Abstract 3008: Limitation of Perioperative Inflammation by the Leukocyte Inhibition Module in Patients Undergoing on-pump Cardiac Surgery: The LIMFRA Trial
Objective: Inflammatory response is one of the major drawbacks of cardiopulmonary bypass (CPB). Filtration of leucocytes showed controversial results in experimental and clinical studies. The leukocyte inhibition module (LIM) is a biofunctional medical device based on immobilized agonistic anti-Fas antibodies. LIM readily induces inactivation and apoptosis of activated neutrophils and can be easily integrated into the CPB circuit. The LIMFRA trial was done to confirm the safety and efficacy of LIM in reducing inflammation in cardiac surgery.
Methods: LIMFRA was designed as a prospective randomized controlled single center trial with 100 elective on-pump cardiac surgery patients who underwent low-risk coronary artery bypass grafting (CABG). LIM (Leukocare AG, Munich) was introduced into the venous line of the heart-lung machine. In the control group (n=50), the sham modules did not contain antibodies. Patients were followed up until one month after surgery. Main end points were safety and attenuation of inflammation, measured by leukocyte counts and plasma concentrations of neutrophil elastase.
Results: Each 50 CABG patients were operated with CPB containing either the LIM or the sham device. Mean CPB time was 95±4 min, median was 85. No LIM-related SAEs were observed in this study. No antibody specific immune reactions against the murine anti-Fas antibody were found one month after surgery. As shown in earlier studies, intra- and postoperative inflammatory parameters were significantly reduced in the LIM group versus control group like the increases in neutrophil counts, neutrophil elastase, myeloperoxydase and lipid peroxidation (p<0.05). When stratified for CPB time (90min) the reduction in inflammation was even more pronounced in the stratification group with longer CPB time.
Conclusion: LIM proved to be a safe and effective biofunctional medical device to limit perioperative neutrophil-mediated inflammation. In contrast to previous studies, LIM biologically prevents overshooting neutrophil effector functions by targeting the neutrophil Fas receptor without systemic application of drugs.