Damage Control Resuscitation in Traumatic Hemorrhage: It is More Than Fixing the Holes and Filling the Tank

Hemorrhagic shock is a time-dependent disease. In trauma patients that survive to hospital admission, the average time to death due to hemorrhage is less than 4 h.  Timely identification of patients at risk for hemorrhage is critical because delays in resuscitative therapy and administration of blood products are associated with increased mortality. Damage control resuscitation is predicated on early blood product transfusion. A widely referenced indicator and trigger for massive resuscitation is the Assessment of Blood Consumption score, which recognizes a heart rate more than 120 beats/min, arterial systolic blood pressure (SBP) less than 90 mmHg, positive Focused Assessment of Sonography in Trauma examination, and penetrating mechanism.  The presence of two or more of these criteria determines a positive Assessment of Blood Consumption score and reflects a sensitivity and specificity of more than 80% to identify patients that received a massive transfusion, defined as more than 10 units of packed red blood cells within 24 h. This score was comparable to other risk stratification scores. The advantage of the Assessment of Blood Consumption score is the relative clinical utility and ease with which it may be performed immediately at the bedside in the trauma bay and does not require delays in waiting for laboratory results, radiographic imaging, or sophisticated computation.

The shock index, calculated as the heart rate divided by arterial SBP, is an additional marker of injury severity.  The utility of the shock index is also evident in the prehospital setting where it easily obtainable and shown to predict the need for blood product transfusion and lifesaving interventions.  Similar to the Assessment of Blood Consumption score, the Revised Assessment of Bleeding and Transfusion score includes an admission shock index greater than 1.0 and the presence of a pelvic fracture in replacement of heart rate and arterial SBP from the Assessment of Blood Consumption score. In multicenter validation, the Revised Assessment of Bleeding and Transfusion score demonstrated superior sensitivity, specificity, and accuracy in identifying patients that received massive transfusion.  The clinical application of the shock index is simplified in that severely injured patients with a heart rate greater than the arterial SBP (i.e., shock index more than 1.0) are at increased risk for physiologic derangement and hemorrhage. There are various scoring systems to identify patients with acute hemorrhage and an increased risk of massive transfusion.  Adoption of these scores is dependent on specific institutional capabilities and resources, and there is no single scoring system that is ideal for every institution. figure 1 depicts a flow chart for initial damage control resuscitation management.

The differences in mechanism of injury are also an important point of discussion regarding early recognition of hemorrhage and consequent injury management. A penetrating mechanism (caused by gunshot, stab/impalement, or laceration) typically follows a trajectory. In the case of gunshot wounds, and even through-and-through stab wounds, it is critical to account for the number of wounds to align trajectory and determine anatomic structures (i.e., blood vessels, hollow and solid organ structures, osseous structures such as the vertebral column) that are at risk for injury. Trajectories that cross multiple body cavities (such as the thorax/mediastinum and abdomen) must also be considered. In addition, the presence of a penetrating mechanism is one of the criteria incorporated into the aforementioned Assessment of Blood Consumption score to identify patients at risk for massive transfusion.

Patients with a blunt mechanism of injury (i.e., motor vehicle collisions, motorcycle crashes, pedestrians struck, or falls from greater than standing height) are at risk for hemorrhage in multiple body cavities that may not be easily diagnosed on the body surface. The role of the Focused Assessment of Sonography in Trauma examination in identifying sources of hemorrhage is specifically useful in blunt trauma patients with hypotension.  It is also worthwhile to note that even falls from a standing height, particularly in patients taking anticoagulation medications, may result in hemorrhage in multiple body cavities, such as the head, chest (i.e., rib fractures or pulmonary lacerations), abdomen, and/or retroperitoneum or pelvis. The goals of resuscitation are impacted by the concomitant risk of traumatic brain injury, which may occur in 25% of patients with a blunt mechanism, and are described in later sections of this review. An appreciation for the mechanism of injury, and that multiple mechanisms may coexist (such as a gunshot wound in combination with being struck by a vehicle or assault), is integral to the initial physical evaluation and early identification of hemorrhage.

Clinician “gestalt” is insufficient to expeditiously identify patients that should receive massive transfusion. Motameni et al.  described that physician decision to initiate massive transfusion was correct in 73% of patients; however, more than half of these occurred in the operating room. Furthermore, the authors reported that, if the Assessment of Blood Consumption score had been applied to identify hemorrhage, the massive transfusion event would have been initiated in the trauma bay in more than 80% of patients. This represents a marked time difference, especially in a clinical setting where delays, measured in minutes, in the delivery of blood products are associated with worse outcomes.  The development of massive transfusion protocols function such that communication among trauma surgeons, anesthesiologists, transfusion medicine, and operating room staff clearly recognize the critical and time-sensitive nature of hemorrhagic shock resuscitation.  The definition of massive transfusion has also evolved over the past two decades with emphasis on damage control resuscitation. Initially described as more than 10 units of erythrocytes within 24 h, this assumes that severely injured patients survive long enough to receive the requisite 10 units of erythrocytes, a concept known as survivor bias. In contemporary damage control resuscitation practice, there is specific attention to balanced, plasma-based resuscitation in hemorrhagic shock and focused correction of coagulopathy (described in later sections of this review) with the goal of minimizing crystalloid administration and overall blood product transfusion, such that many patients with hemorrhage do not require an excess of 10 units of erythrocytes. For example, in the seminal Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial, the median total number of erythrocytes transfused for each patient was 9 units.  The Critical Administration Threshold is described as the receipt of more than 3 units of erythrocytes within 1 h and is a significant predictor of mortality, superior to that of the traditional definition of massive transfusion (i.e., more than 10 units within 24 h).  Trauma patients that are Critical Administration Threshold + within the first hour of hospital admission are more likely to receive large volumes of blood products and are at a greater risk of death. Regardless of how massive transfusion is defined, it is critical to recognize that initiation of such an event does not necessitate that patients receive a requisite number of blood products, but rather functions to identify injured patients and establish communication among multidisciplinary specialists (e.g., trauma surgeons, anesthesiologist, transfusion medicine) to implement time-sensitive resuscitation for severe hemorrhagic shock.

The contemporary practice of damage control resuscitation not only emphasizes timely recognition and transfusion of erythrocytes to patients with hemorrhage, but also early plasma and platelet administration in a ratio that approximates 1:1:1. Multiple retrospective studies described that earlier fresh frozen plasma (FFP) administration in trauma patients receiving massive transfusion was associated with significantly reduced mortality. The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) trial reported more that earlier and aggressive plasma administration was associated with a lower risk of mortality.  During the initial 6 h after trauma center admission, a critical time point when most patients die of hemorrhage, a ratio of FFP:erythrocytes less than 1:2 was associated with a more than three-fold increased risk of death. The association with transfusion ratios and mortality ceased to exist 24 h after admission, highlighting the time-critical nature of hemorrhagic shock resuscitation and early plasma transfusion.

Similar to plasma, early transfusion of platelets is associated with lower risk of death due to hemorrhage after injury.  Historically, platelet transfusion was reserved for after administration of crystalloid, erythrocytes, and FFP when conventional laboratory testing revealed thrombocytopenia (i.e., less than 50,000 platelets). Advancement in coagulation science and viscoelastic hemostatic assays demonstrate that platelet dysfunction is a common occurrence in acute traumatic coagulopathy.  This dysfunction is likely multifactorial, but contributed to, in part, by exhaustion of platelet activation, endothelial damage, hypofibrinogenemia, and impaired thrombin generation.  Observational data suggest that higher ratios of platelets:erythrocytes are associated with improved outcomes. 

