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Berlot G, Carocci P, Votrico V, Iacoviello B, Taverna N, Gerini U, di Maso V, Tomasini A. Real-World Outcomes of Hemoadsorption with CytoSorb ® in Patients with Septic Shock: Insights from a Single-Center Study. J Intensive Care Med 2025:8850666251331905. [PMID: 40170437 DOI: 10.1177/08850666251331905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
BackgroundHemoadsorption is currently employed to treat septic shock and other clinical conditions involving massive inflammatory mediator release. CytoSorb®, a device utilizing synthetic resin microbeads, provides a large adsorption surface for blood purification. This study aimed to review the clinical course of patients with septic shock treated with CytoSorb® in our hospital's intensive care unit (ICU).Patients and MethodsThis study retrospectively analyzed the clinical course of patients with septic shock treated with CytoSorb®, focusing on treatment timing and the volume of blood processed.ResultsBetween July 1, 2016, and December 31, 2023, 175 patients (106 men, 69 women; median age: 67 years, interquartile [IQR]: 58-85) received CytoSorb® therapy. Survivors exhibited a significantly lower simplified acute physiology score at admission than nonsurvivors. CytoSorb® was initiated within 24 h of shock onset in 102 patients (58%, early starters) and between 25 and 48 h in 73 patients (42%, late starters). Hemodynamic improvements elevated mean arterial pressure and reduced lactate, procalcitonin, C-reactive protein, sequential organ failure assessment scores, and noradrenaline doses in survivors. These effects were more pronounced in early starters receiving intensive treatment, who also demonstrated significantly lower lactate levels and higher mean arterial pressure at the end of therapy. Overall, 86 patients (49%) died in the ICU. Survivors underwent longer treatment durations and processed greater blood volumes than nonsurvivors.ConclusionsIn patients with septic shock treated with CytoSorb® within 48 h of onset, treatment intensity-rather than timing-was associated with lower ICU mortality rates.
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Affiliation(s)
- Giorgio Berlot
- Department of Anesthesia, Intensive Care and Pain Therapy, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
| | - Paolo Carocci
- Department of Anesthesia, Intensive Care and Pain Therapy, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
| | - Valentina Votrico
- Department Of Nephrology, Pordenone Hospital, Azienda Sanitaria Friuli Orientale, Pordenone, Italy
| | - Barbara Iacoviello
- Department of Anesthesia, Intensive Care and Pain Therapy, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
| | - Nicolò Taverna
- Department of Anesthesia, Intensive Care and Pain Therapy, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
| | - Ugo Gerini
- Department Of Nephrology, Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Palmanova, Italy
| | - Vittorio di Maso
- Department Of Nephrology, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
| | - Ariella Tomasini
- Department of Anesthesia, Intensive Care and Pain Therapy, Cattinara Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy
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Wustrow V, Gräfe C, Graf H, Scheiermann P, Paal M, Vogeser M, Liebchen U, Scharf C. Lactate Clearance of the Adsorber Cytosorb ® in Critically Ill Patients: A Post-Hoc Analysis of the Cyto-SOLVE Trial. Biomedicines 2025; 13:418. [PMID: 40002832 PMCID: PMC11853421 DOI: 10.3390/biomedicines13020418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 01/29/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Patients with shock suffer from hyperlactatemia, which can lead to endothelial dysfunction. The use of the adsorber Cytosorb® (CS) is recommended in these patients as it may contribute to higher lactate clearance and hemodynamic stabilization. However, it is unclear whether CS can directly adsorb lactate and can therefore increase lactate clearance. Methods: The Cyto-SOLVE trial included patients undergoing continuous kidney replacement therapy combined with CS application. Patients with a lactate concentration > 2 mmol/L and measurements of lactate pre- and post-adsorber, as well as measurements in the blood 10 min and 1, 3, 6, and 12 h after initiation were selected. Lactate clearance was calculated using the following formula: bloodflow(mL/min) × concentrationpre-post/concentrationpre. A t-test was used with the collected samples. Changes in the lactate concentration and vasopressor requirement were recorded before initiation and at the end of therapy. Results: Sixty-five lactate concentrations were measured pre- and post-CS application, as well as in patients' blood, in a total of 14 patients (median age of 52 years, 10 males, median SAPS-II 67). There was no significant change in the lactate concentration pre- and post-CS application (mean pre-CS: 6.7 mmol/L, mean post-CS: 6.9 mmol/L, RR: -0.2, 95% confidence interval (CI): -0.4-0.1, p = 0.13, Cohen's d: 0.90). The mean lactate clearance was -6 mL/min (standard deviation (SD): 21 mL/min), with no correlation with the initial lactate concentration or blood flow. In contrast, the mean lactate clearance measured using the dialyzer was 39 mL/min (SD: 28 mL/min). When comparing values before and after treatment, no significant change was observed in the lactate blood concentrations (mean of 9.0 vs. 8.5 mmol/L), nor in the requirement for vasopressin (median of 1.9 vs. 1.8 IE/h) or norepinephrine (mean of 2.7 vs. 2.6 mg/h). Conclusions: The adsorber CS cannot directly adsorb lactate, unlike kidney replacement therapy. Therefore, it is not suitable for achieving faster extracorporeal lactate elimination. Understanding the adsorption spectrum is of great relevance and should be considered when using CS in clinical practice.
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Affiliation(s)
- Vassilissa Wustrow
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
| | - Caroline Gräfe
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
| | - Helen Graf
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
| | - Patrick Scheiermann
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
| | - Michael Paal
- Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (M.P.)
| | - Michael Vogeser
- Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (M.P.)
| | - Uwe Liebchen
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
| | - Christina Scharf
- Department of Anaesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany; (V.W.)
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Papp M, Ince C, Bakker J, Molnar Z. Endothelial Protection and Improved Micro- and Macrocirculation with Hemoadsorption in Critically Ill Patients. J Clin Med 2024; 13:7044. [PMID: 39685503 DOI: 10.3390/jcm13237044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
A dysregulated immune response is associated with an excessive release of cytokines that can lead to systemic vasoplegia and vasoplegic shock with the development of multiorgan failure that is associated with an increased risk of dying. Under physiological circumstances, the endothelium and the glycocalyx are responsible for maintaining vascular tone, capillary permeability, and hemostasis, and controlling inflammation. In hyperinflammation, the endothelium and glycocalyx become damaged due to the excessive production of certain toxic proteins, along with an overwhelming release of cytokines. It has been shown in both in vitro animal experiments and in humans that extracorporeal hemoadsorption can reduce circulating levels of cytokines and may also remove toxic proteins that directly take part in endothelium and glycocalyx damage. The current review aims to summarize current knowledge, put recent findings into context, and introduce the hypothesis of "endothelial protection with hemoadsorption" in critically ill patients.
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Affiliation(s)
- Marton Papp
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 78 Üllői St., 1082 Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, 22 Baross St., 1085 Budapest, Hungary
| | - Can Ince
- Laboratory for Translational Intensive Care, Department of Intensive Care, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Jan Bakker
- Department of Pulmonary and Critical Care, New York University School of Medicine, New York, NY 10016, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA
- Department of Intensive Care Adults, Erasmus MC University Medical Center, 3000 GD Rotterdam, The Netherlands
- Department of Intensive Care, Pontificia Universidad Católica de Chile, Santiago 8320165, Chile
| | - Zsolt Molnar
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 78 Üllői St., 1082 Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, 22 Baross St., 1085 Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy and Pain Medicine, Poznan University for Medical Sciences, 49 Przybyszewskiego St, 60-355 Poznan, Poland
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Taccone FS, Brunkhorst FM, Bottari G, Hidalgo J, Kribben A, Teboul JL, Tomescu D, Klaus T, Scheier J, Deliargyris E, Ferrer R. The COSMOS Registry of CytoSorb Hemoadsorption Therapy in Critically Ill Patients: Protocol for an International, Prospective Registry. JMIR Res Protoc 2024; 13:e55880. [PMID: 39500494 PMCID: PMC11576605 DOI: 10.2196/55880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 06/03/2024] [Accepted: 08/16/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Extracorporeal blood purification with CytoSorb has been increasingly used as an adjunctive therapy in several hyperinflammatory critical care conditions, as well as to remove elevated levels of myoglobin or bilirubin in patients with rhabdomyolysis or liver failure. Despite the increasing worldwide use of hemoadsorption, data from large international multicenter studies are still lacking. OBJECTIVE The COSMOS (CytoSorb Treatment Of Critically Ill Patients) registry is a company-sponsored registry by CytoSorbents Corporation and CytoSorbents Medical Inc. and will provide a data repository and reporting infrastructure for the surveillance of CytoSorb use in real-world critical care settings in an unselected, critically ill patient population. The gathered data will serve as a comprehensive resource to assess the effects of such therapy on patients' management. METHODS The international COSMOS registry is collecting prospective data for patients treated with CytoSorb during routine care in various critical care indications, based on the decision of the treating physicians. Data are collected at baseline, during CytoSorb therapy, 24 hours thereafter, at discharge from the intensive care unit and the hospital, and on day 90. Key outcomes assessed include change in inflammatory biomarkers, vasopressor requirements, fluid balance, organ function and organ support, length of intensive care unit and hospital stay, occurrence of adverse events, and mortality. RESULTS The COSMOS registry started with the inclusion of the first patient on July 15, 2022, and is now actively enrolling in 4 countries (Germany, Spain, Portugal, and Italy), with plans to expand to other countries outside of Europe. An initial readout is planned for presentation at an international Critical Care conference in 2024. CONCLUSIONS The COSMOS registry is intended to provide comprehensive real-world data on patient outcomes with CytoSorb in various critical care indications, thereby contributing to optimization of patient selection, timing of initiation, and dosing of hemoadsorption treatment. TRIAL REGISTRATION ClinicalTrials.gov NCT05146336; https://clinicaltrials.gov/study/NCT05146336. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/55880.
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Affiliation(s)
- Fabio Silvio Taccone
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Frank Martin Brunkhorst
- Integriertes Forschungs- und Behandlungszentrum (IFB) Sepsis und Sepsisfolgen, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena, Jena, Germany
| | - Gabriella Bottari
- Pediatric Intensive Care Unit, Children Hospital Bambino Gesù, IRCCS, Rome, Italy
| | - Jorge Hidalgo
- General Intensive Care Unit and COVID-19 Unit, Belize Healthcare Partners, Belize City, Belize
| | - Andreas Kribben
- Klinik für Nephrologie, University Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Jean-Louis Teboul
- Paris-Saclay Medical School, Paris-Saclay University, Le Kremlin-Bicêtre, Paris, France
| | - Dana Tomescu
- Department of Anesthesiology and Critical Care, "Carol Davila, Bucharest, Romania
| | | | | | - Efthymios Deliargyris
- CytoSorbents Corporation and CytoSorbents Medical Inc., Princeton, NJ, United States
| | - Ricard Ferrer
- Intensive Care Department, Vall d'Hebron University Hospital, Shock, Organ Dysfunction and Resuscitation Research Group (SODIR), Barcelona, Spain
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Hobbs KJ, Bayless R, Sheats MK. A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses. Cells 2024; 13:1489. [PMID: 39273060 PMCID: PMC11394191 DOI: 10.3390/cells13171489] [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: 06/30/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024] Open
Abstract
With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.
