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

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

The aim of study is to investigate the clinical relevance of blood pressure (BP) excursions below cerebral autoregulatory boundaries in major noncardiac surgery. The study seeks to establish a precedent for a personalized definition of intraoperative arterial hypotension based on non-invasive tissue oxygenation measurements. The feasibility of NIRS-based autoregulation monitoring in major noncardiac surgery and the prognostic relevance of BP excursions below the NIRS-derived lower limit of autoregulation (LLA) with regard to major cardiovascular, renal and neurological complications will be investigated.

Study Overview

• Status: Active, not recruiting
• Conditions: Intraoperative Arterial Hypotension
• Intervention / Treatment: Other: Non-invasive cerebral oximetry monitoring; Other: Non-invasive somatic oximetry monitoring; Other: additional perioperative blood sampling; Other: clinical & telephone assessments; Other: Processed electroencephalogram (pEEG) monitoring

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 aims to investigate the clinical relevance of blood pressure excursions below autoregulatory boundaries and to determine the association of other measures of disturbed intraoperative cerebral autoregulatory function in major noncardiac surgery.

This project will consist of a Main study in which all patients will be enrolled and of substudies on perioperative neurologic injury, tissue perfusion, postoperative hemodynamics, and processed electroencephalogram (EEG), in which selected patients will be enrolled.

• Study Type: Observational
• Enrollment (Actual): 650

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel, Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy
  • Bern, Switzerland, 3010
    • Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine
  • Sankt Gallen, Switzerland, 9007
    • Cantonal Hospital St. Gallen, Division of Perioperative Intensive Care Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients will be screened for eligibility during the preoperative anesthetic visit based on the inclusion/exclusion criteria and the previous medical history using a standardized checklist, helping to minimize bias.

Description

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 the composite major cardiovascular, renal and neurological complications up to 1 year following surgery (ACS, CHF, coronary revascularization, stroke, new CKD or progression of CKD, new need for renal replacement therapy, 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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative organ injury on postoperative days 1-3, a composite of:	o 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) and/or o 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%)	postoperative days 1-3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological injury (neurological injury sub-study)	Perioperative trajectory of serum neurofilament light chain (NFL)	postoperative day 2
Major cardiovascular, renal and neurological complications up to 1 year following surgery, a composite of any of the following:	acute coronary syndrome; acute congestive heart failure (CHF); coronary revascularization; stroke; new or progressive chronic kidney disease (CKD); new need for renal replacement therapy (RRT); all-cause mortality; cardiovascular mortality	up to 1 year following surgery

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Patrick M Wanner, Dr. med., Clinic for Anaesthesia, University Hospital Basel

Publications and helpful links

General Publications

• Wanner PM, Schindler C, Beqiri E, Smielewski P, Hogue CW, Brown CH 4th, Jeon Y, Puelacher C, Murgatroyd Wiles AJ, Yurttas T, Burgi J, Seeberger E, Doyle N, Klein C, Korte W, Pietsch U, Vogt AP, Filipovic M, Steiner LA. Clinical implications and feasibility of cerebral autoregulation-based precision blood pressure monitoring in major noncardiac surgery: A protocol for AUTOREGULATE-NONCARDIAC, a multicentre prospective cohort study and peri-operative precision medicine platform. Eur J Anaesthesiol Intensive Care. 2025 Dec 5;5(1):e0093. doi: 10.1097/EA9.0000000000000093. eCollection 2026 Feb.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Actual): January 29, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: cerebral autoregulation; C-reactive protein (CRP); hypotension; perioperative myocardial injury; neurological injury; near-infrared spectroscopy (NIRS); perioperative acute kidney injury; Neurofilament Light Chain (NFL); major cardiovascular, renal and neurological complications
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Hypotension; Trauma, Nervous System; Charcot-Marie-Tooth disease, Type 1F
• Other Study ID Numbers: 2022-00298; am22Wanner

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No