Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial

Gordana Taleska Stupica, Maja Sostaric, Marija Bozhinovska, Lea Rupert, Zoran Bosnic, Ales Jerin, Alojz Ihan, Tomislav Klokocovnik, Matej Podbregar, Gordana Taleska Stupica, Maja Sostaric, Marija Bozhinovska, Lea Rupert, Zoran Bosnic, Ales Jerin, Alojz Ihan, Tomislav Klokocovnik, Matej Podbregar

Abstract

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1β, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p < 0.001), IL-6 (until 48 h after surgery, p < 0.001), and IL-8 (until 24 h after surgery, p < 0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5th postoperative day (p < 0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p < 0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this article.

Copyright © 2020 Gordana Taleska Stupica et al.

Figures

Figure 1
Figure 1
Flowchart of patients in the randomized trial.
Figure 2
Figure 2
Cytokines and C5a complement.
Figure 3
Figure 3
CD64 and CD163 expression on monocytes, granulocytes, and lymphocytes.
Figure 4
Figure 4
Laboratory secondary outcome measures.
Figure 5
Figure 5
Hemodynamic parameters.
Figure 6
Figure 6
Consumption of noradrenalin (a) and insulin (b).

References

    1. Quaniers J. M., Leruth J., Albert A., Limet R. R., Defraigne J.-O. Comparison of inflammatory responses after off-pump and on-pump coronary surgery using surface modifying additives circuit. The Annals of Thoracic Surgery. 2006;81(5):1683–1690. doi: 10.1016/j.athoracsur.2005.11.059.
    1. Melek F. E., Baroncini L. A. V., Repka J. C. D., Nascimento C. S., PrécomaPrécoma D. B. Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation. Revista Brasileira De Cirurgia Cardiovascular. 2012;27(1):61–65. doi: 10.5935/1678-9741.20120010.
    1. Giomarelli P., Scolletta S., Borrelli E., Biagioli B. Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10. The Annals of Thoracic Surgery. 2003;76(1):117–123. doi: 10.1016/s0003-4975(03)00194-2.
    1. Rubens F. D., Nathan H., Labow R., et al. Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass. The Annals of Thoracic Surgery. 2005;79(2):655–665. doi: 10.1016/j.athoracsur.2004.07.044.
    1. Oliver W. C., Nuttall G. A., Orszulak T. A., et al. Hemofiltration but not steroids results in earlier tracheal extubation following cardiopulmonary bypass. Anesthesiology. 2004;101(2):327–339. doi: 10.1097/00000542-200408000-00013.
    1. Warren O. J., Watret A. L., de Wit K. L., et al. The inflammatory response to cardiopulmonary bypass: part 2-Anti-inflammatory therapeutic strategies. Journal of Cardiothoracic and Vascular Anesthesia. 2009;23(3):384–393. doi: 10.1053/j.jvca.2008.09.007.
    1. Morariu A. M., Loef B. G., Aarts L. P. H. J., et al. Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting. Chest. 2005;128(4):2677–2687. doi: 10.1378/chest.128.4.2677.
    1. Halonen J., Halonen P., Järvinen O., et al. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery. JAMA. 2007;297(14):1562–1567. doi: 10.1001/jama.297.14.1562.
    1. Whitlock R. P., Chan S., Devereaux P. J., et al. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials. European Heart Journal. 2008;29(21):2592–2600. doi: 10.1093/eurheartj/ehn333.
    1. Whitlock R. P., Young E., Noora J., Farrokhyar F., Blackall M., Teoh K. H. Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I. Journal of Surgical Research. 2006;132(2):188–194. doi: 10.1016/j.jss.2006.02.013.
    1. El Azab S. R., Rosseel P. M. J., de Lange J. J., et al. Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery. British Journal of Anaesthesia. 2002;88(4):496–501. doi: 10.1093/bja/88.4.496.
    1. Kilger E., Weis F., Briegel J., et al. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Critical Care Medicine. 2003;31(4):1068–1074. doi: 10.1097/01.ccm.0000059646.89546.98.
    1. Sano T., Morita S., Masuda M., Yasui H. Minor infection encouraged by steroid administration during cardiac surgery. Asian Cardiovascular and Thoracic Annals. 2006;14(6):505–510. doi: 10.1177/021849230601400613.
    1. Kellum J. A., 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. Critical Care Medicine. 2004;32(3):801–805. doi: 10.1097/01.ccm.0000114997.39857.69.
    1. Peng Z.-Y., Carter M. J., Kellum J. A. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Critical Care Medicine. 2008;36(5):1573–1577. doi: 10.1097/ccm.0b013e318170b9a7.
    1. Schefold J. C., von Haehling S., Corsepius M., et al. A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin-6, and complement-activating product 5a. Shock. 2007;28(4):418–425. doi: 10.1097/shk.0b013e31804f5921.
    1. Honore P. M., Jacobs R., Joannes-Boyau O., et al. Newly designed CRRT membranes for sepsis and SIRS-A pragmatic approach for bedside intensivists summarizing the more recent advances. ASAIO Journal. 2013;59(2):99–106. doi: 10.1097/mat.0b013e3182816a75.
    1. Kellum J. A. Hemoadsorption therapy for sepsis syndromes. Critical Care Medicine. 2003;31(1):323–324. doi: 10.1097/00003246-200301000-00060.
