Sepsis pathophysiology and blood purification therapies: a literature review.

Main Article Content

Sertaridou N. Eleni, MD, MSc, PhD Papaioannou E. Vasileios

Abstract

Sepsis represents a lethal dysregulated host response to infection leading to organ dysfunction. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, preventing multiorgan failure. Even in the absence of strong indications deriving from large clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Different therapies have been developed to address certain steps of the immune dysregulation besides classical renal replacement therapy, such us High Volume Hemofiltration, High-cut-off membrane hemofiltration, hemoadsorption treatments and coupled plasma filtration and adsorption. Despite the different underlying mechanisms of action, most of such available devices focus on a single target, such as endotoxins, cytokines, or both, that triggers the inflammatory cascade. The attention in this review is focused on presenting Blood Purification Techniques and the evidence of their clinical effectiveness, clarifying the indications, ideal patient selection, timing, dosing and biomonitoring, important issues that should be solved in the future, to enable usage of these therapies in the best possible and most targeted manner.

Keywords: Sepsis pathophysiology, blood purification, hemoadsorption, hemofiltration

Article Details

How to Cite
ELENI, Sertaridou N.; VASILEIOS, Papaioannou E.. Sepsis pathophysiology and blood purification therapies: a literature review.. Medical Research Archives, [S.l.], v. 12, n. 5, may 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5034>. Date accessed: 19 june 2024. doi: https://doi.org/10.18103/mra.v12i5.5034.
Section
Review Articles

References

1. Font MD, Thyagarajan B, Khanna AK. Sepsis and Septic Shock - Basics of diagnosis, pathophysiology and clinical decision making. Med Clin North Am. 2020;104(4):573-585. doi: 10.1016/j.mcna.2020.02.011.

2. Levy M, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ ESICM/ ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med. 2003;29:53 0.e8. doi: 10.1007/s00134-003-1662-x.

3. Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol. 2021;34(2):77 -84. doi: 10.1097/ACO.0000000000000963.

4. Evans L, Andrew Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021; 47(11):1181-1247. doi: 10.1007/s00134-021-06506-y.

5. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–810. doi: 10.1001/ jama.2016.0287.

6. Giamarellos-Bourboulis EJ, Aschenbrenner AC, Bauer M, Bock C, et al. The pathophysiology of sepsis and precision-medicine-based immunotherapy. Nat Immunol. 2024;25(1):19-28. doi: 10.1038/s41 590-023-01660-5.

7. Monard C, Rimmelé T, Ronco C. Extracorporeal Blood Purification Therapies for Sepsis. Blood Purif. 2019;47 Suppl 3:1-14. doi: 10.1159/000499520.

8. Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;353:i1585. doi: 10.1136/bmj.i1585.

9. 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. doi: 10.1371/journal. pone.0191676. eCollection 2018.

10. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):8 40-51. doi: 10.1056/NEJMra1208623

11. Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn injury. Nat Rev Dis Primers. 2020;6(1):11. doi: 10.1038/s41572-020-0145-5

12. Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011:6:147-63. doi: 10.1146/annurev-pathol-011110-130158.

13. Strnad P, Tacke F, Koch A, Trautwein C. Liver - guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol 2017; 14:55–66. doi: 10.1038/nrgastro.2016.168.

14. Bock C, Vogt B, Mattecka S, et al. C-reactive protein causes blood pressure drop in rabbits and induces intracellular calcium signaling. Front Immunol 2020; 11:1978. doi: 10.3389/fimmu.2020.01978. eCollection 2020.

15. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9:754. doi: 10. 3389/fimmu.2018.00754. eCollection 2018.

16. Liappis AP, Gibbs KW, Nylen ES, et al. Exogenous procalcitonin evokes a proinflammatory cytokine response. Inflamm Res 2011; 60:203–207. doi: 10.1007/s00011-010-0255-8. Epub 2010 Oct 17.

17. Van Westerloo DJ, Choi G, Lo¨ wenberg EC, et al. Acute stress elicited by bungee jumping suppresses human innate immunity. Mol Med 2011; 17:180–188. doi: 10.2119/mol med.2010.00204. Epub 2010 Dec 10.

18. Melis MJ, Miller M, Peters VBM, Singer M. The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction. Clin Sci (Lond). 2023;137(9):707-725. doi: 10.1042/CS20220709.

19. Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18(6): 424-434 doi: 10.1038/s41569-020-00492-2. Epub 2021 Jan 20.

20. L'Heureux M, Sternberg M, Brath L, Turlington J, Kashiouris MG. Sepsis-Induced Cardiomyopathy: a Comprehensive Review. Curr Cardiol Rep. 2020;22(5):35. doi: 10.1007 /s11886-020-01277-2

21. Levy B, Collin S, Sennoun N, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med 2010; 36:2019–2029. doi: 10.1007/s00134-010-2045-8. Epub 2010 Sep 23.

22. Duan C, Yang G, Li T, Liu L. Advances in Vascular Hyporeactivity After Shock: The Mechanisms and Managements. Shock. 2015; 44(6):524-34. doi: 10.1097/SHK.0000000000000457.

23. Gamcrlidze MM, Intskirveli NA, Vardosanidze KD, Chikhladze KhE, Goliadze LSh, Ratiani LR. Vasoplegia in septic shock (review). Georgian Med News. 2015;(239):56-62.

24. Iba T, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Anesthesiology 2020; 132:1238–1245. doi: 10.1097/ALN.0000000000003122.

25. Chen Z, Zhang H, Qu M, et al. Review: The Emerging Role of Neutrophil Extracellular Traps in Sepsis and Sepsis-Associated Thrombosis. Front Cell Infect Microbiol. 2021;11:653228. doi: 10.3389/fcimb.2021.65 3228. eCollection 2021.

26. Kambas K, Mitroulis I, Apostolidou E, et al. Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis. PLoS One. 2012;7(9):e45427. doi: 10.1371/journal.pone. 0045427. Epub 2012 Sep 19.

27. Tsantes AG, Parastatidou S, Tsantes EA, et al. Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines. Life (Basel). 2023;13(2):35 0. doi: 10.3390/life13020350.

28. Suetrong B, Walley KR. Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis and Management. Chest. 2016;149 (1):252-61. doi: 10.1378/chest.15-1703. Epub 2016 Jan 6.

29. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care 2014; 18:503. doi: 10.1186/s13054-014-0503-3.

30. Boldt J, Wollbrück M, Menges T, Diridis K, Hempelmann G. Changes in regulators of circulation in patients undergoing continuous pump-driven veno-venous hemofiltration. Shock. 1994;2(3):157-63. doi: 10.1097/00024 382-199409000-00001.

31. Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I). Intensive Care Med 2017; 43:1751–1763. doi: 10.1007/s00134-017-491 9-5. Epub 2017 Sep 21.

32. Peeters RP, Wouters PJ, Kaptein E, Van Toor H, Visser TJ, Van den Berghe G. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab 2003; 88:32 02–3211. doi: 10.1210/jc.2002-022013.

33. Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997; 95:1122–1125. doi: 10.1161/01.cir.95.5.1122.

34. Chavan SS, Tracey KJ. Essential Neuroscience in Immunology. J Immunol. 2017;198(9):3389-3397. doi: 10.4049/jimmun ol.1601613.

35. Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M. Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis. Am J Respir Crit Care Med. 2016;194(5):550-8. doi: 10.1164/rccm.201604-0862CP.

36. Hotchkiss R, Swanson P, Freeman B, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999;27:1230–1251. doi: 10.1097/ 00003246-199907000-00002.

37. Arulkumaran N, Deutschman CS, Pinsky MR, et al. Mitochondrial function in sepsis. Shock 2016; 45:271–281. doi: 10.1097/SHK. 0000000000000463.

38. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121-137. doi: 10.1038/nr neph.2017.165. Epub 2017 Dec 11.

39. Shalova IN, Lim JY, Chittezhath M, et al. Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α. Immunity 2015;42(3):484–498. doi: 10.1016/j.immuni.2 015.02.001. Epub 2015 Mar 3.

40. Arts RJ, Gresnigt MS, Joosten LA, Netea MG. Cellular metabolism of myeloid cells in sepsis. J Leukoc Biol. 2017;101(1):151–164. doi: 10.1189/jlb.4MR0216-066R. Epub 2016 Jun 6.

41. Liu D, Huang SY, Sun JH, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022;9(1):56. doi: 10.1186/s40779-022-00422-y

42. Torres LK, Pickkers P, van der Poll T. Sepsis-Induced Immunosuppression. Annu Rev Physiol. 2022;84:157-181. doi: 10.1146/ annurev-physiol-061121-040214. Epub 2021 Oct 27.

43. Cao C, Yu M, Chai Y. Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis. Cell Death Dis. 2019;10(10):782. doi: 10.1038/s41 419-019-2015-1.

44. Girardot T, Schneider A, Rimmelé T. Blood Purification Techniques for Sepsis and Septic AKI. Semin Nephrol. 2019;39(5):505-514. doi: 10.1016/j.semnephrol.2019.06.010.

45. Ronco C, Tetta C, Mariano F, Wratten ML, Bonello M, Bordoni V, Cardona X, Inguaggiato P, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003;27(9):792-801. doi: 10.1046/j.1525-1594.2003.07289.x.

46. Honoré PM, Matson JR. Extracorporeal removal for sepsis: Acting at the tissue level--the beginning of a new era for this treatment modality in septic shock. Crit Care Med. 2004;32(3):896-7. doi: 10.1097/01.ccm.00001 15262.31804.46.

47. Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care. 2011;15(1):205. doi: 10.1186/cc9411. Epub 2011 Feb 16.

48. Lee PA, Matson JR, Pryor RW, Hinshaw LB. Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus induced septicemia in immature swine. Crit. Care Med. 1993; 21:914–924. doi: 10.1097/00003246-199306000-00022.

49. Ma S, Xu Q, Deng B, et al. Granulocyte and monocyte adsorptive apheresis ameliorates sepsis in rats. Intensive Care Med. Exp. 2017;5(1):18. doi: 10.1186/s40635-017-0129-2. Epub 2017 Mar 24.

50. Berlot G, Tomasini A, Zanchi S, Moro E. The Techniques of Blood Purification in the Treatment of Sepsis and Other Hyperinflammatory Conditions. J Clin Med. 2023;12(5):1723. doi: 10.3390/jcm12051723.

51. Rimmele T, Kellum JA. High-volume hemofiltration in the intensive care unit: a blood purification therapy. Anesthesiology 2012;116:1377-87 doi: 10.1097/ALN.0b013e 318256f0c0.

52. Ronco C, Clark WR. Haemodialysis membranes. Nat Rev Nephrol. 2018;14(6):394 -410. doi: 10.1038/s41581-018-0002-x.

53. Neri M, Villa G, Garzotto F, et al. Nomenclature Standardization Initiative (NSI) alliance. Nomenclature for renal replacement therapy in acute kidney injury: basic principles. Crit Care. 2016;20(1):318. doi: 10.1186/s13054-016-1489-9.

54. Payen D. Haemoperfusion with polymyxin B membrane: recent results for an old debate! Anaesth Crit Care Pain Med. 2019; 38(1): 3–4. doi: 10.1016/j.accpm.2018.1 2.010. Epub 2019 Jan 8.

55. Ala-Kokko TI, Laurila J, Koskenkari J. A new endotoxin adsorber in septic shock: observational case series. Blood Purif. 2011; 32(4): 303–9. doi: 10.1159/000330323. Epub 2011 Sep 2.

56. Adamik B, Zielinski S, Smiechowicz J, Kübler A. Endotoxin Elimination in Patients with Septic Shock: An Observation Study. Arch Immunol Ther Exp (Warsz). 2015; 63(6): 475–83. doi: 10.1007/s00005-015-0348-8. Epub 2015 Jun 21.

57. Eden G, Schmidt JJ, Büttner S, et al. Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: Results of the first in human study. Crit. Care 2022:26(1):181 . doi: 10.1186/s13054-022-04044-7.

58. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30. doi: 10.1016/S 0140-6736(00)02430-2.

59. Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367(26):2505-14. doi: 10.1056/NEJMct1 206045.

60. Honore PM, Jamez J, Wauthier M, et al. Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med. 2000; 28(11): 3581–7. doi: 10.1097/00003246 -200011000-00001.

61. Cole L, Bellomo R, Journois D, Davenport P, Baldwin I, Tipping P. High-volume haemofiltration in human septic shock. Intensive Care Med. 2001; 27(6): 978–86. doi: 10.1007/s001340100963.

