An update on the pathophysiology of sepsis.

Mortality among critically ill patients has been attributed to the development of sepsis. About 28% of patients with sepsis still die, despite numerous interventions. Trials on sepsis investigated mostly anti-inflammatory strategies, based on the prevailing theory that sepsis represents an uncontrolled inflammatory response. None of these showed convincing benefit in humans, despite promising results in animal studies. The reason for this is becoming clear: sepsis represents a biphasic response to infection, and the initial pro-inflammatory response that we have targeted thus far is invariably followed by a prolonged period of immune suppression. In addition, a patient may oscillate between a pro- and anti-inflammatory state repeatedly. A single magic bullet therapy is thus unlikely to work. The mediators of this process are the cytokines, and a lot of research is focussed on modulating these to achieve a better outcome. In addition, the central role of the coagulation cascade in mediating inflammation and sepsis is becoming clear, and therapies addressing this mechanism are promising.