The Systemic Inflammatory Response Syndrome Following Cardiopulmonary Bypass in Children

  • Harald L. LindbergEmail author
  • Tom N. Hoel


The systemic inflammatory response syndrome (SIRS) is multifaceted. In open-heart surgery, the surgical trauma is a contributor, but even more important is the use of cardiopulmonary bypass. After cardiac repair, reperfusion of the heart and lungs also contributes to the inflammatory response. The consequences of SIRS may be deleterious and sometimes even fatal. However, this is very rare in today’s routine surgery for congenital heart disease. It is obvious that all means to reduce SIRS should be undertaken because this factor contributes most to postoperative mortality and morbidity.


Cardiopulmonary Bypass Systemic Inflammatory Response Syndrome Mild Hypothermia Moderate Hypothermia Capillary Leak Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sheppard KA, Rose DW, Haque ZK, Kurokawa R, McInerney E, Westin S, et al. Transcriptional activation by NF-kappaB requires multiple coactivators. Mol Cell Biol. 1999;19(9):6367–78.PubMedGoogle Scholar
  2. 2.
    Boyle EM, Pohlman TH, Johnson MC, Verrier ED. Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. Ann Thorac Surg. 1997;63(1):277–84.PubMedCrossRefGoogle Scholar
  3. 3.
    Cicala C, Cirino G. Linkage between inflammation and coagulation: an update on the molecular basis of the crosstalk. Life Sci. 1998;62(20):1817–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Elliott MJ, Finn AH. Interaction between neutrophils and endothelium. Ann Thorac Surg. 1993;56(6):1503–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Esmon CT, Fukudome K, Mather T, Bode W, Regan LM, Stearns-Kurosawa DJ, et al. Inflammation, sepsis, and coagulation. Haematologica. 1999;84(3):254–9.PubMedGoogle Scholar
  6. 6.
    Hill GE, Whitten CW. The role of the vascular endothelium in inflammatory syndromes, atherogenesis, and the propagation of disease. J Cardiothorac Vasc Anesth. 1997;11(3):316–21.PubMedCrossRefGoogle Scholar
  7. 7.
    Gott VL, Whiffen JD, Dutton RC. Heparin bonding on colloidal graphite surfaces. Science. 1963;142(3597):1297–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Videm V, Mollnes TE, Garred P, Svennevig JL. Biocompatibility of extracorporeal circulation. In vitro comparison of heparin-coated and uncoated oxygenator circuits. J Thorac Cardiovasc Surg. 1991;101(4):654–60.PubMedGoogle Scholar
  9. 9.
    Baksaas ST, Videm V, Fosse E, Karlsen H, Pedersen T, Mollnes TE, et al. In vitro evaluation of new surface coatings for extracorporeal circulation. Perfusion. 1999;14(1):11–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Videm V, Fosse E, Mollnes TE, Garred P. Complement activation by extracorporeal circulation: effects of precoating a membrane oxygenator circuit with human whole blood. Scand J Thorac Cardiovasc Surg. 1988;22(3):251–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Fosse E, Moen O, Johnson E, Semb G, Brockmeier V, Mollnes TE, et al. Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg. 1994;58(2): 472–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Moen O, Fosse E, Dregelid E, Brockmeier V, Andersson C, Høgåsen K, et al. Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility. Ann Thorac Surg. 1996;62(4):1134–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Paparella D, Radi Al OO, Meng QH, Venner T, Teoh K, Young E. The effects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass. Blood Coagul Fibrinolysis. 2005;16(5):323–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Øvrum E, Tangen G, Tølløfsrud S, Ringdal MAL. Heparin-coated circuits and reduced systemic anticoagulation applied to 2500 consecutive first-time coronary artery bypass grafting procedures. Ann Thorac Surg. 2003;76(4):1144–8. discussion 1148.PubMedCrossRefGoogle Scholar
  15. 15.
    Mangoush O, Purkayastha S, Haj-Yahia S, Kinross J, Hayward M, Bartolozzi F, et al. Heparin-bonded circuits versus nonheparin-bonded circuits: an evaluation of their effect on clinical outcomes. Eur J Cardiothorac Surg. 2007;31(6):1058–69.PubMedCrossRefGoogle Scholar
  16. 16.
    Larm O, Larsson R, Olsson P. A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue. Biomater Med Devices Artif Organs. 1983;11(2–3):161–73.PubMedGoogle Scholar
  17. 17.
