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A Novel Trauma Model: Naturally Occurring Canine Trauma

Hall, Kelly E.*; Sharp, Claire R.; Adams, Cynthia R.; Beilman, Gregory§

doi: 10.1097/SHK.0000000000000058
Review Article
Free

ABSTRACT In human trauma patients, most deaths result from hemorrhage and brain injury, whereas late deaths, although rare, are the result of multiple organ failure and sepsis. A variety of experimental animal models have been developed to investigate the pathophysiology of traumatic injury and evaluate novel interventions. Similar to other experimental models, these trauma models cannot recapitulate conditions of naturally occurring trauma, and therefore therapeutic interventions based on these models are often ineffective. Pet dogs with naturally occurring traumatic injury represent a promising translational model for human trauma that could be used to assess novel therapies. The purpose of this article was to review the naturally occurring canine trauma literature to highlight the similarities between canine and human trauma. The American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma has initiated the establishment of a national network of veterinary trauma centers to enhance uniform delivery of care to canine trauma patients. In addition, the Spontaneous Trauma in Animals Team, a multidisciplinary, multicenter group of researchers has created a clinical research infrastructure for carrying out large-scale clinical trials in canine trauma patients. Moving forward, these national resources can be utilized to facilitate multicenter prospective studies of canine trauma to evaluate therapies and interventions that have shown promise in experimental animal models, thus closing the critical gap in the translation of knowledge from experimental models to humans and increasing the likelihood of success in phases 1 and 2 human clinical trials.

*Veterinary Clinical Sciences, University of Minnesota, St Paul, Minnesota; Cummings School of Veterinary Medicine, Tuft University, Grafton, Massachusetts; Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, Illinois; and §Department of Surgery, University of Minnesota, St Paul, Minnesota

Received 27 Apr 2013; first review completed 13 May 2013; accepted in final form 13 Sep 2013

Address reprint requests to Kelly E. Hall, DVM, MS, DACVECC, University of Minnesota, Veterinary Clinical Sciences, 1352 Boyd Ave, St Paul, MN 55108. E-mail: wilke022@umn.edu.

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INTRODUCTION

Trauma is defined as tissue injury that occurs more or less suddenly and includes physical damage to the body caused by violence or accident (1). Trauma is a major cause of morbidity and mortality in both human and veterinary patients (2–4). In fact, unintentional injury, generally secondary to motor vehicle accidents, is the most common cause of death for individuals younger than 5 years (5). Each year, more than 45,000 people in the United States alone die of motor vehicle accidents, and almost 2.5 million people are injured resulting in medical costs of more than $625.5 billion annually (6).

Most early trauma deaths are due to exsanguination/hemorrhagic shock (with blood loss of >30% of blood volume) and central nervous system injury, whereas late deaths are the result of sepsis and/or multiple organ failure (MOF) (7). Recent epidemiologic data indicate that early mortality attributable to exsanguination has decreased dramatically over the last decade in people (from 25% to 15%) with the advent of the advanced trauma life support concept in rescue systems, changes in resuscitation strategies, early goal-directed therapy in the emergency room, and improvements in hospital diagnostics, surgical techniques, and intensive care unit (ICU) care. There has also been improvement in mortality attributable to the later-stage complications of polytrauma (7, 8). To continue investigation of interventions to improve outcome in trauma patients, it is imperative that ongoing research be directed to furthering our understanding of the pathophysiology of trauma-induced complications and the development of novel interventions.

Despite advances in the management of trauma patients over recent decades, the morbidity and mortality that occur secondary to trauma remain unacceptably high. Although translational research will remain the motor of medical advancement in trauma, there are growing barriers between clinical and basic science, in particular government regulations and financial constraints that make translation challenging (9, 10). Given the similarities between naturally occurring trauma in dogs and trauma in people, the use of a naturally occurring canine model has the potential to bridge this bench to bedside gap, while benefiting both the human and veterinary trauma patient (3).

The objective of this article was to compare the clinical and pathophysiologic human and veterinary literature regarding trauma as an introduction to the potential utility of spontaneous canine trauma as a model of human trauma.

