Journal of Artificial Organs

, Volume 21, Issue 2, pp 188–195 | Cite as

Continuous renal replacement therapy with a polymethyl methacrylate membrane hemofilter suppresses inflammation in patients after open-heart surgery with cardiopulmonary bypass

  • Hiroshi Mukaida
  • Satoshi Matsushita
  • Takahiro Inotani
  • Atsushi Nakamura
  • Atsushi Amano
Original Article Cardiopulmonary Bypass
  • 82 Downloads

Abstract

Cardiopulmonary bypass (CPB) induces a complex inflammatory response involving an increase in inflammatory cytokines, called postperfusion syndrome. Previous studies demonstrated that adsorption of the serum cytokines can reduce acute inflammation and improve clinical outcomes. In this study, patients were placed on continuous renal replacement therapy (CRRT) with a polymethyl methacrylate (PMMA) membrane hemofilter immediately after the start of an open-heart surgery with CPB and throughout the postoperative course to prevent postperfusion syndrome. The aim of this study was to assess whether continuous CRRT using a PMMA filter (PMMA–CRRT) could affect cytokine expression and improve perioperative outcomes. We designed a randomized controlled trial, which included 19 consecutive adult patients on maintenance dialysis and 7 consecutive adult patients who were not on maintenance dialysis (NHD group). Patients on maintenance dialysis were randomly divided into two groups: Ten patients who received CRRT with a polysulfone membrane hemofilter (PS group) and nine patients who received CRRT with a PMMA membrane (PMMA group). Blood samples were collected from the radial or brachial artery at five different time points. Comparisons between the PS, PMMA, and NHD groups revealed a significant main effect of time on changes in serum IL-6 and IL-8 concentrations (p < 0.01) and an interaction (p < 0.05) between time and group. Plasma IL-6 and IL-8 levels after surgery were significantly lower in the PMMA group than in the PS group, while other cytokines measured in this study were not significantly different. In addition, clinical outcomes were not significantly different between the groups. The continuous use of PMMA-CRRT throughout the perioperative period suppressed serum IL-6 and IL-8 concentrations, although there were no differences in clinical outcomes.

Keywords

IL-6 IL-8 Postperfusion syndrome Cytokine 

Notes

Acknowledgements

We thank all the staff for their assistance in conducting this study. This research received no specific Grants from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

