AR-NONCARDIAC: Association of Intraoperative Blood Pressure Excursions Below Cerebral Autoregulatory Boundaries With Organ Injury Following Major Noncardiac Surgery

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05336864

Collaborator

(none)

500

Enrollment

Locations

36.4

Anticipated Duration (Months)

250

Patients Per Site

6.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to investigate the clinical relevance of blood pressure excursions below autoregulatory boundaries in major noncardiac surgery. The study investigates a precedent for a personalized definition of intraoperative arterial hypotension based on non-invasive tissue oxygenation measurements. The feasibility of NIRSbased autoregulation monitoring in major noncardiac surgery and the prognostic relevance of excursions below the NIRS-derived lower limit of autoregulation (LLA) with regard to both short- and long-term major adverse cardiovascular events (MACE) will be analyzed.

This project will consist of a Main study in which all patients will be enrolled and of a Neurologic injury substudy in which select patients will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Intraoperative Arterial Hypotension	Other: NIRS based autoregulation monitoring Other: additional perioperative blood sampling Other: clinical & telephone assessments

Detailed Description

Major adverse cardiovascular events (MACE) are leading causes of perioperative morbidity and mortality following major noncardiac surgery. Intraoperative arterial hypotension is strongly associated with postoperative morbidity and mortality. However, interventional trials have been unable to demonstrate clinically relevant reductions in the incidence of postoperative MACE, which can potentially be explained by the hitherto lacking consideration of patient-specific autoregulatory boundaries. This is especially problematic considering that the presumed mechanism of hypotension-induced organ injury is hypoperfusion due to transgression of the lower limit of blood flow autoregulation. In other clinical settings, excursions below the autoregulatory threshold have been shown to be superior predictors of adverse events than excursions below absolute blood pressure (BP) thresholds, however, there is a paucity of data in major noncardiac surgery.

This prospective, multicenter cohort observation study is to investigate the clinical relevance of blood pressure excursions below autoregulatory boundaries in major noncardiac surgery.

This project will consist of a Main study in which all patients will be enrolled and of a Neurologic injury substudy in which select patients will be enrolled.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Association of Intraoperative Blood Pressure Excursions Below Cerebral Autoregulatory Boundaries With Organ Injury Following Major Noncardiac Surgery (AUTOREGULATE-NONCARDIAC)

Actual Study Start Date :

May 20, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Outcome Measures

Primary Outcome Measures

Perioperative myocardial injury [postoperative days 1-3]
Perioperative myocardial injury, defined as an absolute perioperative rise in high-sensitivity troponin T (hsTnT) of ≥ 14 ng/l above preoperative values (or between two postoperative measurements, if preoperative hs-cTnT is missing)
Perioperative acute kidney injury [postoperative days 1-3]
Perioperative acute kidney injury, defined as absolute perioperative increase in serum creatinine of > 26.4 μmol/l or a percentage perioperative increase in serum creatinine of > 50%

Secondary Outcome Measures

Long-term cardiovascular outcomes [within 1 year postoperatively]
Long-term cardiovascular outcomes: time to major adverse cardiovascular events (MACE) within 1 year postoperatively, a composite defined as any of the following: acute coronary syndrome acute congestive heart failure (CHF) coronary revascularization stroke new diagnosis of chronic kidney disease (CKD) or progression of pre-existing CKD all-cause mortality cardiovascular mortality
Acute coronary syndrome [within 30 days postoperatively]
Diagnosis on discharge letter (notes in medical record: myocardial infarction [type 1 or 2], acute coronary syndrome [type 1 or 2])
Coronary revascularization [within 30 days postoperatively]
Diagnosis on discharge letter (notes in medical record: percutaneous coronary intervention [PCI] or coronary bypass graft surgery [CABG])
Stroke [within 30 days postoperatively]
Diagnosis on discharge letter (notes in medical record: stroke, ischemic stroke, hemorrhagic stroke, intracranial hemorrhage or bleed, cerebrovascular event)
Chronic kidney disease (CKD) [within 30 days postoperatively]
Diagnosis on discharge letter (notes in medical record: chronic kidney disease), CKD defined per the KDOQI/KDOGI Guidelines, defined as "the presence of kidney damage (ie, albuminuria) or decreased kidney function (ie, glomerular filtration rate [GFR] <60 mL/min per 1·73 m²) for 3 months or more"
Cardiovascular mortality [within 30 days postoperatively]
Cardiovascular mortality shall be defined as death attributed to a cardiovascular cause
Postoperative delirium on postoperative days 1-4 (perioperative neurological injury sub-study) [postoperative days 1-4]
Postoperative screening for delirium will be performed on postoperative days 1-4 using: Non-intubated patients: Confusion Assessment Method (CAM) Intubated patients: Confusion Assessment Method for the ICU (CAM-ICU)
Biomarkers of neurological injury (perioperative neurological injury sub-study) [postoperative days 0-2]
Serum biomarkers of neurological injury will be determined perioperatively. Due to the lack of standardized cut-offs defining normal and abnormal perioperative trajectories, no thresholds will be defined a priori in this study. Biomarkers of neuronal injury: Serum NSE Biomarkers of glial injury / blood brain barrier disruption: Serum S100B, GFAP, MMP-9 Biomarkers of axonal injury: Serum neurofilament light chain (NFL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (All patients):

undergoing major noncardiac surgery in general anesthesia will be included. Major noncardiac surgery is defined as:
vascular surgery (with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies)
intraperitoneal surgery
intrathoracic surgery
major orthopedic surgery
at cardiovascular risk, defined as meeting at least 1 of the following 6 criteria:
preoperative NT-proBNP ≥ 200 ng/l
history of coronary artery disease
history of peripheral vascular disease
history of stroke
undergoing major vascular surgery, with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies
fulfillment of any 3 of the 8 following criteria:
undergoing major surgery (intrathoracic, intraperitoneal or suprainguinal vascular surgery)
any history of CHF or history of pulmonary edema
anamnestic transient ischemic attack (TIA)
diabetes under treatment with either oral antidiabetic agent or insulin
age > 70 years
history of hypertension
serum creatinine > 175 mcmol/l or calculated creatinine clearance < 60 l/min/1.73m2 (Cockroft Gault)
history of smoking within 2 years of surgery
intraoperative continuous invasive blood pressure monitoring indicated due to anesthetic or surgical factors
planned surgical time ≥ 90 minutes
planned postoperative hospital stay at least 1 night

Additional inclusion criteria for neurologic injury sub-study:

Age ≥ 65 years

Exclusion Criteria (All patients):

pregnancy (anamnestic)
emergent surgery
urological surgery
renal insufficiency with creatinine clearance < 30 ml/min (Cockroft- Gault equation) or on dialysis
inclusion in an interventional clinical trial with any common endpoints: acute kidney injury, perioperative myocardial injury, components of MACE (ACS, CHF, coronary revascularization, stroke, new CKD or progression of CKD, mortality), neurological injury, delirium, exception: potential inclusion of subset of patients in RCT investigating the perioperative use of colchicine in major noncardiac surgery (COLCAT study).
previously enrolled in this study

Neurologic injury substudy:

Not fluent in German
Severe visual impairment precluding reading

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Basel, Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy	Basel		Switzerland	4031
2	Cantonal Hospital St. Gallen, Division of Anaesthesiology, Intensive Care, Rescue and Pain Medicine	St. Gallen		Switzerland	9007