The effects of remimazolam and dexmedetomidine on emotion, cognitive function, and neuroprotection in patients with ischemic stroke

ISRCTN	ISRCTN28704245
DOI	https://doi.org/10.1186/ISRCTN28704245
Xinjiang "Tianshan Talents" Training Program, Medical and Health High-Level Talent Project: "Research on Key Technologies for Prevention and Treatment of Perioperative Important Organ Dysfunction in Elderly Patients" Project Number	TSYC202401A003
Sponsor	People's Hospital of Xinjiang Uygur Autonomous Region
Funder	Government of Xinjiang Uygur Autonomous Region of China

Submission date: 13/04/2026
Registration date: 20/04/2026
Last edited: 13/04/2026

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Miss Nan Chen
Scientific, Principal investigator, Public

People's Hospital of Xinjiang Uygur Autonomous Region
No. 91 Tianchi Road, Tianshan District, Urumqi City, Xinjiang Uygur Autonomous Region, People's Hospital of Xinjiang Uygur Autonomous Region
Urumqi
830011
China

ORCID ID	0000-0001-9385-7289
Email	13579202240@163.com

Mr Zhichao Yu
Scientific

ORCID ID	0009-0009-9341-415X
Email	13139910597@163.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Active
Assignment	Sequential
Purpose	Prevention
Participant information sheet	49358_PIS_18June2025.pdf
Scientific title	Clinical effects of remimazolam and dexmedetomidine on emotion, cognitive function, and neuroprotection in patients with ischemic stroke
Study objectives
Ethics approval(s)	Approved 25/11/2025, Ethics Committee for Clinical Research, People's Hospital of Xinjiang Uygur Autonomous Region (No. 91 Tianchi Road, Tianshan District, Urumqi City, Xinjiang Uygur Autonomous Region, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, China; +86 0991-856 8013; -), ref: KY2025112417
Health condition(s) or problem(s) studied	Patients with ischemic stroke
Intervention	1. Preoperative Assessment (24 h Before Surgery) Anxiety and depression were evaluated using HADS-A and HADS-D. Cognitive function was assessed by MoCA and MMSE. Neurological impairment was scored with NIHSS. Serum indicators, including cathepsin S (CTSS), inflammatory factors (IL-6, TNF-α, CRP), neuronal injury markers (S-100β, NSE), neurotransmitters (NE, 5-HT), and BDNF, were detected. 2. Study Design and Anesthesia Protocols This was a randomized controlled trial (RCT) with a double-blind design. Randomization was performed using a computer program and sealed envelopes. Patients with ischemic stroke were randomly divided into three groups: remimazolam group (RM), dexmedetomidine group (Dex), and control group (C). All patients received general anesthesia with tracheal intubation. Group RM: Induction with remimazolam 0.2 mg/kg iv; maintenance with remimazolam 0.2–0.5 mg·kg⁻¹·h⁻¹ (BIS 40–60), discontinued 30 min before surgery. Group Dex: Loading dose of dexmedetomidine 0.5 μg/kg iv 10 min before induction; maintenance with 0.2 μg·kg⁻¹·h⁻¹ (BIS 40–60), discontinued 30 min before surgery. Group C: Routine propofol-based anesthesia without remimazolam or dexmedetomidine. Anesthesia induction: Propofol 2–3 mg/kg, sufentanil 0.5 μg/kg, cisatracurium 0.15 mg/kg iv; orotracheal intubation (depth 22–24 cm) followed by mechanical ventilation (FiO₂ 30%, RR 10–12 breaths/min, I:E 1:2–2.5, VT 8–12 mL/kg, ETCO₂ 35–45 mmHg). Anesthesia maintenance: Propofol 4–12 mg·kg⁻¹·h⁻¹ and remifentanil 0.2 μg·kg⁻¹·h⁻¹ iv; additional sufentanil 0.2 μg/kg before skin incision; BIS maintained at 40–60, with dosage adjusted according to vital signs. Fluid therapy included lactated Ringer’s solution and 6% hydroxyethyl starch. Anesthesia emergence: Neuromuscular blockade reversed with atropine 0.5 mg and neostigmine 0.05–0.07 mg/kg iv; tracheal extubation when meeting extubation criteria; patients transferred to the ward when recovery score ≥6 with clear consciousness and no nausea/vomiting. All patients received standard secondary stroke prevention and rehabilitation (physical therapy + cognitive behavioral intervention) postoperatively, with benzodiazepines avoided. 3. Outcome Measures Vital signs (MAP, HR, SpO₂) were recorded at preoperative induction, surgery start, post-thrombectomy, postoperative immediately, 6 h, 12 h, 24 h and 48 h. Adverse events and mental status were documented. Follow-up indicators: HADS-A/HADS-D (1 d, 3 d, 7 d postoperatively and discharge); MoCA/MMSE (3 d, 7 d postoperatively); VAS pain scores (2 h, 12 h, 1 d, 3 d postoperatively); serum CTSS, IL-6, TNF-α, CRP, S-100β, NSE, NE, 5-HT, BDNF and NIHSS scores (24 h, 3 d, 7 d postoperatively). Long-term follow-up (1, 3, 6 months postoperatively) was performed via online platforms to assess anxiety, depression, cognitive function and NIHSS scores.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Remimazolam, dexmedetomidine
Primary outcome measure(s)	Cognitive function measured using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at preoperatively, 3, 7, 30 and 90 days postoperatively
Key secondary outcome measure(s)	Neurological function impairment measured using the NIH Stroke Scale/Score (NIHSS) at preoperatively, 3, 7, 30 and 90 days postoperatively Serum levels of cathepsin S (CTSS), interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor alpha (TNF-a), S100 calcium-binding protein beta (S100-β), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and brain-derived neurotrophic factor (BDNF) measured using enzyme-linked immunosorbent assay (ELISA) at preoperatively, at the end of surgery and 3 days postoperatively Anxiety and depression measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and HADS-depression (HADS-D) at 1, 3, 30 and 90 days postoperatively
Completion date	31/12/2026

