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NCT Number: NCT07631689

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

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Reperfusion Blood Discard

Procedure

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.

Standard Liver Transplantation

Procedure

Conventional liver transplantation without discarding the initial reperfusion blood.

Primary outcomes

  1. Peak alanine aminotransferase (ALT)

    Time frame: Within 72 hours after transplantation

    Peak serum ALT level (U/L) as a biomarker of early graft injury following liver transplantation.

Secondary outcomes

  1. Arterial Pressure

    Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.

    Monitoring arterial pressure (systolic, diastolic e medium) Unit of Measure: mmHg.

  2. Cardiac Rhythm

    Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1

    Cardiac rhythm monitoring with electrocardiography in ECG lead 2 and V5

  3. Cardiac Output

    Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.

    Monitoring continuous cardiac output. Unit of Measure: L/min.

  4. Arterial serum potassium levels

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial potassium levels (Unit of measure: mEq/L).

  5. Blood coagulation thromboelastometry

    Time frame: Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).

    Assessment of intraoperative coagulation changes using rotational thromboelastometry (ROTEM), including EXTEM and FIBTEM parameters, and activated clotting time (ACT).

  6. International normalized ratio (INR)

    Time frame: Daily up to 72 hours after transplantation.

    Assessment of graft function using international normalized ratio (INR).

  7. Aspartate aminotransferase levels (AST)

    Time frame: Daily up to 7 days and weekly up to 30 days after transplantation.

    Assessment of graft injury using serum levels of AST (Unit of measure: U/L).

  8. Serum Tumor Necrosis Factor-alpha (TNF-α)

    Time frame: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.

    Serum levels of inflammatory mediator TNF-α (Unit of measure: pg/mL).

  9. Serum B-type natriuretic peptide (BNP)

    Time frame: At the start of surgery, 30 minutes after reperfusion and postoperative day 1.

    Assessment of BNP levels as a marker of cardiac hemodynamic stress. Unit of Measure: pg/mL.

  10. Serum creatinine levels

    Time frame: Up to 30 days after transplantation.

    Assessment of serum creatinine levels to evaluate renal function (Unit of measure: mg/dL),

  11. Postoperative complications

    Time frame: Within 30 days after transplantation.

    Complications graded according to the Clavien-Dindo classification.

  12. ICU length of stay

    Time frame: Up to 30 days after transplantation.

    Days of length of stay in the intensive care unit.

  13. Hospital length of stay

    Time frame: Up to 30 days after transplantation.

    Total hospital length of stay in days.

  14. Arterial serum sodium levels

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial serum sodium levels (Unit of measure: mEq/L).

  15. Arterial serum lactate levels

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial serum lactate levels (Unit of measure mg/dL),

  16. Arterial serum calcium levels

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial serum calcium levels (Unit of measure mg/dL),

  17. Serum glucose levels

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in serum glucose levels (Unit of measure: mg/dL).

  18. Arterial serum pH

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial pH units.

  19. Arterial serum bicarbonate

    Time frame: Intraoperative and daily from postoperative day 1 up to day 7.

    Perioperative changes in arterial serum bicarbonate (Unit of measure mmol/L)

  20. Factor V activity levels

    Time frame: Daily up to 72 hours after transplantation .

    Assessment of graft function using Factor V activity levels measure as percentage.

  21. Alkaline phosphatase levels

    Time frame: Daily up to 7 days and weekly up to 30 days after transplantation.

    Assessement of graft function using alkaline phosphatase levels (Unit of measure: U/L),

  22. Gamma-glutamyl transferase levels

    Time frame: Daily up to 7 days and weekly up to 30 days after transplantation.

    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).

  23. Serum ammonia levels

    Time frame: Daily up to 7 days and weekly up to 30 days after transplantation.

    Assessment of serum ammonia levels to evaluate liver function.(Unit of measure: mcmol/L).

  24. Serum urea levels

    Time frame: Up to 30 days after transplantation.

    Assessment of serum urea levels to evaluate renal function (Unit of measure: mg/dl),

  25. Urine output

    Time frame: Up to 30 days after transplantation.

    Assessment of renal function measured by daily urine output.

  26. Need for renal replacement therapy

    Time frame: Up to 30 days after transplantation.

    Need for renal replacement therapy (hemodialysis or continuous renal replacement therapy).

  27. Serum Interleukin-6 (IL-6) levels

    Time frame: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.

    Serum levels of inflammatory mediator IL-6 (Unit of measure: pg/mL),

  28. Serum Tumor Necrosis Factor-alpha (TNF-α) levels

    Time frame: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.

    Serum levels of inflammatory mediator TNF-α levels. (Unit of measure: pg/mL)

  29. Serum Interleukin-17 (IL-17) levels

    Time frame: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.

    Serum levels of inflammatory mediator IL-17 (Unit of measure: pg/mL).

Study contacts

Contact information is provided by the study sponsor or research team.

Estela Regina Ramos Figueira, MD, PhD

CONTACT

[email protected]

+55 11 999454871

Joel Avancini Rocha Filho, MD, PhD

CONTACT

[email protected]

+55 11 981422500

Sponsors and collaborators

Lead sponsor

University of Sao Paulo General Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jun 8, 2026
Registry last updated
Jun 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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