Experimental and emerging therapies for sepsis and septic shock.

The underlying principles of sepsis therapy have remained unchanged for decades. These include: prompt institution of antimicrobial agents aimed at the inciting pathogen, source control directed at removal of the infection nidus whenever possible, and support of organ dysfunction. Despite advances in antibiotics, surgical techniques and organ support technology, the morbidity and mortality from sepsis-related diseases have remained substantially unchanged (30 - 50%). Immunomodulation of the inflammatory cascade has been suggested as a crucial but inadequately addressed element in the treatment of sepsis. The list of potential therapeutic targets has been growing as more and more mediators are identified in the pathogenesis of sepsis. To date, numerous anti-inflammatory agents, found to have favourable effects in animal models of septic shock, have been tested in a number of clinical trials on thousands of patients. In this first of a three part series, we go through some of the background and current strategies in sepsis therapy. In this review, we include the two novel therapies that have shown clear survival benefit in large, randomised, placebo-controlled, multi-centre trials, low-dose steroids and recombinant activated protein C. Also included in this review are studies on antithrombin III, platelet-activating factor antagonists, complement modulators, nitric oxide synthase inhibitors and caspase inhibitors (apoptosis inhibitors).