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The refinement of damage control resuscitation (DCR) principles represents one of the major advances in trauma surgery during recent years. The high tempo and large volumes of causalities during combat operations lasting over a decade has provided a crucible for this change. Patients with trauma necessitating a massive transfusion require vigilant attention throughout their treatment—from point of injury, to the first MTF, definitive surgery, and throughout transport. This paradigm is focused on three tenets (1) minimizing crystalloid use during early resuscitation, (2) permissive hypotension, and (3) transfusion of blood products which resemble whole blood as closely as possible.17
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Damage Control Criteria Recognition—The Lethal Triad
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Acute coagulopathy of trauma (ACT) is caused by the combination of severe tissue injury and shock and it is mediated by activated protein C.18 The infusion of high chloride containing crystalloid solutions exacerbates ACT by inducing the lethal triad producing trauma induced coagulopathy (TIC). The lethal triad is defined by the presence of acidosis, hypothermia, and coagulopathy in the setting of traumatic hemorrhage. It is a vicious cycle of clinical findings associated with increased mortality compared with noncoagulopathic patients.19 Once this vicious cycle is induced, it is difficult to reverse as each component of the triad results in worsening of the others. There is tremendous interest in developing criteria to identify patients who require DCR early. Unfortunately, there is no single scoring system which will distinguish all traumatic coagulopathy patients requiring DCR.20 Mechanism and clinical suspicion remain important factors for early recognition. Current predictors used by the US military as established by the Clinical Practice Guideline on DCR at forward facilities are included in Table 52-3 and will be discussed below.7
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Acidosis, generally recognized as a pH less than 7.25, represents part of the lethal triad. A base deficit of greater than 6 has been demonstrated as an independent risk factor for coagulopathy and is associated with increased mortality.21 Recognized via a rapid laboratory value acidosis provides early indication of metabolic derangements from profound hemorrhage. Acidosis impairs both platelet function and the coagulation cascade.20
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Coagulopathy is concerning in the setting of trauma as both an indicator of increased mortality and a barrier to hemorrhage control. An INR greater than 1.5 is an independent predictor of massive transfusion and is usually available in the resuscitation bay.22 Impaired coagulation requires replacement of clotting factors and platelets rather than red cells alone.
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Hemoglobin and Hematocrit
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Anemia secondary to acute blood loss is another measure easily determined in the trauma bay. Traditional teaching dictates that the hemoglobin and hematocrit will not initially change immediately after hemorrhage as red cells and plasma are lost in equal proportions. Based on this premise anemia would not be evident until after plasma levels equilibrate for the lost whole blood volume. However, when hemoglobin measures are obtained within the first 30 minutes of arrival to the emergency department, nearly 90% of trauma patients with major bleeding will be identified.23 A hemoglobin less than 11 g/dL has been determined to be an independent predictor of massive transfusion.22
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Systolic Blood Pressure
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The presence and degree of hypotension provide measures for diagnosis, prognosis, and treatment in the bleeding trauma patient. Systolic blood pressure less than 90 mm Hg is commonly used as the definition of shock. Advanced Trauma Life Support teaching also advocates for the use of blood pressure in its classification of hemorrhage. However, once a systolic blood pressure below 90 mm Hg is reached this already corresponds to a 40% loss of circulating volume—a late finding.24 Earlier changes in blood pressure have been demonstrated to be indicative of changes in prognosis. A large study of NTDB patients found the prognostic cutoff below 110 mm Hg, below which mortality increased by 5% for every decrement of 10 mm Hg.25 An important note, however, is that prognostic criteria cutoffs do not necessarily translate into therapeutic goals. Permissive hypotension is an example of this. A goal of DCR is to keep the SBP at approximately 90 mm Hg prior to definitive surgical hemorrhage control. Previous experiences with SBP goals at normal levels translated into increased mortality.26 While a SBP of less than 110 mm Hg is useful to determine severity of hemorrhagic insult, it should not be used as an early resuscitation target.
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Damage Control Intervention—Resuscitative Fluid Strategies
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Crystalloid Minimization and Selection
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Crystalloids have long been used in trauma as volume expanders to support blood pressure. However, select resuscitative fluids can propagate acidosis and normotension may exacerbate hemorrhage. Rather than being resuscitative as intended, crystalloids can increase morbidity and mortality.