References

  1. 1.
    Westaby S. Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit. Intensive Care Med. 1987;13(2):89–95.CrossRefPubMedGoogle Scholar
  2. 2.
    Kawamura T, Wakusawa R, Okada K, Inada S. Evaluations of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth. 1993;40:1016–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Sawa Y, Shimazaki Y, Kadoba K, Masai T, Fukuda H, Ohata T, et al. Attenuation of cardiopulmonary bypass derived inflammatory reactions reduces myocardial reperfusion injury in open heart surgery. J Thorac Cardiovasc Surg. 1996;111:29–35.CrossRefPubMedGoogle Scholar
  4. 4.
    Engels M, Bilgic E, Pinto A, Vasquez E, Wollschläger L, Steinbrenner H, et al. A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage. J Inflamm. 2014;12:11: 26.CrossRefGoogle Scholar
  5. 5.
    Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Miyazaki M. Immunosuppression following surgical and traumatic injury. Surg Today. 2010;40(9):793–808.CrossRefPubMedGoogle Scholar
  6. 6.
    Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997;112:676–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Moat NE, Shore DF, Evans TW. Organ dysfunction and cardiopulmonary bypass: the role of complement and complement regulatory proteins. Eur J Cardiothorac Surg. 1993;7:563–73.CrossRefPubMedGoogle Scholar
  8. 8.
    Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1983;86:845–57.PubMedGoogle Scholar
  9. 9.
    Steinberg J, Fink G, Picone A, Searles B, Schiller H, Lee HM, et al. Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass. J Extra Corpor Technol. 2001;33(4):218 – 22.PubMedGoogle Scholar
  10. 10.
    Prasad A, Stone GW, Holmes DR, Gersh B. Reperfusion injury, microvascular dysfunction, and cardioprotection: the dark side of reperfusion. Circulation. 2009;120(21):2105–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol. 2011;301(5):H1723-H1741.CrossRefGoogle Scholar
  12. 12.
    Maganti M, Badiwala M, Sheikh A, Scully H, Feindel C, David TE, et al. Predictors of low cardiac output syndrome after isolated mitral valve surgery. J Thorac Cardiovasc Surg. 2010;140(4):790–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Stenvinkel P, Heimbürger O, Lindholm B, Kaysen GA, Bergström J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation, and atherosclerosis (MIA syndrome). Nephrol Dial Transplant. 2000;15:953–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Herbelin A, Ureña P, Nguyen AT, Zingraff J, Descamps-Latscha B. Elevated circulating levels of interleukin-6 in patients with chronic renal failure. Kidney Int. 1991;39(5):954 – 60.CrossRefPubMedGoogle Scholar
  15. 15.
    Shann KG, Likosky DS, Murkin JM, Baker RA, Baribeau YR, DeFoe GR, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: a focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. J Thorac Cardiovasc Surg. 2006; 132(2):283 – 90.CrossRefPubMedGoogle Scholar
  16. 16.
    Jiménez JJ, Iribarren JL, Brouard M, Hernández D, Palmero S, Jiménez A, et al. Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dosedependent, phase IV clinical trial. J Cardiothorac Surg. 2011;14:6: 138.CrossRefGoogle Scholar
  17. 17.
    Zhang X, Zhou C, Zhuang J, Xiao X, Zheng S, Xiong W, et al. Effects of leukocyte depletion on cardiopulmonary protection and inflammation after valve surgery. Int J Artif Organs. 2010;33(11):812–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Blomquist S, Gustafsson V, Manolopoulos T, Pierre L. Clinical experience with a novel endotoxin adsorbtion device in patients undergoing cardiac surgery. Perfusion. 2009;24(1):13–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Pathan N, Hemingway CA, Alizadeh AA, Stephens AC, Boldrick JC, Oragui EE, et al. Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet. 2004;363(9404):203–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Pathan N, Franklin JL, Eleftherohorinou H, Wright VJ, Hemingway CA, Waddell SJ, et al. Myocardial depressant effects of interleukin 6 in meningococcal sepsis are regulated by p38 mitogen-activated protein kinase. Crit Care Med. 2011;39(7):1692–711.CrossRefPubMedGoogle Scholar
  21. 21.
    Stefoni S, La Manna G, Zanchelli F, Dalmastri V, Perna C, Pace G, et al. Clinical biology of artificial organ substitution. Nephrol Dial Transplant. 1998;13(Suppl 7):51–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Heidland A, Sebekova K, Schinzel R. Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis. 2001;38:S100–S106.CrossRefPubMedGoogle Scholar
  23. 23.
    Panihi V, Miglion M, De Pietro S, Taccola D, Bianchi AM, Giovannini L, et al. C-reactive protein and interleukin-6 level are related to renal function in predialytic chronic renal failure. Nephron. 2002;91:594–600.CrossRefGoogle Scholar
  24. 24.
    Halter J, Steinberg J, Fink G, Lutz C, Picone A, Maybury R, et al. Evidence of systemic cytokine release in patients undergoing cardiopulmonary bypass. J Extra Corpor Technol. 2005;37(3):272–7.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Bellomo R, Tipping P, Boyce N. Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients. Crit Care Med. 1993;21:522–26.CrossRefPubMedGoogle Scholar
  26. 26.
    Hirayama Y, Oda S, Tateishi Y, Sadahiro T, Nakamura M, Watanabe E, et al. Comparison of interleukin-6 removal properties among hemofilters consisting of varying membrane materials and surface areas: An in vitro study. Blood Purif. 2011;31:18–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Nakada T, Oda S, Hirosawa H, Sadahiro T, Nakamura M, Abe R, et al. Continuous hemodiafiltration with PMMA hemofilter in the treatment of patients with septic shock. Mol Med. 2008;14:257–63.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Matsuda K, Moriguchi T, Harii N, Goto J. Comparison of efficacy between continuous hemodiafiltration with a PMMA membrane hemofilter and a PAN membrane hemofilter in the treatment of a patient with septic acute renal failure. Transfus Apher Sci. 2009;40:49–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Faubel S, Edelstein CL. Mechanisms and mediators of lung injury after acute kidney injury. Nat Rev Nephrol. 2016;12(1):48–60.CrossRefPubMedGoogle Scholar
  30. 30.
    Yimin H, Wenkui Y, Jialiang S, Qiyi C, Juanhong S, Zhiliang L, et al. Effects of continuous renal replacement therapy on renal inflammatory cytokines during extracorporeal membrane oxygenation in a porcine model. J Cardiothorac Surg. 2013;29:8: 113.CrossRefGoogle Scholar
  31. 31.
    Shi J, Chen Q, Yu W, Shen J, Gong J, He C, et al. Continuous renal replacement therapy reduces the systemic and pulmonary inflammation induced by venovenous extracorporeal membrane oxygenation in a porcine model. Artif Organs. 2014;38(3):215 – 23.CrossRefPubMedGoogle Scholar
  32. 32.
    Liu KD, Himmelfarb J, Paganini E, Ikizler TA, Soroko SH, Mehta RL, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol. 2006;1(5):915–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, et al. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury. J Crit Care. 2009;24(1):129 – 40.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2018

Authors and Affiliations

  • Hiroshi Mukaida
    • 1
    • 2
  • Satoshi Matsushita
    • 1
  • Takahiro Inotani
    • 2
  • Atsushi Nakamura
    • 3
  • Atsushi Amano
    • 1
  1. 1.Department of Cardiovascular SurgeryFaculty of Medicine, Juntendo UniversityTokyoJapan
  2. 2.Department of Clinical EngineeringJuntendo University HospitalTokyoJapan
  3. 3.Department of Clinical EngineeringFaculty of Health Sciences, Kyorin UniversityTokyoJapan

Personalised recommendations