Cytokine adsorption therapy: how to weigh the pros and cons?_West China Medical Journal

Authors：

GE Dong ¹ , SU Xiaolei ¹ ,  YANG Rongli ^1,2

1. Department of Critical Care Medicine, Central Hospital of Dalian University of Technology, Dalian, Liaoning 116033, P. R. China;
2. Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning 116033, P. R. China;

Corresponding author：

YANG Rongli, Email: yever3000@dlut.edu.cn

Keywords：

Cytokine storm; cytokine adsorption; sepsis; cardiac surgery

DOI：

10.7507/1002-0179.202507116

Video：

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Cytokine storm is a life-threatening hyperinflammatory response. Current limited evidence-based research findings suggest that cytokine adsorption technologies do not reduce mortality in patients undergoing cardiac surgery or those with septic shock, nor do they improve hemodynamics or lower interleukin-6 levels. These negative outcomes may be related to improper timing and method of use, insufficient adsorption efficacy and non-specific adsorption of antibiotics, albumin, platelets, and other substances. This article summarizes the optimal timing for initiating and terminating cytokine adsorption therapy, treatment modality selection, as well as treatment duration and frequency, aiming to provide clinical guidance.

1.	Shimizu M. Clinical features of cytokine storm syndrome. Adv Exp Med Biol, 2024, 1448: 33-42.
2.	Athale J, Busch LM, O’Grady NP. Cytokine release syndrome and sepsis: analogous clinical syndromes with distinct causes and challenges in management. Infect Dis Clin North Am, 2022, 36(4): 735-748.
3.	Carcillo JA, Shakoory B. Cytokine storm and sepsis-induced multiple organ dysfunction syndrome. Adv Exp Med Biol, 2024, 1448: 441-457.
4.	Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med, 2020, 383(23): 2255-2273.
5.	Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp, 2018, 6(1): 12.
6.	Nierhaus A, Morales J, Wendt D, et al. Comparison of the CytoSorb^{^®} 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study. Minim Invasive Ther Allied Technol, 2022, 31(7): 1058-1065.
7.	Kielstein JT, Zarbock A. Is this the beginning of the end of cytokine adsorption. Crit Care Med, 2022, 50(6): 1026-1029.
8.	La Manna G, Donati G. Coupled plasma filtration adsorption: a multipurpose extracorporeal detoxification therapy. Blood Purif, 2018, 46(3): 228-238.
9.	Hellman T, Uusalo P, Järvisalo MJ. Renal replacement techniques in septic shock. Int J Mol Sci, 2021, 22(19): 10238.
10.	Pezzi M, Renda S, Giglio AM, et al. The use of coupled plasma filtration adsorption in traumatic rhabdomyolysis. Case Rep Crit Care, 2017, 2017: 5764961.
11.	Rey S, Kulabukhov VM, Popov A, et al. Hemoperfusion using the lps-selective mesoporous polymeric adsorbent in septic shock: a multicenter randomized clinical trial. Shock, 2023, 59(6): 846-854.
12.	Nemeth E, Kovacs E, Racz K, et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study. Clin Transplant, 2018, 32(4): e13211.
13.	Boss K, Jahn M, Wendt D, et al. Extracorporeal cytokine adsorption: significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery. PLoS One, 2021, 16(2): e0246299.
