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Critical care (London, England)
Dec 12, 2024;28 (1): 406.

REmoval of cytokines during CArdiac surgery (RECCAS): a randomised controlled trial.

Andreas Hohn, Nathalie M Malewicz-Oeck, Dirk Buchwald, Thorsten Annecke, Peter K Zahn, Andreas Baumann
Author Information
  1. Andreas Hohn: Faculty of Medicine, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
  2. Nathalie M Malewicz-Oeck: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, Medical Faculty of Ruhr-University Bochum, BG University Hospital Bergmannsheil gGmbH, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
  3. Dirk Buchwald: Department of Cardiothoracic Surgery, BG University Hospital Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
  4. Thorsten Annecke: Faculty of Medicine, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
  5. Peter K Zahn: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, Medical Faculty of Ruhr-University Bochum, BG University Hospital Bergmannsheil gGmbH, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
  6. Andreas Baumann: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, Medical Faculty of Ruhr-University Bochum, BG University Hospital Bergmannsheil gGmbH, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany. andreas.baumann@bergmannsheil.de.
PMID: 39668341 DOI: 10.1186/s13054-024-05175-9

Abstract

BACKGROUND: Cardiopulmonary bypass (CPB) triggers marked cytokine release often followed by a systemic inflammatory response syndrome, associated with adverse postoperative outcomes. This trial investigates the intraoperative use of haemoadsorption (HA) during cardiac surgery with CPB to assess its impact on postoperative systemic inflammatory response.
METHODS: In this prospective randomised controlled trial (ethics approval no. 5094-14DRKS00007928), patients (> 65 years) undergoing elective on-pump cardiac surgery were randomised to intraoperative HA (CytoSorb) during CPB or standard care without HA. Primary outcome was the difference in mean interleukin (IL)-6 serum concentrations between groups on intensive care unit (ICU) admission. The secondary outcomes included various clinical and biochemical endpoints. Statistical methods included paired and unpaired t-tests, Wilcoxon, Mann-Whitney U-tests, and chi-square tests.
RESULTS: Thirty-eight patients were allocated to receive either intraoperative HA (n = 19) or standard care (n = 19). The primary outcome, IL-6 levels on ICU admission, did not differ between the study group and controls (214.4 ± 328.8 vs. 155.8 ± 159.6 pg/ml, p = 0.511). During surgery pre- versus post-adsorber IL-2, IL-6, IL-8, IL-10, heparan sulfate and myoglobin post- levels were reduced. Furthermore, IL-6 levels did not differ between the study groups on day 1 and 2 in the ICU. While sequential organ failure assessment scores, lactate levels, and C-reactive protein and procalcitonin (PCT) showed no statistically significant differences. Regarding haemodynamic stability in the treatment group the cardiac index (3.2 ± 0.7 vs. 2.47 ± 0.47 l/min/m, p = 0.012) on ICU day 2 increased, and lower fluid requirements as well as decreased fibrinogen requirement were observed. Need for renal replacement therapy did not differ though a shorter duration was observed in the treatment group. Time on ventilator, respiratory parameters, infectious complications, delirium scores, ICU and hospital lengths of stay, and mortality did not differ between groups.
CONCLUSION: HA did not reduce the IL-6 level on ICU admission or afterwards. Even though HA reduced cytokine load during cardiac surgery in the treatment group. There were no significant differences between groups in the postoperative course of other cytokine concentrations, organ dysfunction, ICU and hospital lengths of stay and mortality rates. Trial registration prospectively DRKS00007928 and published under: Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A. RECCAS - REmoval of Cytokines during cardiac Surgery: study protocol for a randomised controlled trial.
TRIALS: 2016;17: 137.

