Clinical trial NCT04940689: Opioid-Free Anesthesia in Cardiac Surgery
Official title: Opioid-Free Anesthesia in Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anesthesia
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2021-06-25
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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.
timeFrame: 48 hours post-surgery
Secondary outcomes:
measure: To assess the impact of OFA on the incidence of postoperative nausea and vomiting.
timeFrame: 48 hours post-surgery
measure: To assess the impact of OFA on the incidence of postsurgery pain.
timeFrame: 48 hours post-surgery
measure: To assess the impact of OFA on the incidence of atrial rhythm disturbances and / or ventricular postsurgery shock states.
timeFrame: 48 hours post-surgery
measure: To assess the impact of OFA on the incidence of acute post-surgery renal failure,
timeFrame: 48 hours post-surgery
measure: To assess the impact of the OFA on the incidence of post-surgery adrenal insufficiency,
timeFrame: 24 hours post-surgery
measure: 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
timeFrame: Within 2 months after surgery
measure: Evaluate the impact of the OFA on the incidence of postoperative mortality
timeFrame: Within 2 months after surgery
measure: Persistence of chronic pain evaluated during a telephone call
timeFrame: 3 months after surgery
measure: Persistence of chronic pain evaluated during a telephone call
timeFrame: 3 months after surgery
measure: To assess the impact of OFA on the incidence of shock
timeFrame: 48 hours post-surgery
measure: To assess the myocardial pain
timeFrame: 48 hours post-surgery
measure: To assess the intraoperative safety
timeFrame: intraoperative periode
Other outcomes:
Locations:
city: Rouen
country: France
facility: Rouen University Hospital
state: France, Normandy
city: Amiens
country: France
facility: Amiens Univesrity Hospital
city: Caen
country: France
facility: CAEN university Hospital
city: Lille
country: France
facility: Lille Hopistal University
city: Montpellier
country: France
facility: Montpellier University Hospital
Study officials:
References: