ANTI-ENDOTOXIN NEUTRALIZING ACTIVITY OF SERUM IN PATIENTS PRIOR TO CARDIAC SURGERY

Abstract

Introduction: Low preoperative serum Anti-Endotoxin Core Antibody (EndoCAb) levels have been shown to be an independent predictor of postoperative complications over and above the effects of known preoperative risk factors and total immunoglobulin levels. [1,2] We tested the hypothesis that higher EndoCAb levels are associated with a greater degree of neutralization of a common clinical serotype of E. coli endotoxin using a standard in vitro assay. Methods: Following IRB approval, patients undergoing CABG and/or valvular heart surgery were enrolled. A preoperative serum sample was obtained from these patients prior to anesthetic induction. Serum was assayed for IgG and IgM EndoCAb using a standard ELISA technique. [3] The endotoxin neutralization assay was conducted by incubating a serum sample with a known quantity of E. coli O18 endotoxin for 15 minutes at 37[degree sign]C. Residual endotoxin activity in the serum/endotoxin mixture was subsequently measured using the standard gel clot Limulus Amebocyte Lysate assay (Associates of Cape Cod, MA). Associations between IgG EndoCAb, IgM EndoCAb, and degree of neutralization were tested using logistic regression. Results: Serum samples from 203 patients were studied. EndoCAb levels were expressed as median units (MU) by convention and were (range, median, mean): IgM Class (12-1882, 118, 243), IgG Class (18-1232, 208, 271). There was a positive association between higher IgM EndoCAb level and greater endotoxin neutralization (OR 1.004 per MU increase, p<0.0001). There was a positive association between higher IgG EndoCAb level and greater endotoxin neutralization (OR 1.005 per MU increase, p<0.0001). These factors were additive in the model and there was no statistical evidence of a synergistic effect or of a "plateau" effect. Conclusions: Patients with elevated EndoCAB levels prior to surgery were shown to contain serum with more effective endotoxin neutralizing properties against the endotoxin from a common clinical isolate of E. coli. This finding may account in part for studies which have shown that low preoperative EndoCAB levels are associated with increased complications following cardiac surgery. [1,2] A randomized, blinded clinical trial is currently underway to determine if preoperative administration of EndoCAb to cardiac surgical patients results in improved postoperative outcome.