Perioperative Epidural Anesthesia and Analgesia on Gut Microbiota

Study Overview
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Brief Summary
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As the only curative treatment for end-stage liver diseases, liver transplantation has been widely carried out around the world. The shortage of organs from deceased donors facilitate the adoption of living donor liver transplantation. Living donor hepatectomy is the most massive operation a healthy person could undergo, so donor safety is of utmost importance. However, previous studies focused on the outcomes of liver transplant recipients. There are still many uncertainties about the recovery in living liver donors. The body microorganisms that reside in the human intestinal tract, referred to as the gut microbiota, are essential to human metabolism and immunity. The physiological functions of microbiota include defense against pathogens, providing nutrients such as vitamin B12 folate and vitamin K, and modulating gut integrity and permeability. Despite relatively stable microbiota during life, different illnesses, surgeries, medications dietary factors, and lifestyle changes could contribute to the imbalance of ecosystems resulting many gastrointestinal and extra-gastrointestinal disorders. Many researches have established a relationship between the gut microbiome and patients with liver disease such as liver cirrhosis, alcoholic liver disease and obesity related liver diseases etc. These liver disorders are associated with bacterial overgrowth, dysbiosis, and increased intestinal permeability. However, the relationship between hepatectomy and microbiota has not been fully investigated, especially in healthy liver donors. Many routine perioperative management can impact the state of the microbiome and therefore can impact clinical outcomes, like bowel preparation and antibiotics. Potential factors affecting the gut microbiota also include perioperative manipulation, stress released hormones, and opioids. Maintenance of proper anesthetic depth is beneficial to attenuate surgical stress. However, general anesthesia including volatile anesthetics and opioids, is associated with altered gut microbiota. Therefore, regional anesthesia and analgesia which effectively attenuating surgical stress while efficiently reducing general anesthetics consumption, seem to provide promising advantages. Epidural analgesia has been proved to improve gastrointestinal function in major abdominal and thoracic surgery. However, the effect of perioperative epidural anesthesia and analgesia on microbiota is not clear.

Official Title
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The Effect of Perioperative Epidural Anesthesia and Analgesia on Gut Microbiota and Gastrointestinal Function Recovery in Living Donor Hepatectomy

Conditions
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Living Donor Hepatectomy

Intervention / Treatment
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* Procedure: Patient controlled epidural analgesia
* Drug: Intravenous patient controlled analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected to receive living liver hepatectomy in National Taiwan University Hospital, age between 20 and 55 years old. Exclusion Criteria: Previous use of antibiotics within four weeks. Previous gastrointestinal surgery.

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

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patient controlled epidural analgesia<br>Use of patient controlled epidural analgesia (PCEA) for postoperative pain control | Procedure: Patient controlled epidural analgesia<br>* Patient controlled epidural analgesia with marcaine 0.66mg/ml +fentanyl 1.75mcg/ml for postoperative pain control<br>* Other names: PCEA;|
| Sham Comparator: Intravenous patient controlled analgesia<br>Use of intravenous patient controlled analgesia(IVPCA) for postoperative pain control | Drug: Intravenous patient controlled analgesia<br>* Intravenous patient controlled analgesia with morphine 1mg/ml for postoperative pain control<br>* Other names: IVPCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota analysis | 16S metagenomic sequence processing | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPS-binding protein | LPS-binding protein(mcg/mL) | one month | 
| Intestinal fatty acid binding protein | Intestinal fatty acid binding protein(ng/mL) | one month | 
| IgA | IgA(mcg/mL) | one month | 
| IL-6 | IL-6(ng/mL) | one month | 
| I-FEED scoring | I-FEED scoring system for postoperative gastrointestinal function: Intake(score): tolerating oral diet(0), limited tolerance(1), complete Intolerance(3) Feeling nauseated(score): none(0), responsive to treatment(1), resistant to treatment(3) Emesis(score): none(0), ≧1 episode of low volume(<100mL) and none bilious(1), ≧1 episode of high volume(>100mL) or bilious(3) Exam(score): no distension(0), distension without tympany(1), significant distension with tympany(3) Duration of symptoms(score):0-24hours(0),24-72hours(1),>72hours(2) Total score: 0-2 normal, 3-5 postoperative GI intolerance, >6 postoperative GI dysfunction | one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epidural anesthesia, microbiota