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In far forward prehospital settings, blood products are rarely available and crystalloids remain one of the options available for fluid resuscitation. In these situations it is important to consider which type of crystalloid to utilize. The most common fluids used are normal saline (NS) and lactated Ringer’s (LR). There are several key differences between the two, but the most notable is the fluid pH.
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Saline infusions were developed in 1831 after observed “decreased fluidity” of blood among cholera patients. Despite the widespread use of NS, there is no available scientific basis for its initial use. The closest evidence is an in vitro study by a Dutch chemist, Jakob Hamburger, in 1888 noting a shared freezing point between human plasma and 0.9% NS of –0.52°C.27 Ringer’s solution was developed in the 1880s by Sydney Ringer with the purpose of maintaining activity of a frog myocardium using electrolyte constituents resembling plasma.28 Later, lactate was added to Ringer’s original solution (by Alexis Hartmann) to combat the effects of acidosis through conversion to bicarbonate in the liver.
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Several animal studies over the past decade have supported improved outcomes with LR over NS.29,30,31 Counter-intuitively, hyperkalemia is increased with NS as opposed to LR. Hyperkalemia is attributed to extracellular shift of potassium due to the low pH of 5.0 found in NS (Table 52-4).32 In both LR and NS there is concern for dilution of clotting factors compounding coagulopathy. There are situations when judicious crystalloid resuscitation is appropriate. Part of this strategy includes the target blood pressure for resuscitative efforts.
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Permissive Hypotension
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Walter Cannon, a US Army trauma surgeon during the World War I, noted that restricting fluid administration prior to surgery limited bleeding. Similarly during World War II, anesthesiologist Henry Beecher noted improved outcomes in patients whose SBP was maintained in the 1980s between injury and the OR.26 These early observations have been reconfirmed in current DCR practices.
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Permissive hypotension is designed to avoid clot destabilization prior to definitive hemorrhage control. Fluid restriction contributes to permissive hypotension and avoids acidosis, hypothermia, and coagulopathy caused by high-chloride-containing fluids infused at room temperature.
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Blood Transfusion Strategies
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The third tenet of DCR is transfusion of blood products in ratios resembling whole blood. This strategy comes directly from the military experience after observing mortality trends associated with blood product ratios. Borgman et al reviewed 246 patients at a US Army Combat Support Hospital in Iraq evaluating ratios of plasma to red cell units and association with mortality rates.33 This study revealed a significant decrease in mortality as the ratio approached 1:1. Results of Borgman’s study provided confirmation for changes in the CPGs, which had already taken effect during 2004. The basis for the CPG changes in 2004 had mainly been expert opinion.
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The move away from transfusion of low plasma to red cell ratios marked an important transition from previous practice. The use of individual blood product components had been dictated by laboratory parameters rather than the patient’s clinical situation.17 Patients would receive plasma for an elevated INR or PTT rather than the presence of severe hemorrhage. Similarly, platelet administration had been guided by measured thrombocytopenia. The transition to lower ratios was based on a paradigm shift toward matching the whole blood that was being lost. Despite changes in both military and civilian DCR guidelines, the ideal ratio remains elusive.
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The goal of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study was to provide further evidence regarding blood component ratios, particularly early transfusion of plasma and platelets. A total of 1245 patients from 10 US level 1 trauma centers receiving at least 1 unit of RBCs within 6 hours of admission were in the original study group. Multiple separate subgroup analyses have been published from the data obtained. Among 905 patients from the main study group who also received greater than or equal to 3 component unit transfusions, increased plasma: RBC ratios were independently associated with decreased 6-hour mortality. Hemorrhagic deaths predominated in the first 6 hours. Patients with high ratios either tended to receive a 1:1:1 or 1:1:2 ratio (plasma to platelets to red blood cells).34,35
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The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial further addressed the question of ideal transfusion ratios. A total of 680 patients were randomized to a 1:1:1 versus a 1:1:2 ratio during active resuscitation at 12 level 1 trauma center in the United States. There was no statistically significant difference in 24 hour or 30 day mortality. However, the 1:1:1 group achieved hemostasis more frequently and were less likely to die of hemorrhage in the first 24 hours.36
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First In First Out versus Last In First Out
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There is increasing evidence that increased age of blood is associated with worse outcomes due to the “storage lesion” attributed to decreased 2,3-DPG, depletion of nitric oxide, and impaired RBC conformational change.37,38,39 A correlation has been established between RBC age and infection, organ dysfunction and mortality among trauma patients.40 Thus, it is appealing to use the youngest blood available for the sickest patients.
