Impact of NOL Index Intraoperative Guided Remifentanil Analgesia (Eu-MultiNOL)

Impact of Nociceptive-Level (NOL) Intraoperative Guided Remifentanil Analgesia Versus Standard Clinical Care (SCC) for Elective Major Abdominal Surgery

The Physiological Monitoring Device (PMD-200™) system is comprised of a monitor and a designated finger probe containing 4 sensors. The sensors included are Photoplethysmography (PPG), Galvanic Skin Response (GSR), Accelerometer for movement (ACC) and Thermistor for peripheral temperature (TMP).

The PMD-200 is intended to be used for assessing the nociception level in anesthetized patients.

The purpose of the study is confirmation of a reduction in the dosage of remifentanil allowed by the monitoring of nociception by the NOL which could open the way to a double control of the administration of anesthetic agents: control of the administration of hypnotics by the bispectral index (BIS) and control of the administration of opiate by the NOL.

Study Overview

• Status: Recruiting
• Conditions: Abdominal Surgery
• Intervention / Treatment: Device: Bispectral index; Device: Bispectral index + NOL index

Detailed Description

The PMD-200 continuous pain monitor is intended to be used for assessing changes in pain levels. The system monitors the physiological responses to pain using a relative pain index from 0-100, called the Nociception Level (NOL®) index. In the NOL index, 0 represents no nociception or pain and 100 represents high nociception or pain level.

The PMD-200 system consists of a monitor and a specific finger probe containing 4 sensors. The sensors included are Photoplethysmography (PPG), Galvanic Skin Response (GSR), Accelerometer for movement (ACC) and Thermistor for peripheral temperature (TMP).

The PMD-200™ is intended to be used for assessing the nociception level in anesthetized patients. The device is European Conformity (CE) marked and commercially available.

Meier et al. recently published a randomized trial involving 80 patients for major abdominal surgery, one group receiving routine care and the other NOL-guided analgesia. In the latter group, the remifentanil concentration was reduced when NOL values were below 10 or increased when NOL values were above 25 for at least 1 minute. In both groups, propofol was titrated to have bispectral index values between 45 and 55. Remifentanil administration was reduced in the NOL-guided group: 0.119 ± 0.033 vs 0.086 ± 0.032 μg.kg.min (p < 0.001). In the NOL- guided group, 2 out of 40 (5%) patients had hypotension (mean blood pressure less than 55 mm Hg) compared to 11 out of 40 (28%) in the control group (p = 0.006) and 16 out of 40 (40%) patients received vasoactive drugs vs 25 out of 40 (63%) (p = 0.044).

Previous results cover a small number of patients treated in a single center. The purpose of this study is to confirm this result within a multicenter study involving a larger group of patients. Confirmation of a reduction in the dosage of remifentanil allowed by the monitoring of nociception by the NOL will open the way to a double control of the administration of anesthetic agents: control of the administration of hypnotics by the bispectral index (BIS) and control of the administration of opiate by the NOL.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Morgan LE GUEN, Dr; Phone Number: +33146252998; Email: m.leguen@hopital-foch.com
• Study Contact Backup: Name: Elisabeth HULIER AMMAR, Dr; Phone Number: +33146251175; Email: drci-promotion@hopital-foch.com

Study Locations

• France
  • Suresnes, France, 92150
    • Recruiting
    • Foch Hospital
    • Contact: Morgan LE GUEN, MD; Phone Number: +33146252989; Email: m.leguen@hopital-foch.com
  • Provence-Alpes-Côte d'Azur
    • Toulon, Provence-Alpes-Côte d'Azur, France, 83800
      • Not yet recruiting
      • Hôpital d'Instruction des Armées - Sainte-Anne
      • Contact: Julien Bordes, MD; Phone Number: 06.81.49.81.77; Email: julien.bordes@intradef.gouv.fr
      • Contact: Karine Michaud Grosbenoit; Phone Number: 04.83.76.24.61; Email: karine.dandrieux@intradef.gouv.fr
  • Saint Mandé
    • Saint-Mandé, Saint Mandé, France, 94160
      • Not yet recruiting
      • Hopital d'Instruction des Armees de Begin
      • Contact: Jean Pierre TOURTIER, PhD; Phone Number: 0033767669549; Email: jean-pierre.tourtier@intradef.gouv.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• American Society of Anesthesiologists score (ASA) I, II or III stable
• Laparotomy or laparoscopy for major, planned, digestive, urological or gynecological surgery under total intravenous anesthesia (expected total duration > 90 minutes)
• Having sign an informed consent form prior to any study specific procedure
• Being covered by a national health insurance

