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Resuscitation begins in the prehospital setting and continues in the ED. The priority for prehospital care is treatment of life-threatening conditions and rapid transport to an appropriate facility. For the hemorrhaging patient, this entails assuring adequate ventilation and oxygenation (including securing an airway if necessary), controlling external bleeding (if present), and protecting the spinal cord (if potentially vulnerable).
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In the ED, restore intravascular volume to reverse or limit systemic and regional hypoperfusion, maintain oxygen-carrying capacity so that tissue oxygen delivery meets demand, and limit ongoing blood loss and prevent the development of coagulopathy. From the moment resuscitation begins, prevent the development of hypothermia by keeping the patient warm and administering warmed IV fluids and blood products.11 Endogenous hypothermia occurs when heat production from cellular respiration is decreased by hypoperfusion and inadequate tissue oxygen delivery. Major causes of exogenous hypothermia are exposure and the use of below-body-temperature fluid and blood resuscitation. Apply external warming devices early to prevent external heat escape. Warming devices that allow for the rapid warming of infused fluid and blood should be used for all patients in whom large-volume resuscitation is undertaken.11
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AIRWAY CONTROL, VENTILATION, AND OXYGENATION
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If spontaneous ventilation is not adequate, intubate and ventilate to achieve an arterial hemoglobin oxygen saturation of ≥94%. Identify and treat potential respiratory conditions such as pneumothorax, tension pneumothorax, hemothroax, or upper airway obstruction.
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VASCULAR ACCESS AND MONITORING
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Establish adequate IV access concurrent with airway management. Large-bore (14- to 16-gauge in adults) peripheral lines may be adequate if two or more can be secured. Central venous access may be necessary. Intraosseous lines are suitable for resuscitation.
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Institute continuous ECG heart rate monitoring, continuous pulse oximetry, and, if possible, continuous end-tidal carbon dioxide monitoring. Monitor arterial blood pressure, mental status, and peripheral perfusion frequently. Bedside US is useful to identify intraperitoneal bleeding, assess cardiac function and volume status, and assist in central venous cannulation.12,13
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HEMOSTATIC-HYPOTENSIVE RESUSCITATION
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Hemostatic resuscitation begins in the field. In traumatic shock, the goal is deliberate hypotensive resuscitation, so that intravascular volume expansion is limited and blood pressure is not normalized. Blood pressure goals are systolic blood pressures of 80 to 90 mm Hg (10.7 to 12.0 kPa) in trauma and 90 to 95 mm Hg (12.0 to 12.7 kPa) in head injury. Normalization of blood pressure and the raising of hydrostatic pressure can increase hemorrhage. This is particularly evident in noncompressible hemorrhage where raising blood pressure could potentially "pop the clot" and reestablish active hemorrhage.
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Hypotensive resuscitation targets fluid resuscitation only when systolic blood pressure falls below 70 to 80 mm Hg (9.3 to 10.7 kPa) and/or there is evidence of decreasing mental status and, thus cerebral hypoperfusion. This practice has been widely adopted in combat casualty care (see chapter 302, "Military Medicine") and is partially supported by civilian studies.14 Preliminary results of traumatic injury comparing low versus traditional mean arterial pressure guided resuscitation indicate that a lower mean arterial pressure group sustains less blood loss, requires fewer transfusions, and has improved early and 30-day survival.15
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Hypotensive resuscitation is problematic for a number of reasons, including the inability to obtain frequent and accurate blood pressures and, in the civilian world, its application to the elderly and those with hypertension or cerebral vascular disease. Hypotensive resuscitation should not be used in patients with myocardial disease, cerebral ischemia, or traumatic brain injury. Obviously there is not an unlimited time span that patients can tolerate hypotensive resuscitation. From a cellular standpoint, patients will at some time incur irreversible damage from prolonged tissue hypoxia if adequate tissue oxygenation is not restored.
