The Immunologic System: Perturbations Following Cardiopulmonary Bypass and the Problem of Infection in the Cardiac Surgery Patient

  • Bradley L. Bufkin
  • John Parker Gott
  • Christina T. Mora
  • Jerrold H. Levy


Cardiopulmonary bypass (CPB) predisposes cardiac surgical patients to postoperative wound infections1,2 by altering their immunologic host response and increasing their susceptibility to infection, a primary cause of morbidity and mortality following open-heart surgery. The “cost” of infection after cardiac surgery includes human suffering, hospital confinement, loss of productivity, and mortality. There can be a broad range of infectious complications postoperatively (Table 8.1). Mediastinitis, occurring in 1% to 2% of median sternotomies, has a mortality rate of 60% to 70%.3 Early and late prosthetic valvular endocarditis are associated with mortality rates of 73% and 45%, respectively,4,5 and occur in approximately 2% to 3% of valvular replacement procedures. An assessment of hospital stay following coronary artery bypass surgery demonstrated that infectious complications prolonged hospitalization fourfold, with infection representing the most important variable for increased length of stay.6 A 1990 cost assessment of cardiac surgery patients reported that median sternotomy infections produced a median hospital cost of $58,092 (range $19,966 to $408,632), almost triple the cost of an uncomplicated cardiac procedure.7


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Cardiopulmonary Bypass Acquire Immune Deficiency Syndrome Cardiac Surgery Patient 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kittle CF, Reed WA. Antibiotics and extracorporeal circulation. J Thorac Cardiovasc Surg 1961; 41: 34–48.PubMedGoogle Scholar
  2. 2.
    Lord JW, Imparato AM, Hackel A, et al. Endocarditis complicating open-heart surgery. Circulation 1961; 23: 489–497.PubMedGoogle Scholar
  3. 3.
    Cheung EH, Craver JM, Jones EL, et al. Mediastinitis after cardiac valve operations. Impact upon survival. J Thorac Cardiovasc Surg 1985; 90: 517–522.PubMedGoogle Scholar
  4. 4.
    Watanakunakorn C. Prosthetic valve infective endocarditis. Prog Cardiovasc Dis 1979; 22: 181–192.PubMedCrossRefGoogle Scholar
  5. 5.
    Clark RE, Amos WC, Higgins V, et al. Infection control in cardiac surgery. Surgery 1976; 79: 89–96.PubMedGoogle Scholar
  6. 6.
    Weintraub WS, Jones EL, Craver J, et al. Determinants of prolonged length of hospital stay after coronary bypass surgery. Circulation 1989; 80: 276–284.PubMedCrossRefGoogle Scholar
  7. 7.
    Loop FD, Lytle BW, Cosgrove DM, et al. Sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care. Ann Thorac Surg 1990; 49: 179–186.PubMedCrossRefGoogle Scholar
  8. 8.
    Paul WE. The immune system: an introduction. In: Paul WE, ed. Fundamental Immunology. New York: Raven Press, 1989: 3–19.Google Scholar
  9. 9.
    Ohri SK. The effects of cardiopulmonary bypass on the immune system. Perfusion 1993; 8: 121–137.Google Scholar
  10. 10.
    Stevenson GW, Hall SC, Rudnick S, et al. The effect of anesthetic agents on the human immune response. Anesthesiology 1990; 72: 542–552.PubMedCrossRefGoogle Scholar
  11. 11.
    Levy JH. Anaphylatic Reactions in Anesthesia and Intensive Care. 2nd ed. Boston: Butterworth-Heinemann; 1992.Google Scholar
  12. 12.
    Kirklin JK. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg 1991; 51: 529–531.PubMedCrossRefGoogle Scholar
  13. 13.
    Westaby S. Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit. Int Care Med 1987; 13: 89–95.CrossRefGoogle Scholar
  14. 14.
    Hammerschmidt DE, Stroncek DF, Bowers TK, et al. Complement activation and neutropenia occurring during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1981; 81: 370377.Google Scholar
  15. 15.
    Chenoweth DE, Cooper SW, Hughi TE, et al. Complement activation during cardiopulmonary bypass; evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 1981; 304: 497–503.PubMedCrossRefGoogle Scholar
  16. 16.
    Collett B, Alhaq A, Abdullah NG, et al. Pathways to complement activation during cardiopulmonary bypass. Br Med J 1984; 289: 1251–1254.CrossRefGoogle Scholar
  17. 17.
    Parker DJ, Cantrell JW, Karp RB, et al. Changes in serum complement and immunoglobulins following cardiopulmonary bypass. Surgery 1972; 71: 824–827.PubMedGoogle Scholar
  18. 18.
