Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: RCT

August 29, 2023 updated by: Hossam El-Ashmawi, Cairo University

Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: A Randomized Controlled Trial

Several studies demonstrated the effectiveness of OFA in patients undergoing non-cardiac surgery. Preoperative use of Cox inhibitors, GABA analogues and acetaminophen have been shown to decrease use of opioids postoperatively . Intraoperative use of agents that lead to opioid sparing effects via sodium channel blockade, blockade of G protein-coupled receptors, NMDA blockade, central alpha-2 agonists and anti-inflammatory effects can make opioid-free anesthesia (OFA) possible. On the other hand, there have been no studies demonstrating the effectiveness of an OFA technique in patients undergoing cardiac surgery except for two case reports who successfully implemented the OFA regimen in two patients undergoing valve replacement surgeries. The investigators therefore propose this prospective randomized controlled trial to investigate whether a multimodal opioid-free anesthesia regimen will be suitable as an alternative to conventional opioid-based regimen in patients undergoing valve surgery

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

High-dose opioid anesthesia during cardiac surgery has been the mainstay of cardiac anesthesia for decades due to its ability to preserve hemodynamic stability and attenuate hormonal and metabolic response to surgical stress (1) . However, large doses of long-acting opioids required patients to be ventilated post-operatively for 12-24 h. Modifications in these practices have been dictated by the increasing cost, complications of prolonged mechanical ventilation, and the changes in demographics of patients presenting for cardiac surgery (2) . Moreover, the intraoperative use of large bolus doses or continuous infusions of potent opioids may be associated with postoperative hyperalgesia and tolerance (3). When it comes to ambulatory surgery, opioid related side effects, such as postoperative nausea and vomiting (PONV), prolonged sedation, ileus and urinary retention may delay recovery and discharge or cause unanticipated hospital readmission (4) . Such complications might, at least in part, also apply to cardiac anesthesia.

Recent evidence suggests that increased total dose of opioids during cardiac surgery may lead to increased in-hospital, as well as long-term post-operative pain medication requirements for up to one year (5). Moreover, according to Hirji et al study , ongoing opioid use three months after CABG was present in 21.7% of opioid-exposed patients versus 3.2% of opioid-naive patients (6). In addition, Opioids have many known side effects such as somnolence, brainstem and respiratory depression , and chronic opioid dependence (7-9), and there is a national trend to decrease opioid use during non-cardiac surgery to promote faster recovery and decrease narcotic use post-operatively (1) .

Several studies demonstrated the effectiveness of Opioid-free Anesthesia (OFA) in patients undergoing non-cardiac surgery(4,10,11). Preoperative use of COX inhibitors, GABA analogues and acetaminophen have been shown to decrease use of opioids postoperatively(10). Intraoperative use of agents that lead to opioid sparing effects via sodium channel blockade, blockade of G protein-coupled receptors, NMDA blockade, central alpha-2 agonists and anti-inflammatory effects can make opioid-free anesthesia (OFA) possible (12,13). On the other hand, there have been no studies demonstrating the effectiveness of an OFA technique in patients undergoing cardiac surgery except for two case reports who successfully implemented the OFA regimen in two patients undergoing valve replacement surgeries (14,15). The investigators therefore propose this prospective randomized controlled trial to investigate whether a multimodal opioid-free anesthesia regimen will be suitable as an alternative to conventional opioid-based regimen in patients undergoing valve surgery.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Cairo, Egypt
        • Kasr Al Ainy School of Medicine Cairo University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Patients undergoing cardiac valve surgeries ( replacement or repair ) .
  2. Age (18-80) years
  3. Both sexes

Exclusion Criteria:

  • Patient refusal
  • Known allergy to any of the medications used in the study
  • Combined valve and CABG surgeries
  • Redo surgery
  • Infective endocarditis
  • Patients in heart failure or heart block or with significant systolic dysfunction (EF < 40%) or diastolic dysfunction more than grade II
  • Pregnant females
  • Patients being treated for chronic pain or with recent use (< two weeks) of opioids, gabapentin, or pregabalin.
  • Substance abuse
  • Patients with renal impairment (creatinine > 2 mg/dL) or hepatic impairment (ALT > 2 folds, INR > 1.5 and/or serum albumin < 2.5 g/dl)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Opioid-Free Anesthesia (OFA)

The following drugs will be administered 10 minutes before induction of anesthesia in group I (OFA):

  • Pregabalin 150 mg orally with a small sip of water
  • Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes
  • Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes
  • Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes

For simplicity, the weight-based doses of dexmedetomidine and lidocaine will be prepared in a 20 mL syringe

the following drugs will be administered as a continuous infusion:

  • Dexmedetomidine 0.5 mic/kg/h
  • Lidocaine 0.5 mg/kg/h

Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows:

Group I (OFA):

  • Acetaminophen 1 gm/6h
  • ketorolac 30 mg/8h
  • Pregabalin 150 mg once at night
  • Celecoxib 200 mg/24 hours
Drug: Dexmedetomidine 0.5 mic/kg/h

In Group I (OFA) the following drugs will be administered preoperatively:

Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes

The following drugs will be administered as a continuous infusion throughout the operation:

  • Dexmedetomidine 0.5 mic/kg/h
  • Lidocaine 0.5 mg/kg/h

The following drugs will be administered postoperatively:

Acetaminophen 1 gm/6h ketorolac 30 mg/8h Pregabalin 150 mg once at night Celecoxib 200 mg/24 hours

Other Names:
  • Celecoxib 200 mg
  • Lidocaine 0.5 mg/kg/h
  • Pregabalin 150 mg
  • Acetaminophen 1g
  • Ketorolac 30 mg
Active Comparator: Opioid Anesthesia (OA)

Before induction In Group II (OA) patients will receive placebo pills and normal saline in equivalent volumes .

Maintenance

In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h)

Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows:

• Morphine 0.1 mg /kg PRN every 8 hours
Drug: Fentanyl 1 mic/kg/hr
In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h) Morphine 0.1 mg/kg PRN will be administered every 8 hours for postoperative analgesia
Other Names:
  • Morphine 0.1 mg/kg/hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Extubation time (min)
Time Frame: 24 hours
Extubation time, defined as the time from discontinuation of inhalation agents to extubation
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart rate (beats/min)
Time Frame: 24 hours

HR

o Arterial blood pressure (systolic, diastolic, and mean)
24 hours
Blood pressure (mm Hg)
Time Frame: 24 hours
Systolic, diastolic, and mean blood pressure
24 hours
Postoperative rescue analgesia (number)
Time Frame: 24
The number of patients requiring rescue analgesia with Morphine
24
Postoperative morphine consumption (mg)
Time Frame: 24 hours
The total dose of morphine administered
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Investigators

  • Principal Investigator: hossam El-Ashmawi, Professor, Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2020

Primary Completion (Actual)

August 1, 2022

Study Completion (Actual)

October 1, 2022

Study Registration Dates

First Submitted

November 4, 2020

First Submitted That Met QC Criteria

November 23, 2020

First Posted (Actual)

December 1, 2020

Study Record Updates

Last Update Posted (Actual)

August 30, 2023

Last Update Submitted That Met QC Criteria

August 29, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MD-242-2019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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