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Bottari G, Taccone FS, Corrias A, Irrera M, Currao P, Salvagno M, Cecchetti C, Payen D. Immunomodulation in Pediatric Sepsis: A Narrative Review. J Clin Med 2025; 14:2983. [PMID: 40364014 PMCID: PMC12072531 DOI: 10.3390/jcm14092983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/16/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Pediatric sepsis presents a unique clinical challenge due to the distinct characteristics of the developing immune system. The immune response in children differs significantly from that in adults, exhibiting a unique combination of resistance, disease tolerance, and resilience. These factors influence the clinical presentation and prognosis of pediatric patients with sepsis. Over the past few years, various studies have explored the role of immunomodulatory therapies in managing sepsis, including the use of immunoglobulins, corticosteroids, monoclonal antibodies, and immunostimulatory treatments. However, the heterogeneity of the clinical presentations and individual responses makes it difficult to identify universally effective treatments. Recent research has highlighted the importance of a personalized approach based on specific biomarkers and patient phenotyping. Extracorporeal blood purification techniques have emerged as promising strategies for the modulation of hyperinflammation. However, strong evidence supporting their routine use in pediatric sepsis is lacking. This review provides a comprehensive overview of the current knowledge of the immune response in pediatric sepsis and discusses the main immunomodulatory strategies and future perspectives for personalized therapy. A deeper understanding of the immunological differences between children and adults could improve the prognosis and treatment efficacy, paving the way for new approaches to pediatric sepsis management.
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Affiliation(s)
- Gabriella Bottari
- Pediatric Intensive Care Unit, Children Hospital Bambino Gesù, IRCSS, 00165 Rome, Italy;
| | - Fabio Silvio Taccone
- Department of Intensive Care, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium; (F.S.T.); (M.S.)
| | - Angelica Corrias
- Pediatric Clinic, “Microcitemico—A. Cao” Pediatric Hospital, University of Cagliari, 09124 Cagliari, Italy; (A.C.); (P.C.)
| | - Mariangela Irrera
- Academy of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Paolo Currao
- Pediatric Clinic, “Microcitemico—A. Cao” Pediatric Hospital, University of Cagliari, 09124 Cagliari, Italy; (A.C.); (P.C.)
| | - Michele Salvagno
- Department of Intensive Care, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium; (F.S.T.); (M.S.)
| | - Corrado Cecchetti
- Pediatric Intensive Care Unit, Children Hospital Bambino Gesù, IRCSS, 00165 Rome, Italy;
| | - Didier Payen
- Université Paris Cité Sorbonne, 75006 Paris, France;
- Recherche Service Maladies Infectieuses, CHU de Nice, 06200 Nice, France
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Aidynbek Z, Kakenov E, Mironova O, Ydyrysheva K, Li T, Sazonov V. Extracorporeal Membrane Oxygenation in the Management of Tumor Lysis Syndrome in Children: A Review of Cases. J Clin Med 2025; 14:2771. [PMID: 40283601 PMCID: PMC12027803 DOI: 10.3390/jcm14082771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/11/2025] [Accepted: 04/15/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency that occurs in pediatric patients undergoing chemotherapy. Severe complications, including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and cardiogenic shock, may require extracorporeal membrane oxygenation (ECMO) support. Methods: This paper is a nonsystematic review of cases that synthesizes available case reports to evaluate the efficacy and outcomes of ECMO in pediatric TLS. Results: A systematic search identified five cases in which ECMO was used with a mean duration of 14 days. Survival rates were favorable and ECMO played a critical role in bridging these patients through multi-organ failure. Conclusions: While ECMO is a viable rescue therapy for severe TLS, associated complications, such as infections, bleeding, and neurological impairment, warrant careful patient selection and management. Future studies should explore standardized guidelines for the use of ECMO in pediatric oncology patients.
