Pathogenesis of CPB-induced SIRS

INTRODUCTION Cardiopulmonary bypass (CPB) has often been compared to the pathophysiologic changes occurring in sepsis or systemic inflammatory response syndrome (SIRS). The definitions for SIRS is classically considered to be related to sepsis, shock, and multiple organ dysfunction syndrome (MODS).1 The idea behind defining SIRS was to define a clinical response to a nonspecific insult of either infectious or noninfectious origin. SIRS for sepsis is defined as 2 or more of the following variables: 1) fever of more than 38°C or less than 36°C; 2) heart rate of more than 90 beats per minute; 3) respiratory rate of more than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg; and abnormal white blood cell count (>12,000/μL or < 4,000/μL or >10% bands). However, this definition is not useful for understanding CPB induced SIRS, which is nonspecific and can be caused by multiple factors including inflammation, trauma, infection, or a combination of several insults as seen after cardiac surgery and CPB. However, both of these syndromes share similar inflammatory and mediator pathways that result in MODS. The inflammatory response to CPB represents pathophysiologic changes, like SIRS, that can range from mild organ dysfunction to multisystem organ failure. The clinical manifestations can be quite variable and include coagulopathy, pulmonary dysfunction, and multiorgan system failure. These diverse injuries are a consequence of multiple inflammatory cells and mediators as seen in SIRS including neutrophil activation and liberation of multiple inflammatory pathways including complement, kinins, kallikrein, cytokines, and others. Plasmin and kallikrein amplify the inflammatory response by activating components of the contact activation system and other inflammatory pathways. This may also be important for traumatic injury as antifibrinolytic therapies are increasing being used to manage these patients as well as for CPB.