Comparison of Hemodynamic Stability During Anesthesia Using Remimazolam and Sevoflurane in Minimally Invasive AVR

Study Overview
=================
Brief Summary
-----------------
Anesthetic agents can cause hypotension, and be especially dangerous in patients with severe aortic stenosis, which can lead to even circulatory collapse. Remimazolam is known for its hemodynamic stability compared to propofol. This study is designed to compare effects of remimazolam vs. sevoflurane anesthesia on intraoperative hemodynamics in patients with severe aortic valve stenosis.

Detailed Description
-----------------
Anesthetic agents can cause hypotension due to reduced cardiac contractility and vasodilation. This can be especially dangerous in patients with severe aortic stenosis, which can lead to even circulatory collapse in extreme cases. Remimazolam is a relatively new anesthetic agent and it is a ultra-short acting benzodiazepine with a context sensitive half time of 7.5 minutes. Remimazolam is known for its hemodynamic stability compared to propofol. Previous studies have also shown that remimazolam can be safely used in patients with severe aortic stenosis and in cardiac anesthesia induction and during cardiopulmonary bypass. However, there is no definite data on comparison of hemodynamic variables between remimazolam based total intravenous anesthesia (TIVA) and conventional propofol induction and sevoflurane maintenance anesthesia. Therefore, this study is designed to compare effects of remimazolam vs. sevoflurane anesthesia on intraoperative hemodynamics in patients undergoing minimally invasive aortic valve replacement surgery.

Official Title
-----------------
Comparison of Hemodynamic Stability During Anesthesia Using Remimazolam and Sevoflurane in Patients Undergoing Minimally Invasive Aortic Valve Replacement Surgery : A Prospective Randomized Controlled Study

Conditions
-----------------
Aortic Valve Stenosis, Remimazolam

Intervention / Treatment
-----------------
* Drug: Remimazolam besylate
* Drug: Propofol/ Sevoflurane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients over 19 years old Patients with severe aortic stenosis, undergoing minimally invasive aortic valve replacement surgery Exclusion Criteria: Patients with known allergy to benzodiazepine, flumazenil, propofol Patients with galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Patients with hypersensitivity to Dextran40 Patients who have been taking benzodiazepine for long term Patients with whom heart rate assessment is not accurate, such as atrial fibrillation Patients with end stage renal disease requiring hemodialysis Patients with history of acute angle glaucoma Patients with valve disease severity of grade III or higher, other than aortic valve Emergency operation

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam<br>Induction dose of 6 mg/kg/h of remimazolam with remifentanil TCI 1 4 nanogram/mL are injected together. When patient loses consciousness, rocuronium 0.8 mg/kg is given and endotracheal intubation is performed after confirming that TOF count is less than one. Anesthesia is maintained by using remimazolam dose of 1mg/kg/h 2mg/kg/h with remifentanil to maintain optimal depth of anesthesia, which will checked by Sedline value between 25 to 50. | Drug: Remimazolam besylate<br>* During induction, patients allocated to the remimazolam group will receive remimazolam 6mg/kg/h with remifentanil TCI 1 4 nanogram/mL. After patient loses consciousness, anesthesia will be maintained with remimazolam 1-2mg/kg/h combied with remifetanil.<br>* Other names: Remimazolam besylate, Byfavo Inj., Hana Pharm Col, Ltd., Seoul, Korea;|
| Active Comparator: Propofol/sevoflurane<br>1% propofol 1-2mg/kg is injected with remifentanil TCI 1 4, and when patient loses consciousness, sevoflurane is started and rocuronium 0.8mg/kg is given. After confirming that TOF count is less than one, intubation is performed and anesthesia is maintained with sevoflurane and remifentanil to keep the Sedline value between 25 and 50. | Drug: Propofol/ Sevoflurane<br>* During induction, patients allocated to the P/S group will receive propofol 1% 1-2mg/kg with remifentanil TCI 1 4 nanogram/mL. After patient loses consciousness, anesthesia will be maintained with sevoflurane and remifentanil.<br>* Other names: Fresofol 1% TM, Fresenius;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total dose of vasopressors and inotropics used. | Total dose of vasopressors and inotropics used during anesthesia will be compared between two groups. | Start of anesthesia to end of anesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypotension and bradycardia event duration | Hypotension and bradycardia event duration will be compared | Start of anesthesia to end of anesthesia | 
| Extubation time | Extubation time between the two groups will be compared | End of anesthesia to extubation | 
| Emergence agitation | Emergence agitation will be compared between the two groups using Riker Sedation-Agitation Scale upon arrival at ICU. The Riker Sedation-Agitation Scale uses a numeric score from 1 (unarousable) to 7 (dangerous agitation)to assess the level of patient sedation and identifies seven levels of sedation and agitation, which range from deep sedation (unarousable) to dangerous agitation. | Arrival of patient at ICU | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aortic Valve Stenosis, Remimazolam