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ISOTONIC CRYSTALLOID SOLUTIONS
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Isotonic crystalloids, normal saline, and lactated Ringer's solution are the most commonly used resuscitation fluids in the United States. Concerns about each fluid are: (1) infusion of large volumes of either normal saline or lactated Ringer's solution can cause increased neutrophil activation, (2) lactated Ringer's solution can increase cytokine release and may increase lactic acidosis when given in large volumes, and (3) normal saline can exacerbate intracellular potassium depletion and cause hyperchloremic acidosis.16
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Crystalloid solutions are isotonic but hypo-oncotic, because they lack the large protein molecules present in the plasma. Low oncotic pressure results in substantial shifts of crystalloid to the extravascular space corresponding to the relative size of the intravascular and interstitial fluid compartments (Table 13-2). This was the physiologic basis for the 3:1 ratio for crystalloid to blood. For every amount of blood lost, three times that amount of isotonic crystalloid is required to restore intravascular volume because, at best, about 30% of the infused fluid stays intravascular. Based on this rule, a loss of 1 L of blood (about 15% to 20% of total circulating blood volume) would require about 3 L of isotonic crystalloid to restore normovolemia, assuming no ongoing blood loss. Bearing this in mind, the recommendations for initial fluid resuscitation have been to administer 2 to 3 L of crystalloid solution in acute hemorrhage and assess the response before initiating blood transfusion. In light of the new data reflecting improved outcomes with plasma-based resuscitation in traumatic hemorrhage, no more than 2 L of crystalloid solution should be administered before giving serious consideration to using blood products, especially if ongoing hemorrhage is expected.
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Common modifications of isotonic fluids include use of acetate instead of lactate in Ringer's solution, Hartmann's solution, and Plasma-Lyte (Table 13-3). Plasma-Lyte is the shared name for a family of isotonic crystalloid solutions available worldwide, marketed with variation in composition according to regional preferences. Solutions containing lactate or acetate are considered balanced crystalloids because they are buffered and have a lower chloride concentration compared to normal saline. There is evidence of low confidence that balanced crystalloids are associated with reduced mortality compared with normal saline when used for fluid resuscitation in sepsis.17
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Colloid solutions contain larger molecular weight particles that have oncotic pressures similar to normal plasma proteins. Therefore, colloids theoretically have several advantages during resuscitation. They would be expected to remain in the intravascular space, replacing plasma proteins lost due to hemorrhage, and more effectively restore circulating blood volume than crystalloid solutions. An argument favoring the use of colloids has been the concern that extravascular shift, or third-spacing, of infused crystalloid solutions has potential adverse effects, including pulmonary interstitial edema with impaired oxygen diffusion and intra-abdominal edema with diminished bowel perfusion. However, pathologic conditions, such as hemorrhagic shock and sepsis, lead to increased vascular permeability that can allow for eventual extravascular leakage of these larger colloid molecules.18
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The colloids used as resuscitation fluids are a heterogeneous group of agents with widely varying characteristics and effects. These agents have no proven consistent benefit, and there is evidence of harm in some patients with critical illness.19,20
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Hetastarch is a high-molecular-weight polysaccharide that has no proven benefit in critically ill patients.21 Currently, for logistical reasons of weight and size, hetastarch is the recommended fluid of choice for the far forward resuscitation of battlefield casualties.22 It is used as a part of a hypotensive resuscitation strategy with no more than 1000 mL to be given. The administration of 1000 mL of hetastarch is theoretically equal to the administration of 3 L of isotonic crystalloid.
