Comparing the effects of various fluid resuscitative strategies on Glycocalyx damage in a canine hemorrhage model.

Hemorrhagic shock and subsequent resuscitation can cause significant dysregulation of critical systems, including the vascular endothelium. Following hemorrhage, the endothelial lining (glycocalyx) can shed, causing release of glycocalyx components, endothelial activation, and systemic inflammation. A canine model of hemorrhagic shock was used to evaluate five resuscitation fluids, including Lactated Ringers+Hetastarch, Whole Blood (WB), Fresh Frozen Plasma+packed Red Blood Cells (FFP+pRBC), and two hemoglobin-based oxygen carrier (HBOC) fluids, for their impact on glycocalyx shedding. Under anesthesia, purpose-bred adult canines were instrumented and subjected to a controlled hemorrhage with blood being drawn until a mean arterial pressure of <50 mmHg was reached or 40 % of the estimated blood volume was removed. Canines were left in shock for 45 mins before being resuscitated with one of the resuscitation fluids over 30 mins. Following resuscitation, the dogs were monitored up to 2 weeks. Following an additional 3-4 weeks for washout, the canines repeated the protocol, undergoing each resuscitation fluid individually. Blood samples were collected during each round at various timepoints for serum isolation, which was used for detection of glycocalyx biomarker. Comparison of baseline and post-hemorrhage alone showed a significant reduction in serum protein (p<0.0001), heparan sulfate (p<0.001), and syndecan-1 (p<0.0001) concentrations, and a significant increase in hyaluronan (p<0.0001) concentration. Intercomparisons of resuscitation fluids indicated minimal differences in glycocalyx markers over time. Comparisons within each fluid showed dynamic responses in glycocalyx biomarkers over time. Relative to individual baselines, syndecan-1 was significantly reduced after resuscitation in most cases (p<0.0001), excluding WB and FFP+pRBC. In all cases, VE-cadherin was significantly elevated at 24 hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3 hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3 hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24 hr (p<0.01), except WB. The temporal changes in canine glycocalyx biomarkers were atypical of hemorrhage response in other species. This suggests that the hemorrhage lacked severity and/or typical glycocalyx biomarkers do not reflect the canine endothelium compared to other species. Further research is needed to characterize the canine endothelium and the response to resuscitation fluids.

Incidence of Intra-abdominal Adhesions Following Intraperitoneal Injection of Hemostatic Products in Rabbits.

INTRODUCTION: Definitive management of non-compressible intra-abdominal hemorrhage (NCIAH) currently requires a surgeon and operating room capable of performing damage control surgery. In a wartime scenario or a geographically remote environment, these may not be readily available. In this study, we sought to test the safety of 2 emerging injectable hemostatic agents (CounterFlow and Fast Onset Abdominal Management, or FOAM, poloxamer component) versus normal saline control over a prolonged monitoring duration following administration by a non-surgical provider. MATERIALS AND METHODS: The Institutional Animal Care and Use Committee approved all research conducted in this study. We randomized male New Zealand white rabbits into 2 monitoring cohorts of 24 hours and 2 weeks. Each cohort contained 3 treatment groups (n = 4 rabbits/group): CounterFlow, the testable poloxamer component of FOAM, and normal saline control. We injected each treatment intraperitoneally in the left lower abdominal quadrant. Doses were 15 mL/kg for CounterFlow, 6.3 mL/kg for the poloxamer component of FOAM, and 15 mL/kg for normal saline. We conducted all injections under isoflurane anesthesia monitored by trained veterinary staff. Animals were euthanized at each cohort end point, and a veterinary pathologist blinded to treatment type performed necropsy. The primary outcome was incidence of intra-abdominal adhesions at necropsy. Quantitatively, adhesions when present were graded by the veterinary pathologist on a 1 to 4 scale, where "1" represented adhesions involving from 1 to 25% of the examined abdomen, "2" represented from 26 to 50%, "3" represented from 51 to 75%, and "4" represented from 76 to 100%. Qualitatively, adhesions present were graded by degree ("1" = minimal, "2" = mild, "3" = moderate, and "4" = severe) and chronicity ("1" = acute, "2" = subacute, and "3" = chronic). We also drew d-dimer blood values and measured body weights for each animal. Statistical analysis included either repeated measures 2-way ANOVA or a mixed-effects model (in the case of missing data) with Geisser-Greenhouse correction. We adjusted multiple comparisons using Tukey statistical hypothesis tests. RESULTS: In the 2-week cohort, 3 CounterFlow animals showed adhesions judged to be "1" quantitatively. Qualitatively, 2 of these were assessed as "1" for degree of adhesions and the other demonstrated a "2." On the chronicity of adhesions scale, 1 animal demonstrated a "2" and 2 demonstrated a "3." No animals in other groups (FOAM and control) demonstrated adhesions. CounterFlow-treated animals showed a statistically significant rise in d-dimer values in the 24-hour cohort only. In the 2-week cohort, CounterFlow-treated animals showed a decrease in body weight at 24 hours after injection but returned to their baseline (normal) body weights at 7 days. CONCLUSIONS: Findings from this study demonstrate that the tested ingredients of FOAM poloxamer component are safe for intraperitoneal injection and hold potential for further study directed toward prehospital non-compressible intra-abdominal hemorrhage management by non-surgical providers. Although CounterFlow produced abdominal adhesions in 3 of 4 rabbits in the 2-week cohort, these were determined to be "minimal" or "mild" in degree.

