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Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study
BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoco...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444030/ https://www.ncbi.nlm.nih.gov/pubmed/36072778 http://dx.doi.org/10.2147/JIR.S377494 |
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author | Pande, Gaurav Hatti, Manjunath Rai, Mohit Kumar Rai, Praveer Kumar, Kamlesh VP, Krishna Nehra, Abhimanyu Kumar, Sudeep Ranjan Rout, Smarak Mishra, Sourav Kumar Kumar, Dinesh Kumar, Umesh Mishra, Prabhaker Majeed, Abdul Saraswat, Vivek Anand Singh, Kritika Singh, Harshit Misra, Durga Prasanna Agarwal, Vikas |
author_facet | Pande, Gaurav Hatti, Manjunath Rai, Mohit Kumar Rai, Praveer Kumar, Kamlesh VP, Krishna Nehra, Abhimanyu Kumar, Sudeep Ranjan Rout, Smarak Mishra, Sourav Kumar Kumar, Dinesh Kumar, Umesh Mishra, Prabhaker Majeed, Abdul Saraswat, Vivek Anand Singh, Kritika Singh, Harshit Misra, Durga Prasanna Agarwal, Vikas |
author_sort | Pande, Gaurav |
collection | PubMed |
description | BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. METHODS: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. RESULTS: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. CONCLUSION: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation. |
format | Online Article Text |
id | pubmed-9444030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-94440302022-09-06 Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study Pande, Gaurav Hatti, Manjunath Rai, Mohit Kumar Rai, Praveer Kumar, Kamlesh VP, Krishna Nehra, Abhimanyu Kumar, Sudeep Ranjan Rout, Smarak Mishra, Sourav Kumar Kumar, Dinesh Kumar, Umesh Mishra, Prabhaker Majeed, Abdul Saraswat, Vivek Anand Singh, Kritika Singh, Harshit Misra, Durga Prasanna Agarwal, Vikas J Inflamm Res Original Research BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. METHODS: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. RESULTS: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. CONCLUSION: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation. Dove 2022-09-01 /pmc/articles/PMC9444030/ /pubmed/36072778 http://dx.doi.org/10.2147/JIR.S377494 Text en © 2022 Pande et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Pande, Gaurav Hatti, Manjunath Rai, Mohit Kumar Rai, Praveer Kumar, Kamlesh VP, Krishna Nehra, Abhimanyu Kumar, Sudeep Ranjan Rout, Smarak Mishra, Sourav Kumar Kumar, Dinesh Kumar, Umesh Mishra, Prabhaker Majeed, Abdul Saraswat, Vivek Anand Singh, Kritika Singh, Harshit Misra, Durga Prasanna Agarwal, Vikas Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title | Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title_full | Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title_fullStr | Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title_full_unstemmed | Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title_short | Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study |
title_sort | response guided slow infusion of albumin, vasoconstrictors and furosemide improves ascites mobilization and survival in acute on chronic liver failure: a proof-of-concept study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444030/ https://www.ncbi.nlm.nih.gov/pubmed/36072778 http://dx.doi.org/10.2147/JIR.S377494 |
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