Elizabeth A. Rozanski

Thromboelastographic Evaluation of Hemostatic Function in Dogs with Disseminated Intravascular Coagulation

BACKGROUND There is considerable variation in the coagulation profile of dogs with disseminated intravascular coagulation (DIC), making it difficult to assess overall hemostatic function. OBJECTIVES To characterize the overall hemostatic state in dogs with DIC, by use of tissue factor-activated thromboelastography (TF-TEG), and to determine whether there is an association between hemostasis and outcome. ANIMALS 50 dogs with DIC. METHODS Dogs admitted to the intensive care units, with an underlying disease known to predispose to DIC, were prospectively assessed with TF-TEG. Citrated blood samples were collected daily during hospitalization and an extended coagulation panel and TF-TEG were performed. Diagnosis of DIC was based on expert opinion. RESULTS Hemostatic dysfunction was observed on the TF-TEG profile in 33/50 of the dogs, of which 22/50 were hypercoagulable and 11/50 were hypocoagulable based on the TF-TEG G value alone. There were significant differences in k, alpha, and MA values (P < .0001) among hypo-, normo-, and hypercoagulable dogs. There was a significant difference in case fatality rate between hypo- (64%) and hypercoagulable (32%) dogs (relative risk = 2.38; P= .04). Dogs that died had significantly lower antithrombin activity (P= .03) and higher d-dimer concentration (P= .03) than survivors. CONCLUSIONS The most common overall hemostatic abnormality in dogs diagnosed with DIC was hypercoagulability, and there was significant difference in survival between hyper- and hypocoagulable dogs. The results suggest TF-TEG is valuable in the assessment of hemostatic function in dogs diagnosed with DIC.

Clinical utility of serum N-terminal pro-B-type natriuretic peptide concentration for identifying cardiac disease in dogs and assessing disease severity

OBJECTIVE To determine whether serum N-terminal pro-B-type natriuretic (NT-proBNP) concentration could be used to identify cardiac disease in dogs and to assess disease severity in affected dogs. DESIGN Cross-sectional study. ANIMALS 119 dogs with mitral valve disease, 18 dogs with dilated cardiomyopathy, and 40 healthy control dogs. PROCEDURES Serum NT-proBNP concentration was measured with an ELISA validated for use in dogs. Results of physical examination, thoracic radiography, echocardiography, and serum biochemical analyses were recorded for dogs with cardiac disease. RESULTS Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function. For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease.

Association between outcome and organ system dysfunction in dogs with sepsis: 114 cases (2003-2007)

OBJECTIVE To determine whether multiple organ dysfunction syndrome (MODS) could be identified in dogs with sepsis secondary to gastrointestinal tract leakage, and whether the number of affected organ systems was significantly associated with mortality rate. DESIGN Multicenter retrospective case series. ANIMALS 114 dogs. PROCEDURES Medical records for dogs treated surgically because of sepsis secondary to gastrointestinal tract leakage between 2003 and 2007 were reviewed. Sepsis was diagnosed on the basis of results of bacterial culture of peritoneal fluid, gross evidence of gastrointestinal tract leakage at surgery, or both. Renal dysfunction was defined as a > or = 0.5 mg/dL increase in serum creatinine concentration after surgery. Cardiovascular dysfunction was defined as hypotension requiring vasopressor treatment. Respiratory dysfunction was defined as a need for supplemental oxygen administration or mechanical ventilation. Hepatic dysfunction was defined as a serum bilirubin concentration > 0.5 mg/dL. Dysfunction of coagulation was defined as prolonged prothrombin time, prolonged partial thromboplastin time, or platelet count < or = 100,000/microL. RESULTS 89 (78%) dogs had dysfunction of 1 or more organ systems, and 57 (50%) dogs had MODS. Mortality rate increased as the number of dysfunctional organ systems increased. Mortality rate was 70% (40/57) for dogs with MODS and 25% (14/57) for dogs without. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MODS, defined as dysfunction of at least 2 organ systems, can be identified in dogs with sepsis and that organ system dysfunction increased the odds of death.

Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea

BACKGROUND B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). HYPOTHESIS The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. ANIMALS Three hundred and thirty dogs from 2 large university teaching hospitals. METHODS We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. RESULTS Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) CONCLUSION AND CLINICAL IMPORTANCE Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.

Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in Dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.

RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines.

OBJECTIVE To present a series of evidence-based, consensus guidelines for veterinary CPR in dogs and cats. 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. Questions in five domains were examined: Preparedness and Prevention, Basic Life Support, Advanced Life Support, Monitoring, and Post-Cardiac Arrest Care. Standardized worksheet templates were used for each question, and the results reviewed by the domain members, by the RECOVER committee, and opened for comments by veterinary professionals for 4 weeks. Clinical guidelines were devised from these findings and again reviewed and commented on by the different entities within RECOVER as well as by veterinary professionals. SETTING Academia, referral practice and general practice. RESULTS A total of 74 worksheets were prepared to evaluate questions across the five domains. A series of 101 individual clinical guidelines were generated. In addition, a CPR algorithm, resuscitation drug-dosing scheme, and postcardiac arrest care algorithm were developed. CONCLUSIONS Although many knowledge gaps were identified, specific clinical guidelines for small animal veterinary CPR were generated from this evidence-based process. Future work is needed to objectively evaluate the effects of these new clinical guidelines on CPR outcome, and to address the knowledge gaps identified through this process.

Hypercoagulability in Cats with Cardiomyopathy

BACKGROUND Arterial thromboembolism (ATE) is a common complication of feline cardiomyopathy; however, the pathogenesis of ATE is unknown. HYPOTHESIS Systemic activation of the coagulation cascade (hypercoagulability) and endothelial injury promote ATE in cardiomyopathic cats. ANIMALS Healthy cats (n = 30) and 3 groups of cardiomyopathic cats: Group (1) left atrial enlargement only (LAE [n = 11]), ie, left atrial to aortic ratio >1.4; Group (2) LAE with spontaneous echocardiographic contrast, atrial thrombi or both (SEC-T [n = 16]); and Group (3) acute ATE with LAE (n = 16). METHODS Hypercoagulability was defined by 2 or more laboratory abnormalities reflecting coagulation factor excess (high fibrinogen concentration or Factor VIII coagulant activity), inhibitor deficiency (low antithrombin activity), or thrombin generation (high thrombin-antithrombin complex [TAT] and d-dimer concentrations). High von Willebrand factor antigen concentration (vWF : Ag) was considered a marker of endothelial injury. Data were analyzed using nonparametric statistics. RESULTS The 3 groups of cats with cardiac disease had higher median fibrinogen concentrations than did the healthy cats. Criteria of hypercoagulability were found exclusively in cats with SEC-T (50%) and ATE (56%). Hypercoagulability was not associated with left atrial size or congestive heart failure (CHF). ATE cats had significantly higher median vWF : Ag concentration than did the other groups. CONCLUSION AND CLINICAL IMPORTANCE Systemic hypercoagulability is evident in many cardiomyopathic cats, often without concurrent CHF or overt ATE. Hypercoagulabilty may represent a risk factor for ATE. High vWF : Ag in ATE cats was attributed to downstream endothelial injury from the occlusive thrombus.

