Initial traumatic injury can be a combination of blunt force tissue injury, blood loss and hypoxia due to impaired pulmonary function. This talk will review the pathophysiology of the initial hours of traumatic injury and outline an up-to-date approach to managing traumatic shock in the first 6 hours.
Pathophysiology of Traumatic Shock
Blunt force trauma, caused by incidences such as motor vehicle accidents, dog bite injuries or falling from a height, is associated with changes in tissue perfusion and a cascade of pro-inflammatory mediator release. Lack of oxygen to the tissues leads to release of danger-associated molecular pattern molecules (DAMPs) that act as chemo-attractants and activate immune cells, such as neutrophils and monocytes. Molecules such as high mobility group box-1 (HMGB1) and cell components, such as mitochondrial or cell-free DNA, are released early in trauma and can promote an acute inflammatory response.
Release of DAMPs is likely one of the key early steps to recruitment of neutrophils and monocytes to the site of injury, but DAMPs are also probably one of the main instigators of distant organ injury as a part of a ‘second hit’.
In concert with the release of DAMPs, the innate immune system is promptly activated, including neutrophil recruitment and complement activation. Inflammatory cytokines are also quick to rise within hours of traumatic injury, including interleukin (IL)-6, IL-1β, IL-8, IL-10 and tumour necrosis factor-α (TNFα). They are joined by a host of other pro-inflammatory and vasoactive mediators released from the endothelium, immune cells and damaged cells. These mediators are designed to mediate tissue recovery and repair and mitigate organism invasion; however, the response can be excessive, leading to systemic inflammatory response syndrome (SIRS) and, potentially, multiple organ dysfunction syndrome (MODS).
In addition to the inflammatory cascade that occurs, ischaemia due to hypovolaemia adds additional endothelial and tissue cell injury. After reperfusion, complement activation, production of reactive oxygen species, platelet activation and neutrophil margination prompt a cascade of pro-inflammatory events that can lead to distant organ injury. All of these responses can contribute to increased vascular permeability, loss of vasomotor tone (vasodilation) and remote organ damage in the hours and days after an ischaemic event.
Acute traumatic coagulopathy (ATC) can develop rapidly in trauma patients, not only due to dilution from intravenous fluids but also as a part of the pathophysiological response. The majority of ATC is most likely caused by activation of the protein C pathway. Activated protein C has a direct inhibitory effect on coagulation proteins (V and VIII) and plasminogen activator inhibitor-1, causing hypocoagulation and enhanced fibrinolysis. Tissue plasminogen activator is also released secondary to endothelial activation. One study that measured coagulation variables before intervention in dogs with severe trauma found hypercoagulability in a third of the dogs.1 In contrast, a study in dogs with spontaneous haemoperitoneum found the presence of hypocoagulability, protein C deficiency and hyperfibrinolysis.2 Another study that evaluated dogs with trauma within 12 hours of hospitalization found that hypocoagulation was associated with mortality.3
Both platelet hyperreactivity and hyporeactivity have been also observed in trauma, likely reflecting earlier and later effects of injury, respectively. One canine model of haemorrhagic shock has also identified platelet hyporeactivity,4 whereas another did not.5 Acidosis, associated with shock, interferes with enzymatic reactions in the body and also contributes to hypocoagulation. Hypothermia, often present in the early hours after traumatic injury, also contributes to hypocoagulation and poor peripheral blood flow.
The combination of acidosis, coagulopathy and hypothermia—known as the lethal triad—contributes to morbidity and mortality in human trauma patients. Several studies have associated mortality with acidosis in dogs with trauma.3,6 Hypoxia due to lung injury may also contribute to complications. The damage done by these conditions in combination with hypovolaemia can propagate an ongoing inflammatory response and coagulopathy, for the reasons outlined above. If patients survive the initial 24 hours, then a secondary ‘immune paralysis’ can ensue, making the patient susceptible to sepsis and MODS. These complications can lead to death of the patient despite best efforts to re-establish effective circulating blood volume, replace coagulation factors and achieve metabolic homeostasis.
The First Phase of Resuscitation
Most trauma patients will present with physical examination signs consistent with vasoconstrictive shock, such as tachycardia, pale mucous membranes and weak femoral pulses. Even if the changes appear mild (such as only the presence of tachycardia), the possibility of hypovolaemia should be addressed before any other actions are taken. Even without blood loss, trauma patients may be relatively hypovolaemic due to, for example, shedding of the endothelial glycocalyx or regional vasodilation (such as splanchnic) due to inflammatory mediators. This is especially true for dogs and is why their gut is called the ‘shock’ organ. Although rare, patients may also have an obstruction to blood flow, such as pericardial tamponade.
