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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 132
- Primary Endpoint
- Peak alanine aminotransferase (ALT)
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
This is an open-label study. Due to the nature of the surgical intervention, blinding is not feasible. Outcomes will be assessed using objective clinical and laboratory measures.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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
Intervention: Reperfusion Blood Discard (Procedure)
Conventional Reperfusion
Standard liver transplantation without discarding the initial reperfusion blood.
Intervention: Standard Liver Transplantation (Procedure)
Outcomes
Primary Outcomes
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
- Arterial Pressure(Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.)
- Arterial serum sodium levels(Intraoperative and daily from postoperative day 1 up to day 7.)
- Cardiac Rhythm(Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1)
- Cardiac Output(Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.)
- Arterial serum potassium levels(Intraoperative and daily from postoperative day 1 up to day 7.)
- Blood coagulation thromboelastometry(Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).)
- International normalized ratio (INR)(Daily up to 72 hours after transplantation.)
- Aspartate aminotransferase levels (AST)(Daily up to 7 days and weekly up to 30 days after transplantation.)
- Serum Tumor Necrosis Factor-alpha (TNF-α)(At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.)
- Factor V activity levels(Daily up to 72 hours after transplantation .)
- Serum B-type natriuretic peptide (BNP)(At the start of surgery, 30 minutes after reperfusion and postoperative day 1.)
- Serum creatinine levels(Up to 30 days after transplantation.)
- Postoperative complications(Within 30 days after transplantation.)
- ICU length of stay(Up to 30 days after transplantation.)
- Hospital length of stay(Up to 30 days after transplantation.)
- Arterial serum lactate levels(Intraoperative and daily from postoperative day 1 up to day 7.)
- Arterial serum calcium levels(Intraoperative and daily from postoperative day 1 up to day 7.)
- Serum glucose levels(Intraoperative and daily from postoperative day 1 up to day 7.)
- Arterial serum pH(Intraoperative and daily from postoperative day 1 up to day 7.)
- Arterial serum bicarbonate(Intraoperative and daily from postoperative day 1 up to day 7.)
- Alkaline phosphatase levels(Daily up to 7 days and weekly up to 30 days after transplantation.)
- Gamma-glutamyl transferase levels(Daily up to 7 days and weekly up to 30 days after transplantation.)
- Serum ammonia levels(Daily up to 7 days and weekly up to 30 days after transplantation.)
- Serum urea levels(Up to 30 days after transplantation.)
- Urine output(Up to 30 days after transplantation.)
- Need for renal replacement therapy(Up to 30 days after transplantation.)
- Serum Interleukin-6 (IL-6) levels(At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.)
- Serum Tumor Necrosis Factor-alpha (TNF-α) levels(At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.)
- Serum Interleukin-17 (IL-17) levels(At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.)
Investigators
Joel Avancini Rocha Filho
Collaborating Professor and Liver Transplant Anesthesia Supervisor, Hospital das Clínicas, University of São Paulo Medical School (HCFMUSP)
University of Sao Paulo General Hospital