Testing of blood products in a polytrauma model: Results of a multi-institutional randomized preclinical trial

Hasan B. Alam, Leticia M. Bice, Muhammad U. Butt, S. David Cho, Michael A. Dubick, Michael Duggan, Michael S. Englehart, John B. Holcomb, Melanie S. Morris, M. Dale Prince, Martin Schreiber, Christian Shults, Jill L. Sondeen, Malek Tabbara, Brandon Tieu, Samantha A. Underwood

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Introduction: 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 (3 × shed blood) + induction of hypothermia (33°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.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume67
Issue number4
DOIs
StatePublished - Oct 2009

Fingerprint

Multiple Trauma
Hydroxyethyl Starch Derivatives
Wounds and Injuries
Acidosis
Blood Volume
Hypothermia
Liver
Erythrocytes
Hemodynamics
Hemorrhage
Thrombelastography
International Normalized Ratio
Partial Thromboplastin Time
Mortality
Prothrombin Time
Resuscitation
Femur
Anemia
Shock
Lactic Acid

Keywords

  • Acidosis
  • Coagulopathy
  • Hemorrhage
  • Hypothermia
  • Liver injury
  • Plasma
  • Polytrauma
  • Shock

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Testing of blood products in a polytrauma model : Results of a multi-institutional randomized preclinical trial. / Alam, Hasan B.; Bice, Leticia M.; Butt, Muhammad U.; Cho, S. David; Dubick, Michael A.; Duggan, Michael; Englehart, Michael S.; Holcomb, John B.; Morris, Melanie S.; Prince, M. Dale; Schreiber, Martin; Shults, Christian; Sondeen, Jill L.; Tabbara, Malek; Tieu, Brandon; Underwood, Samantha A.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 67, No. 4, 10.2009, p. 856-864.

Research output: Contribution to journalArticle

Alam, HB, Bice, LM, Butt, MU, Cho, SD, Dubick, MA, Duggan, M, Englehart, MS, Holcomb, JB, Morris, MS, Prince, MD, Schreiber, M, Shults, C, Sondeen, JL, Tabbara, M, Tieu, B & Underwood, SA 2009, 'Testing of blood products in a polytrauma model: Results of a multi-institutional randomized preclinical trial', Journal of Trauma - Injury, Infection and Critical Care, vol. 67, no. 4, pp. 856-864. https://doi.org/10.1097/TA.0b013e3181b5ae75
Alam, Hasan B. ; Bice, Leticia M. ; Butt, Muhammad U. ; Cho, S. David ; Dubick, Michael A. ; Duggan, Michael ; Englehart, Michael S. ; Holcomb, John B. ; Morris, Melanie S. ; Prince, M. Dale ; Schreiber, Martin ; Shults, Christian ; Sondeen, Jill L. ; Tabbara, Malek ; Tieu, Brandon ; Underwood, Samantha A. / Testing of blood products in a polytrauma model : Results of a multi-institutional randomized preclinical trial. In: Journal of Trauma - Injury, Infection and Critical Care. 2009 ; Vol. 67, No. 4. pp. 856-864.
@article{2e4a94664ff14ce1b92cf3e0bb8671a6,
title = "Testing of blood products in a polytrauma model: Results of a multi-institutional randomized preclinical trial",
abstract = "Introduction: 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 (3 × shed blood) + induction of hypothermia (33°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.",
keywords = "Acidosis, Coagulopathy, Hemorrhage, Hypothermia, Liver injury, Plasma, Polytrauma, Shock",
author = "Alam, {Hasan B.} and Bice, {Leticia M.} and Butt, {Muhammad U.} and Cho, {S. David} and Dubick, {Michael A.} and Michael Duggan and Englehart, {Michael S.} and Holcomb, {John B.} and Morris, {Melanie S.} and Prince, {M. Dale} and Martin Schreiber and Christian Shults and Sondeen, {Jill L.} and Malek Tabbara and Brandon Tieu and Underwood, {Samantha A.}",
year = "2009",
month = "10",
doi = "10.1097/TA.0b013e3181b5ae75",
language = "English (US)",
volume = "67",
pages = "856--864",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Testing of blood products in a polytrauma model

T2 - Results of a multi-institutional randomized preclinical trial

AU - Alam, Hasan B.

AU - Bice, Leticia M.

AU - Butt, Muhammad U.

AU - Cho, S. David

AU - Dubick, Michael A.

AU - Duggan, Michael

AU - Englehart, Michael S.

AU - Holcomb, John B.

AU - Morris, Melanie S.

AU - Prince, M. Dale

AU - Schreiber, Martin

AU - Shults, Christian

AU - Sondeen, Jill L.

AU - Tabbara, Malek

AU - Tieu, Brandon

AU - Underwood, Samantha A.

PY - 2009/10

Y1 - 2009/10

N2 - Introduction: 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 (3 × shed blood) + induction of hypothermia (33°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.

AB - Introduction: 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 (3 × shed blood) + induction of hypothermia (33°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.

KW - Acidosis

KW - Coagulopathy

KW - Hemorrhage

KW - Hypothermia

KW - Liver injury

KW - Plasma

KW - Polytrauma

KW - Shock

UR - http://www.scopus.com/inward/record.url?scp=72449209284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72449209284&partnerID=8YFLogxK

U2 - 10.1097/TA.0b013e3181b5ae75

DO - 10.1097/TA.0b013e3181b5ae75

M3 - Article

C2 - 19820596

AN - SCOPUS:72449209284

VL - 67

SP - 856

EP - 864

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 4

ER -