PeRsonalized Blood prEssure Management on Postoperative Complications and Mortality in hIgh-risk Patients Undergoing Major Non-cardiac Surgery (PREMIUM)

Nanfang Hospital, Southern Medical University

Status: Enrolling

Conditions: Hypotension

Treatments: Other: Routine blood pressure management; Other: Personalized blood pressure management

Study type: Interventional

Funder types: Other

Identifiers

NCT06952387

NFEC-2025-134

Details and patient eligibility

About

High-risk populations, particularly elderly individuals and patients with cardiovascular comorbidities, exhibit markedly elevated incidences of postoperative myocardial injury (MINS), acute kidney injury (AKI), and mortality.

Intraoperative hypotension (IOH), a pervasive clinical phenomenon affecting 40%-90% of surgical cases, Substantial observational evidence links IOH severity/duration to ischemic organ injuries (MINS, AKI) and long-term morbidity.Nevertheless, inherent limitations of observational designs-particularly residual confounding-preclude definitive causal inferences. Notably, randomized controlled trials (RCTs) investigating goal-directed hemodynamic interventions demonstrate inconsistent clinical benefits, underscoring the imperative to clarify causal mechanisms between IOH and organ injury. This causal ambiguity arises from two unresolved scientific questions:

(1) Threshold personalization deficit; (2) Therapeutic strategy limitations. In light of current evidence, perioperative hypotension management demands personalized strategies, the investigators propose a multicenter randomized controlled trial (RCT) that aims to clarify the clinical benefits of individualized blood pressure management.

Full description

Anesthesia- and surgery-related complications and mortality constitute a critical global public health burden. Annually, over 300 million surgical procedures are performed worldwide, with postoperative complications and mortality standing as predominant contributors to adverse outcomes. High-risk populations, particularly elderly individuals and patients with cardiovascular comorbidities, exhibit markedly elevated incidences of postoperative myocardial injury (MINS), acute kidney injury (AKI), and mortality. Refinement of perioperative management protocols-especially precision-guided hemodynamic control-has emerged as a pivotal strategy for optimizing patient prognosis.

Intraoperative hypotension (IOH), a pervasive clinical phenomenon affecting 40%-90% of surgical cases, is conventionally defined through either absolute thresholds (e.g., systolic blood pressure (SBP) <90 mmHg or mean arterial pressure (MAP) <65 mmHg) or relative reductions from baseline values (>20% decline). Its high prevalence and association with end-organ hypoperfusion have positioned IOH as a central concern in perioperative care. Substantial observational evidence links IOH severity/duration to ischemic organ injuries (MINS, AKI) and long-term morbidity. Nevertheless, inherent limitations of observational designs-particularly residual confounding-preclude definitive causal inferences. Notably, randomized controlled trials (RCTs) investigating goal-directed hemodynamic interventions demonstrate inconsistent clinical benefits, underscoring the imperative to clarify causal mechanisms between IOH and organ injury.

This causal ambiguity arises from two unresolved scientific questions:

1. Threshold personalization deficit: Current paradigms predominantly apply population-based fixed thresholds (e.g., MAP ≥75-80 mmHg vs. ≥60 mmHg), disregarding interindividual hemodynamic variability. Although The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study used personalized blood pressure targets, its approach of measuring baseline blood pressure during a single clinic visit conflicts with current evidence. Research shows that 24-hour ambulatory monitoring is the most reliable method to capture an individual's true baseline blood pressure and daily fluctuations.
2. Therapeutic strategy limitations: Conventional protocols emphasizing aggressive vasopressor use to achieve arbitrary pressure targets may inadvertently increase complications like anastomotic leakage and AKI. Furthermore, the multifactorial etiology of IOH-encompassing hypovolemia, vasoplegia, and impaired cardiac contractility-demands etiology-specific management algorithms rather than universal interventions.

In light of current evidence, perioperative hypotension management demands personalized strategies. To address this need, the investigators propose a multicenter randomized controlled trial (RCT) that pioneers the integration of ambulatory blood pressure monitoring (ABPM) with etiology-specific intervention protocols. This study aims to clarify the clinical benefits of individualized blood pressure management and establish high-quality evidence to advance precision anesthesia practices in perioperative care.

Enrollment: 1,624 estimated patients

Sex: All

Ages: 65 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 65-90 yr;

• Scheduled to undergo elective non-cardiac major surgery under general anesthesia (with an estimated surgery duration of ≥ 2 hours and an anticipated postoperative hospital stay of ≥ 2 days);

• Patients with high cardiovascular risk, meeting at least one of the following conditions:

  1. History of stroke;
  2. History of coronary artery disease;
  3. History of congestive heart failure;
  4. History of peripheral arterial disease;
  5. Preoperative brain natriuretic peptide (BNP) ≥ 92 mg/L or N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 300 ng/L;
  6. Preoperative cardiac troponin (cTn) or high-sensitivity cardiac troponin (hs-cTn) > upper reference limit;
  7. Hypertension requiring medication treatment;
  8. Diabetes requiring medication treatment;
  9. History of chronic kidney disease;
  10. Continuous smoking for 2 years or more, with interruptions of less than one month before the current hospital admission;
  11. Hypercholesterolemia;
  12. History of transient ischemic attack.

Exclusion criteria

• Refuse to participate this trial;
• Inability to communicate in the preoperative period because of coma, profound dementia, or language barrier;
• Severe uncontrolled hypertension before surgery (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg);
• Severe hepatic dysfunction (Child-Pugh Class C); or severe renal dysfunction required preoperative dialysis; or American Society of Anesthesiologists (ASA) physical status ≥ V; or expectation lifespan ≤ 24h;
• Unstable cardiovascular conditions: acute coronary syndrome, decompensated heart failure, severe arrhythmias, severe valvular heart disease;
• Scheduled to undergo neurosurgical procedures, transplantation, vascular surgery;
• Urgent surgery;
• Diagnosed with sepsis or sepsis shock before surgery.
• Requiring vasopressor treatment before surgery.
• Unable to finish 24-hour automated blood pressure monitor;
• Current participation in another interventional study.
• Any condition deemed ineligible for participation by clinicians.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,624 participants in 2 patient groups

Control group

Other group

Description:

In patients assigned to control group, clinicians were unaware of the results of preoperative automated 24-h blood pressure monitoring and thus managed blood pressure per institutional routine which generally is to maintain MAP above 60 mmHg. Routine blood pressure management started with the induction of anesthesia and lasted for 2 hours after surgery.

Treatment:

Other: Routine blood pressure management

Intervention group

Experimental group

Description:

In patients assigned to intervention group, clinicians were asked to maintain intraoperative MAP above the preoperative baseline MAP (with a maximum MAP target of 110 mmHg and a minimum MAP target of 65mmHg). Personalized blood pressure management started with the induction of anesthesia and lasted for 2 hours after surgery.

Treatment:

Other: Personalized blood pressure management