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METHODS

Using PubMed and cross-referencing articles after review, the canine trauma veterinary literature was collected and inputted into a central database for review by all authors. The human literature highlighting similarities was obtained with PubMed MeSH searching by topic area identified.

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Animal models currently used

Much of the current body of information regarding the body’s response to trauma has been elucidated in experimental rodent models (11). Some large animal models involving dogs, sheep, and pigs have also been evaluated. Early trauma models tended to involve a single insult such as hemorrhage (with or without fluid resuscitation), surgical laparotomy, head injury (12), femur fracture (13), or isolated, blunt lower-limb trauma. More recent models have combined two insults (so-called “two-hit models”), with the aim of better mimicking naturally occurring trauma in people (11), but even these models are far from replicating human trauma.

In hemorrhage models, animals are bled to a predetermined blood volume, arterial blood pressure, cardiac output, or another physiologic end point (14). Subsequently, fluid administration may be performed to create reperfusion injury, as would occur in the clinical setting. Although this controlled hemorrhage creates a somewhat reproducible model and is sufficient alone to induce hyperinflammation and immunosuppression, it fails to mimic the clinical situation because injured patients rarely suffer from isolated hemorrhagic shock (15). Acceptance of these limitations has led researchers to combine hemorrhage with tissue trauma, usually simulated by laparotomy. These combined hemorrhage plus trauma models have been demonstrated to intensify the hemorrhage-induced derangement of the immune system in both rats and mice (15–18). Laparotomy plus pressure-controlled hemorrhagic shock is probably the best studied animal model of multiple trauma; however, even this is still far from the clinical situation because surgical laparotomy is not the common tissue injury in multiple trauma patients, nor is hemorrhage controlled in the clinical setting. Uncontrolled hemorrhage models are most similar to what happens in naturally occurring trauma, but results are highly variable (11). Femur fracture has been used in place of surgical laparotomy, in combination with hemorrhagic shock, and all three insults have also been combined to result in an even more severe pattern of immune derangement (19). Given the significant limitations of experimental animal trauma models, more clinically relevant models of human trauma are urgently needed. Much of the data generated in experimental animal models of trauma have not translated well to the clinical realm for many reasons, including the fact that experimental animals are anesthetized during the manipulations. The success of human clinical trials has therefore been compromised. Naturally occurring canine trauma is very similar to the syndrome in people, making dogs potentially an ideal model for human trauma.

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The naturally occurring canine model

Trauma is a common cause of morbidity and mortality in dogs. Although there is not yet a national database for veterinary patients, traumatic injuries involving dogs are known to be a frequent cause for seeking veterinary care. Large-scale epidemiologic studies show that trauma accounts for approximately 11% to 13% of all cases presenting to urban veterinary teaching hospitals (4, 20, 21). A recent prospective multicenter study documented 315 consecutive canine trauma admissions during an 8-week period at four academic veterinary hospitals (22). In a study evaluating causes of death in more than 74,000 dogs, trauma was the second most common cause of death in juvenile and adult dogs, following infectious disease and neoplasia, respectively (23). More recent studies have documented many of the similarities in injury pattern and mechanism between humans and dogs sustaining trauma, including patient demographics (age and sex distribution), patterns and mechanisms of trauma, frequency of polytrauma, development of MOF, and predictive capabilities of injury scores (3, 24, 25).

Because the proposed model involves animals with naturally occurring disease, evaluating interventions to improve outcome in trauma patients with multifactorial injury will be more similar to the human condition than laboratory-created models. One potential benefit to using naturally occurring canine trauma over experimental models is that, with adequately funded projects, naturally occurring trauma in canine patients could be treated in a manner very similar to that of human trauma patients; importantly, patients experiencing real-life injuries would not be experimentally anesthetized when undergoing injury and treatment. For example, hemorrhagic shock is a common manifestation in canine trauma patients and an area of significant research efforts and dollars in human medicine. The ability to screen new interventions and devices (e.g., hemoglobin-based oxygen carriers, fibrinolysis inhibitors) in a clinical population of canines after proof-of-concept trials in the laboratory may offer a cost- and time-effective method to help accelerate the process of facilitating evaluation of new interventions from the bench to human safety (phase 1) and efficacy (phase 2) trials (bedside). Certainly hemoglobin-based oxygen carriers and fibrinolysis inhibitors have already been evaluated in the human condition, but research in ongoing exploring other interventions to improve outcome in the severely hemorrhaging trauma population. The ultimate vision is to utilize the naturally occurring canine model in conjunction with data obtained in preliminary laboratory models to improve time and cost efficiency in evaluation of new promising interventions for improvement of trauma patient care.

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Similarities in human and canine trauma morbidity and mortality

Age- and sex-specific responses

Similar to the patient demographics seen in the human trauma literature (14), dogs sustaining trauma are usually young to middle aged, and males predominate (3, 25). In addition, there is a significant subset of veterinary geriatric trauma patients, not unlike the human situation. This is of significance because it is well known that the nature of the inflammatory response varies according to age and sex. In human medicine, it is widely accepted that elderly patients have increased morbidity and mortality associated with trauma. However, the reasons for this are largely unknown (11), and currently there are few studies attempting to understand the mechanisms of systemic insults, such as trauma, in aged individuals. The National Trauma Institute has urged translational studies that focus on “the extremes of age” in a long list of traumatic injuries (10). Naturally occurring canine trauma presents an attractive approach to studying this demographic, as 9% (22/239) of canine trauma patients were geriatric in a recent review (25). As with elderly human patients, these dogs had significant comorbidities including heart disease, endocrine disease (including diabetes mellitus), and chronic renal disease. Given the gross inadequacy of current experimental models for application to elderly human trauma patients and the significant subset of geriatric dogs that sustain trauma, the canine model is particularly valuable (Table 1).

Table 1

Table 1

It is well recognized that the immune response to trauma is sex-dimorphic because sex steroids play a decisive role in the depression or maintenance of immune function following injury (26). In particular, estrogen is thought to confer a protective effect because immunosuppression in trauma patients is most severe in young males, ovariectomized females, and aged females (26). The beneficial effects of estrogen and the deleterious effects of testosterone have been demonstrated experimentally with the use of gonadectomized animals as well as by treating animals with hormonal agonists and antagonists in trauma-hemorrhage models (26). However, despite a wealth of recent literature in this field, more studies are needed to understand the precise mechanisms of the beneficial effects of estrogen. Dogs offer a unique opportunity to evaluate the effects of estrogen in trauma, in that we have a population of sexually intact female dogs that can be compared with ovariohysterectomized dogs and male dogs, and the effects of testosterone can be evaluated by comparing sexually intact male dogs to castrated male dogs.

Hypovolemic shock secondary to major bleeding is often seen in polytrauma and accounts for much of the early in hospital mortality in trauma (7). Evidence of hypoperfusion and hypovolemia is common in dogs presenting for evaluation of trauma. In a recent retrospective study of canine trauma, the presenting median lactate concentration in dogs requiring ICU admission was 3.5 mmol/L; mild uncompensated metabolic acidosis was also common (3). Whereas most dogs are treated with intravenous crystalloids for fluid resuscitation, a number of patients also require administration of blood products, as is the case in human medicine. In the aforementioned retrospective study, packed red blood cells (pRBCs) and fresh frozen plasma (FFP) were administered during initial resuscitation in approximately 5% of cases. A significant number of dogs also required blood products later in hospitalization; overall 57 (24%) of 235 and 66 (28%) of 235 received pRBCs and FFP, respectively. In that study, most patients were fluid responsive, and only three required vasopressor support (3).

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Thoracic injury

Dogs and humans have similar incidences of thoracic injury. In human medicine, 42% of polytraumatized patients have therapy-relevant findings on thoracic imaging (27), and chest injuries account for 20% to 30% of trauma-related deaths (28). In dogs, the most common thoracic injuries are pulmonary contusions [38.7% (29), 44% (30), 58% (3)) and pneumothorax (17.5% (31), 21% (32), 24% (29), 47% (3)]. Also seen are hemothorax, rib fractures, pneumomediastinum, diaphragmatic herniation, and flail chest (3, 29, 33, 34).

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Abdominal injury

Abdominal injury is also common in both dogs and people sustaining blunt trauma. Abdominal injury accounted for 6.9% of reported traumatic injuries in 2010 (28). Hemoperitoneum is reported commonly in dogs after blunt trauma, with prevalence ranging from 23% (3) to 38% (32). Urinary tract rupture [2% (32) to 3% (3)] and abdominal hernias (5%) occur in fewer dogs but are nonetheless significant and require surgical intervention (3).

Point-of-care ultrasound (e-FAST examination) allows for the detection of free intraperitoneal, pelvic, pericardial, and pleural fluid as well as pneumothorax and can be completed in less than 5 min with an overall accuracy of 90% to 98% for clinically significant intra-abdominal traumatic injuries in people (35). Similarly, point-of-care ultrasound is considered standard of care in veterinary medicine improving efficiency and appropriate intervention in traumatized patients (36). In a prospective study, 27% of canine trauma patients presented with evidence of free abdominal fluid, and patients with a higher FAST score (fluid in at least three of four sites evaluated) had an increased need for blood transfusion (37).

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Orthopedic injury

Dogs and humans also share orthopedic injury as a significant cause of morbidity and potential mortality. The epidemiology of orthopedic injury in people with polytrauma is poorly described, although likely significant. One author documented that about 20% of the polytrauma patients in their hospital undergo damage control orthopedic surgery (38). A large number of dogs experience orthopedic injuries as well, with common injuries including pelvic fracture (28%), femur fracture (16%), hip luxation (12%), distal limb fracture (8%), spinal fracture (10%), sacral luxation (9%), and sacral fracture (3). Less common but still seen in dogs are thoracic limb orthopedic injuries including scapular fracture (7%), elbow luxation (3%), and radius fracture (2%) (3).

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Head injury

In human medicine, head injury and traumatic brain injury account for 40% to 60% of trauma-related deaths (39–42). Hyperglycemia is particularly problematic in people and animals with head trauma (43, 44). Traumatic brain injury is often evaluated in isolation in experimental models, but traumatic brain injury as part of a polytrauma syndrome is considerably more complex to manage, requiring a more clinically relevant model. Head injury occurs commonly in dogs and is associated with significant morbidity and mortality (45–50).

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Multiple organ failure

Like people, dogs sustaining trauma develop a systemic inflammatory response, and this response underlies the development of MOF. Both canine and human trauma patients usually present with fever, tachycardia, tachypnea, and leukocytosis (3, 8, 51, 52). Likewise, in both species, the cytokine storm in the early proinflammatory state following trauma results in increased plasma concentrations of inflammatory mediators. Various studies in human medicine have documented increased concentrations of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, and chemokine ligand (CX-CL8) (53). Preliminary studies have also documented increased circulating concentrations of proinflammatory cytokines (TNF, IL-6, and CX-CL8) in dogs with trauma-induced systemic inflammation (54).

Other organ dysfunctions of significance that can occur as a result of systemic inflammatory response syndrome (SIRS) and have been documented in human and veterinary trauma patients include metabolic, renal, hepatic, and gastrointestinal dysfunction (25, 55–58).

Lung injury, in its most severe form manifesting as acute respiratory distress syndrome (ARDS), is one of the most frequent and severe sequela in people with posttraumatic SIRS. In SIRS, ARDS is precipitated by the cytokine storm, which damages alveolar epithelial and endothelial cells and is associated with an influx of activated neutrophils and protein-rich fluid into the alveoli (57). Diffuse alveolar damage not only impairs gas exchange, but also reduces endogenous protective mechanisms such that these patients are at increased risk of developing pneumonia. In a large, prospective cohort study evaluating 4020 human blunt trauma patients, 12% developed ARDS, and the development of ARDS was associated with dramatically higher mortality (20% compared with 11.9% in patients without ARDS). Older people are also more likely to develop and succumb to ARDS following trauma (59). Acute respiratory distress syndrome is also a recognized complication in veterinary trauma patients (25, 60). A recent retrospective study documented ARDS in 3% of patients (7/235). In addition to these dogs, another two dogs in that study required mechanical ventilation because of the severity of pulmonary injury (3). Only one of those nine ventilated dogs survived to discharge, highlighting the potential for lung injury to contribute to late-stage mortality in canine trauma patients. Survival rates for dogs ventilated for management of pulmonary contusions in another study were slightly higher (30%). Although not discussed specifically, it appears that these dogs could be considered to have had ARDS based on a mean PaO2:FIO2 ratio of 77.49 (SD, 24.8) before ventilation (60).

The coagulation system is activated concurrently with inflammation in the setting of severe trauma. Trauma results in vascular endothelial damage, resulting in exposure of tissue factor that initiates the coagulation cascade. There is also tight interplay between inflammation and coagulation such that each perpetuates the other. In addition to upregulation of procoagulant pathways, endogenous anticoagulants (such as antithrombin and protein C) are depleted. Both hypercoagulability and hypocoagulability have been described in trauma patients (61, 62), with up to 85% experiencing a hypercoagulable state (63). A recent systematic review of the coagulopathy of trauma that looked for relevant experimental models with which to study early traumatic coagulopathy concluded that there is an utter lack of relevant models and calling for models that more closely resemble human physiology (64). Dogs and humans experience similar hemostatic changes associated with other inflammatory conditions, particularly sepsis (65–71); therefore, dogs are a promising naturally occurring model of this posttraumatic coagulopathy.

At this time, there is no consensus definition of posttraumatic coagulopathy, and we are far from understanding its highly complex pathophysiology (72, 73). The correlation between traditional laboratory tests of coagulation and clinical signs of hemorrhage or thrombosis is poor. Conventional coagulation parameters, such as the prothrombin time (PT) and partial thromboplastin time (PTT), are inadequate alone to interpret a patient’s coagulation status. Thromboelastography is increasingly common and provides a more global evaluation of coagulation and a guide to transfusion therapy in hemorrhage (74). In veterinary medicine, there is a paucity of current literature describing the coagulopathy of trauma. A large retrospective canine study documented mild PT prolongation (25%–50% greater than control) in 13.2% and mild PTT prolongation in 30.2% of cases (3). Moderate PT prolongation (50%–100% greater than control) was observed in 7.5% of dogs, and moderate PTT prolongation in 13.2%. An abstract presented on a more recent prospective study evaluating 40 canine traumatic injuries documented hypocoagulability in more severely injured dogs (75). To the knowledge of the authors, there are no published reports objectively documenting hypercoagulability in veterinary trauma patients. Additional veterinary studies are required to elucidate the role of dysregulated coagulation in veterinary trauma.

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Scoring systems and clinical management

A variety of trauma scoring systems are used in human medicine, of which the Trauma and Injury Severity score is the most widely accepted (28, 76). As in human medicine, scoring systems are used in veterinary medicine for patient stratification. The Animal Trauma Triage (ATT) score has been statistically validated in dogs and cats (77) and has been correlated with survival in multiple subsequent retrospective studies (3, 25). The Glasgow Coma Scale score has also been validated for use in dogs (46). These scoring systems will allow comparison of injury severity between study centers and of treatment effects across different subgroups of injury.

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Differences in canine and human trauma

Although there are many similarities that make naturally occurring trauma in dogs an attractive model for human trauma, as with all animal models of human disease, there are shortcomings. Prehospital care for injured animals is very different from human prehospital care: the animal’s owner most commonly provides transport to veterinary hospitals, generally with no intervention, beyond compression to bleeding sites and covering open wounds, provided en route. The Veterinary Committee on Trauma recognizes this as an area of opportunity to improve trauma patient care and has a “prehospital” subcommittee that will be exploring application of prehospital modalities in regions where veterinary trauma center networks have been developed. Prehospital methods exist in a minor way with respect to working dogs (e.g., police, military, etc.). At the authors’ institutions, transport of canine working dogs is considered an emergency resulting in rapid transport to veterinary hospital facilities via emergency vehicles. The Veterinary Committee on Trauma (VetCOT) Prehospital subcommittee will also be exploring expansion and formalization of training programs (which already exist) provided to human first responders who frequently come across animal injuries in human scenarios (e.g., house fires, car accidents, working dogs at events). Although there may be a difference in prehospital resources, when enrolling canine patients in prospective clinical trials, presentation to the hospital within a certain time period (e.g., 30–60 min) could be a required inclusion criterion. In the recent 8-week canine trauma multicenter study, approximately 70% of canine patients presented to the facility directly after their injury (22).

Another limiting factor in delivery of available clinical resources to clinical canine trauma patients is cost of care. The option to pet owners for euthanasia in veterinary medicine is a difference in clinical patient approach; however, because many similar clinical resources are available to the patient, investigation of interventions through funded clinical trials would help minimize this factor. Multicenter veterinary clinical trials in other areas of translation (e.g., oncology, epilepsy) frequently include study intervention and diagnostic test costs as incentive for the owner. This added incentive (to cover out of pocket expenses occurred by the owner for care) results in large success in recruiting patients to clinical trials. Finally, study design and statistical methods can be used to minimize the impact of this factor, as well.

One common misconception, experienced by the authors (K.E.H., C.R.S.) whose practices are housed in large veterinary tertiary hospitals, is availability of resources for the patient. The guidelines (https://sites.google.com/a/umn.edu/vetcot/) generated by the VetCOT outline resources that must be available in all level I veterinary trauma centers, including blood bank capabilities, advanced imaging 24-7 (computed tomography or magnetic resonance imaging), ability to perform damage control resuscitation, and availability of multiple specialties to the most severely injured canine trauma patient (surgeon, neurologist, ophthalmologist, radiologist, anesthesiologist, etc.). An ICU and emergency room overseen by a board-certified critical care specialist (DACVECC) and staffed separately 24-7-365 are also required of all level I veterinary trauma centers. Although these resources are certainly not available at all veterinary hospitals, the formalization of a veterinary trauma center network will enhance delivery of care to those animals transported to level 1 centers and ensure availability to those resources. One challenge moving forward will be to ensure local practitioners and pet owners living in the veterinary trauma center regions are well aware of the resources available.

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Available canine clinical research infrastructure

A multidisciplinary, multi-institutional group, Spontaneous Trauma in Animals Team (STAT), has been created with a primary goal to improve trauma patient outcome through comparative and translational medicine. The group’s first project enrolled 315 consecutive canine trauma cases at four centers over an 8-week period utilizing a Web-based data capture system (78). Blunt trauma (motor vehicle accident, fall) occurred most commonly (55%) followed by penetrating (34%, gun shot wound, animal interaction, etc.) and unknown (11%) trauma. A majority of the animals (91%) survived to discharge. Admission variables including injury severity scores (ATT) (range, 0–18), modified Glasgow Coma Scale (mGCS) (range, 3–18) and lactate were associated with nonsurvival (ATT score ≥5 [area under the curve {AUC}, 0.91], mGCS ≤17 [AUC, 0.87], lactate ≥4.0 [AUC, 0.79]). Surgery was required in 50% of the cases, with a majority (70%) being soft tissue procedures, 28% orthopedic procedures, and 3% requiring neurologic surgery (22). The STAT infrastructure has been designed in anticipation of performing future intervention studies. Study execution, expertise, and resources for current and future projects will be provided by the site investigator working group made up of veterinary critical care specialists; a data monitoring/advisory committee made up of human trauma surgeons, epidemiologist, biostatistician, and veterinary critical care specialists; and individual center veterinary clinical research organizations (e.g., Clinical Investigation Center, University of Minnesota), which provide research coordinators and clinical research technicians to ensure efficient study logistics. All centers involved require Institutional Animal Care and Use Committee approval for clinical research on client owned animals. Informed client (pet owner) consent with Institutional Animal Care and Use Committee–approved consent forms is required for all veterinary clinical research projects performed at veterinary teaching hospitals.

The concept of evaluating naturally occurring diseases in dogs to enhance human patient care has become more prevalent in recent years, particularly in the fields of oncology (79), epilepsy (80), and gene therapy (81). Dogs represent a powerful tool for evaluating genetic diseases and response to therapy due to large genetic diversity in the overall population (e.g., teacup poodle vs. bull mastiff vs. “mutt”), as well as large populations of uniformly similar bred animals with known heredity maps (e.g., www.akc.org). With completion of the human genome (2004) and canine genome mapping completed in multiple breeds, research interest in applying canine genomics to solve challenges in human medicine has recently expanded rapidly. There are many examples whereby hereditary diseases that are common in certain breeds of dogs, yet uncommon in people, have been investigated and therapeutic interventions created (e.g., Leber congenital amaurosis type 2, Birt-Hogg-Dubé syndrome) (79, 81). With trauma representing approximately 10% to 13% of patients presenting to tertiary veterinary hospitals and the development of the national veterinary trauma network and registry, an opportunity to identify genetic determinants of response to trauma may be possible, as trauma does not have a breed predilection.

Veterinary oncology, epilepsy, and genomic studies are just a few examples of areas that have leveraged similarities in the canine and human condition to advance human and veterinary medicine with well-funded veterinary clinical projects. All of these areas have successfully obtained National Institutes of Health funding to advance the care of humans and animals, alike. Regarding trauma research, specifically, the opportunities to evaluate lightweight, effective, and practical interventions for severely traumatized soldiers (and occasionally their working dogs) are a driver for many government- funded projects (Department of Defense, US Special Operations Command); in fact, some of the military government agencies have funding available specifically for canine trauma studies (US Special Operations Command). Finally, veterinary trials in other areas (e.g., oncology, spinal injury, etc.) have obtained funding from industry partners and private companies interested in interventional trials that are inserted as pre–phase 1 or phase 2 human clinical trials guiding “go/no go” decisions. The infrastructure provided by the STAT group will maximize the ability to facilitate and carry out intervention studies sponsored by the government, industry, and foundation partners, alike (Fig. 1).

In addition to the clinical and translational research-driven STAT group, the American College of Veterinary Emergency and Critical Care Society (the veterinary critical care specialty college) has created the VetCOT, which has established Guidelines for Veterinary Trauma Centers (https://sites.google.com/a/umn.edu/vetcot/), and is creating a network of lead hospitals that seed development of trauma systems. These hospitals will work collaboratively to define high standards of care and disseminate information that improves trauma patient management uniformity, efficiency, and outcome. The VetCOT is also developing a canine trauma registry to allow a large database of information that will be accessible to clinical researchers.

Fig. 1

Fig. 1

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CONCLUSIONS

The clinical management of canine trauma patients presenting to tertiary referral hospitals, such as the authors’ institutions, has many similarities to human medicine. While prehospital treatment in veterinary medicine is generally very limited, most patients are seen by a primary veterinarian within a short interval after the trauma. Emergency room treatment is very similar, involving intravenous fluid resuscitation from shock, damage control surgery, administration of blood products, emergency diagnostics, imaging as needed, and screening blood work. These similarities in patient management will allow data gathered in a canine model of naturally occurring trauma to have translational application.

The canine trauma model offers an opportunity to leverage information learned from experimental canine trauma models in concert with information from naturally occurring canine trauma models that occur in the clinical setting. From this, we can gain a better understanding of the physiologic alterations that occur during traumatic injury and the subsequent development of SIRS, sepsis, and MOF. Prospective, multicenter studies at high-volume veterinary medical centers would enable interventional trials that could be inserted as pre–phase 1 or phase 2 human clinical trials to guide “go/no go” decisions for groups developing therapeutic strategies to improve outcome for human trauma patients, thereby benefiting human and veterinary patients, alike.

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Keywords:

Veterinary; hemorrhagic shock; multiple organ failure; acute respiratory distress syndrome; coagulopathy of trauma

© 2014 by the Shock Society