GOAL-Directed ANalgesia (GOALDAN) (GOALDAN)

Effect of Targeted Analgesia to ANI (Analgesia/ Nociception Index) During General Anesthesia on Immediate Postoperative Pain and Perioperative Hemodynamic: Multicenter Randomized Controlled Study

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.

Study Overview

• Status: Unknown
• Conditions: Immediate Severe Postoperative Pain; Perioperative Hemodynamic
• Intervention / Treatment: Drug: Anesthesic agent guided by ANI (Interventional Group); Drug: Administration of the lowest effective concentration of desflurane (Interventional Group)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63003
      • Recruiting
      • Chu Clermont-Ferrand
      • Principal Investigator: Jean-Etienne BAZIN
      • Sub-Investigator: Bernard ALLAOUICHE
      • Sub-Investigator: Emmanuel FUTIER
      • Sub-Investigator: Lionel BOUVET
      • Sub-Investigator: Régis FUZIER
      • Sub-Investigator: Elizabeth GAERTNER
      • Sub-Investigator: Mathieu JEANNE
      • Sub-Investigator: Hervé MUSELLEC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: usual practice; control group (usual practice): patients receiving a general anesthesia with propofol, ketamine and remifentanil with or without curare for the induction, and desflurane and remifentanil (with or without curare) for the maintenance. The dosage of the anesthetic agent, as well as the prophylactic administration of morphine at the end of the intervention, will be decided by the anesthesiologist.	Drug: Anesthesic agent guided by ANI (Interventional Group); Anesthesic agent guided by ANI (Interventional Group) The remifentanil administration will be piloted by the ANI, as well as the prophylactic administration of morphine at the end of the intervention.; Drug: Administration of the lowest effective concentration of desflurane (Interventional Group); Administration of the lowest effective concentration of desflurane (Interventional Group) Desflurane will be administered with a targeted purpose of minimal alveolar concentration (MAC).
Experimental: targeted analgesia to ANI; experimental group: patients receiving a general anesthesia with propofol, ketamine and remifentanil with or without curare for the induction, and desflurane and remifentanil (with or without curare) for the maintenance, as well as the prophylactic administration of morphine at the end of the intervention, will be administered according to the ANI. - In addition, desflurane will be administered with a targeted purpose of minimal alveolar concentration (MAC).	Drug: Anesthesic agent guided by ANI (Interventional Group); Anesthesic agent guided by ANI (Interventional Group) The remifentanil administration will be piloted by the ANI, as well as the prophylactic administration of morphine at the end of the intervention.; Drug: Administration of the lowest effective concentration of desflurane (Interventional Group); Administration of the lowest effective concentration of desflurane (Interventional Group) Desflurane will be administered with a targeted purpose of minimal alveolar concentration (MAC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	From day 0 to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum pain score during the first postoperative day (numeric rating scale variating from 0 to 10).	The patient chooses on a scale numeric range a number between 0 and 10 to characterise the intensity of the pain during the first postoperative day : 0 if the pain is mild (better outcome), 10 if the pain is severe (worse outcome).This numeric rating scale will be assessed every 6 hours during the 24 first hours (H0 = arrival hour at the recovery room).	every 6 hours during the 24 first hours.
Score Postoperative D1 Pain Management (numeric rating scale variating from 0 to 10)	The patient chooses on a scale numeric range from 0 to 10, a number which characterises the overall satisfaction of pain management : if the pain management is correct (10) or if the pain management is not correct (0).	At day 1
dose of morphine in the recovery room	will be compared between groups by test t of Student or test not parametrize of Mann-Whitney if the conditions of the test t are not respected (study of the normality, homoscedasticity studied by test of Fisher-Snedecor). The results will be expressed in terms of size of effect and reliable interval in associated 95 %. These analyses can be secondly completed, in multivariate situation, by models of regression of linear type; covariables will be considered with regard to the clinical relevance and the results of analyses univariate preliminary. The results will be expressed in terms of coefficients of regression and reliable intervals in associated 95 %.	At day 0
postoperative nausea and vomiting in the recovery room	In both groups, the prevention of the nausea and the vomitings will be administered according to the current recommendations (dexamethasone 4 mg and droperidol 0,625-1,25 mg it peroperatoire at the patients at risk, defined by a score of Apfel 2). In case of NVPO during the first 24 post-operative hours, the administration of 4 mg of ondansétron will be realized, according to the recommendations.	At day 1