14.	Pérez-Fernández X, Ulsamer A, Cámara-Rosell M, et al. Extracorporeal blood purification and acute kidney injury in cardiac surgery: the SIRAKI02 randomized clinical trial. JAMA, 2024, 332(17): 1446-1454.
15.	Bernardi MH, Rinoesl H, Dragosits K, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care, 2016, 20: 96.
16.	Poli EC, Alberio L, Bauer-Doerries A, et al. Cytokine clearance with CytoSorb^{^®} during cardiac surgery: a pilot randomized controlled trial. Crit Care, 2019, 23(1): 108.
17.	Geisler D, Arleth N, Grabenwöger J, et al. Impact of CytoSorb^{^®} on interleukin-6 in cardiac surgery. Front Cardiovasc Med, 2023, 10: 1166093.
18.	Hohn A, Malewicz-Oeck NM, Buchwald D, et al. REmoval of cytokines during CArdiac surgery (RECCAS): a randomised controlled trial. Crit Care, 2024, 28(1): 406.
19.	Nurmykhametova Z, Lesbekov T, Kaliyev R, et al. Preliminary report of extracorporeal blood purification therapy in patients receiving LVAD: Cytosorb or Jafron HA330. J Extra Corpor Technol, 2024, 56(1): 10-15.
20.	Matejic-Spasic M, Lindstedt S, Lebreton G, et al. The role of hemoadsorption in cardiac surgery - a systematic review. BMC Cardiovasc Disord, 2024, 24(1): 258.
21.	Naruka V, Salmasi MY, Arjomandi Rad A, et al. Use of cytokine filters during cardiopulmonary bypass: systematic review and Meta-analysis. Heart Lung Circ, 2022, 31(11): 1493-1503.
22.	Ramírez-Guerrero G, Pedreros-Rosales C. Hemoadsorption in cardiac surgery, limitations of low-risk patient selection and minimal cytokine levels. Crit Care, 2024, 28(1): 437.
23.	Friesecke S, Stecher SS, Gross S, et al. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs, 2017, 20(3): 252-259.
24.	Hawchar F, László I, Öveges N, et al. Extracorporeal cytokine adsorption in septic shock: a proof of concept randomized, controlled pilot study. J Crit Care, 2019, 49: 172-178.
25.	Scharf C, Schroeder I, Paal M, et al. Can the cytokine adsorber CytoSorb^{^®} help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis. Ann Intensive Care, 2021, 11(1): 115.
26.	Wendel Garcia PD, Hilty MP, Held U, et al. Cytokine adsorption in severe, refractory septic shock. Intensive Care Med, 2021, 47(11): 1334-1336.
27.	Stockmann H, Thelen P, Stroben F, et al. 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(6): 964-976.
28.	Onuk S, Akin AK, Sari A, et al. The clinical and laboratory efficacy of HA 330 treatment combined with continuous renal replacement therapy in septic shock patients: a case series. Blood Purif, 2023, 52(2): 140-147.
29.	Saldaña-Gastulo JJC, Llamas-Barbarán MDR, Coronel-Chucos LG, et al. Cytokine hemoadsorption with CytoSorb^{^®} in patients with sepsis: a systematic review and meta-analysis. Crit Care Sci, 2023, 35(2): 217-225.
30.	Orban C, Bratu A, Agapie M, et al. 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, 2025, 13(1): 180.
31.	Heymann M, Schorer R, Putzu A. The effect of CytoSorb on inflammatory markers in critically ill patients: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med, 2023, 51(12): 1659-1673.
32.	Wang G, He Y, Guo Q, et al. Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis. Crit Care, 2023, 27(1): 275.
