Elsevier

Blood Reviews

Volume 23, Issue 6, November 2009, Pages 231-240
Blood Reviews

REVIEW
Resuscitation and transfusion principles for traumatic hemorrhagic shock

https://doi.org/10.1016/j.blre.2009.07.003Get rights and content

Summary

The transfusion approach to massive hemorrhage has continually evolved since it began in the early 1900s. It started with fresh whole blood and currently consists of virtually exclusive use of component and crystalloid therapy. Recent US military experience has reinvigorated the debate on what the most optimal transfusion strategy is for patients with traumatic hemorrhagic shock. In this review we discuss recently described mechanisms that contribute to traumatic coagulopathy, which include increased anti-coagulation factors and hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock for patients with severe life-threatening traumatic injuries. The central tenants of DCR include hypotensive resuscitation, rapid surgical control, prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red blood cells, plasma, and platelets in a 1:1:1 unit ratio and the appropriate use of coagulation factors such as rFVIIa and fibrinogen-containing products (fibrinogen concentrates, cryoprecipitate). Fresh whole blood is also part of DCR in locations where it is available. Additional concepts to DCR since its original description that can be considered are the preferential use of “fresh” RBCs, and when available thromboelastography to direct blood product and hemostatic adjunct (anti-fibrinolytics and coagulation factor) administration. Lastly we discuss the importance of an established massive transfusion protocol to rapidly employ DCR and hemostatic resuscitation principles. While the majority of recent trauma transfusion papers are supportive of these general concepts, there is no Level 1 or 2 data available. Taken together, the preponderance of data suggests that these concepts may significantly decrease mortality in massively transfused trauma patients.

Introduction

Traumatic injury is the leading cause of death for patients between the ages of 1 and 40,1 and approximately 90,000 people die per year in the US from traumatic injuries.2 US military reports estimate that 15–20% of traumatic deaths are potentially preventable and 66–80% of these deaths occur from hemorrhage.[3], 4 Rural civilian data indicate that approximately 10% of traumatic deaths are preventable,[5], [6] and 16% of preventable deaths are due to hemorrhage.7 If 10–20% of 90,000 US civilian traumatic deaths are preventable and 16–80% of these preventable deaths are due to uncontrolled bleeding this translates to between 1400 and 14,000 potentially preventable hemorrhagic trauma deaths per year in the US. Hemorrhagic deaths typically occur very early, usually within the first 6 h of admission.[8], [9], [10], [11] Early hypoperfusion or shock has been demonstrated to promote coagulopathy.[12], [13] Approximately 25% of patients with severe traumatic injury are coagulopathic upon admission.[14], [15] Shock and coagulopathy upon admission have been both independently associated with massive transfusion and increased mortality.[16], [17], [18], [19] Therefore, early identification of patients who are at risk of developing shock and coagulopathy, and subsequent strategies to prevent and control these processes may improve survival.[13], [16], [17], [20], [21]

The transfusion approach to hemorrhage has continually changed since the early 1900s. This evolution has included fresh whole blood and modified whole blood to the current virtually exclusive use of component therapy and crystalloid with whole blood being reserved for uncommon indications.[22], [23], 24, [25] After the development of whole blood fractionation, component therapy now predominates as the primary transfusion approach secondary to concerns for resource utilization and safety.[25], [26], 27 This change occurred without evidence documenting equivalent clinical outcome data between whole blood and component therapy.[25], [26], 27 In addition, regulatory approval of new storage solutions is based on RBC membrane viability and ATP concentrations instead of the ability of RBCs to deliver oxygen to the microvasculature or adverse effects on inflammation or immune function with stored RBCs.28 Current transfusion guidelines regarding indications for blood components were based upon expert opinion, experiments in euvolemic patients requiring elective surgery and data from the modified whole blood era which is no longer commonly available.[25], [26], 27 With new storage solutions, the age of transfused RBCs has progressively increased over time to a current limit of 42 days, without prospective studies evaluating the clinical effect of increased RBC storage length on critically ill patients.[22], [28]

