Clinical trial NCT01696630: Xenon Combined With Intraoperative Thoracic Epidural Analgesia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: anesthesia, epidural anagesia, colorectal surgery, xenon, hemodynamic change
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2012-10-01
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Variation of intraoperative Mean Arterial Pressure (MAP)
timeFrame: Maintenance phase
Secondary outcomes:
measure: Measure of hemodynamic parameters (Systolic Ejection Volume, Heart rate, DeltaPP)
timeFrame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Delay from the surgery to the discharge date
timeFrame: from the surgery to the hospital discharge date
measure: Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)
timeFrame: from the end of surgery up to Post Anesthesia Care Unit's exit
measure: Total dose requirement of Vasopressive and hypotensive agents
timeFrame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Volume of each product infused
timeFrame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Total dose of morphine
timeFrame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Quality of awaking
timeFrame: 5 minutes after eyes opening
measure: Delay to oral feeding recovery
timeFrame: From surgery to oral feeding reintroduction
measure: Post-operative Adverse Events
timeFrame: 45 days after surgery
measure: post-operative pain
timeFrame: At entrance and exit of post operative room and 24 hours after the end of anesthesia
measure: Delay to intestinal transit recovery
timeFrame: Time to postoperative stools
Other outcomes:
Locations:
city: LYON Cedex 08
country: France
facility: Centre Léon Bérard
Study officials:
References:
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citation: Rasmussen LS, Schmehl W, Jakobsson J. Comparison of xenon with propofol for supplementary general anaesthesia for knee replacement: a randomized study. Br J Anaesth. 2006 Aug;97(2):154-9. doi: 10.1093/bja/ael141. Epub 2006 Jun 17.
citation: Salmi E, Laitio RM, Aalto S, Maksimow AT, Langsjo JW, Kaisti KK, Aantaa R, Oikonen V, Metsahonkala L, Nagren K, Korpi ER, Scheinin H. Xenon does not affect gamma-aminobutyric acid type A receptor binding in humans. Anesth Analg. 2008 Jan;106(1):129-34, table of contents. doi: 10.1213/01.ane.0000287658.14763.13.
citation: CULLEN SC, GROSS EG. The anesthetic properties of xenon in animals and human beings, with additional observations on krypton. Science. 1951 May 18;113(2942):580-2. doi: 10.1126/science.113.2942.580. No abstract available.
citation: Wappler F, Rossaint R, Baumert J, Scholz J, Tonner PH, van Aken H, Berendes E, Klein J, Gommers D, Hammerle A, Franke A, Hofmann T, Schulte Esch J; Xenon Multicenter Study Research Group. Multicenter randomized comparison of xenon and isoflurane on left ventricular function in patients undergoing elective surgery. Anesthesiology. 2007 Mar;106(3):463-71. doi: 10.1097/00000542-200703000-00010.
citation: Baumert JH, Hein M, Hecker KE, Satlow S, Schnoor J, Rossaint R. Autonomic cardiac control with xenon anaesthesia in patients at cardiovascular risk. Br J Anaesth. 2007 Jun;98(6):722-7. doi: 10.1093/bja/aem083. Epub 2007 Apr 27.
citation: Luttropp HH, Thomasson R, Dahm S, Persson J, Werner O. Clinical experience with minimal flow xenon anesthesia. Acta Anaesthesiol Scand. 1994 Feb;38(2):121-5. doi: 10.1111/j.1399-6576.1994.tb03852.x.
citation: Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P; Xenon Study Group. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology. 2003 Jan;98(1):6-13. doi: 10.1097/00000542-200301000-00005.
citation: Dupont J, Tavernier B, Ghosez Y, Durinck L, Thevenot A, Moktadir-Chalons N, Ruyffelaere-Moises L, Declerck N, Scherpereel P. Recovery after anaesthesia for pulmonary surgery: desflurane, sevoflurane and isoflurane. Br J Anaesth. 1999 Mar;82(3):355-9. doi: 10.1093/bja/82.3.355.
citation: Stuttmann R, Jakubetz J, Schultz K, Schafer C, Langer S, Ullmann U, Hilbert P. Recovery index, attentiveness and state of memory after xenon or isoflurane anaesthesia: a randomized controlled trial. BMC Anesthesiol. 2010 May 7;10:5. doi: 10.1186/1471-2253-10-5.
citation: Diemunsch P; Societe francaise d'anesthesie et de reanimation. [Conference of experts--short text. Management of postoperative nausea and vomiting. French Society of Anesthesia and Resuscitation]. Ann Fr Anesth Reanim. 2008 Oct;27(10):866-78. doi: 10.1016/j.annfar.2008.09.004. Epub 2008 Oct 25. No abstract available. French.