{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:23Z","timestamp":1787028623920,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Lipopolysaccharide, the main component of the outer membrane of Gram-negative bacteria is a highly potent endotoxin responsible for organ dysfunction in sepsis. It is present in the blood stream not only in Gram-negative infections, but also in Gram-positive and fungal infections, presumably due to sepsis-related disruption of the intestinal barrier. Various pathways, both extra- and intracellular, are involved in sensing endotoxin and non-canonical activation of caspase-mediated pyroptosis is considered to have a major role in sepsis pathophysiology. Endotoxin induces specific pathological alterations in several organs, which contributes to poor outcomes. The adverse consequences of endotoxin in the circulation support the use of anti-endotoxin therapies, yet more than 30 years of experience with endotoxin adsorption therapies have not provided clear evidence in favor of this treatment modality. The results of small studies support timely endotoxin removal guided by measuring the levels of endotoxin; unfortunately, this has not been proven in large, randomized studies. The presence of endotoxemia can be demonstrated in the majority of patients with COVID-19, yet only case reports and case series describing the effects of endotoxin removal in these patients have been published to date. The place of blood purification therapies in the treatment of septic shock has not yet been determined.<\/jats:p>","DOI":"10.3390\/jcm11030619","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T11:02:53Z","timestamp":1643194973000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Rationale and Current Status of Endotoxin Adsorption in the Treatment of Septic Shock"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2649-0541","authenticated-orcid":false,"given":"Jakub","family":"\u015amiechowicz","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1007\/s00134-020-06106-2","article-title":"Epidemiology and Burden of Sepsis Acquired in Hospitals and Intensive Care Units: A Systematic Review and Meta-Analysis","volume":"46","author":"Markwart","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1097\/ALN.0000000000002820","article-title":"Blood Purification and Mortality in Sepsis and Septic Shock","volume":"131","author":"Putzu","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_4","unstructured":"Vincent, J.-L., Abraham, E., Moore, F.A., Kochanek, P.M., and Fink, M.P. (2017). Septic Shock. Textbook of Critical Care, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/09680519020080010101","article-title":"Endotoxin and Anti-Endotoxin: The Contribution of the Schools of Koch and Pasteur: Life, Milestone-Experiments and Concepts of Richard Pfeiffer (Berlin) and Alexandre Besredka (Paris)","volume":"8","author":"Rietschel","year":"2002","journal-title":"J. Endotoxin Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1385\/MB:19:3:279","article-title":"The Biology of Endotoxin","volume":"19","author":"Heine","year":"2001","journal-title":"Mol. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1051\/ocl\/2020025","article-title":"Lipopolysaccharides: Structure, Function and Bacterial Identification","volume":"27","author":"Caroff","year":"2020","journal-title":"OCL"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1021\/acs.chemrev.0c00587","article-title":"Assembly and Maintenance of Lipids at the Bacterial Outer Membrane","volume":"121","author":"Lundstedt","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide Endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bertani, B., and Ruiz, N. (2018). Function and Biogenesis of Lipopolysaccharides. EcoSal Plus, 8.","DOI":"10.1128\/ecosalplus.esp-0001-2018"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1128\/IAI.00939-07","article-title":"Sensing Gram-Negative Bacterial Lipopolysaccharides: A Human Disease Determinant?","volume":"76","author":"Munford","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00046-17","DOI":"10.1128\/mSystems.00046-17","article-title":"Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling","volume":"2","author":"Abubucker","year":"2017","journal-title":"MSystems"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13054-020-02989-1","article-title":"The Gut Microbiome\u2019s Role in the Development, Maintenance, and Outcomes of Sepsis","volume":"24","author":"Adelman","year":"2020","journal-title":"Crit. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/ni1386","article-title":"Virulence Factors of Yersinia Pestis Are Overcome by a Strong Lipopolysaccharide Response","volume":"7","author":"Montminy","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1093\/femsre\/fuw007","article-title":"Lipopolysaccharide Modification in Gram-Negative Bacteria during Chronic Infection","volume":"40","author":"Maldonado","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.00098.2016","article-title":"Gastrointestinal and Hepatic Mechanisms Limiting Entry and Dissemination of Lipopolysaccharide into the Systemic Circulation","volume":"311","author":"Guerville","year":"2016","journal-title":"Am. J. Physiol. -Gastrointest. Liver Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1039\/c5ib00158g","article-title":"On the Translocation of Bacteria and Their Lipopolysaccharides between Blood and Peripheral Locations in Chronic, Inflammatory Diseases: The Central Roles of LPS and LPS-Induced Cell Death","volume":"7","author":"Kell","year":"2015","journal-title":"Integr. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"622935","DOI":"10.3389\/fimmu.2021.622935","article-title":"Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein","volume":"12","author":"Nguyen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00134-006-0432-y","article-title":"Lipoproteins in Inflammation and Sepsis. I. Basic Science","volume":"33","author":"Murch","year":"2007","journal-title":"Intensive Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eabe6729","DOI":"10.1126\/science.abe6729","article-title":"Enterically Derived High-Density Lipoprotein Restrains Liver Injury through the Portal Vein","volume":"373","author":"Han","year":"2021","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"a029181","DOI":"10.1101\/cshperspect.a029181","article-title":"Cell\u2013Cell Junctions Organize Structural and Signaling Networks","volume":"10","author":"Garcia","year":"2018","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_23","first-page":"974","article-title":"Ileus in the Critically Ill: Causes, Treatment and Prevention","volume":"86","author":"Huet","year":"2020","journal-title":"Minerva. Anestesiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000206143","article-title":"Role of Translocation of Pathogen-Associated Molecular Patterns in Sepsis","volume":"26","author":"Tsujimoto","year":"2009","journal-title":"Dig. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3389\/fimmu.2019.00891","article-title":"Challenge to the Intestinal Mucosa During Sepsis","volume":"10","author":"Haussner","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-2567.2004.01976.x","article-title":"Signal Transduction by the Lipopolysaccharide Receptor, Toll-like Receptor-4","volume":"113","year":"2004","journal-title":"Immunology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.coi.2016.10.005","article-title":"Early Innate Immune Responses to Bacterial LPS","volume":"44","author":"Rosadini","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Aluri, J., Cooper, M.A., and Schuettpelz, L.G. (2021). Toll-Like Receptor Signaling in the Establishment and Function of the Immune System. Cells, 10.","DOI":"10.3390\/cells10061374"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1038\/ncomms4125","article-title":"TRPA1 Channels Mediate Acute Neurogenic Inflammation and Pain Produced by Bacterial Endotoxins","volume":"5","author":"Meseguer","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/s41467-017-01201-3","article-title":"TRPV4 Activation Triggers Protective Responses to Bacterial Lipopolysaccharides in Airway Epithelial Cells","volume":"8","author":"Alpizar","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mazgaeen, L., and Gurung, P. (2020). Recent Advances in Lipopolysaccharide Recognition Systems. IJMS, 21.","DOI":"10.3390\/ijms21020379"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41590-019-0368-3","article-title":"Innate Immunity to Intracellular LPS","volume":"20","author":"Rathinam","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"585146","DOI":"10.3389\/fimmu.2020.585146","article-title":"Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4\/11 Mediated Inflammatory Pathways","volume":"11","author":"Zamyatina","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1172\/JCI94495","article-title":"Caspase-11\u2013Mediated Endothelial Pyroptosis Underlies Endotoxemia-Induced Lung Injury","volume":"127","author":"Cheng","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/ALN.0000000000002271","article-title":"Dying