33.	Chen JJ, Lai PC, Huang YT, et al. Bias and potential premature conclusions regarding the clinical benefits of oXiris in septic adult patients. Crit Care, 2023, 27(1): 314.
34.	Siew LY, Lee ZY, Yunos NM, et al. Outcomes of extracorporeal blood purification with oXiris^{^®} membrane in critically ill patients: a systematic review and meta-analysis. J Crit Care, 2024, 83: 154844.
35.	Livigni S, Bertolini G, Rossi C, et al. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open, 2014, 4(1): e003536.
36.	Garbero E, Livigni S, Ferrari F, et al. High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial. Intensive Care Med, 2021, 47(11): 1303-1311.
37.	Giménez-Esparza C, Portillo-Requena C, Colomina-Climent F, et al. The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption. BMJ Open, 2019, 9(12): e030139.
38.	Waalders NJB, Jansen A, Pickkers P. Effect of CytoSorb on interleukin-6. Crit Care Med, 2024, 52(3): e152-e153.
39.	Zhao D, Yang R, Liu S, et al. Study on the characteristics of early cytokine storm response to cardiac surgery. J Interferon Cytokine Res, 2023, 43(8): 351-358.
40.	Chao J, Cui S, Liu C, et al. Detection of early cytokine storm in patients with septic shock after abdominal surgery. J Transl Int Med, 2020, 8(2): 91-98.
41.	Brozat CI, Zoller M, Frank S, et al. Albumin and platelet loss during the application of CytoSorb^{^®} in critically ill patients: a post hoc analysis of the Cyto-SOLVE trial. Blood Purif, 2025, 54(2): 93-101.
42.	Scharf C, Weinelt F, Schroeder I, et al. Does the cytokine adsorber CytoSorb^{^®} reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study. Ann Intensive Care, 2022, 12(1): 44.
43.	Bottari G, Goffredo BM, Marano M, et al. Impact of continuous kidney replacement therapy and hemoadsorption with Cytosorb on antimicrobial drug removal in critically ill children with septic shock: a single-center prospective study on a pediatric cohort. Antibiotics (Basel), 2023, 12(9): 1395.
44.	Wang C, Li C, Yang P, et al. High adsorption capacity of hemoperfusion on imipenem in critically ill patients with septic shock: a case report. BMC Infect Dis, 2024, 24(1): 894.
45.	Girardot T, Schneider A, Rimmelé T. Blood purification techniques for sepsis and septic AKI. Semin Nephrol, 2019, 39(5): 505-514.
46.	Gruda MC, Ruggeberg KG, O’Sullivan P, et al. Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb^{^®} sorbent porous polymer beads. PLoS One, 2018, 13(1): e0191676.
47.	国家重症医学专业医疗质量控制中心重症肾脏学质控亚专业组. 中国重症血液吸附专家指导意见(2025 年). 中国急救医学, 2025, 45(6): 471-475.
48.	关明镜, 张凌. 吸附性血液滤过治疗脓毒症欧洲及亚太专家推荐意见解读. 华西医学, 2022, 37(7): 996-1000.
49.	Wieruszewski PM, Murad MH. Does CytoSorb pose unique challenges to pooled estimates in Meta-analysis?. Crit Care Med, 2023, 51(12): 1819-1821.
50.	Graf H, Gräfe C, Bruegel M, et al. Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb^{^®} in patients with severe rhabdomyolysis: a prospective trial. Ann Intensive Care, 2024, 14(1): 96.
51.	Zhang L, Cove M, Nguyen BG, et al. Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia pacific experience. Chin Med J (Engl), 2021, 134(18): 2258-2260.

