Cardiopulmonary bypass with adequate flow and perfusion pressures prevents endotoxaemia and pathologic cytokine production

Abstract

Endotoxin and cytokine inflammatory mediators comprise the afferent and efferent limbs of the 'acute phase response'. During cardiopulmonary bypass (CPB) there may be gut translocation of endotoxin and contact activation of lymphocytes. It has been hypothesized that the haemodynamic instability encountered following CPB is caused by the 'acute phase response'. In this study we attempted to quantify the acute phase response in patients undergoing open-heart surgery and determine the influence of these cytokines on perioperative morbidity. Four perioperative blood samples were drawn from 20 consecutive patients undergoing coronary artery bypass grafting (CABG). These samples were assayed for endotoxin and four cytokines. In all cases the cardiac index was maintained > 2.4 l/min/m2during nonpulsatile normothermic bypass (37°C) and > 1.8 l/min/m2during nonpulsatile hypothermic bypass (28°C), and the perfusion pressure > 60 mmHg.Endotoxin was not detected in any of the test samples despite positive nonpatient controls. Interleukin 6 (IL-6) and tumour necrosis factor (TNF) were not detected despite an assay sensitivity of 80 and 10 pg/ml, respectively. TNF was detectable with an assay sensitivity of 0.5 pg/ml although there were no significant differences within the group. Interleukin 1 (IL-1) was detected (range = 0.98 - 9.09 ng/ml) in patients and again there were no trends within the group. The platelet activating factor (PAF) values peaked at crossclamp release (1.3 ng/ml versus a baseline of 0.2 ng/ml); however, there was no significant difference within the study.The perioperative rise in PAF suggests that of all the mediators assayed this cytokine has the lowest synthesis threshold in response to stress, related to nonpulsatile CPB, and is unrelated to endotoxaemia (as detected by the limulus amoebocyte lysate (LAL) assay). Despite recent reports outlining the incidence of endotoxaemia, cytokine activation and the benefits of anti inflammatory therapy during CPB, our data suggest that maintenance of high flow and perfusion pressures during nonpulsatile CPB reduces the incidence of any 'acute phase response' of clinical significance.