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Oxidation Reduction Potential (ORP) is Predictive of Complications Following Pediatric Cardiac Surgery

Pediatric Cardiology volume 39, pages 299–306 (2018)Cite this article

Abstract

Oxidation reduction potential (ORP) or Redox is the ratio of activity between oxidizers and reducers. Oxidative stress (OS) can cause cellular injury and death, and is important in the regulation of immune response to injury or disease. In the present study, we investigated changes in the redox system as a function of cardiopulmonary bypass (CPB) in pediatric patients. 664 plasma samples were collected from 162 pediatric patients having cardiac surgery of various CPB times. Lower ORP values at 12 h post-CPB were associated with poor survival rate (mean ± SD 167 ± 20 vs. 138 ± 19, p = 0.005) and higher rate of thrombotic complications (153 ± 21 vs. 168 ± 20, p < 0.008). Similarly, patients who developed infections had lower ORP values at 6 h (149 ± 19 vs. 160 ± 22, p = 0.02) and 12 h (156 ± 17 vs. 168 ± 21, p = 0.004) post-CPB. Patients that developed any post-operative complication also had lower 6 h (149 ± 17 vs. 161 ± 23, p = 0.002) and 12 h (157 ± 18 vs. 170 ± 21, p = 0.0007) post-CPB ORP values. Free hemoglobin and IL-6, IL-10, and CRP were not associated with ORP levels. However, higher haptoglobin levels preoperatively were protective against decreases in ORP. Decreased ORP is a marker for poor outcome and predictive of post-operative thrombosis, infection, and other complications in critically ill pediatric cardiac surgery patients. These results suggest that redox imbalance and OS may contribute to the risk of complications and poor outcome in pediatric CBP patients. Haptoglobin may be a marker for increased resilience to OS in this population.

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References

  1. Bjugstad KB, Rael LT, Levy S, Carrick M, Mains CW, Slone DS, Bar-Or D (2016) Oxidation–reduction potential as a biomarker for severity and acute outcome in traumatic brain injury. Oxid Med Cell Longev 2016:6974257. https://doi.org/10.1155/2016/6974257

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bar-Or D, Bar-Or R, Rael LT, Brody EN (2015) Oxidative stress in severe acute illness. Redox Biol 4:340–345. https://doi.org/10.1016/j.redox.2015.01.006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Bar-Or D, Carrick MM, Mains CW, Rael LT, Slone D, Brody EN (2015) Sepsis, oxidative stress, and hypoxia: are there clues to better treatment? Redox Rep 20:193–197. https://doi.org/10.1179/1351000215Y.0000000005

    Article  PubMed  Google Scholar 

  4. Rael LT, Bar-Or R, Mains CW, Slone DS, Levy AS, Bar-Or D (2009) Plasma oxidation-reduction potential and protein oxidation in traumatic brain injury. J Neurotrauma 26:1203–1211. https://doi.org/10.1089/neu.2008-0816

    Article  PubMed  Google Scholar 

  5. Rael LT, Bar-Or R, Salottolo K, Mains CW, Slone DS, Offner PJ, Bar-Or D (2009) Injury severity and serum amyloid A correlate with plasma oxidation-reduction potential in multi-trauma patients: a retrospective analysis. Scand J Trauma Resusc Emerg Med 17:57. https://doi.org/10.1186/1757-7241-17-57

    Article  PubMed  PubMed Central  Google Scholar 

  6. Spanidis Y, Goutzourelas N, Stagos D, Kolyva AS, Gogos CA, Bar-Or D, Kouretas D (2015) Assessment of oxidative stress in septic and obese patients using markers of oxidation–reduction potential. In Vivo 29:595–600

    CAS  PubMed  Google Scholar 

  7. Spanidis Y, Mpesios A, Stagos D, Goutzourelas N, Bar-Or D, Karapetsa M, Zakynthinos E, Spandidos DA, Tsatsakis AM, Leon G, Kouretas D (2016) Assessment of the redox status in patients with metabolic syndrome and type 2 diabetes reveals great variations. Exp Ther Med 11:895–903. https://doi.org/10.3892/etm.2016.2968

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Levy JH, Tanaka KA (2003) Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 75:S715–S720

    Article  PubMed  Google Scholar 

  9. Gessler P, Pretre R, Hohl V, Rousson V, Fischer J, Dahinden C (2004) CXC-chemokine stimulation of neutrophils correlates with plasma levels of myeloperoxidase and lactoferrin and contributes to clinical outcome after pediatric cardiac surgery. Shock 22:513–520