There are limited prospective, randomized data that define the amount of erythrocytes, FFP, and platelets or the exact ratio of transfusion in damage control resuscitation. In an attempt to definitively answer the question of superiority of a 1:1:1 transfusion strategy in a prospective, multicenter trial, the PROPPR study randomly assigned 680 patients with a positive Assessment of Blood Consumption score or physician judgment to receive more than 10 units of erythrocytes within 24 h to either 1:1:1 or 1:1:2 transfusion of platelets, FFP, and erythrocytes, respectively.  The results demonstrated no difference in the primary outcome of 28-day mortality; however, there was a reported decrease in the secondary outcomes of 24-h mortality related to hemorrhage and earlier hemorrhage control in patients that received the 1:1:1 transfusion, which should be interpreted as exploratory in nature. Both groups of patients also received higher ratios of plasma than was commonly practiced in most trauma centers, and the study demonstrated the feasibility of a balanced resuscitation strategy. While this was considered an overall “negative” trial, the results further suggest the importance of early plasma and platelet transfusion.

An additional point-of-emphasis in damage control resuscitation is minimizing crystalloid administration. Numerous retrospective studies identified that the volume of crystalloid was significantly associated with ARDS, renal failure, delayed abdominal closure, multiple organ failure, and mortality.  The maximum volume of crystalloid that should be delivered to patients with hemorrhage is undefined; however, previous studies suggest that volumes greater than 1.5 to 2 l are associated with greater mortality, and that every 500-ml increment of crystalloid within the first 6 h of resuscitation is associated with a 9% increase in risk for ARDS.  Despite the evolution of damage control techniques in the early 1990s, large volumes of crystalloid, in excess of 10 l during the first 24 h, continued to be administered to patients with hemorrhage. The detrimental effects of crystalloid resuscitation in hemorrhagic shock are well-described in the literature most notably that it lacks oxygen-carrying capacity and contributes to a dilutional coagulopathy. More recently, it has been observed that the administration of crystalloid has a profound effect on endothelial glycocalyx degradation and dysfunction after hemorrhage. An additional contribution from the PROPPR trial suggests that, in the era of damage control resuscitation with a plasma-based resuscitation, there appears to be less crystalloid administration (i.e., approximately 6 l within 24 h)  compared with historical reports of 10 l within 24 h. 

A recent prospective, randomized trial demonstrated a survival advantage with early plasma transfusion in blunt trauma patients with severe hemorrhage. The Prehospital Air Medical Plasma (PAMPer) trial reported that patients who received prehospital plasma had a significantly lower 30-day mortality compared with patients that received either packed red blood cells or crystalloid.  A simultaneous trial conducted in an urban environment where prehospital plasma transfusion was performed by ground ambulance did not observe similar results. There were notable differences in the study populations that would explain these disparate findings. A preplanned, post hoc analysis of data combined from these two trials reported that the greatest benefit of early plasma administration was in patients that had a more than a 20-min prehospital transport time and that sustained a blunt mechanism of injury. Considering the goals of damage control resuscitation, patients also received less crystalloid (approximately 5 l) during the initial 24 h even compared with the aforementioned PROPPR trial. The proposed mechanistic advantage of early plasma transfusion in hemorrhage extends beyond supplementation of clotting factors and hyperoncotic solution. A single unit of FFP contains approximately 65% of normal clotting factor activity. Plasma demonstrates a protective and restorative effect on the endothelial glycocalyx which becomes damaged and dysfunctional in the process of shock-induced endotheliopathy.  Specifically, blunt mechanisms of injury, including traumatic brain injury, may also develop a certain immunologic pathophysiology that benefits from early plasma transfusion. Such explanations are hypothesis generating in the clinical context of the beneficial effects of plasma in hemorrhagic shock resuscitation. Nonetheless, the most recent high-quality data support an early plasma-based blood product transfusion in traumatic hemorrhage.

