BRAIN-targeted Goal-directed Therapy in High-risk Patients undeRgOing Major electIve SurgEry: the BRAIN-PROMISE Study

Study Overview
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Brief Summary
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The aim of the study is to further understand whether the use of non-invasive monitoring NIRS (Near Infrared Spectroscopy) is useful in reducing postoperative complications in high-risk patients undergoing elective surgery.

Detailed Description
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Background: Perioperative complications lead to impaired quality of life as well as prolonged disability. In high risk patients, early hemodynamic optimization with the goal of achieving and maintaining tissue oxygenation in the perioperative period has resulted in an improvement of outcomes and a reduction in surgery-related complications. Maintenance of adequate oxygen delivery to tissue, is one of the fundamental aspects of anesthesia. Regional Oxygen Saturation of the brain tissue (rSO2) as measured by near-infrared spectroscopy (NIRS) is a promising tool in vascular surgery and cardiac surgery for the monitoring of global cerebral perfusion. Objectives: This study has the purpose to assess whether an rSO2-based hemodynamic optimization algorithm is able to reduce overall perioperative complications in high risk patients. Design: BRAIN-PROMISE is a monocentric, randomized controlled trial. Population: Hypertensive elderly or frail patients undergoing major surgery. Experimental Intervention: Cases will be managed using a NIRS-targeted goal directed therapy. Control Intervention: Controls will be managed according to standard care. Outcomes: The primary outcome are the incidence of perioperative complications at 30 days and the percentage of successful reversal of reduction in NIRS. Trial size: A total of 200 patients will be randomized.

Official Title
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BRAIN-targeted Goal-directed Therapy in High-risk Patients undeRgOing Major electIve SurgEry: the BRAIN-PROMISE Study

Conditions
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Surgery, Perioperative Complication

Intervention / Treatment
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* Device: Near Infrared Spectroscopy (NIRS)
* Device: Standard Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hypertensive patients with American Society of Anesthesiologists (ASA) score≥ 3 with either Age ≥ 80 years or frailty score ≥5 presence of an arterial catheter during anesthesia planned high-risk surgery (abdominal, vascular, urologic, thoracic one-lung ventilation (OLV) procedures), longer than 2 hours, in general anesthesia ability to give informed consent according to International Conference on Harmonization ICH/ Good Clinical Practice (GCP), and national/local regulations Exclusion Criteria: Age < 80 years Unable to consent to study inclusion Language barrier Severe neurological or psychiatric disease End-stage dementia Total Intravenous anesthesia Trendelenburg positioning No hypertensive medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Near Infrared Spectroscopy (NIRS)<br> | Device: Near Infrared Spectroscopy (NIRS)<br>* The anesthesiologist will apply optodes before induction of anesthesia and before preoxygenation, to detect baseline NIRS level, NIRS will be monitored continuously up to post-anaesthesia care unit (PACU) discharge, or up to three the investigator's after ICU admission. When a decrease in NIRS value over 10% is detected, or if NIRS value is below 60%, patients will start hemodynamic optimization, to reverse the reduction in NIRS and return to baseline values, according to a predefined protocol.<br>|
| Active Comparator: Standard Care<br> | Device: Standard Care<br>* Controls will be treated according to standard of care, maintaining a MAP≥65 and an adequate cardiac output according to the hemodynamic monitoring chosen by the anesthesiologist (invasive blood pressure monitoring or pulse contour monitors). NIRS will be recorded also in controls, but caring anesthesiologists will be blinded to NIRS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall incidence of perioperative complications (including postoperative cognitive dysfunction and delirium). |  | 30 day after randomization | 
| Percentage of successful reversal of reduction in NIRS, according to the hemodynamic optimization protocol. |  | intraoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NIRS variations over time, and according to interventions |  | intraoperative | 
| Percentage of time with NIRS within safety limits (<10% reduction) |  | intraoperative | 
| Bispectral index (BIS) over time |  | intraoperative | 
| Mean arterial pressure (MAP) over time |  | intraoperative | 
| sevorane concentration over time |  | intraoperative | 
| Use of vasopressors and fluids to maintain MAP |  | intraoperative | 
| Evaluate fluid administration |  | intraoperative |