as a Pathway to Death in Sepsis","volume":"129","author":"Zhang","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of Acute Kidney Injury in Critically Ill Patients: The Multinational AKI-EPI Study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.294.7.813","article-title":"Acute Renal Failure in Critically Ill PatientsA Multinational, Multicenter Study","volume":"294","author":"Uchino","year":"2005","journal-title":"JAMA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/01.CCM.0000194725.48928.3A","article-title":"Sepsis in European Intensive Care Units: Results of the SOAP Study","volume":"34","author":"Vincent","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1164\/rccm.201505-0995OC","article-title":"The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock","volume":"193","author":"Kellum","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1097\/ALN.0b013e31820b8b44","article-title":"Toll-Like Receptor 4 Inhibitor TAK-242 Attenuates Acute Kidney Injury in Endotoxemic Sheep","volume":"114","author":"Fenhammar","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/apha.12798","article-title":"Physiological Aspects of Toll-like Receptor 4 Activation in Sepsis-Induced Acute Kidney Injury","volume":"219","author":"Anderberg","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1681\/ASN.2011020203","article-title":"Endotoxin Uptake by S1 Proximal Tubular Segment Causes Oxidative Stress in the Downstream S2 Segment","volume":"22","author":"Kalakeche","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/SHK.0000000000000473","article-title":"The Endothelium in Sepsis","volume":"45","author":"Ince","year":"2016","journal-title":"Shock"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Czaikoski, P.G., Mota, J.M.S.C., Nascimento, D.C., S\u00f4nego, F., Castanheira, F.V.e.S., Melo, P.H., Scortegagna, G.T., Silva, R.L., Barroso-Sousa, R., and Souto, F.O. (2016). Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148142"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/SHK.0000000000000052","article-title":"A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, Microcirculatory Dysfunction, Bioenergetics, and the Tubular Cell Adaptation to Injury","volume":"41","author":"Gomez","year":"2014","journal-title":"Shock"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cardiores.2006.09.011","article-title":"Toll-like Receptor Stimulation in Cardiomyoctes Decreases Contractility and Initiates an NF-\u039aB Dependent Inflammatory Response","volume":"72","author":"Boyd","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1056\/NEJM198908033210503","article-title":"The Cardiovascular Response of Normal Humans to the Administration of Endotoxin","volume":"321","author":"Suffredini","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.chest.2018.08.1037","article-title":"The Septic Heart","volume":"155","author":"Martin","year":"2019","journal-title":"Chest"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3389\/fimmu.2020.00229","article-title":"LPS Induces Active HMGB1 Release From Hepatocytes Into Exosomes Through the Coordinated Activities of TLR4 and Caspase-11\/GSDMD Signaling","volume":"11","author":"Li","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.immuni.2018.08.016","article-title":"The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis","volume":"49","author":"Deng","year":"2018","journal-title":"Immunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1007\/s10753-021-01442-x","article-title":"Neutrophil-Induced Liver Injury and Interactions Between Neutrophils and Liver Sinusoidal Endothelial Cells","volume":"44","author":"Wang","year":"2021","journal-title":"Inflammation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1378\/chest.99.1.169","article-title":"Endotoxemia in Human Septic Shock","volume":"99","author":"Danner","year":"1991","journal-title":"Chest"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1086\/422254","article-title":"Diagnostic and Prognostic Implications of Endotoxemia in Critical Illness: Results of the MEDIC Study","volume":"190","author":"Marshall","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/shk.0b013e31805363c6","article-title":"Daily Varialtion in Endotoxin Levels Is Associated with Increased Organ Failure in Critically Ill