Keywords

Cardiac Surgery Cardiopulmonary bypass Cytokines Haemoadsorption Heart–lung-machine Inflammation

References

  1. McGuinness J, Bouchier-Hayes D, Redmond JM. Understanding the inflammatory response to cardiac surgery. The Surgeon. 2008;6:162–71. [PMID: 18581753]
  2. Hill GE, Whitten CW, Landers DF. The influence of cardiopulmonary bypass on cytokines and cell-cell communication. J Cardiothorac Vasc Anesth. 1997;11:367–75. [PMID: 9161906]
  3. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 2003;75:S715–20. [PMID: 12607717]
  4. Paparella D. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21:232–44. [PMID: 11825729]
  5. Allan CK, Newburger JW, McGrath E, Elder J, Psoinos C, Laussen PC, et al. The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass. Anesth Analg. 2010;111:1244–51. [PMID: 20829561]
  6. Cremer J, Martin M, Redl H, Bahrami S, Abraham C, Graeter T, et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg. 1996;61:1714–20. [PMID: 8651772]
  7. Mojcik CF, Levy JH. Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg. 2001;71:745–54. [PMID: 11235755]
  8. Sander M, Von Heymann C, Dossow VV, Spaethe C, Konertz WF, Jain U, et al. Increased interleukin-6 after cardiac surgery predicts infection. Anesth Analg. 2006;102:1623–9. [PMID: 16717298]
  9. Ankawi G, Xie Y, Yang B, Xie Y, Xie P, Ronco C. What have we learned about the use of Cytosorb adsorption columns? Blood Purif. 2019;48:196–202. [PMID: 31039564]
  10. Antunes N, Dragosavc D, Petrucci Junior O, Oliveira PPMD, Kosour C, Blotta MHSL, et al. The use of ultrafiltration for inflammatory mediators removal during cardiopulmonary bypass in coronary artery bypass graf surgery. Rev Bras Cir Cardiovasc. 2008;23:175–82. [PMID: 18820779]
  11. Becker S, Lang H, Vollmer Barbosa C, Tian Z, Melk A, Schmidt BMW. Efficacy of CytoSorb®: a systematic review and meta-analysis. Crit Care. 2023;27:215. [PMID: 37259160]
  12. Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery—a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care. 2016;20:96. [PMID: 27059056]
  13. Heymann M, Schorer R, Putzu A. Mortality and adverse events of hemoadsorption with CYTOSORB ® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2022;66:1037–50. [PMID: 35788557]
  14. Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia*. Crit Care Med. 2004;32:801–5. [PMID: 15090965]
  15. Peng Z-Y, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med. 2008;36:1573–7. [PMID: 18434884]
  16. Taniguchi T. Cytokine adsorbing columns. Contrib Nephrol [Internet]. 2010 [cited 2024 Feb 2]; 166. Available from https://pubmed.ncbi.nlm.nih.gov/20473001/
  17. Honore PM, Jacobs R, Joannes-Boyau O, De Regt J, De Waele E, Van Gorp V, et al. Newly designed CRRT membranes for sepsis and SIRS—a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review. ASAIO J. 2013;59:99–106. [PMID: 23438770]
  18. Hawchar F, Tomescu D, Träger K, Joskowiak D, Kogelmann K, Soukup J, et al. Hemoadsorption in the critically ill—final results of the International CytoSorb Registry. PLoS ONE. 2022;17:e0274315. [PMID: 36282800]
  19. Diab M, Lehmann T, Bothe W, Akhyari P, Platzer S, Wendt D, et al. Cytokine hemoadsorption during cardiac surgery versus standard surgical care for infective endocarditis (REMOVE): results from a multicenter randomized controlled trial. Circulation. 2022;145:959–68. [PMID: 35213213]
  20. Poli EC, Alberio L, Bauer-Doerries A, Marcucci C, Roumy A, Kirsch M, et al. Cytokine clearance with CytoSorb® during cardiac surgery: a pilot randomized controlled trial. Crit Care. 2019;23:108. [PMID: 30944029]
  21. Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A. RECCAS—removal of cytokines during CArdiac surgery: study protocol for a randomised controlled trial. Trials. 2016;17:137. [PMID: 26971164]
