Extracorporeal Blood Purification Techniques in Sepsis and ARDS: Evaluation of ECCO₂R and CytoSorb® Hemoadsorption – A Narrative Review
DOI:
https://doi.org/10.12775/JEHS.2026.95.73716Keywords
Extracorporeal carbon dioxide removal (ECCO₂R), CytoSorb, Hemoadsorption, Sepsis, Septic shockAbstract
Background: Sepsis is a life-threatening syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. It is associated with an imbalance between pro-inflammatory and anti-inflammatory pathways, leading to multiple organ injury, including acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS). Despite advances in critical care medicine, sepsis remains one of the leading causes of mortality in intensive care units (ICUs). Increasing interest has focused on extracorporeal blood purification techniques aimed at modulating cytokine levels and facilitating carbon dioxide removal.
Aim: The aim of this study was to provide an overview and critical evaluation of two extracorporeal blood purification modalities—extracorporeal carbon dioxide removal (ECCO₂R) and CytoSorb therapy.
Materials and Methods: A narrative literature review was conducted using the PubMed database. Publications available up to April 2026 were identified using keywords related to CytoSorb, hemoadsorption, ECCO₂R, sepsis, ARDS, and critical care. Priority was given to systematic reviews, meta-analyses, randomized controlled trials, and observational studies. The retrieved evidence was synthesized narratively.
Results: Both ECCO₂R, which facilitates carbon dioxide clearance, and CytoSorb hemoadsorption therapy, which removes circulating cytokines and inflammatory mediators, demonstrate high efficacy. However, current clinical trials have not shown significant improvements in mortality. This discrepancy may be related to patient heterogeneity and the lack of phenotype-based selection. ECCO₂R may be beneficial in ARDS phenotypes characterized by predominant hypercapnia, whereas CytoSorb therapy may be most effective in patients with the hyperinflammatory delta sepsis phenotype.
References
Andersson, U., & Tracey, K. J. (2003). HMGB1 in Sepsis. Scandinavian Journal of Infectious Diseases, 35(9), 577–584. https://doi.org/10.1080/00365540310016286
Bos, L. D. J., & Ware, L. B. (2022). Acute respiratory distress syndrome: Causes, pathophysiology, and phenotypes. The Lancet, 400(10358), 1145–1156. https://doi.org/10.1016/S0140-6736(22)01485-4
Brozat, C. I., Zoller, M., Frank, S., Bruegel, M., Gräfe, C., Rebholz, D., Paal, M., Graf, H., Liebchen, U., & Scharf, C. (2025). Albumin and Platelet Loss during the Application of CytoSorb® in Critically Ill Patients: A post hoc Analysis of the Cyto-SOLVE Trial. Blood Purification, 54(2), 93–101. https://doi.org/10.1159/000542009
Brzozowska, P., Nowińska, B., Lissak, K., Bińczyk, W., Dróżdż, O., Siudek, B., & Wiśniewska, A. (2024). A case report: Acute sinusitis turned into shockingly rapid sepsis at young male adult. Quality in Sport, 16, 52676. https://doi.org/10.12775/QS.2024.16.52676
Daniel, M., Bedoui, Y., Vagner, D., Raffray, L., Ah-Pine, F., Doray, B., & Gasque, P. (2022). Pathophysiology of Sepsis and Genesis of Septic Shock: The Critical Role of Mesenchymal Stem Cells (MSCs). International Journal of Molecular Sciences, 23(16), 9274. https://doi.org/10.3390/ijms23169274
De Backer, D., Donadello, K., Taccone, F. S., Ospina-Tascon, G., Salgado, D., & Vincent, J.-L. (2011). Microcirculatory alterations: Potential mechanisms and implications for therapy. Annals of Intensive Care, 1(1), 27. https://doi.org/10.1186/2110-5820-1-27
Derdak, S. (2022). Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation Effect on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure. JAMA, 327(1), 82. https://doi.org/10.1001/jama.2021.21002
Duffin, J., Mikulis, D. J., & Fisher, J. A. (2021). Control of Cerebral Blood Flow by Blood Gases. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.640075
Ferluga, M., Lucangelo, U., & Blanch, L. (2018). Dead space in acute respiratory distress syndrome. Annals of Translational Medicine, 6(19), 388–388. https://doi.org/10.21037/atm.2018.09.46