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Affiliation(s)
- Kallie J. Hobbs
- Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
| | - Rosemary Bayless
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
| | - M. Katie Sheats
- Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
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Chiscano-Camón L, Ruiz-Sanmartin A, Bajaña I, Bastidas J, Lopez-Martinez R, Franco-Jarava C, Gonzalez JJ, Larrosa N, Riera J, Nuvials-Casals X, Ruiz-Rodríguez JC, Ferrer R. Current perspectives in the management of sepsis and septic shock. Front Med (Lausanne) 2024; 11:1431791. [PMID: 39211340 PMCID: PMC11358069 DOI: 10.3389/fmed.2024.1431791] [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: 05/12/2024] [Accepted: 07/24/2024] [Indexed: 09/04/2024] Open
Abstract
Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms.
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Affiliation(s)
- Luis Chiscano-Camón
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Adolf Ruiz-Sanmartin
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Ivan Bajaña
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Juliana Bastidas
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Rocio Lopez-Martinez
- Immunology Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Clara Franco-Jarava
- Immunology Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Juan José Gonzalez
- Microbiology Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Nieves Larrosa
- Microbiology Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Jordi Riera
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Xavier Nuvials-Casals
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Juan Carlos Ruiz-Rodríguez
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Ricard Ferrer
- Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
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Surasit K, Srisawat N. The Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial. Blood Purif 2024; 53:793-803. [PMID: 39102799 DOI: 10.1159/000540584] [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: 03/12/2024] [Accepted: 07/21/2024] [Indexed: 08/07/2024]
Abstract
INTRODUCTION Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. METHODS In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24-48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). RESULTS A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08-0.81; p = 0.021). All of secondary outcomes were comparable in both groups. CONCLUSION Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.
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Affiliation(s)
- Karjbundid Surasit
- Division of Critical Care, Department of Medicine, Nakornping Hospital, Chiang Mai, Thailand
| | - Nattachai Srisawat
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence in Critical Care Nephrology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Academy of Science, Royal Society of Thailand, Bangkok, Thailand
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Jang JH, Choi E, Kim T, Yeo HJ, Jeon D, Kim YS, Cho WH. Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment. Int J Mol Sci 2024; 25:7396. [PMID: 39000503 PMCID: PMC11242529 DOI: 10.3390/ijms25137396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/27/2024] [Accepted: 07/03/2024] [Indexed: 07/16/2024] Open
Abstract
Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.
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Affiliation(s)
- Jin Ho Jang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Eunjeong Choi
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Taehwa Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Hye Ju Yeo
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Doosoo Jeon
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Yun Seong Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Woo Hyun Cho
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (J.H.J.); (E.C.); (T.K.); (H.J.Y.); (D.J.); (Y.S.K.)
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
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Buhlmann A, Erlebach R, Müller M, David S. The phenomenon of desorption: What are the best adsorber exchange intervals? Crit Care 2024; 28:178. [PMID: 38802971 PMCID: PMC11131296 DOI: 10.1186/s13054-024-04968-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024] Open
Affiliation(s)
- Alix Buhlmann
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Rolf Erlebach
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Mattia Müller
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
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Girardis M, Coloretti I, Antonelli M, Berlot G, Busani S, Cortegiani A, De Pascale G, De Rosa FG, De Rosa S, Donadello K, Donati A, Forfori F, Giannella M, Grasselli G, Montrucchio G, Oliva A, Pasero D, Piazza O, Romagnoli S, Tascini C, Viaggi B, Tumbarello M, Viale P. Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2024; 4:28. [PMID: 38689337 PMCID: PMC11059820 DOI: 10.1186/s44158-024-00165-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 04/18/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.
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Affiliation(s)
- Massimo Girardis
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy.
| | - Irene Coloretti
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Antonelli
- Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Dell'Emergenza, Anestesiologiche E Della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giorgio Berlot
- Anesthesia and Intensive Care, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
| | - Stefano Busani
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea Cortegiani
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy
| | - Gennaro De Pascale
- Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Dell'Emergenza, Anestesiologiche E Della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | | | - Silvia De Rosa
- Anesthesia and Intensive Care, Santa Chiara Regional Hospital, APSS, Trento, Italy
| | - Katia Donadello
- Department of Surgery, Dentistry, Ginaecology and Paediatrics, University of Verona, and Anesthesia and Intensive Care Unit B, University Hospital Integrated Trust of Verona, Verona, Italy
| | - Abele Donati
- Anesthesia and Intensive Care, Azienda Ospedaliero Universitaria Delle Marche, Ancona, Italy
| | - Francesco Forfori
- Anesthesia and Intensive Care, Anesthesia and Resuscitation Department, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Maddalena Giannella
- Department of Medical and Surgical Sciences Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giacomo Grasselli
- Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giorgia Montrucchio
- Department of Surgical Sciences, Departement of Anesthesia, Resuscitation and Emergency Torino, University of Turin, Turin, Italy
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Daniela Pasero
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
| | - Ornella Piazza
- University Hospital "San Giovanni Di Dio E Ruggi d'Aragona", Salerno, Italy
| | - Stefano Romagnoli
- Department of Health Science, Department of Anesthesia and Intensive Care, University of Florence, Careggi University Hospital, Florence, Italy
| | - Carlo Tascini
- Department of Medicine (DAME), Infectious Diseases Clinic, University of Udine, Udine, Italy
| | - Bruno Viaggi
- Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy
| | - Mario Tumbarello
- Infectious and Tropical Diseases Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
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11
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Kovacevic P, Dragic S, Jandric M, Momcicevic D, Malesevic V, Kovacevic T, Matejic-Spasic M, Knezevic T, Zlojutro B. Does adjunctive hemoadsorption provide benefit in the management of ischemia-reperfusion syndrome following near-drowning? A case report. Front Med (Lausanne) 2024; 11:1341156. [PMID: 38633302 PMCID: PMC11021721 DOI: 10.3389/fmed.2024.1341156] [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: 11/19/2023] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Drowning remains a significant global health concern, claiming over 300,000 lives annually, with a disproportionate impact on young individuals in low-and middle-income countries. Conventional mechanical ventilation, while common, falls short in addressing the hypoxemia and hypercapnia often observed in severe near-drowning cases. Veno-venous extracorporeal membrane oxygenation (vvECMO) emerges as a critical intervention for cardiopulmonary failure post-drowning. This case report delves into the pivotal role of ischemia-reperfusion injury (IRI) in a near-drowning-related pathology. Following the initial insult, reoxygenation exacerbates the inflammatory cascade, resulting in a surge of pro-inflammatory mediators. In this context, CytoSorb®, a hemoadsorption cartridge, demonstrates promise by effectively removing these mediators from circulation. This report outlines its application in a critically ill adolescent patient who experienced near-drowning, presenting a compelling case for CytoSorb as an adjunctive therapy in managing IRI-induced hyperinflammation.
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Affiliation(s)
- Pedja Kovacevic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Sasa Dragic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Milka Jandric
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
| | - Danica Momcicevic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Vedrana Malesevic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
| | - Tijana Kovacevic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | | | - Tanja Knezevic
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
| | - Biljana Zlojutro
- Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
- Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
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12
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Mehta Y, Ansari AS, Mandal AK, Chatterjee D, Sharma GS, Sathe P, Umraniya PV, Paul R, Gupta S, Singh V, Singh YP. Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock: An Indian perspective. World J Crit Care Med 2024; 13:89026. [PMID: 38633478 PMCID: PMC11019629 DOI: 10.5492/wjccm.v13.i1.89026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 12/05/2023] [Accepted: 01/17/2024] [Indexed: 03/05/2024] Open
Abstract
BACKGROUND Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. AIM To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. METHODS We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. RESULTS Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". CONCLUSION This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.
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Affiliation(s)
- Yatin Mehta
- Institute of Critical Care and Anesthesiology, Medanta The Medicity, Gurgaon 122001, Haryana, India
| | - Abdul Samad Ansari
- Department of Critical Care, Nanavati Max Super Specialty Hospital, Mumbai 400065, India
| | - Amit Kumar Mandal
- Department of Pulmonology, Sleep and Critical Care, Fortis Hospital, Mohali, Punjab, Mohali 160062, Punjab , India
| | - Dipanjan Chatterjee
- Department of Cardio-Puimonary Critical Care, Medica Superspecialty Hospital, Kolkata 700099, India
| | | | - Prachee Sathe
- Department of Critical Care Medicine, D.Y. Patil Medical College, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad,, Pune 411018, India
| | - Purvesh V Umraniya
- Department of Critical Care Medicine, Bhailal Amin General Hospital, Vadodara 390003, Gujarat, India
| | - Rajib Paul
- Department of Internal Medicine, Apollo Hospitals, Jubilee Hills, Hyderabad 500 033, India
| | - Sachin Gupta
- Department of Anaesthesiology, Narayana Superspeciality Hospital, Gurugram 122002, India
| | - Vinod Singh
- Department of Critical Care Medicine, Institute of Critical Care Medicine, Hospital Name - Sir Ganga Ram Hospital, New Delhi 110001, India
| | - Yogendra Pal Singh
- Department of Critical Care Medicine, Max Super Speciality Hospital, Delhi 110092, India
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13
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Lovrić D, Pašalić M, Križanac S, Kovačić K, Skorić B, Jurin H, Miličić D, Premužić V. The addition of Cytosorb in patients on VA-ECMO improves urinary output and ICU survival. Ther Apher Dial 2024; 28:103-111. [PMID: 37697687 DOI: 10.1111/1744-9987.14064] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 03/18/2023] [Accepted: 09/01/2023] [Indexed: 09/13/2023]
Abstract
INTRODUCTION The aim of this study was to analyze the efficiency of CytoSorb adsorber in patients presenting with cardiogenic shock and treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS Sixteen patients put on VA ECMO due to cardiogenic shock were included, stratified according to the use of Cytosorb adsorber in the first 24 h and compared across different clinical outcomes. RESULTS Significantly lower vasopressor doses were required among patients treated with Cytosorb at the initiation and before weaning from ECMO. Furthermore, these patients showed significantly higher urine output before weaning and lower lactate levels during the extracorporeal support. Finally, the mortality rate was lower among the Cytosorb therapy group (22.2% vs 57.1%). CONCLUSION While a decrease in vasopressor doses was already associated with CytoSorb use, this is the first study showing an increase in urinary output and a trend towards better survival among patients on VA ECMO treated with CytoSorb.