Causes of mortality in military working dog from traumatic injuries.

Introduction: This study aimed to identify the pathophysiologic causes of death following traumatic injuries in military working dogs (MWDs) and determine the risk factors associated with mortality in MWD following traumatic injuries. The results of this study will allow for better targeting of interventions to ameliorate these pathophysiologic causes of death and inform research priorities directed at the pathophysiology that leads to the death of MWDs. Methods: The final dataset for this study was compiled by using two previously established datasets. Based on review of available data and supplemental records (when available), MWDs in which a definitive cause of death could be determined were included in the study population. These MWDs were assigned a cause of death based on categories previously identified in studies evaluating service member casualties. A group of MWDs who survived their traumatic injury and had similar mechanisms of injury and types of injury to the deceased MWDs were included to allow for comparison and establishment of risk factors associated with MWD death. Variables collected included breed, age, sex, mechanism of injury, survival/non-survival, type of trauma, mechanism of injury, pathophysiology that led to death and pre-hospital care provided. Statistical analysis included Fishers exact test for categorical variables and univariable and multivariable logistic regression to identify factors associated with the MWD death. Results: A total of 84 MWDs (33 non-survivors and 51 survivors) were included in this study. Of the 33 MWDs that died, 27 (81.8%) were noted to be dead on arrival. The pathophysiologic causes of death were found to be hemorrhage (45.5% [n = 15]), head trauma (21.2% [n = 7]), catastrophic tissue destruction (15.2% [n = 5]), pneumothorax (9.1% [n = 3]) and one (3% [n = 1]) of each of the following: septic shock, asphyxiation and burns. Military working dogs that did not receive non-DVM care were 3.55 times more likely to die than those that did receive non-DVM care (95% CI 1.03-12.27). The majority of MWDs died of their injuries before reaching veterinary care. Discussion: To increase the survival of MWDs on the battlefield, further research should focus on developing new interventions and techniques to mitigate the effects of the pathophysiology noted to cause MWD death. Furthermore, given that care by a non-DVM was found to be associated with survival, the implementation of pre-hospital care and early resuscitation techniques should be a continued priority for those treating MWDs at both the point of injury and in the prehospital setting.

Deep learning models for interpretation of point of care ultrasound in military working dogs.

