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Orthotopic liver transplantation is the definitive treatment for end-stage liver failure, with renal failure being an important complication of this procedure that has implications for long- and short-term prognosis, affecting ICU stay and hospitalization time. Several studies have suggested that intravenous amino acids, particularly L-arginine, may have protective effects on renal function due to increased renal blood flow, which could be explained by enhanced production of nitric oxide among other mechanisms that are still unclear. In this context, we developed the hypothesis that the infusion of an amino acid solution in the perioperative period could reduce the incidence of acute renal failure in this group of patients; for this, we conducted a monocentric, analytical, prospective, interventional pilot study comparing standard treatment (in historically transplanted patients) with a group of patients who were administered amino acids in the perioperative period, considering that this medication is low-cost and has practically minimal side effects.
The primary objectives will be to measure the occurrence of acute kidney injury according to KDIGO criteria, evaluate the behavior of BUN and creatinine, as well as the initiation and duration of renal replacement therapy if necessary, use of vasopressors, diuresis, liver enzymes and bilirubin, lactate; this will be during the first 10 days postoperatively. Additionally, as a secondary objective, to measure all-cause mortality at 30 days. The study protocol must be approved by the institution's ethics committee. The treatment with amino acids will be carried out using Aminoven 10% from Fresenius Kabi available at the hospital. Fresenius Kabi has not had and will not have any role in the conception, development, data collection, and/or tabulation of data and/or publication of the results of this study. Data collection will be undertaken by specific personnel chosen from among those healthcare providers of liver transplantation, surgery, anesthesiology, and intensive care services.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amino acid interventión group | Experimental | Patients over 18 years old scheduled to undergo liver transplantation who are expected to have an ICU stay of at least 24 hours in the immediate postoperative period, regardless of the cause of liver failure and whether it was stable liver failure or acute on chronic liver failure. They will receive an intravenous infusion of a mixture of amino acids that includes L-arginine, at a dose of 2 g per kg of ideal body weight up to a maximum of 100 g per day, from their admission to the operating room until three days after the surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amino acid solution | Drug | Adult patients scheduled for orthotopic liver transplant to receive an intravenous infusion of a mixture of amino acids including L arginine, at a dose of 2 g per kg of ideal body weight up to a maximum of 100 g per day, from their admission to the operating room until three days after surgery; the infusion will begin in the operating room prior to the start of the surgery, will be administered through an exclusive lumen of a central venous catheter (CVC) immediately after the CVC is in place; the infusion will continue when the patient is in the intensive care unit (ICU); as soon as the patient begins enteral nutrition, the infusion will be reduced to meet the dose of 2 g per kg of protein intake per day up to a maximum of 100 g daily, until completing 72 H of infusion. The Control Group consists of previously transplanted patients at this institution who did not receive this type of therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| acute kidney failiure | measure the incidence of renal failure in the postoperative period of liver transplantation | During the first 10 days of the postoperative period |
| Measure | Description | Time Frame |
|---|---|---|
| liver function post Liver Transplant | serial measurement of liver enzymes and bilirubin, lactate. | For ten days after the postoperative period |
| Need for vasopressors | Doses of noradrenaline, adrenaline, and/or vasopressin |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| GUILLERMO A MOLINA, SPECIALIST IN CRITICAL CARE | Contact | 988258412 | guillermo.molina@sotero.cl |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Sotero Del Rio | Santiago | Puente ALTO | Chile |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38865168 | Background | Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, Brambillasca C, Garofalo E, Scandroglio AM, Viscido C, Paternoster G, Franco A, Porta S, Ferrod F, Calabro MG, Pisano A, Vendramin I, Barucco G, Federici F, Severi L, Belletti A, Cortegiani A, Bruni A, Galbiati C, Covino A, Baryshnikova E, Giardina G, Venditto M, Kroeller D, Nakhnoukh C, Mantovani L, Silvetti S, Licheri M, Guarracino F, Lobreglio R, Di Prima AL, Fresilli S, Labanca R, Mucchetti M, Lembo R, Losiggio R, Bove T, Ranucci M, Fominskiy E, Longhini F, Zangrillo A, Bellomo R; PROTECTION Study Group. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Engl J Med. 2024 Aug 22;391(8):687-698. doi: 10.1056/NEJMoa2403769. Epub 2024 Jun 12. | |
| 30685166 |
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REQUIRES NEW REVIEW BY THE ETHICS COMMITTEE
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| ID | Term |
|---|---|
| D017093 | Liver Failure |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D051437 | Renal Insufficiency |
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| ID | Term |
|---|---|
| C545824 | amino-acid, glucose, and electrolyte solution |
| D001120 | Arginine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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A pilot, prospective, non-randomized, analytical study with intervention, in which adult patients scheduled for orthotopic liver transplantation will be assigned to receive an intravenous infusion of a mixture of amino acids including L-arginine, at a dose of 2 g per kg of ideal body weight up to a maximum of 100 g per day, from their admission to the operating room until three days after the surgery. The infusion will begin in the operating room, prior to the start of the surgery, and will be performed through an exclusive lumen of a central venous catheter (CVC) immediately after the CVC is in place; the infusion will continue when the patient is in the intensive care unit (ICU); as soon as the patient begins enteral nutrition, the infusion will be reduced to meet the 2 g per kg of protein intake per day, up to a maximum of 100 g per day, until completing 72 hours of infusion. The control group consists of cases of previously transplanted patients.
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|
|
| Amino Acid infusion | Drug | adult patients scheduled for orthotopic liver transplant to receive an intravenous infusion of a mixture of amino acids including L arginine, at a dose of 2 g per kg of ideal body weight up to a maximum of 100 g per day, from their admission to the operating room until three days after surgery; the infusion will begin in the operating room prior to the start of the surgery, will be administered through an exclusive lumen of a central venous catheter (CVC) immediately after the CVC is in place; the infusion will continue when the patient is in the intensive care unit (ICU); as soon as the patient begins enteral nutrition, the infusion will be reduced to meet the dose of 2 g per kg of protein intake per day up to a maximum of 100 g daily, until completing 72 H of infusion. The Control Group consists of previously transplanted patients at this institution who did not receive this type of therapy. |
|
|
| For ten days postoperatively. |
| Mortality from all causes. | Mortality from all causes. | At 28 days |
| Background |
| Pu H, Doig GS, Heighes PT, Allingstrup MJ, Wang A, Brereton J, Pollock C, Chesher D, Bellomo R. Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial. J Thorac Cardiovasc Surg. 2019 Jun;157(6):2356-2366. doi: 10.1016/j.jtcvs.2018.11.097. Epub 2018 Dec 15. |
| 39384419 | Background | Pruna A, Losiggio R, Landoni G, Kotani Y, Redaelli MB, Veneziano M, Lee TC, Zangrillo A, Gaudino MFL, Bellomo R; for Protection Study group. Amino Acid Infusion for Perioperative Functional Renal Protection: A Meta-analysis. J Cardiothorac Vasc Anesth. 2024 Dec;38(12):3076-3085. doi: 10.1053/j.jvca.2024.08.033. Epub 2024 Aug 22. |
| 20965621 | Background | Hoffmann K, Buchler MW, Schemmer P. Supplementation of amino acids to prevent reperfusion injury after liver surgery and transplantation--where do we stand today? Clin Nutr. 2011 Apr;30(2):143-7. doi: 10.1016/j.clnu.2010.09.006. Epub 2010 Oct 20. |
| D007674 |
| Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000601 | Amino Acids, Essential |