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Affiliation(s)
- Daniel Lovrić
- Cardiology Clinic, University Hospital Center Zagreb, Zagreb, Croatia
| | - Marijan Pašalić
- Cardiology Clinic, University Hospital Center Zagreb, Zagreb, Croatia
| | | | - Karla Kovačić
- Emergency Medicine Institute of Koprivnica-Križevci County, Koprivnica, Croatia
| | - Boško Skorić
- Cardiology Clinic, University Hospital Center Zagreb, Zagreb, Croatia
| | - Hrvoje Jurin
- Cardiology Clinic, University Hospital Center Zagreb, Zagreb, Croatia
| | - Davor Miličić
- Cardiology Clinic, University Hospital Center Zagreb, Zagreb, Croatia
| | - Vedran Premužić
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
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14
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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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15
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García-Villegas R, Arni S. Hemoadsorption in Organ Preservation and Transplantation: A Narrative Review. Life (Basel) 2023; 14:65. [PMID: 38255680 PMCID: PMC10817660 DOI: 10.3390/life14010065] [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: 10/31/2023] [Revised: 12/19/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such as cytokine storm activation and blood ABO and immune incompatibilities. Cytokine adsorption is also performed for the treatment of various life-threatening conditions, such as endotoxic septic shock, acute respiratory distress syndrome, and cardiogenic shock, all potentially leading to adverse clinical outcomes during transplantation. After surgery, dysmetabolism and stress response limit successful graft survival and can lead to primary or secondary graft dysfunction. In this clinical context, and given that a major problem in transplant medicine is that the demand for organs far exceeds the supply, a technological innovation such as a hemoadsorption system could greatly contribute to increasing the number of usable organ donors. The objectives of this review are to describe the specific advantages and disadvantages of the application of cytokine adsorption in the context of transplantation and examine, before and/or after organ transplantation, the benefits of the addition of a cytokine adsorption therapy protocol.
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Affiliation(s)
- Refugio García-Villegas
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, D.F., Mexico City 07360, Mexico;
| | - Stephan Arni
- Department of Thoracic Surgery, University Hospital Zürich, 8091 Zürich, Switzerland
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16
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Tomescu D, Popescu M, Akil A, Nassiri AA, Wunderlich-Sperl F, Kogelmann K, Molnar Z, Alharthy A, Karakitsos D. The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome. Int J Artif Organs 2023; 46:605-617. [PMID: 38037333 DOI: 10.1177/03913988231211740] [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] [Indexed: 12/02/2023]
Abstract
Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.
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Affiliation(s)
- Dana Tomescu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Department of Anaesthesia and Intensive Care, Bucharest, Romania
| | - Mihai Popescu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Department of Anaesthesia and Intensive Care, Bucharest, Romania
| | - Ali Akil
- Department of Thoracic Surgery, Hans Susemihl Hospital Emden, Emden, Germany
| | - Amir Ahmad Nassiri
- Division of Nephrology, Department of Internal Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Florian Wunderlich-Sperl
- Clinical Department of Anesthesiology and Intensive Care Medicine, University Hospital St. Pölten-Lilienfeld, St. Pölten, Austria
| | - Klaus Kogelmann
- Department of Anesthesiology and Intensive Care Medicine, Hans Susemihl Hospital Emden, Emden, Germany
| | - Zsolt Molnar
- CytoSorbents Europe GmbH, Berlin, Germany
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Dimitrios Karakitsos
- Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia
- Critical Care Department, Keck School of Medicine, USC, Los Angeles, CA, USA
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17
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Mitzner S, Kogelmann K, Ince C, Molnár Z, Ferrer R, Nierhaus A. Adjunctive Hemoadsorption Therapy with CytoSorb in Patients with Septic/Vasoplegic Shock: A Best Practice Consensus Statement. J Clin Med 2023; 12:7199. [PMID: 38068250 PMCID: PMC10707447 DOI: 10.3390/jcm12237199] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/10/2023] [Accepted: 11/18/2023] [Indexed: 05/14/2025] Open
Abstract
A dysregulated host response is a common feature in critically ill patients due to both infectious and non-infectious origins that can lead to life-threatening organ dysfunction, which is still the primary cause of death in intensive care units worldwide. In its course, pathologic, unregulated levels of inflammatory mediators are often released into the circulation, a phenomenon also referred to as a "cytokine storm". To date, there are no approved therapies to modulate the excessive immune response and limit hyperinflammation with the goal of preventing related organ failure and death. In this context, extracorporeal blood purification therapies aiming at the alteration of the host inflammatory response through broad-spectrum, non-selective removal of inflammatory mediators have come into focus. A novel hemoadsorption device (CytoSorb®, CytoSorbents Inc., Princeton, NJ, USA) has shown promising results in patients with hyperinflammation from various origins. Although a significant body of literature exists, there is ongoing research to address many important remaining questions, including the optimal selection of patient groups who might benefit the most, optimal timing for therapy initiation, optimal schedule for adsorber exchanges and therapy duration, as well as an investigation into the potential removal of concomitant antibiotics and other medications. In this review, we discuss the existing evidence and provide a consensus-based best practice guidance for CytoSorb® hemoadsorption therapy in patients with vasoplegic shock.
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Affiliation(s)
- Steffen Mitzner
- Division for Tropical Medicine, Infectious Diseases and Nephrology, Department of Internal Medicine, University of Rostock, 18051 Rostock, Germany;
| | - Klaus Kogelmann
- Department of Anesthesiology and Intensive Care Medicine, Klinikum Leer, 26789 Leer, Germany;
| | - Can Ince
- Department of Intensive Care, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands;
| | - Zsolt Molnár
- Department of Anesthesiology and Intensive Care Medicine, Semmelweis University, 1085 Budapest, Hungary;
- CytoSorbents Europe GmbH, 12587 Berlin, Germany
| | - Ricard Ferrer
- SODIR Research Group, Intensive Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain;
| | - Axel Nierhaus
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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18
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Bottari G, Guzzo I, Cappoli A, Labbadia R, Perdichizzi S, Serpe C, Creteur J, Cecchetti C, Taccone FS. Impact of CytoSorb and CKRT on hemodynamics in pediatric patients with septic shock: the PedCyto study. Front Pediatr 2023; 11:1259384. [PMID: 37780052 PMCID: PMC10540853 DOI: 10.3389/fped.2023.1259384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 08/21/2023] [Indexed: 10/03/2023] Open
Abstract
Background There is a lack of data to support the use of hemoadsorption in pediatric septic shock. The aim of our study was to assess the effectiveness and safety of CytoSorb therapy in this setting. Methods Phase II interventional single arm pilot study in which 17 consecutive children admitted with septic shock who required continuous kidney replacement therapy (CKRT) and weighed ≥10 kg were included. A CytoSorb (CytoSorbents Inc, New Jersey, USA) hemoadsorption cartridge was added to the CKRT every 24 h for a maximum of 96 h. A control group of 13 children with septic shock treated with CKRT but not hemoadsorption at Children's Hospital Bambino Gesù and enrolled in the EuroAKId register was selected as an historical cohort. The primary outcome of the study was a reduction in vasopressor or inotrope dose of >50% from baseline by the end of CytoSorb therapy. Secondary outcomes included hemodynamic and biological changes, changes in severity scores, and 28-day mortality. Results There were significant decreases in the Vasoactive Inotropic Score (VIS) and the Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score at 72 and 96 h from the start of the CytoSorb therapy compared to baseline; the reductions were larger in the hemoadsorption group than in the control group (historical cohort). 28-day mortality was lower, although not significantly, in the hemoadsorption group when compared to the control group (5/17 [29%] vs. 8/13 [61%] OR 0.26 [95% CI: 0.05-1.2]; p = 0.08). Conclusions CytoSorb therapy may have some benefits in pediatric patients with septic shock. Future larger randomized trials are needed in this setting. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT05658588, identifier (Clinicaltrials.gov NCT05658588).
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Affiliation(s)
- Gabriella Bottari
- Pediatric Emergency Department, Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Isabella Guzzo
- Department of Pediatrics, Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Andrea Cappoli
- Department of Pediatrics, Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Raffaella Labbadia
- Department of Pediatrics, Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Salvatore Perdichizzi
- Pediatric Emergency Department, Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Carmela Serpe
- Pediatric Emergency Department, Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Jacques Creteur
- Department of Intensive Care, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Corrado Cecchetti
- Pediatric Emergency Department, Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Fabio Silvio Taccone
- Department of Intensive Care, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
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19
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He J, Lin Y, Cai W, Lin Y, Qin W, Shao Y, Liu Q. EFFICACY OF SUPPLEMENTAL HEMOADSORPTION THERAPY ON SEVERE AND CRITICAL PATIENTS WITH COVID-19: AN EVIDENCE-BASED ANALYSIS. Shock 2023; 60:333-344. [PMID: 37548606 PMCID: PMC10510838 DOI: 10.1097/shk.0000000000002189] [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: 05/19/2023] [Revised: 06/06/2023] [Accepted: 07/17/2023] [Indexed: 08/08/2023]
Abstract
ABSTRACT Background: The COVID-19 pandemic has posed a disproportionately high threat to the global health system and social stability. COVID-19 damage can lead to hyperinflammation and tissue damage due to a "cytokine storm," which in turn contributes to an increase in the mortality rate. Extracorporeal hemoadsorption therapy (HAT) in patients with severe COVID-19 may improve organ function and stabilize hemodynamic status; however, the effects of supplemental HAT remain controversial. Methods: The Cochrane Library, Embase, and PubMed databases were comprehensively searched from inception to August 20, 2022, for potential studies. Results: A total of 648 patients with severe COVID-19 in three randomized controlled trials and 11 observational studies met the inclusion criteria. A meta-analysis indicated that supplemental HAT significantly improved the mortality rate of patients with severe COVID-19 compared with conventional therapy (relative risk [RR] = 0.74, 95% confidence interval [CI] = 0.56 to 0.96, P = 0.026). In subgroup analyses, supplemental HAT significantly decreased mortality rates in patients without extracorporeal membrane oxygenation (ECMO) support (RR = 0.59, 95% CI = 0.44-0.79, P < 0.0001), while a significant difference was not observed in patients requiring ECMO support (RR = 1.61, 95% CI = 0.63-4.09, P = 0.316). Standardized mean difference (SMD) meta-analysis showed that IL-6 removal was more significant in HAT group than conventional therapy group (SMD = 0.46, 95% CI = 0.01 to 0.91, P = 0.043), followed by C-reactive protein (SMD = 0.70, 95% CI = -0.04 to 1.44, P = 0.065) and IL-8 (SMD = 0.36, 95% CI = -0.34 to 1.07, P = 0.311). No evidence of substantial publication bias concerning mortality was observed. Conclusion: Given the better mortality outcomes, HAT confers clinical benefits to patients with severe COVID-19, which correlated with cytokine removal by HAT. Cytokine adsorption may not provide clinical benefits for patients with severe COVID-19 requiring ECMO and should be used with caution. However, because of the very low quality of evidence, multicenter randomized trials with large sample sizes are required to verify these findings.
