Endotoxemia, complement, and white blood cell activation in cardiac surgery: A randomized trial of laxatives and pulsatile perfusion

Abstract

Endotoxin activates complement and white blood cells and all are implicated in the pathologic effects of cardiopuhnonary bypass (CPB). We investigated if reduction in intestinal bacterial load with a laxative and/or pulsatile perfusion to improve bowel circulation during CPB reduced endotoxemia and complement and white blood cell activation. Sixty patients were randomized to four groups in a 2 × 2 factorial structure: group 1 (no laxative, nonpulsatile perfusion); group 2 (laxative, nonpulsatile perfusion); group 3 (no laxative, pulsatile perfusion); and group 4 (laxative, pulsatile perfusion). Plasma concentrations of endotoxin, C3a and C5a, and granulocyte elastase (GE) were measured before anesthesia, skin incision, and heparin administration; during CPB (1, 30, 60, 90, and 120 minutes and after protamine administration); and after CPB at 3, 6,12,24, and 48 hours and 7 days. In all groups there was a small increase in the concentration of endotoxin (overall from 6 ng/L before CPB to 11 ng/L at 90 to 120 minutes; p < 0.001) and significant increases in C3a, C5a, and GE levels but no significant differences among the groups. Endotoxin levels did not correlate with activation of complement or white blood cells. There was a weak correlation between duration of CPB and levels of C3a ( r = 0.14; p < 0.03) and GE ( r = 0.25; p = 0.001) but not endotoxin or C5a. There was a general correlation between levels of C3a and GE but not in individual patients. In conclusion, CPB results in statistically significant increases in endotoxin, C3a, C5a, and GE during CPB. The increase in endotoxin is, however, small, transient, and not influenced by the use of a laxative or pulsatile perfuaion. Increasing duration of CPB is weakly associated with increased levels of C3a and GE but not endotoxin or C5a. There were no obvious major adverse clinical sequelae associated with the increase in any of the measured parameters.