1. Shimizu M. Clinical features of cytokine storm syndrome. Adv Exp Med Biol, 2024, 1448: 33-42.
2. Athale J, Busch LM, O’Grady NP. Cytokine release syndrome and sepsis: analogous clinical syndromes with distinct causes and challenges in management. Infect Dis Clin North Am, 2022, 36(4): 735-748.
3. Carcillo JA, Shakoory B. Cytokine storm and sepsis-induced multiple organ dysfunction syndrome. Adv Exp Med Biol, 2024, 1448: 441-457.
4. Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med, 2020, 383(23): 2255-2273.
5. Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp, 2018, 6(1): 12.
6. Nierhaus A, Morales J, Wendt D, et al. Comparison of the CytoSorb^{^®} 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study. Minim Invasive Ther Allied Technol, 2022, 31(7): 1058-1065.
7. Kielstein JT, Zarbock A. Is this the beginning of the end of cytokine adsorption. Crit Care Med, 2022, 50(6): 1026-1029.
8. La Manna G, Donati G. Coupled plasma filtration adsorption: a multipurpose extracorporeal detoxification therapy. Blood Purif, 2018, 46(3): 228-238.
9. Hellman T, Uusalo P, Järvisalo MJ. Renal replacement techniques in septic shock. Int J Mol Sci, 2021, 22(19): 10238.
10. Pezzi M, Renda S, Giglio AM, et al. The use of coupled plasma filtration adsorption in traumatic rhabdomyolysis. Case Rep Crit Care, 2017, 2017: 5764961.
11. Rey S, Kulabukhov VM, Popov A, et al. Hemoperfusion using the lps-selective mesoporous polymeric adsorbent in septic shock: a multicenter randomized clinical trial. Shock, 2023, 59(6): 846-854.
12. Nemeth E, Kovacs E, Racz K, et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study. Clin Transplant, 2018, 32(4): e13211.
13. Boss K, Jahn M, Wendt D, et al. Extracorporeal cytokine adsorption: significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery. PLoS One, 2021, 16(2): e0246299.
14. Pérez-Fernández X, Ulsamer A, Cámara-Rosell M, et al. Extracorporeal blood purification and acute kidney injury in cardiac surgery: the SIRAKI02 randomized clinical trial. JAMA, 2024, 332(17): 1446-1454.
15. Bernardi MH, Rinoesl H, Dragosits K, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care, 2016, 20: 96.
16. Poli EC, Alberio L, Bauer-Doerries A, et al. Cytokine clearance with CytoSorb^{^®} during cardiac surgery: a pilot randomized controlled trial. Crit Care, 2019, 23(1): 108.
17. Geisler D, Arleth N, Grabenwöger J, et al. Impact of CytoSorb^{^®} on interleukin-6 in cardiac surgery. Front Cardiovasc Med, 2023, 10: 1166093.
18. Hohn A, Malewicz-Oeck NM, Buchwald D, et al. REmoval of cytokines during CArdiac surgery (RECCAS): a randomised controlled trial. Crit Care, 2024, 28(1): 406.
19. Nurmykhametova Z, Lesbekov T, Kaliyev R, et al. Preliminary report of extracorporeal blood purification therapy in patients receiving LVAD: Cytosorb or Jafron HA330. J Extra Corpor Technol, 2024, 56(1): 10-15.
20. Matejic-Spasic M, Lindstedt S, Lebreton G, et al. The role of hemoadsorption in cardiac surgery - a systematic review. BMC Cardiovasc Disord, 2024, 24(1): 258.
21. Naruka V, Salmasi MY, Arjomandi Rad A, et al. Use of cytokine filters during cardiopulmonary bypass: systematic review and Meta-analysis. Heart Lung Circ, 2022, 31(11): 1493-1503.
22. Ramírez-Guerrero G, Pedreros-Rosales C. Hemoadsorption in cardiac surgery, limitations of low-risk patient selection and minimal cytokine levels. Crit Care, 2024, 28(1): 437.
23. Friesecke S, Stecher SS, Gross S, et al. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs, 2017, 20(3): 252-259.
24. Hawchar F, László I, Öveges N, et al. Extracorporeal cytokine adsorption in septic shock: a proof of concept randomized, controlled pilot study. J Crit Care, 2019, 49: 172-178.
25. Scharf C, Schroeder I, Paal M, et al. Can the cytokine adsorber CytoSorb^{^®} help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis. Ann Intensive Care, 2021, 11(1): 115.
26. Wendel Garcia PD, Hilty MP, Held U, et al. Cytokine adsorption in severe, refractory septic shock. Intensive Care Med, 2021, 47(11): 1334-1336.
