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Objective: To discuss the definitions of sepsis in human and veterinary medicine., Design: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine., Setting: Veterinary private practice and university teaching hospitals., Animals: Dogs and cats., Interventions: None., Measurements and Main Results: Sepsis is a life-threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes., Conclusions: This review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence-based criteria for its recognition in veterinary clinical practice., (© 2024 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Objective: To describe a population of sick dogs administered rivaroxaban monitored with a rivaroxaban-calibrated anti-Xa activity assay (aXa)., Design: Descriptive retrospective study., Setting: Two veterinary teaching hospitals., Animals: Client-owned dogs administered rivaroxaban and monitored with aXa from January 2018 to January 2020 were eligible for study., Interventions: None., Measurements and Main Results: Medical records were reviewed and 19 dogs with a variety of underlying disease processes were identified. Rivaroxaban was administered to 12 of 19 dogs (63%) with confirmed thrombosis, 4 of 19 dogs (21%) with a strong clinical suspicion of thrombosis, and in 3 of 19 dogs (16%) with no current evidence of thrombosis. The median rivaroxaban dose administered was 0.96 mg/kg/day (0.62-1.58 mg/kg/day), with 15 of 19 dogs (79%) receiving rivaroxaban once daily. Clopidogrel was concurrently administered to 11 of 19 dogs (58%). Complete or partial thrombus resolution was identified in 5 of 12 (42%) and 3 of 12 (25%) dogs, respectively. Rivaroxaban appeared safe, with only 1 of 19 dogs (5%), concurrently administered clopidogrel, developing evidence of mild hematuria. Posttreatment monitoring revealed that 8 of 19 dogs (42%) had aXa below the target (aXa range of 150-250 ng/ml associated with effective treatment and prevention of venous thrombosis in people). The remaining 3 to 19 dogs (16%) achieved this range, and 8 of 19 dogs (42%) exceeded the range. No significant relationship between the initial rivaroxaban dose administered and the corresponding aXa result was identified. There were also no significant differences in baseline clinicopathological variables in dogs in which aXa fell within or outside this range., Conclusions: aXa was most commonly measured in dogs receiving rivaroxaban with confirmed or suspected thrombosis. Dogs in this study received a range of rivaroxaban dosages and attained variable aXa values that were not directly correlated with dosage., (© Veterinary Emergency and Critical Care Society 2022.)

Objectives: To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis., Design: PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group., Results: Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent., Conclusions: Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field., (© 2022 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Objectives: To expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations., Design: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats)., Results: Of the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism., Conclusions: Associations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies., (© 2022 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Objective: To assess the association of candidate attributes and residency training factors with success on the American College of Veterinary Emergency and Critical Care (ACVECC) board certification examination and to develop multivariable models of first-attempt success., Design: Prospective survey-based study., Setting: Post-assessment ACVECC examination candidates., Animals: None., Interventions: None., Measurements and Main Results: Comprehensive surveys were distributed to ACVECC examination candidates in 2016 to 2018 after completion of their assessments, but prior to publication of examination results. Unique anonymous candidate identification numbers were used to match survey responses to outcome data from the office of the ACVECC Executive Secretary. After curation to retain only the first response from each candidate, there were 97 unique candidate responses available for analysis. Univariate analyses identified multiple factors associated with first-attempt success and multiple differences between academic and private practice residency programs. Multivariable logistic regression modeling suggested that 5 factors were independently associated with first-attempt success on the ACVECC examination, specifically younger age, more weeks of study prior to the examination, training at a facility with more ACVECC Diplomates, training at a facility with more ACVECC residents, and having no requirement to manage both Emergency Room (ER) and Critical Care (CC) cases simultaneously., Conclusions: Numerous resident and training center factors are associated with success in the ACVECC board certification examination. Residents and training centers might be able to use these data to enhance training, but caution must be exercised because these data are associative only., (© Veterinary Emergency and Critical Care Society 2021.)

