Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial.
BACKGROUND
Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model.


METHODS
Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment.


RESULTS
At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy.


CONCLUSIONS
In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.
Alam
Hasan B
HB
Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts 02114, USA. hbalam@partners.org
Bice
Leticia M
LM
Butt
Muhammad U
MU
Cho
S David
SD
Dubick
Michael A
MA
Duggan
Michael
M
Englehart
Michael S
MS
Holcomb
John B
JB
Morris
Melanie S
MS
Prince
M Dale
MD
Schreiber
Martin A
MA
Shults
Christian
C
Sondeen
Jill L
JL
Tabbara
Malek
M
Tieu
Brandon H
BH
Underwood
Samantha A
SA
D000704:Analysis of Variance; D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D001803:Blood Transfusion; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D017707:Erythrocyte Transfusion; D005260:Female; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D008422:Materials Testing; D009104:Multiple Trauma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D010949:Plasma; D010952:Plasma Substitutes / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes