Damage Control and Immediate Resuscitation for Vascular Trauma

Damage Control Definitions

The term “damage control” originates from maritime terminology, relating to the emergency measures used to manage during the emergency crisis of the sinking of a ship. This is the principle that action taken is that which is necessary to keep the ship “afloat” in times of crisis rather than comprehensively completing the repair. When applied to trauma, “damage control” incorporates a mosaic of interventions that collectively provide an effective hematological and mechanical “plug” to arrest blood loss and keep the patient “afloat.”

Damage control resuscitation (DCR) is formally defined as “a systematic approach to major trauma combining the <C>ABC (catastrophic bleeding, airway, breathing, circulation) paradigm with a series of clinical techniques from point of wounding to definitive treatment in order to minimize blood loss, maximize tissue oxygenation, and optimize outcome.” DCR reflects advances in combat casualty care made in the recent military campaigns in Afghanistan and Iraq and spans the spectrum of vascular trauma management. This practice has evolved as an overarching concept that draws together all those interventions. It starts from immediate first aid measures delivered at the point of injury, such as application of tourniquets and optimization for surgical intervention by effective volume resuscitation, through to the critical care unit with the management of coagulopathy, systemic inflammatory response, and any associated organ dysfunction, which is encompassed by the emerging concept of endotheliopathy.

DCR includes damage control surgery (DCS). DCS is the operative stage of DCR that sacrifices the completeness of the immediate surgical repair in order to address the physiological consequences of the injury. DCS has come to mean a time-limited surgical procedure (i.e., abbreviated operation) where the imperative is the minimal intervention to save life and limb before the trauma triad of death of hypothermia, coagulopathy, and metabolic acidosis becomes established.

Currently there is no universally agreed time period where surgical intervention must be complete. Previously this was thought to be time limited to a maximum of 60 minutes. As our understanding and delivery of resuscitation has improved, so this arbitrary 60-minute rule has become less critical. Patients with significant injury severity are arriving to theatres with less physiological derangement, and so increasing the options available to surgeons for their operative repairs. The main determinate of surgical time should be the physiological state of the patient. The more effective and coordinated the early resuscitation, the more options become available to the surgeon.

Once the initial surgery is complete, the resuscitation must continue and this will likely occur in the critical care unit. Unlike DCS, DCR is not time limited and is complete once a patient’s physiology is returned to normal. It is often thought that once a patient has arrived in Critical Care that the job is done. This is not the case and DCR principles, especially the use of blood products, should continue until the patient is fully resuscitated. Thus, from the anesthetist’s perspective, DCR occurs from the point of injury by minimizing the insult, through the initial resuscitation, to optimize the patient for the further insult of surgery, and on to critical care until the patient’s physiology is returned to normal.

Hypothermia

The activation of the coagulation cascade is an enzymatic process and therefore requires two physiological conditions to function. Tissue factor (Factor VIIa) activity decreases by 50% at 28°C and platelet adhesion to Von Willebrand Factor is essentially absent below 30°C. Trauma patients have often suffered a period of exposure during the prehospital phase and, when combined with significant blood loss, are extremely prone to hypothermia. Combined with interventions such as fluid resuscitation with nonwarmed fluids or cold blood products, the vasodilatory effect of general anesthesia, and the exposure of body cavities during surgery, it becomes easy to see how hypothermia is an ever-present risk during this initial phase of DCR.

Clinically significant effects of coagulopathy have been shown where core temperature is below 34°C and mortality from hemorrhage is markedly increased when core temperature is below 32°C ; however, what is not clear is whether the hypothermia in itself is an independent factor or merely a marker of the severity of shock and physiological compromise.

Hemodilution

Where there is significant disruption to the vasculature, larger clots are required, consuming coagulation products such as platelets, coagulation factors, and fibrinogen. Within earlier versions of advanced trauma life support (ATLS) teaching, liberal fluid resuscitation was advocated, which aimed to improve tissue perfusion, but risked worsening coagulopathy by diluting coagulation factors within an already depleted blood volume. Dilution has been shown to have detrimental effects on coagulation and impair hemostasis.

For the same reason, the sole use of packed red cells as a means of volume replacement will also lead to a dilutional coagulopathy as platelets, coagulation factors, and fibrinogen are not replaced. Mathematical models have suggested that use of 1:1:1 ratio with red cells, plasma, and platelets will minimize the dilution and provide a solution closest to whole blood. Experience from recent military campaigns in Afghanistan and Iraq have shown that this ratio is possible and does have better outcomes —findings also replicated in a civilian setting in the PAMPER Trial. Of note, component therapy itself has a dilutional effect as each component has its own additive solutions. In order to minimize the dilutional effects of component therapy, the military, for many years, have used whole blood in the sickest patients. Whole blood for bleeding trauma patients has increased in civilian practice in recent years, particularly in the United States, where the American Association of Blood Banks recently endorsed the use of whole blood. Whole blood in civilian trauma has less uptake outside of the United States, but is now used in the United Kingdom, Israel, and Norway.