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Affiliation(s)
- Zere Aidynbek
- Department of Medicine, School of Medicine, Nazarbayev University, Kerey Zhanibek Handar Street 5/1, Astana Z05K4F4, Kazakhstan;
| | - Erken Kakenov
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Health Center, University Medical Center, Turan 32, Astana Z05G9F0, Kazakhstan
| | - Olga Mironova
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Health Center, University Medical Center, Turan 32, Astana Z05G9F0, Kazakhstan
| | - Karlygash Ydyrysheva
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Health Center, University Medical Center, Turan 32, Astana Z05G9F0, Kazakhstan
| | - Tatyana Li
- Department of Anesthesia and Intensive Care, Heart Center, University Medical Center, Turan 38, Astana Z05G9F9, Kazakhstan
| | - Vitaliy Sazonov
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Health Center, University Medical Center, Turan 32, Astana Z05G9F0, Kazakhstan
- Department of Surgery, School of Medicine, Nazarbayev University, Kerey Zhanibek Handar Street 5/1, Astana Z05K4F4, Kazakhstan
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Valenzuela Córdova R, Rivera Estrella D, Bernardo JF, Jiménez D, Rodríguez Tudero C, Elías R, De La Flor JC. Hemoadsorption in Multiorgan Failure Due to Viscerocutaneous Loxoscelism. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:143. [PMID: 39859124 PMCID: PMC11766656 DOI: 10.3390/medicina61010143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/02/2025] [Accepted: 01/14/2025] [Indexed: 01/30/2025]
Abstract
Background: The bite of the Loxosceles spider is a public health problem around the world, mainly in Latin America. The viscerocutaneous presentation is related to the inoculation of toxins (phospholipase-D) that generates a systemic inflammatory reaction with a subsequent increase in cytokines and chemokines. Hemoadsorption is proposed as a therapy that allows for the removal of the toxin and modulation of the inflammatory response in this disease. Case Report: We present the case of a 31-year-old woman who was admitted to the hospital due to decreased urinary flow and jaundice 48 h after a spider bite. Despite treatment with intravenous (IV) monovalent antiloxoscelism serum, antibiotic therapy, and corticosteroids, the patient's evolution was poor, and she was admitted to the critical care unit for severe multi-organ involvement, including hepatic and kidney damage and coagulation disorders, eventually requiring hemodialysis support and hemoadsorption therapy. After the therapy was administered, rapid improvement was evident with the suspension of vasopressor support and a decrease in inflammatory markers. Conclusions: This case presents hemoadsorption as a therapeutic option, based on its capacity to reduce the intensity of hyperinflammation and to regulate the immunological response.
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Affiliation(s)
- Raúl Valenzuela Córdova
- Department of Nephrology, Hospital Nacional Cayetano Heredia, Lima 15002, Peru; (R.V.C.); (D.R.E.); (J.F.B.); (R.E.)
- Faculty of Medicine, Peruana Cayetano Heredia University, Lima 15002, Peru
| | - David Rivera Estrella
- Department of Nephrology, Hospital Nacional Cayetano Heredia, Lima 15002, Peru; (R.V.C.); (D.R.E.); (J.F.B.); (R.E.)
- Faculty of Medicine, Peruana Cayetano Heredia University, Lima 15002, Peru
| | - José F. Bernardo
- Department of Nephrology, Hospital Nacional Cayetano Heredia, Lima 15002, Peru; (R.V.C.); (D.R.E.); (J.F.B.); (R.E.)
- Faculty of Medicine, Peruana Cayetano Heredia University, Lima 15002, Peru
| | | | - Celia Rodríguez Tudero
- Department of Nephrology, Hospital Universitario de Salamanca, 37007 Salamanca, Spain;
- Surgery Doctoral Program, Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain
| | - Raúl Elías
- Department of Nephrology, Hospital Nacional Cayetano Heredia, Lima 15002, Peru; (R.V.C.); (D.R.E.); (J.F.B.); (R.E.)