Prompted by new data from combat casualties, an evolution of opinion is occurring in the trauma and transfusion medicine communities regarding the optimal resuscitative approach to hemorrhagic shock.27, [29], [30] Damage control resuscitation (DCR) is the overall guiding concept to emerge from the recent military experience.[29], [30], [31], [32] DCR which includes permissive hypotension as first described by Cannon in 1918 can be summarized as allowing the blood pressure to be slightly less than normal to promote thrombus formation while still providing enough perfusion to end organs.33 In other words, the goal of permissive hypotension is to prevent increasing the blood pressure to a threshold where a forming thrombus will not be able to achieve hemostasis, and re-bleeding occurs. This has been called “popping the clot”.34 This concept is practiced prior to surgical control. The practice and literature supporting permissive hypotension have been well documented and will not be discussed further.[32], [33], [34], [35], [36] DCR also advocates for the rapid control of surgical bleeding, prevention of acidosis, hypocalcemia and hypothermia, and for the limitation of excessive crystalloid use to decrease hemodilution. All of these principles are intended to prevent inducing or exacerbating a hypocoagulable state in these patients with severe traumatic injury who are at high risk of developing severe shock and coagulopathy. Hemostatic resuscitation is also a component of DCR and is a term to describe a unified transfusion approach to severe hemorrhagic shock.[31], [37], 38 Hemostatic resuscitation advocates for the transfusion of RBCs, plasma, and platelets in a 1:1:1 ratio and for the use of thawed plasma to achieve this ratio upon admission. This approach is also intended to minimize exacerbating a dilutional coagulopathy by replacing lost blood with plasma and platelet-containing products instead of early and large amounts of crystalloids and RBCs. Hemostatic resuscitation is also theoretically intended to address the consumptive coagulopathy and perhaps improve endothelial function which is currently being evaluated in multiple in vitro experiments. Adjuncts to hemostatic resuscitation include the appropriate use of coagulation factor and fibrinogen-containing products.[39], [40], 41, 42, 43 Fresh whole blood is also part of DCR in locations where it is available. Additional concepts that can be considered as a part of DCR include the preference for fresh RBCs,[19], [44], 45, [46], [47] and the potential use of thromboelastography to fine tune empiric blood product transfusion ratios and to direct the administration of coagulation factor products, and anti-fibrinolytics.24, [48]

The literature supporting these changes advocated by DCR has been met with appropriate caution and skepticism.49 A proposed change of practice should always be done carefully and thoughtfully and in a data-driven fashion, it is important to recognize that the literature supporting the current ATLS standard for the past 25 years was based upon 18 patients.50

While most of the literature reviewed is in patients with traumatic injury, further study is appropriate in different patient populations, such as those massively bleeding from ruptured aortic aneurysms,51 gastrointestinal or obstetric sources to determine if DCR concepts apply in these circumstances.

Section snippets

Traumatic coagulopathy and acute coagulopathy of trauma-shock

Traumatic coagulopathy is a hypocoagulable state that occurs in the most severely injured.[14], [15], 52, [53] There are multiple factors that may contribute to this coagulopathy, which evolve over time. Immediately after injury, hypoperfusion may cause coagulopathy as a result of increased anti-coagulation and hyperfibrinolysis via increased activated protein C production, tissue plasminogen activator and a concomitant decrease in plasminogen activator inhibitor concentrations and thrombin

DCR concepts and tools

Damage control resuscitation and hemostatic resuscitation are concepts that have been recently developed to describe what is currently thought by many to be the optimal resuscitative and transfusion approach to patients with hemorrhagic shock and immediately life-threatening injuries.[29], [30], [31], [32] Similar to damage control surgery the goal of damage control resuscitation is to “stay out of trouble instead of getting out of trouble”. Therefore in patients with severe traumatic injury

Alkaline and calcium therapy

While it appears to be important to prevent acidosis and hypocalcemia there is no evidence to support that the reversal of acidosis and hypocalcemia improve outcomes. In fact there are some studies that indicate when acidosis is treated coagulopathy is not reversed.121 While these practices are controversial and definitive studies have not been performed it is not unusual for alkaline solutions such as sodium bicarbonate or THAM (tromethamine) to be given to reverse acidosis and calcium

Massive transfusion protocols

A recent survey has been reported on the use of massive transfusion protocols (MTPs) world-wide in adult patients.24 In this survey it is self-reported that 45% of respondents use a MTP, 19% use one sporadically, and 34% do not. The development of a massive transfusion protocol for patients with severe life-threatening bleeding is important to standardize the approach to these patients and to provide structure and organization to what is usually a chaotic situation.125 Important aspects of a

Conclusion

Trauma is the most common cause of death for patients 1–40 years of age, death from hemorrhagic shock is the most common cause of preventable death within 6 h of admission, and the rapid identification and treatment of coagulopathy may improve survival. Therefore, it is imperative that we understand the pathophysiology of traumatic coagulopathy and ACoTS better, and develop methods to decrease death from hemorrhage. We must also continue to develop research protocols to determine the optimal

Conflict of interest statement

No conflict of interest.

References (127)

  • R.F. Bellamy

    The causes of death in conventional land warfare: implications for combat casualty care research

    Mil Med

    (1984)
  • J.B. Holcomb et al.

    Causes of death in special operations forces on the modern battlefield: 2001–2006

    Ann Surg

    (2007)
  • T.J. Esposito et al.