    De Somer F, François K, Van Oeveren W, Poelaert J, De Wolf D, Ebels T, et al. Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface. Eur J Cardiothorac Surg. 2000;18(5):602–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Liszewski MK, Post TW, Atkinson JP. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Carroll MC. The complement system in regulation of adaptive immunity. Nat Immunol. 2004;5(10):981–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Christensen VB. The systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children. Acta Anaesthesiol Scand. 2001;45(6):671–9.CrossRefGoogle Scholar
  21. 21.
    Ozawa T, Yoshihara K, Koyama N, Watanabe Y, Shiono N, Takanashi Y. Clinical efficacy of heparin-bonded bypass circuits related to cytokine responses in children. Ann Thorac Surg. 2000;69(2):584–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1993;105(2):234–41.PubMedGoogle Scholar
  23. 23.
    Brix-Christensen V, Petersen TK, Ravn HB, Hjortdal VE, Andersen NT, Tønnesen E. Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs. Acta Anaesthesiol Scand. 2001;45(4):407–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Hauser GJ, Ben-Ari J, Colvin MP, Dalton HJ, Hertzog JH, Bearb M, et al. Interleukin-6 levels in serum and lung lavage fluid of children undergoing open heart surgery correlate with postoperative morbidity. Intensive Care Med. 1998;24(5):481–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Duval EL, Kavelaars A, Veenhuizen L, van Vught AJ, van de Wal HJ, Heijnen CJ. Pro- and anti-inflammatory cytokine patterns during and after cardiac surgery in young children. Eur J Pediatr. 1999;158(5):387–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Eggum R, Ueland T, Mollnes TE, Videm V, Fiane AE, Aukrust P, et al. Perfusion temperature, thyroid hormones and inflammation during pediatric cardiac surgery. Interact Cardiovasc Thorac Surg. 2010;10(1):76–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Tárnok A, Hambsch J, Emmrich F, Sack U, van Son J, Bellinghausen W, et al. Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass. Pediatr Cardiol. 1999;20(2):113–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Seghaye M, Duchateau J, Bruniaux J, Demontoux S, Bosson C, Serraf A, et al. Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg. 1996;111(3):545–53.PubMedCrossRefGoogle Scholar
  29. 29.
    el Habbal MH, Carter H, Smith LJ, Elliott MJ, Strobel S. Neutrophil activation in paediatric extracorporeal circuits: effect of circulation and temperature variation. Cardiovasc Res. 1995;29(1):102–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Behr D, Hernvann A, POUARD P, Spizzi I, Leca F, VOUHE P. Interleukin-6 and C-reactive protein during pediatric cardiopulmonary bypass. Clin Chem. 1995;41(3):467–9.PubMedGoogle Scholar
  31. 31.
    Chew MS, Brandslund I, Brix-Christensen V, Ravn HB, Hjortdal VE, Pedersen J. Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study. Anesthesiology. 2001;94(5):745–53. discussion 5A.PubMedCrossRefGoogle Scholar
  32. 32.
    Chaney MA, Durazo-Arvizu RA, Nikolov MP, Blakeman BP, Bakhos M. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. J Thorac Cardiovasc Surg. 2001;121(3):561–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Seri I, Tan R, Evans J. Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension. Pediatrics. 2001;107(5):1070–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Duffy JY, Nelson DP, Schwartz SM, Wagner CJ, Bauer SM, Lyons JM, et al. Glucocorticoids reduce cardiac dysfunction after cardiopulmonary bypass and circulatory arrest in neonatal piglets. Pediatr Crit Care Med. 2004;5(1):28–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Varan B, Tokel K, Mercan S, Dönmez A, Aslamaci S. Systemic inflammatory response related to cardiopulmonary bypass and its modification by methyl prednisolone: high dose versus low dose. Pediatr Cardiol. 2002;23(4):437–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Niazi Z, Flodin P, Joyce L, Smith J, Mauer H, Lillehei RC. Effects of glucocorticosteroids in patients undergoing coronary artery bypass surgery. Chest. 1979;76(3):262–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Jansen NJ, Van Oeveren W, van den Broek L, Oudemans-van Straaten HM, Stoutenbeek CP, Joen MC. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1991;102(4):515–25.PubMedGoogle Scholar
  38. 38.
    Kawamura T, Inada K, Okada H, Okada K, Wakusawa R. Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. Can J Anaesth. 1995;42(5 Pt 1):399–403.PubMedGoogle Scholar
  39. 39.
