The GUARDIAN Trial - Induction Agent Sub-Study

Inclusion Criteria: 1. At least 45 years old; 2. Scheduled for major noncardiac surgery expected to last at least 2 hours; 3. Having general anesthesia, neuraxial anesthesia, or the combination; 4. Expected to require at least overnight hospitalization (planned ICU admission is acceptable); 5. Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life); 6. Expected to have direct intraoperative blood pressure monitoring with an arterial catheter; 7. Cared for by clinicians willing to follow the GUARDIAN protocol; 8. Subject to at least one of the following risk factors: 1. Age \>65 years; 2. History of peripheral arterial disease; 3. History of coronary artery disease; 4. History of stroke or transient ischemic attack; 5. Serum creatinine \>175 μmol/L (\>2.0 mg/dl) within 6 months; 6. Diabetes requiring medication; 7. Current smoking or 15 pack-year history of smoking tobacco; 8. Scheduled for major vascular surgery; 9. Body mass index ≥35 kg/m2; 10. Preoperative high-sensitivity troponin T \>14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay, \[Borges, unpublished\]), or 25% of the 99% percentile for other assays - all within 6 months; 11. B-type natriuretic protein (BNP) \>80 ng/L or N-terminal B-type natriuretic protein (NTProBNP) \>200 ng/L within six months. Exclusion Criteria: 1. Are scheduled for carotid artery surgery; 2. Are scheduled for intracranial surgery; 3. Are scheduled for partial or complete nephrectomy; 4. Are scheduled for pheochromocytoma surgery; 5. Are scheduled for liver or kidney transplantation; 6. Require preoperative intravenous vasoactive medications; 7. Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension; 8. Require beach-chair positioning; 9. Have a documented history of dementia; 10. Have language, vision, or hearing impairments that may compromise cognitive assessments; 11. Have contraindications to norepinephrine or phenylephrine per clinician judgement; 12. Have previously participated in the GUARDIAN trial.