Evaluation of use of human albumin in critically ill dogs: 73 cases (2003–2006)

OBJECTIVES To evaluate the use of human albumin in critically ill dogs. Design-Retrospective case series. ANIMALS 73 client-owned hospitalized dogs. PROCEDURES Medical records of dogs that received human albumin were reviewed to assess effects of the use of human albumin on serum albumin concentration, colloid osmotic pressure, and total protein concentration; determine the relationships between these variables and outcome; and assess its safety. Data for signalment, diagnoses, physiologic variables, dosage, amount of crystalloid fluid administered prior to human albumin administration, complications, and outcome were reviewed. Additionally, pre- and postadministration values for serum albumin, colloid osmotic pressure, and total protein were recorded. RESULTS Administration of human albumin resulted in significant changes in serum albumin, colloid osmotic pressure, and total protein. The serum albumin, total protein, degree of improvement in serum albumin, colloid osmotic pressure, and dosage of human albumin were significantly greater in survivors. Seventeen of 73 (23%) dogs had at least 1 complication that could be potentially associated with the administration of human albumin that occurred during or immediately following administration of human albumin. Three of 73 (4%) dogs had severe delayed complications. CONCLUSIONS AND CLINICAL RELEVANCE Administration of human albumin significantly increased serum albumin, and total protein concentrations and colloid osmotic pressure, especially in survivors. Because of the high mortality rate of the study population and other confounding factors, it was uncertain whether complications were associated with the underlying disease or with human albumin administration. Acute and delayed complications may have been under-recognized.

Assessment of serum N-terminal pro-B-type natriuretic peptide concentration for differentiation of congestive heart failure from primary respiratory tract disease as the cause of respiratory signs in dogs

OBJECTIVE To determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is useful in discriminating between cardiac and noncardiac (ie, primary respiratory tract disease) causes of respiratory signs (ie, coughing, stertor, stridor, excessive panting, increased respiratory effort, tachypnea, or overt respiratory distress) in dogs. DESIGN Multicenter cross-sectional study. ANIMALS P 115 dogs with respiratory signs. PROCEDURES Dogs with respiratory signs were solicited for study. Physical examination, thoracic radiography, and echocardiography were used to determine whether respiratory signs were the result of cardiac (ie, congestive heart failure) or noncardiac (ie, primary respiratory tract disease) causes. Serum samples for NT-proBNP assay were obtained at time of admission for each dog. Receiver-operating characteristic curves were constructed to determine the ability of serum NT-proBNP concentration to discriminate between cardiac and noncardiac causes of respiratory signs. RESULTS Serum NT-proBNP concentration was significantly higher in dogs with cardiac versus noncardiac causes of respiratory signs. In dogs with primary respiratory tract disease, serum NT-proBNP concentration was significantly higher in those with concurrent pulmonary hypertension than in those without. A serum NT-proBNP cutoff concentration > 1,158 pmol/L discriminated between dogs with congestive heart failure and dogs with primary respiratory tract disease with a sensitivity of 85.5% and a specificity of 81.3%. CONCLUSIONS AND CLINICAL RELEVANCE Measuring serum NT-proBNP concentration in dogs with respiratory signs helps to differentiate between congestive heart failure and primary respiratory tract disease as an underlying cause.

Relationship among plasma amino acids, C-reactive protein, illness severity, and outcome in critically ill dogs.

BACKGROUND Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease. HYPOTHESIS/OBJECTIVES To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome. ANIMALS Forty-eight critically ill dogs and 24 healthy control dogs. METHODS Plasma was analyzed for amino acids and C-reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated. RESULTS Median CRP concentrations were significantly higher in the critically ill dogs compared with controls (P < .001). Critically ill dogs had significantly lower concentrations of alanine (P= .001), arginine (P < .001), citrulline (P < .001), glycine (P < .001), methionine (P < .001), proline (P < .001), and serine (P= .001) but significantly higher concentrations of lysine (P= .02) and phenylalanine (P < .001; Table 1). This pattern resulted in a significantly lower Fischer ratio (P= .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived (P= .03). Concentrations of arginine (P= .02), isoleucine (P= .01), leucine (P= .04), serine (P= .04), valine (P= .04), total BCAA (P= .03), and the Fischer ratio (P= .03) were significantly higher in survivors compared with nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE Critically ill dogs have altered amino acid profiles and additional research to investigate potential benefits of amino acid supplementation is warranted.