    Jorens PG, De Jongh R, De Backer W, Van Damme J, Van Overveld F, Bossaert L. Interleukin-8 production in patients undergoing cardiopulmonary bypass. The influence of pretreatment with methylprednisolone. Am Rev Respir Dis. 1993;148(4 Pt 1):890–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Butler J, Pathi V, Paton R, Logan R. Acute-phase responses to cardiopulmonary bypass in children weighing less than 10 kilograms. Ann Thorac Surg. 1996;62(2):538–42.PubMedCrossRefGoogle Scholar
  41. 41.
    Seghaye MC, Grabitz RG, Duchateau J, Busse S, Däbritz S, Koch D, et al. Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. J Thorac Cardiovasc Surg. 1996;112(3):687–97.PubMedCrossRefGoogle Scholar
  42. 42.
    Gessler P, Hohl V, Carrel T, Pfenninger J, Schmid ER, Baenziger O. Administration of steroids in pediatric cardiac surgery: impact on clinical outcome and systemic inflammatory response. Pediatr Cardiol. 2005;26(5):595–600.PubMedCrossRefGoogle Scholar
  43. 43.
    Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, et al. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med. 2003;31(6):1742–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Clarizia NA, Manlhiot C, Schwartz SM, Sivarajan VB, Maratta R, Holtby HM, et al. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Ann Thorac Surg. 2011;91(4):1222–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Weerasinghe A, Taylor KM. The platelet in cardiopulmonary bypass. Ann Thorac Surg. 1998;66(6):2145.PubMedCrossRefGoogle Scholar
  46. 46.
    Boisclair M, Lane D, Philippou H. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood. 1993;82(11):3350–7.PubMedGoogle Scholar
  47. 47.
    Gluszko P, Rucinski B, Musial J. Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuit. Am J Physiol. 1987;252(3 Pt 2):H615–21.PubMedGoogle Scholar
  48. 48.
    Dewanjee MK. Molecular biology of nitric oxide synthases. Reduction of complications of cardiopulmonary bypass from platelets and neutrophils by nitric oxide generation from L-arginine and nitric oxide donors. ASAIO J. 1997;43(3):151–9.PubMedGoogle Scholar
  49. 49.
    Lumadue JA, Lanzkron SM, Kennedy SD, Kuhl DT, Kickler TS. Cytokine induction of platelet activation. Am J Clin Pathol. 1996;106(6):795–8.PubMedGoogle Scholar
  50. 50.
    Nannizzi-Alaimo L, Rubenstein MH, Alves VL, Leong GY, Phillips DR, Gold HK. Cardiopulmonary bypass induces release of soluble CD40 ligand. Circulation. 2002;105(24):2849–54.PubMedCrossRefGoogle Scholar
  51. 51.
    Day J. The systemic inflammatory response syndrome and cardiopulmonary bypass. Int J Surg. 2005;3(2):129–40.PubMedCrossRefGoogle Scholar
  52. 52.
    Bergseth G, Lappegård KT, Videm V, Mollnes TE. A novel enzyme immunoassay for plasma thrombospondin. Comparison with beta-thromboglobulin as platelet activation marker in vitro and in vivo. Thromb Res. 2000;99(1):41–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Laffey JG, Boylan JF, Cheng DCH. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97(1):215–52.PubMedCrossRefGoogle Scholar
  54. 54.
    Warltier DC, Laffey JG, Boylan JF, Cheng DCH. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97(1):215.CrossRefGoogle Scholar
  55. 55.
    Menasché P, Peynet J, Haeffner-Cavaillon N, Carreno MP, de Chaumaray T, Dillisse V. Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass. Circulation. 1995;92(9 Suppl):II334–40.PubMedGoogle Scholar
  56. 56.
    Alcaraz AJ, Manzano L, Sancho L, Vigil MD, Esquivel F, Maroto E. Different proinflammatory cytokine serum pattern in neonate patients undergoing open heart surgery. Relevance of IL-8. J Clin Immunol. 2005;25(3):238–45.PubMedCrossRefGoogle Scholar
  57. 57.
    Hickey E, Karamlou T, You X, Komanapalli C, Person T, Wehrley K, et al. Seiler Resident Award paper. The use of a miniaturized circuit and bloodless prime to avoid cerebral no-reflow after neonatal cardiopulmonary bypass. Ann Thorac Surg. 2007;83(3):895–901.PubMedCrossRefGoogle Scholar
  58. 58.
    Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 2003;75(2):S715–20.PubMedCrossRefGoogle Scholar
  59. 59.