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Hypertonic saline (7.5% saline) has been proposed as a potential crystalloid alternative that would limit the tissue edema effects that are often of concern with isotonic crystalloid solutions. Hypertonic saline has anti-inflammatory and immunomodulatory effects, with demonstrable decrease in lung and intestinal injury in animal models of hemorrhagic shock.18 The intravascular shift of fluid from the extravascular space may be potentially beneficial in head trauma patients by limiting cerebral edema, lowering intracranial pressure, and improving cerebral perfusion. The addition of dextran to hypertonic saline was aimed at sustaining the hemodynamic effect of the hypertonic saline. The volume of hypertonic saline solution that can be given during resuscitation is limited due to the potential for hypernatremia. Similar to hetastarch, an approach using smaller volumes (250 mL) of hypertonic saline (7.5%) has also been advocated. Randomized controlled trials have not demonstrated a clinically significant difference in outcome when hypertonic saline was compared with conventional isotonic fluid.23 However, these studies did not generally incorporate hypotensive resuscitation as a part of the overall strategy, and in the prehospital trail, transport times to trauma centers were short.24
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PACKED RED BLOOD CELLS
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Packed red blood cells (PRBCs) are the most commonly transfused blood product (see chapter 238). Using only PRBCs in the patient with traumatic shock and ongoing bleeding (without plasma and platelets) will do little to promote hemostasis and may not restore tissue oxygenation. If hemorrhage is definitively controlled, do not transfuse if the hemoglobin concentration is > 10 g/dL (> 100 g/L). Consensus recommendations for transfusion are a hemoglobin concentration between 6 and 7 g/dL (60 to 70 g/L) for those without cardiopulmonary, cerebral, or peripheral vascular disease.25 For a hemoglobin between 6 and 10 g/dL (60 to 100 g/L), use clinical judgement for transfusion.
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When possible, typed and cross-matched blood is preferable. However, if time and the patient's clinical status do not permit full cross-matching, type-specific blood is the next option, followed by low-titer O-negative blood. In U.S. blood banks, whole blood is not stocked, and only PRBCs are available (see the chapter 302 for further discussion of whole-blood transfusion).
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PRBC transfusion obviously restores lost hemoglobin. Using current preservatives, PRBCs can be stored for up to 45 days, and the average age of a unit of blood administered in the United States is about 21 days. Stored red blood cells can lose deformability, limiting their ability to pass normally through capillary beds or even resulting in capillary plugging. The oxygen dissociation curve is altered by loss of 2,3-diphosphoglycerate in the erythrocytes of stored PRBCs, impeding the off-loading of oxygen at the tissue level.26 Despite these changes, no consistent harm has been identified with use of "older" stored blood.27,28
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Fresh frozen plasma (FFP) is plasma obtained after the separation of whole blood from red blood cells and platelets and then frozen within 8 hours. A unit of FFP has a volume of 200 to 250 mL and contains all the coagulation factors present in fresh blood. Kept frozen, FFP can be stored for up to a year after the unit was collected. It takes between 15 and 20 minutes to thaw a unit of FFP in a 37°C water bath, which can limit availability in a massive transfusion situation. However, some major trauma centers and their respective blood banks keep thawed FFP (kept at 1°C to 6°C) available for immediate use. FFP may be kept thawed at this temperature for up to 5 days with little degradation of plasma proteins. FFP ABO compatibility is required, but because there are no red cells in FFP, Rh compatibility is less important, and universal donor FFP is typically AB+ (see chapter 238, "Transfusion Therapy").
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Platelets are collected from whole-blood donations or from single donors using apheresis techniques and can only be stored for up to 5 days. Six units of pooled random-donor platelet concentrate or one apheresis-collected single-donor platelet concentrate in an adult will increase platelet count up to 50,000/mm3 (50 × 109/L).
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MASSIVE TRANSFUSION PROTOCOLS
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Massive transfusion is generally defined as the requirement for >10 units of PRBCs within the first 24 hours of injury. Massive transfusion is not a substitute for definitive surgical hemostasis but enhances the ability to achieve surgical hemostasis and to limit complications.29,30 Draw sufficient specimens from the patient early in anticipated massive transfusion because once the patient has received close to one blood volume of transfused products, new blood specimens will contain so much donor blood that cross-matching of subsequent units is difficult. Initially use isotonic solutions to begin resuscitation in predetermined aliquots (250 to 500 mL) while assessing the likelihood of ongoing active hemorrhage and the need for, type, and timing of hemostasis and for hypotensive resuscitation.31,32 Variables predictive of need for massive transfusion include penetrating mechanism of injury, positive FAST examination, blood pressure <90 mm Hg (< 12.0 kPa), and pulse rate >120 beats/min.33,34 If hemorrhage is clinically significant and immediate hemostasis is not achievable, transition from crystalloid-based resuscitation to a plasma-based massive transfusion protocol.