- Faculty of Medicine, Peruana Cayetano Heredia University, Lima 15002, Peru
| | - José C. De La Flor
- Department of Nephrology, Hospital Central de la Defensa Gómez Ulla, 28047 Madrid, Spain
- Health Sciences Doctoral Program, Faculty of Medicine, Alcala University, 28805 Madrid, Spain
- Department of Medicine and Medical Specialties, Faculty of Medicine, Alcala University, 28805 Madrid, Spain
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Bottari G, Ranieri VM, Ince C, Pesenti A, Aucella F, Scandroglio AM, Ronco C, Vincent JL. Use of extracorporeal blood purification therapies in sepsis: the current paradigm, available evidence, and future perspectives. Crit Care 2024; 28:432. [PMID: 39722012 PMCID: PMC11670469 DOI: 10.1186/s13054-024-05220-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/16/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Sepsis is the result of a dysregulated immune response to infection and is associated with acute organ dysfunction. The syndrome's complexity is contingent upon the underlying pathology and individual patient characteristics, including their immune response. The involvement of multiple organs and physiological functions adds complexity, with "organ cross-talk" emerging as a pivotal pathophysiological and clinical aspect. This narrative review to evaluate the rationale and available clinical evidence supporting the use of extracorporeal blood purification therapies as adjunctive therapy in patients with sepsis and septic shock. MAIN BODY A search of the PubMed, Embase, Web of Science and Scopus databases for relevant literature from August 2002 to May 2024 has been conducted. The search was performed using the terms: 1) "blood purification" or "hemadsorption" or "plasma exchange" AND 2) "sepsis" or "septic shock". Therefore the authors have focused our discussion on several key areas such as conducting well-designed trials, developing more personalized protocols, ensuring optimal management and monitoring. CONCLUSIONS Given the heterogeneity of patients with sepsis, conducting traditional randomized clinical trials in this domain can be a daunting task. However, statistical techniques such as Bayesian methods, propensity score analysis, and emulated clinical trials using clinical databases hold promise for enhancing comparability between the study groups. Indeed, to comprehend the clinical efficacy of extracorporeal blood purification techniques in patients with sepsis, it is imperative to assemble homogeneous groups of patients receiving uniform treatments. Clinical strategies should be individualized, signaling the end of the "one size fits all" approach in sepsis therapy and the need for personalized treatments.
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Affiliation(s)
- Gabriella Bottari
- Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Piazzale Sant'Onofrio 65, Rome, Italy.
| | - Vito Marco Ranieri
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University Aldo Moro Bari, Bari, Italy
- Department of Anesthesia and Critical Care Medicine, Policlinico Bari, Bari, Italy
| | - Can Ince
- Laboratory of Translational Intensive Care, Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Antonio Pesenti
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Filippo Aucella
- Nephrology and Dialysis Unit, Casa Solievo Della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | | | - Claudio Ronco
- International Renal Research Institute Vicenza, IRRIV, Vicenza, Italy
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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Ryazanova D, Tobylbayeva Z, Mironova O, Kakenov E, Sazonov V. Comparison of CytoSorb and Jafron HA330 Hemoadsorption Devices in Pediatric Oncological Patients with Sepsis: Retrospective Observational Study. J Clin Med 2024; 13:7694. [PMID: 39768616 PMCID: PMC11676993 DOI: 10.3390/jcm13247694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Pediatric sepsis presents a severe risk to immunocompromised children, especially those with cancer or pre-existing conditions, posing a significant threat to their lives. Cytokine hemadsorption has emerged as a promising therapeutic approach for managing sepsis and severe inflammatory conditions in critically ill patients. This innovative method involves eliminating pro-inflammatory cytokines from the bloodstream, targeting the underlying hyper-inflammatory response often seen in critical illnesses. Study aim: The study aim is to examine and compare the efficacy of HA330 and CytoSorb for extracorporeal blood purification in septic children with oncology. Methods: In this retrospective observational study, we examine 20 cases to assess the effectiveness of hemoperfusion therapy using hemoadsorption devices in pediatric septic patients with oncology. Our focus is on the use of HA330 and Cytosorb hemoadsorption devices, both designed to remove bacterial toxins and inflammatory agents from the bloodstream. Results: Our study reveals that hemoadsorption with HA330 and CytoSorb effectively treats septic children with oncological conditions. Conclusions: The presented findings suggest no statistically significant difference between the two devices in reducing the levels of the assessed parameters for extracorporeal blood purification in this patient population.
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Affiliation(s)
- Diana Ryazanova
- Department of Medicine, School of Medicine, Nazarbayev University, Astana Z05K4F4, Kazakhstan;
| | - Zaure Tobylbayeva
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Center, “University Medical Center”, Astana Z05K4F4, Kazakhstan
| | - Olga Mironova
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Center, “University Medical Center”, Astana Z05K4F4, Kazakhstan
| | - Erken Kakenov
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Center, “University Medical Center”, Astana Z05K4F4, Kazakhstan
| | - Vitaliy Sazonov
- Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Center, “University Medical Center”, Astana Z05K4F4, Kazakhstan
- Department of Surgery, School of Medicine, Nazarbayev University, Astana Z05K4F4, Kazakhstan
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Bellomo R, Ankawi G, Bagshaw SM, Baldwin I, Basu R, Bottari G, Cantaluppi V, Clark W, De Rosa S, Forni LG, Fuhrman D, Goldstein S, Gomez H, Husain-Syed F, Joannidis M, Kashani K, Lorenzin A, Mehta R, Murray PT, Murugan R, Ostermann M, Pannu N, Premuzic V, Prowle J, Reis T, Rimmelé T, Ronco C, Rosner M, Schneider A, See E, Soranno D, Villa G, Whaley-Connell A, Zarbock A. Hemoadsorption: consensus report of the 30th Acute Disease Quality Initiative workgroup. Nephrol Dial Transplant 2024; 39:1945-1964. [PMID: 38621759 DOI: 10.1093/ndt/gfae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Indexed: 04/17/2024] Open
Abstract
Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.
