Nol-Index Guided Remifentanil Analgesia Versus Standard Analgesia During Moderate-to-High Risk Cardiovascular Surgery

Study Overview
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Brief Summary
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This study will investigate the potential of guiding remifentanil analgesia during cardiac and vascular surgery in moderate to high risk patients requiring general anesthesia.

Detailed Description
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Justification: Moderate-to-high risk cardiovascular surgery is associated with perioperative morbidity and mortality. These patients undergo general anesthesia and often require tight blood pressure control (e.g., using norepinephrine titration) to avoid the complications associated with hypotension and reduced cardiac output. Standard analgesia opioid titration to control nociception (i.e., the patient's unconscious response to noxious stimuli) is based on the anesthesiologist's experience and variations in the patient's heart rate and blood pressure. This causes anesthesiologists to often give too much analgesic, which can lead to inhibition of the sympathetic autonomic nervous system, hypotension, and associated side effects. A recently developed nociception monitor, the PMD-200 (Medasense, Israel), is capable of measuring the patient's level of nociception-antinociception balance and can guide opioid administration. This monitor may allow anesthesiologists to administer only the required amount of opioid, which may lead to better hemodynamic stability and better postoperative outcome. Objectives: The goal of this study is to determine if titrating analgesia using the Nol-Index, when compared to standard care, leads to decreased infused remifentanil, decreased norepinephrine, increased cardiac output, more stable blood pressure control, and decreased postoperative complications in moderate-to-high risk patients undergoing cardiac or vascular surgery.

Official Title
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Nol-Index Guided Remifentanil Analgesia Versus Standard Analgesia During Moderate-to-High Risk Cardiovascular Surgery: a Randomized Controlled Trial

Conditions
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Nociceptive Pain, Goal-directed Therapy, Hemodynamic Instability, Nol-Index, Remifentanil, Cardiac Surgery, Vascular Surgery, General Anesthesia

Intervention / Treatment
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* Device: Nol-Index guided analgesia
* Other: Standard Analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: moderate-to-high risk cardiac or vascular surgery ASA 2-4 Exclusion Criteria: chronic arrhythmia (e.g. atrial fibrillation) aortic insufficiency pacemaker implanted defibrillator valve surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nol-Guided Analgesia Group<br>In the Nol-Guided Analgesia Group remifentanil effect site concentration will be adapted to maintain the NOL-index between 10 and 25 throughout the anesthetic. | Device: Nol-Index guided analgesia<br>* Monitor that indicates the level of nociception-antinociception balance<br>|
| Active Comparator: Standard Analgesia Group<br>Remifentanil titration in the Standard Analgesia Group will be left at the anesthesiologists discretion (i.e., guided by heart rate, blood pressure, and experience). | Other: Standard Analgesia<br>* Administration of remifentanil based guided by heart rate, blood pressure, and experience<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remifentanil requirement | µg/kg/hour required during general anesthesia | 2 to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Norepinephrine requirement | µg/kg/hour required during general anesthesia | 2 to 8 hours | 
| propofol requirement | mg/kg/hour required during general anesthesia | 2 to 8 hours | 
| nicardipine requirement | mg/kg/hour required during general anesthesia | 2 to 8 hours | 
| esmolol requirement | mg/kg/hour required during general anesthesia | 2 to 8 hours | 
| Intraoperative hemodynamic instability | Occurence of hypotension, hypertension, bradycardia or tachycardia | 2 to 8 hours | 
| Number of patients with 28 day composite and individual adverse outcomes | renal failure, cardiac ischemia, ileus, stroke, new onset arrhythmia, etc | 28 days | 
| Heart Rate | Heart rate during anesthesia | 2 to 8 hours | 
| Systolic Blood Pressure | systolic blood pressure during anesthesia | 2 to 8 hours | 
| Diastolic Blood Pressure | diastolic blood pressure during anesthesia | 2 to 8 hours | 
| Mean Blood Pressure | mean blood pressure during anesthesia | 2 to 8 hours | 
| Cardiac Output | cardiac output during anesthesia | 2 to 8 hours |