    Analysis of preventable trauma deaths and inappropriate trauma care in a rural state

    J Trauma

    (1995)
  • T.J. Esposito et al.

    Effect of a voluntary trauma system on preventable death and inappropriate care in a rural state

    J Trauma

    (2003)
  • H.C. Tien et al.

    Preventable deaths from hemorrhage at a level I Canadian trauma center

    J Trauma

    (2007)
  • F.A. Moore et al.

    Massive transfusion in trauma patients: tissue hemoglobin oxygen saturation predicts poor outcome

    J Trauma

    (2008)
  • R. Peng et al.

    Epidemiology of immediate and early trauma deaths at an urban level I trauma center

    Am Surg

    (1998)
  • A. Sauaia et al.

    Epidemiology of trauma deaths: a reassessment

    J Trauma

    (1995)
  • J.R. Hess et al.

    The coagulopathy of trauma: a review of mechanisms

    J Trauma

    (2008)
  • K. Brohi et al.

    Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis

    J Trauma

    (2008)
  • K. Brohi et al.

    Acute traumatic coagulopathy

    J Trauma

    (2003)
  • J.B. MacLeod et al.

    Early coagulopathy predicts mortality in trauma

    J Trauma

    (2003)
  • D.F. McLaughlin et al.

    A predictive model for massive transfusion in combat casualty patients

    J Trauma

    (2008)
  • P.C. Spinella et al.

    Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries

    J Trauma

    (2008)
  • P.C. Spinella et al.

    Warm fresh whole blood is independently associated with improved survival for patients with combat-related traumatic injuries

    J Trauma

    (2009)
  • S.E. Niles et al.

    Increased mortality associated with the early coagulopathy of trauma in combat casualties

    J Trauma

    (2008)
  • J.R. Hess et al.

    Giving plasma at a 1:1 ratio with red cells in resuscitation: who might benefit?

    Transfusion

    (2008)
  • J.R. Hess et al.

    Blood use in war and disaster: lessons from the past century

    Transfusion

    (2003)
  • D. Starr

    Blood

    (2002)
  • D.B. Hoyt et al.

    Management of coagulopathy in the patients with multiple injuries: results from an international survey of clinical practice

    J Trauma

    (2008)
  • T.B. Repine et al.

    The use of fresh whole blood in massive transfusion

    J Trauma

    (2006)
  • N.R. McMullin et al.

    Hemostatic resuscitation

  • A.B. Zimrin et al.

    Current issues relating to the transfusion of stored red blood cells

    Vox Sang

    (2009)
  • J.R. Hess et al.

    Damage control resuscitation: the need for specific blood products to treat the coagulopathy of trauma

    Transfusion

    (2006)
  • J.B. Holcomb et al.

    Damage control resuscitation: directly addressing the early coagulopathy of trauma

    J Trauma

    (2007)
  • A.C. Beekley

    Damage control resuscitation: a sensible approach to the exsanguinating surgical patient

    Crit Care Med

    (2008)
  • J.B. Holcomb

    Fluid resuscitation in modern combat casualty care: lessons learned from Somalia

    J Trauma

    (2003)
  • W.B. Cannon

    The preventive treatment of wound shock

    JAMA

    (1918)
  • J.L. Sondeen et al.

    Blood pressure at which rebleeding occurs after resuscitation in swine with aortic injury

    J Trauma

    (2003)
  • W.H. Bickell et al.

    Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries

    N Engl J Med

    (1994)
  • H.K. Beecher

    Preparation of battle casualties for surgery

    Ann Surg

    (1945)
  • O.L. Gunter et al.

    Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival

    J Trauma

    (2008)
  • J.C. Duchesne et al.

    Review of current blood transfusions strategies in a mature level I trauma center: were we wrong for the last 60 years?

    J Trauma

    (2008)
  • D. Fries et al.

    The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model

    Anesth Analg

    (2006)
  • H.K. Stinger et al.

    The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital

    J Trauma

    (2008)
  • K.D. Boffard et al.

    Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials

    J Trauma

    (2005)
  • P.C. Spinella et al.

    The effect of recombinant activated factor VII on mortality in combat-related casualties with severe trauma and massive transfusion

    J Trauma

    (2008)
  • P.C. Spinella et al.

    The risks associated with fresh whole blood and RBC transfusions in a combat support hospital

    Crit Care Med

    (2007)
  • J.A. Weinberg et al.

    Age of transfused blood: an independent predictor of mortality despite universal leukoreduction

    J Trauma

    (2008)
  • P.C. Spinella et al.

    Increased risk of DVT and mortality with the transfusion of older RBCs for patients with traumatic injuries

    Crit Care Med

    (2008)
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