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

Phase 3

Completed

• Conditions: Heart; Surgery, Heart, Functional Disturbance as Result; Opioid Use; Anesthesia
• Interventions: Drug: Opioid Anesthetics; Drug: Non Opioid Analgesics

• Registration Number: NCT04197570
• Lead Sponsor: Benaroya Research Institute

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-12-11
• Study First Submitted QC: 2019-12-11
• Study First Posted: 2019-12-13
• Study Start: 2020-02-04
• Primary Completion: 2020-03-14
• Study Completion: 2020-03-14
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-24
• Last Update Posted: 2020-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Opioid-based anesthetic	Opioid Anesthetics	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
Opioid-free anesthetic	Non Opioid Analgesics	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

Primary Outcome Measures

Name	Time	Method
Mean arterial blood pressure-time integral	10 minutes	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.

Secondary Outcome Measures

Name	Time	Method
Blood pressure variability pre-cardiopulmonary bypass	2 hours	highest and lowest blood pressure from induction to start of bypass
Heart rate variability pre-cardiopulmonary bypass	2 hours	highest and lowest heart rate from induction to start of bypass
Vasopressor usage intra- and post-operatively	18 hours	Number of vasopressors and doses from induction to start of cardiopulmonary bypass, leaving operating room and 12 hours postop
Arrhythmias or EKG changes	14 days	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.
Delirium medications	24 hours	Delirium medications administered 24 hours after ICU admission
Delirium	24 hours	CAM-ICU scores at 12 hours and 24 hours after ICU admission
Postoperative pain scores	24 hours	Numerical Rating Scale Pain Scores (Range: 0-10, where 0 is no pain and 10 is the worst pain)
Opioid consumption	24 hours	Total opioid utilization 24hours postoperatively (morphine equivalent dose)
Postoperative nausea/vomiting	24 hours	Number of antiemetic doses administered
Time to extubation	1-36 hours	Time from arrival in ICU to extubation
ICU length of stay	1-5 days	Time from arrival in ICU to time of transfer order out of ICU
Hospital length of stay	3-14 days	Time begins day of surgery to day of discharge. Time in days
Reintubation or readmission to ICU	0-14 days	After being extubated or being transferred out of ICU
major adverse cardiovascular event or mortality	30 days	Major adverse cardiovascular event (eg., myocardial ischemia, stroke) or death
Postoperative pain questionnaire	6 months	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)

Trial Locations

Locations (1)

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States