Perioperative Epidural Anesthesia and Analgesia on Gut Microbiota

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

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.

Study Overview

• Status: Completed
• Conditions: Living Donor Hepatectomy
• Intervention / Treatment: Procedure: Patient controlled epidural analgesia; Drug: Intravenous patient controlled analgesia

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Department of Anesthesiology, National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Expected to receive living liver hepatectomy in National Taiwan University Hospital, age between 20 and 55 years old.

Exclusion Criteria:

1. Previous use of antibiotics within four weeks.
2. Previous gastrointestinal surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Kuang-Cheng Chan, M.D.,PhD, Department of Anesthesiology, Natioanal Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2019
• Primary Completion (Actual): September 25, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: microbiota; epidural anesthesia
• Additional Relevant MeSH Terms: Anesthesia and Analgesia; Analgesia; Analgesia, Patient-Controlled
• Other Study ID Numbers: 201812090RINC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No