Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?

OBJECTIVE Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

[1]  P. Parsons,et al.  Peripheral Bypass‐Induced Pulmonary and Coronary Vascular Injury Association With Increased Levels of Tumor Necrosis Factor , 1993, Circulation.

[2]  D. Sharpe,et al.  Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine and dopexamine , 1999, Perfusion.

[3]  H. Brechtelsbauer,et al.  Thoracic duct lymph flow and composition in conscious dogs and the influence of anaesthesia and passive limb movement , 1977, Pflügers Archiv.

[4]  R. Dummer,et al.  Interleukin 2-induced increase of vascular permeability without decrease of the intravascular albumin pool. , 1995, British Journal of Cancer.

[5]  C. Hack,et al.  Acute lung injury after aortic surgery: the relation between lung and leg microvascular permeability to 111indium-labelled transferrin and circulating mediators. , 1997, Thorax.

[6]  B. Folkow,et al.  Studies on the relationship between flow resistance, capillary filtration coefficient and regional blood volume in the intestine of the cat. , 1963, Acta physiologica Scandinavica.

[7]  R. Lange,et al.  Effect of cardiopulmonary bypass and hemofiltration on plasma cytokines and protein leakage in pigs. , 2000, The Thoracic and cardiovascular surgeon.

[8]  N. Lassen,et al.  Increased transcapillary escape rate of albumin, IgG, and IgM after plasma volume expansion. , 1974, The American journal of physiology.

[9]  P. Padfield,et al.  SYSTEMIC CAPILLARY LEAK SYNDROME , 1989, The Lancet.

[10]  S. Allen,et al.  Analysis of intestinal microvascular permeability associated with cardiopulmonary bypass. , 1999, The Journal of surgical research.

[11]  W. van Oeveren,et al.  Blood activation during neonatal extracorporeal life support. , 1993, The Journal of thoracic and cardiovascular surgery.

[12]  G. von Bernuth,et al.  Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. , 1996, The Journal of thoracic and cardiovascular surgery.

[13]  E. Ferrannini,et al.  Effect of Insulin on Systemic and Renal Handling of Albumin in Nondiabetic and NIDDM Subjects , 1997, Diabetes.

[14]  C. Martin,et al.  Increased gut permeability and bacterial translocation in Pseudomonas pneumonia-induced sepsis , 2000, Critical care medicine.

[15]  K. Calman,et al.  INCREASED VASCULAR PERMEABILITY: A MAJOR CAUSE OF HYPOALBUMINAEMIA IN DISEASE AND INJURY , 1985, The Lancet.

[16]  S. Bandinelli,et al.  Transvascular and urinary leakage of albumin in atherosclerotic and hypertensive men. , 1998, Hypertension.

[17]  H. S. Mayerson,et al.  Mechanism of plasma protein changes following saline infusions. , 1952, The American journal of physiology.

[18]  B. Rippe,et al.  Transcapillary passage of albumin, effects of tissue cooling and of increases in filtration and plasma colloid osmotic pressure. , 1979, Acta physiologica Scandinavica.

[19]  J. Ferriss,et al.  Poor metabolic control, hypertension and microangiopathy independently increase the transcapillary escape rate of albumin in diabetes , 1983, Diabetologia.

[20]  E. Moore,et al.  Interleukin-8 increases endothelial permeability independent of neutrophils. , 1995, The Journal of trauma.

[21]  R. Landymore,et al.  Midazolam-sufentanilvs sufentanil-enflurane for induction of anaesthesia for CABG surgery , 1998, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[22]  J. A. Johnson,et al.  Equilibrium and kinetic properties of the Evans blue-albumin system. , 1969, The American journal of physiology.

[23]  W. Mcbride,et al.  Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. , 1995, British journal of anaesthesia.

[24]  S. Westaby Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit , 2004, Intensive Care Medicine.

[25]  G. Beck,et al.  Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. A clinical severity score. , 1992, JAMA.

[26]  T. Evans,et al.  Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress. , 1997, Critical care medicine.

[27]  S. Allen,et al.  Extracorporeal circulation exacerbates microvascular permeability after endotoxemia. , 2000, The Journal of surgical research.

[28]  M. Elliott,et al.  Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. , 1993, The Journal of thoracic and cardiovascular surgery.

[29]  E. Nadel,et al.  Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia. , 1997, Journal of applied physiology.

[30]  J. Richalet,et al.  Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia. , 1994, Journal of applied physiology.

[31]  E. Blackstone,et al.  Cardiopulmonary bypass: studies on its damaging effects. , 1987, Blood purification.

[32]  J. Levy,et al.  Inflammation and cardiopulmonary bypass , 1993, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[33]  S. Bhagwanjee,et al.  American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. , 1997, Critical care medicine.

[34]  A. Malik,et al.  Pyrrolidine dithiocarbamate prevents I-kappaB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs. , 1999, Molecular pharmacology.

[35]  A. Fokin,et al.  Sternal Instability After Midline Sternotomy , 2000, The Thoracic and cardiovascular surgeon.

[36]  I. Morita,et al.  IL-6 increases endothelial permeability in vitro. , 1992, Endocrinology.

[37]  H. Meisner,et al.  Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting. , 2000, The Annals of thoracic surgery.

[38]  R. Bonser,et al.  von Willebrand factor and urinary albumin excretion are possible indicators of endothelial dysfunction in cardiopulmonary bypass. , 1998, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.