Anesthetic Methods and Liver Transplantation

The Impact of Different Anesthetic Methods on Ischemia Reperfusion Injury Following Liver Transplantation

Postoperative pulmonary complications are not uncommon after liver transplantation. They can not only prolong the stay in intensive care unit and in hospital but also increase the morbidity and mortality rate. The underlying mechanisms are multifactorial, however, oxidative stress following hepatic ischemia reperfusion and the ensuing pulmonary leukocyte infiltration play an important part in the pulmonary complications. Various drugs and methods such as ischemic preconditioning have been used to lessen the production of oxidative free radicals following hepatic ischemia reperfusion. The choice of different anesthetic agents could aslo change the degree of production of oxygen species and antioxidant capacity during the operation.

Volatile and intravenous anesthetic agents can decrease oxidative injuries through different mechanisms, however, which is better in preventing the pulmonary leukocyte infiltration is still unknown.

We attempt the compare the oxidative stress and cytokine level in liver transplant recipients under desflurane or propofol anesthesia to evaluate which kind of anesthetic agent is better in this kind of surgery.

Study Overview

• Status: Unknown
• Conditions: Acute Lung Injury
• Intervention / Treatment: Drug: propofol during liver transplantation.; Drug: Desflurane during liver transplantation.

Detailed Description

The occurrence of postoperative pulmonary complications after hepatic reperfusion, such as in patients undergoing liver transplantation, is a major concern in the intensive care unit. Not only neutrophil infiltration, but also oxidative injuries, have been demonstrated after intra-operative hepatic ischemia/reperfusion (I/R) management. Previous studies have shown that reactive oxygen species (ROS) paly a major role in the ensuing damage, although I/R-induced remote organ injury is a complex and multifactorial process. Methods to reduce ROS generation, such as ischemic preconditioning, attenuate both liver and lung damage after hepatic I/R. Considering the intra-operative ROS production occurs after hepatic reperfusion , the choice of anesthetics may alter the magnitude of ROS production and the antioxidant capacity.

Volatile and non-volatile anesthetics can exert their antioxidant capacity through different mechanisms. Propofol (2,6-diisopropylphenol) has been reported to provide antioxidant capacity by scavenging free radicals. However, volatile anesthetics such as isoflurane, desflurane or sevoflurane can reduce the oxidative damage through anesthetic preconditioning. Several animal studies demonstrate that volatile anesthetics offer more protection against ischemia-reperfusion injury than intravenous anesthetics. On the contrary, intravenous anesthetics may be more protective against sepsis-induced hepatic injury than volatile anesthetics. However, there are few investigations concerning the effects of different anesthetics on remote pulmonary injuries in clinical settings.

In this study, propofol and desflurane will be used for the maintenance of anesthesia during liver transplantation. The heart function, respiratory function, liver function, kidney function, the oxidative injuries and inflammatory mediators will be compared between the two groups.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kuang Cheng Chan, M.D.; Phone Number: 62158 886-2-23123456; Email: jkjchan@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Department of Anesthesiology, NTUH, Taipei, Taiwan
    • Contact: Kuang Cheng Chan, M.D.
    • Principal Investigator: Kuang Cheng Chan, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• End stage liver disease scheduled for liver transplantation in National Taiwan University Hospital

Exclusion Criteria:

• Pre-existing pulmonary disease
• coma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: propofol; The anesthesia was maintained with propofol during liver transplantation.	Drug: propofol during liver transplantation.; The anesthesia was maintained with propofol during liver transplantation.; Other Names: propofol
Active Comparator: Desflurane; The anesthesia was maintained with desflurane during liver transplantation.	Drug: Desflurane during liver transplantation.; The anesthesia was maintained with desflurane during liver transplantation.; Other Names: Desflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of cardiac output perioperatively	Cardiac output(l/min) was measured by thermodilution method perioperatively.	one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lung injury score	PaO2/FiO2(Arterial oxygen tension/fraction of inspired oxygen)	one week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive oxygen species	Reactive oxygen species measured by chemiluminescence method	one week

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Publications and helpful links

General Publications

• Aduen JF, Stapelfeldt WH, Johnson MM, Jolles HI, Grinton SF, Divertie GD, Burger CD. Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation. Liver Transpl. 2003 Jul;9(7):764-71. doi: 10.1053/jlts.2003.50103.
• Wu CY, Cheng YJ, Hung MH, Lin IJ, Sun WZ, Chan KC. Association between Early Acute Respiratory Distress Syndrome after Living-Donor Liver Transplantation and Perioperative Serum Biomarkers: The Role of Club Cell Protein 16. Biomed Res Int. 2019 Apr 11;2019:8958069. doi: 10.1155/2019/8958069. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: August 27, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimate): September 6, 2013

Study Record Updates

• Last Update Posted (Estimate): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Liver transplantation, reactive oxygen species, antioxidant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Anesthetics, Inhalation; Hematinics; Propofol; Desflurane; Liver Extracts
• Other Study ID Numbers: 201003116M