Opioid-Free Anesthesia in Cardiac Surgery (OFACS)

The use of morphine derivatives is widespread for performing general anesthesia. However, opioids have their own side effects: respiratory depression, digestive ileus, cognitive dysfunction, postoperative hyperalgesia, nausea-vomiting or even negative effects on inflammation or adrenal function. The advent of new molecules, with analgesic properties that do not pass through opioid receptors, has allowed the emergence of the concept of anesthesia without morphine (opioid free anesthesia OFA). These molecules are essentially: dexmedetomidine, ketamine, lidocaine. Thus, the use of ketamine is currently recommended in the event of major surgery in order to limit postoperative pain and hyperalgesia. Likewise, the use of dexmedetomidine in place of an opioid during bariatric surgeries has been shown to reduce postoperative pain and intraoperative hemodynamic manifestations. In addition, it would also reduce the incidence of postoperative cognitive dysfunction. A recent meta-analysis even suggested a decrease in length of stay, mechanical ventilation, atrial fibrillation and mortality with the use of dexmedetomidine in the perioperative period. The combined use of various non-morphine analgesic molecules therefore opens the way to anesthesia without morphine, and a French multicenter study on this strategy in general non-cardiac surgery is currently underway. Cardiac surgery is characterized by significant postoperative pain, a high incidence of cognitive dysfunction, and frequent and sometimes significant respiratory complications. An OFA strategy could therefore be beneficial to these patients, but no study has yet addressed the subject.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Remifentanil; Drug: Dexmédétomidine 0.5 g/kg + lidocaine 1.5 mg/kg

Detailed Description

The objective of our work is therefore to assess the beneficial effects of OFA versus strategy with intraoperative opioids on postoperative complications related to opioids.

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • Amiens Univesrity Hospital
  • Caen, France
    • Caen University Hospital
  • Lille, France
    • Lille Hopistal University
  • Montpellier, France
    • Montpellier University Hospital
  • France, Normandy
    • Rouen, France, Normandy, France, 76031
      • Rouen University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients having planned cardiac surgery under cardiopulmonary bypass, with at least one coronary artery bypass grafting and rf at least one internal mammary artery as graft; possible association with aortic valve replacement
• Patient having red and understood the information letter and signed the consent form
• For women : of childbearing age, need to confirm the absence of an active pregnancy by a negative blood pregnancy test within 48 hours prior to inclusion / menopausal (amenorrhea not medically induced for at least 12 months before the inclusion visit)
• Patient affiliated to a social security scheme

Exclusion Criteria:

• Preoperative treatment with morphine or its derivatives (including tramadol) in the 15 days preceding the inclusion visit
• Pre-existing high-degree conduction disorder
• Bradycardia < 50 bpm
• Oxygen therapy prior to inclusion
• Heart failure with LVEF <40%
• BMI ≥ 35 kg/m²
• Myocardial suffering in the 5 days preceding inclusion
• Patient in shock
• Known adrenal insufficiency and / or long-term systemic corticosteroid treatment (equivalent to hydrocortisone hemisuccinate ≥ 20 mg / day)
• Combined surgery other than aortic valve
• Long-term non-invasive ventilation (including for obstructive sleep apnea syndrome)
• Any antecedent or active practice (s) of drug addiction;
• Contraindication to one of the experimental and / or non-experimental treatments: dexmedetomidine, lidocaine, dexamethasone, ketamine, remifentanil or morphine
• Acute cerebrovascular pathology,
• Severe hepatic insufficiency (factor V level <50%),
• Pre-existing cognitive disorders,
• Patient for whom the CAM-ICU questionnaire cannot be carried out (deaf patients for example),
• Pregnant or parturient or breastfeeding woman
• Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection / under guardianship or guardianship
• Patient participating in another drug trial or having participated in another drug trial within 1 month before randomization

