The future is predetermined in severe sepsis, so what are the implications?

A high rate of death from septic shock persists despite general improvements in care. The relative failure of mechanistically based therapies in various clinical trials should also trigger a reconsideration of such mechanistic approaches. Despite reversion of shock by hydrocortisone, the similar death rate compared with nonsteroid-treated patients suggests that factors other than shock itself are responsible for death. This may be predetermined and relate to gene variants, the functionality of gene expression, age, an association with chronic diseases such as diabetes and cancer, or perhaps the treatments being given for these diseases. These aspects are discussed in this review in the light of arguments that support a hypothesis of outcome predetermination. Not only constitutive factors, but also acute and chronic environmental factors may be responsible. An important consequence would be the ability to perform early prognostication in an individual patient using biomarkers. On this basis, new therapies could be tested to reduce mortality rates with the response and toxicity of these therapies being predefined using pharmacogenetic testing.