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Effects of Synthetic Versus Natural Colloid Resuscitation on Inducing Dilutional Coagulopathy and Increasing Hemorrhage in Rabbits

Kheirabadi, Bijan S. PhD; Crissey, Jacqueline M. BS; Deguzman, Rodolfo MS; Perez, Michael R. MS; Cox, Ashley B. MS; Dubick, Michael A. PhD; Holcomb, John B. MD

The Journal of Trauma: Injury, Infection, and Critical Care: May 2008 - Volume 64 - Issue 5 - p 1218-1229
doi: 10.1097/TA.0b013e31816c5c6c
Original Articles

Background: On the basis of logistic benefits of colloids over crystalloids, the U.S. military selected Hextend for resuscitation of combat casualties in the field. We investigated the effects of resuscitation with this fluid, as well as other colloids, on coagulation and uncontrolled bleeding in rabbits subjected to a splenic injury.

Methods: Anesthetized male New Zealand white rabbits (3.3 kg ± 0.2 kg) were divided into three groups and subjected to hypothermia (35°C ± 0.5°C) and ∼40% isovolemic blood exchange (hemodilution) with Hextend (H); Dextran70 (D); or 5% human albumin (A) solution (n = 8/group). Complete blood count, arterial blood gas, and coagulation values were measured before and after hemodilution. Laparotomy was performed and a standard splenic injury causing uncontrolled hemorrhage was made. Rabbits were resuscitated (25 mL/kg) with the same colloid used for hemodilution to restore baseline blood pressure. Animals were monitored for 2 hours or until death. Blood loss and survival times were measured.

Results: There were no differences among groups in pH, Hct, fibrinogen, or platelets before or after hemodilution. Hct, fibrinogen, and platelets were reduced by 45% to 60% in all groups. Prothrombin time (PT) and activated partial thromboplastin time were prolonged in all the rabbits with the greatest increase in A group. Thrombelastograph (TEG) analysis showed longer initial reaction (R) and clotting (K) times, slower clotting rate and lower clot strength in H and D than A diluted blood. R time was faster and K time remained unchanged in A group after hemodilution. Thrombin generation potential and peak concentration of thrombin were unchanged in A samples but significantly reduced in H and D diluted samples. Subsequent splenic injury led to almost equal blood losses (∼54 ± 1 mL/kg) in H and D groups, which were higher (p < 0.01) than in A rabbits (37 ± 4 mL/kg). This resulted in death of 100% (H), 75% (D), and 50% (A) of the rabbits with significant difference in survival time among the groups.

Conclusion: TEG and thrombin generation assays identified more severe coagulopathy development with H and D than A dilution, whereas plasma PT and activated partial thromboplastin time measurements did not differentiate between these colloids. These results suggest that resuscitation with albumin maintained coagulation function, decreased blood loss, and improved survival time compared with the synthetic colloids.

From the U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas.

Received for publication September 14, 2007.

Accepted for publication February 7, 2008.

Presented at the 66th Annual Meeting of the American Association for the Surgery of Trauma, September 27–29, 2007, Las Vegas, Nevada.

The opinions or assertions expressed herein are the private views of the authors and are not to be construed as official or as reflecting the views of the United states, Department of the Army or the U.S. Department of Defense.

Address for reprints: Bijan S. Kheirabadi, PhD, U.S. Army Institute of Surgical Research, 3400 Rawley E. Chambers Avenue, Building No. 3611, Fort Sam Houston, TX; email:

© 2008 Lippincott Williams & Wilkins, Inc.