Clinical trial NCT01120743: Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Instability
Official title: Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Stability During Liver Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Transplantation
Keywords: liver failure
cytokines
hemodynamic instability
Lead sponsor: Penn State University
Sponsor class: OTHER
First posted: 2010-05-11
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study will include adult patients with end-stage liver disease accepted for liver transplantation.

Brief summary: The primary goal of this project is to identify the source of cytokines that are released into circulation during graft reperfusion. Seventeen patients scheduled to have adult cadaveric liver transplantation at the Milton S. Hershey Medical Center were contacted as prospective participants. Blood samples were obtained from the radial artery, the portal vein, and from the graft irrigation. The level of pro-inflammatory cytokines was verified and compared with the amount of catecholamines used to maintain hemodynamic stability.

Detailed description: Reperfusion of the graft is the most critical part of liver transplantation because of the difficulties in managing the resulting severe hemodynamic instability. The patients who are accepted to be listed for liver transplantation undergo evaluation of their cardiac function and are usually relatively stable with, at most, minimal cardiac problems (a requirement for inclusion in the liver transplantation program). Additionally, we observe completely unpredictable hemodynamic reactions during and after the graft reperfusion, requiring vastly different doses of catecholamine in order to maintain an acceptable level of perfusion pressure. The adverse cardiopulmonary effects are thought to be associated with the preexisting level of various proinflammatory factors, including cytokines (TNF-alpha, IL-6) and proinflammatory phospholipase A2 (sPLA2) produced in the graft as a reaction to the conservation solution and cold temperature (necessary to keep the organ capable for transplantation) and released into the bloodstream during reperfusion. The massive release of cytokines after unclamping of the graft may be responsible for negative inotropy and significant vasodilatation.

Eligibility criteria: Inclusion Criteria:

* All adult patients scheduled for liver transplantation will be offered the opportunity to participate in this research.

Exclusion Criteria:

* Patients unable or unwilling to provide adequate informed consent will be excluded.

Primary outcomes:
measure: Measurement of cytokine levels (TNF-alpha, IL-1, Il-2, IL-6, IL-8) in the portal vein, radial artery and "flush" (from irrigation of the liver used to remove preservation solution from the liver graft) blood.
timeFrame: A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion.
Secondary outcomes:
measure: Correlation between the level of cytokines and hemodynamic stability during reperfusion.
timeFrame: A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion.
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center, Penn State College of Medicine
state: Pennsylvania
Study officials:
affiliation: Penn State Milton S. Hershey Medical Center, Penn State College of Medicine
name: Dmitri Bezinover, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bezinover D, Kadry Z, McCullough P, McQuillan PM, Uemura T, Welker K, Mastro AM, Janicki PK. Release of cytokines and hemodynamic instability during the reperfusion of a liver graft. Liver Transpl. 2011 Mar;17(3):324-30. doi: 10.1002/lt.22227.