Introduction: Military working dogs (MWDs) are essential for military operations in a wide range of missions. With this pivotal role, MWDs can become casualties requiring specialized veterinary care that may not always be available far forward on the battlefield. Some injuries such as pneumothorax, hemothorax, or abdominal hemorrhage can be diagnosed using point of care ultrasound (POCUS) such as the Global FAST® exam. This presents a unique opportunity for artificial intelligence (AI) to aid in the interpretation of ultrasound images. In this article, deep learning classification neural networks were developed for POCUS assessment in MWDs. Methods: Images were collected in five MWDs under general anesthesia or deep sedation for all scan points in the Global FAST® exam. For representative injuries, a cadaver model was used from which positive and negative injury images were captured. A total of 327 ultrasound clips were captured and split across scan points for training three different AI network architectures: MobileNetV2, DarkNet-19, and ShrapML. Gradient class activation mapping (GradCAM) overlays were generated for representative images to better explain AI predictions. Results: Performance of AI models reached over 82% accuracy for all scan points. The model with the highest performance was trained with the MobileNetV2 network for the cystocolic scan point achieving 99.8% accuracy. Across all trained networks the diaphragmatic hepatorenal scan point had the best overall performance. However, GradCAM overlays showed that the models with highest accuracy, like MobileNetV2, were not always identifying relevant features. Conversely, the GradCAM heatmaps for ShrapML show general agreement with regions most indicative of fluid accumulation. Discussion: Overall, the AI models developed can automate POCUS predictions in MWDs. Preliminarily, ShrapML had the strongest performance and prediction rate paired with accurately tracking fluid accumulation sites, making it the most suitable option for eventual real-time deployment with ultrasound systems. Further integration of this technology with imaging technologies will expand use of POCUS-based triage of MWDs.

Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock.

BACKGROUND: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01). CONCLUSION: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.

The use of a kaolin-based hemostatic dressing to attenuate bleeding in dogs: A series of 4 cases.

OBJECTIVE: To describe the use of a synthetic hemostatic dressing, QuikClot Combat Gauze (QCG), in dogs with bleeding wounds. CASE SERIES SUMMARY: Two dogs presented with bleeding traumatic wounds, and QCG was used to achieve hemostasis during stabilization of these dogs. In the other 2 dogs, QCG was used to help attenuate bleeding associated with a surgical procedure. NEW OR UNIQUE INFORMATION PROVIDED: While hemostatic dressings have been widely studied and used in human medicine, there is minimal information on the use and efficacy of these hemostatic dressings in veterinary medicine. This case series describes the use of QCG in dogs with hemorrhaging wounds. QCG could be a valuable resource in veterinary emergency and critical care settings.

In vitro evaluation of hyperosmotic canine plasma suitable for infusion.

OBJECTIVE: To determine the characteristics of canine freeze-dried plasma (cFDP) as it is serially diluted with sterile water. DESIGN: In vitro experimental study. SETTING: Government blood and coagulation research laboratory. ANIMALS: cFDP from a commercial manufacturer. INTERVENTIONS: Ten units of cFDP were reconstituted to 100%, 90%, 80%, 70%, 60%, 50%, and 40% of the recommended volume with sterile water. The resultant solutions were analyzed for coagulation factor activity (factors II, V, VII, VIII, IX, X, and XII as well as antithrombin), fibrinogen concentration, prothrombin time, activated partial thromboplastin time, viscosity, osmolality, and kaolin-activated thromboelastography. MEASUREMENTS AND MAIN RESULTS: Viscosity, osmolality, and turbidity properties of plasma were increased in a reconstitution volume-dependent manner, with the 40% suggested volume generating approximately 2-fold increases in each. Similarly, factor activity levels and fibrinogen concentration increased by approximately 2-fold over this range in a concentration-dependent manner. Prothrombin time declined from 11.4 seconds at 100% volume to 10.9 seconds at 70% before increasing to 11.9 seconds at 40%. Activated partial thromboplastin time increased exponentially from 21.8 seconds at 100% rehydration to 100.0 seconds at 40%. R-time on TEG increased from 3.1 to 13.9 minutes at 50% rehydration, while alpha angle declined from 61.3° to 24.7° over the same range, and the maximum amplitude initially increased from 13.2 mm at 100% water to 18.6 mm at 70% water before dropping back down to 14.6 mm at 50% water. No clotting was observed with 40% rehydration. CONCLUSIONS: The creation of hyperosmotic plasma from cFDP appears feasible with preservation of concentrated coagulation factors, although there are some unexplained effects that happen to coagulation functions at the highest concentrations tested using only 40%-50% of recommended rehydration volume. Further studies are needed to evaluate the hyperosmotic product in vivo.

Identification of Potentially Preventable Traumatic Injury Among Military Working Dogs Deployed During the Global War on Terror.

BACKGROUND: Prevention of deployment-related injury is critical for readiness of US military working dogs (MWDs). This study evaluated deployment-related injuries to determine if they were potentially preventable and identify possible abatement strategies. METHODS: Data were collected on 195 MWD injury events that occurred between 11 September 2001 and 31 December 2018. Injuries were reviewed by a panel of veterinarians and categorized into groups based on panel consensus. The panel also established which interventions could have been effective for mitigating injuries. Multipurpose canine (MPC) and conventional MWD injury event characteristics were compared to identify meaningful differences. RESULTS: Of the 195 injuries, 101 (52%) were classified as preventable or potentially preventable. Most (72%) of the potentially preventable injuries occurred in conventional MWDs, with penetrating injuries (64%) being the most common type of trauma. For the preventable/potentially preventable injuries, the most common preventative intervention identified was handler training (53%) followed by protective equipment (46%). There were differences between MPCs and conventional MWDs for injury prevention category, type of trauma, mechanism of injury, and preventative intervention (all p < .001). CONCLUSION: The application of a preventable review process to MWD populations may be beneficial in identifying potentially preventable injuries and preventative intervention strategies.

Comparison of assessment of coagulation in healthy dogs by the TEG 6s and TEG 5000 viscoelastic analyzers.

The TEG 6s (Haemonetics) point-of-care viscoelastic analyzer is portable, compact, simple to use, and has the potential for rapid viscoelastic analysis that can guide the treatment of veterinary patients at the site of care. Although approved for use in people, the TEG 6s has yet to be evaluated for hemostatic analysis in veterinary medicine. Citrated whole blood (CWB) was collected from 27 healthy dogs. An aliquot of CWB from each dog was diluted by 33% with an isotonic crystalloid, representing an in vitro model of hemodilution. Unaltered and diluted CWB samples were analyzed using 2 TEG 6s and 6 TEG 5000 (Haemonetics) analyzers. The 6 TEG 5000 analyzers ran duplicate analyses of either unaltered or diluted samples using 1 of 3 reagents (Haemonetics): Kaolin TEG, RapidTEG, or TEG Functional Fibrinogen. Duplicate TEG 5000 analyses were averaged and compared with a single TEG 6s analysis. Lin concordance correlation coefficient and Bland-Altman plots were used to evaluate agreement of reaction time, kinetic time, alpha angle, maximum amplitude (MA), and G value (G) for samples activated with Kaolin TEG, and agreement of MA for samples activated with RapidTEG between the 2 machines. Overall, agreement between the TEG 6s and TEG 5000 analyzers was poor. Viscoelastic measurements by the TEG 6s and TEG 5000 in healthy dogs were not all interchangeable. Agreement was satisfactory only for MA and G measurements of diluted blood samples activated with Kaolin TEG, and MA measurements for both unaltered and diluted blood samples activated with RapidTEG.

Hemoglobin-Based Oxygen Carrier for the Reconstitution of Canine Freeze-Dried Plasma in an In Vitro Model of Resuscitation.

Military working dogs (MWDs) are force multipliers that are at risk for severe trauma when employed on the battlefield. When in severe hemorrhagic shock, MWDs require both oxygen- carrying capacity and replacement of vascular volume and coagulation factors. The objective of this study was to evaluate the hemostatic capacity of canine freeze-dried plasma (cFDP) with a Food and Drug Administration (FDA)-approved hemoglobin- based oxygen carrier (HBOC) in an in vitro model of resuscitation. Whole blood (WB) was collected from 10 MWDs, and these samples were diluted by 10%, 25%, or 40% with either cFDP (reconstituted with water), HBOC, cFDP (reconstituted with HBOC), or an equal volume of a 1:1 ratio of cFDP (reconstituted with water) and HBOC. Hemostatic parameters were minimally changed based on evaluation of prothrombin time, activated partial thromboplastin time, fibrinogen and thromboelastography at the 10% and 25% dilutions, and parameters consistent with a hypocoagulability were seen at dilutions of 40%. Based on the results of this study, additional research is warranted to determine if cFDP reconstituted with HBOC is a viable resuscitation product in canine trauma.

Hemorrhagic shock and hemostatic resuscitation in canine trauma.

Hemorrhage is a significant cause of death among military working dogs and in civilian canine trauma. While research specifically aimed at canine trauma is limited, many principles from human trauma resuscitation apply. Trauma with significant hemorrhage results in shock and inadequate oxygen delivery to tissues. This leads to aberrations in cellular metabolism, including anaerobic metabolism, decreased energy production, acidosis, cell swelling, and eventual cell death. Considering blood and endothelium as a single organ system, blood failure is a syndrome of endotheliopathy, coagulopathy, and platelet dysfunction. In severe cases following injury, blood failure develops and is induced by inadequate oxygen delivery in the presence of hemorrhage, tissue injury, and acute stress from trauma. Severe hemorrhagic shock is best treated with hemostatic resuscitation, wherein blood products are used to restore effective circulating volume and increase oxygen delivery to tissues without exacerbating blood failure. The principles of hemostatic resuscitation have been demonstrated in severely injured people and the authors propose an algorithm for applying this to canine patients. The use of plasma and whole blood to resuscitate severely injured canines while minimizing the use of crystalloids and colloids could prove instrumental in improving both mortality and morbidity. More work is needed to understand the canine patient that would benefit from hemostatic resuscitation, as well as to determine the optimal resuscitation strategy for these patients.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine - Part 2: Transfusion Advances.

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.

Comparison of trauma sustained by civilian dogs and deployed military working dogs.

OBJECTIVE: To compare the prevalence of types of trauma, mechanisms of injury, and outcomes among military working dogs (MWDs), operational canines (OpK9s), and civilian dogs (CDs) that sustained traumatic injury. DESIGN: Retrospective descriptive analysis. ANIMALS: One hundred and ninety-three cases of MWD trauma, 26,099 cases of CD trauma, 35 cases of OpK9 trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of MWDs that incurred trauma while deployed to the Middle East were identified, and information was extracted from these records. The resultant database was compared to CD and OpK9s in the American College of Veterinary Emergency and Critical Care (ACVECC) Veterinary Committee on Trauma registry. All 3 groups showed similar trends with regard to type of trauma: penetrating injuries occurred most frequently, followed by blunt injuries for CDs and OpK9s. An equal proportion of blunt and blunt and penetrating traumas were observed in MWDs. Only MWDs sustained trauma from explosions, which accounted for 22.3% of injuries in this group. Animal bite/scratch/quilling and motor vehicle accidents (MVAs) were significantly more prevalent among CDs than MWDs (P < 0.01), whereas injuries from gunshot wounds (GSW) or a knife/sharp object were more common among MWDs compared to CDs (P < 0.01). No statistical differences in survival were observed between CDs and MWDs after excluding civilian dogs euthanized due to financial limitations. CONCLUSIONS: MWDs, OpK9s, and CDs experience differences in injury type, mechanism, and outcome. Regardless, MWDs and CDs have good prognosis for survival to discharge after trauma.

Hemostatic capacity of canine chilled whole blood over time.

OBJECTIVE: To determine the hemostatic potential of canine chilled whole blood maintained at clinically relevant storage conditions. DESIGN: In vitro experimental study. SETTING: Government blood and coagulation research laboratory and government referral veterinary hospital. ANIMALS: Ten healthy Department of Defense military working dogs. INTERVENTIONS: One unit of fresh whole blood was collected from each of 10 military working dogs using aseptic technique. Blood was maintained in a medical-grade refrigerator for 28 days at 4°C (39°F) and analyzed before refrigeration (day 0) and after (days 2, 4, 7, 9, 11, 14, 21, and 28). MEASUREMENTS AND MAIN RESULTS: Ten units of canine blood were analyzed with whole blood platelet aggregation, thromboelastography, CBC, biochemical analysis, blood gas, and prothrombin/activated partial thromboplastin/fibrinogen assay. Clotting strength of chilled blood was maintained up to 21 days despite significant decreases in platelet aggregation to ADP, collagen, or γ-thrombin, significant prolongation of prothrombin and activated partial thromboplastin times, and reduced speed of clot formation (K time, alpha angle). Fibrinogen concentration, WBC, RBC, and platelet counts did not change over time. CONCLUSIONS: Chilled canine whole blood loses a small percentage of clot strength through 21 days of refrigerated storage. Further research is needed to determine if this hemostatic potential is clinically relevant in hemorrhaging dogs who require surgical intervention or are exposed to traumatic events.

Effects of refrigerated storage on hemostatic stability of four canine plasma products.

OBJECTIVE: To assess clotting times, coagulation factor activities, sterility, and thromboelastographic parameters of liquid plasma (LP), thawed fresh frozen plasma (FFP-T), and 2 novel formulations of freeze-dried plasma (FDP) stored refrigerated over 35 days. SAMPLE: 6 units of canine LP and FFP-T from a commercial animal blood bank and 5 units each of 2 formulations of canine FDP. PROCEDURES: Prothrombin time; activated partial thromboplastin time; activities of coagulation factors II, V, VII, VIII, IX, X, XI, and XII; and thromboelastographic parameters were determined for each product on days 0 (baseline), 3, 7, 14, 21, 28, and 35. For each day, a sample of each product was also submitted for aerobic bacterial culture. RESULTS: Small changes in coagulation factor activities and mild increased time to initial clot formation in LP and FFP-T were noted over the 35-day storage period. Activities of factor VIII in FDP1 and factor XII in FDP2 were < 50% at baseline but varied throughout. Compared with FFP-T, time to initial clot formation was increased and clot strength was preserved or increased for the FDPs throughout the study. One FDP had decreased pH, compared with other products. No plasma product yielded bacterial growth. CONCLUSIONS AND CLINICAL RELEVANCE: Liquid plasma and FFP-T would be reasonable to use when stored refrigerated for up to 35 days. Both FDP products showed variability in coagulation factor activities. Studies investigating the usefulness of these plasma products (FDPs) in dogs and the variable days of refrigerated storage (all products) are warranted. (Am J Vet Res 2020;81:964-972).

Canine Tactical Combat Casualty Care (K9TCCC) Guidelines.

First introduced in 1996, Tactical Combat Casualty Care (TCCC) redefined prehospital, point-of-injury (POI), battlefield trauma care for the human combat casualty. Today, many consider TCCC as one of the most influential interventions for reducing combat-related case fatality rates from preventable deaths in human combat casualties. Throughout history, Military Working Dogs (MWDs) have proved and continue to prove themselves as force multipliers in the success of many military operations. Since the start of the Global War on Terror in 2001, these elite canine operators have experienced an upsurge in combat-related deployments, placing them at a higher risk for combat-related injuries. Until recently, consensus- based Canine-TCCC (K9TCCC) guidelines for POI battlefield trauma care did not exist for the MWD, leaving a critical knowledge gap significantly jeopardizing MWD survival. In 2019, the Canine Combat Casualty Care Committee was formed as an affiliate of the Committee on Tactical Combat Casualty Care with the intent of developing evidence- based, best practice K9TCCC guidelines. Modeled after the same principles of the human TCCC, K9TCCC focuses on simple, evidence-based, field-proven medical interventions to eliminate preventable deaths and to improve MWD survival. Customized for the battlefield, K9TCCC uniquely adapts the techniques of TCCC to compensate for canine-specific anatomic and physiological differences.

Purification of canine albumin by heat denaturation in a plasma bag.

OBJECTIVE: To design and evaluate a method to purify canine albumin from fresh frozen plasma (FFP) or stored plasma (SP) in a manner that could be applied clinically. DESIGN: In vitro experimental study. SETTING: FDA licensed Blood Bank Laboratory and University biochemistry laboratory. ANIMALS: None. INTERVENTIONS: Using equipment that is typically found in veterinary blood banks, plasma bags were thawed, injected with the heat stabilizing agent, sodium caprylate, and then heated and acidified to denature all but albumin proteins. Albumin-rich supernatant was removed, the pH was neutralized, and then pasteurized and refrigerated. Albumin and total plasma protein concentrations were measured and the product was cultured for bacteria at 0, 7, 14, 30, and 60 days post-processing. MEASUREMENTS AND MAIN RESULTS: Seventeen bags of plasma were analyzed for purity, yield, and sterility of the finished albumin product. Bags were divided into categories based on the age of the frozen plasma. Mean yield of albumin for all bags was 77.3% and mean purity was 91.2%. There was no difference between old stored plasma, new stored plasma, and FFP with regard to yield (P = 0.31) or purity (P = 0.24) based on one-way analysis of variances. Overall 1 of 17 bags of plasma (5.9%) tested positive for bacterial contamination on day 60 after processing. CONCLUSIONS: Sodium caprylate is able to stabilize canine albumin enabling it to withstand heating that denatures other plasma proteins. The resulting albumin product is of sufficient quality to potentially be used therapeutically as a colloidal resuscitative fluid. Further study is needed into its safety and effect in dogs.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine-Part 1: Hemorrhage Control.