    Hairston P, Manos JP, Braber CD, et al. Depression of immunologic surveillance by pump-oxygenation perfusion. J Surg Res 1969; 9: 587–593.PubMedCrossRefGoogle Scholar
  19. 19.
    Moore FD, Warner KG, Assousa S, et al. The effects of complement activation during cardiopulmonary bypass. Ann Surg 1988; 208: 95–103.PubMedCrossRefGoogle Scholar
  20. 20.
    Todd RF III, Arnaout MA, Rosen RE, et al. Subcellular localisation of the large subunit of Mol, a surface of glycoprotein associated with neutrophil adhesion. J Clin Invest 1984; 74: 1280–1290.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Shea JJ, Brown EJ, Seligmann BE, et al. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol 1985; 134: 2580–2587.PubMedGoogle Scholar
  22. 22.
    Cavarocchi NC, Pluth JR, Schaff HV, et al. Complement activation during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1986; 91: 252–258.PubMedGoogle Scholar
  23. 23.
    Bubeuik O, Meakins JL. Neutrophil chemotaxis in surgical patients: effect of cardiopulmonary bypass. Surg Forum 1976; 27: 267–269.Google Scholar
  24. 24.
    Mayer JE, McCullough J, Weiblen BJ, et al. Effects of cardiopulmonary bypass on neutrophil chemotaxis. Surg Forum 1976; 27: 285–287.PubMedGoogle Scholar
  25. 25.
    Subramanian VA, Gay WA, Dineen PAP. Effect of cardiopulmonary bypass on in vivo clearance of live Klebsiella aerogens. Surg Forum 1977; 28: 255–256.PubMedGoogle Scholar
  26. 26.
    Masson PL, Herremans JF, Schonne EJ. Lactoferrin, an iron-binding protein in neutrophil leukocytes. J Exp Med 1969; 130: 643–658.PubMedCrossRefGoogle Scholar
  27. 27.
    Bos A, Wever R, Roos D. Characterization and quantification of the peroxidase in human monocytes. Biochem Biophys Acta 1978; 525: 37–44.PubMedGoogle Scholar
  28. 28.
    Baehner RL, Johnston RB Jr. Monocyte function in children with neutropenia and chronic infections. Blood 1972; 40: 31–41.PubMedGoogle Scholar
  29. 29.
    Neumann S, Henrich N, Gunzer G, et al. Enzyme-linked immunoassay for human granulocyte elastase in complex with α1-proteinase inhibitor. In: Horl WH, Heidland A, eds. Protease, Potential Role in Health and Disease. New York: Plenum Press, 1984: 379–390.Google Scholar
  30. 30.
    Deby-DuPont G, Pincemail J, Thirion A, et al. A radioimmunoassay for polymorphonuclear leukocytes in myeloperoxidase: preliminary results. Arch Int Physiol Biochem 1987; 95: 59.Google Scholar
  31. 31.
    Bakkenist ARJ, Wever R, Vulsma T, et al. Isolation procedure and some properties of myeloperoxidase from human leukocytes. Biochem Biophys Acta 1978; 524: 45–54.PubMedGoogle Scholar
  32. 32.
    Deby-DuPont G, Pincemail J, Reuter AM. Iodination of polymorphonuclear leucocyte myeloperoxidase. Arch Int Physiol Biochem 1988; 96: B25.CrossRefGoogle Scholar
  33. 33.
    Wood WG, Stella G, Muller OA, et al. A rapid and specific method for separation of bound and free antigen in radioimmunoassay systems. J Clin Chem Clin Biochem 1979; 17: 111–114.PubMedGoogle Scholar
  34. 34.
    Benacerraf B, Sebestyen MM, Schlossman JA. A quantitative study of the kinetics of blood clearance of P32 labelled Escherichia coli and staphylococci by the reticuloendothelial system. J Exp Med 1959; 110: 27–48.PubMedCrossRefGoogle Scholar
  35. 35.
    Haeffner-Cavaillon N, Roussellier N, Ponzio O, et al. Induction of interleukin-1 production in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989; 98: 1100–1106.PubMedGoogle Scholar
  36. 36.
    Kilbourn RG, Belloni P. Endothelial cell production of nitrogen oxides with response to interferon in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Nat Cancer Inst 1990; 82: 772–776.PubMedCrossRefGoogle Scholar
  37. 37.
    Whitten CW, Latson TW, Allison PM, et al. Does aprotinin inhibit cardiopulmonary bypass-induced inflammation. Anesthesiology 1992; 77: A266.CrossRefGoogle Scholar
  38. 38.