  22. Turner L, Shamseer L, Altman DG, Weeks L, Peters J, Kober T, et al. Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals. Cochrane Database Syst Rev. 2012. https://doi.org/10.1002/14651858.MR000030.pub2 . [DOI: 10.1002/14651858.MR000030.pub2]
  23. Bartholmes F, Malewicz NM, Ebel M, Zahn PK, Meyer-Frießem CH. Pupillometric monitoring of nociception in cardiac anesthesia. Dtsch Arztebl Int. 2020;117(49):833–40. [PMID: 33593477]
  24. Meyer-Frießem CH, Hüsken S, Kaisler M, Malewicz NM, Zahn PK, Baumann A. Isoflurane not at the expense of postoperative nausea and vomiting in cardiac anesthesia—an observational study. Curr Med Res Opin. 2021;37:2035. [PMID: 34515599]
  25. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120:c179-184. [PMID: 22890468]
  26. Boussekey N, Chiche A, Faure K, Devos P, Guery B, d’Escrivan T, et al. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. Intensive Care Med. 2008;34:1646–53. [PMID: 18542921]
  27. Haase M, Silvester W, Uchino S, Goldsmith D, Davenport P, Tipping P, et al. A pilot study of high-adsorption hemofiltration in human septic shock. Int J Artif Organs. 2007;30:108–17. [PMID: 17377905]
  28. Ronco C, Brendolan A, Lonnemann G, Bellomo R, Piccinni P, Digito A, et al. A pilot study of coupled plasma filtration with adsorption in septic shock*. Crit Care Med. 2002;30:1250–5. [PMID: 12072677]
  29. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95: 103208. [PMID: 31078660]
  30. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81. [PMID: 18929686]
  31. Baksaas ST, Flom-Halvorsen HI, Øvrum E, Videm V, Mollnes TE, Brosstad F, et al. Leucocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery. Perfusion. 1999;14:107–17. [PMID: 10338322]
  32. Deng MC, Dasch B, Erren M, Möllhoff T, Scheld HH. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg. 1996;62:184–90. [PMID: 8678641]
  33. Rimmelé T, Venkataraman R, Madden NJ, Elder MM, Wei LM, Pellegrini RV, et al. Comparison of inflammatory response during on-pump and off-pump coronary artery bypass surgery. Int J Artif Organs. 2010;33:131–8. [PMID: 20383854]
  34. Goetz G, Hawlik K, Wild C. Extracorporeal cytokine adsorption therapy as a preventive measure in cardiac surgery and as a therapeutic add-on treatment in sepsis: an update systematic review of comparative efficacy and safety. Crit Care Med. 2021. https://doi.org/10.1097/CCM.0000000000005023 . [DOI: 10.1097/CCM.0000000000005023]
  35. Gleason TG, Argenziano M, Bavaria JE, Kane LC, Coselli JS, Engelman RM, et al. Hemoadsorption to reduce plasma-free hemoglobin during cardiac surgery: results of REFRESH I pilot study. Semin Thorac Cardiovasc Surg. 2019;31:783–93. [PMID: 31085219]
  36. Asch S, Kaufmann TP, Walter M, Leistner M, Danner BC, Perl T, et al. The effect of perioperative hemadsorption in patients operated for acute infective endocarditis-a randomized controlled study. Artif Organs. 2021;45:1328–37. [PMID: 34152632]
  37. Garau I, März A, Sehner S, Reuter DA, Reichenspurner H, Zöllner C, et al. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor α serum levels in cardiac surgery: a randomized controlled trial. Minerva Anestesiol. 2019;85:715–23. [PMID: 30481999]
  38. Roth-Isigkeit A, Hasselbach L, Ocklitz E, Brückner S, Ros A, Gehring H, et al. Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass. Clin Exp Immunol. 2001;125:80–8. [PMID: 11472429]
  39. Tylutka A, Walas Ł, Zembron-Lacny A. Level of IL-6, TNF, and IL-1β and age-related diseases: a systematic review and meta-analysis. Front Immunol. 2024. https://doi.org/10.3389/fimmu.2024.1330386/full . [DOI: 10.3389/fimmu.2024.1330386/full]
  40. Klinkmann G, Koball S, Reuter DA, Mitzner S. Hemoperfusion with CytoSorb®: current knowledge on patient selection, timing, and dosing. In: Bellomo R, Ronco C (eds) Contrib Nephrol. S. Karger AG; 2023 [cited 2023 Aug 16]. pp. 17–24. https://doi.org/10.1159/000527774
  41. Kühne L-U, Binczyk R, Rieß F-C. Comparison of intraoperative versus intraoperative plus postoperative hemoadsorption therapy in cardiac surgery patients with endocarditis. Int J Artif Organs. 2019;42:194–200. [PMID: 30803290]