    1. Rittirsch D., Hoesel L. M., Ward P. A. The disconnect between animal models of sepsis and human sepsis. Journal of Leukocyte Biology. 2006;81(1):137–143. doi: 10.1189/jlb.0806542.
    1. Song M., Winchester J., Albright R. L., Capponi V. J., Choquette M. D., Kellum J. A. Cytokine removal with a novel adsorbent polymer. Blood Purification. 2004;22(5):428–434. doi: 10.1159/000080235.
    1. Born F., Pichlmaier M., Peter S., Khaladj N., Hagl C. SIRS in heart surgery: new possibilities for treatment through the use of a cytokine absorber during ECC? Kardiotechnik. 2014;23:41–46.
    1. Garau I., März A., Sehner S., et al. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor α serum levels in cardiac surgery: a randomized controlled trial. Minerva Anestesiologica. 2018;85(7) doi: 10.23736/S0375-9393.18.12898-7.
    1. Bernardi M. H., Rinoesl H., Dragosits K., et al. Effect of hemoadsorption during cardiopulmonary bypass surgery—a blinded, randomized, controlled pilot study using a novel adsorbent. Critical Care. 2016;20(1):p. 96. doi: 10.1186/s13054-016-1270-0.
    1. Demsar J. Statistical comparisons of classifiers over multiple data sets. Journal of Machine Learning Research. 2006;7:1–30.
    1. Poli E. C., Alberio L., Bauer-Doerries A., et al. Cytokine clearance with cytosorb during cardiac surgery: a pilot randomized controlled trial. Critical Care. 2019;23(1):p. 108. doi: 10.1186/s13054-019-2399-4.
    1. TrägerTräger K., Skrabal C., Fischer G., et al. Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass—a case series. The International Journal of Artificial Organs. 2017;40(5):240–249. doi: 10.5301/ijao.5000583.
    1. TrägerTräger K., Fritzler D., Fischer G., et al. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series. The International Journal of Artificial Organs. 2016;39(3):141–146. doi: 10.5301/ijao.5000492.
    1. Marek S., Gamper G., Reining G., Bergmann P., Mayr H., Kliegel A. ECMO and cytokine removal for bridging to surgery in a patient with ischemic ventricular septal defect—a case report. The International Journal of Artificial Organs. 2017;40(9):526–529. doi: 10.5301/ijao.5000600.
    1. Groselj-Grenc M., Ihan A., Derganc M. Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes. Mediators of Inflammation. 2008;2008:10. doi: 10.1155/2008/202646.202646
    1. Thornton S., Tan R., Sproles A., et al. A multiparameter flow cytometry analysis panel to assess CD163 mRNA and protein in monocyte and macrophage populations in hyperinflammatory diseases. The Journal of Immunology. 2019;202(5):1635–1643. doi: 10.4049/jimmunol.1800765.
    1. Comi M., Avancini D., Santoni de Sio F., et al. Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10) Cellular & Molecular Immunology. 2019;17(1):95–107. doi: 10.1038/s41423-019-0218-0.
    1. Kolackova M., Kudlova M., Kunes P., et al. Early expression of FcγRI (CD64) on monocytes of cardiac surgical patients and higher density of monocyte anti-inflammatory scavenger CD163 receptor in “on-pump” patients. Mediators of Inflammation. 2008;2008:6. doi: 10.1155/2008/235461.235461
    1. Trinchieri G. Type I interferon: friend or foe? The Journal of Experimental Medicine. 2010;207(10):2053–2063. doi: 10.1084/jem.20101664.
    1. Ivashkiv L. B., Donlin L. T. Regulation of type I interferon responses. Nature Reviews Immunology. 2014;14(1):36–49. doi: 10.1038/nri3581.
    1. Li Y., Lee P. Y., Kellner E. S., et al. Monocyte surface expression of Fcγ receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus. Arthritis Research & Therapy. 2010;12(3):p. R90. doi: 10.1186/ar3017.
    1. 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) doi: 10.1371/journal.pone.0187015.e0187015
    1. Kristeller J. L., Jankowski A., Reinaker T. Role of corticosteroids during cardiopulmonary bypass. Hospital Pharmacy. 2014;49(3):232–236. doi: 10.1310/hpj4903-232.
    1. Dvirnik N., Belley-Cote E. P., Hanif H., et al. Steroids in cardiac surgery: a systematic review and meta-analysis. British Journal of Anaesthesia. 2018;120(4):657–667. doi: 10.1016/j.bja.2017.10.025.
    1. Dieleman J., van Dijk D. Corticosteroids for cardiac surgery: a summary of two large randomised trials. Netherlands Journal of Critical Care. 2016;24(5):6–10.
    1. Whitten C. W., Hill G. E., Ivy R., Greilich P. E., Lipton J. M. Does the duration of cardiopulmonary bypass or aortic cross-clamp, in the absence of blood and/or blood product administration, influence the IL-6 response to cardiac surgery? Anesthesia & Analgesia. 1998;86(1):28–33. doi: 10.1097/00000539-199801000-00006.
    1. Laffey J. G., John F., Boylan J. F., Cheng D. C. H. The systemic inflammatory response to cardiac surgery. Implications for the anesthesiologist. Anesthesiology. 2002;97(1):215–252. doi: 10.1097/00000542-200207000-00030.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する