total dose of morphine during the first postoperative day (mg)	will be compared between groups by test t of Student or test not parametrique of Mann-Whitney if the conditions of the test t are not respected (study of the normality, homoscedasticity studied by test of Fisher-Snedecor). The results will be expressed in terms of size of effect and reliable interval in associated 95 %. These analyses can be secondly completed, in multivariate situation, by models of regression of linear type; covariables will be considered with regard to the clinical relevance and the results of analyses univariées preliminary. The results will be expressed in terms of coefficients of regression and reliable intervals in associated 95 %.	At day 1
regional anesthesia for postoperative analgesic purposes		At day 1
the duration in the recovery room (time to obtain an Aldrete score ≥9) (min)	will be compared between groups by test t of Student or test not parametrize of Mann-Whitney if the conditions of the test t are not respected (study of the normality, homoscedasticity studied by test of Fisher-Snedecor). The results will be expressed in terms of size of effect and reliable interval in associated 95 %. These analyses can be secondly completed, in multivariate situation, by models of regression of linear type; covariables will be considered with regard to the clinical relevance and the results of analyses univariées preliminary. The results will be expressed in terms of coefficients of regression and reliable intervals in associated 95 %.	From day 0 to day 28
destination of the patient after surgery (unit of surgery, continuous care, resuscitation).	Test of chi² or exact test of Fisher if necessary. Secondly, this analysis can be completed, in multivariate situation, by a mixed generalized linear model of logistic type allowing to take into account variability inter and intracentre. Covariables will be considered with regard to the clinical relevance (other treatments, use of vasopresseurs continuous, type of surgery) and results of analyses univariate preliminary. The results will be expressed in terms of reports of the quotations and the reliable intervals in associated 95 %.	From day 0 to day 28
incidence of postoperative complications on the first and seventh postoperative days for hospitalized patients using Post-Operative Morbidity Survey (POMS).	Post-operative complications in the first and seventh day post-operative will be compared by test of chi² or where necessary, by the exact test of Fisher. Secondly, this analysis can be completed, in multivariate situation, by a mixed generalized linear model of logistic type allowing to take into account variability inter and intracentre. Covariables will be considered with regard to the clinical relevance (other treatments, use of vasopresseurs continuous, type of surgery) and results of analyses univariées preliminary. The results will be expressed in terms of reports of the quotations and the reliable intervals in associated 95 %.	From day 0 to day 1 and until day 7
duration of the hospitalization (day)	Duration of hospitalization will be compared between groups by test t of Student or test not paramétrique of Mann-Whitney if the conditions of the test t are not respected (study of the normality, homoscédasticité studied by test of Fisher-Snedecor). The results will be expressed in terms of size of effect and reliable interval in associated 95 %. These analyses can be secondly completed, in multivariate situation, by models of regression of linear type; covariables will be considered with regard to the clinical relevance and the results of analyses univariées preliminary. The results will be expressed in terms of coefficients of regression and reliable intervals in associated 95 %.	From day 0 to day 28
Mortality at Day 28	The survival to day 28 comment surgery will be estimated(esteemed) by curve of Kaplan-Meier and compared between groups of randomization by test of the log-rank in univariate situation and model of Cox in multivariated analysis. The results will be expressed in terms of relationship of immediate risks and reliable intervals in associated 95 %.	At day 28

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Fondation Apicil

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Anticipated): May 13, 2022
• Study Completion (Anticipated): August 13, 2022

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 7, 2018

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: prospective; multicenter; Postoperative pain; randomized; single blind; controlled; Analgesia Nociception Index (ANI)
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Desflurane
• Other Study ID Numbers: CHU-401; 2017-A03268-45 (Other Identifier: 2017-A03268-45)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No