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An estimated 10% of military trauma patients and 3% to 5% of civilian trauma patients receive massive transfusion.1 Soldiers receiving high ratios of plasma to PRBC (a plasma:PRBC ratio of about 1:1.4) have significantly improved survival rates than those receiving lower ratios (between 1:1.8 and 1:2.5). Additional evidence supporting this also comes from combat casualty care data suggesting that early administration of fresh whole blood (something not currently practical in civilian trauma) offers survival advantages.18,35 These survival observations using high plasma-to-PRBC ratios were confirmed by civilian studies, which also appear to indicate less incidence of trauma-induced coagulopathy.33,36
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High plasma-to-PRBC ratio resuscitation appears to also offer survival benefit independent of coagulopathy, and plasma may enhance cell survival by endothelial repair and reducing vascular permeability. It may also be that plasma is simply a superior fluid for perfusion and tissue oxygenation restoration. In addition, many trauma centers now include early platelet administration in predetermined ratios to plasma and PRBC in their resuscitation protocols based on findings that platelet function can rapidly decrease soon after trauma.1,34
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Studies routinely using FFP and platelets with PRBCs during massive transfusion have yielded mixed results on reducing mortality.34,37 The best ratio of PRBCs to platelets to FFP during massive transfusion is controversial.38 Some experts advocate a 1:1:1 ratio, although lower ratios of platelets and FFP have been used without evidence of inferiority.39 Likewise, the benefits with adjunctive agents such as calcium chloride, prothrombin complex concentrates, and fibrinogen concentrate included in some protocols are unknown. Tranexamic acid (an antifibrinolytic) is advocated early in the resuscitation process of major trauma victims based on the early fibrinolytic phase of trauma-induced coagulopathy and on clinical studies suggesting improved survival.40 An institution-specific massive transfusion protocol is recommended to guide the clinician when ordering blood components and to facilitate release from the blood bank (Figure 13-4). Tranexamic acid, an antifibrinolytic agent, is not currently a component of massive transfusion protocols in the United States. Its use is discussed in the chapters 254, "Trauma in Adults" and 302, "Military Medicine." If given, it must be administered as soon as possible and within 3 hours of injury. The dose is 1 gram IV bolus in 100 mL normal saline.
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PRBCs and FFP contain citrate that can complex calcium, producing life-threatening hypocalcemia.41 Most massive transfusion protocols include the administration of calcium and monitoring of ionized calcium. Calcium chloride is preferred over calcium gluconate because a well-perfused liver is required to liberate more free calcium from calcium gluconate. Maintain ionized calcium levels at or above 0.9 mmol/L.42
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Thromboelastography and Thromboelastometry
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The blood coagulation system consists of nearly 80 very tightly coupled biochemical reactions. Conventional coagulation testing such as the prothrombin time and activated partial thromboplastin time do not take into account the cellular components of the clot such as red cells and platelets. Because the blood clot itself consists of a complex three-dimensional network of cross-linked fibers made of fibrin, platelets, and red cells entrapped within this mesh, newer viscoelastic tests such as thromboelastography or thromboelastometry are being developed to measure the physical and dynamic characteristics of clotting. Thromboelastography and thromboelastometry can detect trauma-induced coagulopathy and can be used to guide massive transfusion protocols better than traditional prothrombin time and activated partial thromboplastin time assays.43 However, impact on clinical care is uncertain at this time.43