As established, vascular disruption with concomitant hemorrhage remains the leading cause of potentially preventable death for military personnel injured on operations. The development of an immediately available advanced resuscitative and hemostatic agent targeting internal hemorrhage would provide a significant decrease in early battlefield mortality and be widely applicable in civilian trauma. This fluid would be characterized as a Multi-function Resuscitation Fluid (MRF) and would leverage components both from blood products and pharmaceutical adjuncts to achieve both effective oxygen delivery and hemorrhage control.
The use of pre-hospital blood, although described, requires a large logistical chain, is inefficient and bulky to transport. This is also compounded by the allogenic nature of the fluid and potential for transfusion related complications. Thus, synthetic fluids have been, and remain, the current standard of care, but are far from satisfactory. While assisting with volume expansion, they can induce coagulopathy by diluting endogenous clotting factors, which drives further bleeding.
In support of AFMSA, the MHRF is collaborating with the Oregon Health and Science Institute and the Office of Naval Research to evaluate improved, alternative resuscitation fluids to support pre-hospital resuscitation needs. One fluid in particular, lyophilized plasma, is already in use in the combat theater as an alternative to the current trauma and combat casualty standard of care. Additional blood products like spray-dried plasma (SDP), a pooled-donor, spray-dried, pathogen inactivated plasma, have to potential to offer the benefits observed with blood product based resuscitation but with a much better safety profile. These characteristics make SDP an ideal “backbone” for a multi-function resuscitation fluid.
An effective multi-function resuscitation fluid will also require the inclusion of additional pro-coagulation agents. Platelet Derived Hemostatic Agents (PDHAs) are platelet-derived pharmaceutical products that have improved shelf stability versus their liquid platelet counterparts and promote clotting in traumatic injury. The multi-function resuscitation fluid formulation must have hemostatic capability in addition to that imparted by SDP alone. We therefore propose to include a select PDHA in the multi-function resuscitation formulation assessment.
Finally, while diluents or vehicles like SDP exhibit advantageous characteristics, SDPs do not possess an inherent oxygen carrying capability. The ideal multi-function resuscitation formulation should not only enhance the delivery of oxygen by increasing circulatory volume and cardiac output but should also enhance the total oxygen carrying capacity as would be expected in contemporary component blood product resuscitation (damage control resuscitation). Perfluorocarbons (PFCs) and hemoglobin based oxygen carriers (HBOCs) are well suited and will be evaluated to fulfill this role for enhanced oxygen carrying capacity in our multi-function resuscitation formulation assessments.