Balanced blood product administration in damage control resuscitation attempts to achieve ratios of erythrocytes, FFP, and platelets that approximate whole blood. However, the biologic content of these components does not equate to the hemostatic profile that exists in whole blood. For example, when combined in a 1:1:1 ratio of erythrocytes, FFP, and a unit of apheresed platelets, there is a hematocrit of approximately 29%, coagulation factor function of 65%, platelet count of 87,000, respectively, and the fibrinogen content is 850 mg.  Compared with a single unit of whole blood that reflects more of a physiologic character, component therapy also introduces more additive solution that lacks oxygen-carrying capacity and may further contribute to dilutional coagulopathy. Whole blood resuscitation is not a new concept and was the common means of transfusion for hemorrhage during World War I and World War II. With advances in transfusion medicine and the ability to partition component blood products for specific transfusion indications, whole blood resuscitation became less common during the mid-twentieth century. Only during recent military conflict has whole blood re-emerged as a potential resuscitative strategy. Low-titer whole blood is approved for use by the American Association of Blood Banks and is advocated by the Trauma Hemostasis and Oxygen Research Network and the Joint Trauma Systems Tactical Combat Casualty Care. The advantages of whole blood resuscitation are that it involves transfusion of a single unit of whole blood that originates from one donor with less risk of immune exposure to exogenous antigens when compared with separate components of erythrocytes, FFP, and platelets in a 1:1:1 strategy that are derived from multiple donors. There is also less volume administered with a single unit of whole blood and is an important consideration in damage control resuscitation, which aims to minimize excessive volume administration and the associated risk of transfusion-associated circulatory overload. Multiple retrospective studies in the civilian environment now demonstrate that cold-stored low-titer whole blood is feasible, without any observable increased risk in complications, such as mismatch incompatibility; and is associated with decreased mortality.  Two multicenter, randomized trials are underway in the United States to investigate whole blood resuscitation for traumatic hemorrhage in both the prehospital and in-hospital setting.

In addition to minimal crystalloid administration, certain advocates of damage control resuscitation reference hypotensive resuscitation as a practice that improves mortality.  Achieving a lower arterial systolic and mean arterial blood pressure would intuitively reduce bleeding from uncontrolled sources. A meta-analysis of five randomized trials stated that hypotensive resuscitation reduces mortality in bleeding trauma patients, even though the quality of evidence is low.  Critical appraisal of the data reveals that the goal of a lower arterial systolic or mean arterial blood pressure was not achieved in any of these studies, which questions whether hypotensive resuscitation was clinically obtained. The seminal trial by Bickel et al. demonstrated that minimal prehospital crystalloid administration resulted in lower mortality in patients with penetrating torso trauma. These results have been misinterpreted to suggest that hypotensive resuscitation reduces mortality, even though arrival arterial SBP was not clinically different. A later investigation on prehospital hypotensive resuscitation suggested that there was an association with lower mortality in a subgroup of patients with blunt trauma; even though there was no difference in arterial SBP at hospital arrival between groups, the intervention group received smaller volumes of prehospital crystalloid.  These results should be interpreted cautiously and within an appropriate context, especially considering the detrimental impact of hypotension in patients with traumatic brain injury. The optimal arterial systolic and mean arterial blood pressure in patients with hemorrhage is not clearly defined and likely dependent on patient-specific and injury characteristics (i.e., brain and spinal cord injury).

Vasopressor administration to patients with traumatic hemorrhage has historically been discouraged in North American trauma systems due to an increased risk of multiple organ failure and mortality. However, the data supporting this practice are limited and based on biased retrospective evidence.  Based on previous work in hypovolemic patients, there is biologic plausibility that specific vasopressors are indicated in hemorrhaging trauma patients that remain hypotensive and unresponsive to further blood product administration because these patients are vasodilated.  Two prospective, randomized trials that evaluated a vasopressin infusion in patients at risk for massive transfusion observed an overall lower volume of transfused blood products in patients that received vasopressin, and no difference in mortality.  It may be extrapolated that appropriate administration of specific vasopressors (i.e., vasopressin) minimizes overall volume of blood product transfusion and is potentially beneficial. However, it is important to recognize that these studies do not define the ideal blood pressure for resuscitation in hemorrhagic shock or damage control resuscitation. Different recommendations exist regarding blood pressure goals in patients with hemorrhage, specifically traumatic brain injury, and we refer the reader to statements from the Trauma Hemostasis and Oxygenation Research Network, Brain Trauma Foundation Guidelines,  and European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma. 