In humans, the leading cause of potentially preventable death on the modern battlefield is undoubtedly exsanguination from massive hemorrhage. The US military and allied nations have devoted enormous effort to combat hemorrhagic shock and massive hemorrhage. This has yielded numerous advances designed to stop bleeding and save lives. The development of extremity, junctional and truncal tourniquets applied by first responders have saved countless lives both on the battlefield and in civilian settings. Additional devices such as resuscitative endovascular balloon occlusion of the aorta (REBOA) and intraperitoneal hemostatic foams show great promise to address control the most difficult forms (non-compressible) of hemorrhage. The development of next generation hemostatic dressings has reduced bleeding both in the prehospital setting as well as in the operating room. Furthermore, the research and fielding of antifibrinolytics such as tranexamic acid have shown incredible promise to ameliorate the effects of acute traumatic coagulopathy which has led to significant morbidity and mortality in service members. Advances from lessons learned on the battlefield have numerous potential parallels in veterinary medicine and these lessons are ripe for translation to veterinary medicine.

Fluids of the Future.

Fluids are a vital tool in the armament of acute care clinicians in both civilian and military resuscitation. We now better understand complications from inappropriate resuscitation with currently available fluids; however, fluid resuscitation undeniably remains a life-saving intervention. Military research has driven the most significant advances in the field of fluid resuscitation and is currently leading the search for the fluids of the future. The veterinary community, much like our civilian human counterparts, should expect the fluid of the future to be the fruit of military research. The fluids of the future not only are expected to improve patient outcomes but also be field expedient. Those fluids should be compatible with military environments or natural disaster environments. For decades, military personnel and disaster responders have faced the peculiar demands of austere environments, prolonged field care, and delayed evacuation. Large scale natural disasters present field limitations often similar to those encountered in the battlefield. The fluids of the future should, therefore, have a long shelf-life, a small footprint, and be resistant to large temperature swings, for instance. Traumatic brain injury and hemorrhagic shock are the leading causes of preventable death for military casualties and a significant burden in civilian populations. The military and civilian health systems are focusing efforts on field-expedient fluids that will be specifically relevant for the management of those conditions. Fluids are expected to be compatible with blood products, increase oxygen-carrying capabilities, promote hemostasis, and be easy to administer in the prehospital setting, to match the broad spectrum of current acute care challenges, such as sepsis and severe systemic inflammation. This article will review historical military and civilian contributions to current resuscitation strategies, describe the expectations for the fluids of the future, and describe select ongoing research efforts with a review of current animal data.

In Vitro Compatibility of Canine and Human Blood: A Pilot Study.

Military working dogs (MWDs) are force multipliers that are exposed to the same risks as their human counterparts on the battlefield. Hemostatic resuscitation using blood products is a cornerstone of damage control resuscitation protocols for both humans and dogs. Canine-specific blood products are in short supply in mature theaters due to logistic and regulatory concerns and are almost nonexistent in austere environments, whereas human blood products are readily available at most surgical facilities. The objective of this study was to evaluate the in vitro compatibility of human and canine blood by using standard crossmatching techniques with the canine blood acting as the recipient and the human blood acting as the donor. Blood samples were collected from 20 government-owned canines (GOCs) and 7 healthy human volunteers in addition to washed red blood cells (RBCs) from a commercial blood typing kit. Major and minor crossmatches were conducted as well as a protein denatured crossmatch. All samples in this study showed strong cross-reactivity, with the majority demonstrating profound hemolysis and a minority showing substantial agglutination. Based on the results of this study, transfusion of human blood to an MWD cannot be recommended at this time.