27. Stockmann H, Thelen P, Stroben F, et al. 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(6): 964-976.
28. Onuk S, Akin AK, Sari A, et al. The clinical and laboratory efficacy of HA 330 treatment combined with continuous renal replacement therapy in septic shock patients: a case series. Blood Purif, 2023, 52(2): 140-147.
29. Saldaña-Gastulo JJC, Llamas-Barbarán MDR, Coronel-Chucos LG, et al. Cytokine hemoadsorption with CytoSorb^{^®} in patients with sepsis: a systematic review and meta-analysis. Crit Care Sci, 2023, 35(2): 217-225.
30. Orban C, Bratu A, Agapie M, et al. 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, 2025, 13(1): 180.
31. Heymann M, Schorer R, Putzu A. The effect of CytoSorb on inflammatory markers in critically ill patients: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med, 2023, 51(12): 1659-1673.
32. Wang G, He Y, Guo Q, et al. Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis. Crit Care, 2023, 27(1): 275.
33. Chen JJ, Lai PC, Huang YT, et al. Bias and potential premature conclusions regarding the clinical benefits of oXiris in septic adult patients. Crit Care, 2023, 27(1): 314.
34. Siew LY, Lee ZY, Yunos NM, et al. Outcomes of extracorporeal blood purification with oXiris^{^®} membrane in critically ill patients: a systematic review and meta-analysis. J Crit Care, 2024, 83: 154844.
35. Livigni S, Bertolini G, Rossi C, et al. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open, 2014, 4(1): e003536.
36. Garbero E, Livigni S, Ferrari F, et al. High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial. Intensive Care Med, 2021, 47(11): 1303-1311.
37. Giménez-Esparza C, Portillo-Requena C, Colomina-Climent F, et al. The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption. BMJ Open, 2019, 9(12): e030139.
38. Waalders NJB, Jansen A, Pickkers P. Effect of CytoSorb on interleukin-6. Crit Care Med, 2024, 52(3): e152-e153.
39. Zhao D, Yang R, Liu S, et al. Study on the characteristics of early cytokine storm response to cardiac surgery. J Interferon Cytokine Res, 2023, 43(8): 351-358.
40. Chao J, Cui S, Liu C, et al. Detection of early cytokine storm in patients with septic shock after abdominal surgery. J Transl Int Med, 2020, 8(2): 91-98.
41. Brozat CI, Zoller M, Frank S, et al. Albumin and platelet loss during the application of CytoSorb^{^®} in critically ill patients: a post hoc analysis of the Cyto-SOLVE trial. Blood Purif, 2025, 54(2): 93-101.
42. Scharf C, Weinelt F, Schroeder I, et al. Does the cytokine adsorber CytoSorb^{^®} reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study. Ann Intensive Care, 2022, 12(1): 44.
43. Bottari G, Goffredo BM, Marano M, et al. Impact of continuous kidney replacement therapy and hemoadsorption with Cytosorb on antimicrobial drug removal in critically ill children with septic shock: a single-center prospective study on a pediatric cohort. Antibiotics (Basel), 2023, 12(9): 1395.
44. Wang C, Li C, Yang P, et al. High adsorption capacity of hemoperfusion on imipenem in critically ill patients with septic shock: a case report. BMC Infect Dis, 2024, 24(1): 894.
45. Girardot T, Schneider A, Rimmelé T. Blood purification techniques for sepsis and septic AKI. Semin Nephrol, 2019, 39(5): 505-514.
46. Gruda MC, Ruggeberg KG, O’Sullivan P, et al. Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb^{^®} sorbent porous polymer beads. PLoS One, 2018, 13(1): e0191676.
47. 国家重症医学专业医疗质量控制中心重症肾脏学质控亚专业组. 中国重症血液吸附专家指导意见(2025 年). 中国急救医学, 2025, 45(6): 471-475.
48. 关明镜, 张凌. 吸附性血液滤过治疗脓毒症欧洲及亚太专家推荐意见解读. 华西医学, 2022, 37(7): 996-1000.
49. Wieruszewski PM, Murad MH. Does CytoSorb pose unique challenges to pooled estimates in Meta-analysis?. Crit Care Med, 2023, 51(12): 1819-1821.
50. Graf H, Gräfe C, Bruegel M, et al. Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb^{^®} in patients with severe rhabdomyolysis: a prospective trial. Ann Intensive Care, 2024, 14(1): 96.
51. Zhang L, Cove M, Nguyen BG, et al. Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia pacific experience. Chin Med J (Engl), 2021, 134(18): 2258-2260.

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