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	72
Key inclusion criteria	1. Diagnosis of acute anterior circulation ischemic stroke (internal carotid artery / M1–M2 segment of middle cerebral artery), with penumbra confirmed by CTP/MRP 2. Age 18–80 years, no gender restriction, ASA physical status I–III 3. Admission within 24 hours of symptom onset 4. NIHSS score 4–15 (mild-to-moderate neurological injury[7]), mRS score ≤4 5. No preoperative history of anxiety/depression (HADS score ≤7) or cognitive impairment (MoCA ≥26, MMSE ≥24) 6. Prior to the study, the patient or legal representative understood and voluntarily signed the informed consent approved by the ethics committee, agreed to randomization, and cooperated with follow-up
Key exclusion criteria	1. Diagnosis of global aphasia, transient ischemic attack, visual or auditory impairment, or severe dementia (MMSE < 17, unable to complete scales) 2. Patients with severe uncontrolled medical conditions including diabetes mellitus, hypertension, heart disease, chronic active viral hepatitis, or a history of schizophrenia and other psychiatric disorders; patients receiving preoperative anxiolytics or antidepressants 3. Abnormal hepatic or renal function, severe arrhythmia, bradycardia, or major organ failure such as decompensated cardiopulmonary failure 4. Intraoperative blood loss ≥ 300 mL 5. Patients requiring intraoperative blood transfusion 6. Operation duration ≥ 3 hours 7. Hypersensitivity to remimazolam, dexmedetomidine (DEX), or α₂ agonists 8. Exclusion by neuroimaging: large-area infarction (ASPECTS score < 6 or infarct core volume > 70 mL); complicated with intracranial hemorrhage (type PH2 hematoma) or mass effect 9. Anesthesia-related exclusion: difficult airway, severe intraoperative hypotension (MAP < 60 mmHg for > 10 minutes), or requirement for high-dose vasoactive drugs
Date of first enrolment	01/12/2025
Date of final enrolment	13/04/2026

Locations

Countries of recruitment

China

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet		18/06/2025	13/04/2026	No	Yes

Additional files

49358_PIS_18June2025.pdf: Participant information sheet

Editorial Notes

13/04/2026: Study’s existence confirmed by the Clinical Research Ethics Committee of the People's Hospital of Xinjiang Uygur Autonomous Region, China.