Detection and significance of endotoxin in children following cardiopulmonary bypass

Introduction: Low cardiac output syndrome is a major cause of morbidity and mortality following repair of congenital heart defects. The role of endotoxin (LPS) in the pathogenesis of this syndrome remains in question, likely due to rapid clearance from the circulation and previously unreliable LPS assays. Lipopolysaccharide-binding protein (LBP), recently demonstrated to be a surrogate marker for endotoxin, rises following cardiopulmonary bypass (CPB) in adult patients. The purpose of this study is to measure LPS and LBP prior to and following CPB in children and to correlate their presence with clinical outcome. Methods: We prospectively studied children undergoing correction of congenital heart disease. All patients had LPS and LBP levels drawn prior to surgery and 1,8,24,48 and 72 hours after completion of CPB. Levels of inotropic support and fluid administration required postoperatively were prospectively defined to identify the degree of cardiac output depression. Results: The 29 patients studied ranged in age from 4 days to 402 days (median age 75 days), and had a variety of congenital heart defects. 28 of 29 patients had evidence of endotoxemia at some point during the study, either by measurement of LPS directly or LBP. Prior to CPB, 11 patients had plasma LPS elevation. Patients without elevation of plasma LPS preoperatively, displayed a significant rise in LPS at the 1,8 and 24 hour time-points (p<.03). As a group there was a statistically significant rise in LBP but not LPS, at all time points following CPB (p<.001). Those patients characterized by increased inotropic support and fluid requirements had significantly higher plasma LBP when compared to the patients with lower fluid and inotrope requirements, both preoperatively (p=.001) and immediately post CPB (p=.016). Conclusions: Measurement of both LPS and LBP supports the hypothesis that endotoxin is a mediator of the systemic inflammatory response involved in the pathogenesis of post-CPB myocardial dysfunction in children.