The Medasense Study

Study Overview
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Brief Summary
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Despite various efforts there is still the need for adequate monitoring of pain and nociception during anesthesia. In a previous protocol the investigators measured pain responses during anesthesia based on single end-points, eg heart rate,blood pressure and pulse transit time. None of these parameters provided sufficient information regarding nociception. The investigators therefore want to further investigate this matter using a composite parameter, the Nociception Level or NoL. The NoL is a novel index that measures the magnitude of the autonomic response to painful stimuli. The NoL combines information from several physiological parameters, which represent different autonomic pathways. The multi-parameter approach empowered with state-of-the-art signal processing and machine learning techniques. In the current study the investigators will measure the NoL in ASA 1-3 patients undergoing elective surgery under general anesthesia. The investigators will measure NoL responses and the occurrence of patient movement upon the administration of a painful stimulus: Introduction of the laryngoscope, Insertion of the endotracheal tube, Insertion of the gastric tube, Insertion of the bladder catheter and Skin incision.

Official Title
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Measurement of Nociceptive Index During General Anesthesia in ASA 1-3 Patients Undergoing Elective Surgery Using the Nociception Level (NoL) Index

Conditions
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Pain

Intervention / Treatment
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* Drug: Propofol
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-80 years; Sex: male or female; Surgery: Any surgery under general anesthesia; ASA status: 1, 2 or 3. Exclusion Criteria: Age: < 18 or > 80 years; Unable to give written informed consent; Pregnancy/lactation; Extreme obesity: BMI > 35; Perceived difficult intubation. Patients requiring a rapid sequence induction Patients on beta-blockers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PROPOFOL ONLY GROUP<br>In this study group measurements will be obtained before intubation or opioid administration. To that end plasma propofol concentration will be increased slowly from 0 to 4 μg/ml in steps of 0.5 μg/mL. After the highest target is reached, the propofol target concentration will be lowered to get a BIS value of 50. After 5-min, the laryngoscope will be inserted into the mouth. Next the laryngoscope will be removed. After 5-min the laryngoscope will be placed again and the patient will be intubated. This will be done without additional administration of muscle relaxant. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;|
| Experimental: PROPOFOL + REMIFENTANIL TARGET A<br>The subject will be intubated according to the design of group 1. The propofol concentration will be 2-5 μg/kg, aimed at a BIS of 50, with 1 ng/ml remifentanil. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL + REMIFENTANIL TARGET B<br>The subject will be intubated according to the design of group 1. The propofol concentration will be 2-5 μg/kg, aimed at a BIS of 50, with 2 ng/ml remifentanil | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL + REMIFENTANIL TARGET C<br>The subject will be intubated according to the design of group 1. The propofol concentration will be 2-5 μg/kg, aimed at a BIS of 50, with 3 ng/ml remifentanil. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL + REMIFENTANIL TARGET D<br>The subject will be intubated according to the design of group 1. The propofol concentration will be 2-5 μg/kg, aimed at a BIS of 50, with 4 ng/ml remifentanil. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL + REMIFENTANIL TARGET E<br>The subject will be intubated according to the design of group 1. The propofol concentration will be 2-5 μg/kg, aimed at a BIS of 50, with 5 ng/ml remifentanil. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL TARGET BIS 30 + REMIFENTANIL TARGET C<br>The subject will be intubated according to the design of group 1. The remifentanil target will be 3 ng/ml remifentanil. The propofol concentration will aim a BIS of 30. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|
| Experimental: PROPOFOL TARGET BIS 70 + REMIFENTANIL TARGET C<br>The subject will be intubated according to the design of group 1. The remifentanil target will be 3 ng/ml remifentanil. The propofol concentration will aim a BIS 70. | Drug: Propofol<br>* Propofol will be titrated via a target controlled infusion to reach a specific target BIS (as specified in treatment arm)<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be provided by a target controlled infusion to a specific effect site concentration (as specified in treatment arm)<br>* Other names: Ultiva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nociception level index (NoI) | The NoL measures the magnitude of the autonomic responses to painful stimuli. The NoL combines information from several physiological parameters which represent different autonomic pathways. | Between induction and first incision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular parameters | Individual pain related cardiovascular parameters, as heart rate, blood pressure and PPG wave amplitude. | Between induction and first incision | 
| Movement | Visible occurence of movement during painfull stimuli. | Between induction and first incision | 
| Depth of anesthesia | Depth of anesthesia is measured by a Bispectral Index monitor. Changes in depth of anesthesia will be recorded during painfull stimuli | Between induction and first incision | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nociception, General anesthesia