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Affiliation(s)
- Rinaldo Bellomo
- Department of Critical Care, The University of Melbourne, Melbourne, Australia
| | - Ghada Ankawi
- Department of Internal Medicine and Nephrology, Kind Abdulaziz University, Jeddah, Saudi Arabia
| | - Sean M Bagshaw
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Canada
| | - Ian Baldwin
- Department of Intensive Care and Clinical Research, Austin Hospital Health, Melbourne, Australia
| | - Rajit Basu
- Department of Critical Care Medicine, Luri Children's Hospital, Chicago, IL, USA
| | - Gabriella Bottari
- Pediatric Intensive Care Unit, Children Hospital Bambino Gesù, IRCSS, Rome, Italy
| | - Vincenzo Cantaluppi
- Nephrology and Kidney Transplantation Unit, University of Piemonte Orientale (UPO), AOU "Maggiore della Carità", Novara, Italy
| | - William Clark
- Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA
| | - Silvia De Rosa
- Centre for Medical Science - CISMed, University of Trento, Trento, Italy
| | - Lui G Forni
- Department of Critical Care, Royal Surrey Hospital Foundation Trust, Egerton Road, Guildford, Surrey, UK; School of Medicine, Faculty of Health Sciences, Kate Granger Building, University of Surrey, Guildford, Surrey, UK
| | - Dana Fuhrman
- Department of Critical Care Medicine and Pediatrics, Program for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Stuart Goldstein
- Department of Nephrology and Center for Acute Nephrology, University of Cincinnati Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Hernando Gomez
- Department of Critical Care, University of Pittsburgh Medical Centre, Pittsburgh, PA, USA
| | - Faeq Husain-Syed
- Department of Internal Medicine II, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany
| | - Michael Joannidis
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Kianoush Kashani
- Division of Nephrology and Hypertension, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Anna Lorenzin
- Department of Nephrology, Dialysis, and Transplantation, St Bortolo Hospital, Vicenza, Italy International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy
| | - Ravindra Mehta
- Department of Medicine, University of California at San Diego, San Diego, CA, USA
| | | | - Ragi Murugan
- Program for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Marlies Ostermann
- King's College London, Guy's & St Thomas' Hospital, Department of Critical Care, London, UK
| | - Neesh Pannu
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Vedran Premuzic
- Department of Nephrology, Hypertension, Dialysis and Transplantation, UHC Zagreb; School of Medicine, University of Zagreb, Zagreb, Croatia
| | - John Prowle
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Thomas Rimmelé
- Anesthesiology and Critical Care Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Claudio Ronco
- Department of Medcine, Padua University, Padua, Italy; Nephrology, Department of Nephrology, San Bortolo Hospital, Vicenza, Italy; International Renal Research Institute, Vicenza, Italy
| | - Mitch Rosner
- University of Virginia Health, Division of Nephrology, Charlottesville, VA, USA
| | - Antoine Schneider
- Adult Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Emily See
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia
| | - Danielle Soranno
- Indiana University School of Medicine, Departments of Pediatric, Pediatric Nephrology, Indianapolis, IN, USA; Purdue University, Department of Bioengineering, West Lafayette, IN, USA
| | - Gianluca Villa
- Department of Intensive Care, University of Florence, Florence, Italy
| | - Adam Whaley-Connell
- Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA; Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, MO, USA; Division of Nephrology and Hypertension, University of Missouri-Columbia School of Medicine, Columbia, MO, USA; Division of Endocrinology and Metabolism, University of Missouri Columbia School of Medicine, Columbia, MO, USA; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA
| | - Alexander Zarbock
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany; and Outcomes Research Consortium, Cleveland, OH, USA
