Thirty years of anti-mediator treatment in sepsis and septic shock - what have we learned?

Sepsis, the systemic response (specific and non-specific) of the body to an infection, is an increasing clinical problem. During the last 30 years, nearly 50 clinical trials involving more than 10,000 patients have failed to demonstrate improvement of patients' outcome with different "anti-mediator" strategies. The wrong conceptional approaches to interact with the complex mediator network and flaws in study design and conduct are the main reasons for this disappointing situation. We learned, however, that the systemic host response is more than persistent un controlled Inflammation; it is also a stimulation of the counter regulatory network. Although it is important to analyse the complex picture, we have now reached a point where more sophisticated strategies for describing complexity and novel attempts for synthesis are needed. Along this line, improved study designs (decrease of "signal-to-noise ratio") are mandatory. In addition, secondary prevent ive strategies are emphasised.