    Hariston P, Manos JP, Gruber CD, et al. Depression of immunologic surveillance by pump-oxygenation perfusion. J Surg Res 1969; 9: 587–593.CrossRefGoogle Scholar
  39. 39.
    van Oeveren W, Kazatchkine MD, Descamps-Latscha B, et al. Deleterious effects of cardiopulmonary bypass: a prospective study of bubble versus membrane oxygenation. J Thorac Cardiovasc Surg 1985; 89: 888–899.PubMedGoogle Scholar
  40. 40.
    Hisatomi K, Isamura T, Kawara T, et al. Changes in lymphocyte subsets, mitogen responsiveness and interleukin-2 production after cardiac operations. J Thorac Cardiovasc Surg 1989; 98: 580–591.PubMedGoogle Scholar
  41. 41.
    Eskola J, Salo M, Viljanen MK, et al. Impaired B lymphocyte function during open heart surgery. Br JAnaesth 1984; 56: 333–337.CrossRefGoogle Scholar
  42. 42.
    Brody JI, Pickering NJ, Fink GB, et al. Altered lymphocyte subsets during cardiopulmonary bypass. Am J Clin Pathol 1987; 87: 626–628.PubMedGoogle Scholar
  43. 43.
    Pollock R, Ames F, Rubio P, et al. Protracted severe immune dysregulation induced by cardiopulmonary bypass; a predisposing etiologic factor in blood transfusion-related AIDS. J Clin Lab Immunol 1987; 22: 1–5.PubMedGoogle Scholar
  44. 44.
    Nguyen DM, Mulder DS, Shennib H. Effect of cardiopulmonary bypass on circulating lymphocyte function. Ann Thorac Surg 1992; 53: 611–616.PubMedCrossRefGoogle Scholar
  45. 45.
    Ide H, Matsumoto H; Takayama T, et al. The effect of interleukin-2 and plasma factors in the impaired lymphocyte function after cardiopulmonary bypass. Eur Surg Res 1988; 20: 29–30.CrossRefGoogle Scholar
  46. 46.
    Ide H, Kakiuchi T, Ino T, et al. The role of interleukin-2 in the impaired lymphocyte function after open heart surgery. J Jpn Assoc Thorac Surg 1989; 37: 1526–1531.Google Scholar
  47. 47.
    Suzuki R, Hand K, Itoh K, et al. Natural killer (NK) cells as a responder to interleukin-2 (IL-2). I Proliferative response and establishment of cloned cells. J Immunol 1983; 130: 981–987.PubMedGoogle Scholar
  48. 48.
    Palacios R. Mechanisms of T-cell activation; role and functional relationship of HLA-DR antigens and interleukins Immunol Rev 1982; 63: 73–110.PubMedCrossRefGoogle Scholar
  49. 49.
    Pauly JL, Russel CW, Planusek JA, et al. Studies of cultured human T lymphocytes. I. Production of the T cell growth promoting lymphokine interleukin-2. J Immunol Methods 1982; 50: 173–178.PubMedCrossRefGoogle Scholar
  50. 50.
    Verkkala K, Makela P, Ojajarvi J, et al. Air contamination in open heart surgery with disposable coveralls, gowns, and drapes. Ann Thorac Surg 1990; 50: 757–761.PubMedCrossRefGoogle Scholar
  51. 51.
    Sompolinsky D, Hermann Z, Oeding P, et al. A series of postoperative infections. J Infect Dis 1956; 100: 1–11.CrossRefGoogle Scholar
  52. 52.
    Blakemore WS, McGarrity GJ, Thurer RJ, et al. Infection by air borne bacteria with cardiopulmonary bypass. Surgery 1971; 70: 830–838.PubMedGoogle Scholar
  53. 53.
    Geldof WCP, Brom AG. Infections through blood from heart-lung machine. Thorax 1972; 27: 395–397.PubMedCrossRefGoogle Scholar
  54. 54.
    Kluge RM, Calia FM, McLaughlin JS, et al. Sources of contamination in open heart surgery. JAMA 1974; 230: 1415–1418.Google Scholar
  55. 55.
    Ankeney JL. Discussion of Amoury RA, Bowman FO Jr, Malm JR: Endocarditis associated with intracardiac prosthesis. J Thorac Cardiovasc Surg 1966; 51: 48.Google Scholar
  56. 56.
    Ankeney JL, Parker RF. Staphylococcal endocarditis following open-heart surgery related to positive intraoperative blood cultures. In: Brewer LA III, ed. Prosthetic Heart Valves. Springfield, IL: Charles C. Thomas; 1968: 719–730.Google Scholar
  57. 57.
