Abstract Introduction Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. Methods We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. Findings Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. Conclusions There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.

Katherine Crawford

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 2, Page 280-282, July 15, 2018.

Christian Brun-Buisson

Meta-analyses of accuracy of the qSOFA to predict hospital mortality of patients with suspected infection show suboptimal performance of this abridged score. However, a score composed of only 3 clinical variables, such as the qSOFA or CRB can hardly be very accurate, but can serve as a warning integrated into clinical decision making, to help triaging patients in the ED. qSOFA does not help identifying infection. More complete, generic severity scores are nevertheless of major interest for stratification or analyses of epidemiolgical studies and clinical trials in septic patients.