On initial assessment when abnormal perfusion parameters are first identified, the ‘first phase’ of resuscitation should be commenced immediately. This includes a fluid challenge to test if the patient’s physical examination abnormalities respond to blood volume expansion. Blood volume expansion can be achieved by a number of different types of fluid therapy including isotonic crystalloids, hypertonic saline and synthetic colloid fluids. Transfusion products are only appropriate for the first phase if there is evidence of massive bleeding combined with severe shock.
Isotonic crystalloids provide rapid blood volume expansion to re-establish tissue perfusion and are easily excreted. They can be titrated according to the volume deficit. However, aggressive resuscitation with isotonic crystalloids in the first phase can contribute to bleeding, damage to the endothelium and peripheral oedema. All fluids that dilute plasma constituents cause a dilutional coagulopathy. This is often recognised by mildly prolonged coagulation tests after a bolus. This effect may not be clinically relevant unless combined with bleeding and traumatic coagulopathy. Also, the larger volume causes a spike in blood volume expansion before redistribution,7 which may disrupt an established blood clot. Other effects of rapid fluid administration may contribute to inflammation (see notes for ‘The Adverse Effects of Rapid Fluid Administration’). Doses of isotonic crystalloids should be judicious and titrated to effect for these reasons. However, the benefits of isotonic crystalloids usually outweigh the adverse effects and remain the most appropriate fluid for the first phase of resuscitation. Overdosing crystalloids likely has less adverse effects than overdosing other fluid types.
Hypertonic saline has limited effects in regard to blood volume expansion,7 though it can be useful for reducing cerebral oedema in traumatic brain injury.8 The use of synthetic colloids has become controversial.9 There is experimental evidence that some synthetic colloids cause mild platelet dysfunction and deficits on coagulation tests, whereas other studies have shown no effect beyond hemodilution. There is currently no strong evidence that synthetic colloids cause clinically relevant harm in veterinary patients. However, in the actively bleeding patient, these fluids must be used judiciously and in small doses, if at all. If blood products are an immediate option, then they should be considered instead. Based on our group’s research that is yet to be published, gelatine products are best avoided due to multiple adverse effects in the experimental setting.
Second Phase of Resuscitation
During initial blood volume expansion, the patient is usually surveyed again by physical examination as well as point-of-care ultrasonography, if available. This gives the clinician an idea of where the major injuries are located, if there may be significant blood loss (such as intra-abdominal) and if other immediate interventions are required, such as thoracocentesis. If the patient continues to show signs of shock, despite initial blood volume expansion and analgesia, then there are several options to consider, including further fluid therapy, transfusion, antifibrinolytic therapy and, in rare cases, immediate surgical intervention.
Transfusion products, especially transfusion of stored red cells, are associated with increased free iron concentrations and a pro-inflammatory response. Red cell products that have been stored for a longer period have been associated with coagulation disturbances and thromboembolic disease in canine recipients.10 There is also risk of acute reaction with transfusion of red cells and plasma.11 Due to these known adverse effects of transfusion products, they should only be administered for the clinical indications of anaemia and coagulopathy.
If the patient requires further blood volume expansion, has no evidence of coagulopathy or active bleeding, has no prior history of renal disease and there is physiologic justification for restricting interstitial fluid accumulation, then synthetic colloid solutions may be considered in this phase of resuscitation (preferably low-molecular-weight hydroxyethyl starch [HES]). If a patient requires blood volume expansion and there is a good reason to avoid isotonic crystalloids, then synthetic colloids currently have the least amount of clinical evidence associated with harm, compared to plasma and human albumin products. However, due to the possible adverse effects of coagulopathy in a trauma patient, doses should be limited to less than 20 mL/kg in a 24-hour period. Prospective clinical trials are still needed to determine if synthetic colloids, particularly HES, are harmful to veterinary patients.
Administration of an antifibrinolytic may be beneficial in the initial phases of resuscitation, especially for patients with active bleeding or evidence of hyperfibrinolysis on viscoelastic coagulation tests. Although the benefits of antifibrinolytic therapy, such as tranexamic acid, have been well identified in human trauma patients, the evidence in veterinary medicine is limited. However, tranexamic acid is unlikely to cause harm when administered as a slow IV bolus followed by a constant-rate infusion for several hours,12 and may be beneficial in a bleeding patient.
Decision-making trees will be presented in this talk, reflecting the author’s approach to traumatic shock. Attendees are welcome to request a copy of the flow diagrams by email.
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