Multiple organ failure. How valid is the "two hit" model?

Inflammatory "one hit" and "two hit" models have recently been proposed to account for the development of multiple organ failure (MOF) in trauma and critically ill surgical patients when no source of infection can be found. In the "one hit" model, the initial insult is so massive that a systemic inflammatory response syndrome is triggered and leads rapidly to MOF. In the "two hit" scenario, initially less severely injured patients eventually develop MOF as a result of a reactivation of their inflammatory response caused by an adverse and often minor intercurrent event. At first sight, the theory is attractive because it seems to fit commonly observed clinical patterns. Indeed, injured patients often respond to initial resuscitation but, after an insult of some sort, develop organ dysfunction and die. The "two hit" model is furthermore mirrored at the cellular level. Inflammatory cells are indeed susceptible of being primed by an initial stimulus and reactivated subsequently by a relatively innocuous insult. However, in the absence of clinical and biological corroboration based on cytokine secretion patterns, these models should not be accepted uncritically.