62. Ratanarat R, Brendolan A, Piccinni P, et al. Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival. Crit Care. 2005; 9(4):R294–302 doi: 10.1186/cc3529. Epub 2005 Apr 28.

63. Ghani RA, Zainudin S, Ctkong N, Rahman AFA, Wafa SRWSH, Mohamad M, Manaf MRA, Ismail R. Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration. Nephrology (Carlton). 2006;1 1(5):386-93. doi: 10.1111/j.1440-1797.2006. 00600.x.

64. Boussekey N, Chiche A, Faure K, Devos P, Guery B, D' Escrivan T, Georges H, Leroy O. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. Intensive Care Med. 2008;34(9):1646-53. doi: 10.1007/s00134-008-1127-3. Epub 2008 Apr 30.

65. Zhang P, Yang Y, Lv R, Zhang Y, Xie W, Chen J. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial. Nephrol Dial Transplant. 2012;27(3):967-73. doi: 10.1093 /ndt/gfr486. Epub 2011 Sep 2.

66. Tapia P, Chinchón E, Morales D, Stehberg J, Simon F. Effectiveness of short-term 6-hour high-volume hemofiltration during refractory severe septic shock. J Trauma Acute Care Surg. 2012; 72(5): 1228–37; discussion 1237-8. doi: 10.1097/TA.0b013 e318248bc6c.

67. Joannes-Boyau O, Honoré PM, Perez P, et al. Highvolume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013; 39(9): 1535–46. doi: 10.1007/s00134-013-2967-z. Epub 2013 Jun 6.

68. Chang T, Tu YK, Lee CT, et al. 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. Crit Care Med. 2017; 45(8):e858–64. doi: 10.1097/CCM.0000000000002362.

69. Atan R, Peck L, Visvanathan K, et al. High cut-off hemofiltration versus standard hemofiltration: effect on plasma cytokines. Int J Artif Organs. 2016;39(9):479-486. doi: 10.5301/ijao.5000527. Epub 2016 Nov 10.

70. Kade G, Lubas A, Rzeszotarska A, Korsak J, Niemczyk S. Effectiveness of High Cut-Off Hemofilters in the Removal of Selected Cytokines in Patients During Septic Shock Accompanied by Acute Kidney Injury-Preliminary Study. Med Sci Monit. 2016;22:43 38-4344. doi: 10.12659/MSM.896819.

71. Vincent JL, Laterre PF, Cohen J, et al. A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection. Shock. 2005;23(5):400-5. doi: 10.1097/01.shk.0000159930.87737.8a.

72. Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301( 23):2445-52. doi: 10.1001/jama.2009.856.

73. Coudroy R, Payen D, Launey Y, et al. Modulation by Polymyxin-B Hemoperfusion of Inflammatory Response Related to Severe Peritonitis. Shock. 2017;47(1):93-99. doi: 10.1097/SHK.0000000000000725.

74. Dellinger RP, Bagshaw SM, Antonelli M, et al. Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial. JAMA. 2018;320( 14):1455-1463. doi: 10.1001/jama.2018.14618.

75. Yaroustovsky M, Abramyan M, Popok Z, et al. Preliminary report regarding the use of selective sorbents in complex cardiac surgery patients with extensive sepsis and prolonged intensive care stay. Blood Purif. 2009; 28(3): 227–33. doi: 10.1159/000231988. Epub 2009 Aug 14.

76. Lipcsey M, Tenhunen J, Pischke SE, et al. Endotoxin Removal in Septic Shock with the Alteco LPS Adsorber Was Safe But Showed no Benefit Compared to Placebo in the Double-Blind Randomized Controlled Trial-the Asset Study. Shock. 2020;54(2):224-231. doi: 10.109 7/SHK.0000000000001503.

77. Kogelmann K, Jarczak D, Scheller M, Drüner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care. 2017; 21(1): 74. doi: 10.1186/s13054-017-1662-9.

78. Schädler D, Pausch C, Heise D, et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial. PLoS One. 2017; 12(10):e0187015. doi: 10.1 371/journal.pone.0187015. eCollection 2017.

79. Hawchar F, László I, Öveges N, Trásy D, Ondrik Z, Molnar Z. Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study. J Crit Care. 2019;49:172-178. doi: 10.1016/j.jcrc.20 18.11.003. Epub 2018 Nov 10.

