Effect of Discarding Initial Reperfusion Blood on Hemodynamics, Liver Function, and 30-Day Outcomes in Liver Transplantation

Assessment of the Impact of Discarding the Initial Reperfusion Blood on Early Liver Function, Cardiovascular and Metabolic Changes and on 30-Day Liver and Renal Outcomes. A Prospective Randomized Trial in Liver Transplantation

Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury.

Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may affect not only immediate intraoperative stability but also short- and long-term outcomes for both the patient and the graft.

The abrupt restoration of blood flow to the transplanted liver leads to the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, contributing to a systemic inflammatory response that may impact distant organs, including the kidneys and heart.

Several revascularization strategies have been investigated to mitigate reperfusion-related injury: initial reperfusion via the portal vein, initial reperfusion through the hepatic artery, and simultaneous reperfusion through the portal vein and hepatic artery.

A less frequently used and insufficiently studied strategy, not routinely or systematically implemented, involves diverting the initial reperfusion blood from the graft to the surgical field, followed by the restoration of hepatic blood outflow to the systemic circulation.

This study hypothesizes that discarding the initial reperfusion blood via the infrahepatic vena cava will attenuate early hemodynamic, metabolic, and inflammatory changes and reduce postoperative complications compared to conventional reperfusion techniques.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Transplantation; Ischaemia Reperfusion Injury; Perioperative Complications
• Intervention / Treatment: Procedure: Reperfusion Blood Discard; Procedure: Standard Liver Transplantation

Detailed Description

Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury.

Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may compromise immediate intraoperative stability and have been associated with adverse short- and long-term outcomes for both the recipient and the graft.

The abrupt restoration of blood flow to the transplanted liver results in the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, triggering a systemic inflammatory response that may extend beyond the liver and affect distant organs, including the kidneys and heart.

Several revascularization strategies have been investigated to mitigate reperfusion-related injury, including portal vein, hepatic artery, and simultaneous reperfusion approaches. However, none have consistently demonstrated a clear benefit in reducing ischemia-reperfusion injury or improving clinical outcomes. An alternative and less explored strategy involves diverting and discarding the initial reperfusion blood from the graft before restoring venous outflow to the systemic circulation.

Patients listed for liver transplantation at the study center will be systematically screened for eligibility. Written informed consent will be obtained from all eligible participants prior to enrollment, in accordance with institutional ethical standards.

This study is a prospective randomized clinical trial designed to evaluate whether discarding the initial reperfusion blood via the infrahepatic vena cava attenuates early hemodynamic, metabolic, and inflammatory disturbances and improves postoperative outcomes compared with conventional reperfusion techniques.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joel Avancini Rocha Filho, MD, PhD; Phone Number: +55 11 981422500; Email: joel.rocha@hc.fm.usp.br
• Study Contact Backup: Name: Estela Regina Ramos Figueira, MD, PhD; Phone Number: +55 11 999454871; Email: estela.figueira@hc.fm.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Candidates for liver transplantation at Hospital das Clínicas, University of São Paulo Medical School (HCFMUSP)
• Able to provide written informed consent

Exclusion Criteria:

• Inability to provide informed consent
• Previous liver surgery
• Fulminant hepatitis
• Specific liver diseases associated with severe electrolyte disturbances
• End-stage renal disease requiring dialysis
• Combined organ transplantation
• Living donor liver transplantation
• Liver retransplantation
• Highly sensitized patients with limited availability of blood products
• Hematologic diseases
• Portal vein thrombosis involving more than 50% of the lumen
• Portopulmonary hypertension (mean pulmonary artery pressure > 20 mmHg), diagnosed preoperatively or intraoperatively

