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

Intraoperative Arterial Hypotension Clinical Trial

— AR-NONCARDIAC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05336864
• Other study ID #: 2022-00298; am22Wanner
• Status: Recruiting
• Start date: May 20, 2022
• Est. completion date: June 2025

Study information

• Verified date: September 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Patrick M Wanner, Dr. med.
• Phone: +41 61 328 72 54
• Email: patrick.wanner[@]usb.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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 both short- and long-term major adverse cardiovascular events (MACE) will be investigated.

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 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 and postoperative hemodynamics, in which select patients will be enrolled.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypotension
• Intraoperative Arterial Hypotension

Intervention

Other:
• Non-invasive cerebral oximetry monitoring
Main study (all patients): Continuous bilateral frontal cerebral near-infrared spectroscopy (NIRS) monitoring will be performed in all patients for the duration of general anesthesia. Intraoperative parameters including NIRS and invasive blood pressure will be collected and recorded in real-time using the software ICM+. Postoperative hemodynamics substudy (facultative): Cerebral NIRS monitoring will be continued postoperatively in a subset of patients being admitted to the ICU.
• additional perioperative blood sampling
Main study (all patients): Creatinine, high-sensitivity troponin (T hs-cTnT), Growth/Differentiation Factor-15 (GDF-15), Hemoglobin Neurological injury substudy (facultative): Neurofilament Light Chain (NFL)
• clinical & telephone assessments
Main study (all patients): Telephone follow-up (1-year MACE).
• Non-invasive somatic oximetry monitoring
Tissue perfusion substudy (facultative): Continuous somatic NIRS monitoring of an extremity (i.e. on skin of leg or arm) will be performed intraoperatively and postoperatively in a subset of patients being admitted postoperatively to the ICU.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy	Basel
Switzerland	Cantonal Hospital St. Gallen, Division of Anaesthesiology, Intensive Care, Rescue and Pain Medicine	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perioperative organ injury (by composite measurement of perioperative myocardial injury and perioperative acute kidney injury):	a composite of 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 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	Long-term cardiovascular outcomes, a composite of the following outcomes (main study):	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	within 1 year postoperatively
Secondary	Neurological injury (neurological injury sub-study)	Perioperative trajectory of serum neurofilament light chain (NFL)	postoperative day 2