CytoSorbents Corporation (CTSO)

[andy55q]

Severe Sepsis and Septic Shock
SEARCH FOR NEW THERAPIES
Recent Failures
One of the great disappointments during the past 30 years has been the failure to convert advances in our understanding of the underlying biologic features of sepsis into effective new therapies.60 Researchers have tested both highly specific agents and agents exerting more pleiotropic effects. The specific agents can be divided into those designed to interrupt the initial cytokine cascade (e.g., antilipopolysaccharide or anti–proinflammatory cytokine strategies) and those designed to interfere with dysregulated coagulation (e.g., antithrombin or activated protein C).61 The only new agent that gained regulatory approval was activated protein C.62 However, postapproval concern about the safety and efficacy of activated protein C prompted a repeat study, which did not show a benefit and led the manufacturer, Eli Lilly, to withdraw the drug from the market.11 All other strategies thus far have not shown efficacy. With the recent decision to stop further clinical development of CytoFab, a polyclonal anti–tumor necrosis factor antibody (ClinicalTrials.gov number, NCT01145560), there are no current large-scale trials of anticytokine strategies in the treatment of sepsis.
Among the agents with broader immunomodulatory effects, glucocorticoids have received the most attention. Intravenous immune globulin is also associated with a potential benefit,63 but important questions remain, and its use is not part of routine practice.23 Despite a large number of observational studies suggesting that the use of statins reduces the incidence or improves the outcome of sepsis and severe infection,64 such findings have not been confirmed in randomized, controlled trials, so the use of statins is not part of routine sepsis care. 23
http://www.nejm.org/doi/full/10.1056/NEJMra1208623