Effect of infusion of equine plasma or 6% hydroxyethyl starch (600/0.75) solution on plasma colloid osmotic pressure in healthy horses

Erica C. McKenzie Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Melissa M. Esser Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Sarah E. McNitt Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Mark E. Payton Department of Statistics, Oklahoma State University, Stillwater, OK 74078.

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Abstract

OBJECTIVE To compare the effects of equivalent volumes of equine plasma and 6% hydroxyethyl starch (600/0.75) solution (hetastarch) administered IV on plasma colloid osmotic pressure (pCOP) and commonly monitored clinicopathologic variables in horses.

ANIMALS 6 healthy mares.

PROCEDURES In a randomized, crossover study, horses were administered hetastarch or plasma (both 10 mL/kg, IV) 18 months apart. The pCOP and variables of interest were measured before (baseline), immediately after, and at intervals up to 96 or 120 hours after infusion. Prothrombin and activated partial thromboplastin times were measured before and at 2 and 8 hours after each infusion.

RESULTS Prior to hetastarch and plasma infusions, mean ± SEM pCOP was 19.4 ± 0.5 mm Hg and 19.4 ± 0.8 mm Hg, respectively. In general, hetastarch and plasma infusions comparably increased pCOP from baseline for 48 hours, with maximum increases of 2.0 and 2.3 mm Hg, respectively. Mean Hct and hemoglobin, total protein, and albumin concentrations were decreased for a period of 72, 96, or 120 hours after hetastarch infusion with maximum decrements of 8.8%, 3.2 g/dL, 1.2 g/dL, and 0.6 g/dL, respectively. Plasma infusion decreased (albeit not always significantly) hemoglobin concentration and Hct for 20 and 24 hours (maximum changes of 1.5 g/dL and 6.6%, respectively) and increased total solids concentration (maximum change of 0.6 g/dL) for 48 hours. Platelet count and coagulation times were minimally affected.

CONCLUSIONS AND CLINICAL RELEVANCE Overall, the hetastarch and plasma infusions comparably increased pCOP in healthy horses for up to 48 hours. Hetastarch induced greater, more persistent perturbations in clinicopathologic variables.

Abstract

OBJECTIVE To compare the effects of equivalent volumes of equine plasma and 6% hydroxyethyl starch (600/0.75) solution (hetastarch) administered IV on plasma colloid osmotic pressure (pCOP) and commonly monitored clinicopathologic variables in horses.

ANIMALS 6 healthy mares.

PROCEDURES In a randomized, crossover study, horses were administered hetastarch or plasma (both 10 mL/kg, IV) 18 months apart. The pCOP and variables of interest were measured before (baseline), immediately after, and at intervals up to 96 or 120 hours after infusion. Prothrombin and activated partial thromboplastin times were measured before and at 2 and 8 hours after each infusion.

RESULTS Prior to hetastarch and plasma infusions, mean ± SEM pCOP was 19.4 ± 0.5 mm Hg and 19.4 ± 0.8 mm Hg, respectively. In general, hetastarch and plasma infusions comparably increased pCOP from baseline for 48 hours, with maximum increases of 2.0 and 2.3 mm Hg, respectively. Mean Hct and hemoglobin, total protein, and albumin concentrations were decreased for a period of 72, 96, or 120 hours after hetastarch infusion with maximum decrements of 8.8%, 3.2 g/dL, 1.2 g/dL, and 0.6 g/dL, respectively. Plasma infusion decreased (albeit not always significantly) hemoglobin concentration and Hct for 20 and 24 hours (maximum changes of 1.5 g/dL and 6.6%, respectively) and increased total solids concentration (maximum change of 0.6 g/dL) for 48 hours. Platelet count and coagulation times were minimally affected.

CONCLUSIONS AND CLINICAL RELEVANCE Overall, the hetastarch and plasma infusions comparably increased pCOP in healthy horses for up to 48 hours. Hetastarch induced greater, more persistent perturbations in clinicopathologic variables.

In systemically ill horses, hypoproteinemia is a common derangement that arises from various disease conditions including acute and chronic gastrointestinal tract disease, hemorrhage, failure of passive transfer, sepsis, acute and chronic urinary tract disorders, and inflammatory conditions of the pleural or peritoneal cavities.1 Additionally, horses undergoing elective or emergency general anesthesia are also at risk of progressive and substantial decrements in plasma total protein concentration.2,3 Hypoproteinemia reduces intravascular colloid osmotic pressure and, when severe, can impede tissue perfusion and promote the development of tissue and organ edema. Therefore, administration of synthetic or natural colloid substances to horses is commonly performed to maintain or correct systemic oncotic pressure and protein concentrations and to restore hemodynamic stability and organ perfusion.4–6 Colloid products that have been used clinically in horses include plasma, whole blood, polymerized hemoglobin, gelatins, dextrans, and hydroxyethylated starches.4–6 The hydroxyethylated starches represent a variety of synthetic products derived from the addition of hydroxyethyl ether groups into amylopectin. Hydroxyethylated starches differ in their mean molecular weight, molar substitution (which reflects the ratio of hydroxyethyl groups to glucose units), location of hydroxyethyl residues (represented by the C2:C6 ratio), and carrier solutions, all of which ultimately influence their pharmacokinetic properties and clinical effects.7–9

Commercially available equine plasma (a natural colloid product) and 6% hydroxyethyl starch (600/0.75) in saline (0.9% NaCl) solution (hetastarch, a synthetic colloid product) are commonly administered alone or in combination for the treatment of hypoproteinemia and hypoperfusion in systemically ill horses.4–6 Compared with equine plasma, hetastarch is relatively inexpensive, has a substantially higher oncotic pressure, is not associated with transmission of infectious disease, and can be stored without freezing, all of which represent considerable advantages.5 However, unlike plasma, hetastarch does not provide albumin, globulins, fibronectin, clotting factors, or anti-thrombin, and the potential for impaired hemostasis after hetastarch infusion represents an additional disadvantage.4,5,10,11

Previous studies evaluating hetastarch administration (10 mL/kg, IV) in healthy ponies and horses revealed significant increases in pCOP, central venous pressure, and mean arterial pressure.10,12 Administration of hetastarch (8 to 10 mL/kg, IV) to 11 horses with naturally occurring hypoproteinemia also resulted in improvement in pCOP for 24 hours after infusion.13 Infusion of lower doses of hetastarch (2.5 mL/kg, IV) to anesthetized horses undergoing nonabdominal surgical procedures apparently failed to ameliorate progressive decrements in pCOP.14 However, despite the existence of some data regarding the effects of hetastarch administration to healthy and diseased horses, there is a dearth of published studies that directly compare the efficacy of hetastarch with equine plasma, another commonly used colloid product.6,10,12–15 Therefore, the purpose of the study reported here was to compare the effects of equivalent volumes of equine plasma and hetastarch on pCOP and several commonly monitored clinicopathologic variables in healthy adult horses.

Materials and Methods

Six healthy adult mares from the Oregon State University teaching herd were used in the study. The horses ranged in weight from 484 to 575 kg (mean weight, 534 kg) and were 11 to 25 years old (mean age, 15.6 years). Prior to inclusion in the study, the horses were deemed healthy on the basis of medical history, results of a physical examination, and Hct and plasma total solids concentration within reference intervals. The horses were confined in stalls within the hospital during the periods of assessment and transfusion and were provided grass hay and water ad libitum; between those periods they were maintained in a pasture environment. All procedures were approved in advance by the Oregon State University Institutional Animal Care and Use Committee.

A randomized, crossover study design was used so that each horse received each infusion; an interval of 18 months elapsed between experimental periods because of the availability of personnel and funding. Prior to each infusion in each horse, hair from the skin overlying the left jugular vein was clipped and the site was aseptically prepared. After SC infusion of a local anesthetic agent, a 14-gauge single-lumen IV cathetera was placed into the left jugular vein and sutured to the skin. The IV catheter was used for colloid infusions and subsequent collection of all blood samples and remained in place for 5 days (removed thereafter). Initially, 3 of the 6 horses were administered 6% hydroxyethyl starch (600/0.75) in saline solutionb (hetastarch; 10 mL/kg) and the remaining 3 horses were administered commercial equine plasmac (10 mL/kg). Each infusion was administered via constant drip through an IV transfusion set over a period of 3 hours, during which time the horse was under continuous visual observation. The dose of 10 mL/kg was selected on the basis of previously published reports5,12,13 and clinical relevance. Investigators performing the infusions (ECM, MME, and SEM) and those performing data collection were not blinded to administered treatments. Eighteen months later, the experimental protocol was repeated in an identical fashion for each of the horses, but at that time, the alternate treatment was administered.

