Opioid-Free Anesthesia in Cardiac Surgery

NCT04940689 | Completed Phase 3 DMC

• 2 other identifiers: 2019/0399/HP2020-002126-90
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• To assess the impact of OFA on the incidence of postoperative nausea and vomiting.

  48 hours post-surgery

• To assess the impact of OFA on the incidence of postsurgery pain.

  48 hours post-surgery

• To assess the impact of OFA on the incidence of atrial rhythm disturbances and / or ventricular postsurgery shock states.

  48 hours post-surgery

• To assess the impact of OFA on the incidence of acute post-surgery renal failure,

  48 hours post-surgery

• To assess the impact of the OFA on the incidence of post-surgery adrenal insufficiency,

  24 hours post-surgery

Study Arms (2)

Standard arm

ACTIVE COMPARATOR

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

OFA arm

EXPERIMENTAL

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

Interventions

Remifentanil DRUG

The patient will be anesthetized with morphin.

Also known as: Control

Standard arm

Dexmédétomidine 0.5 g/kg + lidocaine 1.5 mg/kg DRUG

The patient will be anesthetized with Dexmedetomidine 0.5 g / kg + lidocaine 1.5 mg / kg for the induction instead of morphin.

Also known as: experimental

OFA arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient affiliated to a social security scheme

You may not qualify if:

• Pre-existing high-degree conduction disorder
• Bradycardia \< 50 bpm
• Heart failure with LVEF \<40%
• BMI ≥ 35 kg/m²
• 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

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (5)

Rouen University Hospital

Rouen, France, Normandy, 76031, France

Location

Amiens Univesrity Hospital

Amiens, France

Location

CAEN university Hospital

Caen, France

Location

Lille Hopistal University

Lille, France

Location

Montpellier University Hospital

Montpellier, France

Location

Related Publications (1)

• 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.

  PMID: 38830745 DERIVED

MeSH Terms

Interventions

Dexmedetomidine; Lidocaine; Remifentanil

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Propionates; Acids, Acyclic; Carboxylic Acids; Piperidines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: June 25, 2021
• Study Start: July 22, 2021
• Primary Completion: August 28, 2024
• Study Completion: August 28, 2024
• Last Updated: March 31, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: From results publication to 10 years

Locations

FR (5)