Aortic Aneurysm of the Proximal Arch, Aortic Aneurysms Arch, Aortic Arch Disease, Postoperative Delirium, POSTOPERATIVE DELIRIUM AND POSTOPERATIVE COGNITIVE DECLINE, Postoperative Delirium (POD)
Conditions
Keywords
Remimazolam, Propofol, Arch surgery, Arch disease, postoperative delirium, POCD (postoperative clinical decline)
Brief summary
The purpose of this study is to compare remimazolam- and propofol-based anesthesia for their effects on postoperative cognitive dysfunction in patients undergoing aortic arch surgery. These procedures involve a substantial risk of cerebral ischemia and reperfusion injury, which may contribute to postoperative cognitive decline. Although experimental studies have suggested potential neuroprotective effects of remimazolam, clinical evidence in patients undergoing high-risk aortic arch surgery remains limited. This prospective, randomized controlled trial will compare the incidence of postoperative cognitive dysfunction between patients receiving remimazolam- or propofol-based anesthesia. In addition, changes in circulating neuroinflammatory and neuronal injury biomarkers will be evaluated to explore the potential mechanisms underlying any neuroprotective effect of remimazolam. The findings may provide clinical evidence to guide anesthetic selection and improve neurological outcomes in patients undergoing aortic arch surgery.
Interventions
DRUGRemimazolam Besylate
\- Continuous drug: remimazolam diluted to 2 mg/mL in normal saline - Maintenance: 1-2 mg/kg/h (titrated to BIS 40-60, max 2 mg/kg/h)
DRUGpropofol
Continuous drug: propofol (undiluted, 20 mg/mL) - Administration: target-controlled infusion (TCI, Marsh model) - Maintenance: 1-1.5 μg/mL (titrated to BIS 40-60)
Sponsors
Seoul National University Hospital
Hana Pharm Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 19 years or older * Patients scheduled to undergo total or partial aortic arch replacement for aortic arch disease, with planned circulatory arrest and/or selective cerebral perfusion as a cerebral protection strategy during surgery
Exclusion criteria
* Pre-existing cognitive impairment, defined as Mini-Mental State Examination (MMSE) score \<24 * Acute cerebral hemorrhage or cerebral infarction within the previous 3 months * History of hypersensitivity to remimazolam or other benzodiazepines * History of alcohol or substance abuse * Chronic use of opioids or benzodiazepines * Severe hepatic impairment (Child-Pugh class C) * Acute or chronic renal failure requiring dialysis Emergency surgery or acute aortic dissection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative cognitive decline | Preoperative baseline to postoperative day 7 or before hospital discharge | Postoperative cognitive function will be assessed using the Korean Mini-Mental State Examination (K-MMSE) and the Korean version of the Montreal Cognitive Assessment (MoCA-K). Both assessments will be performed preoperatively and again on postoperative day 7 or before hospital discharge. Postoperative cognitive dysfunction will be defined as a decrease of ≥2 points from the preoperative baseline score in either the K-MMSE or MoCA-K. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in plasma IL-1β concentration | Preoperative baseline to 2-4 hours after completion of cardiopulmonary bypass | Plasma interleukin-1 beta (IL-1β) concentration will be measured at preoperative baseline and 2-4 hours after completion of cardiopulmonary bypass. The change from baseline will be compared between the remimazolam and propofol groups. Plasma IL-1β concentration will be measured in pg/mL using the Meso Scale Discovery assay. |
| Change in plasma TNF-α concentration | Preoperative baseline to 2-4 hours after completion of cardiopulmonary bypass | Plasma tumor necrosis factor-alpha (TNF-α) concentration will be measured at preoperative baseline and 2-4 hours after completion of cardiopulmonary bypass. The change from baseline will be compared between the remimazolam and propofol groups. Plasma TNF-α concentration will be measured in pg/mL using the Meso Scale Discovery assay. |
| Change in plasma IL-6 concentration | Preoperative baseline to 24 hours after completion of cardiopulmonary bypass | Plasma interleukin-6 (IL-6) concentration will be measured at preoperative baseline and 24 hours after completion of cardiopulmonary bypass. The change from baseline will be compared between the remimazolam and propofol groups. Plasma IL-6 concentration will be measured in pg/mL using the Meso Scale Discovery assay. |
| Change in plasma IL-10 concentration | Preoperative baseline to 24 hours after completion of cardiopulmonary bypass | Plasma interleukin-10 (IL-10) concentration will be measured at preoperative baseline and 24 hours after completion of cardiopulmonary bypass. The change from baseline will be compared between the remimazolam and propofol groups. Plasma IL-10 concentration will be measured in pg/mL using the Meso Scale Discovery assay. |
| Change in plasma HMGB1 concentration | Preoperative baseline through 24 hours after completion of cardiopulmonary bypass | Plasma high mobility group box 1 (HMGB1) concentration will be measured at preoperative baseline, 2-4 hours after completion of cardiopulmonary bypass, and 24 hours after completion of cardiopulmonary bypass. Changes from baseline will be compared between the remimazolam and propofol groups. Plasma HMGB1 concentration will be measured in pg/mL using the Multiplex bead assay. |
| Change in plasma GFAP concentration | Preoperative baseline to 24 hours after completion of cardiopulmonary bypass | Plasma glial fibrillary acidic protein (GFAP) concentration will be measured at preoperative baseline and 24 hours after completion of cardiopulmonary bypass. The change from baseline will be compared between the remimazolam and propofol groups. GFAP will be analyzed using the Single Molecule Array (Simoa) assay. |
Countries
South Korea
Contacts
CONTACTYoun Joung Cho, M.D., Ph.D.
Outcome results
None listed