The maturation of damage control resuscitation over the past two decades coincides with advances in the understanding of complex pathophysiologic process of coagulopathy and hemorrhage. The cell-based model of hemostasis has significantly contributed to the science of traumatic coagulopathy.  What was initially attributed to excess crystalloid administration and the absence of expeditious plasma transfusion, it is now recognized that acute traumatic coagulopathy is present after injury in 25% of trauma patients.  Further compounding the effects of traumatic coagulopathy are hypothermia, acidosis, and hypocalcemia. Hypothermia is a common occurrence at hospital presentation after traumatic injury that exacerbates coagulopathy.  Multiple techniques to correct hypothermia are available, including minimizing unnecessary body exposure in the resuscitation room or operating room, forced-air warming devices, increasing ambient room temperature, intravascular warming devices, or even extracorporeal support, such as renal replacement therapy and extracorporeal membrane oxygenation. Similarly, hypocalcemia is common in patients at risk for massive transfusion and is associated with increased mortality.  It is unknown if early and aggressive calcium supplementation results in improved outcomes; however, vigilant monitoring and maintenance of normal ionized calcium levels is included in the most recent European guidelines on management of severe bleeding.

The principals of damage control resuscitation have mitigated the adverse effects of a crystalloid-based resuscitation and subsequent dilutional coagulopathy while emphasizing aggressive plasma transfusion; however, it is unclear if such a resuscitation strategy inherently corrects the underlying clotting abnormalities present in severely hemorrhaging trauma patients. It is reported that platelet dysfunction is a dynamic phenomenon observed in injured patients.  Coupled with rapid fibrinogen depletion during massive hemorrhage, these processes contribute to a coagulopathy characterized by poor clot strength. This further deteriorates with an inability to rapidly generate adequate clotting factor activity and thrombin generation, which is necessary for the conversion of fibrinogen into a stable foundation of fibrin on which platelet binding and hemostatic clotting occur.  Critical hypofibrinogenemia is underrecognized in bleeding patients, likely due to the fact that the threshold for which low fibrinogen is associated with poor outcomes is much higher (i.e., less than 150 to 200 mg/dL) than historically taught.  Additionally, the fibrinogen content of a single unit of FFP is less than 1 g, and it is unclear if a plasma-based resuscitation is sufficient to ameliorate the effects of hypofibrinogenemia in traumatic hemorrhage. 

More widespread utilization of viscoelastic hemostatic assays is providing rapid and specific data on clotting abnormalities in the context of damage control resuscitation (fig. 1). These assays generate numeric and graphic information that plot the clotting profile over time, with attention to clot initiation, amplification, propagation, and stabilization. Viscoelastic hemostatic assays have demonstrated predictive value in determining the need for massive transfusion and increased risk of mortality. In theory, identification of the specific coagulation abnormalities with viscoelastic testing would initiate appropriate and timely transfusion of hemostatic products directed at the specific coagulation deficit. A single-center series reported that viscoelastic-guided resuscitation reduced blood product transfusions and mortality; however, the Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC) trial did not observe a difference in mortality or transfusion volumes in the viscoelastic-guided intervention group compared with the control group of ratio-based blood products.⁶⁰  There were specific limitations to this study that question the overall validity in a population of severely injured and bleeding trauma patients.

Coagulation disorders, such as hypofibrinogenemia and clotting factor depletion, are known to occur and contribute to traumatic coagulopathy. Although viscoelastic testing did not demonstrate superiority with regard to lower mortality in the iTACTIC trial, a number of prospective randomized studies have investigated empiric administration of cryoprecipitate and fibrinogen concentrate in trauma patients at risk of hemorrhage. Results suggest that early fibrinogen replacement is feasible and results in greater serum fibrinogen levels and improved viscoelastic clotting profiles; however, these studies were not designed to demonstrate mortality as a primary outcome.  Ongoing trials are underway that are expected to address this question. A recent prospective, randomized study from 12 French trauma centers also investigated the impact of empiric administration of 4-factor prothrombin complex concentrate (PCC) in patients at risk for massive transfusion.  There was no significant difference in the primary outcome of total 24-h transfusion volume nor was there an observed difference in mortality at all time points. There were significantly more thrombotic complications in the PCC treatment group. It is noteworthy that, in these studies, fibrinogen concentrate, cryoprecipitate, and PCCs were administered empirically and not guided by viscoelastic or conventional laboratory testing. Therefore, it is plausible that the specific treatment was not warranted in a number of participants. It does not appear that routine administration of fibrinogen or PCCs is justified in all patients as a part of damage control resuscitation. Based on available clinical evidence it is also unclear if viscoelastic-guided resuscitation is superior to ratio-based transfusion.

Routine administration of tranexamic acid to trauma patients at risk of bleeding gained enthusiasm after the results of the Clinical Randomization of an Antifibrinolytic in Hemorrhage-2 (CRASH-2) trial that tranexamic acid within 3 h of injury demonstrated a significant reduction in mortality.  There were numerous methodologic objections, most notably that only half of the enrolled patients actually received a blood product transfusion. More recent investigations provide greater insight into the benefit of early tranexamic acid in patients with traumatic hemorrhage (table 1). The Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) trial prospectively randomly assigned 927 patients at risk of hemorrhage to prehospital administration of tranexamic acid versus placebo.  Although there was no significant difference in mortality, the treatment effect was similar to the results of CRASH-2, and likely reflects an underpowered sample size. A post hoc analysis of the STAAMP trial demonstrated that the greatest observable benefit of tranexamic acid occurred in patients with hypotension (SBP less than 70 mmHg) and who received tranexamic acid within 1 h of injury and is similar to that which was observed in CRASH-2. The optimal dose of tranexamic acid is unknown; however, bolus dosing of 2 g, with an additional 1 g infusion greater than 8 h, was safe and effective.  In damage control resuscitation, early tranexamic acid administration within 3 h of injury appears beneficial in patients with severe hemorrhage. 

Further controversy on the topic persisted, specifically regarding the different phenotypes of fibrinolysis (i.e., fibrinolysis shutdown, physiologic fibrinolysis, and hyperfibrinolysis).  Observations with viscoelastic hemostatic assays, which includes the later portions of clot formation and analysis of physiologic clot breakdown to prevent unnecessary and excessive clot formation (e.g., physiologic fibrinolysis), suggested that a portion of severely injured patients with profound shock (i.e., hypotension, elevated lactate) and greater injury severity burden demonstrate excessive clot breakdown, known as hyperfibrinolysis. This is proposed to occur through vascular endothelial damage and the generation of tissue plasminogen activator. The effect of tranexamic acid to inhibit the conversion of plasminogen to plasmin would seemingly be most beneficial to those patients with hyperfibrinolysis. On the opposite end of the fibrinolysis spectrum are patients with impaired fibrinolysis (e.g., fibrinolysis shutdown), which is associated with excessive plasminogen activator inhibitor-1 and represents a majority of trauma patients in reported series.  It was hypothesized that tranexamic acid administration to patients with fibrinolysis shutdown would result in increased thrombotic complications, multiple organ failure, and death.  However, due to methodologic limitations these findings are strictly hypothesis generating and have not been confirmed in a prospective, randomized fashion. It is important to recognize that none of the randomized trials on tranexamic acid have evaluated administration based on viscoelastic test results. Additional data also suggest that fibrinolysis is a complex and temporal phenomenon that evolves over the initial period after severe injury, with certain patients transitioning through different fibrinolysis phenotypes. Further work is necessary to determine the interaction of tranexamic acid among the various fibrinolysis phenotypes and association with clinical outcomes.

The early initiation of damage control resuscitation with transfusion of balanced ratios of blood products and the management of coagulopathy is solidified throughout the trauma literature. However, the question of “when does damage control resuscitation stop?” is not as clearly defined. A retrospective investigation described specific criteria in which cessation of massive transfusion was appropriate. There is limited evidence to guide massive transfusion termination, and there are multiple clinical variables that affect when resuscitation is complete.  Importantly, massive transfusion termination communicates with the blood bank that preparation of large quantities of erythrocytes, FFP, platelets, or whole blood is no longer necessary. After termination of massive transfusion events it is likely that patients will continue to receive blood products, however, not at the same intensity (e.g., less than 3 units erythrocytes per h). Obvious indications that hemorrhage is controlled include minimal visible bleeding in the operative site, or from any other sources of injury. Evaluation of volume responsiveness is a maneuver to determine if further resuscitation results in improved cardiovascular function and hemodynamics. End-tidal carbon dioxide (ETco₂) is a useful marker to assess improved cardiac output as a result of fluid responsiveness. A bolus of 4 ml/kg of intravascular volume that produces an increase in ETco₂ ≥ 2 is an accurate predictor of volume responsiveness in critically ill patients.  In the absence of volume responsiveness, an assessment of intrinsic cardiac function is necessary. The utility of transesophageal echocardiography is well-described to differentiate various etiologies of shock and likely serves a critical role in damage control resuscitation. However, reports of widespread use of intraoperative transesophageal echocardiography in trauma are limited.