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Traditionally, blood banks have used a strategy of “first in first out” (FIFO) for blood product allocation. This concept is similar to stocking milk at the grocery store—even though younger cartons may be available older ones are sold first to prevent waste due to expiration. The unit closest to the expiration date of 42 days will always be given first.
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Due to recognized risks of aged blood, alternative allocation strategies have been proposed. One group of investigators from Stanford was able to create a model which allowed for an RBC age cutoff of 14 days and a “last in, first out” strategy without increased unit utilization or waste. Success of their model resulted from a supply excess with a supply (donations) to demand (blood products used) ratio of 1.06.41 Due to documented improvements in survival and recent feasibility studies, current military experts and the US Army CPGs advocate for a last in first out (LIFO) strategy during massive transfusion (cite DCR CPG).18 This strategy does result in a significant waste of blood product but the benefit to the patient is believed to outweigh the cost of the wasted blood products. Two recently published prospective randomized trials performed in critical care patients and cardiac surgery patients (ABLE and RECESS published this week in NEJM) revealed no differences in clinical outcomes in patients who received older red blood cells versus younger red blood cells but a similar trial has not been performed in trauma patients.
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Adjuncts and Alternatives to Component Therapy—Lyophilized Plasma and Cryopreserved Red Blood Cells
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Storage conditions remain a limiting constraint on the availability of blood products during military operations. For the combat medic weight is paramount as everything needs to be carried and refrigeration is rarely available. At the FST or CSH the refrigerated shelf life of PRBCs can limit availability of this product.
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The benefits of early plasma transfusions have been recognized with new information on component therapy ratios. The most common form of plasma, fresh frozen plasma (FFT), must be stored at –18°C and then undergo a thawing process in a warming bath for approximately 15–20 minutes.42 Both of these processes require specialized bulky equipment which is difficult to house or completely absent at far forward facilities and for first responders. However, lyophilized (freeze dried) plasma represents a light-weight, easily carried option which can be stored at room temperature. Lyophilized plasma represents another rediscovery of previous military advances finding new uses again today. In World War II lyophilized plasma was used due to the same concerns as today—transport and shelf life. Unfortunately, pooled plasma that was not screened for viral pathogens was used at that time—with associated increased viral infection risk. Thus, the practice was abandoned. With the ability to screen and test for disease more effectively, lyophilized plasma is being reinvented. Recent work evaluating the properties of lyophilized plasma have demonstrated 86% of prelyophilization coagulation factor activity (18) and decreased blood loss compared with FFP in a combat relevant swine model.43,44 European production of lyophilized plasma has continued in recent years with notable use by the French and Germans in overseas military activities at Roles 1, 2, and 3 facilities and MEDEVAC platforms.45
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Cryopreserved red blood cells (CPRBC) were first used on a large scale use by the US military during the Vietnam War after large volumes of standard PRBC preparations were being discarded due to age. The technique currently approved for use by the FDA involves the use of a glycerol buffer to prevent crystal formation associated membrane disruption and cellular damage due to large temperature changes. The red cells are stored at –80°C with 40% glycerol weight/volume within 6 days of collection. They can be stored for up to 10 years before they are thawed and deglycerolized for patient use.46,47 The storage lesion is minimized while also allowing for larger inventories of blood in settings with sporadic or unpredictable use. Despite these benefits, including FDA approval, CPRBCs are only being employed in rare specific situations today. This is likely attributed to the increased time (~90 minutes) and cost associated with the thawing and deglycerolizing process. They have been used increasingly in current military operations with hundreds of units provided and are used in an equivalent manner to PRBCs. They are also part of the response plan for potential large-scale natural or man-made disasters domestically.
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Whole Blood versus Component Therapy
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Historically, the first blood transfusions in the early 1900s were whole blood as opposed to component therapy (CT) in common use today.48 During the first two world wars a combination of warm fresh whole blood (WFHB) and stored whole blood was used with a peak of 2000 units per day in 1945.49 Military medicine played a significant role in the initial transition to component therapy during the Vietnam era when long distances and transport times were associated with expiration of whole blood units. However, this transition to CT occurred in the absence of evidence comparing its risks, benefits or efficacy with whole blood.50 Despite this paucity of initial evidence, CT has become the standard for blood banking.
