The goal of this randomized controlled trial is to compare total intravenous anesthesia with remimazolam vs total intravenous anesthesia with propofol in moderate-to-high risk patients undergoing major elective noncardiac surgery under general anesthesia. The primary hypothesis is that total intravenous anesthesia with remimazolam can increase days alive and out of hospital at postoperative day 30 compared with total intravenous anesthesia with propofol.

Inclusion Criteria:

• Age ≥45 years;

• Undergoing elective major surgery under general anesthesia (expected surgery time >2 h, expected length of postoperative stay >2 d);

• Fulfilling ≥1 of the following criteria:

  1. history of coronary artery disease;
  2. history of stroke;
  3. history of congestive heart failure;
  4. preoperative NT-proBNP >200 pg/mL or BNP>92 pg/mL;
  5. age ≥70 years;
  6. diabetes requiring medical treatment;
  7. ASA status 3 or 4;
  8. history of chronic kidney disease (preoperative sCr >133 μmol/L or 1.5 mg/dL);
  9. history of peripheral arterial disease;
  10. preoperative serum albumin <30 g/L;
  11. preoperative hemoglobin <100 g/L.

Exclusion Criteria:

• Undergoing organ transplantation, cardiac, craniocerebral, burn or interventional operations;
• Low risk or minor surgery
• End-stage renal disease requiring renal-replacement therapy;
• Hepatic dysfunction (Child B or C);
• Previous liver or kidney transplantation;
• Previous allergy to general anesthetics;
• Unable to receive bispectral index monitoring;
• ASA score ≥5;
• Exposure to general anesthesia in prior 30 days or anticipated re-exposure to general anesthesia within 30 days after surgery;
• Need for prolonged airway protection or mechanical ventilatory support after surgery;
• Current participation in another interventional study;
• Previous participation in this study;
• Pregnant or breastfeeding women.

One year after the main trial result is published.