Patients","volume":"28","author":"Klein","year":"2007","journal-title":"Shock"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1085","DOI":"10.1097\/MD.0000000000001085","article-title":"Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate","volume":"94","author":"Adamik","year":"2015","journal-title":"Medicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"R102","DOI":"10.1186\/cc7934","article-title":"Prevalence of Endotoxemia after Surgery and Its Association with ICU Length of Stay","volume":"13","author":"Valenza","year":"2009","journal-title":"Crit. Care"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1086\/315093","article-title":"Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS-Binding Protein in Patients with Severe Sepsis and Septic Shock","volume":"180","author":"Opal","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1007\/s00134-018-5463-7","article-title":"Polymyxin B Hemoperfusion in Endotoxemic Septic Shock Patients without Extreme Endotoxemia: A Post Hoc Analysis of the EUPHRATES Trial","volume":"44","author":"Klein","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00005-015-0348-8","article-title":"Endotoxin Elimination in Patients with Septic Shock: An Observation Study","volume":"63","author":"Adamik","year":"2015","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/SHK.0000000000000565","article-title":"Mechanisms of Intestinal Barrier Dysfunction in Sepsis","volume":"46","author":"Yoseph","year":"2016","journal-title":"Shock"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.hlc.2016.10.012","article-title":"Prolonged Cardiopulmonary Bypass Is a Risk Factor for Intestinal Ischaemic Damage and Endotoxaemia","volume":"26","author":"Adamik","year":"2017","journal-title":"Heart Lung Circ."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s15010-018-1178-5","article-title":"Gut-Origin Sepsis in the Critically Ill Patient: Pathophysiology and Treatment","volume":"46","author":"Assimakopoulos","year":"2018","journal-title":"Infection"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ccc.2005.01.005","article-title":"Epithelial Barrier Dysfunction: A Unifying Theme to Explain the Pathogenesis of Multiple Organ Dysfunction at the Cellular Level","volume":"21","author":"Fink","year":"2005","journal-title":"Crit. Care Clin."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-121-1-199407010-00001","article-title":"Treatment of Septic Shock with Human Monoclonal Antibody HA-1A: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"121","author":"McCloskey","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1001\/jama.283.13.1723","article-title":"E5 Murine Monoclonal Antiendotoxin Antibody in Gram-Negative SepsisA Randomized Controlled Trial","volume":"283","author":"Angus","year":"2000","journal-title":"JAMA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1097\/CCM.0b013e3181b0266c","article-title":"Efficacy and Safety of a Phospholipid Emulsion (GR270773) in Gram-Negative Severe Sepsis: Results of a Phase II Multicenter, Randomized, Placebo-Controlled, Dose-Finding Clinical Trial","volume":"37","author":"Tomayko","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0140-6736(00)02712-4","article-title":"Recombinant Bactericidal\/Permeability-Increasing Protein (RBPI21) as Adjunctive Treatment for Children with Severe Meningococcal Sepsis: A Randomised Trial","volume":"356","author":"Levin","year":"2000","journal-title":"Lancet"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1001\/jama.2013.2194","article-title":"Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis: The ACCESS Randomized Trial","volume":"309","author":"Opal","year":"2013","journal-title":"JAMA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1046\/j.1526-0968.2003.00006.x","article-title":"Endotoxin Adsorption by Polymyxin B Immobilized Fiber Column in Patients with Systemic Inflammatory Response Syndrome: The Japanese Experience","volume":"7","author":"Sato","year":"2003","journal-title":"Ther. Apher. Dial."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.transci.2017.08.015","article-title":"Endotoxin Adsorption: Direct Hemoperfusion with the Polymyxin B-Immobilized Fiber Column (PMX)","volume":"56","author":"Shimizu","year":"2017","journal-title":"Transfus. Apher. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R47","DOI":"10.1186\/cc5780","article-title":"Effectiveness of Polymyxin B-Immobilized Fiber Column in Sepsis: A Systematic Review","volume":"11","author":"Cruz","year":"2007","journal-title":"Crit. Care"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/01.shk.0000159930.87737.8a","article-title":"A Pilot-Controlled Study of a Polymyxin B-Immobilized Hemoperfusion Cartridge in Patients with Severe Sepsis Secondary to Intra-Abdominal Infection","volume":"23","author":"Vincent","year":"2005","journal-title":"Shock"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1001\/jama.2009.856","article-title":"Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock: The EUPHAS Randomized Controlled Trial","volume":"301","author":"Cruz","year":"2009","journal-title":"JAMA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1001\/jama.2009.1606","article-title":"Polymyxin B Hemoperfusion and Mortality in Abdominal Septic Shock","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s00134-018-5481-5","article-title":"Treatment with a Polymyxin B Filter to Capture Endotoxin in Sepsis Patients: Is There a Signal for Therapeutic Efficacy?","volume":"45","author":"Pickkers","year":"2019","journal-title":"Intensive Care Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"The ABDOMIX Group, Payen, D.M., Guilhot, J., Launey, Y., Lukaszewicz, A.C., Kaaki, M., Veber, B., Pottecher, J., Joannes-Boyau, O., and Martin-Lefevre, L. (2015). Early Use of Polymyxin B Hemoperfusion in Patients with Septic Shock Due to Peritonitis: A Multicenter Randomized Control Trial. Intensive Care Med., 41, 975\u2013984.","DOI":"10.1007\/s00134-015-3751-z"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s00134-015-3931-x","article-title":"Polymyxin B Hemoperfusion in Septic Shock: Just Look at the Evidence!","volume":"41","author":"Antonelli","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1001\/jama.2018.14618","article-title":"Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial","volume":"320","author":"Dellinger","year":"2018","journal-title":"JAMA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000475982","article-title":"Novel Insights into the Direct Removal of Endotoxin by Polymyxin B Hemoperfusion","volume":"44","author":"Romaschin","year":"2017","journal-title":"Blood Purif."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00134-017-5004-9","article-title":"Polymyxin B-Immobilized Hemoperfusion and Mortality in Critically Ill Adult Patients with Sepsis\/Septic Shock: A Systematic Review with Meta-Analysis and Trial Sequential Analysis","volume":"44","author":"Fujii","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"206","DOI":"10.21037\/atm.2018.05.41","article-title":"Impact of Polymyxin B Hemoperfusion in the Treatment of Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Controlled Trials","volume":"6","author":"Kuriyama","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e858","DOI":"10.1097\/CCM.0000000000002362","article-title":"Effects of Polymyxin B Hemoperfusion on Mortality in Patients With Severe Sepsis and Septic Shock: A Systemic Review, Meta-Analysis Update, and Disease Severity Subgroup Meta-Analysis","volume":"45","author":"Chang","year":"2017","journal-title":"Crit. Care Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jcrc.2020.09.007","article-title":"Effectiveness of Polymyxin B-Immobilized Hemoperfusion against Sepsis and Septic Shock: A Systematic Review and Meta-Analysis","volume":"63","author":"Li","year":"2021","journal-title":"J. Crit. Care"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"The EUPHAS 2 Collaborative Group, Cutuli, S.L., Artigas, A., Fumagalli, R., Monti, G., Ranieri, V.M., Ronco, C., and Antonelli, M. (2016). Polymyxin-B Hemoperfusion in Septic Patients: Analysis of a Multicenter Registry. Ann. Intensive Care, 6, 77.","DOI":"10.1186\/s13613-016-0178-9"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000444474","article-title":"Potential Survival Benefit of Polymyxin B Hemoperfusion in Septic Shock Patients on Continuous Renal Replacement Therapy: A Propensity-Matched Analysis","volume":"42","author":"Iwagami","year":"2016","journal-title":"Blood Purif."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1097\/CCM.0000000000000150","article-title":"Postoperative Polymyxin B Hemoperfusion and Mortality in Patients with Abdominal Septic Shock: A Propensity-Matched Analysis","volume":"42","author":"Iwagami","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40635-020-00362-8","article-title":"Endotoxemia and Circulating Bacteriome in Severe COVID-19 Patients","volume":"8","author":"Sirivongrangson","year":"2020","journal-title":"Intensive Care Med. Exp."