Pathogenesis of multiple organ dysfunction syndrome: gut origin, protection, and decontamination

Abstract

Clinical and experimental studies performed over the past several decades have implicated bacterial and endotoxin translocation (BET) from the gut to distant organs in the pathogenesis of multiple organ dysfunction syndrome (MODS). Experimental studies in animals directed at maintaining the integrity of the intestinal mucosa have shown efficacy in preventing BET and the induction of distant inflammatory processes, suggesting that the egress of bacteria and their surface endotoxins might be pivotal in inducing MODS. However, clinical studies have failed to convincingly recapitulate these beneficial effects. Selective digestive decontamination, although it effectively decreases rates of respiratory infection, has failed to reduce MODS in critically ill patients and, except in certain patient subsets, has had no demonstrable effect on mortality. Nevertheless, the gut is an immunologically active organ that, irrespective of BET occurrence, appears to contribute significantly to the development of distant organ dysfunction following ischemia/reperfusion injury. Resuscitation strategies aimed at minimizing the inflammatory effects of gut-derived mediators, such as toxic oxygen species, appear promising in preventing the development of distant organ injury in the critically ill patient.