    Bentley DW, Lepper MH. Septicemia related to indwelling venous catheter. JAMA 1968; 206: 1749–1752.PubMedCrossRefGoogle Scholar
  58. 58.
    Weinstein RA, Jones EL, Schwarzmann SW, et al. Sternal osteomyelitis and mediastinitis after open-heart operation: pathogenesis and prevention. Ann Thorac Surg 1976; 21: 442–444.PubMedCrossRefGoogle Scholar
  59. 59.
    Schwieger IM, Gallagher CJ, Finlayson DC, et al. Incidence of cell-saver contamination during cardiopulmonary bypass. Ann Thorac Surg 1989; 48: 51–53.PubMedCrossRefGoogle Scholar
  60. 60.
    Beam TR. Perioperative prevention of infection in cardiac surgery. Antibiot Chemother 1985; 33: 114–139.PubMedGoogle Scholar
  61. 61.
    Bernard HR, Cole WR. The epidemiology of postoperative surgical infection. Surg Clin NAm 1965; 45: 509–519.Google Scholar
  62. 62.
    Beyer RH, Mills SA, Hudspeth AS, et al. A prospective study of sternal wound complications. Ann Thorac Surg 1984; 37: 412–416.CrossRefGoogle Scholar
  63. 63.
    Nagachinta T, Stephens M, Reitz B, et al. Risk factors for surgical-wound infection following cardiac surgery. J Infect Dis 1987; 156: 967–973.PubMedCrossRefGoogle Scholar
  64. 64.
    Culliford AT, Cunningham JN, Zeff RH, et al. Sternal and costochondral infections following open-heart surgery. J Thorac Cardiovasc Surg 1976; 72: 714–726.PubMedGoogle Scholar
  65. 65.
    Kaiser AB, Kernodle DS, Barg NL, et al. Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers. Ann Thorac Surg 1988; 45: 35–38.PubMedCrossRefGoogle Scholar
  66. 66.
    Ko W, Lazenby WD, Zelano JA, et al. Effects of shaving methods and intraoperative irrigation on suppurative mediastinitis after bypass operations. Ann Thorac Surg 1992; 53: 301–305.PubMedCrossRefGoogle Scholar
  67. 67.
    Connell JF, Rousselot LM. Povidoneiodine, Extensive surgical evaluation of a new antiseptic agent. Am J Surg 1964; 108: 849–855.PubMedCrossRefGoogle Scholar
  68. 68.
    Joress SM. A study of disinfection of the skin: a comparison of povidine-iodine with other agents used for surgical scrubs. Ann Surg 1962; 155: 296–304.PubMedGoogle Scholar
  69. 69.
    Fong IW, Baker CB, McKee DC. The value of prophylactic antibiotics in aorta-coronary bypass operations. J Thorac Cardiovasc Surg 1979; 78: 908–913.PubMedGoogle Scholar
  70. 70.
    Goldman DA, Hopkins CC, Karchmer AW, et al. Cephalothin prophylaxis in cardiac valve surgery. J Thorac Cardiovasc Surg 1977; 73: 470–479.Google Scholar
  71. 71.
    Levy JH, Nagle DM, Curling PE, et al. Contamination reduction during central venous catheterization. Crit Care Med 1988; 16: 165–167.PubMedCrossRefGoogle Scholar
  72. 72.
    Ferrazzi P, Allen R, Crupi G, et al. Reduction of infection after cardiac surgery: a clinical trial. Ann Thorac Surg 1986; 42: 321–325.PubMedCrossRefGoogle Scholar
  73. 73.
    Ottino G, DePaulis R, Pansini S, et al. Major sternal wound infection after open-heart surgery: a multivariate analysis of risk factors in 2,579 consecutive operative procedures. Ann Thorac Surg 1987; 44: 173–179.PubMedCrossRefGoogle Scholar
  74. 74.
    Stoney WS. Median sternotomy. In: Van der Salm TJ, ed. Cardiac Surgery: State of the Art Reviews. Philadelphia: Hanley & Belfus Inc., 1988: 431–436.Google Scholar
  75. 75.
    Arnold M. The surgical anatomy of sternal blood supply. J Thorac Cardiovasc Surg 1972; 64: 596–610.PubMedGoogle Scholar
  76. 76.
    Seyfer AE, Shriver CD, Miller TR, et al. Sternal blood flow after median sternotomy and mobilization of the internal mammary arteries. Surgery 1988; 104: 899–904.PubMedGoogle Scholar
  77. 77.
