Xenon-anesthesia on Patients Undergoing Major Liver-resection

Study Overview
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Brief Summary
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The aim of this study is to compare the postoperative outcome of patients undergoing major liver resection under xenon- compared to desflurane-anesthesia.

Detailed Description
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The aim of this study is to compare the postoperative liver function and additional outcome parameters of patients undergoing major liver resection under xenon- compared to desflurane-anesthesia. Xenon is known to maintain hemodynamic stability and consecutive tissue perfusion. Together with its potential for ischemic pre-conditioning, we hypothesize a protective effect of xenon on post-operative liver failure and ischemia/reperfusion injury.

Official Title
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Xenon-anesthesia on Patients Undergoing Major Liver-resection: Randomized Controlled Trial

Conditions
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Liver Function After Partial Liver Resection

Intervention / Treatment
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* Drug: Xenon
* Drug: Desflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 3 segments liver resection ≥ 18 years Both gender American Society of Anesthesiologists (ASA) classification I-III Written informed consent prior to study participation Exclusion Criteria: Subjects, fulfilling one or more of the following exclusion criteria will not be included in the study: Severe pulmonary or airway disease Severe liver disease, accompanied by a Child-Pugh class >A Allergy/hypersensitivity to study medications ASA ≥ IV Patients susceptible to malignant hyperthermia Women who are pregnant, breast-feeding or women of childbearing potential not using adequate contraceptive methods Patients with preeclampsia or eclampsia Patients legally unable to give written informed consent. Patients with risk of high oxygen demand Patient with seriously impaired cardiac function All contraindications for xenon anesthesia according to the summary of product characteristics LENOXe Patient participates in a parallel interventional clinical trial during this study or receives an investigational drug within 30 days prior to inclusion into this study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center, controlled, double-blinded, randomized, two-arm parallel, interventional clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xenon<br>Xenon concentration of 50-60 % will be used for maintenance of general anesthesia and will be adjusted to maintain Bispectral index (BIS) value between 40 and 60. | Drug: Xenon<br>* inhalation to maintain anesthesia<br>* Other names: LenoXe;|
| Active Comparator: Desflurane<br>Desflurane concentrations of 4-5%/0.8 minimum alveolar concentration (MAC) respectively will be used for maintenance of general anesthesia and will be adjusted to maintain BIS index value between 40 and 60. | Drug: Desflurane<br>* inhalation to maintain anesthesia<br>* Other names: Suprane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-course of postoperative liver injury and function | The primary study outcome is the difference in postoperative liver injury and function between the two study arms, measured by the perioperative time-course of the liver transaminase alanine-aminotransferase (ALAT) preoperative and on postoperative days (POD) 1-3, 5 and 7. | Within the first 7 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra- and postoperative blood loss | Difference of intra- and postoperative blood loss between the two study arms until discharge from ICU or POD 7 (whichever occurs first) | Surgery and ICU stay (maximum POD 7) | 
| Quantity of intra- and postoperative infusions | Difference in quantity of infused crystalloids abd colloids between the two study arms until discharge from ICU or POD 7 (whichever occurs first) | Surgery and ICU stay (maximum POD 7) | 
| Quantity of intra- and postoperative blood products | Difference in quantity of transfused packed red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrates between the two study arms until discharge from ICU or POD 7 (whichever occurs first) | Surgery and ICU stay (maximum POD 7) | 
| Quantity of intra- and postoperative coagulation products | Difference in quantity of administered tranexamic acid, fibrinogen and prothrombin complex concentrates between the two study arms until discharge from ICU or POD 7 (whichever occurs first) | Surgery and ICU stay (maximum POD 7) | 
| Necessity and duration of surgical pringle maneuver | Difference in necessity and duration of intraoperative pringle maneuver performed by the surgeon between study groups | Surgery | 
| Necessity and duration of surgical total vascular occlusion | Difference in necessity and duration of intraoperative total vascular occlusion performed by the surgeon between study groups | Surgery | 
| Surgery time | Difference in surgery time between study groups | Surgery | 
| Fibrosis in the resected liver tissue | Difference in fibrosis in the resected liver tissue between the two study arms | Surgery | 
