2011 Volume 22 Issue 3 Pages 85-116
There has been much progress in elucidation of the pathophysiology of severe sepsis / septic shock. Now it is widely accepted that fundamental process of severe sepsis / septic shock is the cytokine production through intracellular signal transduction activated by both pathogen-associated molecular patterns (PAMPS) and alarmin through pattern recognition receptors such as toll-like receptors. And it is also widely accepted that pro-inflammatory and anti-inflammatory hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. As for cell death which is an important pathophysiological feature of sepsis-induced organ failure, recently autophagy becomes main target of the research even though anoxic necrosis and apoptosis drew attentions in the past decades. Genetic polymorphisms are also very important issue in elucidation of the pathophysiology of sepsis, because, an individual with cytokine- and innate immunity -related genetic polymorphisms shows severer inflammatory response to infectious insult, and shows less effectiveness to certain therapeutic approaches compared to septic patients without such genetic polymorphisms. Immunoparalysis is also important issue in the pathophysiology of severe sepsis and septic shock, since it is an important causative factor of serious superimposing infectious complication in the clinical course of sepsis. As for the treatment of severe sepsis / septic shock, Surviving Sepsis Campaign guidelines (SSCG) has gained popularity all over the world and has been applied in many ICU's even in Japan. However, there are some problems when we apply SSCG in our country. First, there are no descriptions on the countermeasures against hypercytokinemia even though it is now widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of severe sepsis / septic shock as mentioned above. Second, the majority of the therapeutic recommendations in SSCG are supported by the evidence gained by the randomized controlled trial on Caucasian populations who have different distribution of genetic polymorphisms compared to Japanese. We applied continuous hemodiafiltration with a cytokine-adsorbing hemofilter as countermeasure against hypercytokinemia and placed it as a mainstay of therapeutic approach to severe sepsis / septic shock. And we achieved excellent outcome with this therapeutic strategy compared to the outcome in previous reports from foreign countries. In future we should apply micro-RNA analysis to elucidate pathophysiology more precisely and stem cell therapy should be considered for the better survival and/or intact survival of severe sepsis / septic shock patients.