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The reexamination of WFHB in the current era was also led by the military community. Logistical restraints are imposed on effective CT transfusion at forward operating bases owing to long supply chains and limited processing and storage of components. Platelets have a very short shelf life (5 days) and require constant agitation. FFP and cryoprecipitate must be stored at –20°C and require the capacity for thawing. Additionally, the storage capacity for all components is limited.51 WFHB addresses many of these limitations.
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The theoretical clinical benefits of WFHB include avoidance of dilution, absence of anticoagulant additives, consistency with damage control surgery principles and blood product age. As discussed earlier, the ideal transfusion ratio for RBCs, platelets, and plasma is 1:1:1 and WFHB intrinsically matches this ratio. The “storage lesion” is a concern with whole blood that is distributed centrally due to long transit times. However, negligible storage time is present when WFHB is obtained locally.
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In practice, WFHB requires a “walking blood bank” consisting of volunteer donors who are not needed immediately for warfighting activities or active resuscitation of the patient(s). The operating base must be of sufficient size to have enough blood donors who meet the above criteria. The most forward and remote facilities which could benefit most from WFHB capabilities often do not have enough personnel to maintain a walking blood bank. Additionally, coalition forces frequently have their own rules regarding who can either donate or receive WFHB, citing the inability to perform robust serologic testing of transmissible disease. It is not uncommon for a participating force to restrict donation and transfusion of WFHB to their own nationality. Current US practice is guided by the US Army Institute of Surgical Research Clinical Practice Guideline for Massive Transfusions.7
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WFHB transfusion was instituted due to the need for blood early in resuscitation at remote locations. More recently the outcomes of this decision have been reported with encouraging findings. In a retrospective review of 354 patients comparing those who received WFHB versus those who received CT alone in a deployed setting both 24-hour and 30-day mortality were significantly decreased supporting findings from a previous study by the same author.48,52 Prospective trials comparing WFHB versus CT have not been performed. However, excitement regarding early results has been tempered by the inherent limitations of comprehensive transmissible disease donor screening.
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Damage Control Interventions: Temporary and Definitive Direct Hemorrhage Control
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The general principle of damage control in the combat environment is to provide only the interventions required to safely get the patient to the next echelon/role of care. This approach begins at the point of injury with the teachings of TCCC including tourniquets and topical hemostatic agents. It continues through the FST with a variety of vascular control and repair techniques. The goal is to salvage potentially survivable injuries, over 90% of which are associated with hemorrhage.53
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Topical Hemostatic Agents
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Research and development of novel topical hemostatic agents has seen much interest during the current era of combat casualty care. Initially based on chitosan (treated crustacean shell) or clay derived powders these hemostatic agents undergo an exothermic reaction when exposed to hemorrhagic wounds. When used as a straight powder or impregnated gauze these agents can provide hemorrhage control alone or as an adjunct to tourniquet use. As addressed in the “Tactical Field Care” section earlier, Combat Gauze is used as the primary hemostatic by the first responder based on CoTCCC guidelines. The gauze has been selected over powder formulations for ease of use and ability to provide compression in cavitary wounds. Hemostatic gauze products continue to be useful in the operating room as well and have become commonplace in civilian settings. There has been an explosion of improvements and options for topic hemostatic agents in recent years with several new agents in being investigated currently.
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Self-expanding foam represents a promising new technique to provide hemostasis for otherwise noncompressible intra-abdominal hemorrhage. A polyurethane foam is under investigation which can be delivered in an intracavitary manner and increase in volume to temporize hemorrhage until definitive surgical control.54
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Expandable sponges under the label XSTAT (RevMededx, Wilsonville, OR) have also been developed through military research with FDA approval for use in 2014 (Figure 52-11). The device consists of a large syringe that can deliver many pill-sized, nonabsorbable, radio-opaque sponges, which expand within 20 seconds of contact with moisture. The volume of material delivered and the size of the delivery device provides tamponade control of junctional wounds in the groin and axilla.
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The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH-2) study, an international prospective randomized trial of over 20,000 trauma patients, demonstrated a mortality benefit.55 When studied in a military Role 3 hospital, the Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study also revealed a mortality advantage.56 In both studies the benefit was seen only if provided early after injury (less than 3 hours). As such, tranexamic acid (TXA) is advocated by the current DCR guidelines from the Joint Trauma System (reference DCR CPG).
