PeRsonalized Blood prEssure Management on Postoperative Complications and Mortality in hIgh-risk Patients Undergoing Major Non-cardiac Surgery (PREMIUM)
- Conditions
- Hypotension
- Registration Number
- NCT06952387
- Lead Sponsor
- Nanfang Hospital, Southern Medical University
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1624
-
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:
- History of stroke;
- History of coronary artery disease;
- History of congestive heart failure;
- History of peripheral arterial disease;
- Preoperative brain natriuretic peptide (BNP) ≥ 92 mg/L or N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 300 ng/L;
- Preoperative cardiac troponin (cTn) or high-sensitivity cardiac troponin (hs-cTn) > upper reference limit;
- Hypertension requiring medication treatment;
- Diabetes requiring medication treatment;
- History of chronic kidney disease;
- Continuous smoking for 2 years or more, with interruptions of less than one month before the current hospital admission;
- Hypercholesterolemia;
- History of transient ischemic attack.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method A composite of postoperative complications and mortality within 30 days after surgery Up to 30 days after surgery Defined as a composite of myocardial injury after non-cardiac surgery (MINS), myocardial infarction (MI), postoperative acute heart failure, non-fatal cardiac arrest, stroke, acute kidney injury (AKI), all-cause mortality.
- Secondary Outcome Measures
Name Time Method Length of stay in ICU after surgery Up to 30 days after surgery For patients admitted to ICU after surgery, the investigators record the length of stay in the unit.
The individual components of the primary composite outcome within 30 days after surgery Up to 30 days after surgery The incidence of individual components of the primary composite outcome (MINS, MI, postoperative acute heart failure, non-fatal cardiac arrest, stroke, AKI and all-cause mortality).
Proportion of ICU admission after surgery Up to 30 days after surgery Proportion of patients admitted in intensive care unit after surgery.
Length of stay in the hospital after surgery Up to 30 days after surgery Length of stay in the hospital after surgery.
Other major postoperative complications within 30 days after surgery Up to 30 days after surgery Defined as new onset medical events other than primary composite outcome that were deemed harmful and required therapeutic intervention, that is, Grade II or higher on the Clavien-Dindo classification.
Time to first oral intake after surgery Up to 30 days after surgery Defined as the time interval from surgery completion to first oral intake.
Time to first flatus passage after surgery Up to 30 days after surgery Defined as the time interval from surgery completion to first flatus passage
Trial Locations
- Locations (7)
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Affiliated Panyu Central Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
The Third People's Hospital of Shenzhen
🇨🇳Shenzhen, Guangdong, China
The Fifth Affiliated Hospital of Sun Yat-sen University
🇨🇳Zhuhai, Guangdong, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China