Effect of General Anesthesia and Mechanical Ventilation on Plasma Metabolite in Patient With Colorectal Cancer Resection

Study Overview
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Brief Summary
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As a newly developed subject, metabolomics can detect accurately and quantitatively small molecule metabolites such as proteins, carbohydrates and lipids from plasma, tissue and even single cell, which aims to analyze systemic dynamic change during physiological and pathological processes, and thus reveals certain reactions that whole organism responds to specific stimulation. Colorectal cancer is one of common gastrointestinal tumors, whose morbidity rate tends to increase in recent years for modern diet and life style, and colectomy serves as one standard treatment for it. Under total stimulation of surgical operation, general anesthesia and mechanical ventilation, a series of stress reactions happen complicatedly to colorectal patients during anesthesia-ventilation process. Without timely recognition and management of adverse reactions, side effects like hypoxemia, hemorrhage, inflammation, and even death will happen intraoperatively or postoperatively. With different metabolomics methods applied to collect, detect and analyze blood samples, metabolomics provides an innovatory approach to elucidate systemic response during anesthesia-colectomy process with multi-factors included. By analyzing and comparing dramatic alteration of small molecule metabolites in colorectal cancer patients' or healthy controls' plasma in this project, data can reflect the influence of certain disease (colorectal cancer), anesthetics and mechanical ventilation on colorectal patients with colectomy, which is helpful for prevention and treatment of intraoperative and postoperative complications.

Detailed Description
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Nowadays, more and more attention are paid to system biology and its relative techniques, such as gene sequencing，nuclear magnetic resonance， mass spectrometry and so on. As a newly developed subject, metabolomics can detect accurately and quantitatively small molecule metabolites such as proteins, carbohydrates and lipids from plasma, tissue and even single cell, which aims to analyze systemic dynamic change during physiological and pathological processes, and thus reveals certain reactions that whole organism responds to specific stimulation. Colorectal cancer is one of common gastrointestinal tumors, whose morbidity rate tends to increase in recent years for modern diet and life style, and colectomy serves as one standard treatment for it. Under total stimulation of surgical operation, general anesthesia and mechanical ventilation, a series of stress reactions happen complicatedly to colorectal patients during anesthesia-ventilation process. Without timely recognition and management of adverse reactions, side effects like hypoxemia, hemorrhage, inflammation, and even death will happen intraoperatively or postoperatively. With different metabolomics methods applied to collect, detect and analyze blood samples, metabolomics provides an innovatory approach to elucidate systemic response during anesthesia-colectomy process with multi-factors included. By analyzing and comparing dramatic alteration of small molecule metabolites in colorectal cancer patients' or healthy controls' plasma in this project, data can reflect the influence of certain disease (colorectal cancer), anesthetics and mechanical ventilation on colorectal patients with colectomy, which is helpful for prevention and treatment of intraoperative and postoperative complications.

Official Title
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Study on the Effect of Conventional General Anesthesia and Mechanical Ventilation on Plasma Small Molecule Metabolites in Patients With Colorectal Cancer Resection

Conditions
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Metabolomics

Intervention / Treatment
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* Other: colectomy, GA and MV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colorectal cancer patients inclusion criteria: undergo elective colectomy with general anesthesia and mechanical ventilation lasting for > 3.5 hours; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved. Healthy controls inclusion criteria: volunteers with regular physical examination in nearly three years；without chronic disease; without recent infection in three months; Written informed consent is approved. Exclusion Criteria: Distant metastases; hemodilution with massive fluid supply; recent anaesthetics or mechanical ventilation treatment；children；women during pregnancy or lactation; being involved in other clinical subjects.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients undergoing colectomy, GA and MV<br>venous blood samples collected from colorectal cancer patients undergoing selective colectomy with general anesthesia(GA) and mechanical ventilation(MV) before general anethesia and the third hour after | Other: colectomy, GA and MV<br>* general anesthesia protocol: anesthesia induction (midazolam 0.1mg/kg, sufentanil 0.5ug/kg, etomidate 0.3mg/kg, cisatracurium 0.2mg/kg); anesthesia maintenance [sevoflurane 1.5-3%, cisatracurium 0.1mg/kg/h, sufentanil is supplemented during the entire surgical procedure according to patients' anesthetic situation, dexmedetomidine（used conditionally）0.4ug/kg/h]. mechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cmH2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5.<br>|
| healthy controls<br>donated venous blood samples from healthy people undergoing physical examination but not general anesthesia or mechanical ventilation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolomics | Thaw Frozen plasma, add methanol and shake. Isolate supernatant after centrifugation. Employ Globle LC-Q-TOF-MS profiling to analyze metabolites of plasma via an Agilent-1200 LC system, coupled with an electrospray Ionization source and an Agilent-6520 Q-TOF mass spectrometry. Utilize Agilent's Mass Hunter Qualitative Analysis Software to process the MS spectra for peak detection, and generate a list detected peak intensities with the retention time-m/z data pairs as identiers. Process integrated raw RHPLC-Q-TOF-MS data with Agilent Mass Hunter Qualitative Analysis and Mass Profiler software. Optimize and choose parameters as follows: the range of m/z values from 80 to 100, and peak filters set to centroid height with > 100 counts, and compound filters set the base peak to > 1000 counts. MHD files will be create, containing compound IDs, and further processing will be performed with Mass Profiler software, which aligns mass features across multiple LC-MS data files. | Outcome measure will be assessed right after all samples are collected, which is expected to on May 5, 2017, and MHD files containing compound IDs, m/z values and so on will be reported about 10 days later. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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general anesthesia,mechanical ventilation,colectomy