Objective: To quantify plasma cytokine concentrations in dogs with sepsis and noninfectious systemic inflammation and to evaluate the association between plasma cytokines and outcome in dogs with sepsis., Design: Prospective, observational cohort study., Setting: University teaching hospital., Animals: Forty-five dogs with sepsis, 10 dogs with noninfectious systemic inflammation (nSIRS), and 15 healthy controls were consecutively enrolled from June 2015 to February 2016 and followed to hospital discharge. Dogs with sepsis satisfied ≥2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs with nSIRS satisfied ≥2 SIRS criteria but had no evidence of infection. Dogs <3 kg and those with documented coagulopathy were excluded., Interventions: Measurement of inflammatory cytokines and high-mobility group box-1 (HMGB-1) was performed on each group., Measurements and Main Results: High-mobility group box-1 concentrations were analyzed by ELISA. Plasma concentrations of 13 cytokines were measured in singlet using multiplex magnetic bead assays. Kruskal-Wallis with Dunn's multiple comparison tests were used to compare biomarker concentrations between groups. Mann-Whitney U-tests were used to compare biomarker concentrations between survivors and nonsurvivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Independent outcome predictors were identified using multivariable logistic regression. Alpha was set at 0.05. Concentrations of interleukin (IL)-6, C-X-C motif chemokine (CXCL)-8, keratinocyte-derived chemokine (KC)-like, C-C motif chemokine ligand 2 (CCL2), and HMGB-1 were significantly greater in dogs with sepsis versus healthy controls (all P ≤ 0.034). In dogs with sepsis, only CCL2 was independently associated with survival (odds ratio [OR] 0.996, 95% CI 0.993-0.999, P = 0.004). A cut-off of 385 pg/mL for CCL2 was 80% sensitive and 91.4% specific for nonsurvival (area under the ROC curve [AUROC] 0.866)., Conclusions: Dogs with sepsis have significantly increased concentrations of HMGB-1 and inflammatory cytokines, including IL-6, CXCL8, and KC-like. Increased CCL2 concentration is a negative prognostic indicator in dogs with sepsis. These findings should be confirmed using duplicate analyses in larger, distinct populations of dogs with sepsis before applying them to clinical patients., (© Veterinary Emergency and Critical Care Society 2019.)

Objective: To evaluate procedure time, ease of placement, and complication rates of percutaneous dilatational tracheostomy (PDT) compared to surgical tracheostomy (ST) in canine cadavers., Design: Randomized crossover experimental manikin and cadaver study involving 6 novice veterinary students., Setting: University teaching hospital., Animals: Canine tracheostomy training manikin, 24 canine cadavers., Interventions: None., Measurements and Main Results: For training, each student performed 10 PDT and 10 ST procedures on a training manikin, followed by 2 PDT and 2 ST procedures on a canine cadaver. After each training procedure, feedback from bronchoscopy and observers was provided. Final PDT and ST tube placements using new equipment were performed in unused cadavers. Placements were timed, ease of placement was scored using visual analog scales (VAS, 0-10 cm), and complications were assessed by two independent observers using ordinal scales (0-3). Cadaver tracheas were explanted postprocedure to evaluate anatomical damage scores (0-3). Procedure time and VAS scores for PDT and ST procedures were analyzed using mixed-effects linear models, accounting for student, technique, and procedure number with post hoc pairwise comparisons. Data are presented as median (range). For the final cadaver placement, there were no significant differences in placement time (300 seconds [230-1020] vs 188 seconds [116-414], P = 0.210), ease of placement (3.8 cm [2.1-5.7] vs 1.9 cm [0-4.7], P = 0.132), anatomical damage score (1 [0-2] vs 0 [0-1], P = 0.063), or equipment complications score (0 [0-1] vs 0 [0-0], P = 1.000) between PDT and ST, respectively., Conclusions: These data suggest that PDT can be performed as quickly, as easily, and as safely as ST in a canine cadaver by novice veterinary students following manikin training. Additional studies will be required to determine if these findings can be translated into veterinary clinical practice., (© Veterinary Emergency and Critical Care Society 2019.)

Objective: To illustrate the application of the Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines to the management of dogs and cats at risk of developing thrombosis using a case-based approach., Etiology: Dogs and cats become at risk of developing thrombosis from a wide range of conditions. These conditions often involve a specific insult followed by an inflammatory response and when combined with other contributing factors (eg, hypercoagulability, vascular endothelial injury, hemodynamic changes) create favorable conditions for thrombosis., Diagnosis: Development of thrombosis in small animals remains challenging to demonstrate. Compatible clinical signs, the presence of known risk factors, and supporting diagnostic tests may be highly suggestive of the development of thrombosis., Therapy: Therapeutic recommendations in accordance with the CURATIVE guidelines for dogs and cats are described in specific case vignettes presented. Discussion is centered on antithrombotic drug choices and dosing protocols, as outlined in Domains 2 and 3 of the CURATIVE guidelines. Where appropriate, guidelines related to therapeutic monitoring (Domain 4) and discontinuation of antithrombotics (Domain 5) were included., Prognosis: In small animals at risk of developing thrombosis, overall prognosis may be improved by following consensus-based recommendations on the use of antithrombotics as outlined in the CURATIVE guidelines. Whether such interventions have any impact on outcome requires further investigation., (© Veterinary Emergency and Critical Care Society 2019.)

Objectives: To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with antithrombotics., Design: Standardized, systematic evaluation of the literature (identified by searching Medline via PubMed and CAB abstracts) was carried out in 5 domains (Defining populations at risk; Defining rational therapeutic use; Defining evidence-based protocols; Refining and monitoring antithrombotic therapies; and Discontinuing antithrombotic therapies). Evidence evaluation was carried out using Population, Intervention, Comparison, Outcome generated within each domain questions to address specific aims. This was followed by categorization of relevant articles according to level of evidence and quality (Good, Fair, or Poor). Synthesis of these data led to the development of a series of statements. Consensus on the final guidelines was achieved via Delphi-style surveys. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication., Settings: Academic and referral veterinary medical centers., Results: Over 500 studies were reviewed in detail. Worksheets from all 5 domains generated 59 statements with 83 guideline recommendations that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations., Conclusions: Overall, systematic evidence evaluations yielded more than 80 recommendations for the treatment of small animals with or at risk of developing thrombosis. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field., (© Veterinary Emergency and Critical Care Society 2019.)

Objectives: Thrombosis is a well-recognized phenomenon in dogs and cats with a significant impact on morbidity and mortality. Despite growing awareness of thrombosis and increased use of antithrombotic therapy, there is little information in the veterinary literature to guide the use of anticoagulant and antiplatelet medications. The goal of Domain 1 was to explore the association between disease and thrombosis in a number of conditions identified as potential risk factors in the current veterinary literature, to provide the basis for prescribing recommendations., Design: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. Revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated included immune-mediated hemolytic anemia, protein-losing nephropathy, pancreatitis, glucocorticoid therapy, hyperadrenocorticism, neoplasia, sepsis, cerebrovascular disease, and cardiac disease., Settings: Academic and referral veterinary medical centers., Results: Of the diseases evaluated, a high risk for thrombosis was defined as dogs with immune-mediated hemolytic anemia or protein-losing nephropathy, cats with cardiomyopathy and associated risk factors, or dogs/cats with >1 disease or risk factor for thrombosis. Low or moderate risk for thrombosis was defined as dogs or cats with a single risk factor or disease, or dogs or cats with known risk factor conditions that are likely to resolve in days to weeks following treatment., Conclusions: Documented disease associations with thrombosis provide the basis for recommendations on prescribing provided in subsequent domains. Numerous knowledge gaps were identified that represent opportunities for future study., (© Veterinary Emergency and Critical Care Society 2019.)

Objectives: To systematically review available evidence to determine when small animals at risk of thrombosis should be treated with antiplatelet agents and anticoagulants, which antiplatelet and anticoagulant agents are most effective, and when multimodal therapy is indicated., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication., Settings: Academic and referral veterinary medical centers., Results: Databases searched included Medline via PubMed and CAB abstracts. Twelve Population Intervention Comparison Outcome questions were devised and generated corresponding worksheets investigating indications for use of antithrombotic drugs in small animals. Seventy-eight studies were reviewed in detail. Most studies assessed were experimentally controlled laboratory studies in companion animals (56 LOE 3) with smaller numbers of LOE 2 (1), LOE 4 (5), LOE 5 (6), and LOE 6 (4) studies assessed. Only 5 randomized controlled clinical trials were identified (LOE 1, Good-Fair). The 12 worksheets generated 21 guidelines with 17 guideline statements that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations during the Delphi process., Conclusions: Overall, systematic evidence evaluations generated 2 strong recommendations, 19 weak recommendations (formulated as suggestions), 9 situations where the evidence was insufficient to make strong recommendations, and 8 situations where no relevant evidence was retrieved to aid guideline generation. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field., (© Veterinary Emergency and Critical Care Society 2019.)

Objectives: To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other antithrombotic therapies, to reduce the risk of complications or improve outcomes in dogs and cats at risk for thrombosis., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice., Settings: Academic and referral veterinary medical centers., Results: Databases searched included Medline via PubMed and CAB abstracts. Eight different antithrombotic drugs were investigated using a standardized Patient, Intervention, Comparison, Outcome (PICO) question format both for dogs and cats, including aspirin, clopidogrel, warfarin, unfractionated heparin (UFH), dalteparin, enoxaparin, fondaparinux, and rivaroxaban, generating a total of 16 worksheets. Most studies identified were experimental controlled laboratory studies in companion animals (LOE 3) with only four randomized controlled clinical trials in companion animals (LOE 1)., Conclusions: Overall, evidence-based recommendations concerning specific protocols could not be formulated for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (eg, aspirin in dogs) or the lack of evidence in the current literature. However, clopidogrel administration in dogs and cats at risk of arterial thrombosis, notably in cats at risk of cardiogenic thromboembolism, is supported by the literature, and specific protocols were recommended. Comparably, aspirin should not be used as a sole antithrombotic in cats with cardiomyopathy. Using the available safety profile information contained in the literature, the panel reached consensus on suggested dosage schemes for most antithrombotics. Significant knowledge gaps were highlighted, which will hopefully drive novel research., (© Veterinary Emergency and Critical Care Society 2019.)

