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

NCT04648540 | Completed Early Phase 1

• 1 other identifier: MD-242-2019
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (1)

• Extubation time (min)

  Extubation time, defined as the time from discontinuation of inhalation agents to extubation

  24 hours

Secondary Outcomes (4)

• Heart rate (beats/min)

  24 hours

• Blood pressure (mm Hg)

  24 hours

• Postoperative rescue analgesia (number)

  24

• Postoperative morphine consumption (mg)

  24 hours

Study Arms (2)

Opioid-Free Anesthesia (OFA)

EXPERIMENTAL

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

Opioid Anesthesia (OA)

ACTIVE COMPARATOR

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

Interventions

Dexmedetomidine 0.5 mic/kg/h DRUG

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

Also known as: Lidocaine 0.5 mg/kg/h, Pregabalin 150 mg, Acetaminophen 1g, Ketorolac 30 mg, Celecoxib 200 mg

Opioid-Free Anesthesia (OFA)

Fentanyl 1 mic/kg/hr DRUG

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

Also known as: Morphine 0.1 mg/kg/hr

Opioid Anesthesia (OA)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Kasr Al Ainy School of Medicine Cairo University

Cairo, Egypt

Location

Related Publications (14)

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  PMID: 30870677 BACKGROUND

• Wong WT, Lai VK, Chee YE, Lee A. Fast-track cardiac care for adult cardiac surgical patients. Cochrane Database Syst Rev. 2016 Sep 12;9(9):CD003587. doi: 10.1002/14651858.CD003587.pub3.

  PMID: 27616189 BACKGROUND

• Lavand'homme P, Steyaert A. Opioid-free anesthesia opioid side effects: Tolerance and hyperalgesia. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):487-498. doi: 10.1016/j.bpa.2017.05.003. Epub 2017 May 17.

  PMID: 29739537 BACKGROUND

• Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Braz J Anesthesiol. 2015 May-Jun;65(3):191-9. doi: 10.1016/j.bjane.2014.05.001. Epub 2014 Jun 3.

  PMID: 25925031 BACKGROUND

• van Gulik L, Ahlers SJ, van de Garde EM, Bruins P, van Boven WJ, Tibboel D, van Dongen EP, Knibbe CA. Remifentanil during cardiac surgery is associated with chronic thoracic pain 1 yr after sternotomy. Br J Anaesth. 2012 Oct;109(4):616-22. doi: 10.1093/bja/aes247. Epub 2012 Jul 24.

  PMID: 22831889 BACKGROUND

• Hirji SA, Landino S, Cote C, Lee J, Orhurhu V, Shah RM, McGurk S, Kaneko T, Shekar P, Pelletier MP. Chronic opioid use after coronary bypass surgery. J Card Surg. 2019 Feb;34(2):67-73. doi: 10.1111/jocs.13981. Epub 2019 Jan 9.

  PMID: 30625257 BACKGROUND

• Macintyre PE, Walker SM. The scientific evidence for acute pain treatment. Curr Opin Anaesthesiol. 2010 Oct;23(5):623-8. doi: 10.1097/ACO.0b013e32833c33ed.

  PMID: 20811175 BACKGROUND

• Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.

  PMID: 16508405 BACKGROUND

• Alam A, Juurlink DN. The prescription opioid epidemic: an overview for anesthesiologists. Can J Anaesth. 2016 Jan;63(1):61-8. doi: 10.1007/s12630-015-0520-y. Epub 2015 Oct 27.

  PMID: 26507535 BACKGROUND

• McCarthy GC, Megalla SA, Habib AS. Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery: a systematic review of randomized controlled trials. Drugs. 2010 Jun 18;70(9):1149-63. doi: 10.2165/10898560-000000000-00000.

  PMID: 20518581 BACKGROUND

• James MF. Magnesium: an emerging drug in anaesthesia. Br J Anaesth. 2009 Oct;103(4):465-7. doi: 10.1093/bja/aep242. No abstract available.

  PMID: 19749114 BACKGROUND

• Landry E, Burns S, Pelletier MP, Muehlschlegel JD. A Successful Opioid-Free Anesthetic in a Patient Undergoing Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019 Sep;33(9):2517-2520. doi: 10.1053/j.jvca.2018.11.040. Epub 2018 Nov 28. No abstract available.

  PMID: 30611614 BACKGROUND

• Cardinale JP, Gilly G. Opiate-Free Tricuspid Valve Replacement: Case Report. Semin Cardiothorac Vasc Anesth. 2018 Dec;22(4):407-413. doi: 10.1177/1089253218771342. Epub 2018 Apr 20.

  PMID: 29676223 BACKGROUND

• Salah M, Hosny H, Salah M, Saad H. Impact of immediate versus delayed tracheal extubation on length of ICU stay of cardiac surgical patients, a randomized trial. Heart Lung Vessel. 2015;7(4):311-9.

  PMID: 26811837 BACKGROUND

MeSH Terms

Interventions

Lidocaine; Pregabalin; Acetaminophen; Ketorolac; Celecoxib; Morphine

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• hossam El-Ashmawi, Professor

  Cairo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of anesthiology and pain management

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: December 1, 2020
• Study Start: December 1, 2020
• Primary Completion: August 1, 2022
• Study Completion: October 1, 2022
• Last Updated: August 30, 2023

Record last verified: 2023-08

Locations

EG (1)