REmimazolam vs PrOpofol on Intraoperative hypotenSion in Major Noncardiac surgEry

Study Overview
=================
Brief Summary
-----------------
Intraoperative hypotension is common during major noncardiac surgery and is associated with adverse postoperative outcomes. Propofol, the most commonly used intravenous anesthetic agent worldwide, is associated with hypotension on induction and maintenance of general anesthesia. Remimazolam is a newly developed short-acting benzodiazepine drug and has been approved for use in procedural sedation and general anesthesia. It was associated with a lower incidence of hypotension during procedural sedation in previous studies. The aim of this study is to tested the primary hypothesis that total intravenous anesthesia with remimazolam reduces the duration and severity of hypotension during major noncardiac surgery compared with total intravenous anesthesia with propofol.

Official Title
-----------------
Effects of Total Intravenous Anesthesia With Remimazolam vs Propofol on Intraoperative Hypotension in Major Noncardiac Surgery: a Randomized Controlled Trial

Conditions
-----------------
Intraoperative Hypotension

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥45 years; Undergoing elective major surgery under general anesthesia (expected surgery time >2 h, expected length of postoperative stay >2 d); Need for intraoperative invasive blood pressure monitoring via arterial line; Fulfilling ≥1 of the following criteria (a-k): history of coronary artery disease; history of stroke; history of congestive heart failure; preoperative NT-proBNP >200 pg/mL; preoperative high sensitivity troponin T > 14 ng/L; age ≥70 years; diabetes requiring medical treatment; ASA status 3 or 4; history of chronic kidney disease (preoperative sCr >133μmol/L or 1.5 mg/dL); preoperative serum albumin <30 g/L; preoperative hemoglobin <100 g/L. Exclusion Criteria: Undergoing organ transplantation, cardiac, neurological, or adrenal gland surgery; Planned intraoperative MAP higher or lower than 65 mmHg; Severe untreated or uncontrolled hypertension (preoperative SBP >180 mmHg and/or DBP >110 mmHg); End-stage renal disease requiring renal-replacement therapy; ASA score ≥5; Preoperative requirement of vasopressor infusion; Unable to receive bispectral index monitoring; Known allergy to benzodiazepines, propofol, opioids or cisatracurium; Current participation in another interventional study; Previous participation in this study; Pregnant or breastfeeding women.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam TIVA<br>Induction: Remimazolam, sufentanil, cisatracurium. Maintenance: Remimazolam, remifentanil, cisatracurium. | Drug: Remimazolam<br>* Remimazolam is administered intravenously for induction and maintenance of general anesthesia. The dose is titrated to maintain Bispectral Index value between 40 and 60.<br>|
| Active Comparator: Propofol TIVA<br>Induction: Propofol, sufentanil, cisatracurium. Maintenance: Propofol, remifentanil, cisatracurium. | Drug: Propofol<br>* Propofol is administered intravenously for induction and maintenance of general anesthesia. The dose is titrated to maintain Bispectral Index value between 40 and 60.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted average (TWA) intraoperative mean arterial pressure (MAP) under 65 mmHg. | TWA-MAP under 65 mmHg for each patient is derived by dividing area under the curve (AUC)-MAP under 65 mmHg by the time interval between the first and the last MAP measurements. | MAP measurements are recorded every minute from of anesthesia induction to end of wound closure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC-MAP under 65 mmHg. | AUC-MAP under 65 mmHg for each patient is derived by depth of hypotension in millimeters of mercury below a MAP of 65 mmHg × time in minutes spent below a MAP of 65 mmHg. | From of anesthesia induction to end of wound closure. | 
| Duration of MAP under 65 mmHg. | Duration of MAP under 65 mmHg is the total amount of time in minutes that the MAP is under 65 mmHg. | From of anesthesia induction to end of wound closure. | 
| Time-weighted average (TWA) intraoperative mean arterial pressure (MAP) under 70 mmHg. | TWA-MAP under 70 mmHg for each patient is derived by dividing area under the curve (AUC)-MAP under 70 mmHg by the time interval between the first and the last MAP measurements. | From of anesthesia induction to end of wound closure. | 
| AUC-MAP under 70 mmHg. | AUC-MAP under 70 mmHg for each patient is derived by depth of hypotension in millimeters of mercury below a MAP of 70 mmHg × time in minutes spent below a MAP of 70 mmHg. | From of anesthesia induction to end of wound closure. | 
| Duration of MAP under 70 mmHg. | Duration of MAP under 70 mmHg is the total amount of time in minutes that the MAP is under 70 mmHg. | From of anesthesia induction to end of wound closure. | 
| Time-weighted average (TWA) intraoperative mean arterial pressure (MAP) under 60 mmHg. | TWA-MAP under 60 mmHg for each patient is derived by dividing area under the curve (AUC)-MAP under 60 mmHg by the time interval between the first and the last MAP measurements. | From of anesthesia induction to end of wound closure. | 
| AUC-MAP under 60 mmHg. | AUC-MAP under 60 mmHg for each patient is derived by depth of hypotension in millimeters of mercury below a MAP of 60 mmHg × time in minutes spent below a MAP of 60 mmHg. | From of anesthesia induction to end of wound closure. | 
| Duration of MAP under 60 mmHg. | Duration of MAP under 60 mmHg is the total amount of time in minutes that the MAP is under 60 mmHg. | From of anesthesia induction to end of wound closure. | 
| Postoperative complications. | A composite of in-hospital all-cause mortality and cardiovascular, neurological, renal, respiratory, and infectious complications. | From end of surgery to 30 days after surgery. | 
| Days alive and at home. | Number of days alive and at home within 30 days after surgery. | From end of surgery to 30 days after surgery. | 
| Postoperative quality of recovery. | Patient-reported quality of recovery after surgery and anesthesia with the QoR-15, ranging from 0 (poor recovery) to 150 (excellent recovery) | At postoperative day 1. |