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Paper text:
as the study by dr peiniger and colleagues   correctly indicates , many retrospective studies have demonstrated a survival benefit from transfusion strategies using an early and more balanced ratio between fresh frozen plasma ( ffp ) and red blood cell ( rbc ) transfusions in patients with acute traumatic coagulopathy requiring massive transfusion within the first 24 hours of hospitalization .
however , this topic has never been explored in depth in patients with concomitant severe traumatic brain injury ( tbi ) .
previous studies have included these patients , but they were not the focus of investigation . while the study by dr peiniger and colleagues is retrospective and certainly not a substitute for a well - designed prospective trial , the authors nonetheless should be commended for addressing this issue with their current work .
currently , the optimum fluid resuscitation paradigm for patients with both severe tbi and other injuries requiring significant volume resuscitation is not clear .
the brain trauma foundation guidelines are silent on the issue of ffp : rbc ratios . resuscitation and avoidance of hypotension
is a primary goal , but the actual fluid within which to accomplish an optimal resuscitation is unknown . bulger and colleagues   recently demonstrated that among injured patients with hypovolemic shock , initial resuscitation fluid treatment with either hypertonic saline or hypertonic saline / dextran compared with normal saline did not result in superior 28-day survival .
the novelty of this current study is its focus on a high ffp : rbc ratio in resuscitation of profoundly hypovolemic tbi patients .
as the authors point out in their introduction , a major issue with these patients is coagulopathy at initial presentation .
coagulopathy in severe tbi patients can lead to profound hematoma expansion resulting in significant morbidity and mortality .
a current active area of tbi research is the study of the mechanisms by which cerebral contusions expand . additionally , tbi patients in general are susceptible to cytotoxic edema .
mechanisms that lead to cerebral edema in tbi patients are currently being actively investigated in the hope of developing treatment strategies to limit this problem and its sequelae .
simard and colleagues   have reported data from rat studies that suggest that tbi leads to upregulation and activation of sulfonylurea receptor 1 ( sur1)-regulated nc(ca - atp ) channels in capillary endothelial cells , which predisposes them to oncotic death and catastrophic failure of capillary integrity .
it is this failure of capillary integrity caused by upregulation of sur1 expression that is hypothesized to cause development of progressive secondary hemorrhage . with unchecked progressive secondary hemorrhage ,
ohsumi and colleagues   have also suggested that astrocytic gap junctions participate in pathophysiological processes after tbi in rats .
gap junctions are conductive channels formed by membrane proteins termed connexins , which permit the intercellular exchange of metabolites , ions , and small molecules . in this animal study ,
expression of the connexin p - cx43 in the ipsilateral hippocampus was significantly induced at 1 hour after tbi , and remained at a high level until 24 hours after injury .
the p - cx43 protein content reached a maximum level at 6 hours after injury .
this increased expression of p - cx43 suggests a mechanism by which ions and water could enter cells and lead to oncotic cell death .
a better understanding of the optimal resuscitation paradigm for hypovolemic patients with severe tbi could potentially help our understanding of both of these pathophysiological processes .
a major barrier in the study of resuscitation of tbi subjects with concomitant hypovolemic shock is lack of a good animal model for the process .
development of a reliable animal model would be the first step in addressing this clinical problem .
first , the animal model could address issues regarding the optimum fluid resuscitation regimen for hypovolemic , severe tbi patients .
and in patients requiring rbc transfusion , what is the ideal ffp : rbc ratio ?
such an animal model could potentially give us mechanistic clues and information as to why a specific resuscitation paradigm involving ffp is optimum .
is it possible that ffp resuscitation helps reverse the early coagulopathy seen in severely injured patients , and restore vascular stability , thus decreasing permeability and subsequent pathologic edema ? with good reproducible animal data and the retrospective data reported here by peiniger and colleagues , it would then be important to design prospective studies to study this problem .
ultimately , developing an optimum resuscitation paradigm for these patients could broaden our understanding of tbi pathophysiology in general .
if a particular paradigm with a certain ffp : rbc ratio is shown to be superior to others , we would be in a position to understand why it is better . while many authors have described improved outcomes associated with increased ffp : rbc ratios , only now are mechanistic data starting to appear . perhaps a certain treatment may most effectively decrease mortality because it prevents unchecked progressive secondary hemorrhage .
alternatively , a given resuscitation paradigm may be superior because it is best at suppressing pathological expression of astrocytic gap junctions , thus decreasing edema progression . with both good animal data and results from prospective human studies in place
, we should be in the position to significantly improve the care of severe tbi patients .
ffp : fresh frozen plasma ; rbc : red blood cell ; tbi : traumatic brain injury .
the study by dr peiniger and colleagues in a recent issue of critical care indicates that transfusion strategies using an early and more balanced ratio between fresh frozen plasma and red blood cell transfusions provide a survival benefit in patients with acute traumatic coagulopathy requiring massive transfusion within the first 24 hours of hospitalization . 
 however , this topic has never been explored in depth in patients with concomitant severe traumatic brain injury . while the study is retrospective and certainly not a substitute for a well - designed prospective trial , 
 the authors nonetheless should be commended for addressing this issue with their current work . 
 currently , the optimum fluid resuscitation paradigm for patients with both severe traumatic brain injury and other injuries requiring significant volume resuscitation is not clear .