Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses.

A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10 mL/kg bolus of each formulation (600/0.75 and 130/0.4) of hydroxyethyl starch solution in a randomized crossover design. Blood was collected, and plasma was harvested for plasma levels over 24 h. Pharmacokinetic parameters for each horse were estimated from a noncompartmental analysis. Treatment with 600/0.75 resulted in a higher initial plasma concentration (C0 ), systemic half-life (t1/2 ), and overall drug exposure (AUC0-inf ) in addition to decreased elimination rate (ß), volume of distribution (Vd), and clearance (CL), compared to treatment with 130/0.4 (P < 0.001). The pharmacokinetic findings combined with previous pharmacodynamics findings suggest that 130/0.4 can provide similar benefits to 600/0.75 with a lower risk of accumulation in the circulation.

Cardiovascular, colloid osmotic pressure, and hemostatic effects of 2 formulations of hydroxyethyl starch in healthy horses.

BACKGROUND: Lower molecular weight and molar substitution formulations of hydroxyethyl starch (HES) solutions might maximize cardiovascular function and colloid osmotic pressure (COP) and minimize adverse effects on coagulation. HYPOTHESIS/OBJECTIVES: To compare effects of 1 low and 1 high molecular weight and molar substitution HES solution on cardiovascular variables, COP, and hemostasis in normal horses. ANIMALS: Eight healthy adult horses. METHODS: Randomized, crossover designed study: 10 mL/kg bolus of 6% HES (600/0.75) (hetastarch) (HS), 6% HES (130/0.4) tetrastarch (TS), and 0.9% NaCl (NS). Variables recorded included central venous pressure (CVP), noninvasive arterial blood pressure, packed cell volume (PCV), COP, and automated platelet analysis (CT). RESULTS: Central venous pressure was increased for 8 hours after all treatment (baseline = 8.4 ± 3.8; 8 hours = 10.3 ± 3.5 cm H2 O; P < .001). HS and TS produced an increase in systolic arterial pressure (HS = 109.1 ± 11.9; TS = 109.5 ± 10.9 mmHg) and mean arterial pressure (HS = 80.4 ± 13.0; TS = 82.3 ± 10.1 mmHg) compared to NS (SAP = 103.2 ± 13.2 [P = .023]; MAP = 74.2 ± 11.4 mmHg [P = .048]). PCV decreased transiently with HS (baseline = 37.1 ± 4.4%; 1.5 hours = 31.6 ± 3.9%) and TS (baseline = 38.4 ± 3.9%; 1.5 hours = 32.2 ± 3.3%), but not NS (P = .007). COP was greater with HS (1 hour; 24.0 ± 2.1 mmHg) and TS (8 hours; 25.9 ± 2.1 mmHg) than NS (1 hour = 20.8 ± 2.6; 8 hours = 22.9 ± 3.1 mmHg; P < .001). CT was greater at 8 (HS = 178.6 ± 36.9; TS = 121.9 ± 33.3; NS = 108.3 ± 23.6 seconds) and 24 hours (HS = 174.2 ± 41.7; TS = 100.8 ± 26.0; NS = 118.7 ± 38.7 seconds; P < .001) in horses receiving HS than TS or NS. CONCLUSION AND CLINICAL IMPORTANCE: Both TS and HS resulted in more effective volume expansion and arterial pressure support than NS. TS produced a more sustained effect on COP with shorter duration of adverse effects on platelet function than HS.

An evaluation of the Abaxis VSPro for the measurement of equine plasma fibrinogen concentrations.

REASONS FOR PERFORMING STUDY: Accurate measurement of plasma fibrinogen concentrations is an important tool for assessment of horses with inflammatory diseases. OBJECTIVES: To determine the precision and accuracy of a benchtop instrument using both fresh and frozen equine plasma by comparing the plasma fibrinogen concentration measured by a benchtop instrument to 2 separate laboratory standard methods (ACL 100 and STA Compact) for fibrinogen measurement. METHODS: Accuracy and precision of the VSPro was evaluated using both human fibrinogen standards and samples from horses. Fifty frozen samples from horses with gastrointestinal disease had the fibrinogen concentration measured using the ACL 1000 and the VSPro. Fifty fresh samples were collected from hospitalised horses and fibrinogen concentration was measured using the STA Compact coagulation machine and the VSPro. Correlations for measurements were performed, as well as Bland-Altman analysis. RESULTS: Coefficients of variability for the VSPro ranged from 7% to 15%. The VSPro fibrinogen values were well correlated to both the ACL 1000 (r = 0.94, P<0.001) and the STA Compact measurements (r = 0.926, P<0.001). Bland-Altman analysis showed a mean bias of -0.83 g/l (95% confidence interval -2.03-0.324 g/l) for the ACL 1000 and a mean bias of -0.024 g/l (95% confidence interval -1.434-1.386 g/l) for the STA Compact. CONCLUSIONS: The VSPro appears to have adequate accuracy and precision for clinical measurement of plasma fibrinogen concentrations. POTENTIAL RELEVANCE: The VSPro provides a measurement of equine plasma fibrinogen concentration using a benchtop instrument with a rapid test time that has comparable accuracy to the fibrinogen concentration obtained from reference laboratories.

