Clinical trial NCT03618082: GOAL-Directed ANalgesia (GOALDAN)
Official title: Effect of Targeted Analgesia to ANI (Analgesia/ Nociception Index) During General Anesthesia on Immediate Postoperative Pain and Perioperative Hemodynamic: Multicenter Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Immediate Severe Postoperative Pain
Perioperative Hemodynamic
Keywords: prospective
single blind
multicenter
randomized
controlled
Analgesia Nociception Index (ANI)
Postoperative pain
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Fondation Apicil
First posted: 2018-08-07
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization in 2 groups 1- control group : patients receiving a general anesthesia with propofol, ketamine and remifentanil with or without curare for the induction, desflurane, remifentanil (curare or not) for the maintenance, the dosage of the anesthetic agents will be decided by the anesthesiologist responsible for the patient based on the usual practice. 2- experimental group : patients receiving a general anesthesia with propofol, ketamine and remifentanil with or without curare for the induction, desflurane, remifentanil (curare or not) for the maintenance, administered according to a specific algorithm. In this group, the remifentanil administration will be piloted by the ANI (50 to 80), as well as the prophylactic administration of morphine at the end of the intervention. Administration of 2mg of morphine immediately before the extubating if ANI\<50. And, desflurane will be administered with a targeted purpose of 0.8 to 1.2 MAC.
Primary purpose: PREVENTION

Brief summary: The primary purpose of GOALDAN study is to demonstrate the superiority of a targeted perioperative analgesic strategy by the ANI over the usual practice on the incidence of immediate postoperative pain.

The investigators hypothesized that a prophylactic administration of morphine in patients with risk of postoperative pain determined by the ANI at the end of the intervention would reduce the incidence of immediate postoperative pain and that the targeted analgesia to ANI and minimal alveolar concentration (MAC) of desflurane could improve the perioperative hemodynamic, and the postoperative becoming.

Detailed description: Visits:

* The patient will arrive in the department the day before the surgical intervention (D-1). During this preoperative visit (D-1), the investigator

  * will preselect potentially eligible patients
  * will offer to participate to this study
  * will give the notice form to the patients
  * will present the research: objectives, benefits and constraints for the patients
  * will check that patients understand the verbally administered Numeric Rating Scale (NRS) for the assessment of the postoperative This verbally administered NRS is routinely presented to all patients at a surgical intervention.
* The intervention day (D0):

The investigator will collect the signed consent form after having ascertained the understanding of the notice form by the patient and checking the inclusion and non-inclusion criteria.

The randomization will be done via the eCRF module (allocation group and number) and the preoperative data registration in the eCRF.

• Surgical intervention (D0): All patients will receive a usual multimodal analgesia associating level 1 analgesics (acetaminophen, ketoprofen, nefopam) or level 2 (tramadol) administered 30 to 60 min before the foreseeable end of the surgical intervention. All patients will receive 0.1 to 0.2 mg/kg of morphine within the 30 min preceding the end of the surgical intervention according to the usual practice.

Once the patient transferred to the recovery room, the assessment of the primary outcome (verbally administered NRS) will be done by the nurse responsible for the patient, when the patient arrives, during the stay and when the patient leaves the recovery room. If the verbally NRS \> 3, a morphine titration by IV administration of 2 to 3 mg of morphine will be realised then the verbally NRS will be collected 5 min after, according to the usual practice. This morphine titration will continued until the obtaining of a verbal NRS ≤ 3.

As an alternative to this morphine titration, where possible, a peripheral nerve block may be proposed to the patient and performed by the investigator to relieve the patient.

If the patient is transferred directly in ICU without being extubated at the end of the intervention and so without transiting by the recovery room, the patient will be excluded from the study.

Eligibility criteria: Inclusion Criteria:

* 18≤ Age \<65 years old
* Patient operated on a scheduled surgery under general anesthesia
* Patient with a American Society of Anesthesiologists (ASA) score of I to III
* Patient having given his consent in the manner described in Article L1122-1-1 of the Public Health Code
* Patient affiliated with a social security regimen or beneficiary of such a regimen

Exclusion Criteria:

* general anesthesia without extubating (laryngeal mask)
* neuraxial preoperative regional anesthesia (epidural or rachianalgesia)
* opioid-free anesthesia
* preoperative peripheral nerve block with analgesic aim (infiltration of a local surgical anesthetic or transversus abdominis plane block-TAP block-authorized)
* arrhythmia or the presence of a pacemaker
* ambulatory surgery
* cardiac or cerebral surgery
* obstetrical surgery (caesarean)
* surgery performed with neuraxial regional anesthesia or peripheral anesthesia alone
* surgery performed in prone position
* urgent surgery
* endoscopic procedure or interventional radiology
* chronic pain treated with opiates
* expected surgery duration \< 1h
* pathology of the autonomic nervous system (epilepsy, history of transient attack or stroke, paraplegia, hemiplegia, orthostatic hypotension, autonomic dysfunction)
* Patient with cardiogenic or septic shock
* Continuous infusion of vasoactive agents (ephedrine, phenylephrine, adrenaline, or noradrenaline)
* Postoperative transfer planned in intensive care unit (intubated patient) after surgery
* Person under tutorship or curatorship
* Pregnancy
* Breastfeeding

Primary outcomes:
measure: immediate maximum postoperative pain in recovery room defined by a score > 3 on a verbally administered numeric rating scale (NRS) variating from 0 to 10.
timeFrame: From day 0 to day 28
Secondary outcomes:
measure: Maximum pain score during the first postoperative day (numeric rating scale variating from 0 to 10).
timeFrame: every 6 hours during the 24 first hours.
measure: Score Postoperative D1 Pain Management (numeric rating scale variating from 0 to 10)
timeFrame: At day 1
measure: dose of morphine in the recovery room
timeFrame: At day 0
measure: postoperative nausea and vomiting in the recovery room
timeFrame: At day 1
measure: total dose of morphine during the first postoperative day (mg)
timeFrame: At day 1
measure: regional anesthesia for postoperative analgesic purposes
timeFrame: At day 1
measure: the duration in the recovery room (time to obtain an Aldrete score ≥9) (min)
timeFrame: From day 0 to day 28
measure: destination of the patient after surgery (unit of surgery, continuous care, resuscitation).
timeFrame: From day 0 to day 28
measure: incidence of postoperative complications on the first and seventh postoperative days for hospitalized patients using Post-Operative Morbidity Survey (POMS).
timeFrame: From day 0 to day 1 and until day 7
measure: duration of the hospitalization (day)
timeFrame: From day 0 to day 28
measure: Mortality at Day 28
timeFrame: At day 28
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
state: Auvergne
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Jean-Etienne BAZIN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michalot A, Bazin JE, Richebe P, Allaouchiche B, Boselli E. Effect of GOAL-Directed ANalgesia using ANI (Analgesia/Nociception Index) during general anesthesia on immediate postoperative pain and intraoperative hemodynamics in adult patients (GOALDAN study): a study protocol for randomized, controlled, multicenter trial. Trials. 2022 Apr 25;23(1):353. doi: 10.1186/s13063-022-06273-1.