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Affiliation(s)
- Junbing He
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Yao Lin
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Weiming Cai
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Yingying Lin
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Wanbing Qin
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Yiming Shao
- The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Qinghua Liu
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
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20
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Ozturk M, Popov AF. Hemoadsorption in LVAD Surgery: Suitable in Theory? J Cardiovasc Dev Dis 2023; 10:286. [PMID: 37504542 PMCID: PMC10380647 DOI: 10.3390/jcdd10070286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 07/03/2023] [Indexed: 07/29/2023] Open
Abstract
The incidence of patients with heart failure is growing steadily, particularly due to advancements in medical therapy [...].
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Affiliation(s)
- Mahmut Ozturk
- Division of Cardiac Surgery, Children's National Hospital, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20010, USA
| | - Aron Frederik Popov
- Department of Cardiothoracic Surgery, Hannover Medical School, 30625 Hannover, Germany
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21
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Hayanga JWA, Song T, Durham L, Garrison L, Smith D, Molnar Z, Scheier J, Deliargyris EN, Moazami N. Extracorporeal hemoadsorption in critically ill COVID-19 patients on VV ECMO: the CytoSorb therapy in COVID-19 (CTC) registry. Crit Care 2023; 27:243. [PMID: 37337243 PMCID: PMC10280833 DOI: 10.1186/s13054-023-04517-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 06/02/2023] [Indexed: 06/21/2023] Open
Abstract
OBJECTIVES The CytoSorb therapy in COVID-19 (CTC) registry evaluated the clinical performance and treatment parameters of extracorporeal hemoadsorption integrated with veno-venous extracorporeal membrane oxygenation (VV ECMO) in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) and respiratory failure under US FDA Emergency Use Authorization. DESIGN Multicenter, observational, registry (NCT04391920). SETTING Intensive care units (ICUs) in five major US academic centers between April 2020 and January 2022. PATIENTS A total of 100 critically ill adults with COVID-19-related ARDS requiring VV ECMO support, who were treated with extracorporeal hemoadsorption. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Baseline demographics, clinical characteristics, laboratory values and outcomes were recorded following individual ethics committee approval at each center. Detailed data on organ support utilization parameters and hemoadsorption treatments were also collected. Biomarker data were collected according to the standard practice at each participating site, and available values were compared before and after hemoadsorption. The primary outcome of mortality was evaluated using a time-to-event analysis. A total of 100 patients (63% male; age 44 ± 11 years) were included. Survival rates were 86% at 30 days and 74% at 90 days. Median time from ICU admission to the initiation of hemoadsorption was 87 h and was used to define two post hoc groups: ≤ 87 h (group-early start, GE) and > 87 h (group-late start, GL). After the start of hemoadsorption, patients in the GE versus GL had significantly shorter median duration of mechanical ventilation (7 [2-26] vs. 17 [7-37] days, p = 0.02), ECMO support (13 [8-24] vs. 29 [14-38] days, p = 0.021) and ICU stay (17 [10-40] vs 36 [19-55] days, p = 0.002). Survival at 90 days in GE was 82% compared to 66% in GL (p = 0.14). No device-related adverse events were reported. CONCLUSIONS In critically ill patients with severe COVID-19-related ARDS treated with the combination of VV-ECMO and hemoadsorption, 90-day survival was 74% and earlier intervention was associated with shorter need for organ support and ICU stay. These results lend support to the concept of "enhanced lung rest" with the combined use of VV-ECMO plus hemoadsorption in patients with ARDS.
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Affiliation(s)
- J W Awori Hayanga
- Department of Cardiovascular and Thoracic Surgery, West Virginia University, 1 Medical Center Drive, Morgantown, WV, 26506, USA.
| | - Tae Song
- University of Chicago Medicine, Chicago, USA
| | | | | | - Deane Smith
- New York University School of Medicine, New York, USA
| | - Zsolt Molnar
- CytoSorbents Europe, Berlin, Germany
- Semmelweis University, Budapest, Hungary
| | | | | | - Nader Moazami
- New York University School of Medicine, New York, USA
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22
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Jansen A, Waalders NJB, van Lier DPT, Kox M, Pickkers P. CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo. Crit Care 2023; 27:117. [PMID: 36945034 PMCID: PMC10029173 DOI: 10.1186/s13054-023-04391-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/03/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND The CytoSorb hemoadsorption device has been demonstrated to be capable of clearing inflammatory cytokines, but has not yet been shown to attenuate plasma cytokine concentrations. We investigated the effects of CytoSorb hemoperfusion on plasma levels of various cytokines using the repeated human experimental endotoxemia model, a highly standardized and reproducible human in vivo model of systemic inflammation and immunological tolerance induced by administration of bacterial lipopolysaccharide (LPS). METHODS Twenty-four healthy male volunteers (age 18-35) were intravenously challenged with LPS (a bolus of 1 ng/kg followed by continuous infusion of 0.5 ng/kg/hr for three hours) twice: on day 0 to quantify the initial cytokine response and on day 7 to quantify the degree of endotoxin tolerance. Subjects either received CytoSorb hemoperfusion during the first LPS challenge (CytoSorb group), or no intervention (control group). Plasma cytokine concentrations and clearance rates were determined serially. This study was registered at ClinicalTrials.gov (NCT04643639, date of registration November 24th 2020). RESULTS LPS administration led to a profound increase in plasma cytokine concentrations during both LPS challenge days. Compared to the control group, significantly lower plasma levels of tumor necrosis factor (TNF, - 58%, p < 0.0001), interleukin (IL)-6 ( - 71%, p = 0.003), IL-8 ( - 48%, p = 0.02) and IL-10 ( - 26%, p = 0.03) were observed in the CytoSorb group during the first LPS challenge. No differences in cytokine responses were observed during the second LPS challenge. CONCLUSIONS CytoSorb hemoperfusion effectively attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo, whereas it does not affect long-term immune function. Therefore, CytoSorb therapy may be of benefit in conditions characterized by excessive cytokine release.
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Affiliation(s)
- Aron Jansen
- Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands.
- Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, the Netherlands.
| | - Nicole J B Waalders
- Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands
- Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, the Netherlands
| | - Dirk P T van Lier
- Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands
- Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, the Netherlands
| | - Matthijs Kox
- Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands
- Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, the Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands.
- Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, the Netherlands.
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23
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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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24
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Kielstein JT. [Hemoperfusion and plasmapheresis in the intensive care unit]. WIENER KLINISCHES MAGAZIN : BEILAGE ZUR WIENER KLINISCHEN WOCHENSCHRIFT 2023; 26:1-6. [PMID: 37359739 PMCID: PMC9975843 DOI: 10.1007/s00740-023-00486-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
Abstract
In addition to kidney replacement procedures, several other extracorporeal procedures are employed in the intensive care unit. Hemoperfusion with activated charcoal was the predominant treatment used for removal of toxins from the 1970s until the millennium. Nowadays, this treatment does no longer play a clinically meaningful role as even strongly protein-bound toxins can be removed by effective dialysis procedures in case poisoning. The concept of a cytokine adsorber was introduced 10 years ago, which is directed towards withstanding the cytokine storm. Despite negative data from prospective randomized controlled studies, its use is steadily increasing in Germany. A totally different treatment concept is the biomimetic pathogen adsorber, which removes bacteria, viruses and fungi from the bloodstream by binding to immobilized heparin. Whether this rapid reduction of the pathogen load translates into an improvement of clinically relevant endpoints is unclear, as prospective randomized controlled studies are lacking. For the early hours of septic shock a very old procedure, plasmapheresis, has recently regained interest. The results of two large randomized controlled studies in this setting from Europe and Canada will become available in 2025/2026. The rationale to use plasma exchange in early sepsis is that this procedure not only removes cytokines but also replenishes reduced levels of protective factors, such as angiopoietin‑1, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) and protein C, if fresh plasma is used as exchange fluid. All afore mentioned procedures do not only have a different mode of action but are also used at seperate time points of bloodstream infections and/or sepsis.
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Affiliation(s)
- Jan T. Kielstein
- Medizinische Klinik V (Nephrologie | Rheumatologie | Blutreinigungsverfahren), Städtisches Klinikum Braunschweig, Salzdahlumer Str. 90, 38126 Braunschweig, Deutschland
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25
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Roberts SH, Goodwin ML, Bobba CM, Al-Qudsi O, Satyapriya SV, Tripathi RS, Papadimos TJ, Whitson BA. Continuous renal replacement therapy and extracorporeal membrane oxygenation: implications in the COVID-19 era. Perfusion 2023; 38:18-27. [PMID: 34494489 DOI: 10.1177/02676591211042561] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%-70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact.
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Affiliation(s)
- Sophia H Roberts
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.,The Ohio State University College of Medicine, Columbus, OH, USA
| | - Matthew L Goodwin
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Christopher M Bobba
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.,The Ohio State University College of Medicine, Columbus, OH, USA
| | - Omar Al-Qudsi
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - S Veena Satyapriya
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ravi S Tripathi
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Thomas J Papadimos
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Bryan A Whitson
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Hämoperfusion und Plasmapherese auf der Intensivstation. DIE NEPHROLOGIE 2022. [PMCID: PMC9768770 DOI: 10.1007/s11560-022-00620-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Neben Nierenersatzverfahren werden auf der Intensivstation mehrere andere extrakorporale Verfahren eingesetzt. In den 1970er- bis 2000er-Jahren stand die Hämoperfusion mit Aktivkohlekapseln zur Entfernung von Toxinen im Vordergrund. Dies ist mittlerweile aufgrund der effektiven Dialyseverfahren, die im Vergiftungsfall auch stark proteingebundene Toxine entfernen, fast bedeutungslos geworden. Vor 10 Jahren erlebte ein Zytokinadsorber die Markteinführung, der darauf gerichtet ist, den „Zytokinsturm“ zu überstehen. Dieser erfreut sich trotz ernüchternder Daten aus prospektiven, randomisierten, kontrollierten Studien wachsender Beliebtheit. Ein gänzlich anderes Therapiekonzept ist der biomimetische Pathogenadsorber, der Bakterien, Viren und Pilze durch Bindung an immobilisiertes Heparin aus dem Blutstrom entfernt. Ob sich diese schnelle Reduktion der Pathogenlast in eine Verbesserung klinisch relevanter Endpunkte übersetzt, ist unklar, da hier prospektive, randomisierte und kontrollierte Studien gänzlich fehlen. Für ein sehr altes Verfahren, nämlich die Plasmapherese, werden wir für die Frühphase der Sepsis bis zum Jahr 2025/2026 Ergebnisse aus 2 großen randomisierten, kontrollierten Studien aus Europa und Kanada erhalten. Neben der Entfernung von Zytokinen erhofft man sich durch die Verwendung von Frischplasma als Austauschflüssigkeit auch das Wiederauffüllen reduzierter protektiver Faktoren wie Angiopoietin 1, ADAMTS13 („a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13“) und Protein C. Alle genannten Verfahren funktionieren nicht nur unterschiedlich, sondern werden auch zu unterschiedlichen Zeitpunkten der Blutstrominfektion/Sepsis eingesetzt.
