Opioid-Free Anesthesia in Cardiac Surgery

NCT ID: NCT04940689

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 268 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-22
• Study Completion Date: 2024-08-28

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.

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.

Conditions

Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Remifentanil

Intervention Type: DRUG

The patient will be anesthetized with morphin.

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.

Group Type: EXPERIMENTAL

Dexmédétomidine 0.5 g/kg + lidocaine 1.5 mg/kg

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Remifentanil

The patient will be anesthetized with morphin.

Intervention Type: DRUG

Other Intervention Names

experimental; Control

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rouen University Hospital

Rouen, France, Normandy, France

Amiens Univesrity Hospital

Amiens, , France

CAEN university Hospital

Caen, , France

Lille Hopistal University

Lille, , France

Montpellier University Hospital

Montpellier, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 38830745 (View on PubMed)

Other Identifiers

2019/0399/HP

Identifier Type: -

Identifier Source: org_study_id