The role of contact system in septic shock: the next target? An overview of the current evidence

BACKGROUND: Septic shock remains challenging to intensive care units worldwide, despite recent documented improvement in mortality over the years. Multiple new therapies have been attempted without success in large clinical trials. Evidence concerning the role of the contact system and bradykinin on septic shock physiological manifestations is shown by this article. OBJECTIVES: The objective of the study is to review the current evidence linking contact system activation and septic shock, as well as efficacy of available therapies targeting this pathophysiological pathway and to evaluate the potential of further researching the matter. RESULTS: Multiple animal studies are already available and suggestive of a meaningful role of contact system activation on septic shock. However, human trials are still scarce, and the ones available are not enough to establish such a strong connection. Furthermore, attempted therapies have been successful across multiple species, but not as much in humans. Therefore, contact system and septic shock relationship remains plentiful in questions to be answered in the coming years or decades. CONCLUSIONS: Whether the contact system is not as relevant in humans as it is in animals or there is only lack of evidence remains to be explained. The subject is an attractive open field for further research aiming to aid in tackling such a burdensome condition.