Zusammenfassung
Hintergrund
Hämoperfusion ist ein Verfahren zur Elimination von endogenen und exogenen Toxinen und schädlichen Mediatoren durch Adsorption. Mittlerweile vertreiben diverse Anbieter Systeme mit unterschiedlichen Technologien.
Fragestellung
Ziel dieser Arbeit ist es zu bewerten, welche Chancen, Risiken und Evidenz die unterschiedlichen Systeme haben, wie die Funktionsweise ist und für welche Indikationen sie in Deutschland zugelassen sind.
Methodik
Zur Zielerreichung wurde eine narrative Bewertung der vorhandenen Literatur und Leitlinien für verschiedene Indikationen vorgenommen. Der Fokus lag dabei auf In-vivo-Studien.
Ergebnisse
Die meisten Adsorber wurden zur Zytokin- und Endotoxinentfernung im Rahmen der Sepsis entwickelt. Bisher konnte aber keine randomisierte kontrollierte Studie (RCT) einen Überlebensvorteil durch den Einsatz von Hämoperfusion zeigen. Die S3-Leitlinie zur Therapie der Sepsis und die Leitlinie der Surviving Sepsis Campaign (SSC) raten deswegen von der routinemäßigen Anwendung ab.
Zu Beginn der Coronapandemie wurde die Hämoperfusion als vielversprechender Therapieansatz gehandelt. Aktuelle Daten zeigen allerdings keine positiven Ergebnisse, sodass der Einsatz nicht routinemäßig empfohlen werden kann.
Die Anwendung von Adsorptionsverfahren bei PatientInnen mit Leberversagen und Rhabdomyolyse ist nur rudimentär untersucht, sodass aktuell keine Empfehlung für oder gegen einen Einsatz ausgesprochen werden kann. Auch im operativen Setting (v. a. Herzchirurgie) und für die Elimination unerwünschter Medikamente gibt es keine ausreichende Evidenz, um die Anwendung regelhaft zu empfehlen.
Diskussion
Diverse Adsorptionsverfahren können verschiedene Stoffe eliminieren. Aktuell fehlen für alle Indikationen und Systeme Nachweise, die den routinemäßigen Einsatz fernab klinischer Studien rechtfertigen.
Abstract
Background
Hemoperfusion is a technique for the extracorporeal elimination of endogenous and exogenous toxins and harmful mediators by adsorption. It can be used as a stand-alone device, as part of a heart-lung machine or extracorporeal membrane oxygenation (ECMO) or, as is currently the case, integrated into a kidney replacement procedure. In the meantime, various suppliers offer devices with different technologies.
Objective
The aim of this work was to evaluate the benefits, risks and evidence of the different systems, how they work and for which indications they are approved in Germany.
Method
To achieve this goal, a narrative assessment of the existing literature and guidelines for different indications was performed. The focus was on in vivo studies.
Results
In principle, a distinction must be made in adsorption techniques between pure adsorption and the combination as adsorption and kidney replacement therapy. The adsorbers available in Germany include Cytosorb®, HA-330, Seraph®-100 and Toraymyxin. Combined procedures (adsorption and kidney replacement) are offered with coupled plasma filtration and adsorption (CPFA) and o**ris®.
Most adsorbers have been developed for cytokine and endotoxin removal in patients with sepsis; however, to date, no randomized controlled trial (RCT) has demonstrated a survival benefit when using hemoperfusion. Therefore, the S3 guidelines for treatment of sepsis and the surviving sepsis campaign guidelines advise against its routine use.
When the corona pandemic began, hemoperfusion was considered as a promising therapeutic approach. Cytosorb®, Seraph®-100, and o**ris® received emergency approval by the FDA to be used in critically ill patients with COVID-19, so questions arose about the appropriateness and importance of its use; however, the data generated did not show positive results, so its use cannot be recommended routinely either. In addition, they are not mentioned as a treatment option in the current guidelines.
The use of adsorption procedures in patients with liver failure and rhabdomyolysis has only been rudimentarily studied, so any evidence is currently lacking. The only adsorber that has CE approval in Germany for both applications is Cytosorb®. In the next few years, studies will have to follow that investigate the efficacy and thus either justify or refute the use in clinical routine.
Hemoperfusion procedures are used in the heart-lung machine as part of cardiac surgery for either cytokine or anticoagulant adsorption. No congruent data are available to support the use for the elimination of cytokines. If emergency cardiac surgery is required in a patient with pre-existing anticoagulation, hemoperfusion procedures can be used to prevent bleeding complications. Cytosorb® has CE approval for this indication.
All available techniques are nonselective adsorption processes, so that adsorption of known and unknown substances can occur. Unintentional adsorption of drugs, such as various anti-infective agents is a relevant risk, especially when used in patients with sepsis.
