A UNIFYING HYPOTHESIS OF MULTIPLE SYSTEMS ORGAN FAILURE - FAILURE OF HOST DEFENSE HOMEOSTASIS

Multiple systems organ failure (MSOF) represents the culmination of a process of progressive remote organ system dysfunction that evolves following numerous forms of critical illness. The process is pathogenstically related to sepsis; if a septic nidus exists and is not eradicated, organs remote from the initial site of tissue injury fail and the disease process ultimately ends in death. We hypothesize that the underlying process is an uncontrolled (malignant) intravascular inflammatory response, usually to a septic challenge. Dysfunction of individual organs appears to be less important than global cellular function. Thus, single organ-directed treatments during systemic sepsis do little to reverse the process that initially created the organ dysfunction. Since the liver plays a central role in host-defense homeostasis, its performance is primary in determining the systemic expression of MSOF and its outcome. Both the level of intravascular inflammation and its duration may be equally important in the development of MSOF. Accordingly, therapeutic strategies that minimize the systemic nature of the host inflammatory response, while eradicating the stimulus and maintaining tissue viability, should be more successful at improving survival in MSOF than the present organ-specific approach. © 1990.