Abstract
Hemorrhagic shock from traumatic injury results in a massive systemic response with activation of the hypothalamic-pituitary-adrenal (HPA) axis, pro-thrombotic and clot-lysis pathways as well as development of an endotheliopathy. With ongoing hemorrhage, these responses become dysregulated and are associated with worsening coagulopathy, microvascular dysfunction, and increased transfusion requirements. Our transfusion practices as well as our understanding of the molecular response to hemorrhage have undergone significant advancement during war. Currently, resuscitation practices address the benefit of the early recognition and management of acute coagulopathy and advocates for balanced resuscitation with either whole blood or a 1:1 ratio of packed red blood cells to fresh frozen plasma (respectively). However, a significant volume of evidence in the last two decades has recognized the importance of the early modulation of traumatic endotheliopathy and the HPA axis via the early administration of plasma, whole blood, and adjunctive treatments such as tranexamic acid (TXA) and calcium. This evidence compels us to rethink our understanding of 'balanced resuscitation' and begin creating a more structured practice to address additional competing priorities beyond coagulopathy. The following manuscript reviews the benefits of addressing the additional interrelated physiologic responses to hemorrhage and seeks to expand beyond our understanding of 'balanced resuscitation'.