Graf, H., Gräfe, C., Bruegel, M., Happich, F. L., Wustrow, V., Wegener, A., Wilfert, W., Zoller, M., Liebchen, U., Paal, M., & Scharf, C. (2024). Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb® in Patients with Hyperinflammation: A Prospective Study. Infectious Diseases and Therapy, 13(9), 2089–2101. https://doi.org/10.1007/s40121-024-01028-8
Graf, H., Gräfe, C., Bruegel, M., Zoller, M., Maciuga, N., Frank, S., Weidhase, L., Paal, M., & Scharf, C. (2024). Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb® in patients with severe rhabdomyolysis: A prospective trial. Annals of Intensive Care, 14(1), 96. https://doi.org/10.1186/s13613-024-01334-x
Harm, S., Gabor, F., & Hartmann, J. (2015). Characterization of Adsorbents for Cytokine Removal from Blood in an In Vitro Model. Journal of Immunology Research, 2015, 1–11. https://doi.org/10.1155/2015/484736
Hawchar, F., Rao, C., Akil, A., Mehta, Y., Rugg, C., Scheier, J., Adamson, H., Deliargyris, E., & Molnar, Z. (2021). The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock. Biomedicines, 9(7). https://doi.org/10.3390/biomedicines9070768
Hotchkiss, R. S., Moldawer, L. L., Opal, S. M., Reinhart, K., Turnbull, I. R., & Vincent, J.-L. (2016). Sepsis and septic shock. Nature Reviews Disease Primers, 2(1), 16045. https://doi.org/10.1038/nrdp.2016.45
Jansen, A., Waalders, N. J. B., van Lier, D. P. T., Kox, M., & Pickkers, P. (2023). CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo. Critical Care, 27(1), 117. https://doi.org/10.1186/s13054-023-04391-z
Karagiannidis, C., Hesselmann, F., & Fan, E. (2019). Physiological and Technical Considerations of Extracorporeal CO2 Removal. Critical Care, 23(1), 75. https://doi.org/10.1186/s13054-019-2367-z
Kenda, S., Gubenšek, J., & Vovk, T. (2026). Antibiotics and Other Drugs Removal by the CytoSorb® Haemoadsorber: A Systematic Review of Available Evidence. Antibiotics, 15(4), 409. https://doi.org/10.3390/antibiotics15040409
Körtge, A., Klinkmann, G., Kamper, C., Wasserkort, R., & Mitzner, S. (2026). Effects of hemoadsorption on plasma catecholamine levels: An in vitro study. Scientific Reports, 16(1). https://doi.org/10.1038/s41598-026-49101-1
Lindskog, S. (1997). Structure and mechanism of carbonic anhydrase. Pharmacology & Therapeutics, 74(1), 1–20. https://doi.org/10.1016/S0163-7258(96)00198-2
Lopez-Castejon, G., & Brough, D. (2011). Understanding the mechanism of IL-1β secretion. Cytokine & Growth Factor Reviews, 22(4), 189–195. https://doi.org/10.1016/j.cytogfr.2011.10.001
Lotz, C., Heckelmann, J., Lendzian, C., Herrmann, J., Haack, B., Gieselmann, M., Wedekink, F., Röder, D., Schlegel, N., Meybohm, P., Wischhusen, J., & Notz, Q. (2026). Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled Trial. Shock, 65(4), 637–647. https://doi.org/10.1097/SHK.0000000000002802
Malhotra, A. (2007). Low-Tidal-Volume Ventilation in the Acute Respiratory Distress Syndrome. New England Journal of Medicine, 357(11), 1113–1120. https://doi.org/10.1056/NEJMct074213
Millar, J. E., Boyle, A. J., Drake, T. M., Adams, C. E., Glass, A. W., Blackwood, B., McNamee, J. J., & McAuley, D. F. (2022). Extracorporeal carbon dioxide removal in acute hypoxaemic respiratory failure: A systematic review, Bayesian meta-analysis and trial sequential analysis. European Respiratory Review, 31(166), 220030. https://doi.org/10.1183/16000617.0030-2022
Orban, C., Bratu, A., Agapie, M., Borjog, T., Jafal, M., Sima, R.-M., Dumitrașcu, O. C., & Popescu, M. (2025). To Hemoadsorb or Not to Hemoadsorb—Do We Have the Answer Yet? An Updated Meta-Analysis on the Use of CytoSorb in Sepsis and Septic Shock. Biomedicines, 13(1), 180. https://doi.org/10.3390/biomedicines13010180
Polyovyy, V., Dzyubanovsky, I., Kovalchuk, A., Dzyubanovsky, O., & Dzhyvak, V. (2021). Dynamics of cytokine profile in patients with abdominal sepsis caused by pancreonecrosis. Journal of Education, Health and Sport, 11(5), 207–212. https://doi.org/10.12775/JEHS.2021.11.05.021
Prescott, H. C., Antonelli, M., Alhazzani, W., Møller, M. H., Alshamsi, F., Azevedo, L. C. P., Belley-Cote, E., De Waele, J., Derde, L., Dionne, J. C., Evans, L., Gershengorn, H. B., Hodgson, C. L., Honarmand, K., Kesecioglu, J., McIntyre, L., Mer, M., Nunnally, M. E., Oczkowski, S. J. W., … Coopersmith, C. M. (2026). Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Critical Care Medicine. https://doi.org/10.1097/CCM.0000000000007075