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27
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Persic V, Jerman A, Malgaj Vrecko M, Berden J, Gorjup V, Stecher A, Lukic M, Jereb M, Taleska Stupica G, Gubensek J. Effect of CytoSorb Coupled with Hemodialysis on Interleukin-6 and Hemodynamic Parameters in Patients with Systemic Inflammatory Response Syndrome: A Retrospective Cohort Study. J Clin Med 2022; 11:jcm11247500. [PMID: 36556116 PMCID: PMC9788171 DOI: 10.3390/jcm11247500] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 12/11/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Excessive release of cytokines during systemic inflammatory response syndrome (SIRS) often leads to refractory hypotension and multiple organ failure with high mortality. Cytokine removal with hemoadsorption has emerged as a possible adjuvant therapy, but data on interleukin-6 (IL-6) reduction and outcomes in clinical practice are scarce. We aimed to evaluate the effect of CytoSorb hemoadsorption on laboratory and clinical outcomes in shocked patients with SIRS. We designed a retrospective analysis of all patients with SIRS treated with CytoSorb in intensive care units (ICU). IL-6, laboratory and hemodynamic parameters were analyzed at approximate time intervals during CytoSorb treatment in the whole cohort and in a subgroup with septic shock. Observed and predicted mortality rates were compared. We included 118 patients with various etiologies of SIRS (septic shock 69%, post-resuscitation shock 16%, SIRS with acute pancreatitis 6%, other 9%); in all but one patient, CytoSorb was coupled with renal replacement therapy. A statistically significant decrease in IL-6 and vasopressor index with an increase in pH and mean arterial pressure was observed from 6 h onward. The reduction of lactate became significant at 48 h. Results were similar in a subgroup of patients with septic shock. Observed ICU and in-hospital mortalities were lower than predicted by Sequential Organ Failure Assessment (SOFA) (61% vs. 79%, p = 0.005) and Acute Physiology and Chronic Health Evaluation (APACHE) II (64% vs. 78%, p = 0.031) scores. To conclude, hemoadsorption in shocked patients with SIRS was associated with a rapid decrease in IL-6 and hemodynamic improvement, with improved observed vs. predicted survival. These results need to be confirmed in a randomized study.
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Affiliation(s)
- Vanja Persic
- Center for Acute and Complicated Dialysis and Vascular Access, Department of Nephrology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Alexander Jerman
- Center for Acute and Complicated Dialysis and Vascular Access, Department of Nephrology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Marija Malgaj Vrecko
- Center for Acute and Complicated Dialysis and Vascular Access, Department of Nephrology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Jernej Berden
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Center of Intensive Internal Medicine, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Vojka Gorjup
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Center of Intensive Internal Medicine, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Adela Stecher
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Anesthesiology and Surgical Intensive Therapy, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Milica Lukic
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Infectious Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Matjaz Jereb
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Infectious Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Gordana Taleska Stupica
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Anesthesiology and Surgical Intensive Therapy, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
| | - Jakob Gubensek
- Center for Acute and Complicated Dialysis and Vascular Access, Department of Nephrology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Correspondence: ; Tel.: +386-1-522-31-21
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Ruiz-Rodríguez JC, Plata-Menchaca EP, Chiscano-Camón L, Ruiz-Sanmartin A, Ferrer R. Blood purification in sepsis and COVID-19: what´s new in cytokine and endotoxin hemoadsorption. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2022. [PMCID: PMC8978509 DOI: 10.1186/s44158-022-00043-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sepsis and COVID-19 are two clinical conditions that can lead to a dysregulated inflammatory state causing multiorgan dysfunction, hypercytokinemia, and a high risk of death. Specific subgroups of critically ill patients with particular characteristics could benefit from rescue treatment with hemoadsorption. There is a lack of adequately designed randomized controlled trials evaluating the potential benefits of cytokine or endotoxin hemoadsorption. Critically ill COVID-19 patients with severe acute respiratory failure poorly responsive to conventional treatment could be candidates to receive cytokine hemoadsorption in the presence of high levels of interleukin 6. This treatment can also be suitable for patients with refractory septic shock and hypercytokinemia. In the context of high endotoxin activity, hemoadsorption with polymyxin B could improve clinical parameters and the prognosis of patients with refractory septic shock. Predictive enrichment, using biomarkers or other individual features, identifies potential responders to cytokine, endotoxin, or sequential hemoadsorption. Besides, recognizing the particular subsets of patients likely to respond to one or both types of hemoadsorption will aid the design of future studies that accurately validate the effectiveness of these therapies.
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Fiedler MO, Muellenbach RM, Rolfes C, Lotz C, Nickel F, Müller-Stich BP, Supady A, Lepper PM, Weigand MA, Meybohm P, Kalenka A, Reyher C. Pumpless Extracorporeal Hemadsorption Technique (pEHAT): A Proof-of-Concept Animal Study. J Clin Med 2022; 11:jcm11226815. [PMID: 36431292 PMCID: PMC9692831 DOI: 10.3390/jcm11226815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/07/2022] [Accepted: 11/12/2022] [Indexed: 11/19/2022] Open
Abstract
Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45-85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] - 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.
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Affiliation(s)
- Mascha O. Fiedler
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Correspondence: ; Tel.: +49-(0)62221-56-39434
| | - Ralf M. Muellenbach
- Department of Anesthesiology, Critical Care Medicine, Emergency Medicine and Pain Therapy, Campus Kassel of the University of Southampton, 34125 Kassel, Germany
| | - Caroline Rolfes
- Department of Anesthesiology, Critical Care Medicine, Emergency Medicine and Pain Therapy, Campus Kassel of the University of Southampton, 34125 Kassel, Germany
| | - Christopher Lotz
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Felix Nickel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Beat P. Müller-Stich
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Alexander Supady
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, 79106 Freiburg, Germany
- Heidelberg Institute of Global Health, University of Heidelberg, 69117 Heidelberg, Germany
| | - Philipp M. Lepper
- Department of Internal Medicine V—Pneumology, Allergology and Critical Care Medicine, University Medical Centre, Saarland University, 66424 Homburg, Germany
| | - Markus A. Weigand
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Patrick Meybohm
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Armin Kalenka
- Department of Anesthesiology and Intensive Care Medicine, Hospital Bergstrasse, 64646 Heppenheim, Germany
| | - Christian Reyher
- Department of Anesthesiology, Critical Care Medicine, Emergency Medicine and Pain Therapy, Campus Kassel of the University of Southampton, 34125 Kassel, Germany
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Hawchar F, Tomescu D, Träger K, Joskowiak D, Kogelmann K, Soukup J, Friesecke S, Jacob D, Gummert J, Faltlhauser A, Aucella F, van Tellingen M, Malbrain MLNG, Bogdanski R, Weiss G, Herbrich A, Utzolino S, Nierhaus A, Baumann A, Hartjes A, Henzler D, Grigoryev E, Fritz H, Bach F, Schröder S, Weyland A, Gottschaldt U, Menzel M, Zachariae O, Novak R, Berden J, Haake H, Quintel M, Kloesel S, Kortgen A, Stecher S, Torti P, Nestler F, Nitsch M, Olboeter D, Muck P, Findeisen M, Bitzinger D, Kraßler J, Benad M, Schott M, Schumacher U, Molnar Z, Brunkhorst FM. Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry. PLoS One 2022; 17:e0274315. [PMID: 36282800 PMCID: PMC9595535 DOI: 10.1371/journal.pone.0274315] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 08/25/2022] [Indexed: 12/23/2022] Open
Abstract
The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).
