Automatic Remifentanil Administration Guided by ANI During Propofol Anesthesia (ANI-LOOP)

Automatic Remifentanil Administration Guided by the Analgesia Nociception Index During Propofol Anesthesia

Prospective Randomized Monocentric Clinical Trial during propofol anesthesia. The aim of the study is to test whether the use of a medical device designed to automatically administer remifentanil during surgery based on expert rules and continuous reading of heart rate, blood pressure and the Analgesia Nociception Index results in lower overall remifentanil administration versus standard practice.

Study Overview

• Status: Completed
• Conditions: Surgical Procedure, Unspecified; Nociceptive Pain
• Intervention / Treatment: Device: ANI-REMI-loop; Drug: Remifentanil; Drug: Propofol; Device: remifentanil pK/pD target administration device; Device: ANI monitor

Detailed Description

Prospective Randomized Monocentric Clinical Trial during propofol anesthesia.

• inclusion: ASA 1, 2 or 3 adult patients scheduled to undergo burn wound surgery in a Burn Center (University Hospital of Lille, France)
• arm 1 : Remifentanil will be automatically administered by an expert system guided by heart rate, blood pressure and the Analgesia Nociception Index (ANI).
• arm 2 : Remifentanil will be administered by a target controlled device using the Minto pK/pD model.
• propofol is administered throughout the procedure with a target controlled device using the pK/pD model of Schnider. The target will be guided by the BiSpectral index values.
• primary endpoint : overall normalized remifentanil administration.
• secondary endpoints : relative amount of time spent in a state of hemodynamic reactivity ; relative amount of time the ANI spends in the [0-50], [50-70] and [70-100] windows ; relative amount of time the BIS spends in the [0-40], [40-60] and [60-100] ; hemodynamic status at various times during anesthesia ; total amount of target modifications of remifentanil and propofol ; total amount of morphine administered in PACU ; total amount of ketamine administered in PACU ; incidence of nausea/vomiting in PACU ;

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hôpital Roger Salengro, CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA 1, 2 or 3 adult patients scheduled to undergo burn wound surgery at the Burn Center of the University Hospital of Lille

Exclusion Criteria:

• BMI outside [17 - 35 kg/m2]
• pregnancy or breast feeding women
• non sinus cardiac rhythm
• documented dysautonomia
• complicated diabetes mellitus
• known allergy to a drug used in the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ANI-loop; arm 1 : remifentanil is automatically administered by a medical device using expert rules and continuous reading of heart rate, blood pressure and Analgesia Nociception Index (MDMS, Loos, France)	Device: ANI-REMI-loop; experimental medical device using expert rules and continuous reading of heart rate, blood pressure and Analgesia Nociception Index for automatic remifentanil administration; Drug: Remifentanil; Remifentanil Ce target can range from 0 to 10 ng.ml-1. Remifentanil target is adapted in order to maintain Analgesia Nociception Index (MDMS, Loos, France) in the [50-70] range.; Drug: Propofol; propofol is used for induction and maintenance of general anesthesia using Schnider pK/pD model. Propofol Ce target is adapted in order to maintain BiSpectral Index in [40-60] range
ACTIVE_COMPARATOR: std_practice; arm 2: remifentanil is administered by a target control device using Minto's remifentanil pK/pD model. This is standard practice for this type of surgery at the Burn Center of the University Hospital of Lille, France.	Drug: Remifentanil; Remifentanil Ce target can range from 0 to 10 ng.ml-1. Remifentanil target is adapted in order to maintain Analgesia Nociception Index (MDMS, Loos, France) in the [50-70] range.; Drug: Propofol; propofol is used for induction and maintenance of general anesthesia using Schnider pK/pD model. Propofol Ce target is adapted in order to maintain BiSpectral Index in [40-60] range; Device: remifentanil pK/pD target administration device; standard practice, remifentanil administration using Minto's pK/pD model; Device: ANI monitor; ANI (Analgesia Nociception Index) value is used in the "std_practice" arm for guidance of the remifentanil Ce target; Other Names: PhysioDoloris (MDMS, Loos, France)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
normalized remifentanil administration	ratio of total amount of administered remifentanil with body weight and duration of administration	During the surgery, an average Three hours and a half

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemodynamic reactivity or bradycardia or hypotension	relative amount of time during which heart rate or SBP exceed 120% of baseline, or heart rate drops below 40/min, or SBP drops below 75 mmHg.	During the surgery, an average Three hours and a half
total administered ephedrine	total amount of ephedrine administered during general anesthesia	duration of general anesthesia
Analgesia Nociception Index (ANI)	relative amount of time spent with ANIi in the [0-50], [50-70] and [70-100] windows. Same with ANIm	During the surgery, an average Three hours and a half
Bispectral Index (BIS)	relative amount of time spent with BIS in the [0-40], [40-60] and [60-100] windows.	During the surgery, an average Three hours and a half
Change antinociception/nociception balance status	composite measure: heart rate, blood pressure, ANIi, ANIm, end-tidal CO2, PeakPressure	5 min before start of nociception, 5 min after start of nociception and 20 min after start of nociception
Pain in PACU	Visual Analog Scale every 15 min in PACU The pain VAS is a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme (0, 10).	During the first two postoperative hours
morphine in PACU	Total amount of administered morphine during PACU stay	During the first two postoperative hours
ketamine in PACU	Total amount of administered ketamine during PACU stay	During the first two postoperative hours
nausea/vomiting in PACU	reported number of nausea/vomiting during PACU stay	During the first two postoperative hours
remi target changes	total number of target changes during general anesthesia	During the surgery, an average Three hours and a half
propofol target changes	total number of target changes during general anesthesia	During the surgery, an average Three hours and a half
normalized propofol administration	ratio of total amount of propofol administered with body weight and duration of general anesthesia	During the surgery, an average Three hours and a half
ANI-REMI-loop switch to manual	number of interventions on ANI-REMI-loop device: switch to manual	During the surgery, an average Three hours and a half

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Mathieu JEANNE, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2018
• Primary Completion (ACTUAL): June 14, 2022
• Study Completion (ACTUAL): November 22, 2022

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (ACTUAL): June 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: general anesthesia; expert system; analgesia/nociception balance monitoring
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nociceptive Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Propofol
• Other Study ID Numbers: 2016_48; 2017-A00858-45 (OTHER: ID-RCB number, ANSM)

Drug and device information, study documents

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