| Number of hepatocytes in synthesis phase in the resected liver tissue | Difference in number of hepatocytes in synthesis phase in the resected liver tissue between the two study arms | Surgery | 
| Number of macrophages in the resected liver tissue | Difference in number of macrophages in the resected liver tissue between the two study arms | Surgery | 
| Expression of Interleukin 6 (IL-6) in the resected liver tissue | Difference in expression of Interleukin 6 (IL-6) in the resected liver tissue between the two study arms | Surgery | 
| Expression of tumor necrosis factor (TNF) in the resected liver tissue | Difference in expression of tumor necrosis factor (TNF) in the resected liver tissue between the two study arms | Surgery | 
| Expression of hepatocyte growth factor (HGF) in the resected liver tissue | Difference in expression of hepatocyte growth factor (HGF) in the resected liver tissue between the two study arms | Surgery | 
| Expression of epidermal growth factor (EGF) in the resected liver tissue | Difference in expression of epidermal growth factor (EGF) in the resected liver tissue between the two study arms | Surgery | 
| Expression of fibroblast growth factor (FGF) in the resected liver tissue | Difference in expression of fibroblast growth factor (FGF) in the resected liver tissue between the two study arms | Surgery | 
| Expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue | Difference in expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue between the two study arms | Surgery | 
| Weight of the resected liver tissue | Difference in weight of the resected liver tissue normalized to body weight (%BW) between the two study arms | Surgery | 
| Computer tomography-assisted planimetry of the resected liver tissue | Difference in area of the resected liver tissue, assessed with computer tomography assisted planimetry, between the two study arms | Surgery | 
| Time-course of hemoglobin (Hb) | Difference in laboratory data, measured by the time-course of hemoglobin (Hb), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of platelet count | Difference in laboratory data, measured by the time-course of platelet count, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of prothrombin time (PT) | Difference in laboratory data, measured by the time-course of prothrombin time (PT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of partial thromboplastin time (PTT) | Difference in laboratory data, measured by the time-course of partial thromboplastin time (PTT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of bilirubin | Difference in laboratory data, measured by the time-course of bilirubin, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of aspartate aminotransferase (ASAT) | Difference in laboratory data, measured by the time-course of aspartate aminotransferase (ASAT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of creatinine | Difference in laboratory data, measured by the time-course of creatinine, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of lactate | Difference in laboratory data, measured by the time-course of lactate, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of albumin | Difference in laboratory data, measured by the time-course of albumin, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Time-course of international normalized ratio (INR) | Difference in laboratory data, measured by the time-course of international normalized ratio (INR) levels, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first) | Within the first 7 postoperative days | 
| Postoperative peak of blood lactate | Difference in postoperative peak of blood lactate between the two study groups until discharge from ICU or POD 7 (whichever occurs first) | During ICU stay, maximum POD 7 | 
| Length of ICU stay | Difference in ICU length of stay between the two study arms | Until postoperative day 30 | 
| Length of hospital stay | Difference in hospital length of stay between the two study arms | Until postoperative day 30 | 
| Postoperative mortality | Difference in mortality between the two study arms until postoperative day 30 | Until postoperative day 30 | 
| Adverse events | Difference in quality and quantity of adverse events between the two study arms | Until postoperative day 30 | 
| Difference in mortality, assessed by 30 days follow up via phone | Difference in mortality between the two study arms | Postoperative day 30 | 
| Difference in coagulation disorder, assessed by 30 days follow up via phone | Difference in coagulation disorder between the two study arms | Postoperative day 30 | 
| Difference in re-admission to hospital, assessed by 30 days follow up via phone | Difference in re-admission to hospital between the two study arms | Postoperative day 30 | 
| Difference in other adverse events, assessed by 30 days follow up via phone | Difference in other adverse events between the two study arms | Postoperative day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xenon, Liver resection, post-operative liver failure, anesthetics, inhalation, Desflurane, Randomized controlled trail, RCT