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

Official 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

Overview

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.

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.

Interventions

• 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.
• Procedure Standard Liver Transplantation
  Conventional liver transplantation without discarding the initial reperfusion blood.

Primary outcome measures

• Peak alanine aminotransferase (ALT) [Time frame: Within 72 hours after transplantation]

Secondary outcome measures (12)

• Arterial Pressure [Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.]
• Cardiac Rhythm [Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1]
• Cardiac Output [Time frame: Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.]
• Arterial serum potassium levels [Time frame: Intraoperative and daily from postoperative day 1 up to day 7.]
• Blood coagulation thromboelastometry [Time frame: Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).]
• International normalized ratio (INR) [Time frame: Daily up to 72 hours after transplantation.]
• Aspartate aminotransferase levels (AST) [Time frame: Daily up to 7 days and weekly up to 30 days after transplantation.]
• 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 B-type natriuretic peptide (BNP) [Time frame: At the start of surgery, 30 minutes after reperfusion and postoperative day 1.]
• Serum creatinine levels [Time frame: Up to 30 days after transplantation.]
• Postoperative complications [Time frame: Within 30 days after transplantation.]
• ICU length of stay [Time frame: Up to 30 days after transplantation.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07631689 · 92854125.8.0000.0068 · 2025/09932-0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