Samuel D. A. Hurcombe

Blood Arginine Vasopressin, Adrenocorticotropin Hormone, and Cortisol Concentrations at Admission in Septic and Critically Ill Foals and their Association with Survival

BACKGROUND Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. HYPOTHESIS Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. ANIMALS Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. METHODS Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. RESULTS AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. CONCLUSIONS AND CLINICAL IMPORTANCE Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.

Insulin, Glucagon, and Leptin in Critically Ill Foals

BACKGROUND Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. HYPOTHESIS Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvival. ANIMALS Forty-four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age. METHODS In this prospective multicenter cross-sectional study, blood samples were collected at admission. Foals with positive blood culture or sepsis score ≥12 were considered septic. RESULTS Septic foals had lower glucose and insulin and higher triglyceride and glucagon concentrations than did healthy foals. Glucagon concentrations were not different between septic foals that died (n = 14) or survived (n = 30). Higher insulin and lower leptin concentrations were associated with mortality. Quantitative insulin-sensitivity check index was higher in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE Energy metabolism and the endocrine response of related hormones in septic foals are characterized by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high glucagon concentration. Leptin and insulin may have prognostic value for nonsurvival in septic foals. The hormonal response related to energy metabolism in critical illness differs between foals and humans.

Calcium Regulating Hormones and Serum Calcium and Magnesium Concentrations in Septic and Critically Ill Foals and their Association with Survival

BACKGROUND Disorders of calcium regulation are frequently found in humans with critical illness, yet limited information exists in foals with similar conditions including septicemia. The purpose of this study was to determine whether disorders of calcium exist in septic foals, and to determine any association with survival. HYPOTHESIS Blood concentrations of ionized calcium (Ca(2+)) and magnesium (Mg(2+)) will be lower in septic foals with concomitant increases in parathyroid hormone (PTH), calcitonin (CT), and parathyroid-related peptide (PTHrP) compared with healthy foals. The magnitude of these differences will be negatively associated with survival. ANIMALS Eighty-two septic, 40 sick nonseptic, and 24 healthy foals of <or=7 days were included. METHODS Prospective, observational study. Blood was collected at initial examination for analysis. Foals with positive blood culture or sepsis score >or=14 were considered septic. Foals with disease other than sepsis and healthy foals were used as controls. Hormone concentrations were measured with validated immunoassays. RESULTS Septic foals had decreased Ca(2+) (5.6 versus 6.1 mg/dL, P < .01) and increased serum PTH (16.2 versus 3.2 pmol/L, P < .05), and phosphorus concentrations (7.1 versus 6.3 mg/dL, P < .01). No differences in serum Mg(2+), PTHrP, and CT concentrations were found. Nonsurviving septic foals (n = 42/82) had higher PTH concentrations (41.1 versus 10.7 pmol/L, P < .01) than survivors (n = 40/82). CONCLUSIONS AND CLINICAL IMPORTANCE Septic foals were more likely to have disorders of calcium regulation compared with healthy foals, where hyperparathyroidemia was associated with nonsurvival.

Multicentric mast cell tumors in a horse

A 6-year-old female Rocky Mountain horse was presented for evaluation of draining tracts and distal limb subcutaneous edema on the left front and left hind limbs that had been present for 2 weeks. Direct smears of fluid collected by fine-needle aspiration of subcutaneous fluid from both limbs were highly cellular with a predominance of eosinophils accompanied by numerous, moderately atypical, variably granulated mast cells. The cytologic diagnosis was mast cell tumor (MCT) with prominent eosinophilic infiltration with a differential diagnosis of eosinophilic granuloma. Histologic evaluation of surgical biopsies of lesions from both limbs was performed on sections stained with H&E, toluidine blue, and Luna stains. The histologic diagnosis was MCT, and staining with toluidine blue and Luna stains confirmed the presence of mast cells and eosinophils, respectively. In addition, the mast cells strongly expressed CD117. This is the first reported case of cutaneous mast cell neoplasia in a horse in which primary presenting complaints were draining tracts and distal limb subcutaneous edema involving multiple limbs. This case illustrates the utility of staining for CD117 expression in combination with traditional stains, such as toluidine blue and Luna, in differentiating MCTs from other eosinophilic lesions in horses.

Serum protein concentrations as predictors of serum immunoglobulin G concentration in neonatal foals.

OBJECTIVE To determine the predictive value of serum concentrations of total protein (sTP), albumin (sAlb), and globulin (sGlob) measured by automated calorimetric assays to estimate serum immunoglobulin G (sIgG) concentrations in neonatal foals and identify failure of transfer of passive immunity when compared to turbidoimmunometric assay determinations of sIgG. DESIGN Retrospective and prospective analysis of laboratory data. SETTING University tertiary care facility. ANIMALS Group 1 (retrospective): foals (n = 45) ≤7 days of age in which sIgG, sGlob, sAlb, and sTP concentrations were measured on an automated chemistry analyzer. Group 2 (prospective): foals (n = 31) ≤7 days of age with same laboratory data collected used to validate equations generated from group 1 foals. INTERVENTIONS Spearman rank correlations between measured sIgG and serum protein concentrations were performed. When significant correlation was found, sIgG was estimated using an sGlob simple linear regression and estimated using a sGlob, sTP, and sAlb multiple linear regression. Comparisons between estimated and measured sIgG was performed using Kruskal-Wallis testing. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to identify foals with sIgG < 8.0 g/L [<800 mg/dL]. MEASUREMENTS AND MAIN RESULTS sIgG was correlated with sGlob, sTP, and sAlb (ρ = 0.8, 0.6, and -0.3, respectively; P < 0.05). Estimated sIgG and measured sIgG were not different (P > 0.9). In group 1 foals, the sensitivity, specificity, positive predictive value, and negative predictive value were 73%, 76%, 73%, and 83%, respectively, for sGlob, and 90%, 76%, 75%, and 90%, respectively, for multiple proteins estimated sIgG identification of failure of transfer of passive immunity. Test qualities were improved in group 2 foals. CONCLUSIONS Serum protein concentrations may be used to estimate sIgG concentrations in newborn foals. Further investigation using a larger sample size is needed to validate this methodology of assessing humoral immunity in neonatal foals.