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OFA arm; General anesthesia strategy without morphine; Within 10 minutes before the induction of general anesthesia: pre-induction dose of dexmedetomidine 0.5 g / kg and lidocaine 1.5 mg / kg by slow IV.; The anesthetic induction will be carried out by an intravenous hypnotic (propofol or etomidate) combined with an IV curare; The maintenance of the anesthesia will be carried out by propofol or a halogenated gas (sevoflurane or desflurane) in continuous administration (qsp bispectral index 40-60), dexmedetomidine 0.5-1.0 g / kg / h, lidocaine 2 mg / kg / h. The administration of curare will be carried out as needed.	Drug: Dexmédétomidine 0.5 g/kg + lidocaine 1.5 mg/kg; The patient will be anesthetized with Dexmedetomidine 0.5 g / kg + lidocaine 1.5 mg / kg for the induction instead of morphin.; Other Names: experimental
Active Comparator: Standard arm; General anesthesia strategy with morphine: Within 10 minutes before the induction of general anesthesia: administration of a placebo of 50 mL of 0.9% NaCl by slow IV; The anesthetic induction will be carried out by an intravenous hypnotic (propofol or etomidate) combined with IV curare and remifentanil (morphine derivative) IV for a concentration target of 4 ng / mL.; Maintenance of anesthesia will be carried out with propofol or a halogenated gas (sevoflurane or desflurane) in continuous administration (qs bispectral index 40-60) and remifentanil (target concentration 1-10 ng / mL). The administration of curare will be carried out as needed. In order to anticipate the sudden end of the analgesia, an administration of morphine 0.15 mg / kg IV will be carried out 30 minutes before the end of the intervention as recommended	Drug: Remifentanil; The patient will be anesthetized with morphin.; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of general anesthesia strategy without the use of opioids (OFA) on the incidence of major postoperative complications related to opioids compared to the reference strategy using opioids.	Composite criterion consisting of the appearance 48 hours after the surgery of an intestinal ileus, and / or of an alteration of the neurological state, and / or of an acute respiratory failure, and / or of a death	48 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of OFA on the incidence of postoperative nausea and vomiting.	Existence of post-surgery nausea	48 hours post-surgery
To assess the impact of OFA on the incidence of acute post-surgery renal failure,	Onset of acute renal failure defined by a KDIGO score ≥ 1	48 hours post-surgery
Evaluate the impact of the OFA on the incidence of postoperative mortality	Number of deaths	Within 2 months after surgery
To assess the impact of OFA on the incidence of postsurgery pain.	Number of post-surgery pain episodes at rest (VAS ≥ 3) and total morphine consumption	48 hours post-surgery
Persistence of chronic pain evaluated during a telephone call	simple numerical scale, from 0 to 10	3 months after surgery
Persistence of chronic pain evaluated during a telephone call	neuropatic pain questionnaire (DN4), from 0 to 10	3 months after surgery
To assess the impact of OFA on the incidence of shock	Presence of cardiogenic shock and vasoplegic syndrome	48 hours post-surgery
To assess the intraoperative safety	Existence of bradycardia requiring atropine adminitsrtation and/or appearance of arterial hypotension or hypertension	intraoperative periode
To assess the impact of OFA on the incidence of atrial rhythm disturbances and / or ventricular postsurgery shock states.	Appearance of non-preexisting atrial fibrillation and/or of postsurgery ventricular rhythm disturbances and/or high degree cardiac conduction disorders	48 hours post-surgery
To assess the impact of the OFA on the incidence of post-surgery adrenal insufficiency,	Incidence of relative adrenal insufficiency 24 hours postoperatively by performing a synacthene test. An increase in cortisol levels <250 nmol / L within one hour of the injection of 250 µg of tetracosactide is a diagnosis	24 hours post-surgery
Evaluate the impact of the OFA on the impact of the length of ICU and hospital stay Evaluate the impact of the OFA on the impact of the length of post-surgeryhospital stay	Number of days in the hospital	Within 2 months after surgery
To assess the myocardial pain	maximum troponin plasma level	48 hours post-surgery

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Publications and helpful links

General Publications

• Besnier E, Moussa MD, Thill C, Vallin F, Donnadieu N, Ruault S, Lorne E, Scherrer V, Lanoiselee J, Lefebvre T, Sentenac P, Abou-Arab O. Opioid-free anaesthesia with dexmedetomidine and lidocaine versus remifentanil-based anaesthesia in cardiac surgery: study protocol of a French randomised, multicentre and single-blinded OFACS trial. BMJ Open. 2024 Jun 3;14(6):e079984. doi: 10.1136/bmjopen-2023-079984.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2021
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Acids, Acyclic; Carboxylic Acids; Imidazoles; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Piperidines; Propionates; Remifentanil; Lidocaine; Dexmedetomidine
• Other Study ID Numbers: 2019/0399/HP; 2020-002126-90 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated by this trial will not be publicly available but upon reasonable request to the corresponding author (Emmanuel Besnier, emmanuel.besnier@chu-rouen.fr). In this case, data will be totally deidentified. Requesters should provide a structured and detailed protocol for the proposed study and the reasons for reusing data.
• IPD Sharing Time Frame: From results publication to 10 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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