Hypotension is often the result of vasodilation with severe hemorrhage.  While vasopressors, such as norepinephrine or vasopressin, may be indicated, these should be used in conjunction with strong clinical decision making so as not to conclude volume resuscitation efforts and overlook concomitant hypovolemia or depressed cardiac contractility. Metabolic and acid-base parameters should improve before the cessation of damage control resuscitation, and arterial pH > 7.20 is associated with optimal clot formation.  There is no high-quality evidence that sodium bicarbonate administration improves mortality in critically ill trauma patients, and the role of other hydrogen ion buffers is an area of interest regarding the management of metabolic disturbances.  Serum lactate is a valuable marker for injury severity and depth of clinical shock. Observational data demonstrate that earlier resolution of lactate is associated with clinical outcomes however, targeted attempts to correct an elevated lactate to a specified value, or determine the optimal threshold for lactate correction, have not resulted in improved mortality. Overall, the conclusion of damage control resuscitation indicates adequate hemostatic control of hemorrhage, intravascular resuscitation, and improving metabolic parameters.

Damage control techniques have evolved during the past 20 yr and demonstrate lower rates of morbidity and mortality for traumatically injured patients. Specifically, damage control resuscitation emphasizes rapid identification of hemorrhage, implementation of massive transfusion protocols, resuscitation with plasma-based blood products, correction of coagulopathy, and management of metabolic derangements (i.e., acidemia, hypocalcemia, and hypothermia). There is limited prospective, randomized evidence to definitively prove that specific components of damage control resuscitation result in superior clinical outcomes (i.e., 1:1:1 blood product resuscitation, whole blood transfusion, minimal crystalloid administration, or early fibrinogen supplementation). However, quality improvement studies suggest that attention to damage control resuscitation is associated with increased rates of definitive injury repair and improved patient morbidity.  It is important to recognize that modern damage control resuscitation can exist in the absence of damage control operative techniques (i.e., abbreviated laparotomy with delayed abdominal closure). With more widespread adoption of damage control resuscitation principals there is earlier identification of hemorrhage, transfusion of balanced blood products, and correction of metabolic derangements to optimize patient physiology and allow earlier definitive injury repair.

The development of artificial intelligence algorithms and sophisticated continuous vital sign monitoring that predict the need for early blood product transfusion and lifesaving interventions represent future applications within damage control resuscitation.  The potential for this technology to rapidly identify and implement specific therapy will be valuable in providing immediate care for patients with severe hemorrhage. Prehospital point-of-care technology is also providing earlier identification of patients at risk for hemorrhage and life-saving interventions. Due to the successes of damage control resuscitation, it is likely that, as more patients with severe traumatic injuries survive the early resuscitation, the burden of profound shock and systemic inflammation will persist and reflect continued organ dysfunction, such as vasoplegia, pulmonary failure, renal failure, and hematopoietic failure or coagulopathy. Further research is necessary to better understand the role and timing of organ support in these critically ill patients. Additionally, more recent work in the complex dynamics of coagulation and platelet function after injury is providing valuable insight into the different phenotypic characteristics of patients that receive damage control resuscitation and the relationship of endothelial vascular injury, microvascular thrombosis, and organ dysfunction.  Anesthesiologists and perioperative physicians remain intricately involved in the management of hemorrhagic shock and serve a vital role in the advancement of damage control resuscitation.