Objective: The clinical diagnosis of disseminated intravascular coagulation (DIC) in dogs is challenging. It was hypothesized that dogs with laboratory abnormalities consistent with overt DIC have increased mortality and hence survival could be used to evaluate the performance of DIC scoring systems. Four DIC scoring systems were compared in clinically ill dogs: The International Society of Thrombosis and Haemostasis (ISTH) score; a previously published veterinary DIC score; a system using in-house reference intervals (RIs) for coagulation assays; and the published veterinary DIC score modified by use of in-house RI values., Design: Retrospective cohort study., Setting: University teaching hospital., Animals: Eight hundred four client-owned dogs with underlying disorders associated with DIC., Interventions: None., Measurements and Main Results: Medical records were reviewed to identify dogs for which a coagulation panel consisting of coagulation times, D-dimer concentration, antithrombin activity, fibrinogen concentration, and platelet count had been analyzed. Four methods for overt DIC scoring were then applied, and the ability of these scores to predict mortality was evaluated. Use of institution RIs for diagnosis of overt DIC provided the most accurate prognostic assessment. A score based on abnormalities in 3 of 6 parameters to identify overt DIC was 72.7% sensitive and 80.9% specific for mortality and was accurate in 78.4% of cases. The mortality rate of dogs diagnosed with overt DIC via this method was 62.5%, compared to 12.9% in the dogs not in overt DIC, a relative risk of nonsurvival of 4.84 (95% confidence interval 3.80-6.16)., Conclusions: In dogs at-risk for DIC, an in-house RI scoring system accurately predicted mortality. With further prospective validation, this system holds promise as a diagnostic tool for consistent characterization of overt DIC in clinical studies and clinical practice., (© Veterinary Emergency and Critical Care Society 2018.)

Objective: To investigate the use of plasma cell-free DNA (cfDNA) and nucleosome concentrations as prognostic biomarkers in canine sepsis., Design: Prospective, observational cohort study conducted from June 2015 to February 2016., Setting: University teaching hospital., Animals: Forty-five dogs with sepsis, 10 dogs with nonseptic systemic inflammatory response syndrome (nSIRS), and 15 healthy controls were consecutively enrolled and followed to hospital discharge. Patients were eligible for enrollment if they met ≥2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs <3 kg or with a known coagulopathy were excluded., Interventions: None., Measurements and Main Results: Acute Patient Physiology and Laboratory Evaluation scores (APPLE) were calculated and outcomes recorded. Plasma cfDNA was measured using a benchtop fluorimeter. Plasma nucleosome concentrations were determined by ELISA. Plasma nucleosome and cfDNA concentrations in dogs with sepsis or nSIRS were compared to those of healthy controls and cfDNA concentrations in septic dogs with and without bacteremia were compared. Associations between cfDNA concentrations and nucleosomes, leukocyte count, neutrophil count, and APPLE scores were evaluated. For septic dogs, cfDNA concentrations relative to neutrophil count and nucleosome concentrations in survivors and nonsurvivors were compared. Alpha was set at 0.05. cfDNA concentrations were significantly higher in dogs with sepsis or nSIRS compared to healthy controls (P < 0.0001 and P = 0.0034, respectively). Nucleosome concentrations were significantly higher in dogs with sepsis compared to healthy controls (P = 0.007). There was limited association between cfDNA and nucleosome concentrations (r s  = 0.266), and no association between cfDNA concentration and leukocyte count, neutrophil count, and APPLE full scores. Concentrations of cfDNA were positively correlated with APPLE fast score (r s  = 0.335, P = 0.025); however, cfDNA concentrations were significantly higher in dogs with bacteremia (P = 0.0299). In dogs with sepsis, cfDNA concentrations relative to neutrophil count were significantly higher in nonsurvivors than in survivors (P = 0.008)., Conclusions: In dogs with sepsis, high cfDNA concentrations relative to neutrophil count are associated with nonsurvival. Point-of-care cfDNA measurement may aid identification of bacteremia., (© Veterinary Emergency and Critical Care Society 2018.)

