Opioid-free Anesthesia for Open Cardiac Surgery: A Prospective Randomized Controlled Trial

Study Overview
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Brief Summary
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This study will compare an opioid free anesthetic, using dexmedetomidine, to a traditional opioid based anesthetic, using fentanyl, for patients undergoing cardiac surgery with regards to hemodynamic stability in the first 10 minutes after induction.

Detailed Description
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This is a single center, blinded, prospective, randomized controlled trial. A total of 158 subjects (79 subjects in each arm) are planned. The control group will receive a traditional cardiac anesthetic using opioids, for which induction will include fentanyl and propofol. The experimental arm will receive an opioid free anesthetic with an induction bolus of dexmedetomidine and propofol. The investigators hypothesize that using the opioid free technique will be more hemodynamically stable within the first 10 minutes of induction.

Official Title
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Opioid-free Anesthesia for Open Cardiac Surgery: A Prospective Randomized Controlled Trial

Conditions
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Opioid Use, Heart; Surgery, Heart, Functional Disturbance as Result, Anesthesia

Intervention / Treatment
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* Drug: Opioid Anesthetics
* Drug: Non Opioid Analgesics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age at the time of consent. Undergoing non-emergent open cardiac procedures requiring cardiopulmonary bypass support, including: CABG, aortic aneurysm repair, valve repair/replacement, or CABG in combination with valve repair/replacement. Ability and willingness to provide written informed consent. Exclusion Criteria: Chronic opioid use defined as preoperative MED >100 daily. Hypersensitivity or contraindication to any of the study medications. Pre-existing Alzheimer's/vascular dementia. Pre-existing psychiatric disorder precluding ability to provide informed consent or use a visual analogue scale for pain. Childs-Pugh Class C liver failure or acute liver failure. Emergent open heart surgery, including type A aortic dissections, trauma, or conversion (bail out) from another procedure such as cardiac catheterization, ablation, transcatheter aortic valve replacement or any other general surgical procedure. Pregnancy or lactating. Inability to comply with the requirements of the study, per investigator judgment. Patients determined to need an awake intubation.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The investigators plan to enroll 158 subjects at Virginia Mason Medical Center that are undergoing open cardiac surgery. Subjects who volunteer to be involved in the study will be randomized to either the opioid free or traditional anesthetic arm. Subjects will be blinded to the assigned arm.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Opioid-based anesthetic<br>Premedication -midazolam 2mg IV x 1 as need for anxiety, at the discretion of the anesthesiologist Induction Fentanyl 2-4 mcg/kg IV bolus Propofol 1-3 mg/kg IV Paralytic and vasoactive medications at the discretion of the anesthesiologist Maintenance Fentanyl 1-2 mcg/kg IV bolus immediately prior to sternotomy & aortic cannulation Fentanyl 1-2mcg/kg IV bolus immediately following removal of bypass cannula Dexmedetomidine 0.4 mcg/kg/hr IV infusion Isoflurane titrated at the discretion of the anesthesiologist Vasoactive medications at the discretion of the anesthesiologist for hemodynamic management During chest closure: start Propofol 25-75mcg/kg/min IV infusion continue dexmedetomidine 0.4mcg/kg/hr IV infusion titrate off isoflurane Acetaminophen 1000mg IV | Drug: Opioid Anesthetics<br>* see arm/group description<br>* Other names: Opioid-based anesthetic;|
| Experimental: Opioid-free anesthetic<br>Premedication -midazolam 2mg IVx1 as needed for anxiety, at the discretion of the anesthesiologist Induction Dexmedetomidine 1mcg/kg IV Propofol 1-3mg/kg IV Paralytic and vasoactive medications at the discretion of the anesthesiologist Maintenance Dexmedetomidine 0.8-1.0 mcg/kg/hr IV infusion Isoflurane titrated at the discretion of the anesthesiologist May add propofol infusion if clinically indicated Vasoactive medications at the discretion of the anesthesiologist for hemodynamic management During chest closure: start Propofol 25-75mcg/kg/min IV infusion continue dexmedetomidine 0.4 - 1.0 mcg/kg/hr IV infusion titrate off isoflurane Acetaminophen 1000mg IV | Drug: Non Opioid Analgesics<br>* see arm/group description<br>* Other names: Opioid-free anesthetic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean arterial blood pressure-time integral | The primary endpoint is the area under the baseline mean arterial pressure (MAP) over the first 10 minutes after induction, called the MAP-time integral. | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure variability pre-cardiopulmonary bypass | highest and lowest blood pressure from induction to start of bypass | 2 hours | 
| Heart rate variability pre-cardiopulmonary bypass | highest and lowest heart rate from induction to start of bypass | 2 hours | 
| Vasopressor usage intra- and post-operatively | Number of vasopressors and doses from induction to start of cardiopulmonary bypass, leaving operating room and 12 hours postop | 18 hours | 
| Arrhythmias or EKG changes | Intraoperative EKG changes or evidence of echocardiographic ischemia prior to heparin. Antiarrhythmic medications given intraoperative or in first 24 hours postop. New permanent pacemaker placed during hospital admission. | 14 days | 
| Delirium medications | Delirium medications administered 24 hours after ICU admission | 24 hours | 
| Delirium | CAM-ICU scores at 12 hours and 24 hours after ICU admission | 24 hours | 
| Postoperative pain scores | Numerical Rating Scale Pain Scores (Range: 0-10, where 0 is no pain and 10 is the worst pain) | 24 hours | 
| Opioid consumption | Total opioid utilization 24hours postoperatively (morphine equivalent dose) | 24 hours | 
| Postoperative nausea/vomiting | Number of antiemetic doses administered | 24 hours | 
| Time to extubation | Time from arrival in ICU to extubation | 1-36 hours | 
| ICU length of stay | Time from arrival in ICU to time of transfer order out of ICU | 1-5 days | 
| Hospital length of stay | Time begins day of surgery to day of discharge. Time in days | 3-14 days | 
| Reintubation or readmission to ICU | After being extubated or being transferred out of ICU | 0-14 days | 
| major adverse cardiovascular event or mortality | Major adverse cardiovascular event (eg., myocardial ischemia, stroke) or death | 30 days | 
| Postoperative pain questionnaire | 30 day, 3 month and 6 month pain questionnaire as well as post-sternotomy opioid use (as determined by reviewing Washington PMP data). Numerical Rating Scale Pain Scores (Range: 0-10, where 0 is no pain and 10 is the worst pain) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiopulmonary Bypass, post sternotomy pain, Opioid Free Anesthesia, Cardiac Surgery, Non-opioid Anesthesia, Dexmedetomidine, Hemodynamic, Opioid, Fentanyl, Cardiac Anesthesia