    CAS  Article  PubMed  Google Scholar 

  10. Edmunds LH (1998) Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 66:S12–S16 discussion S25-8

    Article  PubMed  Google Scholar 

  11. Allen ML, Hoschtitzky JA, Peters MJ, Elliott M, Goldman A, James I, Klein NJ (2006) Interleukin-10 and its role in clinical immunoparalysis following pediatric cardiac surgery. Crit Care Med 34:2658–2665. https://doi.org/10.1097/01.CCM.0000240243.28129.36

    CAS  Article  PubMed  Google Scholar 

  12. Madhok AB, Ojamaa K, Haridas V, Parnell VA, Pahwa S, Chowdhury D (2006) Cytokine response in children undergoing surgery for congenital heart disease. Pediatr Cardiol 27:408–413. https://doi.org/10.1007/s00246-006-0934-y

    Article  PubMed  Google Scholar 

  13. Holmes JHT, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, Hall RA (2002) Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res 51:579–586

    CAS  Article  PubMed  Google Scholar 

  14. Hirai S (2003) Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. Ann Thorac Cardiovasc Surg 9:365–370

    PubMed  Google Scholar 

  15. Gando S, Nishihira J, Kemmotsu O, Kobayashi S, Morimoto Y, Matsui Y, Yasuda K (2000) An increase in macrophage migration inhibitory factor release in patients with cardiopulmonary bypass surgery. Surg Today 30:689–694. https://doi.org/10.1007/s005950050041

    CAS  Article  PubMed  Google Scholar 

  16. Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N (2012) Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial. Pediatr Crit Care Med 13:290–299. https://doi.org/10.1097/PCC.0b013e31822f173c

    Article  PubMed  Google Scholar 

  17. Kalmin ND, Brown DJ (1982) Platelet washing with a blood cell processor. Transfusion 22:125–127

    CAS  Article  PubMed  Google Scholar 

  18. Vesilind GW, Simpson MB, Shifman MA, Colman RE, Kao KJ (1988) Evaluation of a centrifugal blood cell processor for washing platelet concentrates. Transfusion 28:46–51

    CAS  Article  PubMed  Google Scholar 

  19. Rael LTB-OR, Kelly MT, Carrick MM, Bar-Or D (2015) Assessment of oxidative stress in patients with an isolated traumatic brain injury using disposable electrochemical test strips. Electroanalysis 27:2567–2573

    CAS  Article  Google Scholar 

  20. Donadee C, Raat NJ, Kanias T, Tejero J, Lee JS, Kelley EE, Zhao X, Liu C, Reynolds H, Azarov I, Frizzell S, Meyer EM, Donnenberg AD, Qu L, Triulzi D, Kim-Shapiro DB, Gladwin MT (2011) Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation 124:465–476. https://doi.org/10.1161/CIRCULATIONAHA.110.008698

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Yalcin O, Ortiz D, Tsai AG, Johnson PC, Cabrales P (2014) Microhemodynamic aberrations created by transfusion of stored blood. Transfusion 54:1015–1027. https://doi.org/10.1111/trf.12361

    Article  PubMed  Google Scholar 

  22. Hess JR (2010) Red cell changes during storage. Transfus Apher Sci 43:51–59. https://doi.org/10.1016/j.transci.2010.05.009

    Article  PubMed  Google Scholar 

  23. Stapley R, Owusu BY, Brandon A, Cusick M, Rodriguez C, Marques MB, Kerby JD, Barnum SR, Weinberg JA, Lancaster JR Jr, Patel RP (2012) Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity. Biochem J 446:499–508. https://doi.org/10.1042/BJ20120675

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Sullivan JS, Kilpatrick L, Costarino AT Jr, Lee SC, Harris MC (1992) Correlation of plasma cytokine elevations with mortality rate in children with sepsis. J Pediatr 120:510–515

    CAS  Article  PubMed  Google Scholar 

  25. Gessler P, Pfenninger J, Pfammatter JP, Carrel T, Baenziger O, Dahinden C (2003) Plasma levels of interleukin-8 and expression of interleukin-8 receptors on circulating neutrophils and monocytes after cardiopulmonary bypass in children. J Thorac Cardiovasc Surg 126:718–725

    CAS  Article  PubMed  Google Scholar 

  26. Eggum R, Ueland T, Mollnes TE, Videm V, Aukrust P, Fiane AE, Lindberg HL (2008) Effect of perfusion temperature on the inflammatory response during pediatric cardiac surgery. Ann Thorac Surg 85:611–617. https://doi.org/10.1016/j.athoracsur.2007.10.062

