Postoperative and Opioid Free Anesthesia

Anesthesia Clinical Trial

— POFA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03316339
• Other study ID #: 35RC16_9842_POFA
• Status: Terminated
• Phase: Phase 3
• Start date: November 29, 2017
• Est. completion date: June 19, 2019

Study information

• Verified date: October 2019
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 316
• Est. completion date: June 19, 2019
• Est. primary completion date: January 29, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anesthesia
• Opioid-Related Disorders

Intervention

Drug:
• Dexmedetomidine
Opioid-free anesthesia
• Remifentanil
Opioid anesthesia

Locations

Country	Name	City	State
France	Clermont-Ferrand University Hospital	Clermont-Ferrand
France	Beaujon Hospital	Clichy
France	Lille University Hospital	Lille
France	Metz-Thionville Hospital	Metz
France	Montpellier University Hospital	Montpellier
France	Nantes University Hospital	Nantes
France	Nimes University Hospital	Nîmes
France	Perigueux Hospital	Périgueux
France	Rennes University Hospital	Rennes
France	Saint-Brieuc Hospital	Saint-Brieuc
France	Toulouse University Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of a severe postoperative opioid-related adverse event defined as : postoperative hypoxemia or postoperative ileus (POI) or postoperative cognitive dysfunction (POCD).	Postoperative hypoxemia is defined as an oxygen saturation (SpO2) < 95% with a need for oxygen supplementation within the first 48h after extubation; the duration of oxygen treatment will also be recorded.; Postoperative ileus is defined as an absence of flatus or stools within the first 48h after extubation.; Postoperative cognitive dysfunction will be evaluated using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) by a care provider (either anesthesiologist or nurse).	Within the first 48 hours after extubation
Secondary	Number of episodes of postoperative pain (numeric rating scale = 3), at rest		Within 48 hours after extubation
Secondary	Opioid consumption		During the 48 hours following extubation
Secondary	Time between the end of remifentanil or dexmedetomidine administration and an Aldrete score > 9 (when applicable)		Within 48 hours after extubation
Secondary	Time between the end of remifentanil or dexmedetomidine administration and extubation		Hour 0 = extubation
Secondary	Rate of unscheduled admission in intensive care unit		Within 48 hours after extubation
Secondary	Number of postoperative nausea and vomiting (PONV) episodes		During the 48 hours following extubation
Secondary	Hospital length of stay (max 28 days) defined as the number of days after extubation before first hospital discharge		Day 28
Secondary	Number of bradycardia, hypotension and hypertension events during surgery and number of rescue medications during surgery	Bradycardia is defined as the number of episodes with atropine administration. Hypotension is defined as mean arterial blood pressure < 65 mmHg. Hypertension is defined as mean arterial blood pressure > 90 mmHg.	During surgery (maximum duration of 7 hours)