Clinical trial NCT03316339: Postoperative and Opioid Free Anesthesia
Official title: Effect of Opioid-free Anesthesia on Postoperative Opioid-related Adverse Events After Major or Intermediate Non-cardiac Surgery: a Multicenter Prospective Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Anesthesia
Opioid-Related Disorders
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2017-10-20
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Since the 1960's, intraoperative administration of opioids is considered a keystone of anesthesia as well as hypnotics and muscle relaxants. Synthetic opioids were introduced to achieve hemodynamic stability during anesthesia. They allow an inhibition of the sympathetic system without cardiovascular collapse and histamine release. Since then, anesthesia has changed from inhalation to multimodal anesthesia with lower doses of hypnotic. In 2017, the intraoperative objectives of hypnosis, hemodynamic stability, immobility and anticipation of postoperative analgesia can be achieved without opioids. Moreover, opioid administration consequences are neither scarce nor benign for the patient. Perioperative opioids are associated with nausea and vomiting, sedation, ileus, confusion/delirium, respiratory depression, increased postoperative pain and morphine consumption, immunodepression, hyperalgesia and chronic postoperative pain. Among these complications, hypoxemia, ileus and confusion/delirium are the most frequent.

Efficacious multimodal analgesia and anesthesia are the basis of successful fast-track surgery. These multidrug regimens aim at decreasing postoperative pain, intra- and postoperative opioid requirements, and subsequently, opioid-related adverse effects and to fasten recovery. Opioid-free postoperative analgesia has been recommended for more than 10 years. Opioid-free anesthesia (OFA) is based on the idea that hemodynamic stability can be achieved without opioids during anesthesia. OFA is multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and alpha-2 agonists (Dexmedetomidine).

Proofs of the effect of OFA on reducing opioid-related adverse effects after major or intermediate non-cardiac surgery are still scarce. We hypothesized that the reduced opioid consumption during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events.


Eligibility criteria: Inclusion Criteria:

* Undergoing a scheduled major or intermediate non-cardiac surgery,
* Benefiting from the health insurance system,
* Having signed an informed consent.

Exclusion Criteria:

* Pregnant or breast feeding women,
* Allergy to dexmedetomidine or one of its excipients,
* Allergy to one of the drugs used for anesthesia or one of their excipients,
* Urgent surgery,
* Intracranial surgery,
* Transplant surgery or transplanted patients,
* Surgery with planned regional anesthesia,
* Outpatient surgery,
* Atrioventricular block, intraventricular or sinoatrial block,
* Treatment by chronic betablockers and HR \< 50 bpm,
* Heart failure with LVEF \< 40%,
* Adam-Stokes syndrome,
* Epilepsy or seizures,
* Uncontrolled hypotension,
* Acute cerebral pathology,
* Obstructive sleep apnea syndrome,
* Severe hepatic insufficiency (Prothrombin Ratio \< 15%),
* Patients in whom the CAM-ICU cannot be performed (deaf patients for example)
* Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.

Primary outcomes:
measure: Occurence of a severe postoperative opioid-related adverse event defined as : postoperative hypoxemia or postoperative ileus (POI) or postoperative cognitive dysfunction (POCD).
timeFrame: Within the first 48 hours after extubation
Secondary outcomes:
measure: Number of episodes of postoperative pain (numeric rating scale ≥ 3), at rest
timeFrame: Within 48 hours after extubation
measure: Opioid consumption
timeFrame: During the 48 hours following extubation
measure: Time between the end of remifentanil or dexmedetomidine administration and an Aldrete score > 9 (when applicable)
timeFrame: Within 48 hours after extubation
measure: Time between the end of remifentanil or dexmedetomidine administration and extubation
timeFrame: Hour 0 = extubation
measure: Rate of unscheduled admission in intensive care unit
timeFrame: Within 48 hours after extubation
measure: Number of postoperative nausea and vomiting (PONV) episodes
timeFrame: During the 48 hours following extubation
measure: Hospital length of stay (max 28 days) defined as the number of days after extubation before first hospital discharge
timeFrame: Day 28
measure: Number of bradycardia, hypotension and hypertension events during surgery and number of rescue medications during surgery
timeFrame: During surgery (maximum duration of 7 hours)
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
city: Clichy
country: France
facility: Beaujon Hospital
city: Lille
country: France
facility: Lille University Hospital
city: Metz
country: France
facility: Metz-Thionville Hospital
city: Montpellier
country: France
facility: Montpellier University Hospital
city: Nantes
country: France
facility: Nantes University Hospital
city: Nîmes
country: France
facility: Nimes University Hospital
city: Périgueux
country: France
facility: Perigueux Hospital
city: Rennes
country: France
facility: Rennes University Hospital
city: Saint-Brieuc
country: France
facility: Saint-Brieuc Hospital
city: Toulouse
country: France
facility: Toulouse University Hospital
Study officials:
affiliation: Rennes University Hospital
name: Hélène BELOEIL
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beloeil H, Laviolle B, Menard C, Paugam-Burtz C, Garot M, Asehnoune K, Minville V, Cuvillon P, Oger S, Nadaud J, Lecoeur S, Chanques G, Futier E; SFAR research network. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. BMJ Open. 2018 Jun 30;8(6):e020873. doi: 10.1136/bmjopen-2017-020873.