Xenon Combined With Intraoperative Thoracic Epidural Analgesia

Study Overview
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Brief Summary
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This is a monocentric study in 2 steps: A safety part to assess the feasibility of using Xenon in association with a thoracic epidural analgesia (TEA) with a sequential recruitment of 3, 6 or 9 patients according to predefined safety rules. The second part will randomly allocated patients (1:1) to receive TEA+Xenon or TEA+Desflurane. 28 patients will be enrolled and followed over 45 days.

Detailed Description
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The first step is divided into 3 parts. 9 patients will be sequentially enrolled (3 patients in each part). The patients will be followed during 45 days and the following rules will be used to assess the safety: First part: if no toxicity: initiation of the randomised part. If 1/3 toxicity: start of the second part. If 2 or 3/3 toxicity: end of the study. Second part: same rules and possible start of the third part. Third part: if no toxicity: initiation of the randomised part. If 1 or more toxicity: end of the study. The safety will be assessed after each part by an independent data safety monitoring board.

Official Title
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Phase II Study, Randomized, Monocentric, Single-blind, Comparing the Efficacy of Xenon and Desflurane, in Association With a Thoracic Epidural Analgesia in the Maintenance Phase of a Colorectal Oncologic Surgery

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Xenon
* Drug: Desflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years old Planned surgery for oncologic colic and/or rectal surgery ASA score I or II Indication of complementary thoracic epidural analgesia Agree to use an effective form of contraception Patients who can understand, read and write French language Covered by a medical insurance Patients who have dated/signed an inform consent Exclusion Criteria: Unstable angina within the 30 last days Myocardial infarction within 28 days prior to surgery Uncontrolled arterial high blood pressure Severe cardiac insufficiency Severe chronic obstructive pneumopathy Patient who requires FiO2 > 40% Patient already enrolled in a clinical study which may interfere with the present study Known hypersensitivity to one of the study drugs History or familial history of malignant hyperthermia Documented high intracranial pressure Eclampsia or pre-eclampsia Pregnant or breastfeeding woman Liver injury (icterus) and/or unexplained fever and/or eosinophilia after halogen exposure Failure in epidural anesthesia installation Patient refusal Patient who can't be compliant to the present protocol

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Desflurane<br>Desflurane 6.5% (+/-0.5%) in association with a thoracic epidural analgesia in maintenance phase | Drug: Desflurane<br> <br> |
| Experimental: Xenon<br>Xenon 60% (+/-5%) in association with a thoracic epidural analgesia in maintenance phase | Drug: Xenon<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of intraoperative Mean Arterial Pressure (MAP) | Variation between the Mean Arterial Pressure (MAP) at induction and the mean of intraoperative MAP values in each patient and comparaison between arms. | Maintenance phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of hemodynamic parameters (Systolic Ejection Volume, Heart rate, DeltaPP) | monitoring device (automatic recorder) | Throughout the maintenance of anesthesia, an expected average of 6 hours | 
| Delay from the surgery to the discharge date | Delay from the date of surgery to the date of hospital discharge (days) | from the surgery to the hospital discharge date | 
| Delay between the end of surgery and Post Anesthesia Care Unit's exit (min) | Delay between the end of surgery and Post Anesthesia Care Unit's exit (min) | from the end of surgery up to Post Anesthesia Care Unit's exit | 
| Total dose requirement of Vasopressive and hypotensive agents |  | Throughout the maintenance of anesthesia, an expected average of 6 hours | 
| Volume of each product infused |  | Throughout the maintenance of anesthesia, an expected average of 6 hours | 
| Total dose of morphine | Total dose of morphine required to maintain BIS between 40 and 60 (in mg/kg) | Throughout the maintenance of anesthesia, an expected average of 6 hours | 
| Quality of awaking | Modified Aldrete score and Recovery Index | 5 minutes after eyes opening | 
| Delay to oral feeding recovery | Time from the date of surgery to the date of first subsequent oral food intake | From surgery to oral feeding reintroduction | 
| Post-operative Adverse Events | Post-operative Adverse Events (according to the NCI-CTC version 4.03) | 45 days after surgery | 
| post-operative pain | Score to Visual Analog Scale | At entrance and exit of post operative room and 24 hours after the end of anesthesia | 
| Delay to intestinal transit recovery | Time from the date of surgery to the date of first postoperative stools | Time to postoperative stools | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anesthesia, epidural anagesia, colorectal surgery, xenon, hemodynamic change