Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin I11 activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin I11 activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with grarr-negative bacteremia, but not with the presence of endotoxin or coagulopathy.Key words: Coagulation; Endotoxin; Equine; Fibrinolysis; Hemostasis; Neonate; Sepsis.epticemia is a common cause of death in equine neo-S nates.' The most common etiologic agents isolated in foals with septicemia are gram-negative bacteria. Endotoxin, a lipopolysaccharide component of the outer cell membrane of gram-negative bacteria, is released during cell multiplication or bacteriolysis. Consequently, endotoxemia is a common sequela to gram-negative septicemia in foals2Endotoxemia has been associated with higher mortality rates in septicemic human patients and adult horses with gastrointestinal d i~e a s e .~.~ Endotoxin exerts its detrimental effects on the host by interacting with components of the coagulation, inflammatory, and immune s y s t e m~.~.~ During endotoxemic or septic shock, the delicate balance of procoagulant, anticoagulant, and fibrinolytic factors that maintains homeostasis of the coagulation system is ...

Summary Reasons for performing study: A safe, affordable and effective treatment for endotoxaemia in horses is needed in order to reduce the incidence of this potentially fatal condition. Objective: To evaluate the effect of polymyxin B (PMB) on signs of experimentally‐induced endotoxaemia. Hypothesis: PMB ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity. Methods: Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg bwt i.v. over 30 mins. Additionally, each group received one of the following i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30 mins after endotoxin infusion; 1000 u PMB/kg bwt 30 mins prior to endotoxin infusion; or saline. Clinical response data and samples were collected to determine neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to creatinine ratio. Results: Treatment with PMB before or after administration of endotoxin significantly reduced fever, tachycardia and serum TNF, compared to horses receiving saline. The differences in response to endotoxin were greatest between horses that received saline vs. those that received 5000 u PMB/kg bwt prior to endotoxin. Urine GGT:creatinine did not change significantly. Conclusions and potential relevance: This study indicates that PMB may be a safe and effective treatment of endotoxaemia, even when administered after onset. Although nephrotoxicity was not demonstrated with this model, caution should be exercised when using PMB in azotaemic patients.

Among distance groups, distance ridden, speed, level of fitness, and years of experience of horses had little effect on the variables examined. Electrolyte and water supplementation and earlier arrival at the event may be beneficial for horses that are transported long distances to endurance competition.

Background: Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/ high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals.Hypothesis: Foal age will significantly affect cortisol responses to a paired 10 and 100 mg dose cosyntropin stimulation test in healthy neonatal foals.Animals: Twenty healthy neonatal foals.Methods: HPA axis function was assessed in 12 foals at birth and at 12-24, 36-48 hours, and 5-7 days of age. At each age, basal cortisol and ACTH concentrations were measured and cortisol responses to 10 and 100 mg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36-48-hour-old foals received saline instead of 10 mg cosyntropin in the same-paired ACTH stimulation test design.Results: At birth, foals had significantly higher basal cortisol and ACTH concentrations and higher basal ACTH : cortisol ratios compared with foals in all other age groups. A significant cortisol response to both the 10 and 100 mg doses of cosyntropin was observed in all foals. The magnitude of the cortisol response to both doses of cosyntropin was significantly different across age groups, with the most marked responses in younger foals. There was no effect of the paired ACTH stimulation test design itself on cortisol responses.Conclusions and Clinical Importance: A paired 10 and 100 mg cosyntropin stimulation test can be used to evaluate HPA axis function in neonatal foals. Consideration of foal age is important in interpretation of HPA axis assessment.

Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.