Clinical trial NCT04402242: Impact of NOL Index Intraoperative Guided Remifentanil Analgesia
Official title: Impact of Nociceptive-Level (NOL) Intraoperative Guided Remifentanil Analgesia Versus Standard Clinical Care (SCC) for Elective Major Abdominal Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Abdominal Surgery
Lead sponsor: Hopital Foch
Sponsor class: OTHER
First posted: 2020-05-26
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, multi-center, single blinded interventional study with 2 parallel groups: standard clinical care (SCC group, control group) and NOL-guided analgesia (NOL guided analgesia group, interventional group), stratified by site
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Remifentanil consumption during maintenance
timeFrame: surgery day (D0)
Secondary outcomes:
measure: Remifentanil consumption during induction
timeFrame: surgery day (D0)
measure: Propofol consumption during induction
timeFrame: surgery day (D0)
measure: Propofol consumption during maintenance
timeFrame: surgery day (D0)
measure: Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during induction
timeFrame: surgery day (D0)
measure: Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during maintenance
timeFrame: surgery day (D0)
measure: Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during induction
timeFrame: surgery day (D0)
measure: Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during maintenance
timeFrame: surgery day (D0)
measure: Wake up time
timeFrame: surgery day (D0)
measure: Intensity of pain in PACU (post-anesthesia care unit)
timeFrame: surgery day (D0)
Other outcomes:
Locations:
city: Toulon
country: France
facility: Hôpital d'Instruction des Armées - Sainte-Anne
state: Provence-Alpes-Côte d'Azur
city: Saint-Mandé
country: France
facility: Hopital d'Instruction des Armées de Bégin
state: Saint Mandé
city: Suresnes
country: France
facility: Foch Hospital
Study officials:
affiliation: Foch HOSPITAL
name: Morgan LE GUEN, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.