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reperfusion Blood Discard; Liver transplantation with discarding of the initial 180 mL of reperfusion blood via the infrahepatic vena cava prior to restoration of hepatic blood outflow to the systemic circulation	Procedure: Reperfusion Blood Discard; Discarding of the initial 180 mL of reperfusion blood from the graft via the infrahepatic vena cava during liver transplantation prior to restoration of hepatic venous outflow to systemic circulation.
Active Comparator: Conventional Reperfusion; Standard liver transplantation without discarding the initial reperfusion blood.	Procedure: Standard Liver Transplantation; Conventional liver transplantation without discarding the initial reperfusion blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak alanine aminotransferase (ALT)	Peak serum ALT level (U/L) as a biomarker of early graft injury following liver transplantation.	Within 72 hours after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Pressure	Monitoring arterial pressure (systolic, diastolic e medium) Unit of Measure: mmHg.	Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
Cardiac Rhythm	Cardiac rhythm monitoring with electrocardiography in ECG lead 2 and V5	Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
Cardiac Output	Monitoring continuous cardiac output. Unit of Measure: L/min.	Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
Arterial serum potassium levels	Perioperative changes in arterial potassium levels (Unit of measure: mEq/L).	Intraoperative and daily from postoperative day 1 up to day 7.
Blood coagulation thromboelastometry	Assessment of intraoperative coagulation changes using rotational thromboelastometry (ROTEM), including EXTEM and FIBTEM parameters, and activated clotting time (ACT).	Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).
International normalized ratio (INR)	Assessment of graft function using international normalized ratio (INR).	Daily up to 72 hours after transplantation.
Aspartate aminotransferase levels (AST)	Assessment of graft injury using serum levels of AST (Unit of measure: U/L).	Daily up to 7 days and weekly up to 30 days after transplantation.
Serum Tumor Necrosis Factor-alpha (TNF-α)	Serum levels of inflammatory mediator TNF-α (Unit of measure: pg/mL).	At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
Serum B-type natriuretic peptide (BNP)	Assessment of BNP levels as a marker of cardiac hemodynamic stress. Unit of Measure: pg/mL.	At the start of surgery, 30 minutes after reperfusion and postoperative day 1.
Serum creatinine levels	Assessment of serum creatinine levels to evaluate renal function (Unit of measure: mg/dL),	Up to 30 days after transplantation.
Postoperative complications	Complications graded according to the Clavien-Dindo classification.	Within 30 days after transplantation.
ICU length of stay	Days of length of stay in the intensive care unit.	Up to 30 days after transplantation.
Hospital length of stay	Total hospital length of stay in days.	Up to 30 days after transplantation.
Arterial serum sodium levels	Perioperative changes in arterial serum sodium levels (Unit of measure: mEq/L).	Intraoperative and daily from postoperative day 1 up to day 7.
Arterial serum lactate levels	Perioperative changes in arterial serum lactate levels (Unit of measure mg/dL),	Intraoperative and daily from postoperative day 1 up to day 7.
Arterial serum calcium levels	Perioperative changes in arterial serum calcium levels (Unit of measure mg/dL),	Intraoperative and daily from postoperative day 1 up to day 7.
Serum glucose levels	Perioperative changes in serum glucose levels (Unit of measure: mg/dL).	Intraoperative and daily from postoperative day 1 up to day 7.
Arterial serum pH	Perioperative changes in arterial pH units.	Intraoperative and daily from postoperative day 1 up to day 7.
Arterial serum bicarbonate	Perioperative changes in arterial serum bicarbonate (Unit of measure mmol/L)	Intraoperative and daily from postoperative day 1 up to day 7.
Factor V activity levels	Assessment of graft function using Factor V activity levels measure as percentage.	Daily up to 72 hours after transplantation .
Alkaline phosphatase levels	Assessement of graft function using alkaline phosphatase levels (Unit of measure: U/L),	Daily up to 7 days and weekly up to 30 days after transplantation.
Gamma-glutamyl transferase levels	Assessment of liver function using serum levels of gamma-glutamyl transferase up to 7 days and weekly up to 30 days after transplantation (Unit of measure: U/L).	Daily up to 7 days and weekly up to 30 days after transplantation.
Serum ammonia levels	Assessment of serum ammonia levels to evaluate liver function.(Unit of measure: mcmol/L).	Daily up to 7 days and weekly up to 30 days after transplantation.
Serum urea levels	Assessment of serum urea levels to evaluate renal function (Unit of measure: mg/dl),	Up to 30 days after transplantation.
Urine output	Assessment of renal function measured by daily urine output.	Up to 30 days after transplantation.
Need for renal replacement therapy	Need for renal replacement therapy (hemodialysis or continuous renal replacement therapy).	Up to 30 days after transplantation.
Serum Interleukin-6 (IL-6) levels	Serum levels of inflammatory mediator IL-6 (Unit of measure: pg/mL),	At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
Serum Tumor Necrosis Factor-alpha (TNF-α) levels	Serum levels of inflammatory mediator TNF-α levels. (Unit of measure: pg/mL)	At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
Serum Interleukin-17 (IL-17) levels	Serum levels of inflammatory mediator IL-17 (Unit of measure: pg/mL).	At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Joel Avancini Rocha Filho, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School; Study Director: Estela Regina Ramos Figueira, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School; Study Director: Maria Jose Carvalho Carmona, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School; Study Director: Wellington Andraus, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School; Study Director: Rui Carlos Detsch Junior, MD, Hospital das Clínicas, University of São Paulo Medical School; Study Director: Luciana Bertocco Paiva Haddad, MD, PhD, Hospital das Clínicas, University of São Paulo Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: anesthesia; liver transplantation; hemodynamics; ischemia-reperfusion injury; perioperative complications; liver graft function; inflamatory response
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Reperfusion Injury
• Other Study ID Numbers: 92854125.8.0000.0068; 2025/09932-0 (Other Grant/Funding Number: São Paulo Research Foundation (FAPESP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to institutional and privacy considerations.

Drug and device information, study documents

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