Objective: To evaluate whether cell-free DNA (cfDNA) concentrations are increased in dogs with exertional rhabdomyolysis and whether concentrations are correlated with serum myoglobin concentration and creatine kinase activity., Design: Observational cohort study., Setting: Yukon Quest 1,000-mile International Sled Dog Race 2015., Animals: Twelve normal competitive sled dogs; 5 dogs with rhabdomyolysis., Interventions: None., Measurements and Main Results: Blood was collected from all confirmed cases of exertional rhabdomyolysis and compared to the winning team at the midrace point. Results indicate that median cfDNA did not increase, but decreased by the race finish (prerace = 314.2 ng/mL versus midrace = 283.7 ng/mL versus postrace = 249.5 ng/mL). There were no rises in median cfDNA in dogs with rhabdomyolysis (255 ng/mL) negating its potential utility as a measure of acute skeletal muscle compromise. In contrast, myoglobin concentration and creatine kinase activity at the midrace point for normal dogs were significantly lower than dogs with rhabdomyolysis. Values for myoglobin and creatine kinase were strongly positively correlated (R = 0.91)., Conclusions: cfDNA is not a useful biomarker for exertional rhabdomyolysis in contrast to myoglobin and creatine kinase. Further evaluation of timing and clinical signs suggests that exertional rhabdomyolysis occurs early in endurance activities. Among the dogs with rhabdomyolysis, the dog that demonstrated clinical signs had the highest serum creatine kinase activity and myoglobin concentration., (© Veterinary Emergency and Critical Care Society 2018.)

Objective: To establish and compare the repeatability and reproducibility of activated thromboelastography (TEG) and thromboelastometry (ROTEM) assays., Design: Multicenter in vitro test standardization., Setting: Veterinary academic centers., Animals: Test samples were obtained from normal, healthy dogs. Sixty identical 5 mL aliquots of canine platelet-rich plasma collected by apheresis, frozen in 6% dimethyl sulfoxide, were tested initially. Sixty identical 6 mL aliquots of canine fresh frozen plasma with admixed cryoprecipitate were subsequently evaluated., Interventions: None., Measurements and Main Results: Frozen study samples, quality controls, reagents, and consumables were distributed to participating centers (7 TEG and 3 ROTEM). TEG centers analyzed study samples with kaolin and tissue factor activated assays; ROTEM centers ran proprietary ellagic acid activated and tissue factor activated assays. All machines underwent quality control prior to sample analysis. Within- and between-center coefficients of variation (CVs) were calculated and compared using Mann-Whitney tests and calculation of intraclass correlation coefficients. Within and between centers, individual parameters for both TEG and ROTEM assays were comparable. Both within-center and between-center CVs varied markedly (0.7-120.5% and 1.4-116.5%, respectively) with assay type, instrument, and parameter. CVs for equivalent parameters were not significantly different between the 2 platforms. Intraclass correlation coefficients suggested moderate agreement between centers. In general, individual parameter CVs for platelet-rich plasma samples were lower in TEG centers, while CVs for canine fresh frozen plasma with admixed cryoprecipitate samples were lower in ROTEM centers., Conclusions: More variation within and between centers was identified than anticipated, but some parameters such as alpha angle were repeatable and reproducible. Sample types for future multicenter standardization efforts will require further optimization and may need to be adapted separately to each platform. Individual centers using viscoelastic tests for evaluation and management of clinical patients should take steps to minimize preanalytical and analytical sources of variation., (© Veterinary Emergency and Critical Care Society 2018.)

Objective: To examine the animal trauma triage (ATT) and modified Glasgow Coma Scale (mGCS) scores as predictors of mortality outcome (death or euthanasia) in injured dogs., Design: Observational cohort study conducted from September 2013 to March 2015 with follow-up until death or hospital discharge., Setting: Nine veterinary hospitals including private referral and veterinary teaching hospitals., Animals: Consecutive sample of 3,599 dogs with complete data entries recruited into the Veterinary Committee on Trauma patient registry., Interventions: None., Measurements and Main Results: We compared the predictive power (area under receiver operating characteristic [AUROC]) and calibration of the ATT and mGCS scores to their components. Overall mortality risk was 7.3% (n = 264). Incidence of head trauma was 9.5% (n = 341). The ATT score showed a linear relationship with mortality risk. Discriminatory performance of the ATT score was excellent with AUROC = 0.92 (95% confidence interval [CI] 0.91 to 0.94) and pseudo R 2 = 0.42. Each ATT score increase of 1 point was associated with an increase in mortality odds of 2.07 (95% CI = 1.94-2.21, P < 0.001). The "eye/muscle/integument" category of the ATT showed poor discrimination (AUROC = 0.55). When this component together with the skeletal and cardiac components were omitted from calculation of the overall score, there was no loss in discriminatory capacity (AUROC = 0.92 vs 0.91, P = 0.09) compared with the full score. The mGCS showed good performance overall, but performance improved when restricted to head trauma patients (AUROC = 0.84, 95% CI = 0.79-0.90, n = 341 vs 0.82, 95% CI = 0.79-0.85, n = 3599). The motor component of the mGCS showed the best predictive performance (AUROC = 0.79 vs 0.66/0.69); however, the full score performed better than the motor component alone (P = 0.002). When assessment was restricted to patients with head injury (n = 341), the ATT score still performed better than the mGCS (AUROC = 0.90 vs 0.84, P = 0.04)., Conclusions: In external validation on a large, multicenter dataset, the ATT score showed excellent discrimination and calibration; however, a more parsimonious score calculated on only the perfusion, respiratory, and neurological categories showed equivalent performance., (© Veterinary Emergency and Critical Care Society 2018.)