Commencing immediately before and throughout each infusion, each horse's demeanor, heart rate, and rectal temperature were recorded every 10 minutes for 120 minutes, and then these variables were recorded once every 20 minutes until the infusion ceased. Additionally, physical examination of all horses was performed twice daily throughout each experimental period. Demeanor was assessed by subjective observation of behavior and appetite, and heart rate was determined by cardiothoracic auscultation.

Immediately prior to each infusion (baseline) in each horse, approximately 20 mL of venous blood was obtained from the IV catheter for measurement of blood hemoglobin concentration, spun Hct, and platelet count; plasma total solids and serum total protein and albumin concentrations; and pCOP. Blood samples (20 mL each) were also obtained immediately after each infusion was completed (0 hours), and at 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, and 96 hours after infusion for measurement of the same variables. Additional measurements of pCOP, plasma total solids concentration, and Hct were obtained at 120 hours after each infusion. Blood samples were collected into evacuated tubes containing sodium heparin for the measurement of pCOP; into evacuated tubes containing EDTA for the measurement of Hct, platelet count, and total solids and hemoglobin concentrations; and into evacuated tubes without anticoagulant for the measurement of total protein and albumin concentrations. In addition, before infusion and at 2 and 8 hours after infusions ceased, 2 mL of blood was collected via the jugular catheter into evacuated tubes containing sodium citrate for the measurement of prothrombin and activated partial thromboplastin times. Time points for blood sample collection were selected on the basis of the expected duration of the effect of hetastarch on the variables under investigation.10,16 A total of 12 mL of venous blood was removed from the IV catheter into a plastic syringe before each sample collection and was returned to the horse immediately after sample collection was completed. After sample collection, IV catheters were flushed with 6 mL of saline solution with heparin.

For pCOP measurement, blood samples containing heparin were centrifuged and the plasma fraction was extracted and refrigerated (−4°C) until colloid osmometryd was performed within 12 hours after collection. Blood samples for prothrombin and partial thromboplastin time assessments were analyzed immediately by use of a fibrometere with the exception of samples collected at 8 hours after infusion, which were centrifuged and frozen before analysis (analysis performed within 24 hours after collection). The remaining analyses were performed within 4 hours after collection at a laboratoryf by use of standard techniques as recommended by the specific manufacturer. Platelet count and hemoglobin concentration were determined by use of a hematology system,g and visual assessment of slides was performed to identify major platelet clumping. Serum total protein and albumin concentrations were measured by use of an automated serum biochemistry analyzer.h The Hct was recorded, and total solids concentration in the plasma fraction of the sample was evaluated by refractometry.

Statistical analysis

Data were analyzed via repeated-measures ANOVA by use of statistical software program.i An autoregressive covariance structure was used to model the intra-horse correlation. Horse was considered a blocking variable to account for the crossover nature of the study. Simple effects of treatments and time on heart rate and rectal temperature during infusion, pCOP, and the remaining variables were assessed by use of planned contrasts and pairwise t tests to compare treatments when significance was detected. Results are reported as mean ± SEM. Significance was declared at a value of P < 0.05.

Results

pCOP

The infusions of plasma and hetastarch both resulted in mild, significant (P ≤ 0.01) increases in pCOP, compared with baseline values, but no difference in pCOP was detected between the 2 treatments at any time point (Figure 1). Plasma infusion significantly (P <0.03) increased pCOP from baseline at 2, 4, 8, and 12 hours after infusion and at 36 and 48 hours after infusion. Infusion with hetastarch significantly (P < 0.01) increased pCOP at 4, 8, 12, and 16 hours after infusion and at 24, 36, and 48 hours after infusion.

Figure 1—
Figure 1—

Mean ± SEM pCOP in 6 healthy adult horses before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or 6% hydroxyethyl starch (600/0.75) in saline (0.9% NaCl) solution (hetastarch [circles]) at a dose of 10 mL/kg in a crossover study. Each horse received each infusion at an interval of 18 months. Infusions were administered via constant drip over a 3-hour period through an IV catheter in the left jugular vein; blood samples were collected via that catheter before each infusion (baseline), immediately after each infusion was completed (0 hours), and at 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours after infusion. *At this time point after horses received the plasma infusion, the value differed significantly (P < 0.05) from baseline. †At this time point after horses received the hetastarch infusion, the value differed significantly (P < 0.05) from baseline.

