Nitrous Oxide - Sevoflurane-Remifentanil Interaction

Study Overview
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Brief Summary
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patients are allocated to one of the two study groups. In both groups a mixture of 60% nitrous oxide and 40% oxygen is administered through a face mask. In the first group the patient receives a constant concentration of sevoflurane. In this group the remifentanil concentration will be injected via an intravenous line in a step up protocol. In the second group remifentanil is injected in a fixed rate and sevoflurane is administered in a step up concentration. During the study, at predefined times, we will assess different levels of sedation (OAA/S score) and the reaction on tetanic stimulation of the ulnar nerve, insertion of a laryngeal mask airway and laryngoscopy. In addition heart rate, SpO2 and capnography will be recorded continuously and non invasive bloodpressure will be recorded using a 1 minute interval time. Spectral entropy and BIS derived from the frontal EEG will be used to monitor clinical cerebral drug effect. The null hypothesis is that remifentanil lowers the concentration of sevoflurane dissolved in a mixture of 60% nitrous oxide and 40% oxygen to (1) tolerate a specific stimulation and to (2) obtain a certain electroencephalographic parameter value and vice versa. Additionally the results of this study will be compared with a former interaction study of the same study group that did not involve nitrous oxide, in order to depict the shift in the response surface evoked by nitrous oxide.

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

Conditions
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ASA Class I/II Patients Scheduled for Surgery Under General Anesthesia

Intervention / Treatment
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* Drug: remifentanil injected
* Drug: sevoflurane in step up concentration


Participation Criteria
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Eligibility Criteria
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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, pulmonary disease, gastric diseases, endocrinological diseases recent use of psycho-active medication, including alcohol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: remifentanil injected<br>a mixture of 60% nitrous oxide and 40% oxygen is administered through a face mask. In the first group the patient receives a constant concentration of sevoflurane. In this group the remifentanil concentration will be injected via an intravenous line in a step up protocol. | Drug: remifentanil injected<br>* mixture of 60% nitrous oxide and 40% oxygen is administered through a face mask. In the first group the patient receives a constant concentration of sevoflurane. In this group the remifentanil concentration will be injected via an intravenous line in a step up protocol.<br>|
| Active Comparator: sevoflurane in step up concentration<br>a mixture of 60% nitrous oxide and 40% oxygen is administered through a face mask. remifentanil is injected in a fixed rate and sevoflurane is administered in a step up concentration. | Drug: sevoflurane in step up concentration<br>* of 60% nitrous oxide and 40% oxygen is administered through a face mask.remifentanil is injected in a fixed rate and sevoflurane is administered in a step up concentration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the pharmacodynamic interaction between nitrous oxide, sevoflurane and remifentanil | The interaction is studied on response surfaces including several clinical endpoints: the observer assessment of alertness and sedation scale, the heart rate, pulse oximetry, blood pressure, EEG and the derived parameters from it: spectral entropy and BIS | Every 12 minutes during induction and maintenance of anesthesia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASA class I/II patients, with surgery under general anesthesia