Sevoflurane-Remifentanil Interaction: Multiple Response Surfaces, Validation of Calibration Stimuli, Validation of the Intraoperative Isobole Concept and Investigating Remifentanil Induced Opioid Tolerance

Study Overview
=================
Brief Summary
-----------------
During this study, the pharmacodynamic interactions between sevoflurane and remifentanil will be studied.

Official Title
-----------------
Sevoflurane-Remifentanil Interaction: Multiple Response Surfaces, Validation of Calibration Stimuli, Validation of the Intraoperative Isobole Concept and Investigating Remifentanil Induced Opioid Tolerance

Conditions
-----------------
Anesthesia

Intervention / Treatment
-----------------
* Drug: Fixed sevoflurane dose 1
* Drug: Fixed sevoflurane dose 2
* Drug: Fixed sevoflurane dose 3
* Drug: Fixed sevoflurane dose 4
* Drug: Fixed sevoflurane dose 5
* Drug: Fixed sevoflurane dose 6
* Drug: Fixed remifentanil dose 1
* Drug: Fixed remifentanil dose 2
* Drug: Fixed remifentanil dose 3
* Drug: Fixed remifentanil dose 4
* Drug: Fixed remifentanil dose 5
* Drug: Fixed remifentanil dose 6


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: American Society of Anesthesia class I and II patients Aged 18-60 years Scheduled for surgery under general anesthesia Exclusion Criteria: Weight less than 70% or more than 130% of ideal body weight Neurological disorder Diseases involving the cardiovascular system (hypertension, coronary artery disease, prior acute myocardial infarction (AMI), any valvular and/or muscular disease involving decrease of the ejection fraction, arrhythmias, which are either symptomatic or require continuous medication/pacemaker/automatic implantable cardioverter defibrillator [AICD]) Pulmonary disease including asthma, severe chronic obstructive pulmonary disease (COPD), etc. Gastric diseases including reflux, endocrinological diseases Recent use of psycho-active medication, including alcohol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Fixed sevoflurane dose 1 | Drug: Fixed sevoflurane dose 1<br>* Dose 1 of sevoflurane<br>|
| Experimental: 2<br>Fixed sevoflurane dose 2 | Drug: Fixed sevoflurane dose 2<br>* Dose 2 of sevoflurane<br>|
| Experimental: 3<br>Fixed sevoflurane dose 3 | Drug: Fixed sevoflurane dose 3<br>* Dose 3 of sevoflurane<br>|
| Experimental: 4<br>Fixed sevoflurane dose 4 | Drug: Fixed sevoflurane dose 4<br>* Dose 4 of sevoflurane<br>|
| Experimental: 5<br>Fixed sevoflurane dose 5 | Drug: Fixed sevoflurane dose 5<br>* Dose 5 of sevoflurane<br>|
| Experimental: 6<br>Fixed sevoflurane dose 6 | Drug: Fixed sevoflurane dose 6<br>* Dose 6 of sevoflurane<br>|
| Experimental: 7<br>Fixed remifentanil dose 1 | Drug: Fixed remifentanil dose 1<br>* Dose 1 of remifentanil<br>|
| Experimental: 8<br>Fixed remifentanil dose 2 | Drug: Fixed remifentanil dose 2<br>* Dose 2 of remifentanil<br>|
| Experimental: 9<br>Fixed remifentanil dose 3 | Drug: Fixed remifentanil dose 3<br>* Dose 3 of remifentanil<br>|
| Experimental: 10<br>Fixed remifentanil dose 4 | Drug: Fixed remifentanil dose 4<br>* Dose 4 of remifentanil<br>|
| Experimental: 11<br>Fixed remifentanil dose 5 | Drug: Fixed remifentanil dose 5<br>* Dose 5 of remifentanil<br>|
| Experimental: 12<br>Fixed remifentanil dose 6 | Drug: Fixed remifentanil dose 6<br>* Dose 6 of remifentanil<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG depression and arousal reactions in response to different clinically relevant stimuli |  | 60 to 90 minutes |