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Li Y, Han M, Yang M, Su B. Hemoperfusion with the HA330/HA380 Cartridge in Intensive Care Settings: A State-Of-The-Art Review. Blood Purif 2024; 54:122-137. [PMID: 39571561 DOI: 10.1159/000542469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 11/01/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND Hemoperfusion with the HA330/HA380 cartridge has markedly evolved during the past decade and has thus been widely used in intensive care settings to treat critical or hyperinflammatory illnesses. Numerous clinical studies have demonstrated that HA330/HA380 hemoperfusion might mitigate systemic inflammatory response syndrome and organ dysfunction in ICU patients by removing inflammatory mediators and metabolic toxins from the blood. However, there is currently lacking a systematic evaluation on the safety and efficacy of HA330/HA380 hemoperfusion in intensive care settings. SUMMARY We searched the PubMed database, Chinese Clinical Trial Registry, and ClinicalTrials.gov for articles published from inception to June 20, 2024 (updated on September 10, 2024) to perform a state-of-the-art review of HA330/HA380 hemoperfusion in daily critical care practice. We discuss the basic technique characteristics and ex vivo investigations of the HA330/HA380 cartridge and summarize the latest clinical evidence regarding the use of HA330/HA380 hemoperfusion for the treatment of sepsis, severe COVID-19, cardiac surgery, acute pancreatitis, liver failure, and blunt trauma. Ex vivo studies suggest that the HA330/HA380 cartridge demonstrates satisfactory biocompatibility and substantial adsorption capacity for inflammatory cytokines, such as interleukin-6, interleukin-10, and tumor necrosis factor-α. Small-scale clinical studies indicate that HA330/HA380 hemoperfusion may help reduce plasma levels of inflammatory mediators, alleviate organ dysfunction, and improve survival in some critically ill patients with sepsis, severe COVID-19, acute pancreatitis, and blunt trauma. KEY MESSAGES (i) The HA330/HA380 cartridge contains abundant, coated, biocompatible sorbent beads made of styrene-divinylbenzene copolymers. (ii) HA330/HA380 hemoperfusion, with or without combined continuous renal replacement therapy, is a promising treatment option for some critically ill patients by removing proinflammatory mediators and alleviating organ dysfunction. (iii) The HA330/HA380 cartridge may adversely adsorb antibiotics, and appropriate antibiotic dosing adjustment and plasma drug level monitoring is recommended. (iv) There are currently numerous ongoing clinical trials evaluating the safety and efficacy of HA330/HA380 hemoperfusion in critically ill patients who develop sepsis or undergo cardiopulmonary bypass, which will certainly sharpen our future practice of HA330/HA380 hemoperfusion in ICU.
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Affiliation(s)
- Yupei Li
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China,
| | - Mei Han
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China
| | - Mei Yang
- Department of Nephrology, The First People's Hospital of Shuangliu District, Chengdu, China
| | - Baihai Su
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China
- Med+ Biomaterial Institute of West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
- Med-X Center for Materials, Sichuan University, Chengdu, China
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8
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Chen H, Liu S, Fang G. Knockdown of OLFM4 protects cardiomyocytes from sepsis by inhibiting apoptosis and inflammatory responses. Allergol Immunopathol (Madr) 2024; 52:15-20. [PMID: 39278846 DOI: 10.15586/aei.v52i5.1145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 08/04/2024] [Indexed: 09/18/2024]
Abstract
Sepsis is a systemic inflammatory response that can result in cardiac insufficiency or heart failure known as septic myocardial injury. A previous study identified OLFM4 as an important gene in sepsis through bioinformatics analysis. However, there is limited research on the regulatory functions of OLFM4 in sepsis-triggered myocardial injury, and the related molecular mechanisms remain unclear. In this study, the protein expression of OLFM4 was found to be significantly elevated in LPS-stimulated H9C2 cells, and its suppression enhanced cell proliferation and reduced cell apoptosis in LPS-triggered H9C2 cells. The inflammatory factors TNF-α, IL-6, and IL-1β were increased after LPS treatment, and these effects were mitigated after silencing OLFM4. Moreover, it was confirmed that inhibition of OLFM4 attenuated the NF-κB signaling pathway. In conclusion, the knockdown of OLFM4 protected cardiomyocytes from sepsis by inhibiting apoptosis and inflammatory responses via the NF-κB pathway. These findings provide important insights into the regulatory functions of OLFM4 in the progression of septic myocardial injury.
