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

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Opioid Use; Heart; Surgery, Heart, Functional Disturbance as Result
• Intervention / Treatment: Drug: Opioid Anesthetics; Drug: Non Opioid Analgesics

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Opioid-based anesthetic; 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; see arm/group description; Other Names: Opioid-based anesthetic
EXPERIMENTAL: Opioid-free anesthetic; 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; see arm/group description; Other Names: Opioid-free anesthetic

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Benaroya Research Institute
• Collaborators: Virginia Mason Hospital/Medical Center
• Investigators: Principal Investigator: Sarah Bain, Virginia Mason Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 4, 2020
• Primary Completion (ACTUAL): March 14, 2020
• Study Completion (ACTUAL): March 14, 2020

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 11, 2019
• First Posted (ACTUAL): December 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Hemodynamic; Opioid; Cardiac Surgery; Fentanyl; Dexmedetomidine; Cardiopulmonary Bypass; Opioid Free Anesthesia; Non-opioid Anesthesia; Cardiac Anesthesia; post sternotomy pain
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Narcotics; Anesthetics; Analgesics, Opioid; Analgesics; Analgesics, Non-Narcotic
• Other Study ID Numbers: IRB19-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No