Discussion
Various adsorption systems can eliminate different known and unknown substances. Currently, there is a lack of evidence for all indications and systems to justify their routine use except in clinical trials. Future clinical trials should evaluate the potential benefits but also dangers, so that in the meantime the routine use can be justified or a recommendation against the use can be given.
Literatur
Ronco C, Bellomo R (2022) Hemoperfusion: technical aspects and state of the art. Crit Care 26(1):135. https://doi.org/10.1186/s13054-022-04009-w
Fiedler MO, Reyher C, Kalenka A, Rolfes C, Lotz C, Muellenbach RM (2021) Pumpless extracorporeal hemadsorption technique: a new method for early cytokine elimination? Blood Purif 50(6):968–970. https://doi.org/10.1159/000512983
Shimokawa K, Takakuwa R, Wada Y, Yamazaki N, Ishii F (2013) Adsorption of various antimicrobial agents to endotoxin removal polymyxin‑B immobilized fiber (Toraymyxin(R)). Part 2: Adsorption of two drugs to Toraymyxin PMX-20R cartridges. Colloids Surf B Biointerfaces 101:350–352. https://doi.org/10.1016/j.colsurfb.2012.06.032
Poli EC, Rimmele T, Schneider AG (2019) Hemoadsorption with CytoSorb((R)). Intensive Care Med 45(2):236–239. https://doi.org/10.1007/s00134-018-5464-6
Ankawi G, Fan W, Pomare Montin D et al (2019) A new series of sorbent devices for multiple clinical purposes: current evidence and future directions. Blood Purif 47(1):94–100. https://doi.org/10.1159/000493523
Chitty SA, Mobbs S, Rifkin BS et al (2022) A multicenter evaluation of the seraph 100 Microbind affinity blood filter for the treatment of severe COVID-19. Crit Care Explor 4(4):e662. https://doi.org/10.1097/CCE.0000000000000662
Broman ME, Hansson F, Vincent JL, Bodelsson M (2019) Endotoxin and cytokine reducing properties of the o**ris membrane in patients with septic shock: A randomized crossover double-blind study. Plos One 14(8):e220444. https://doi.org/10.1371/journal.pone.0220444
Abdul Cader R, Abdul Gafor H, Mohd R, Yen Kong W, Arshad N, Kong N (2013) Coupled plasma filtration and adsorption (CPFA): a single center experience. Nephrourol Mon 5(4):891–896. https://doi.org/10.5812/numonthly.11904
Cruz DN, Antonelli M, Fumagalli R et al (2009) Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 301(23):2445–2452. https://doi.org/10.1001/jama.2009.856
Li X, Liu C, Mao Z, Qi S, Song R, Zhou F (2021) Effectiveness of polymyxin B‑immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis. J Crit Care 63:187–195. https://doi.org/10.1016/j.jcrc.2020.09.007
Terayama T, Yamakawa K, Umemura Y, Aihara M, Fujimi S (2017) Polymyxin B hemoperfusion for sepsis and septic shock: a systematic review and meta-analysis. Surg Infect 18(3):225–233. https://doi.org/10.1089/sur.2016.168
Dellinger RP, Bagshaw SM, Antonelli M et al (2018) 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 320(14):1455–1463. https://doi.org/10.1001/jama.2018.14618
Smiechowicz J (2022) The rationale and current status of endotoxin adsorption in the treatment of septic shock. J Clin Med 11(3):619. https://doi.org/10.3390/jcm11030619
Kogelmann K, Jarczak D, Scheller M, Druner M (2017) Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care 21(1):74. https://doi.org/10.1186/s13054-017-1662-9
Hawchar F, Laszlo I, Oveges N, Trasy D, Ondrik Z, Molnar Z (2019) Extracorporeal cytokine adsorption in septic shock: a proof of concept randomized, controlled pilot study. J Crit Care 49:172–178. https://doi.org/10.1016/j.jcrc.2018.11.003
Schadler D, Pausch C, Heise D et al (2017) The effect of a novel extracorporeal cytokine hemoadsorption device on IL‑6 elimination in septic patients: A randomized controlled trial. Plos One 12(10):e187015. https://doi.org/10.1371/journal.pone.0187015
Wendel Garcia PD, Hilty MP, Held U, Kleinert EM, Maggiorini M (2021) Cytokine adsorption in severe, refractory septic shock. intensive Care Med 47(11):1334–1336. https://doi.org/10.1007/s00134-021-06512-0
Scharf C, Weinelt F, Schroeder I et al (2022) Does the cytokine adsorber CytoSorb((R)) reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study. Ann Intensive Care 12(1):44. https://doi.org/10.1186/s13613-022-01017-5
Liebchen U, Scharf C, Zoller M, Weinelt F, Kloft C (2021) CytoMero collaboration t. No clinically relevant removal of meropenem by cytokine adsorber CytoSorb((R)) in critically ill patients with sepsis or septic shock. Intensive Care Med 47(11):1332–1333. https://doi.org/10.1007/s00134-021-06487-y
Konig C, Rohr AC, Frey OR et al (2019) In vitro removal of anti-infective agents by a novel cytokine adsorbent system. Int J Artif Organs 42(2):57–64. https://doi.org/10.1177/0391398818812601
Chu L, Li G, Yu Y, Bao X, Wei H, Hu M (2020) Clinical effects of hemoperfusion combined with pulse high-volume hemofiltration on septic shock. Medicine 99(9):e19058. https://doi.org/10.1097/MD.0000000000019058
Eden G, Schmidt JJ, Buttner S et al (2022) Safety and efficacy of the Seraph(R) 100 Microbind(R) Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study. Crit Care 26(1):181. https://doi.org/10.1186/s13054-022-04044-7
Selig DJ, Reed T, Chung KK, Kress AT, Stewart IJ, DeLuca JP (2022) Hemoperfusion with seraph 100 microbind affinity blood filter unlikely to require increased antibiotic dosing: a simulations study using a Pharmacokinetic/Pharmacodynamic approach. blood Purif. https://doi.org/10.1159/000524457
Feng J, Zhang S, Ai T et al (2022) Effect of CRRT with o**ris filter on hemodynamic instability in surgical septic shock with AKI: a pilot randomized controlled trial. Int J Artif Organs 45(10):801–808. https://doi.org/10.1177/03913988221107947
Livigni S, Bertolini G, Rossi C et al (2014) Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open 4(1):e3536. https://doi.org/10.1136/bmjopen-2013-003536
Garbero E, Livigni S, Ferrari F et al (2021) 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 47(11):1303–1311. https://doi.org/10.1007/s00134-021-06501-3
Martin-Loeches I, Nunnally ME, Hellman J et al (2021) Surviving sepsis campaign: research opportunities for infection and blood purification therapies. Crit Care Explor 3(9):e511. https://doi.org/10.1097/CCE.0000000000000511
Brunkhorst FM, Weigand MA, Pletz M et al (2020) S3 guideline sepsis-prevention, diagnosis, therapy, and aftercare : long version. Med Klin Intensivmed Notfmed 115(Suppl 2):37–109. https://doi.org/10.1007/s00063-020-00685-0 (S3-Leitlinie Sepsis – Pravention, Diagnose, Therapie und Nachsorge : Langfassung)
De Rosa S, Cutuli SL, Ferrer R, Antonelli M, Ronco C, Group C‑EC. (2021) Polymyxin B hemoperfusion in coronavirus disease 2019 patients with endotoxic shock: Case series from EUPHAS2 registry. Artif Organs 45(6):E187–E194. https://doi.org/10.1111/aor.13900
Jarczak D, Roedl K, Fischer M et al (2022) Effect of hemadsorption therapy in critically ill patients with COVID-19 (CYTOCOV-19): a prospective randomized controlled pilot trial. Blood Purif. https://doi.org/10.1159/000526446
Stockmann H, Thelen P, Stroben F et al (2022) CytoSorb rescue for COVID-19 patients with vasoplegic shock and multiple organ failure: a prospective, open-label, randomized controlled pilot study. Crit Care Med 50(6):964–976. https://doi.org/10.1097/CCM.0000000000005493
Supady A, Weber E, Rieder M et al (2021) Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial. Lancet Respir Med 9(7):755–762. https://doi.org/10.1016/S2213-2600(21)00177-6
Abdullayev R, Gul F, Bilgili B, Seven S, Cinel I (2022) Cytokine adsorption in critically IIl COVID-19 patients, a case-control study. J Intensive Care Med 37(9):1223–1228. https://doi.org/10.1177/08850666221085185
Scharf C, Liebchen U, Paal M et al (2021) Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study. Sci Rep 11(1):10190. https://doi.org/10.1038/s41598-021-89712-4
Liebchen U, Paal M, Grafe C, Zoller M, Scharf C, Cyto SSG (2023) The cytokine adsorber Cytosorb(R) does not reduce ammonia concentrations in critically ill patients with liver failure. Intensive Care Med 49(3):360–362. https://doi.org/10.1007/s00134-023-06998-w
Donati G, Angeletti A, Gasperoni L et al (2021) Detoxification of bilirubin and bile acids with intermittent coupled plasmafiltration and adsorption in liver failure (HERCOLE study). J Nephrol 34(1):77–88. https://doi.org/10.1007/s40620-020-00799-w
Scharf C, Liebchen U, Paal M, Irlbeck M, Zoller M, Schroeder I (2021) Blood purification with a cytokine adsorber for the elimination of myoglobin in critically ill patients with severe rhabdomyolysis. Crit Care 25(1):41. https://doi.org/10.1186/s13054-021-03468-x