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Affiliation(s)
- Hailu Chen
- Department of Infectious Diseases and Tropical Diseases, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Shuna Liu
- Department of Infectious Diseases and Tropical Diseases, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Guihua Fang
- Department of Infectious Diseases and Tropical Diseases, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;
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9
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Zhou J, Li H, Zhang L, Chen G, Wang G, Zhu H, Hao Y, Wu G. Removal of inflammatory factors and prognosis of patients with septic shock complicated with acute kidney injury by hemodiafiltration combined with HA330-II hemoperfusion. Ther Apher Dial 2024; 28:460-466. [PMID: 38317412 DOI: 10.1111/1744-9987.14108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 01/08/2024] [Accepted: 01/12/2024] [Indexed: 02/07/2024]
Abstract
INTRODUCTION To explore the effect of CRRT using CVVHDF + HP on the removal of inflammatory mediators in patients with septic shock complicated with AKI. METHODS A total of 20 patients between January 1, 2018, and December 31, 2021, were included. The patients were randomly divided into the treatment group (CVVHDF + HP) and the control group (CVVHDF). Changes in inflammatory factors, including IL-1β, IL-6, IL-8, TNF-α, PCT, and CRP were compared. Other observed measures were also analyzed, for example, Lac, Scr, BUN, SOFA, and norepinephrine (NE) dosage. The clinical outcomes of both groups were followed up for 28 days. RESULTS The IL-6 and PCT levels in the treatment group were significantly lower (p = 0.005, 0.007). Although the IL-1β, TNFα, and CRP levels in the treatment group decreased, there were no statistical differences (p > 0.05). There were significant differences in Lac, SOFA, and NE dosage levels between both groups (p = 0.023, 0.01, 0.023). Survival analysis showed that the 28-day survival rate was significantly higher in the treatment group. CONCLUSION CRRT using CVVHDF+HP can effectively remove inflammatory factors and improve the prognosis of patients.
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Affiliation(s)
- Juan Zhou
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Haopeng Li
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lei Zhang
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guangjian Chen
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Gang Wang
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - HuiHui Zhu
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yingxin Hao
- Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Gang Wu
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
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10
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Zikou X, Vaia D, Vasiliki P, Panagiotis C, Stavros A. Use of Therapeutic Apheresis methods in ICU. Transfus Apher Sci 2024; 63:103853. [PMID: 38049358 DOI: 10.1016/j.transci.2023.103853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.
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11
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Parrey AH, Koka M, Kassana B, Ismail M. Procalcitonin and qSOFA as a Marker of Mortality in Sepsis. Rev Recent Clin Trials 2024; 19:196-203. [PMID: 38644718 DOI: 10.2174/0115748871288534240322083746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 04/23/2024]
Abstract
BACKGROUND Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The qSOFA and procalcitonin are currently used for both diagnostic as well as prognostic purposes. OBJECTIVE To explore the combined use of day one procalcitonin level and qSOFA scores for prognostication of sepsis-related mortality. DESIGN This was a prospective observational study. PARTICIPANTS All patients who fulfilled the inclusion criteria for sepsis with an age of more than 16 years were enrolled in the study. RESULTS In this study of 211 patients, 15 patients died (7.1%) during hospital stay. Among the 15 patients who died, the highest mortality of 29.4% was seen in patients with qSOFA of "3", qSOFA of "2" had a mortality of 12.8%, qSOFA of "1" had a mortality of 1% and qSOFA of "0" had zero mortality. In this study, procalcitonin had a statistically significant positive correlation/association with both qSOFA and mortality. CONCLUSION The qSOFA and procalcitonin at presentation to the emergency department in septic patients have a significant correlation with mortality in patients hospitalized with sepsis. Obtaining these two parameters at presentation will help in managing aggressively these patients who at presentation have higher qSOFA and procalcitonin levels.
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Affiliation(s)
| | - Manzoor Koka
- Internal Medicine Government Medical College, Srinagar, India
| | | | - Mohd Ismail
- Internal Medicine Government Medical College, Srinagar, India
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12
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Li Z, Zhang F, Sun M, Liu J, Zhao L, Liu S, Li S, Wang B. The modulatory effects of gut microbes and metabolites on blood–brain barrier integrity and brain function in sepsis-associated encephalopathy. PeerJ 2023; 11:e15122. [PMID: 37009158 PMCID: PMC10064995 DOI: 10.7717/peerj.15122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/03/2023] [Indexed: 03/30/2023] Open
Abstract
Background
Intestinal microbiota homeostasis and the gut-brain axis are key players associated with host health and alterations in metabolic, inflammatory, and neurodegenerative disorders. Sepsis-associated encephalopathy (SAE), which is closely associated with bacterial translocation, is a common secondary organ dysfunction and an urgent, unsolved problem affecting patient quality of life. Our study examined the neuroprotective effects of the gut microbiome and short-chain fatty acid (SCFA) metabolites on SAE.