Romay, E., & Ferrer, R. (2016). Extracorporeal CO2 removal: Technical and physiological fundaments and principal indications. Medicina Intensiva (English Edition), 40(1), 33–38. https://doi.org/10.1016/j.medine.2015.12.002
Ronco, C., Ricci, Z., & Husain-Syed, F. (2019). From Multiple Organ Support Therapy to Extracorporeal Organ Support in Critically Ill Patients. Blood Purification, 48(2), 99–105. https://doi.org/10.1159/000490694
Scharf, C., Weinelt, F., Schroeder, I., Paal, M., Weigand, M., Zoller, M., Irlbeck, M., Kloft, C., Briegel, J., & Liebchen, U. (2022). Does the cytokine adsorber CytoSorb® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? A prospective observational study. Annals of Intensive Care, 12(1), 44. https://doi.org/10.1186/s13613-022-01017-5
Seymour, C. W., Kennedy, J. N., Wang, S., Chang, C.-C. H., Elliott, C. F., Xu, Z., Berry, S., Clermont, G., Cooper, G., Gomez, H., Huang, D. T., Kellum, J. A., Mi, Q., Opal, S. M., Talisa, V., van der Poll, T., Visweswaran, S., Vodovotz, Y., Weiss, J. C., … Angus, D. C. (2019). Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA, 321(20), 2003. https://doi.org/10.1001/jama.2019.5791
Slobod, D., Damia, A., Leali, M., Spinelli, E., & Mauri, T. (2022). Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome. Biology, 12(1), 67. https://doi.org/10.3390/biology12010067
Slutsky, A. S., & Ranieri, V. M. (2013). Ventilator-Induced Lung Injury. New England Journal of Medicine, 369(22), 2126–2136. https://doi.org/10.1056/NEJMra1208707
Spatola, L., Granata, A., D’Amico, M., Oddo, G., & Gambaro, A. (2025). Hemadsorption with CytoSorb®: Focus on the latest experiences in cardiac surgery patients. Journal of Artificial Organs, 28(3), 317–328. https://doi.org/10.1007/s10047-024-01485-5
Srzić, I. (2022). Sepsis definition: What’s new in the Treatment Guidelines. Acta Clinica Croatica. https://doi.org/10.20471/acc.2022.61.s1.11
Steindl, D., Schroeder, T., Krannich, A., & Nee, J. (2025). Hemoadsorption in the Management of Septic Shock: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine, 14(7), 2285. https://doi.org/10.3390/jcm14072285
Stommel, A.-M., Herkner, H., Kienbacher, C. L., Wildner, B., Hermann, A., & Staudinger, T. (2024). Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: A systematic review and meta-analysis. Critical Care, 28(1), 146. https://doi.org/10.1186/s13054-024-04927-x
Suchomska, M., Halota, W., & Olczak, A. (2019). Systemic inflammatory response syndrome and sepsis – epidemiology, differentiation, diagnostics in in clinical practice. https://doi.org/10.5281/ZENODO.2579349
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295–a016295. https://doi.org/10.1101/cshperspect.a016295
Thompson, B. T., Chambers, R. C., & Liu, K. D. (2017). Acute Respiratory Distress Syndrome. New England Journal of Medicine, 377(6), 562–572. https://doi.org/10.1056/NEJMra1608077
Tiruvoipati, R., Akkanti, B., Dinh, K., Barrett, N., May, A., Kimmel, J., & Conrad, S. A. (2023). Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study*. Critical Care Medicine, 51(7), 892–902. https://doi.org/10.1097/CCM.0000000000005845
Worku, E., Brodie, D., Ling, R. R., Ramanathan, K., Combes, A., & Shekar, K. (2023). Venovenous extracorporeal CO 2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature. Perfusion, 38(5), 1062–1079. https://doi.org/10.1177/02676591221096225
Xu, J. (2023). A review: Continuous renal replacement therapy for sepsis-associated acute kidney injury. All Life, 16(1). https://doi.org/10.1080/26895293.2022.2163305
Yu, T. Z., Tatum, R. T., Saxena, A., Ahmad, D., Yost, C. C., Maynes, E. J., O’Malley, T. J., Massey, H. T., Swol, J., Whitson, B. A., & Tchantchaleishvili, V. (2022). Utilization and outcomes of extracorporeal CO 2 removal (ECCO 2 R): Systematic review and meta‐analysis of arterio‐venous and veno‐venous ECCO 2 R approaches. Artificial Organs, 46(5), 763–774. https://doi.org/10.1111/aor.14130
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Julia Jasińska, Dominik Iskrzyński, Aleksandra Bułat, Aleksandra Gródek, Julia Iglantowicz, Sylwia Sanakiewicz, Patryk Obajtek, Wiktoria Dubiel, Mikołaj Dubiel
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 88
Number of citations: 0