Objectives: To disseminate information regarding the annual pass rates for the American College of Veterinary Emergency and Critical Care (ACVECC) certifying examination. To compare the first-time pass rates (FTPR) of ACVECC residents trained in academic and private practice settings., Design: Retrospective study., Setting: ACVECC examination., Animals: None., Interventions: None., Measurements and Main Results: Anonymized ACVECC examination performance data from 2010-2015 inclusive were analyzed. Overall pass rates and FTPR were calculated for all candidates and categorized by type of residency training program. The overall pass rate for all candidates was 64.3%. The median pass rate for the 6-year period was 63.8% [IQR 59.3-67.3%]. The FTPR for residents trained in academic programs was significantly higher than for residents trained in private practice (77.1% vs 47.2%, P < 0.0001). When residents were subdivided by species-focus of training program, there was no significant difference between academic versus private practice training programs for large-animal candidates (P = 0.2), but there remained a significant difference between residency training programs for small-animal candidates (P < 0.0001)., Conclusions: Between 2010 and 2015 residents trained in academic training programs were significantly more likely to pass the ACVECC certifying examination compared to those trained in private practice training programs. The causes of this difference are uncertain, are likely multifactorial and warrant further investigation., (© Veterinary Emergency and Critical Care Society 2018.)

Objectives: To determine if cell-free DNA (cfDNA) was identifiable in canine plasma, to evaluate 3 techniques for the measurement of plasma cfDNA concentrations in dogs presented to an emergency service, and to compare the plasma cfDNA concentrations of healthy dogs to those with sepsis, trauma, and neoplasia., Design: Retrospective study of banked canine plasma samples collected between May 2014 and December 2014., Setting: Dogs presented to the emergency service of a university veterinary teaching hospital., Animals: Plasma cfDNA was measured on residual plasma samples obtained from 15 dogs with sepsis, 15 dogs with moderate-severe trauma, 15 dogs diagnosed with a sarcoma. Plasma cfDNA was also measured in 15 healthy dogs., Interventions: None., Measurements and Main Results: Assay linearity, repeatability, and reproducibility were evaluated. Quantification of cfDNA was performed in duplicate on diluted citrated plasma and following DNA purification using 2 fluorescence assays (SYBR-Gold; Quant-iT) and by ultraviolet absorbance spectroscopy. Fluorescence intensities (FIs) were converted to cfDNA concentrations using standard curves. Median FI values and cfDNA concentrations were compared to healthy controls using the Kruskal-Wallis test, with adjustment for multiple comparisons. Alpha was set at 0.05. Both assays had excellent linearity, and acceptable repeatability and reproducibility. Compared to controls, plasma cfDNA concentrations were significantly increased in dogs with sepsis or moderate-severe trauma with both assays (P ≤ 0.003). Dogs with neoplasia had significantly increased cfDNA concentrations with the Quant-iT assay only (P = 0.003). When measurements were performed on purified DNA, only dogs with moderate-severe trauma had significantly increased cfDNA concentrations (P < 0.001; SYBR-Gold assay)., Conclusions: cfDNA can be readily identified in canine plasma using 2 fluorescence assays. DNA extraction offers no advantage over direct measurement. Compared to healthy controls, dogs with sepsis or moderate-severe trauma have significantly increased plasma cfDNA concentrations., (© Veterinary Emergency and Critical Care Society 2017.)