Methods
Male C57BL/6 mice were administered SCFAs in drinking water, then subjected to cecal ligation and puncture (CLP) surgery to induce SAE. 16S rRNA sequencing was used to investigate gut microbiome changes. The open field test (OFT) and Y-maze were performed to evaluate brain function. The permeability of the blood–brain barrier (BBB) was assessed by Evans blue (EB) staining. Hematoxylin and eosin (HE) staining was used to examine intestinal tissue morphology. The expression levels of tight junction (TJ) proteins and inflammatory cytokines was assessed by western blots and immunohistochemistry. In vitro, bEND.3 cells were incubated with SCFAs and then with lipopolysaccharide (LPS). Immunofluorescence was used to examine the expression of TJ proteins.
Results
The composition of the gut microbiota was altered in SAE mice; this change may be related to SCFA metabolism. SCFA treatment significantly alleviated behavioral dysfunction and neuroinflammation in SAE mice. SCFAs upregulated occludin and ZO-1 expression in the intestine and brain in SAE mice and LPS-treated cerebromicrovascular cells.
Conclusions
These findings suggested that disturbances in the gut microbiota and SCFA metabolites play key roles in SAE. SCFA supplementation could exert neuroprotective effects against SAE by preserving BBB integrity.
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Affiliation(s)
- Zhaoying Li
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
- Institute of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Fangxiang Zhang
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Meisha Sun
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Jia Liu
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Li Zhao
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Shuchun Liu
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Shanshan Li
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
| | - Bin Wang
- Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
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13
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Mehta Y, Paul R, Ansari AS, Banerjee T, Gunaydin S, Nassiri AA, Pappalardo F, Premužić V, Sathe P, Singh V, Vela ER. Extracorporeal blood purification strategies in sepsis and septic shock: An insight into recent advancements. World J Crit Care Med 2023; 12:71-88. [PMID: 37034019 PMCID: PMC10075046 DOI: 10.5492/wjccm.v12.i2.71] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/05/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Despite various therapies to treat sepsis, it is one of the leading causes of mortality in the intensive care unit patients globally. Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies (ECT) which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.
AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.
METHODS In this review, an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis. A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.
RESULTS Results showed that ECT techniques such as high-volume hemofiltration, coupled plasma adsorption/filtration, resin or polymer adsorbers, and CytoSorb® are emerging as adjunct therapies to improve hemodynamic stability in sepsis. CytoSorb® has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores, lactate levels, total leucocyte count, platelet count, interleukin- IL-6, IL-10, and TNF levels.
CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials. In addition to patient-tailored therapies, future research developments with therapies targeting the cellular level of the immune response are expected.
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Affiliation(s)
- Yatin Mehta
- Institute of Critical Care and Anesthesiology, Medanta the Medicity, Gurugram 12201, India
| | - Rajib Paul
- Department of Internal Medicine, Apollo Hospitals, Jubilee Hills, Hyderabad 500033, India
| | - Abdul Samad Ansari
- Department of Critical Care, Nanavati Max Super Specialty Hospital, Mumbai 400065, India
| | - Tanmay Banerjee
- Department of Internal Medicine & Critical Care, Medica Institute of Critical Care Medicine, Medica Superspecialty Hospital, Kolkata 700099, India
| | - Serdar Gunaydin
- Department of Cardiovascular Surgery, University of Health Sciences, Ankara City Hospital Campus, Ankara 06933, Turkey
| | - Amir Ahmad Nassiri
- Department of Nephrology, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Federico Pappalardo
- Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria 15121, Italy
| | - Vedran Premužić
- Department of Nephrology, Clinical Hospital Zagreb, Clinic for internal diseases, Zagreb 10000, Croatia
| | - Prachee Sathe
- Department of Critical Care Medicine, D.Y. Patil Medical College, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Pune 411018, India
| | - Vinod Singh
- Department of Critical Care Medicine, Institute of critical care Medicine, Hospital Name - Sir Ganga Ram Hospital, New Delhi 110001, India
| | - Emilio Rey Vela
- Cardiac Surgery Intensive Care Unit, Samaritan University Hospital, Bogotá 11, Colombia
