Automatic Remifentanil Administration Guided by ANI During Propofol Anesthesia

Study Overview
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Brief Summary
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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.

Detailed Description
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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 ;

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

Conditions
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Nociceptive Pain, Surgical Procedure, Unspecified

Intervention / Treatment
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* Device: ANI-REMI-loop
* Device: remifentanil pK/pD target administration device
* Drug: Remifentanil
* Drug: Propofol
* Device: ANI monitor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Monocentric prospective randomized controlled clinical trial arm 1: medical device automatically administering remifentanil, guided by expert rules and continuous reading of heart rate, blood pressure and Analgesia Nociception Index (MDMS, Loos, France) arm 2 : standard practice : remifentanil is administered using a target controlled device using a pK/pD model of Minto
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANI-loop<br>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<br>* experimental medical device using expert rules and continuous reading of heart rate, blood pressure and Analgesia Nociception Index for automatic remifentanil administration<br>Drug: Remifentanil<br>* 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.<br>Drug: Propofol<br>* 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<br>|
| Active Comparator: std_practice<br>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. | Device: remifentanil pK/pD target administration device<br>* standard practice, remifentanil administration using Minto's pK/pD model<br>Drug: Remifentanil<br>* 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.<br>Drug: Propofol<br>* 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<br>Device: ANI monitor<br>* ANI (Analgesia Nociception Index) value is used in the std_practice arm for guidance of the remifentanil Ce target<br>* Other names: PhysioDoloris (MDMS, Loos, France);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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general anesthesia, analgesia/nociception balance monitoring, expert system