Non-Inclusion Criteria:

• Pregnancy/lactation
• Patient with antiarrhythmic agents
• Patient with Central nervous system disorder
• Patient with veinous approach difficulties
• Patient at risk of difficult mask ventilation or difficult intubation
• Concomitant use of any type of anesthesia other than general anesthesia (epidural anesthesia, spinal anesthesia, wall block, pericatricial infiltration). Wall blocks and pericatricial infiltrations are allowed if they are carried out at the end of the intervention
• Allergy or intolerance to any of the study drugs
• Patient not understanding French language
• Being deprived of liberty or under guardianship

Exclusion Criteria:

• Patient requiring the administration of succinylcholine
• Patient with hemodynamic abnormality just before induction of anesthesia (mean arterial pressure < 65 mm Hg or > 110 mm Hg, heart rate < 45/min or > 90/min
• Concomitant use of any type of anesthesia other than general anesthesia (epidural anesthesia, spinal anesthesia, wall block, pericatricial infiltration). Wall blocks and pericatricial infiltrations are allowed if they are carried out at the end of the intervention
• Concomitant use of IV lidocaine or continuous ketamine (IV, SE) during anaesthesia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: "SCS" Group; Receiving anesthesia according to routine standard care, with the use of the "hidden" NOL (used to compare the data at the end of anesthesia with those of the classic BIS - without monitoring of the anesthesia by the NOL (without adjustment of treatments ))	Device: Bispectral index; Anesthesia monitoring
Experimental: NOL Group; Receiving anesthesia monitored by the NOL	Device: Bispectral index + NOL index; Anesthesia monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remifentanil consumption during maintenance	Remifentanil consumption during anesthesia maintenance in μg/kg/min	surgery day (D0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remifentanil consumption during induction	Remifentanil consumption during anesthesia induction in μg/kg/min	surgery day (D0)
Propofol consumption during induction	Propofol consumption during anesthesia induction in μg/kg/min	surgery day (D0)
Propofol consumption during maintenance	Propofol consumption during anesthesia maintenance in μg/kg/min	surgery day (D0)
Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during induction	A hemodynamic abnormality is defined as: administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine); and/or average blood pressure < 55 mmHg or < 60 mmHg or < 65 mmHg for any length of time; an/or a systolic blood pressure > 140 mmHg for any length of time; and/or a heart rate < 45 or > 90 /min	surgery day (D0)
Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during maintenance	Mean Blood pressure events during anesthesia inductio A hemodynamic abnormality is defined as: administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine); and/or average blood pressure < 55 mmHg or < 60 mmHg or < 65 mmHg for any length of time; an/or a systolic blood pressure > 140 mmHg for any length of time; and/or a heart rate < 45 or > 90 /min	surgery day (D0)
Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during induction	An anesthetic abnormality is defined as: a bispectral (BIS) index < 40 or > 60 for at least one minute; and/or a Burst Suppression Ratio (BSR) index > 10% during one minute; and/or a NOL index > 25 or < 10 for at least 2 minutes	surgery day (D0)
Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during maintenance	An anesthetic abnormality is defined as: a bispectral (BIS) index < 40 or > 60 for at least one minute; and/or a Burst Suppression Ratio (BSR) index > 10% during one minute; and/or a NOL index > 25 or < 10 for at least 2 minutes	surgery day (D0)
Wake up time	delay between the end of Propofol or Sugammadex/Neostigmine and extubation	surgery day (D0)
Intensity of pain in PACU (post-anesthesia care unit)	Morphine consumption in PACU (post-anesthesia care unit)	surgery day (D0)

Collaborators and Investigators

• Sponsor: Hopital Foch
• Investigators: Principal Investigator: Morgan LE GUEN, MD, Foch Hospital

Publications and helpful links

General Publications

• Meijer FS, Martini CH, Broens S, Boon M, Niesters M, Aarts L, Olofsen E, van Velzen M, Dahan A. Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial. Anesthesiology. 2019 May;130(5):745-755. doi: 10.1097/ALN.0000000000002634.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2019_0051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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