    Tassani P, Barankay A, Haas F, Paek SU, Heilmaier M, Hess J, et al. Cardiac surgery with deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass in newborns. J Thorac Cardiovasc Surg. 2002;123(4):648–54.PubMedCrossRefGoogle Scholar
  60. 60.
    Diestel A, Roessler J, Berger F, Schmitt KRL. Hypothermia downregulates inflammation but enhances IL-6 secretion by stimulated endothelial cells. Cryobiology. 2008;57(3):216–22.PubMedCrossRefGoogle Scholar
  61. 61.
    Diestel A, Roessler J, Pohl-Schickinger A, Koster A, Drescher C, Berger F, et al. Specific p38 inhibition in stimulated endothelial cells: a possible new anti-inflammatory strategy after hypothermia and rewarming. Vascul Pharmacol. 2009;51(4):246–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Eggum R, Ueland T, Mollnes TE, Videm V, Aukrust P, Fiane AE, et al. Effect of perfusion temperature on the inflammatory response during pediatric cardiac surgery. Ann Thorac Surg. 2008;85(2):611–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Qing M, Nimmesgern A, Heinrich PC, Schumacher K, Vazquez-Jimenez JF, Hess J, et al. Intrahepatic synthesis of tumor necrosis factor-alpha related to cardiac surgery is inhibited by interleukin-10 via the Janus kinase (Jak)/signal transducers and activator of transcription (STAT) pathway. Crit Care Med. 2003;31(12):2769–75.PubMedCrossRefGoogle Scholar
  64. 64.
    Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, et al. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg. 1994;108(4):626–35.PubMedGoogle Scholar
  65. 65.
    Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.PubMedCrossRefGoogle Scholar
  66. 66.
    Feigin VL, Anderson CS, Rodgers A, Anderson NE, Gunn AJ. The emerging role of induced hypothermia in the management of acute stroke. J Clin Neurosci. 2002;9(5):502–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhi D, Zhang S, Lin X. Study on therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury. Surg Neurol. 2003;59(5):381–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Dixon SR, Whitbourn RJ, Dae MW, Grube E, Sherman W, Schaer GL. Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol. 2002;40(11):1928–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Bes S, Roussel P, Laubriet A, Vandroux D, Tissier C, Rochette L, et al. Influence of deep hypothermia on the tolerance of the isolated cardiomyocyte to ischemia-reperfusion. J Mol Cell Cardiol. 2001;33(11):1973–88.PubMedCrossRefGoogle Scholar
  70. 70.
    Qing M, Vazquez-Jimenez JF, Klosterhalfen B, Sigler M, Schumacher K, Duchateau J, et al. Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance, and post-operative organ damage. Shock. 2001;15(5):372–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Stocker CF, Shekerdemian LS, Horton SB, Lee KJ, Eyres R, D’Udekem Y, et al. The influence of bypass temperature on the systemic inflammatory response and organ injury after pediatric open surgery: a randomized trial. J Thorac Cardiovasc Surg. 2011;142(1):174–80.PubMedCrossRefGoogle Scholar
  72. 72.
    Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol. 2004;22:891–928.PubMedCrossRefGoogle Scholar
  73. 73.
    Caputo M, Bays S, Rogers C, Pawade A. Randomized comparison between normothermic and hypothermic cardiopulmonary bypass in pediatric open-heart surgery. Ann Thorac Surg. 2005;80:982–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Rasmussen L, Sztuk F, Christiansen M. Normothermic versus hypothermic cardiopulmonary bypass during repair of congenital heart disease. J Cardiothorac Vasc Anesth. 2001;15(5):563–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Walther T, Rastan A, Dähnert I, Jacobs S, Scheer K, Wild F, et al. Moderate versus deep hypothermia for arterial switch operation. Thorac Cardiovasc Surg. 2006;54(4):255–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Pouard P, Pouard P, Mauriat P, Mauriat P, Ek F, Ek F, et al. Normothermic cardiopulmonary bypass and myocardial cardioplegic protection for neonatal arterial switch operation. Eur J Cardiothorac Surg. 2006;30(5):695–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Durandy Y, Hulin S, Lecompte Y. Normothermic cardiopulmonary bypass in pediatric surgery. J Thorac Cardiovasc Surg. 2002;123(1):194.PubMedCrossRefGoogle Scholar

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© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Thoracic and Cardiovascular SurgeryUniversity of Oslo, Rikshospitalet University HospitalOsloNorway

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