In Brief

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Injuries are a leading cause of death across the world, especially in the developed countries. They predominantly affect the young and the most productive segment of our society, resulting not only in lost lives but also in a huge financial impact. Most of the deaths in trauma patients are acute, with bleeding and severe traumatic brain injury being the leading etiologies. Between these 2, bleeding is clearly more amenable to surgical interventions, which makes it the number 1 cause of preventable deaths. It is therefore very appropriate that hemorrhage control and resuscitation are among the key tenets of early trauma care. Despite hemorrhage being a common problem, the optimal resuscitative strategy remains controversial, with vigorous debates about the type of fluid, volume, rate, route of administration, and end points of resuscitation. This review focuses on recent advances in resuscitation strategies that have taken place as our understanding of the body's response to hemorrhage and resuscitation has improved. We also discuss some exciting novel developments that are likely to influence the clinical practice in the near future.

The history of fluid resuscitation is relatively short and all the significant advances are closely tied to the major wars over the last century. At the time of World War I, there was no real concept of intravenous fluid resuscitation, and the etiology of hemorrhagic/traumatic shock was poorly understood. During World War II, colloids, such as plasma, were used and blood transfusion was adopted for the treatment of hemorrhagic shock. The Korean conflict witnessed more common use of blood and plasma, and the establishment of rapid evacuation and treatment systems. These included helicopter transfers to the Mobile Army Surgical Hospitals for early treatment of combat casualties. All of these methods did not have a major impact on the Killed in Action rate, but they significantly decreased the rate of Died of Wounds through better first responder treatment, rapid evacuation to higher echelons of care, quicker resuscitation, and earlier surgical interventions, along with use of antibiotics and improved postoperative care. Intravenous fluids for resuscitation were first used on a wide scale during the Vietnam conflict, and it was during this period that “shock lung/Da Nang lung” (later termed acute respiratory distress syndrome or ARDS) was first described in soldiers that received massive crystalloid resuscitation. With the explosive growth in technology and medical research, and payment for health services by the government in the 1960s (Medicare and Medicaid), close to 95% of all acute care hospitals established some sort of critical care unit. In 1970, the Society of Critical Care Medicine was established, which played a key role in advancing the science of critical care, including resuscitation techniques. During this period, we learned that major fluid shifts take place following shock and resuscitation. It was discovered that resuscitation was needed not only to replace the lost intravascular volume, but also to replenish the interstitial fluid deficits. This prompted clinicians to administer increasingly larger volumes of intravenous fluids to their trauma patients. In the 1980s this concept reached its zenith with the adoption of “supra-normal” resuscitation techniques, where physiological parameters were aggressively pushed with fluids, blood, and drugs to maximize the delivery of oxygen to the tissues. Subsequent studies proved that this approach not only failed to improve outcomes but was in fact associated with numerous unintended side effects. Massively edematous patients (trauma “Michelin Men”) became a common sight in critical care units across the world. “You must swell to get well” was a common mantra for the trauma surgeons that trained during the 1990s. Complications, such as ARDS, compartment syndromes, open body cavities, and prolonged need for mechanical ventilation were considered an expected consequence of trauma resuscitation.

The pendulum started to swing back in the mid-1990s when many basic science and clinical researchers challenged the dogma of large-volume resuscitation. However, it was the lessons learned during the next war that finally delegated large-volume crystalloid resuscitation to the history books. During the early phases of operations in Afghanistan and Iraq, battlefronts were extremely rapid and nonlinear. Emphasis was on a smaller logistical footprint and mobility. Thus, unlike the previous wars, the military no longer had the luxury of large field hospitals in close proximity to the frontlines. In addition, transport to sea- or land-based tertiary care hospitals was often not readily available, which delayed definitive surgical care. In these settings it was logistically impractical to perform the typical large-volume crystalloid resuscitation (each liter of fluid weighs 1 kg and takes up precious space). This also coincided with the publication of numerous studies, including a seminal report by the Institute of Medicine, which highlighted the adverse consequences of reckless fluid resuscitation. The USA military responded to these challenges by sponsoring multiple consensus conferences where experts reviewed all of these data to overhaul the battlefield resuscitation guidelines. As a result, early hemorrhage control was prioritized over aggressive resuscitation. Only selected patients were considered appropriate for fluid resuscitation. When performed, fluid resuscitation was low-volume and aimed for a more modest blood pressure goal. Blood products were used early instead of crystalloids, and higher ratios of plasma and platelets (or fresh whole blood) were infused. Results of this approach, in the form of combat casualty data, have been analyzed carefully and debated vigorously. The overall concept that has emerged from this experience is termed “damage control” or “hemostatic” resuscitation. The basic tenets of this approach are to (1) prioritize hemorrhage control; (2) avoid crystalloids; (3) aim for permissive hypotension whenever possible; (4) prevent coagulopathy through early use of blood products; (5) prevent the development of the vicious cycle of acidosis, coagulopathy, and hypothermia (“triad of death”). This monograph evaluates the rationale behind the development of this concept and the data that support it.

Use of blood products for the treatment of trauma-associated coagulopathy has some logistic limitations, especially in austere environments, such as a battlefield. These include need for refrigerated storage and transportation, limited shelf life, type and screen, dependence on available donors, and long thaw times. Since most of the trauma deaths take place before reaching a medical facility, there is a clear need for the development of innovative and effective strategies for the early (prehospital) treatment of coagulopathy. One solution is to convert blood components into shelf-stable, lyophilized freeze-dried products. Such products would have several potential advantages, including storage at ambient temperature, longer shelf life, quicker preparation time, ABO universality, and reliable viral inactivation methods. Freeze-drying technology has been used to preserve different components of the blood with variable success. Aggressive efforts, mostly funded by the US Department of Defense, are underway to refine and produce a preserved plasma product for clinical use in the near future. Hemoglobin-based oxygen-carrying solutions have a long and checkered history, but the newer generations of these solutions are much closer to the desired ideal. Similarly, there is huge interest in finding a role for recombinant clotting factors or prothrombin complex concentrates in the treatment or prevention of trauma-associated coagulopathy.

There are some new developments in this arena that have the potential of transforming clinical practice. Resuscitation fluids/blood products simply replace the lost intravascular volume, but have no inherent prosurvival properties. It seems logical to use therapies that can create a “prosurvival phenotype.” These may include drugs to either improve tissue perfusion, or more specifically up-regulate innate prosurvival pathways. Historically, trauma resuscitation has focused on delivering more oxygen to the cells as a primary endpoint. Although desirable, it is not always possible. Excessive oxygen delivery can also cause reperfusion injury. A very different approach is to focus on enhancing the capability of cells/organs to survive shock, regardless of the poor oxygen delivery (ie, optimize the prosurvival potential of the cells). There are now several drugs that fit this bill, and many of these are already in clinical use for other indications (nontrauma). Pharmacologic resuscitation is also an attractive therapy for austere settings and battlefields as a bridge to definitive care.

Once exsanguination progresses to full cardiac arrest, nothing really works. Even if the source of bleeding can be controlled and circulation restored, ischemia lasting more than a few minutes invariably results in severe brain damage. Often the underlying injuries are reparable but the patient dies of irreversible shock or severe cerebral damage. In this setting, strategies to maintain cerebral and cardiac viability long enough to gain control of hemorrhage and restore intravascular volume could be life-saving. This requires an entirely new approach to the problem, with emphasis on rapid total body preservation, repair of injuries during metabolic arrest, and controlled resuscitation: emergency preservation and resuscitation. Currently, hypothermia is the most effective method for preserving cellular viability during prolonged periods of ischemia. Numerous well-designed preclinical studies clearly support this concept, and a multi-institutional clinical trial is about to start that will test the benefits of hypothermia in trauma patients. This monograph highlights resuscitation research that can potentially revolutionize the care of the injured patients in the near future.