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Affiliation(s)
- Fatime Hawchar
- Department of Anesthesiology and Intensive Care, University of Szeged, Szeged, Hungary
- * E-mail:
| | - Dana Tomescu
- Department of Anaesthesia and Critical Care, Fundeni Clinical Institute, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy Bucharest, Bucharest, Romania
| | - Karl Träger
- Kardioanasthesiologie, Universitätsklinikum Ulm, Ulm, Germany
| | - Dominik Joskowiak
- Universitätsklinikum der LMU München, Herzchirurgische Klinik und Poliklinik, Munich, Germany
| | - Klaus Kogelmann
- Klinik für Anästhesiologie und Intensivmedizin, Hans-Susemihl-Krankenhaus GmbH, Emden, Germany
| | - Jens Soukup
- Klinik für Anästhesiologie, Intensivtherapie und Palliativmedizin, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany
| | - Singrun Friesecke
- Klinik und Poliklinik für Innere Medizin B, Universitätsmedizin Greifswald, Greifswald, Germany
| | - David Jacob
- Universitätsklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Magdeburg, Magdeburg, Germany
| | - Jan Gummert
- Herz- und Diabeteszentrum NRW, Klinische Studien Chirurgie, Bad Oeynhausen, Germany
| | | | - Filippo Aucella
- Research Hospital "Casa Sollievo della Sofferenza" Medical Science, Nephrology and Dialysis Unit, San Giovanni, Rotondo, Italy
| | | | - Manu L. N. G. Malbrain
- First Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland
- Medical Data Management, Medaman, Geel, Belgium
- International Fluid Academy, Lovenjoel, Belgium
| | - Ralph Bogdanski
- Klinik für Anästhesiologie, AG Hämodynamik, Klinikumrechts der Isar TU München, München, Germany
| | - Günter Weiss
- Krankenhaus Hietzing, Wiener Krankenanstaltenverbund, A, Wien, Austria
| | - Andreas Herbrich
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Klinikum Region Hannover Nordstadt, Hannover, Germany
| | - Stefan Utzolino
- Universitätsklinikum Freiburg, Abteilung Allgemein- und Viszeralchirurgie, Freiburg, Germany
| | - Axel Nierhaus
- Klinik für Intensivmedizin, Universitätsklinikum Hamburg- Eppendorf, Hamburg, Germany
| | - Andreas Baumann
- Klinik für Anästhesie, Intensiv-, Palliativ- und Schmerzmedizin, Berufsgenossensch Uniklinik Bergmannsheil, Bochum, Germany
| | | | - Dietrich Henzler
- Klinikum Herford, UK Anästhesie, Intensivmedizin, Rettungsmedizin, Schmerztherapie, Herford, Germany
| | - Evgeny Grigoryev
- Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation
| | - Harald Fritz
- Krankenhaus Martha Maria Halle Klinik für Anaesthesiologie und Intensivmedizin, Halle, Germany
| | - Friedhelm Bach
- Klinik für Anästhesiologie, Intensiv-, Notfallmedizin, Transfusionsmedizin und Schmerztherapie, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
| | - Stefan Schröder
- Krankenhaus Düren gem. GmbH, Klinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Düren, Germany
| | - Andreas Weyland
- Universitätsklinik für Anästhesiologie/Intensiv-/Notfallmedizin/Schmerztherapie, Klinikum Oldenburg GmbH, Carl von Ossietzky Universität, Oldenburg, Germany
| | | | - Matthias Menzel
- Klinikum Wolfsburg, Klinik für Anästhesie und Intensivmedizin, Wolfsburg, Germany
| | - Olivier Zachariae
- Klinikum Wolfsburg, Klinik für Anästhesie und Intensivmedizin, Wolfsburg, Germany
| | - Radovan Novak
- Klinikum Oberlausitzer Bergland GmbH, Zittau, Germany
| | - Jernej Berden
- University Medical Centre Ljubljana, Dep. Of Internal medicine, ICU, Ljubljana, Slovenia
| | - Hendrik Haake
- Klinik für Kardiologie und Intensivmedizin, Kliniken Maria Hilf GmbH, Mönchengladbach, Germany
| | - Michael Quintel
- Zentrum Anästhesiologie, Rettungs-und Intensivmedizin, Universitätsklinikum Göttingen, Göttingen, Germany
| | - Stephan Kloesel
- GPR Klinikum Rüsselsheim, Abteilung Anästhesie, Rüsselsheim, Germany
| | - Andreas Kortgen
- Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin, Jena, Germany
| | - Stephanie Stecher
- Medizinische Klinik und Poliklinik II, Klinikum der Universität München, München, Germany
| | - Patricia Torti
- Rianimazione Ospedale U. Parini, S.C. Anestesia e Rianimazione, Aosta, Italy
| | | | - Markus Nitsch
- Klinik für Anästhesie, Intensiv-, Notfallmedizin und Schmerztherapie, Krankenhaus St. Elisabeth und St. Barbara, Halle, Germany
| | - Detlef Olboeter
- Krankenhaus Herzberg, Elbe-Elster-Klinikum GmbH, Herzberg, Germany
| | - Philip Muck
- Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
| | - Michael Findeisen
- Klinik für Pneumologie, Gastroenterologie, Internistische Intensiv- und Beatmungsmedizin, Städtisches Klinikum München GmbH, Klinikum Harlaching, Munich, Germany
| | - Diane Bitzinger
- Universitätsklinikum Regensburg, Klinik für Anästhesiologie, Regensburg, Germany
| | - Jens Kraßler
- Fachkrankenhaus Coswig, Klinik für Anästhesiologie und Intensivmedizin, Coswig, Germany
| | - Martin Benad
- Bodden Kliniken Ribnitz Damgarten, Ribnitz Damgarten, Germany
| | | | - Ulrike Schumacher
- Center for Clinical Studies Jena (ZKS), Jena University Hospital, Jena, Germany
| | - Zsolt Molnar
- Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, School of Medicine, University of Pécs, Pécs, Hungary
- Department of Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland
- Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
| | - Frank Martin Brunkhorst
- Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
- Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
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Akil A, Napp LC, Rao C, Klaus T, Scheier J, Pappalardo F. Use of CytoSorb© Hemoadsorption in Patients on Veno-Venous ECMO Support for Severe Acute Respiratory Distress Syndrome: A Systematic Review. J Clin Med 2022; 11:jcm11205990. [PMID: 36294309 PMCID: PMC9604472 DOI: 10.3390/jcm11205990] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/30/2022] [Accepted: 10/04/2022] [Indexed: 11/23/2022] Open
Abstract
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Adjunct hemoadsorption is increasingly utilized to target underlying hyperinflammation derived from ARDS. This article aims to review available data on the use of CytoSorb© therapy in combination with V-V ECMO in severe ARDS, and to assess the effects on inflammatory, laboratory and clinical parameters, as well as on patient outcomes. A systematic literature review was conducted and reported in compliance with principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. When applicable, a before-and-after analysis for relevant biomarkers and clinical parameters was carried out. CytoSorb© use was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively). Increases in PaO2/FiO2 reached significance as well (p = 0.028), while norepinephrine dosage reductions showed a non-significant trend (p = 0.067). Mortality rates in CytoSorb© patients tended to be lower than those of control groups of most included studies, which, however, were characterized by high heterogeneity and low power. In an exploratory analysis on 90-day mortality in COVID-19 patients supported with V-V ECMO, the therapy was associated with a significantly reduced risk of death. Based on the reviewed data, CytoSorb© therapy is able to reduce inflammation and potentially improves survival in ARDS patients treated with V-V ECMO. Early initiation of CytoSorb© in conjunction with ECMO might offer a new approach to enhance lung rest and promote recovery in patients with severe ARDS.
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Affiliation(s)
- Ali Akil
- Department of Thoracic Surgery and Lung Support, Ibbenbueren General Hospital, 49477 Ibbenbueren, Germany
| | - L. Christian Napp
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
| | | | | | | | - Federico Pappalardo
- Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS. Antonio e Biagio e Cesare Arrigo, 15100 Alessandria, Italy
- Correspondence:
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Nierhaus A, Morales J, Wendt D, Scheier J, Gutzler D, Jarczak D, Born F, Hagl C, Deliargyris E, Mehta Y. Comparison of the CytoSorb ® 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study. MINIM INVASIV THER 2022; 31:1058-1065. [PMID: 35913784 DOI: 10.1080/13645706.2022.2104617] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
INTRODUCTION We performed an analysis of two blood purification systems to determine their performance for removing interleukins (ILs)-6 and 10, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 from blood. MATERIAL AND METHODS An in vitro hemoperfusion blood recirculation circuit was used to compare the CytoSorb® 300 mL (CytoSorbents Inc., Princeton, NJ) and Jafron HA 380 (Jafron Biomedical Co., Ltd., Zhuhai City, China) devices. The removal of purified recombinant human IL-6, IL-10, TNFα and MCP-1 by the adsorbers was compared at various timepoints. Three runs were completed and removal was evaluated as the mean area under the curve (AUC). RESULTS Both devices showed effective removal of the tested cytokines. IL-6, IL-10, TNFα and MCP-1 were removed faster and to a higher extent by the CytoSorb® 300 mL device. At maximal time of 12 h, overall removal according to AUC of remaining concentrations was significantly lower with CytoSorb® 300 mL compared with HA 380 (IL-6: 1075.5 ± 665.9 vs. 4345.1 ± 1499.3 (p = 0.01), IL-10: 5065.7 ± 882.5 vs. 11,939.7 ± 4523.1 (p = 0.03), TNF-α: 6519.9 ± 997.6 vs. 10,303.7 ± 2347.0 (p = 0.03) and MCP-1: 278.9 ± 40.7 vs. 607.3 ± 84.4 (p = 0.001)). CONCLUSIONS Both the CytoSorb® and the Jafron HA 380 devices are capable of removing cytokines from blood in a benchtop model. The CytoSorb® 300 device was significantly more efficient achieving the bulk of the removal in the first 120 min.
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Affiliation(s)
- Axel Nierhaus
- Clinic for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany.,Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Daniel Wendt
- CytoSorbents, Princeton, NJ, USA.,Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, Essen, Germany
| | | | | | - Dominik Jarczak
- Clinic for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany.,Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Born
- Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Christian Hagl
- Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany
| | | | - Yatin Mehta
- Medanta Institute of Critical Care and Anesthesiology, Gurgaon, India
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Heymann M, Schorer R, Putzu A. Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand 2022; 66:1037-1050. [PMID: 35788557 PMCID: PMC9541789 DOI: 10.1111/aas.14115] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 05/08/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND The effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial. METHODS We performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized-controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow-up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI). RESULTS Fourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow-up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04-1.49], p = .02, [TSA-adjusted CI, 0.92-1.68]) and at 30-days or in-hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06-1.88], p = .02, [TSA-adjusted CI, 0.44-4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low. CONCLUSION Low certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high-quality randomized trials to clarify mortality and adverse events related to CytoSorb®. EDITORIAL COMMENT Hemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient-important benefits. The findings from this systematic review and meta-analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.
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Affiliation(s)
- Marc Heymann
- Division of Anesthesiology, Department of Acute MedicineGeneva University HospitalsGenevaSwitzerland
| | - Raoul Schorer
- Division of Anesthesiology, Department of Acute MedicineGeneva University HospitalsGenevaSwitzerland
| | - Alessandro Putzu
- Division of Anesthesiology, Department of Acute MedicineGeneva University HospitalsGenevaSwitzerland
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Immunomodulation by Hemoadsorption—Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study. Biomedicines 2022; 10:biomedicines10102340. [PMID: 36289602 PMCID: PMC9598581 DOI: 10.3390/biomedicines10102340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 11/26/2022] Open
Abstract
Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. Method: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. Results: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism.
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Naruka V, Salmasi MY, Arjomandi Rad A, Marczin N, Lazopoulos G, Moscarelli M, Casula R, Athanasiou T. Use of Cytokine Filters During Cardiopulmonary Bypass: Systematic Review and Meta-Analysis. Heart Lung Circ 2022; 31:1493-1503. [PMID: 36041987 DOI: 10.1016/j.hlc.2022.07.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 06/25/2022] [Accepted: 07/11/2022] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Cardiac surgery involving cardiopulmonary bypass (CPB) activates an inflammatory response releasing cytokines that are associated with less favourable outcomes. This study aims to compare i) CPB during cardiac surgery (control) versus ii) CPB with haemoadsorption therapy; and assess the effect of adding this therapy in reducing the inflammatory cytokines burden. METHODS A systematic literature review with metanalysis was conducted regarding the main outcomes (operative mortality, ventilation duration, intensive care unit [ICU] and hospital stays) and day-1 inflammatory markers levels post-surgery. Fifteen (15) studies were included for final analysis (eight randomised controlled trials, seven observational studies) with no evidence of publication bias. RESULTS Subgroup analysis of non-elective surgeries across observational studies (emergency and infective endocarditis) significantly favoured cytokine filters in terms of 30-day mortality (OR 0.40, 95% CI 0.20, 0.83; p=0.01) and shorter ICU stay (MD -42.36, 95% CI -68.07, -16.65; p=0.001). At day-1 post-surgery, there was a significant difference favouring the cytokine filter group in c-reactive protein (CRP) (MD -0.71, 95% CI -0.84, -0.59; p<0.001) with no differences in white blood count (WBC), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), IL-6, IL-8 and lactate. When comparing cytokine filters and control across all studies there was no significant difference in operative mortality, ventilation duration, hospital stay and ICU length of stay. Also, there were no statistical differences in randomised controlled trials (RCTs) using haemadsorption filters. CONCLUSIONS A significant reduction in 30-day mortality and ICU stay could be obtained by using haemadsorption therapy during non-elective cardiac surgery, especially emergency surgery and in patients with higher inflammatory burden such as infective endocarditis.