Thrombelastography in horses with acute gastrointestinal disease.

BACKGROUND: Coagulopathies in horses with gastrointestinal disease are frequently identified and associated with morbidity and fatality. OBJECTIVE: Determine if thrombelastography (TEG) identifies abnormalities associated with lesion type, presence of systemic inflammatory response syndrome (SIRS), morbidity, and fatality more consistently than traditional coagulation testing. ANIMALS: One-hundred and one horses examined for gastrointestinal disease and 20 healthy horses. METHODS: TEG, tissue factor (TF)-TEG, and traditional coagulation panels parameters and percentages of horses with coagulopathies were compared for lesion type, presence of SIRS, complications, and survival. RESULTS: Changes in individual parameters and increased incidence of coagulopathies were associated with fatality (R, P= .007; k-value [K], P= .004; clot lysis [CL]30, P= .037; CL60, P= .050; angle [Ang], P= .0003; maximum amplitude [MA], P= .006; lysis [Ly]30, P= .042; Ly60, P= .027; CI, P= .0004; ≥ 2 TEG coagulopathies, P= .013; ≥ 3 TEG coagulopathies, P= .038; TF-R, P= .037; TF-K, P= .004; TF-CL30, P < .0001; TF-CL60, P < .0001; TF-Ang, P= .005; TF-Ly30, P= .0002; TF-Ly60, P < .0001; TF-CI, P= .043; ≥ 1 TF-TEG coagulopathies, P= .003; ≥ 2 TF-TEG coagulopathies, P= .0004; prothrombin tme [PT], P < .0001; activated partial throboplastin time [aPTT], P= .021), inflammatory lesions (MA, P= .013; TF-CL30, P= .033; TF-CL60, P= .010; TF-Ly60, P= .011; ≥ 1 TF-TEG coagulopathy, P= .036; ≥ 2 TF-TEG coagulopathy, P= .0007; PT, P= .0005; fibrinogen, P= .019), SIRS (MA, P= .004; TF-CL30, P= .019; TF-CL60, P= .013; TF-Ly30, P= .020; TF-Ly60, P= .010; PT, P < .0001; aPTT, P= .032; disseminated intravascular coagulation, P= .005), and complications (ileus: aPTT, P= .020; diarrhea: TF-CL30, P= .040; TF-Ly30, P= .041; thrombophlebitis: ≥ 1 TF-TEG coagulopathy, P= .018; laminitis: MA, P= .004; CL60, P= .045; CI, P= .036; TF-MA, P= .019; TF-TEG CI, P= .019). Abnormalities in TEG and TF-TEG parameters were indicative of hypocoagulation and hypofibrinolysis. CONCLUSIONS AND CLINICAL IMPORTANCE: TEG identifies changes in coagulation and fibrinolysis associated with lesion type, SIRS, morbidity, and fatality in horses with gastrointestinal disease.

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses.

BACKGROUND: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. OBJECTIVES: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. ANIMALS: Six healthy adult horses. METHODS: Horses received clopidogrel (2 mg/kg p.o. q24h) or ASA (5 mg/kg p.o. q24h) for 5 days in a prospective randomized cross-over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B(2) (TXB(2) ) by ELISA were evaluated. In horses receiving clopidogrel, high-performance liquid chromatography analysis for clopidogrel and its carboxylic-acid metabolite SR 26334 was performed. RESULTS: SR 26334 was identified in all clopidogrel-treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP-induced platelet aggregation persisting for 120 hours after the final dose. ADP-induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen-induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB(2) from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.

Results of plate fixation of type 5 olecranon fractures in 20 horses.

REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small proportion of type 5 fractures, mostly treated with conservative therapy. OBJECTIVES: To evaluate the clinical details and outcome of type 5 olecranon fractures in a large group of horses treated by tension band plate fixation and to compare results with other treatment methods. METHODS: Medical records of 97 cases, including 32 (33%) classified as type 5, were reviewed. Subject details, history, radiographic findings, treatment and follow-up results (2-146 months post operatively) were recorded. RESULTS: Treatment included open reduction and internal fixation using a narrow or broad dynamic compression plate (n = 20), conservative therapy (n = 7) and euthanasia (n = 5). Long-term follow-up was available in 15 cases treated surgically, of which 2 were sound and in training, 11 sound and performing athletically and 2 unsound. Distal semilunar notch involvement, comminution or open status did not appear to affect prognosis. CONCLUSIONS: Internal plate fixation provides an excellent prognosis for an animal to be capable of athletic performance. POTENTIAL RELEVANCE: Describing tension band plate fixation and results offers a method of fracture repair that should improve treatment and prognosis for type 5 olecranon fractures.