  42. Pérez-Fernández X, Ulsamer A, Cámara-Rosell M, Sbraga F, Boza-Hernández E, Moret-Ruíz E, Plata-Menchaca E, Santiago-Bautista D, Boronat-García P, Gumucio-Sanguino V, Peñafiel-Muñoz J, Camacho-Pérez M, Betbesé-Roig A, Forni L, Campos-Gómez A, Sabater-Riera J, SIRAKI02 Study Group. Extracorporeal blood purification and acute kidney injury in cardiac surgery: the SIRAKI02 randomized clinical trial. JAMA. 2024;332(17):1446–54. https://doi.org/10.1001/jama.2024.20630 . [DOI: 10.1001/jama.2024.20630]
  43. Scheier J, Nelson PJ, Schneider A, Colombier S, Kindgen-Milles D, Deliargyris EN, et al. Mechanistic considerations and pharmacokinetic implications on concomitant drug administration during CytoSorb therapy. Crit Care Explor. 2022;4: e0688. [PMID: 35783552]
  44. Schneider AG, André P, Scheier J, Schmidt M, Ziervogel H, Buclin T, et al. Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption. Sci Rep. 2021;11:10493. [PMID: 34006946]
  45. König C, Röhr AC, Frey OR, Brinkmann A, Roberts JA, Wichmann D, et al. In vitro removal of anti-infective agents by a novel cytokine adsorbent system. Int J Artif Organs. 2019;42:57–64. [PMID: 30545255]
  46. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996;24:1125–8. [PMID: 8674323]
  47. Franke A, Lante W, Fackeldey V, Becker HP, Thode C, Kuhlmann WD, et al. Proinflammatory and antiinflammatory cytokines after cardiac operation: different cellular sources at different times. Ann Thorac Surg. 2002;74:363–70. [PMID: 12173814]
  48. Haveman J. The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring and treatment. Neth J Med. 1999;55:132–41. [PMID: 10509072]
  49. Hohn A, Baumann A, Pietroschinsky E, Franklin J, Illerhaus A, Buchwald D, et al. Hemoadsorption: effective in reducing circulating fragments of the endothelial glycocalyx during cardiopulmonary bypass in patients undergoing on-pump cardiac surgery? Minerva Anestesiol. 2021 [cited 2023 Jul 3];87. Available from https://www.minervamedica.it/index2.php?show=R02Y2021N01A0035
  50. Naruka V, Salmasi MY, Arjomandi Rad A, Marczin N, Lazopoulos G, Moscarelli M, et al. Use of cytokine filters during cardiopulmonary bypass: systematic review and meta-analysis. Heart Lung Circ. 2022;31:1493–503. [PMID: 36041987]
  51. Haidari Z, Wendt D, Thielmann M, Mackowiak M, Neuhäuser M, Jakob H, et al. Intraoperative hemoadsorption in patients with native mitral valve infective endocarditis. Ann Thorac Surg. 2020;110:890–6. [PMID: 32059855]
  52. Träger K, Skrabal C, Fischer G, Datzmann T, Schroeder J, Fritzler D, et al. Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass—a case series. Int J Artif Organs. 2017;40:240–9. [PMID: 28525670]
  53. Schädler D, Pausch C, Heise D, Meier-Hellmann A, Brederlau J, Weiler N, 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:e0187015. [PMID: 29084247]
  54. Vercaemst L. Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. J Extra Corpor Technol. 2008;40:257–67. [PMID: 19192755]
  55. Boss K, Jahn M, Wendt D, Haidari Z, Demircioglu E, Thielmann M, et al. Extracorporeal cytokine adsorption: significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery. PLoS ONE. 2021;16:e0246299. [PMID: 33556101]
  56. Mitzner S, Kogelmann K, Ince C, Molnár Z, Ferrer R, Nierhaus A. Adjunctive hemoadsorption therapy with CytoSorb in patients with septic/vasoplegic shock: a best practice consensus statement. J Clin Med. 2023;12:7199. [PMID: 38068250]
  57. Belletti A, Lerose CC, Zangrillo A, Landoni G. Vasoactive-inotropic score: evolution, clinical utility, and pitfalls. J Cardiothorac Vasc Anesth. 2021;35:3067–77. [PMID: 33069558]
  58. Manohar M, Jawali V, Neginahal S, Gt S, Muniraj G, Chakravarthy M. Hemoadsorption in complex cardiac surgery—a single center experience. J Clin Med. 2022;11:7005. [PMID: 36498579]