Acidosis

Trauma to vasculature leads to significant blood loss, which itself will lead to hypovolemia and therefore hypoperfusion, along with reduced oxygen delivery to peripheral tissues. At the cellular level, anaerobic respiration becomes the predominant means of energy production, which leads to the production of lactic acid and therefore a metabolic acidosis. Within animal studies, acidosis has shown to have multiple effects on coagulation, such as reducing the activity of clotting factors (50% at pH 7.2, 70% at pH 7.0, and 90% at pH 6.8) and increasing degradation of fibrinogen, i.e., hyperfibrinolysis.

Tissue Trauma

Although acidosis does play a significant part in trauma coagulopathy, it is not the only factor, as significant clinical coagulopathy is detected even with mild degrees of acidosis, and coagulopathy can still occur even when acidosis is corrected. It is now apparent that tissue damage and disruption of the endothelium, which leads to the exposure of the subendothelial layer and release of tissue factor, also has implications for coagulation.

The exposure of subendothelial layer leads to activation of plasma proteases, which leads to the activation of the coagulation cascade and so the formation of thrombin and fibrin. In significant trauma, where there are multiple sites of endothelial disruption, there is activation of procoagulation factors such as X, II, V, and VIII. These factors then subsequently enter the systemic circulation and generate thrombin, affecting macro and microvascular flow as well as giving rise to a process where platelets, coagulation factors, and fibrinogen are consumed and coagulopathy develops.

Tissue disruption also leads to release of tissue-type plasminogen activator (tPA) and increased tissue expression of tPA. tPA activates plasmin from plasminogen, which lyses the clot, i.e., fibrinolysis. Within the context of hemorrhagic trauma, hypoperfusion leads to further release of tPA from the Weibel-Palade bodies within endothelium and further weakening of the clot.

The combination of excessive activation of coagulation with hyperfibrinolysis has led to trauma-induced/-associated coagulopathy described as the “fibrolytic phenotype” of disseminated intravascular coagulation.

Endothelial Dysfunction

The formation of lactic acid and other metabolites can be seen as a surrogate for oxygen debt, which needs to be addressed and “repaid” in a timely manner, or else excessive morbidity and mortality due to multiorgan failure is risked. Multiorgan failure is traditionally viewed as dysfunction of one or more of the respiratory, cardiac, renal, and hepatic systems. The blood and endothelium unit should also be considered an organ, which may also suffer from the effects of prolonged hypoxia and acidemia and thus oxygen debt. This concept has been described as “blood failure” by the Trauma Hemostasis and Oxygenation Research (THOR) Network.

In health, the endothelium undertakes a range of physiological functions including control of vasomotor tone, maintenance of blood fluidity, and regulated transfer of water, nutrients, and leukocytes across the vascular wall, as well as regulation of immunological cell migration. The inner endothelial wall has anticoagulative properties via various systems such as the thrombomodulin/protein C system, heparinoid-lined glycocalyx, and potential release of tPA and urokinase plasminogen activator. Although not fully understood, it has been proposed that damage to the endothelium, either by direct damage by trauma or by hypoperfusion, leads to the release of these anticoagulative factors and the glycocalyx into the systemic circulation, leading to global hypocoagulability should the insult be of significant magnitude.

Other factors may lead to further endothelial dysfunction. The initial procoagulative state leads to microemboli and therefore microvascular occlusion, compromising flow and oxygen delivery. There is also increased paracellular permeability due to loss of endothelial integrity and tissue edema—compounding the impairment of oxygen delivery and increasing oxygen deficit. In the face of global hypoperfusion, there will be hyperstimulation of the sympathetic-adrenal system leading to high circulating levels of catecholamines. High levels of catecholamines have been implicated as a proposed mechanism of endothelial damage known as shock-induced endotheliopathy, which may be common to other acute critical illness syndromes such as postcardiac arrest syndrome, sepsis, and myocardial infarction.

As a better understanding of the mechanisms of trauma-related coagulopathy is developed, we will find better tools to quantify the contributory factors described previously. Although the extent of tissue damage and therefore the extent of endothelial damage is not a reversible factor, trying to limit endothelial dysfunction and further damage by ensuring adequate oxygen delivery and limiting oxygen debt is desirable. Currently, there is no way of measuring or quantifying oxygen debt and, although lactate clearance has been quoted as a useful marker for resuscitation end point in the critically ill (and probably our best widely measurable marker), it does not signal whether oxygen debt has been repaid.