Impact of Nociception Level (NOL)-Guided Remifentanil Infusion on Intraoperative Arterial Pressure and Vasopressor Necessity

Study Overview
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Brief Summary
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The aim of this study is to determine if Nociception Level (NOL)-guided Remifentanil analgesia, combined with Entropy-guided Propofol anesthesia, has a significant beneficial effect on the incidence of intraoperative hypotension episodes and/or on vasopressor requirements, during long-lasting major surgeries for high risk patients. The investigator will also investigate the effects of guided anesthesia on postoperative Myocardial Injury in Non-cardiac Surgery (MINS) and Postoperative cognitive dysfunction (POCD), amongst other frequent postoperative complications, in this population.

Official Title
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Impact of Nociception Level (NOL)-Guided Remifentanil Infusion and Entropy-guided Propofol Infusion on Intraoperative Arterial Pressure and Vasopressor Necessity A Prospective, Randomized, Controlled Trial.

Conditions
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Head and Neck Surgery, Maxillofacial Surgery

Intervention / Treatment
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* Other: Entropy and NOL-Guided Goal Directed Anesthesia
* Other: Standard of Care Group (Entropy and blinded NOL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 Elective high-risk head and neck or maxillo-facial surgery Exclusion Criteria: Patient refusal Reduced ejection fraction below 40% and heart failure History of atrial Fibrillation, pulmonary embolism, recent cardioversion, recent cardiac ischemic episode, chronic hypotension, chronic kidney insufficiency (serum creatinine > 1.5) Septic state Baseline heart-rate < 50 or > 90 bpm History of psychiatric disease or 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entropy and NOL-Guided Goal Directed Anesthesia<br> | Other: Entropy and NOL-Guided Goal Directed Anesthesia<br>* Entropy-guided Anesthesia (Propofol infusion in order to maintain Entropy between 45 and 55) and NOL-guided Analgesia (Remifentanil infusion in order to maintain NOL-Index between 10 and 25).<br>|
| Active Comparator: Standard of Care Group (Entropy and blinded NOL)<br> | Other: Standard of Care Group (Entropy and blinded NOL)<br>* Entropy-guided Anesthesia (Propofol infusion in order to obtain Entropy between 45 and 55) and Remifentanil infusion at the discretion of the anesthetist in charge, based on current practice: patient vitals (Heart Rate, Blood Pressure, Respiratory Rate…), movements, spontaneous breathing, experience.... In this group, nociception monitor screen will be concealed and the NOL index will not be available for guidance of remifentanil dosing).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of intraoperative hypotension | Occurrence of intraoperative hypotension is defined by at least 1 minute under the hypotension thresholds. Moderate and Severe Hypotension are respectively defined as a Mean Blood Pressure <65 mmHg or <55 mmHg and <75 or <65 mmHg for patient with history of chronic hypertension | during surgery | 
| Total Vasopressor Dose | Total Vasopressor Dose used throughout the intervention to maintain Arterial Pressure within a pre-defined individualized ranges (≥ 65 mmHg or ≥75 mmHg for patient with history of chronic hypertension, and ≤ 100 mmHg) | during surgery | 
| Number of interventions to cure intraoperative hypotension | Number of vasopressor boli or vasopressor infusion dose adjustments | during surgery | 
| Total Time under hypotension thresholds | Hypotension Thresholds ( <65 mmHg or < 75mmHg for patient with history of chronic hypertension) | during surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Injury in Non-Cardiac Surgery (MINS) marker (Troponin T) | Troponin T level measured before surgery, at end of surgery, 4 hours, 8 hours, 24 hours, 36 hours and 48 hours after surgery. The threshold is a postoperative concentration ≥ 20 ng/L with an increase from baseline of at least 5 ng/L, or a postoperative concentration ≥ 65 ng/L. | up to 48 hours after surgery | 
| Postoperative Acute Kidney Injury (AKI) marker (creatinin/Glomerular Filtration Rate) | Creatinin level measured before surgery, at end of surgery, 24 hours and 48 hours after surgery. The thresholds are defined by the Kidney Disease: Improving Global Outcomes (KDIGO) classification without the oliguria criteria. | up to 48 hours after surgery | 
| Postoperative Cognitive Decline (POCD) | POCD will be evaluated by cognitive dysfunction battery tests (written Montreal Cognitive Assessment (MOCA) Test) at days 5,10, 15, hospital discharge, 3 and 6 postoperative months | up to 6 months after surgery | 
| PostOperative Delirium (PO Delirium) | PO Delirium will be evaluated by the Confusion Assessment Method (CAM) at days 5, 10, 15, hospital discharge, 3 and 6 postoperative months | up to 6 months after surgery | 
| Dosage of Stress Hormones | Adrenocorticotropic Hormone (ACTH) and Cortisol will be measured in blood samples at the end of surgery, at the arrival in the ICU and at 4 hours after surgery. | up to 4 hours after surgery | 
| Dosage of Neuro-Inflammatory Markers | Interleukine-6 and Interleukine-8 will be measured in blood and saliva samples before surgery and during the postoperative period (4 hours, 24 hours and 48 hours after surgery). | up to 48 hours after surgery | 
| Olfactory Function assessment as an indicator of Neuro-Inflammation | A rapid quantitative olfactory function test, the University of Pennsylvania Smell Identification -Test (UPSIT-Test) will be performed before surgery and during the postoperative period (4 hours, 24 hours and 48 hours after surgery). | up to 48 hours after surgery | 
| Length of Intensive Unit Care (IUC) stay |  | up to 10 Days after surgery | 
| Length of hospital stay |  | up to 15 Days after surgery | 
| Adverse Event (blood loss, infection) |  | up to 15 Days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nociception, Entropy, Analgesia, Goal Directed Anesthesia Therapy (GDAT), Remifentanil, Intraoperative Hypotension, Myocardial Injury in Non-Cardiac Surgery (MINS), Postoperative Cognitive Dysfunction (POCD)