    Article  PubMed  Google Scholar 

  27. Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP (2003) Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation 107:2823–2828. https://doi.org/10.1161/01.CIR.0000070955.55636.25

    CAS  Article  PubMed  Google Scholar 

  28. Hietbrink F, Koenderman L, Rijkers G, Leenen L (2006) Trauma: the role of the innate immune system. World J Emerg Surg 1:15. https://doi.org/10.1186/1749-7922-1-15

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Mokart D, Capo C, Blache JL, Delpero JR, Houvenaeghel G, Martin C, Mege JL (2002) Early postoperative compensatory anti-inflammatory response syndrome is associated with septic complications after major surgical trauma in patients with cancer. Br J Surg 89:1450–1456. https://doi.org/10.1046/j.1365-2168.2002.02218.x

    CAS  Article  PubMed  Google Scholar 

  30. Seekamp A, Jochum M, Ziegler M, van Griensven M, Martin M, Regel G (1998) Cytokines and adhesion molecules in elective and accidental trauma-related ischemia/reperfusion. J Trauma 44:874–882

    CAS  Article  PubMed  Google Scholar 

  31. Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC (2000) Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med 26:1076–1081

    CAS  Article  PubMed  Google Scholar 

  32. Hatherill M, Tibby SM, Turner C, Ratnavel N, Murdoch IA (2000) Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock. Crit Care Med 28:2591–2594

    CAS  Article  PubMed  Google Scholar 

  33. Harris MC, D’Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L (2005) Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing enterocolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr 147:462–468. https://doi.org/10.1016/j.jpeds.2005.04.037

    CAS  Article  PubMed  Google Scholar 

  34. Bilgin YM, van de Watering LM, Versteegh MI, van Oers MH, Brand A (2010) Effects of allogeneic leukocytes in blood transfusions during cardiac surgery on inflammatory mediators and postoperative complications. Crit Care Med 38:546–552. https://doi.org/10.1097/CCM.0b013e3181c0de7b

    CAS  Article  PubMed  Google Scholar 

  35. Scudellari M (2015) The science myths that will not die. Nature 528:322–325. https://doi.org/10.1038/528322a

    CAS  Article  PubMed  Google Scholar 

  36. Rael LT, Bar-Or R, Kelly MT, Carrick MM, Bar-Or D (2015) Assessment of oxidative stress in patients with an isolated traumatic brain injury using disposable electrochemical test strips. Electroanalysis 27(2567–2573):37

    Google Scholar 

  37. Watson JD (2014) Type 2 diabetes as a redox disease. Lancet 383:841–843. https://doi.org/10.1016/S0140-6736(13)62365-X

    Article  PubMed  Google Scholar 

  38. Zhi L, Hu X, Han C (2014) Biphasic changes (overreduction and overoxidation) of plasma redox status and clinical implications in early stage of severe burns. J Crit Care 29:1063–1068. https://doi.org/10.1016/j.jcrc.2014.06.013

    CAS  Article  PubMed  Google Scholar 

  39. Cowley HC, Bacon PJ, Goode HF, Webster NR, Jones JG, Menon DK (1996) Plasma antioxidant potential in severe sepsis: a comparison of survivors and nonsurvivors. Crit Care Med 24:1179–1183

    CAS  Article  PubMed  Google Scholar 

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Funding

This study was funded by a grant from Aytu Bioscience.

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Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA

    Amy E. Schmidt, Emily Gore, Kelly F. Henrichs, Grace Conley, Majed A. Refaai & Neil Blumberg

  2. Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA

    Jill M. Cholette

  3. Aytu Biosciences, Englewood, CO, USA

    Charles Dorsey & Kimberly B. Bjugstad

Authors
  1. Amy E. Schmidt
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  2. Emily Gore
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  4. Grace Conley
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  6. Kimberly B. Bjugstad
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  9. Jill M. Cholette
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Correspondence to Amy E. Schmidt.

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Conflict of interest

Dr. Amy Schmidt received a research grant from Aytu Biosciences. All of the remaining authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Schmidt, A.E., Gore, E., Henrichs, K.F. et al. Oxidation Reduction Potential (ORP) is Predictive of Complications Following Pediatric Cardiac Surgery. Pediatr Cardiol 39, 299–306 (2018). https://doi.org/10.1007/s00246-017-1755-x

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  • DOI: https://doi.org/10.1007/s00246-017-1755-x

Keywords

  • Blood
  • Red blood cells
  • Oxidation reduction potential
  • Cardiac surgery
  • Pediatrics
  • Complications