PRECISION: Impact of Personalised Cardiac Anaesthesia and Cerebral Autoregulation on Neurological Outcomes in Patients Undergoing Cardiac Surgery

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05595954

Collaborator

(none)

500

Enrollment

Locations

35.3

Anticipated Duration (Months)

125

Patients Per Site

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This international, multicentre prospective cohort study will assess whether perioperative duration and magnitude of mean arterial pressure (MAP) outside of an individual's cerebral autoregulation (CA) limits using near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) are associated with adverse neurological events. It is to investigate whether patients with a higher burden of cerebral haemodynamic insults have an increased incidence or poorer neurological outcomes. Associations between neurologic outcomes, neurobiomarkers and genetic tests will be explored.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Delirium Postoperative Stroke Postoperative Cognitive Dysfunction	Other: Preoperative data collection Diagnostic Test: Intraoperative NIRS Diagnostic Test: Intraoperative TCD Diagnostic Test: Intraoperative invasive MAP Diagnostic Test: Postoperative NIRS Other: Postoperative data collection Diagnostic Test: Collection of serum biomarker panel Diagnostic Test: Collection of blood sample for genetic study

Detailed Description

Adverse neurological events include perioperative neurocognitive disorders and stroke and remain one of the major risks after cardiac surgery. A lack of a comprehensive knowledge of their causes and neuroprotective strategies has hindered the development of strategies to effectively reduce these complications. Against this background, this research project will take three approaches. First, non-invasive, personalised cerebral autoregulation-oriented blood pressure monitoring aims to reduce complications by uncovering blood pressure targets tailored to individual characteristics. In parallel, establishing biological associations between adverse neurological outcomes, brain injury biomarkers and genetic studies are complementary strategies that make a move to a proactive patient-tailored paradigm, ultimately understanding the mechanisms and improving patient outcomes, patient safety and quality of life.

Therefore, this international, multicentre prospective cohort study will assess whether perioperative duration and magnitude of MAP outside of an individual's CA limits using NIRS and TCD are associated with adverse neurological events. It is to investigate whether patients with a higher burden of cerebral haemodynamic insults, defined by the duration and magnitude spent outside of an individual's CA limits based on NIRS and/or TCD, have an increased incidence of postoperative delirium (POD), stroke or cognitive decline. Biological associations between adverse neurological outcomes, the role of brain injury serum biomarkers will be explored. Genetic studies will be conducted on participants who give written informed consent for these further investigations.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Impact of Personalised Cardiac Anaesthesia and Cerebral Autoregulation on Neurological Outcomes in Patients Undergoing Cardiac Surgery (PRECISION)

Actual Study Start Date :

Jan 23, 2023

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jan 1, 2026

Outcome Measures

Primary Outcome Measures

Change in 3D-CAM to assess postoperative delirium (POD) [Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)]
Change in 3D-CAM to assess POD. The 3D-CAM rates four diagnostic features, including acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. Delirium scored as 'present' (1) or 'absent' (0) based on question responses.
Change in Confusion Assessment Method for the ICU (CAM-ICU) to assess postoperative delirium (POD) [Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)]
CAM-ICU is an adaptation of the CAM to be usable by clinicians to screen for delirium in the intensive care unit setting designed for intubated patients. The CAM-ICU utilizes the CAM diagnostic algorithm. There are four core features including acute onset or fluctuating course, inattention, disorganized thinking, and altered level of consciousness rated with 8 items. 3 of the 4 features must be present for CAM-ICU to be considered positive, according to the original CAM algorithm. Items are rated absent/present base on specific thresholds.

Secondary Outcome Measures

Change in modified National Institutes of Health Stroke Scale (mNIHSS) [Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)]
Change in mNIHSS to assess postoperative clinical stroke
Change in Montreal Cognitive Assessment (MoCA) [Between 6 weeks and 12 weeks, and up to 12 months after surgery]
Change in MoCA to assess postoperative neurocognitive disorder
Postoperative increase in serum creatinine [Within 48 hours after surgery]
Postoperative increase in serum creatinine of ≥ 26.5 μmol/l (≥ 0.3 mg/dl) within 48 hours or ≥ 1.5 times of baseline to assess acute kidney injury
De novo renal replacement therapy [Within postoperative day 7 (or up to discharge)]
De novo renal replacement therapy
Major morbidity [Within postoperative day 7 (or up to discharge)]
Major morbidity as defined by the Society of Thoracic Surgeons as having at least one of the following adverse outcomes: stroke, surgical re-exploration for any cardiac reason (bleeding, coronary graft occlusion, valve dysfunction, and others), renal failure, deep sternal wound infection/mediastinitis, and prolonged ventilation (> 24 hours)
Intensive care unit (ICU) stay (in hours) [From day of surgery until discharge from ICU (approx. 1 day)]
Number of hours in ICU
Length of hospital stay (in days) [From day of surgery until discharge from hospital (approx. 7 days)]
Number of days in hospital
Perioperative mortality [Within within 30 days after surgery]
Perioperative mortality, defined as any in-hospital or postdischarge death within 30 days after surgery, regardless of cause, or any death occurring during the hospitalisation, even after 30 days
Change in brain injury biomarker panel [At preoperative screening; at day of surgery; at postoperative day 1, 2 and 7; between 6 weeks and 12 weeks after surgery]
The serum biomarker panel consists of four markers of neurological injury: glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total-tau and ubiquitin-C-terminal-hydrolase-L1 (UCH-L1).

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Elective primary or reoperative coronary artery bypass graft and/or valvular and/or ascending aorta surgery requiring cardiopulmonary bypass.

Exclusion Criteria:

Surgery requiring moderate or deep hypothermic circulatory arrest;
Heart and/or lung transplantation;
Urgent and emergency surgery;
Inability to follow procedures or insufficient knowledge in English or German;
Inability to give consent.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Herzzentrum Dresden GmbH Universitätsklinik, Institut für Kardioanästhesiologie	Dresden	Germany	01307
2	Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel	Basel	Switzerland	4031
3	Cambridge University Hospitals, Division of Anaesthesia and Brain Physics Lab	Cambridge	United Kingdom	CB2 0QQ
4	Royal Papworth Hospital, Department of Anaesthesia and Intensive Care	Cambridge	United Kingdom	CB2 0QQ

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

Principal Investigator: Nuno V. Gomes, MD, Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel