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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
132
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.
Conventional liver transplantation without discarding the initial reperfusion blood.
Peak alanine aminotransferase (ALT)
Peak serum ALT level (U/L) as a biomarker of early graft injury following liver transplantation.
Time frame: Within 72 hours after transplantation
Arterial Pressure
Monitoring arterial pressure (systolic, diastolic e medium) Unit of Measure: mmHg.
Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
Cardiac Rhythm
Cardiac rhythm monitoring with electrocardiography in ECG lead 2 and V5
Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
Cardiac Output
Monitoring continuous cardiac output. Unit of Measure: L/min.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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),
Time frame: Up to 30 days after transplantation.
Postoperative complications
Complications graded according to the Clavien-Dindo classification.
Time frame: Within 30 days after transplantation.
ICU length of stay
Days of length of stay in the intensive care unit.
Time frame: Up to 30 days after transplantation.
Hospital length of stay
Total hospital length of stay in days.
Time frame: Up to 30 days after transplantation.
Arterial serum sodium levels
Perioperative changes in arterial serum sodium levels (Unit of measure: mEq/L).
Time frame: 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),
Time frame: 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),
Time frame: 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).
Time frame: Intraoperative and daily from postoperative day 1 up to day 7.
Arterial serum pH
Perioperative changes in arterial pH units.
Time frame: 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)
Time frame: 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.
Time frame: Daily up to 72 hours after transplantation .
Alkaline phosphatase levels
Assessement of graft function using alkaline phosphatase levels (Unit of measure: U/L),
Time frame: 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).
Time frame: 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).
Time frame: 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),
Time frame: Up to 30 days after transplantation.
Urine output
Assessment of renal function measured by daily urine output.
Time frame: Up to 30 days after transplantation.
Need for renal replacement therapy
Need for renal replacement therapy (hemodialysis or continuous renal replacement therapy).
Time frame: Up to 30 days after transplantation.
Serum Interleukin-6 (IL-6) levels
Serum levels of inflammatory mediator IL-6 (Unit of measure: pg/mL),
Time frame: 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)
Time frame: 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).
Time frame: At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
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