Pathophysiology and Therapy of End-Organ Failure in Critical Illness

Abstract

The pattern of death of critically ill patients aggressively treated with lifesustaining therapies following the initial resuscitative effort is remarkably similar across patient groups (1). Most of the critically ill patients who eventually go on to die during that hospitalization in whom initial resuscitative efforts are successful do so because of progressive multi-system deterioration often punctuated by infectious episodes and a non-specific septic state. The clinical expression of this initial process a sepsis or sepsis syndrome has been termed the systemic inflammatory response syndrome or SIRS by a recent consensus conference (2). The deterioration of these patients over time with progressive failure of multiple often unrelated organ systems is referred to a multiple organ dysfunction syndrome or MODS to underscore the continuum of tissue injury which may develop rather than by defining a threshold level to indicate the presence of organ failure. Patients usually first express SIRS and then MODS, progressing along a clinical pathway from initial partial recovery following resuscitation, though relapses and septic episodes to death. Diverse disease states such as infection, trauma and burns, pancreatitis and organ rejection share this common process (1). It is our hypothesis that MODS represents the phenomenological process of progressive and cumulative organ system dysfunction that may occur after a variety of diseases characterized by continual intravascular inflammation (3). According to this hypothesis, specific organ dysfunction is less important to outcome than the cumulative tissue burden of SIRS.