairment, 19-23 signifies moderate impairment, and a score ≤18 points to severe impairment.	On the first postoperative day.

Collaborators and Investigators

• Sponsor: Jun Zhang
• Investigators: Principal Investigator: Jun Zhang, Fudan University Shanghai Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2025
• Primary Completion (Actual): February 28, 2026
• Study Completion (Actual): March 1, 2026

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Propofol; Cerebral blood flow; Remimazolam
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Propofol; remimazolam
• Other Study ID Numbers: 2510-Exp296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data sets are available from the corresponding author on reasonable request

Drug and device information, study documents

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