    He GW, Ryan WH, Acuff TE, et al. Risk factors for operative mortality and sternal wound infection in bilateral internal mammary artery grafting. J Thorac Cardiovasc Surg 1994; 107: 196–202.PubMedGoogle Scholar
  78. 78.
    Gu YJ, Wanag YS, Chiang BY, et al. Membrane oxygenator prevents lung reperfusion injury in canine cardiopulmonary bypass. Ann Thorac Surg 1991; 51: 573–578.PubMedCrossRefGoogle Scholar
  79. 79.
    Cavarocchi NC, Pluth JR, Schaff HV, et al. Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators. J Thorac Cardiovasc Surg 1986; 91: 252–258.PubMedGoogle Scholar
  80. 80.
    Gu YJ, Oeveren W, Akkerman C, et al. Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993; 55: 917–922.PubMedCrossRefGoogle Scholar
  81. 81.
    Videm V, Svennevig JL, Fosse E, et al. Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations. J Thorac Cardiovasc Surg 1992; 103: 806–813.PubMedGoogle Scholar
  82. 82.
    Hisatomi K, Isomura T, Galli SJ, et al. Augmentation of interleukin-2 production after cardiac operations in patients treated with erythropoietin. J Thorac Cardiovasc Surg 1992; 104: 278–283.PubMedGoogle Scholar
  83. 83.
    Faist E, Ertel W, Salem B, et al. The immune-enhancing effect of perioperative thymopentin administration in elderly patients undergoing major surgery. Arch Surg 1988; 123: 1449–1453.PubMedGoogle Scholar
  84. 84.
    Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1961; 50: 161–168.PubMedGoogle Scholar
  85. 85.
    Austin TW, Coles JC, Burnett R, et al. Aortocoronary bypass procedures and sternotomy infections: a study of anti-staphylococcal prophylaxis. Can J Surg 1980; 23: 483–485.PubMedGoogle Scholar
  86. 86.
    Kreter B, Woods M. Antibiotic prophylaxis for cardiothoracic operations. J Thorac Cardiovasc Surg 1992; 104: 590–599.PubMedGoogle Scholar
  87. 87.
    Hirschmann JV, Inui TS. Antimicrobial prophylaxis: a critique of recent trials. Rev Infect Dis 1980; 2: 1–23.PubMedCrossRefGoogle Scholar
  88. 88.
    Sarr MG, Gott VL, Townsend TR. Mediastinal infection after cardiac surgery. Ann Thorac Surg 1984; 38: 415–423.PubMedCrossRefGoogle Scholar
  89. 89.
    Wells FC, Newsom SWB, Rowlands C. Hospital Practice. Wound infection in cardiothoracic surgery. Lancet 1983; 1: 1209–1210.PubMedCrossRefGoogle Scholar
  90. 90.
    Farrington M, Webster M, Fenn A, et al. Wound infection in cardiothoracic surgery. Lancet 1983; 2: 395–396.PubMedCrossRefGoogle Scholar
  91. 91.
    Goldman DA, Hopkins CC, Karchmer AW, et al. Cephalothin prophylaxis in cardiac valve surgery. J Thorac Cardiovasc Surg 1977; 73: 470–479.Google Scholar
  92. 92.
    Conte JE, Cohen SN, Roe BB, et al. Antibiotic prophylaxis and cardiac surgery. Ann Intern Med 1972; 76: 943–949.PubMedGoogle Scholar
  93. 93.
    Moss AR, Cahetti P, Osmond D, et al. Sero-positivity for HIV and the development of AIDS or related condition: three-year follow-up of the San Francisco General Hospital cohort. Br Med J 1988; 296: 745–750.CrossRefGoogle Scholar
  94. 94.
    Fahey JL, Taylor JMG, Detels R, et al. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med 1990; 322: 166172.Google Scholar
  95. 95.
    Uva MS, Jebara VA, Fabiani JN, et al. Cardiac surgery in patients with human immunodeficiency virus infection: indications and results. J Cardiac Surg 1992; 7: 240–244.CrossRefGoogle Scholar
  96. 96.
    Frater RWM, Sisto D, Condit D. Cardiac surgery in human immunodeficiency virus-(HIV) carriers. Eur J Cardiothorac Surg 1989; 3: 146–150.PubMedCrossRefGoogle Scholar
  97. 97.
    Nahass RG, Weinstein MP, Bartels J, et al. Infective endocarditis in intravenous drug users: a comparison of human immunodeficiency virus type 1-negative and -positive patients. J Infect Dis 1990; 162: 967–970.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1995

Authors and Affiliations

  • Bradley L. Bufkin
  • John Parker Gott
  • Christina T. Mora
  • Jerrold H. Levy

There are no affiliations available

Personalised recommendations