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Affiliation(s)
- Vinci Naruka
- Department of Surgery and Cancer, Imperial College, London, UK; Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK
| | | | | | - Nandor Marczin
- Department of Surgery and Cancer, Imperial College, London, UK
| | - George Lazopoulos
- Department of Cardiothoracic Surgery, University Hospital of Heraklion, Crete, Greece
| | | | - Roberto Casula
- Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK
| | - Thanos Athanasiou
- Department of Surgery and Cancer, Imperial College, London, UK; Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK.
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Ghaidan H, Stenlo M, Niroomand A, Mittendorfer M, Hirdman G, Gvazava N, Edström D, Silva IAN, Broberg E, Hallgren O, Olm F, Wagner DE, Pierre L, Hyllén S, Lindstedt S. Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation. Nat Commun 2022; 13:4173. [PMID: 35882835 PMCID: PMC9325745 DOI: 10.1038/s41467-022-31811-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient. Lung transplantation is hindered by the scarcity of organs and by mortality following primary graft dysfunction. Here, the authors show that cytokine absorption can be used in donor lungs during ex vivo lung perfusion and post-transplant, and leads to restored lung function and reduced primary graft dysfunction in animal models.
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Affiliation(s)
- Haider Ghaidan
- Department of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, Sweden.,Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Martin Stenlo
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Cardiothoracic Anaesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden
| | - Anna Niroomand
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Rutgers Robert University, New Brunswick, NJ, USA
| | - Margareta Mittendorfer
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Gabriel Hirdman
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Nika Gvazava
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Experimental Medical Sciences, Lung Bioengineering and Regeneration, Lund University, Lund, Sweden
| | - Dag Edström
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Cardiothoracic Anaesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden
| | - Iran A N Silva
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Experimental Medical Sciences, Lung Bioengineering and Regeneration, Lund University, Lund, Sweden
| | - Ellen Broberg
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Cardiothoracic Anaesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden
| | - Oskar Hallgren
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Franziska Olm
- Department of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, Sweden.,Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Darcy E Wagner
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Experimental Medical Sciences, Lung Bioengineering and Regeneration, Lund University, Lund, Sweden
| | - Leif Pierre
- Department of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, Sweden.,Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden
| | - Snejana Hyllén
- Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden.,Lund Stem Cell Center, Lund University, Lund, Sweden.,Department of Cardiothoracic Anaesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden
| | - Sandra Lindstedt
- Department of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, Sweden. .,Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden. .,Department of Clinical Sciences, Lund University, Lund, Sweden. .,Lund Stem Cell Center, Lund University, Lund, Sweden.
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Ghinolfi D, Melandro F, Patrono D, Lai Q, De Carlis R, Camagni S, Gambella A, Ruberto F, De Simone P. A new ex-situ machine perfusion device. A preliminary evaluation using a model of donors after circulatory death pig livers. Artif Organs 2022; 46:2493-2499. [PMID: 36136037 DOI: 10.1111/aor.14351] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 05/09/2022] [Accepted: 06/16/2022] [Indexed: 12/01/2022]
Abstract
We herein describe a new ex-situ machine perfusion device as a "technology spotlight" using a model of donors after circulatory death liver grafts procured from slaughterhouse pigs. Fourteen pig liver grafts were included. The device allowed stable perfusion in both hypothermic (n = 6) and normothermic (n = 8) conditions and no technical failure was observed. During perfusion, perfusate and bile samples were collected to assess liver metabolism and viability. An integrated adsorption device showed efficient removal of inflammatory cytokines during treatment. This preliminary experience represents the starting point for further investigations on the potential clinical benefits of cytokines and other inflammatory mediators adsorption during machine perfusion.
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Affiliation(s)
- Davide Ghinolfi
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Fabio Melandro
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Damiano Patrono
- General Surgery 2U-Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Quirino Lai
- Division of General Surgery and Organ Transplantation, Sapienza Università di Roma, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Stefania Camagni
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Alessandro Gambella
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Franco Ruberto
- Division of General Surgery and Organ Transplantation, Sapienza Università di Roma, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy
| | - Paolo De Simone
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
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38
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Akil A, Ziegeler S, Rehers S, Ernst EC, Fischer S. Blood purification therapy in patients with severe COVID-19 requiring veno-venous ECMO therapy: A retrospective study. Int J Artif Organs 2022; 45:615-622. [PMID: 35695200 DOI: 10.1177/03913988221103287] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Patients with severe manifestations of COVID-19 might exhibit characteristics of a sepsis-like syndrome that can progress to multiple organ failure and ultimately death. Underlying mechanism have been explored and suggest a profound dysregulation of the immune system associated with hyperinflammation, hemodynamic instability and respiratory failure. Besides standard intensive care treatment, approaches modulating the dysregulated immune response, such as CytoSorb hemoadsorption, have been used. However, data of ECMO-dependent patients in comparison to a control cohort remain scarce. METHODS Included were 26 critically ill COVID-19 patients requiring high-flow veno-venous extracorporeal membrane oxygenation (high-flow VV ECMO) therapy due to severe acute respiratory distress syndrome (ARDS), of whom 16 were additionally treated with an extracorporeal hemoadsorption device, and compared to a control group of 10 patients. Assessed were levels of inflammatory markers, vasopressor requirements, oxygenation parameters, as well as clinically relevant outcome variables. Data were prospectively recorded and retrospectively analyzed. RESULTS Treatment with the applied multimodal therapy approach resulted in a stabilization in hemodynamics, a control of the hyperinflammatory response as evidenced by a significant reduction in inflammatory mediators, as well as a marked improvement in lung function. No device related adverse events were observed while treatment appeared safe and feasible. CONCLUSION Treatment of a critically ill COVID-19 ARDS patients with combined VV ECMO support and hemoadsorption therapy led to a rapid and sustained hemodynamic stabilization, a control of the uncontrolled inflammatory response and an improvement in oxygenation. Given these signals pointing toward a patient-oriented benefit of extracorporeal hemoadsorption therapy in those patients, future controlled, randomized studies should focus on the investigation of the appropriate timing and dosing of this promising treatment modality.
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Affiliation(s)
- Ali Akil
- Department of Thoracic Surgery and Lung Support, Ibbenbueren General Hospital, Ibbenbueren, Germany
| | - Stephan Ziegeler
- Department of Anesthesiology, Intensive Care Medicine and Pain Management, Ibbenbueren General Hospital, Ibbenbueren, Germany
| | - Stephanie Rehers
- Department of Anesthesiology, Intensive Care Medicine and Pain Management, Ibbenbueren General Hospital, Ibbenbueren, Germany
| | - Erik Christian Ernst
- Department of Respiratory Medicine and Pulmonary Rehabilitation, Karl-Hansen-Hospital, Bad Lippspringe, Germany
| | - Stefan Fischer
- Department of Thoracic Surgery and Lung Support, Ibbenbueren General Hospital, Ibbenbueren, Germany
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Application of Extracorporeal Apheresis in Treatment of COVID-19: a Rapid Review. BIONANOSCIENCE 2022; 12:979-993. [PMID: 35578681 PMCID: PMC9096332 DOI: 10.1007/s12668-022-00987-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 01/08/2023]
Abstract
Spread of a novel coronavirus infection in 2019 caused by SARS-CoV-2 virus has become a real threat to public health all around the world. The new pandemic required the mobilization of all resources for effective treatment of COVID-19 patients. Extracorporeal apheresis methods were suggested as an addition to the therapy of severe COVID-19 patients, especially when there is a threat of cytokine storm. Cytokine storm has a complex and not fully understood mechanism, and it can result in the multiple organ failure syndrome, associated with high mortality. The main cytokines that play the key role in the cytokine storm are IL-6, IL-10, and TNF-alpha. Removal of the target pro-inflammatory cytokines from the bloodstream can be beneficial in reducing the risk of complications as well as the mortality rate. We describe and compare different methods of extracorporeal apheresis: hemoadsorption, selective plasma filtration, and plasma exchange therapy in the context of their potential use in COVID-19 treatment.
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Rasch S, Sancak S, Erber J, Wießner J, Schulz D, Huberle C, Algül H, Schmid RM, Lahmer T. Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study. Artif Organs 2022; 46:1019-1026. [PMID: 35182395 DOI: 10.1111/aor.14195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/02/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro-inflammatory cytokines and potentially improves the outcome of sepsis. METHODS Sixteen patients with SAP, presenting within 7 days upon onset of pain, an APACHE-II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24-h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE-II score-matched retrospective control group of 32 patients. RESULTS The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p = 0.007), respectively. The cytokine adsorption significantly reduced IL-6 (-1998 pg/ml, p = 0.005) serum levels and resulted in stable CRP (p = 0.101) and decreased PCT (p = 0.003) levels in contrast to increased CRP (p = 0.014) and stable PCT levels (p = 0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72 h postcytokine adsorption [-1 vs. 0, p = 0.005]) and the SOFA score significantly decreased (day 5: -1.8 ± 2.0 vs. 1 ± 3.8, p = 0.013) in the intervention group. CONCLUSION Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro-inflammatory marker IL-6 and stabilizes organ function according to serial SOFA score assessments.
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Affiliation(s)
- Sebastian Rasch
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Sengül Sancak
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Johanna Erber
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Johannes Wießner
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Dominik Schulz
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Christina Huberle
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Hana Algül
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany.,Comprehensive Cancer Center Munich CCCM (TUM), Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Roland M Schmid
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Tobias Lahmer
- Department of Internal Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
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41
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CytoSorb Rescue for COVID-19 Patients With Vasoplegic Shock and Multiple Organ Failure: A Prospective, Open-Label, Randomized Controlled Pilot Study. Crit Care Med 2022; 50:964-976. [PMID: 35135967 PMCID: PMC9112514 DOI: 10.1097/ccm.0000000000005493] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19–associated vasoplegic shock.
