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

Postoperative Delirium Clinical Trial

— PRECISION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05595954
• Other study ID #: 2022-01457; am22Gomes
• Status: Recruiting
• Start date: January 23, 2023
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Nuno V. Gomes, MD
• Phone: +41 61 328 64 46
• Email: nuno.gomes[@]usb.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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 (< 24 hours) and emergency surgery;
• Inability to follow procedures or insufficient knowledge in English, German or French;
• Inability to give consent. Participants from the University Hospital Basel who undergo cardiac surgery under minimal extracorporeal circulation will also be excluded.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• Emergence Delirium
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Delirium

Intervention

Other:
• Preoperative data collection
Preoperatively, patients will be assessed with Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Frailty Scale, 3-minute Diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM, incl. severity score), modified National Institutes of Health Stroke Scale (mNIHSS), and hand grip strength measurement (using a hand dynamometer) to establish a baseline measurement of the physical, cognitive and mental status.

Diagnostic Test:
• Intraoperative NIRS
Intraoperatively, NIRS data will be collected and recorded in real-time.
• Intraoperative TCD
Intraoperatively, TCD data will be collected and recorded in real-time.
• Intraoperative invasive MAP
Intraoperatively, invasive arterial blood pressure data will be collected and recorded in real-time.
• Postoperative NIRS
Postoperatively, NIRS monitoring will be continued in the ICU after the surgery until (i) endotracheal extubation, or (ii) for the first 24 hours or (iii) until emergency re-operation, whichever occurs first.

Other:
• Postoperative data collection
Postoperatively patients will be evaluated for POD with 3D-CAM or CAM-ICU and for clinical stroke with mNIHSS. Postoperative neurocognitive disorders will be assessed using MoCA.

Diagnostic Test:
• Collection of serum biomarker panel
The serum biomarker panel will consist of four markers of neurological injury glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), t-tau and ubiquitin-C-terminal-hydrolase-L1 (UCH-L1). Blood samples will be obtained preoperatively, after ICU admission, on postoperative day 1, 2, 6 (or hospital discharge, whichever occurs first) and between 6 and 12 weeks after surgery.
• Collection of blood sample for genetic study
A blood sample for the genetic study will be obtained preoperatively.

Locations

Country	Name	City	State
Germany	Herzzentrum Dresden GmbH Universitätsklinik, Institut für Kardioanästhesiologie	Dresden
Switzerland	Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel	Basel
Switzerland	Inselspital, Bern University Hospital	Bern
United Kingdom	Cambridge University Hospitals, Division of Anaesthesia and Brain Physics Lab	Cambridge
United Kingdom	Royal Papworth Hospital, Department of Anaesthesia and Intensive Care	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Countries where clinical trial is conducted

Germany,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 3D-CAM to assess postoperative delirium (POD)	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.	Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)
Primary	Change in Confusion Assessment Method for the ICU (CAM-ICU) to assess postoperative delirium (POD)	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.	Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)
Secondary	Change in modified National Institutes of Health Stroke Scale (mNIHSS)	Change in mNIHSS to assess postoperative clinical stroke	Assessed daily on postoperative days 0 to 7 (or up to discharge, whichever occurs earlier)
Secondary	Change in Montreal Cognitive Assessment (MoCA)	Change in MoCA to assess postoperative neurocognitive disorder	Between 6 weeks and 12 weeks, and up to 12 months after surgery
Secondary	Postoperative increase in serum creatinine	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	Within 48 hours after surgery
Secondary	De novo renal replacement therapy	De novo renal replacement therapy	Within postoperative day 7 (or up to discharge)
Secondary	Major morbidity	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)	Within postoperative day 7 (or up to discharge)
Secondary	Intensive care unit (ICU) stay (in hours)	Number of hours in ICU	From day of surgery until discharge from ICU (approx. 1 day)
Secondary	Length of hospital stay (in days)	Number of days in hospital	From day of surgery until discharge from hospital (approx. 7 days)
Secondary	Perioperative mortality	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	Within within 30 days after surgery
Secondary	Change in brain injury biomarker panel	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).	At preoperative screening; at day of surgery; at postoperative day 1, 2 and 7; between 6 weeks and 12 weeks after surgery