MeSH Term

Humans
Male
Female
Aged
Prospective Studies
Cardiac Surgical Procedures
Cytokines
Intensive Care Units
Cardiopulmonary Bypass
Interleukin-6

Chemicals

Cytokines
Interleukin-6
Journal Article Randomized Controlled Trial
Article has an altmetric score of 21

Word Cloud

Created with Highcharts 10.0.0ICUHAsurgerytrialcardiacrandomisedgroupsIL-6levelsdiffergroupCPBcytokinepostoperativeintraoperativecontrolledcareadmissionstudy2treatmentCardiopulmonarybypasssystemicinflammatoryresponseoutcomespatientsstandardoutcomeconcentrationsincludedn = 19vsp = 0reduceddayorganscoressignificantdifferencesobservedthoughhospitallengthsstaymortalityRECCASREmovalCytokinesCardiacBACKGROUND:triggersmarkedreleaseoftenfollowedsyndromeassociatedadverseinvestigatesusehaemoadsorptionassessimpactMETHODS:prospectiveethicsapproval5094-14DRKS00007928> 65yearsundergoingelectiveon-pumpCytoSorbwithoutPrimarydifferencemeaninterleukinIL-6serumintensiveunitsecondaryvariousclinicalbiochemicalendpointsStatisticalmethodspairedunpairedt-testsWilcoxonMann-WhitneyU-testschi-squaretestsRESULTS:Thirty-eightallocatedreceiveeitherprimarycontrols2144 ± 32881558 ± 1596 pg/ml511pre-versuspost-adsorberIL-2IL-8IL-10heparansulfatemyoglobinpost-Furthermore1sequentialfailureassessmentlactateC-reactiveproteinprocalcitoninPCTshowedstatisticallyRegardinghaemodynamicstabilityindex32 ± 0747 ± 047l/min/m012increasedlowerfluidrequirementswelldecreasedfibrinogenrequirementNeedrenalreplacementtherapyshorterdurationTimeventilatorrespiratoryparametersinfectiouscomplicationsdeliriumCONCLUSION:reducelevelafterwardsEvenloadcoursedysfunctionratesTrialregistrationprospectivelyDRKS00007928publishedunder:BaumannBuchwaldDAnneckeTHellmichMZahnPKHohn-Surgery:protocolTRIALS:201617:137cytokinesCArdiac:SurgeryHaemoadsorptionHeart–lung-machineInflammation

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