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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Joel Avancini Rocha Filho, MD, PhD
- 電話番号：+55 11 981422500
- メール：joel.rocha@hc.fm.usp.br
研究連絡先のバックアップ
- 名前：Estela Regina Ramos Figueira, MD, PhD
- 電話番号：+55 11 999454871
- メール：estela.figueira@hc.fm.usp.br
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
|
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.
|
|
アクティブコンパレータ：Conventional Reperfusion
Standard liver transplantation without discarding the initial reperfusion blood.
|
Conventional liver transplantation without discarding the initial reperfusion blood.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Peak alanine aminotransferase (ALT)
時間枠：Within 72 hours after transplantation
|
Peak serum ALT level (U/L) as a biomarker of early graft injury following liver transplantation.
|
Within 72 hours after transplantation
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Arterial Pressure
時間枠：Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
Monitoring arterial pressure (systolic, diastolic e medium) Unit of Measure: mmHg.
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
|
Cardiac Rhythm
時間枠：Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
|
Cardiac rhythm monitoring with electrocardiography in ECG lead 2 and V5
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1
|
|
Cardiac Output
時間枠：Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
Monitoring continuous cardiac output.
Unit of Measure: L/min.
|
Intraoperative, during reperfussion, 30 minutes after reperfusion, and postoperative day 1.
|
|
Arterial serum potassium levels
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：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).
|
Intraoperative (at the start of surgery, 5 minutes after reperfusion, and at the end of surgery).
|
|
International normalized ratio (INR)
時間枠：Daily up to 72 hours after transplantation.
|
Assessment of graft function using international normalized ratio (INR).
|
Daily up to 72 hours after transplantation.
|
|
Aspartate aminotransferase levels (AST)
時間枠：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).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum Tumor Necrosis Factor-alpha (TNF-α)
時間枠：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).
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum B-type natriuretic peptide (BNP)
時間枠：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.
|
At the start of surgery, 30 minutes after reperfusion and postoperative day 1.
|
|
Serum creatinine levels
時間枠：Up to 30 days after transplantation.
|
Assessment of serum creatinine levels to evaluate renal function (Unit of measure: mg/dL),
|
Up to 30 days after transplantation.
|
|
Postoperative complications
時間枠：Within 30 days after transplantation.
|
Complications graded according to the Clavien-Dindo classification.
|
Within 30 days after transplantation.
|
|
ICU length of stay
時間枠：Up to 30 days after transplantation.
|
Days of length of stay in the intensive care unit.
|
Up to 30 days after transplantation.
|
|
Hospital length of stay
時間枠：Up to 30 days after transplantation.
|
Total hospital length of stay in days.
|
Up to 30 days after transplantation.
|
|
Arterial serum sodium levels
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
Perioperative changes in arterial pH units.
|
Intraoperative and daily from postoperative day 1 up to day 7.
|
|
Arterial serum bicarbonate
時間枠：Intraoperative and daily from postoperative day 1 up to day 7.
|
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
時間枠：Daily up to 72 hours after transplantation .
|
Assessment of graft function using Factor V activity levels measure as percentage.
|
Daily up to 72 hours after transplantation .
|
|
Alkaline phosphatase levels
時間枠：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),
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Gamma-glutamyl transferase levels
時間枠：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).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum ammonia levels
時間枠：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).
|
Daily up to 7 days and weekly up to 30 days after transplantation.
|
|
Serum urea levels
時間枠：Up to 30 days after transplantation.
|
Assessment of serum urea levels to evaluate renal function (Unit of measure: mg/dl),
|
Up to 30 days after transplantation.
|
|
Urine output
時間枠：Up to 30 days after transplantation.
|
Assessment of renal function measured by daily urine output.
|
Up to 30 days after transplantation.
|
|
Need for renal replacement therapy
時間枠：Up to 30 days after transplantation.
|
Need for renal replacement therapy (hemodialysis or continuous renal replacement therapy).
|
Up to 30 days after transplantation.
|
|
Serum Interleukin-6 (IL-6) levels
時間枠：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),
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum Tumor Necrosis Factor-alpha (TNF-α) levels
時間枠：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)
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
|
Serum Interleukin-17 (IL-17) levels
時間枠：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).
|
At the start of surgery, end of surgery, postoperative day 1, and postoperative day 3.
|
協力者と研究者
捜査官
- 主任研究者：Joel Avancini Rocha Filho, MD, PhD、Hospital das Clínicas, University of São Paulo Medical School
- スタディディレクター：Estela Regina Ramos Figueira, MD, PhD、Hospital das Clínicas, University of São Paulo Medical School
- スタディディレクター：Maria Jose Carvalho Carmona, MD, PhD、Hospital das Clínicas, University of São Paulo Medical School
- スタディディレクター：Wellington Andraus, MD, PhD、Hospital das Clínicas, University of São Paulo Medical School
- スタディディレクター：Rui Carlos Detsch Junior, MD、Hospital das Clínicas, University of São Paulo Medical School
- スタディディレクター：Luciana Bertocco Paiva Haddad, MD, PhD、Hospital das Clínicas, University of São Paulo Medical School
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 92854125.8.0000.0068
- 2025/09932-0 (その他の助成金/資金番号：São Paulo Research Foundation (FAPESP))
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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