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Traumatic Arrest and Profound Shock
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Combat casualties have a high frequency of penetrating injury from mechanisms designed to be lethal. Traumatic arrest or profound shock en route to the first surgical facility are realities which must be anticipated. Aortic occlusion represents a means to limit hemorrhage and maintain perfusion to neurologic and central structures. However, this remains a very aggressive maneuver and patient selection is paramount.
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Resuscitative Thoracotomy
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The indication for resuscitative thoracotomy is usually loss, or impending loss, of vital signs in the initial resuscitation setting after penetrating trauma. The specific indications for this extreme measure vary between institutions and remain an area of contentious debate. It is promoted as the “last opportunity” to save a life. However, the nature of the procedure poses risk to medical personnel in terms of infectious disease exposure from sharp rib fractures or instruments. A large series of emergency thoracotomies during a 4-year period in Iraq revealed an overall survival rate of 11%.57 The current US military indication for emergency thoracotomy is limited to penetrating trauma, without isolated head injury and not if vital signs have been lost for over 10 minutes.7
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Resuscitative Endovascular Balloon Occlusion of the Aorta
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The use of intra-arterial balloon occlusion of the aorta was first reported in 1954 by Colonel Carl Hughes.58 However, it has only recently gained popularity in the current era of expanded endovascular technologies. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has several potential advantages over emergent thoracotomy. In terms of risk to providers, this catheter-based technique reduces the opportunities for direct exposure to biohazardous materials through puncture by broken ribs. As the balloon can be inflated at different locations, selective occlusion—either in the chest or inferior to the renal arteries can be performed. Particularly for the patient with exsanguinating isolated pelvic trauma the benefits of aortic occlusion while maintaining renal and visceral blood flow is possible. REBOA does require a specialized skill set and equipment that may not be available in all circumstances. Recent promising experiences with REBOA have prompted the creation of military-specific indications for its use (CPG).5
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Operative Resuscitation
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Operative intervention in the setting of DCR is an extension of prehospital and initial MTF intervention goals of hemorrhage and coagulopathy management. Unlike most civilian settings both tactical and physiologic considerations mush be considered. A prime example is the FST which often operates in a split-based configuration (2 general surgeons or 1 general surgeon/1 orthopedic surgeon) with 1 OR and only 6 hours of holding capacity postsurgery. The focus includes rapidly assessing the patient, controlling hemorrhage, minimizing contamination, and facilitating evacuation to the next higher level (role/echelon) of care. As time and resources are limited only those interventions which are required to stabilize the patient for transport to the next level of care are performed.
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Damage control laparotomy is a familiar component of DCR in the setting of intra-abdominal or lower extremity junctional hemorrhage. Hemorrhage is controlled by ligation, repair, compression, or shunting. Injured bowel requiring resection is left in discontinuity. The abdomen is packed and left open in a nearly universal manner. This allows for an abbreviated operative time, facilitating expedient return to the ICU for further resuscitation. Additionally, the OR is made available more rapidly for the next patient(s)—who regularly arrive in multiples. The chaos inherent in a war zone can adversely affect communication concerning the patient’s injuries. An open abdomen allows the next-higher receiving MTF the ability to directly visualize the injuries sustained when communication is impaired. The abdominal pack dressing is routinely labeled with indelible ink as an additional means to ensure the full extent of injuries is recognized and can be appropriately treated (Fig. 52-12).
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Major arterial injury presents conflicting priorities of control to prevent exsanguination and preservation of flow to maintain viability of tissues distant to the injury. The primacy of life over limb remains. When the limb can be salvaged while preserving the patient’s life the intervention used is contingent upon the resources available. Extra time spent on a formal repair may place other casualties needing operative intervention at unacceptable risk. Generally speaking, at Role 2 facilities, the employment of temporary vascular shunts is encouraged over formal repair—which is best left to the Role 3 or higher. Exploration, proximal and distal control, thrombectomy, and local heparinization are still utilized for shunting (CPG of vascular injuries). Not all vessels can or should be shunted, a list of major vessel considerations for shunting is provided in Table 52-5.11 When an extremity’s vascular inflow is maintained through shunting or repair a fasciotomy is currently recommended. The amount of soft tissue compartment swelling after injury in young, muscular patients is often profound.
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