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42
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Berlot G, Samola V, Barbaresco I, Tomasini A, di Maso V, Bianco F, Gerini U. Effects of the timing and intensity of treatment on septic shock patients treated with CytoSorb ®: Clinical experience. Int J Artif Organs 2022; 45:249-253. [PMID: 35075942 DOI: 10.1177/03913988211073812] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. METHODS The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. RESULTS Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. CONCLUSIONS In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.
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Affiliation(s)
- Giorgio Berlot
- Department of Anesthesia and Intensive Care Medicine, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Valentina Samola
- Department of Anesthesia and Intensive Care Medicine, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Ilaria Barbaresco
- Department of Anesthesia and Intensive Care Medicine, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Ariella Tomasini
- Department of Anesthesia and Intensive Care Medicine, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Vittorio di Maso
- Department of Nephrology, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Francesco Bianco
- Department of Nephrology, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
| | - Ugo Gerini
- Department of Nephrology, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Friuli-Venezia Giulia, Italy
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Ruiz-Rodriguez JC, Plata-Menchaca EP, Chiscano-Camón L, Ruiz-Sanmartin A, Pérez-Carrasco M, Palmada C, Ribas V, Martínez-Gallo M, Hernández-González M, Gonzalez-Lopez JJ, Larrosa N, Ferrer R. Precision medicine in sepsis and septic shock: From omics to clinical tools. World J Crit Care Med 2022; 11:1-21. [PMID: 35433311 PMCID: PMC8788206 DOI: 10.5492/wjccm.v11.i1.1] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/23/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.
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Affiliation(s)
- Juan Carlos Ruiz-Rodriguez
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Erika P Plata-Menchaca
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Department of Intensive Care, Hospital Clínic de Barcelona, Barcelona 08036, Spain
| | - Luis Chiscano-Camón
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Adolfo Ruiz-Sanmartin
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Marcos Pérez-Carrasco
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
| | - Clara Palmada
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
| | - Vicent Ribas
- Data Analytics in Medicine, Digital Health Unit, Eurecat, Centre Tecnològic de Catalunya, Barcelona 08005, Spain
| | - Mónica Martínez-Gallo
- Immunology Division, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Diagnostic Immunology Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Manuel Hernández-González
- Immunology Division, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Diagnostic Immunology Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Juan J Gonzalez-Lopez
- Department of Clinical Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Department of Microbiology and Genetics, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Nieves Larrosa
- Department of Clinical Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Department of Microbiology and Genetics, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
| | - Ricard Ferrer
- Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
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Rachunek K, Krause M, Thiel JT, Kolbenschlag J, Daigeler A, Bury A. Technical Note: Novel Use of CytoSorb™ Haemadsorption to Provide Wound Healing Support in Case of Severe Burn Trauma via Reduction of Hyperbilirubinaemia. Front Surg 2022; 8:743571. [PMID: 34977137 PMCID: PMC8718512 DOI: 10.3389/fsurg.2021.743571] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 11/29/2021] [Indexed: 11/21/2022] Open
Abstract
Hyperbilirubinaemia has been shown to compromise wound healing in severely burned patients. The therapy options for patients with impairment of wound healing and subsequent severe liver dysfunction are limited. A novel extracorporeal treatment, CytoSorb® (CytoSorbents Corp, USA), is a whole blood adsorber composed of highly biocompatible and porous polystyrene divinylbenzene copolymer beads covered in a polyvinylpyrrolidone coating. It is capable of extracting mainly hydrophobic middle-sized (up to 55 kDa) molecules from blood via size exclusion, including cytokines and bilirubin. We performed therapy with CytoSorb® on a severely burned (48% Total Body Surface Area-TBSA) patient with secondary sclerosing cholangitis (SCC) to promote the wound healing process by reducing bilirubin concentrations and to bridge the time to spontaneous liver regeneration or eventually to liver transplantation after two skin transplantations had failed to provide wound closure. In the first 6 days the cartridge was changed on a daily basis and later after every 2–4 days. The therapy with six adsorbers decreased a total bilirubin concentration from 14.02 to 4.29 mg/dl. By maintaining a stable bilirubin concentration under 5 mg/dl, debridement of abdomen and upper extremities with autologous skin grafting and, 4 weeks later, autologous skin grafting of the back from scrotum and lower extremities were performed successfully. After wound healing had been achieved, the CytoSorb therapy was discontinued after 57 days and 27 adsorber changes. CytoSorb therapy can be a promising support of wound and skin graft healing in patients with severe burns and liver dysfunction due to a significant reduction of total bilirubin concentration.
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Affiliation(s)
- Katarzyna Rachunek
- Department of Hand, Plastic, Reconstructive and Burn Surgery, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - Maja Krause
- Department of Hand, Plastic, Reconstructive and Burn Surgery, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - Johannes Tobias Thiel
- Department of Hand, Plastic, Reconstructive and Burn Surgery, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - Jonas Kolbenschlag
- Department of Hand, Plastic, Reconstructive and Burn Surgery, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - Adrien Daigeler
- Department of Hand, Plastic, Reconstructive and Burn Surgery, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - Andreas Bury
- Department of Anesthesiology and Intensive Care Medicine, BG Trauma Center, Eberhard Karls University of Tuebingen, Tuebingen, Germany
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45
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Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy. Cells 2021; 11:cells11010091. [PMID: 35011653 PMCID: PMC8750486 DOI: 10.3390/cells11010091] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/22/2021] [Accepted: 12/26/2021] [Indexed: 02/06/2023] Open
Abstract
Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply.
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Burov AI, Abramov TA, Kostritca NS, Korotkov DS, Danilov GV, Strunina YV, Savin IA. Observational case series: six neurosurgical patients with septic shock demonstrating clinical improvement after a combination of standard care and blood purification. Eur J Med Res 2021; 26:151. [PMID: 34930484 PMCID: PMC8691076 DOI: 10.1186/s40001-021-00614-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 11/20/2021] [Indexed: 11/10/2022] Open
Abstract
Background For patients with primary brain injury, septic shock is especially dangerous due to the possibility of secondary cerebral damage. The key factor of sepsis-associated brain injury is inflammatory mediators, pathogen and damage-associated molecular patterns (PAMPs, DAMPs) release. Theoretically, blood purification may be beneficial for patients with primary brain injury due to its possibility for fast removal of inflammatory mediators. Case presentation We report on six post-neurosurgery septic shock patients treated with combined blood purification (CBP), which included CRRT with high adsorption capacity membrane in combination with CytoSorb adsorber. Clinical improvement in the course of CBP was registered in all patients. Three patients had a stable clinical improvement; the other three patients had only a transient improvement due to underlying neurological and cardiac deficits aggravation. We observed septic shock reversal in four patients. The key observations of the case series are a significant decrease in MOF severity (measured by SOFA score) and in catecholamine need (not statistically significant). By the end of CBP we observed a significant decrease in blood lactate, PCT and IL-6 levels. Two patients demonstrated level of consciousness increase in the setting of CBP therapy measured by GCS and FOUR score. Conclusion This case series demonstrates that CBP therapy may have a role for septic shock patients with primary brain injury.
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Affiliation(s)
- A I Burov
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.
| | - T A Abramov
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - N S Kostritca
- Federal State Budget Educational Institution of Higher Education M. V. Lomonosov Moscow State University, Moscow, Russian Federation
| | - D S Korotkov
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - G V Danilov
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - Y V Strunina
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - I A Savin
- Federal State Autonomous Institution N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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Shi Y, Zhu ML, Wu Q, Huang Y, Xu XL, Chen W. The Potential of Drug Delivery Nanosystems for Sepsis Treatment. J Inflamm Res 2021; 14:7065-7077. [PMID: 34984019 PMCID: PMC8702780 DOI: 10.2147/jir.s339113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/08/2021] [Indexed: 12/19/2022] Open
Abstract
Sepsis is a major immune response disorder caused by infection, with very high incidence and mortality rates. In the clinic, sepsis and its complications are mainly controlled and treated with antibiotics, anti-inflammatory, and antioxidant drugs. However, these treatments have some shortcomings, such as rapid metabolism and severe side effects. The emergence of drug delivery nanosystems can significantly improve tissue permeability, prolong drugs' circulation time, and reduce side effects. In this paper, we reviewed recent drug delivery nanosystems designed for sepsis treatment based on their mechanisms (anti-bacterial, anti-inflammatory, and antioxidant). Although great progress has been made recently, clinical practice transformation is still very difficult. Therefore, we also discussed key obstacles, including tissue distribution, overcoming bacterial resistance, and single treatment modes. Finally, a rigorous optimization of drug delivery nanosystems is expected to present great potential for sepsis therapy.
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Affiliation(s)
- Yi Shi
- ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Meng-Lu Zhu
- Department of Pharmacy, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 310006, People’s Republic of China
| | - Qian Wu
- ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Yi Huang
- ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
| | - Xiao-Ling Xu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310004, People’s Republic of China
| | - Wei Chen
- ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China
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Abstract
PURPOSE OF REVIEW Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. RECENT FINDINGS The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. SUMMARY The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.
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Köhler T, Schwier E, Praxenthaler J, Kirchner C, Henzler D, Eickmeyer C. Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb ®-Basics, Indications and Perspectives-A Scoping Review. Int J Mol Sci 2021; 22:12786. [PMID: 34884590 PMCID: PMC8657779 DOI: 10.3390/ijms222312786] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/21/2021] [Accepted: 11/22/2021] [Indexed: 01/08/2023] Open
Abstract
The "normal" immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels ("cytokine storm") could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.
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Affiliation(s)
- Thomas Köhler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany; (E.S.); (J.P.); (D.H.); (C.E.)
| | - Elke Schwier
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany; (E.S.); (J.P.); (D.H.); (C.E.)
| | - Janina Praxenthaler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany; (E.S.); (J.P.); (D.H.); (C.E.)
| | - Carmen Kirchner
- Department of General and Visceral Surgery, Thoracic Surgery and Proctology, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany;
| | - Dietrich Henzler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany; (E.S.); (J.P.); (D.H.); (C.E.)
| | - Claas Eickmeyer
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr University Bochum, Klinikum Herford, 32120 Herford, Germany; (E.S.); (J.P.); (D.H.); (C.E.)
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Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis. Signal Transduct Target Ther 2021; 6:407. [PMID: 34824200 PMCID: PMC8613465 DOI: 10.1038/s41392-021-00816-9] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 10/19/2021] [Accepted: 10/26/2021] [Indexed: 12/12/2022] Open
Abstract
Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host-microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.
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Affiliation(s)
- Yun-Yu Zhang
- Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China
| | - Bo-Tao Ning
- Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
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