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Volume 3 Supplement 2

International Symposium on the Pathophysiology of Cardiopulmonary Bypass

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Inflammatory response to cardiopulmonary bypass in neonates and young children: endotoxin release, cytokine production, and gastrointestinal permeability


Neonates and young children are considered as high-risk patients in developing postoperative complication following open-heart surgery. This usually results from an over-stimulated inflammatory response to cardiopulmonary bypass (CPB), which is thought to be initiated by a number of processes, including blood contact with the artificial surface and reperfusion injury. We performed a study to examine whether there is an increase in gastrointestinal permeability during and after CPB in these young patients, and whether the increase in gastrointestinal permeability will lead to release of endotoxin and further production of tumor necrosis factor α (TNFα).


Eleven pediatric patients whose body weight was less than 10 kg were prospectively included in this study. Blood samples were taken before, during, and at the end of CPB, and at 1 h, 3 h, 12 h, 24 h and 48 h postoperatively. Endotoxin was measured from platelet rich plasma by the limulus amebocyte lysate assay. TNFα production was measured by enzyme-immunoassay. At postoperative 0 h, 12 h, 24 h, and 48 h, gastrointestinal permeability was determined by the sugar absorption test that measures the ratio of urinary excretion of lactulose/L-rhamnose (non-mediated diffusion), D-xylose (passive) and 3-O-methyl-D-glucose (active carrier mediated transport) after oral administration.


Endotoxin concentrations were found very low (< 3 pg/ml) in most of the samples during and after CPB. Only in one patient high levels of endotoxin were observed at 20 min CPB (16 pg/ml) and 12 h post CPB (17 pg/ml). TNFα increased progressively during the postoperative period (from 1.5 ± 0.5 pg/ml at baseline to 4.2 ± 0.8 pg/ml 48 h postoperatively). An increase in gastrointestinal permeability was found in most of patients (10 of 11) up to 48 h postoperatively, as indicated by increased lactulose/L-rhamnose ratio and decreased D-xylose and 3-O-methyl-D-glucose excretion percentage. No correlation was found between increased gastrointestinal permeability and plasma concentration of endotoxin, nor between endotoxin and TNFα production.


These results suggest that gastrointestinal permeability increases in neonates and young children undergoing CPB. However, this increase does not lead to clinical significant endotoxemia. TNFα production during and after CPB is likely due to other mechanisms than endotoxin only.

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Schreurs, H., Wijers, M., Piena-Spoel, M. et al. Inflammatory response to cardiopulmonary bypass in neonates and young children: endotoxin release, cytokine production, and gastrointestinal permeability. Crit Care 3 (Suppl 2), P08 (1999).

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