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14
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Wang S, Chen Y. Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-ĸB/STAT3 axis. Allergol Immunopathol (Madr) 2022; 50:39-46. [PMID: 36086962 DOI: 10.15586/aei.v50i5.626] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023]
Abstract
Sepsis induces multiple organ dysfunction syndromes, such as acute kidney, liver, or lung injury. Septic lung injury is associated with excessive apoptosis and inflammatory responses in hepatocytes. Deoxyelephantopin is a sesquiterpene lactone found in Elephantopus scaber L, and has immunomodulatory, antibacterial, anti-inflammatory, and antifungal properties. The role of deoxyelephantopin in sepsis-associated lung injury was investigated. First, human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were treated with lipopolysaccharide to induce cytotoxicity. Treatment with lipopolysaccharide reduced cell viability of BEAS-2B and HPAEC, and promoted cell apoptosis through down-regulation of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma 2 (Bcl-2), and up-regulation of cleaved PARP and B-cell lymphoma-associated X protein (Bax). Second, lipopolysaccharide-treated BEAS-2B and HPAEC were incubated with increasing concentrations of deoxyelephantopin, that is, 1, 5, or 10 μM. Deoxyelephantopin enhanced cell viability and reduced cell apoptosis of lipopolysaccharide-treated BEAS-2B and HPAEC. Third, deoxyelephantopin attenuated lipopolysaccharide-induced decrease of superoxide dismutase and glutathione, and increase of malondialdehyde and myeloperoxidase in BEAS-2B and HPAEC. Moreover, deoxyelephantopin also weakened lipopolysaccharide-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, deoxyelephantopin decreased protein expression of p-p65 and p-signal transducer and activator of transcription 3 (STAT3) in lipopolysaccharide-treated BEAS-2B and HPAEC. In conclusion, deoxyelephantopin exhibited anti-oxidative and anti-inflammatory effects against lipopolysaccharide-treated BEAS-2B and HPAEC through inactivation of nuclear factor kappa B/STAT3 signaling.
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Affiliation(s)
- Shu Wang
- Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
| | - Yuefeng Chen
- Emergency Room, the Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, P.R. China
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15
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Ronco C, Bellomo R. Hemoperfusion: technical aspects and state of the art. Crit Care 2022; 26:135. [PMID: 35549999 PMCID: PMC9097563 DOI: 10.1186/s13054-022-04009-w] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 04/25/2022] [Indexed: 11/10/2022] Open
Abstract
Background Blood purification through the removal of plasma solutes by adsorption to beads of charcoal or resins contained in a cartridge (hemoperfusion) has a long and imperfect history. Developments in production and coating technology, however, have recently increased the biocompatibility of sorbents and have spurred renewed interest in hemoperfusion. Methods We performed a narrative assessment of the literature with focus on the technology, characteristics, and principles of hemoperfusion. We assessed publications in ex vivo, animal, and human studies. We synthesized such literature in a technical and state-of-the-art summary. Results Early hemoperfusion studies were hampered by bioincompatibility. Recent technology, however, has improved its safety. Hemoperfusion has been used with positive effects in chronic dialysis and chronic liver disease. It has also demonstrated extraction of a variety of toxins and drugs during episodes of overdose. Trials with endotoxin binding polymyxin B have shown mixed results in septic shock and are under active investigation. The role of non-selective hemoperfusion in sepsis or inflammation remains. Although new technologies have made sorbents more biocompatible, the research agenda in the field remains vast. Conclusion New sorbents markedly differ from those used in the past because of greater biocompatibility and safety. Initial studies of novel sorbent-based hemoperfusion show some promise in specific chronic conditions and some acute states. Systematic studies of novel sorbent-based hemoperfusion are now both necessary and justified.
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Affiliation(s)
- Claudio Ronco
- Department of Medicine, University of Padova, Padua, Italy.,International Renal Research Institute of Vicenza (IRRV), Vicenza, Italy.,Department of Nephrology, San Bortolo Hospital, Vicenza, Italy
| | - Rinaldo Bellomo
- Department of Critical Care, University of Melbourne, Melbourne, Australia. .,Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia. .,Data Analytics Research and Evaluation Centre, Austin Hospital, Melbourne, Australia. .,Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC, 3084, Australia. .,Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia.
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