Objective: To systematically examine the evidence on system comparability between the thromboelastography and the rotational thromboelastometry viscoelastic point-of-care instruments and to identify knowledge gaps., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: Medline via PubMed, CAB abstracts, and Google Scholar were searched. A total of 8 relevant articles were chosen, none were in support of the question, 1 was neutral to the question (level of evidence [LOE] 6, Poor), and 7 were in opposition to the question (LOE 3 Good; LOE 6 Good; LOE 6 Fair; LOE 6 Poor)., Conclusions: Results from the 2 analyzers are not directly comparable and extrapolation of the results from one machine to the other should be avoided. Standardization of the preanalytical variables (eg, blood collection, holding time, and temperature during holding) is strongly recommended. It is recommended that each site create their own "site specific" reference values for each machine and that test samples be compared only to the standardized reference values established at that center. Start-up and consumable costs vary between countries and local comparisons should be performed. Decisions should be made based on the expected use of the machine and if multiple operators will be using it., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To systematically examine evidence surrounding definitions and reporting of data for viscoelastic testing in veterinary medicine., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: Databases searched included Medline, CAB abstracts, and Google Scholar., Conclusions: All 4 standard thromboelastography (TEG) and rotational thromboelastometry (ROTEM) variables should be universally reported, and the reporting of shear elastic modulus in addition to maximum amplitude (MA) is encouraged. There is insufficient evidence to support universal usage of the coagulation index at this time. The K value and clot formation time are the most variable of the 4 parameters, with alpha angle, MA, and maximum clot firmness generally the least variable. Individual studies should report sufficient data on patients and institutional controls to enable definitions of hypo- and hypercoagulability to be evaluated post-hoc, and it is recommended that all studies specifically report how these conditions were defined. In reporting data relating to fibrinolysis, the TEG variables LY30, LY60, CL30, CL60, and the ROTEM variables LI30, LI60, ML, LOT, and LT should be documented. Studies should report sufficient data on patients and controls to enable definitions of hyper- and hypofibrinolysis to be evaluated post-hoc, and we suggest that standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in companion animals. We recommend that every center establish reference intervals, which are specific to either TEG or ROTEM. These reference intervals should be established using veterinary clinical pathology guidelines, standardized protocols, and a minimum of 40 healthy animals. There are currently insufficient data in companion animals to suggest a utility for Vcurve variables beyond that of standard TEG variables., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To systematically examine the evidence relating to the performance of rotational viscoelastic testing in companion animals, to develop assay guidelines, and to identify knowledge gaps., Design: Multiple questions were considered within 5 parent domains, specifically system comparability, sample handling, assay activation and test protocol, definitions and data reporting, and nonstandard assays. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence and assessed for quality. Consensus was developed regarding conclusions for application of concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: Databases searched included Medline, Commonwealth Agricultural Bureaux abstracts, and Google Scholar. Worksheets were prepared evaluating 28 questions across the 5 domains and generating 84 assay guidelines., Conclusions: Evidence-based guidelines for the performance of thromboelastography in companion animals were generated through this process. Some of these guidelines are well supported while others will benefit from additional evidence. Many knowledge gaps were identified and future work should be directed to address these gaps and to objectively evaluate the impact of these guidelines on assay comparability within and between centers., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To examine systematically the evidence on sample acquisition and handling for the thrombo elastography (TEG) and rotational thromboelastometry (ROTEM) viscoelastic point of care instruments and to identify knowledge gaps., Design: Six questions were considered, addressing sampling site, collection system, anticoagulant, collection procedure, and sample storage. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence (LOE). Consensus was developed regarding conclusions for application of concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: PubMed and CAB abstracts were searched. Eighteen papers were initially chosen; 5 of these papers applied to > 1 domain question. Three papers were used to address 2 questions each, and 2 papers were used to address 3 questions each. Most papers were judged LOE 3 (Good or Fair). Two of 5 papers were judged to be the same LOE each time they were used; 2 papers were judged to be LOE 3, Fair for 1 question and 3, Good for a second question; 1 paper used to address 3 questions was judged LOE 3, Good twice and 3, Fair once. Fourteen additional papers were evaluated post hoc during manuscript preparation., Conclusions: Jugular venipuncture is recommended, but samples from IV catheters can be used. Consistent technique is important for serial sampling, and standardized sampling protocols are recommended for individual centers performing TEG/ROTEM. There is insufficient evidence to recommend use of a specific blood collection system, although use of evacuated blood tubes and 21-Ga or larger needles is suggested. Use of 3.2% buffered sodium citrate in a strict 1:9 ratio of citrate to blood is suggested. Suggested tube draw order is discard/serum, followed by citrate, EDTA, and then heparin. Samples should be held at room temperature for 30 minutes prior to analysis., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To systematically examine the evidence on activating agents and test protocols for the thrombelastography (TEG) and rotational thrombelastometry (ROTEM) viscoelastic point-of-care instruments and to identify knowledge gaps., Design: Ten questions were considered, the primary question addressed the use of activating agents and secondary questions addressed assay temperature, length of analysis, pipetting, sample volume, reproducibility, and quality controls. Standardized, systematic evaluation of the literature was performed. Relevant articles were categorized according to level of evidence (LOE). Consensus was developed regarding conclusions for application of concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: PubMed and CAB abstracts were searched. Twenty papers were initially identified concerning the primary question; 16 were in support of the questions (LOE 2 Good, LOE 3 Good, LOE 5 Good, LOE 6 Good, LOE 5 Fair, LOE 6 Fair); and 4 were neutral (LOE 3 Good, LOE 6 Good, LOE Fair, LOE 5 Fair). Additional papers were evaluated post hoc during manuscript preparation., Conclusions: Overall, there is a body of evidence from veterinary and human medicine that strongly suggests that TEG or ROTEM assays using citrated samples that employ an activator have significantly lower inherent variability than those that use recalcification alone. There is also strong evidence in dogs, cats, and humans that the results obtained using different activators are not directly comparable. There is no evidence to suggest that any one activating agent is superior to another for all patient populations, or drug monitoring indications. As such, use of more than one assay for complete thromboelastographic evaluation of a patient's coagulation system may be warranted. Standardization of the concentrations of activators would be beneficial., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To systematically examine the evidence on nontraditional uses of viscoelastic coagulation monitoring in veterinary species., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice., Setting: Academic and referral veterinary medical centers., Results: Databases searched included Medline, CAB abstracts, and Google Scholar., Conclusions: Nontraditional assays identified included thrombelastography (TEG)-PlateletMapping (PM), functional fibrinogen assessment, and rapid-TEG (r-TEG). Direct veterinary evidence was found for only the ADP-activated PM, which appears to generate valid data in dogs but not cats or horses. Arachidonic acid activated PM shows high variability and requires further assessment and validation in veterinary species. Functional fibrinogen assays may be performed in veterinary species but may require modification due to species differences in response to abciximab. While tissue factor (TF)-activated TEG has been well described in the veterinary literature, the specific r-TEG assay has not been assessed, but presumably would be effective for generating TEG tracings and values for maximum amplitude and angle in shorter periods of time than some traditional assays., (© Veterinary Emergency and Critical Care Society 2014.)