Sudden death of a horse with supraventricular tachycardia following oral administration of flecainide acetate.

OBJECTIVE To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. CASE SUMMARY An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. NEW OR UNIQUE INFORMATION PROVIDED Atrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.Objective To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. Case Summary An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. New or Unique Information Provided Atrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.

Hypothalamic-Pituitary Gland Axis Function and Dysfunction in Horses

Hypothalamic-pituitary (HP) dysfunction has been documented in a limited capacity in horses and foals associated with critical illness, stress, and pain. This article reviews species-specific details of anatomy, function, hormones, receptors, and testing of the HP axis in the horse. A discussion of critical care medicine relevant to HP dysfunction in the horse with some reference to current understanding in human medicine is made, focusing primarily on current and relevant literature. A brief mention of other conditions described in human and veterinary medicine is also provided for reference only, such as syndrome of inappropriate antidiuretic hormone secretion and other conditions.

Development of a Likelihood of Survival Scoring System for Hospitalized Equine Neonates Using Generalized Boosted Regression Modeling

Background Medical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission. Methods and Results Data from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively. Conclusions The survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed.

Somatotropic axis resistance and ghrelin in critically ill foals

REASONS FOR PERFORMING STUDY Resistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals. OBJECTIVES To investigate components of the somatotropic axis (ghrelin, growth hormone and insulin-like growth factor-1 [IGF-1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase and IGF-1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals. STUDY DESIGN Prospective multicentre cross-sectional study. METHODS Blood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged <7 days. Foals with positive blood cultures or sepsis scores ≥12 were considered septic, foals with sepsis scores of 5-11 were classified as SNS. Data were analysed by nonparametric methods and multivariate logistic regression. RESULTS Septic foals had higher ghrelin, growth hormone and triglyceride and lower IGF-1 and glucose concentrations than healthy foals (P<0.01). Sick nonseptic foals had higher growth hormone and triglycerides and lower IGF-1 concentrations than healthy foals (P<0.05). Growth hormone:IGF-1 ratio was higher in septic and SNS foals than healthy foals (P<0.05). Hormone concentrations were not different between septic nonsurvivors (n = 14) and survivors (n = 30), but the growth hormone:IGF-1 ratio was lower in nonsurvivors (P = 0.043). CONCLUSIONS Somatotropic axis resistance, characterised by a high growth hormone:IGF-1 ratio, was frequent in sick foals, associated with the energy status (hypoglycaemia, hypertriglyceridaemia) and with mortality in septic foals. POTENTIAL RELEVANCE A functional somatotropic axis appears to be important for foal survival during sepsis. Somatotropic resistance is likely to contribute to severity of disease, a catabolic state and likelihood of recovery.

Presumptive bacterial translocation in horses with strangulating small intestinal lesions requiring resection and anastomosis

Objective To document whether presumptive bacterial translocation (PBT) occurs in horses with small intestinal strangulation (SIS). Design Prospective clinical cohort study. Setting University tertiary care facility. Animals Thirty-six adult horses with SIS (clinical cases) and 10 adult horses without gastrointestinal disease (control cases). Interventions Sterile collection and bacterial culture of samples from peripheral venous blood, mesenteric venous blood, mesenteric lymphatic tissue, and intestinal aspirates from horses with SIS and control horses without gastrointestinal disease. Measurements and Main Results Five of 36 (13.8%) horses with SIS had at least 1 sample yield a positive result. Shorter SIS bowel segments were more likely to yield a positive culture result. (P < 0.01). Two of 10 of control horses had positive culture results with different bacterial species identified compared to horses with SIS. Antimicrobial usage did not influence bacterial culture status (P = 0.31). There were no differences between culture-positive and culture-negative horses with SIS regarding admission, clinical, or clinicopathologic variables. Conclusions PBT occurs in normal horses and in horses with SIS. Bacterial genera differed between groups. A low incidence of PBT occurs in horses with SIS suggesting postoperative morbidity in some cases may be due to other factors.OBJECTIVE To document whether presumptive bacterial translocation (PBT) occurs in horses with small intestinal strangulation (SIS). DESIGN Prospective clinical cohort study. SETTING University tertiary care facility. ANIMALS Thirty-six adult horses with SIS (clinical cases) and 10 adult horses without gastrointestinal disease (control cases). INTERVENTIONS Sterile collection and bacterial culture of samples from peripheral venous blood, mesenteric venous blood, mesenteric lymphatic tissue, and intestinal aspirates from horses with SIS and control horses without gastrointestinal disease. MEASUREMENTS AND MAIN RESULTS Five of 36 (13.8%) horses with SIS had at least 1 sample yield a positive result. Shorter SIS bowel segments were more likely to yield a positive culture result. (P < 0.01). Two of 10 of control horses had positive culture results with different bacterial species identified compared to horses with SIS. Antimicrobial usage did not influence bacterial culture status (P = 0.31). There were no differences between culture-positive and culture-negative horses with SIS regarding admission, clinical, or clinicopathologic variables. CONCLUSIONS PBT occurs in normal horses and in horses with SIS. Bacterial genera differed between groups. A low incidence of PBT occurs in horses with SIS suggesting postoperative morbidity in some cases may be due to other factors.