Pezzi M, Renda S, Giglio AM et al (2017) The use of coupled plasma filtration adsorption in traumatic rhabdomyolysis. Case Rep Crit Care 2017:5764961. https://doi.org/10.1155/2017/5764961
Breuer TGK, Quast DR, Wiciok S, Labedi A, Ellrichmann G (2021) Successful treatment of severe Digitoxin intoxication with CytoSorb(R) hemoadsorption. Blood Purif 50(1):137–140. https://doi.org/10.1159/000510292
Lang CN, Sommer MJ, Neukamm MA et al (2020) Use of the CytoSorb adsorption device in MDMA intoxication: a first-in-man application and in vitro study. Intensive Care Med Exp 8(1):21. https://doi.org/10.1186/s40635-020-00313-3
Zickler D, Nee J, Arnold T et al (2021) Use of hemoadsorption in patients with severe intoxication requiring extracorporeal cardiopulmonary support—A case series. ASIO J 67(11):e186–e190. https://doi.org/10.1097/MAT.0000000000001362
Hsu CW, Lin JL, Lin-Tan DT et al (2012) Early hemoperfusion may improve survival of severely paraquat-poisoned patients. Plos One 7(10):e48397. https://doi.org/10.1371/journal.pone.0048397
Asch S, Kaufmann TP, Walter M et al (2021) The effect of perioperative hemadsorption in patients operated for acute infective endocarditis—A randomized controlled study. Artif Organs 45(11):1328–1337. https://doi.org/10.1111/aor.14019
Diab M, Lehmann T, Bothe W et al (2022) Cytokine hemoadsorption during cardiac surgery versus standard surgical care for infective Endocarditis (REMOVE): results from a multicenter randomized controlled trial. Circulation 145(13):959–968. https://doi.org/10.1161/CIRCULATIONAHA.121.056940
Garau I, Marz A, Sehner S et al (2019) Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor alpha serum levels in cardiac surgery: a randomized controlled trial. Minerva Anestesiol 85(7):715–723. https://doi.org/10.23736/S0375-9393.18.12898-7
Zhigalov K, Van den Eynde J, Zubarevich A et al (2022) Initial experience with CytoSorb therapy in patients receiving left ventricular assist devices. Artif Organs 46(1):95–105. https://doi.org/10.1111/aor.14099
Saller T, Hagl C, Woitsch S et al (2019) Haemadsorption improves intraoperative haemodynamics and metabolic changes during aortic surgery with hypothermic circulatory arrest. Eur J Cardiothorac Surg 56(4):731–737. https://doi.org/10.1093/ejcts/ezz074
Hassan K, Kannmacher J, Wohlmuth P, Budde U, Schmoeckel M, Geidel S (2019) Cytosorb adsorption during emergency cardiac operations in patients at high risk of bleeding. Ann Thorac Surg 108(1):45–51. https://doi.org/10.1016/j.athoracsur.2018.12.032
Hassan K, Bruning T, Caspary M et al (2022) Hemoadsorption of Rivaroxaban and Ticagrelor during acute type A aortic dissection operations. Ann Thorac Cardiovasc Surg 28(3):186–192. https://doi.org/10.5761/atcs.oa.21-00154
Koster A, Warkentin H, von Dossow V, Morshuis M (2022) Use of the CytoSorb(R) filter for elimination of residual therapeutic argatroban concentrations during heparinized cardiopulmonary bypass for heart transplantation. Perfusion. https://doi.org/10.1177/02676591221093875
Kietaibl S, Ahmed A, Afshari A et al (2023) Management of severe peri-operative bleeding: guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022. Eur J Anaesthesiol 40(4):226–304. https://doi.org/10.1097/EJA.0000000000001803
Becker S, Lang H, Vollmer Barbosa C, Tian Z, Melk A, Schmidt BMW (2023) Efficacy of CytoSorb(R): a systematic review and meta-analysis. Crit Care 27(1):215. https://doi.org/10.1186/s13054-023-04492-9
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C. Gräfe, L. Weidhase und M.A. Weigand geben an, dass kein Interessenkonflikt besteht. C. Scharf und U. Liebchen erhalten finanzielle Unterstützung der Fa. Cytosorbents Germany GmbH.
Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.
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Gräfe, C., Weidhase, L., Liebchen, U. et al. Hämoperfusion in Anästhesie und Intensivmedizin: Chancen, Risiken und Evidenz verschiedener Systeme. Anaesthesiologie 72, 843–851 (2023). https://doi.org/10.1007/s00101-023-01341-w
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DOI: https://doi.org/10.1007/s00101-023-01341-w