Objective: To review the receptors and signal transduction pathways involved in platelet plug formation and to highlight links between platelets, leukocytes, endothelium, and the coagulation system., Data Sources: Original studies, review articles, and book chapters in the human and veterinary medical fields., Data Synthesis: Platelets express numerous surface receptors. Critical among these are glycoprotein VI, the glycoprotein Ib-IX-V complex, integrin α(IIb) β(3) , and the G-protein-coupled receptors for thrombin, ADP, and thromboxane. Activation of these receptors leads to various important functional events, in particular activation of the principal adhesion receptor α(IIb) β(3) . Integrin activation allows binding of ligands such as fibrinogen, mediating platelet-platelet interaction in the process of aggregation. Signals activated by these receptors also couple to 3 other important functional events, secretion of granule contents, change in cell shape through cytoskeletal rearrangement, and procoagulant membrane expression. These processes generate a stable thrombus to limit blood loss and promote restoration of endothelial integrity., Conclusions: Improvements in our understanding of how platelets operate through their signaling networks are critical for diagnosis of unusual primary hemostatic disorders and for rational antithrombotic drug design., (© Veterinary Emergency and Critical Care Society 2012.)

Objective: To review the pathophysiology, clinical signs, diagnosis, and treatment of pulmonary thromboembolism (PTE) in small animals., Data Sources: Human and veterinary clinical studies, reviews, texts, and recent research in canine and feline PTE diagnosis and thromboembolic therapeutics., Human Data Synthesis: In humans, clinical probability assessment and point-of-care D-dimer-based algorithms are widely used. Computed tomography pulmonary angiography is the gold standard for PTE diagnosis in humans. Echocardiography is increasingly used for bedside assessment of affected patients. In low-risk human patients anticoagulants alone are recommended while patients with cardiogenic shock are treated with thrombolytics followed by anticoagulation., Veterinary Data Synthesis: PTE is associated with numerous predisposing conditions causing hypercoagulability, blood flow stasis, or endothelial injury. Identifying at-risk patients is key to diagnosis in small animals. Thromboelastography provides a method for identifying hypercoagulable patients. Computed tomography pulmonary angiography may replace selective pulmonary angiography as the imaging technique of choice for PTE diagnosis. PTE therapy consists of supportive treatment combined with appropriate, individualized thromboembolic pharmacotherapy for acute treatment and chronic management. Thrombolytic therapy for PTE remains controversial but may be indicated in hemodynamically unstable acute PTE. Thromboprophylaxis in specific conditions is rational although evidence of efficacy is limited. Prognosis depends upon degree of cardiopulmonary compromise and patient response to therapy. Mortality rates in small animals are unknown., Conclusions: New diagnostic techniques and advances in therapy offer significant potential for improvements in the identification and treatment of PTE in small animals. Further study must be directed to validating new diagnostic modalities and evaluating therapeutic regimes.