Endotoxemia related to cardiopulmonary bypass is associated with increased risk of infection after cardiac surgery : a prospective observational study

Introduction: Previous studies have documented a high frequency of endotoxemia associated with cardiopulmonary bypass (CPB). Endotoxemia may be responsible for some of the complications associated with cardiac surgery. The purpose of the study was to examine the prevalence of endotoxemia during cardiopulmonary bypass supported aortocoronary bypass grafting surgery (ACB) using a new assay, the Endotoxin Activity Assay (EAA), and explore the association between endotoxemia and post-operative infection. Methods: The study was a single center prospective observational study measuring EAA during the perioperative period for elective ACB. Blood samples were drawn at induction of anesthesia (T1), immediately prior to release of the aortic cross-clamp (T2), and on the first post-operative morning (T3). The primary outcome was the prevalence of endotoxemia. Secondary outcomes assessed included infection rates, intensive care unit (ICU) and hospital length of stay. An EAA of < 0.40 units was interpreted as “low”, 0.41 to 0.59 units as “intermediate”, and ≥0.60 units as “high”. Results: A total of 57 patients were enrolled and 54 patients were analyzable. The mean EAA at T1 was 0.38 +/0.14, at T2 0.39 +/0.18, and at T3 0.33 +/0.18. At T2 only 13.5% (7/52) of patients had an EAA in the high range. There was a positive correlation between EAA and duration of surgery (P = 0.02). In patients with EAA ≥0.40 at T2, 26.1% (6/23) of patients developed post-operative infections compared to 3.5% (1/29) of those that had a normal EAA (P = 0.0354). Maximum EAA over the first 24 hours was also strongly correlated with risk of post-operative infection (P = 0.0276). Conclusions: High levels of endotoxin occur less frequently during ACB than previously documented. However, endotoxemia is associated with a significantly increased risk of the development of post-operative infection. Measuring endotoxin levels during ACB may provide a mechanism to identify and target a high risk patient population. Introduction Since the beginnings of cardiopulmonary bypass (CPB) supported cardiac surgery in the 1950’s, clinicians and surgeons have faced the challenge of balancing the desire to achieve optimal surgical results, while minimizing the consequences of exposure to cardiac bypass [1,2]. The inflammatory response to CPB has been implicated in many of the post-operative clinical problems that often occur in these patients including coagulopathy, respiratory failure, post-operative shock states, and multiple organ failure [3]. The pathophysiology of this inflammatory response is thought to involve a cascade of complement activation, activation of intrinsic and extrinsic coagulation systems, as well as activation of cellular components of inflammation and alterations in immune function [3]. Numerous cytokines and inflammatory mediators have been found to rise in patients exposed to CPB including IL-1b, IL-6, IL-8, TNF-a [4-6]. Endotoxin, or lipopolysaccharide (LPS), is a key component of the cell membrane of gram negative bacteria. * Correspondence: kleind@smh.ca Department of Critical Care and the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, 4-054C Queen Wing, 30 Bond Street, Toronto, ON M5B 1W8, Canada Full list of author information is available at the end of the article Klein et al. Critical Care 2011, 15:R69 http://ccforum.com/content/15/1/R69 © 2011 Klein et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Endotoxin is one of the most potent known activators of innate immunity and the inflammatory response in humans [7]. It was first identified in the serum of patients undergoing CPB over 20 years ago and proposed as a potential mediator of multiple organ failure and prolonged recovery after cardiac surgery [8]. Endotoxin is hypothesized to enter the systemic circulation during CPB by translocation of gut commensal microbes or LPS fragments across the intestinal mucosal barrier during the period of relative hypotension and hypoperfusion associated with extracorporeal support [9]. The prevalence of endotoxemia in patients on cardiopulmonary bypass has been estimated at up to 100% of ACB patients, although estimates are highly variable [8,9]. Endotoxin’s true pathologic role during and after CPB, however, has been called into question as it has been difficult to correlate the degree of endotoxemia with adverse clinical outcomes. Several therapeutic strategies directed at minimizing or treating endotoxemia as a consequence of CPB including selective gut decontamination, pulsatile flow extracorporeal pumps, and LPS receptor inhibitors have been tried in patients without success [10-12]. In addition, the estimated prevalence of endotoxemia during cardiopulmonary bypass may be unreliable due to the challenges of assaying endotoxin in vivo using the traditional Limulus Amoebocyte Lysate (LAL) assay [13]. To clarify the role of endotoxemia, we investigated the prevalence of endotoxemia related to CPB in a cohort of patients undergoing elective cardiac surgery using the EAA for the measurement of endotoxin in blood. We further investigated the association between endotoxemia and the development of adverse clinical events including length of stay and development of post-operative infections. Materials and methods