80. Singh YP, Chhabra SC, Lashkari K, et al. Hemoadsorption by extracorporeal cytokine adsorption therapy (CytoSorb®) in the management of septic shock: A retrospective observational study. Int J Artif Organs. 2020;4 3(6):372-378 doi: 10.1177/0391398819891739. Epub 2019 Dec 23.

81. Paul R, Sathe P, Kumar S, Prasad S, Aleem M, Sakhalvalkar P. Multicentered prospective investigator initiated study to evaluate the clinical outcomes with extracorporeal cytokine adsorption device (CytoSorb®) in patients with sepsis and septic shock. World J Crit Care Med. 2021;10(1):22-34. doi: 10.5492/wjccm.v 10.i1.22.

82. Shum HP, Chan KC, Kwan MC, Yan WW. Application of endotoxin and cytokine adsorption haemofilter in septic acute kidney injury due to Gram-negative bacterial infection. Hong Kong Med J 2013;19(6):491-7. doi: 10.12809/hkmj133910. Epub 2013 May 6.

83. Turani F, Barchetta R, Falco M, Busatti S, Weltert L. Continuous Renal Replacement Therapy with the Adsorbing Filter oXiris in Septic Patients: A Case Series. Blood Purif. 2019:47 Suppl 3:1-5. doi: 10.1159/000499589 . Epub 2019 Apr 12.

84. Broman ME, Hansson F, Vincent JL, Bodelsson M. Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: A randomized crossover double-blind study. PLoS One. 2019;14(8):e0220444. doi: 10.1371/journal.p one.0220444. eCollection 2019.

85. Zhai Y, Pan J, Zhang C. The application value of oXiris-endotoxin adsorption in sepsis. Am J Transl Res. 2021;13(4):3839-3844.

86. Zang S, Chen Q, Zhang Y, Xu L, Chen J. Comparison of the Clinical Effectiveness of AN69-oXiris versus AN69-ST Filter in Septic Patients: A Single-Centre Study. Blood Purif. 2022;51(7):617-629. doi: 10.1159/00051916 6. Epub 2021 Oct 5.

87. Schmidt JJ, Borchina DN, Van't Klooster M, et al. Interim analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry. Nephrol Dial Transplant. 2022;37(4):673-680 doi: 10.1 093/ndt/gfab347.

88. Chitty SA, Mobbs S, Rifkin BS, et al. A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19. Crit Care Explor. 2022;4(4):e0662. doi: 10.1097/CCE.0 000000000000662. eCollection 2022 Apr

89. 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. doi: 10.1136/bmjopen-2013-003536.

90. Mariano F, Hollo' Z, Depetris N, et al. Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy. Burns. 2020;46(1):190-198. doi: 10.1016/j.burns.2019.05.017. Epub 2019 Nov 29.

91. 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. doi: 10.1007/s00134-021-06501-3. Epub 2021 Oct 3.

92. Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002;28(10):1434-9. doi: 10.1007/s0013 4-002-1410-7. Epub 2002 Jul 23.

93. Knaup H, Stahl K, Schmidt BMW, et al. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care. 2018;22(1):285. doi: 10.1186/s13054-018-2220-9

94. Stahl Κ, Wand P, Seeliger B, et al. Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial. Crit Care. 2022;26(1):134. doi: 10.1186/s13054-022-04003-2.

95. David S, Bode C, Stahl K; EXCHANGE-2 Study group. EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock-a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial. Trials. 2023;24(1):277. doi: 10.1186/s13063-023-07300-5.

96. 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. doi: 10.1186/s40635-018-0177-2.

97. Hawchar F, Tomescu D, Träger K et al. Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry. PLoS ONE 2022;17(10):e0274315. doi: 10.13 71/journal.pone.0274315. eCollection 2022.

98. Honoré PM, David De Bels D, Spapen HD. An update on membranes and cartridges for extracorporeal blood purification in sepsis and septic shock. Curr Opin Crit Care. 2018;2 4(6):463-468. doi: 10.1097/MCC.0000000000000542

99. Zamora AP, Roig RJ, Badosa EL, et al. Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane. J Antimicrob Chemother. 2019;74(10):2979-2983. doi: 10.1093/jac/dkz299.