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.abc6261","article-title":"Systems Biological Assessment of Immunity to Mild versus Severe COVID-19 Infection in Humans","volume":"369","author":"Arunachalam","year":"2020","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Khan, S., Bolotova, O., Sahib, H., Foster, D., and Mallipattu, S.K. (2021). Endotoxemia in Critically Ill Patients with COVID-19. Blood Purif., 1\u20137.","DOI":"10.1159\/000518230"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.21873\/invivo.12528","article-title":"Intestinal Barrier Biomarker ZO1 and Endotoxin Are Increased in Blood of Patients With COVID-19-Associated Pneumonia","volume":"35","author":"Assimakopoulos","year":"2021","journal-title":"In Vivo"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e00348","DOI":"10.14309\/ctg.0000000000000348","article-title":"Low-Grade Endotoxemia and Thrombosis in COVID-19","volume":"12","author":"Oliva","year":"2021","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_93","first-page":"E187","article-title":"Polymyxin B Hemoperfusion in Coronavirus Disease 2019 Patients with Endotoxic Shock: Case Series from EUPHAS2 Registry","volume":"45","author":"Cutuli","year":"2021","journal-title":"Artif. Organs"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1159\/000515628","article-title":"Endotoxin Adsorbent Therapy in Severe COVID-19 Pneumonia","volume":"51","author":"Peerapornratana","year":"2021","journal-title":"Blood Purif."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/jca.21861","article-title":"Direct Hemoperfusion Using a Polymyxin B-immobilized Polystyrene Column for COVID-19","volume":"36","author":"Katagiri","year":"2021","journal-title":"J. Clin. Apher."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000336341","article-title":"Time to Initiation of Treatment with Polymyxin B Cartridge Hemoperfusion in Septic Shock Patients","volume":"33","author":"Takeyama","year":"2012","journal-title":"Blood Purif."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10047-016-0922-9","article-title":"Early Induction of Direct Hemoperfusion with a Polymyxin-B Immobilized Column Is Associated with Amelioration of Hemodynamic Derangement and Mortality in Patients with Septic Shock","volume":"20","author":"Chihara","year":"2017","journal-title":"J. Artif. Organs"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e446","DOI":"10.1002\/ams2.446","article-title":"Impact of Timing of Polymyxin B-immobilized Fiber Column Direct Hemoperfusion on Outcome in Patients with Septic Shock: A Single-center Observational Study","volume":"7","author":"Tanaka","year":"2020","journal-title":"Acute Med. Surg."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/1744-9987.12339","article-title":"Clinical Effects of a Longer Duration of Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion Therapy for Severe Sepsis and Septic Shock: Longer Duration of PMX-DHP Therapy","volume":"19","author":"Yamashita","year":"2015","journal-title":"Apher. Dial."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40560-017-0214-3","article-title":"Prolonged Direct Hemoperfusion Using a Polymyxin B Immobilized Fiber Cartridge Provides Sustained Circulatory Stabilization in Patients with Septic Shock: A Retrospective Observational before-after Study","volume":"5","author":"Miyamoto","year":"2017","journal-title":"J. Intensive Care"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000515685","article-title":"Impact of Extended Duration of Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion on Hemodynamics, Vasoactive Substance Requirement, and Pulmonary Oxygenation in Patients with Sepsis: An Observational Study","volume":"51","author":"Mitaka","year":"2021","journal-title":"Blood Purif."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000315923","article-title":"Early Management of Endotoxemia Using the Endotoxin Activity Assay and Polymyxin B-Based Hemoperfusion","volume":"Volume 167","author":"Ronco","year":"2010","journal-title":"Contributions to Nephrology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e0083","DOI":"10.1097\/CCE.0000000000000083","article-title":"Importance of Endotoxin Clearance in Endotoxemic Septic Shock: An Analysis from the Evaluating Use of PolymyxinB Hemoperfusion in a Randomized Controlled Trial of Adults Treated for Endotoxemic Septic Shock (EUPHRATES) Trial","volume":"2","author":"Rachoin","year":"2020","journal-title":"Crit. Care Explor."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:08:07Z","timestamp":1760134087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":103,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jcm11030619"],"URL":"https:\/\/doi.org\/10.3390\/jcm11030619","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]}}}