Although sepsis is a systemic process, the pathophysiological cascade may vary from organ to organ. There are few data regarding systemic and local responses during peritonitis in humans and on their correlation to patients outcomes [12–14]. Based on findings of high concentrations of cytokines in the peritoneal compartment, some evidences suggested

that intra-abdominal sepsis may result in a cytokine-mediated inflammatory response that is initially compartmentalized in the peritoneal cavity [15, 16]. Animal models have shown that peritonitis is associated with a significant and prolonged peritoneal inflammatory response which is adversely correlated with survival outcome [17]. The levels of selected peritoneal cytokines have been reported to be significantly different between animals that survived as compared to those who died following a septic challenge [18]. Plausibility Metabolism inhibitor of peritoneal compartmentalization of initial inflammatory response during peritonitis was highlighted by a recent prospective cohort study of patients with secondary generalized peritonitis [19]. It confirmed that IL-1, TNFα, IL-6, IL-10 and IFNγ are present at high concentrations in the peritoneal fluid of patients with peritonitis. The Defactinib mw results of this study showed a large

gradient between peritoneal fluid and plasma concentrations of cytokines, with no correlation between peritoneal and plasma levels, suggesting that plasma levels may increase only after saturation of tissues within the abdominal compartment. The inflammatory response in patients with sepsis depends Pembrolizumab manufacturer on the causative pathogen and the PP2 research buy host (genetic characteristics and coexisting illnesses), with differential responses at local, regional, and systemic levels [20]. The host inflammatory response probably changes over time in parallel with the clinical course. Sepsis, in the early stages of the inflammatory process, should be considered

as a local/peritoneal disease. In advanced stages, severe sepsis and septic shock should be considered as a systemic disease, and patients who are extremely unstable and exhibit high rates of mortality should be managed more aggressively. In certain patients peritonitis can quickly lead to an excessive inflammatory response, and early and aggressive mechanical peritoneal control is determinant for stopping the septic process. In those patients inability to control or interrupt the local inflammatory response is associated with poor outcomes. In patients with ongoing sepsis, several laparotomies may be required. Under these circumstances, open abdomen allows the surgeon to perform subsequent laparotomies more efficiently and prevent the onset of abdominal compartment syndrome that may further worsen the systemic disease. The review focuses on management of patients with severe sepsis or septic shock in the specific setting of severe peritonitis.