Citation: American Journal of Veterinary Research 77, 7; 10.2460/ajvr.77.7.708

Platelet count, Hct, and hemoglobin concentration

Among the 6 horses, platelet count, Hct, and hemoglobin concentration prior to the 2 treatments did not differ significantly. Neither treatment induced significant changes in platelet count. (Table 1). Infusion of plasma immediately and significantly (P ≤ 0.01) decreased the horses' Hct for 24 hours (Figure 2). Infusion of hetastarch created an immediate, more profound, and significant (P < 0.01) decrement in Hct that persisted to the 120-hour time point. At most time points, there was a significant (P < 0.03) difference in Hct between the 2 treatments. Infusion of plasma immediately decreased blood hemoglobin concentration for up to 20 hours; the decreases, compared with baseline, were significant (P < 0.01) with the exception of those at 8 and 12 hours. Infusion of hetastarch induced a more profound and significant (P < 0.01) decrease in blood hemoglobin concentration that persisted for 72 hours; at most time points, there was a significant (P < 0.03) difference in blood hemoglobin concentration between the 2 treatments.

Table 1—

Mean ± SEM platelet count and blood hemoglobin and plasma total solids concentrations in 6 healthy adult horses before (baseline), immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma or 6% hydroxyethyl starch (600/0.75) in saline (0.9% NaCl) solution (hetastarch) at a dose of 10 mL/kg in a crossover study.

 Platelet count (× 103/μL)Hemoglobin (g/dL)Total solids (g/dL)
Time pointHetastarchPlasmaHetastarchPlasmaHetastarchPlasma
Baseline144 ± 13158 ± 1912.2 ± 0.412.2 ± 0.56.3 ± 0.26.4 ± 0.2
Time after infusion (h) 0133 ± 11150 ± 229.6 ± 0.510.8 ± 0.5*6.1 ± 0.26.9 ± 0.2*
1138 ± 13148 ± 209.0 ± 0.410.7 ± 0.4*6.2 ± 0.16.9 ± 0.2*
2131 ± 13147 ± 209.1 ± 0.411.3 ± 0.5*6.1 ± 0.26.8 ± 0.2*
4135 ± 10144 ± 209.5 ± 0.610.9 ± 0.3*6.3 ± 0.26.9 ± 0.3*
8139 ± 1016I ± 229.9 ± 0.411.6 ± 0.36.4 ± 0.26.8 ± 0.2*
12142 ± 7163 ± 2210.5 ± 0.5*11.4 ± 0.46.4 ± 0.17.0 ± 0.2*
16145 ± 11164 ± 209.7 ± 0.411.1 ± 0.4*6.3 ± 0.16.9 ± 0.2*
20145 ± 11171 ± 2610.0 ± 0.811.0 ± 0.3*6.2 ± 0.26.7 ± 0.1*
24143 ± 12154 ± I910.8 ± 0.711.4 ± 0.46.5 ± 0.16.8 ± 0.1*
36149 ± 10167 ± 2410.4 ± 0.612.2 ± 0.46.4 ± 0.27.0 ± 0.1*
48145 ± 10147 ± 2010.8 ± 0.712.4 ± 0.66.4 ± 0.16.8 ± 0.1*
72145 ± 8155 ± 2011.2 ± 0.612.3 ± 0.76.1 ± 0.26.5 ± 0.2
96147 ± 10158 ± 2011.7 ± 0.811.9 ± 0.46.2 ± 0.16.4 ± 0.1
120NANANANA6.1 ± 0.16.7 ± 0.1

Each horse received each infusion at an interval of 18 months. Infusions were administered via constant drip over a 3-hour period through an IV catheter in the left jugular vein; blood samples were collected via that catheter before each infusion (baseline), immediately after each infusion was completed (0 hours), and at 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours after infusion.

At this time point after horses received the plasma infusion, the value differed significantly (P < 0.05) from baseline.

At this time point after horses received the hetastarch infusion, the value differed significantly (P < 0.05) from baseline.

For a given variable at this time point, values for each treatment differed significantly (P < 0.05).

NA = Not assessed.

Figure 2—
Figure 2—

Mean ± SEM Hct in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. ‡At this time point, values for each treatment differed significantly (P < 0.05). See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 77, 7; 10.2460/ajvr.77.7.708

Serum total protein and albumin concentrations and plasma total solids concentration

Among the 6 horses, chemically measured serum total protein (Figure 3) and albumin (Figure 4) concentrations and plasma total solids concentrations (Table 1) prior to the 2 treatments were not significantly different. Infusion of plasma resulted in minimal change in total protein and albumin concentrations. However, plasma total solids concentration increased significantly (P < 0.04) for 48 hours after plasma infusion, with values exceeding those recorded after hetastarch infusion for 72 hours. Infusion of hetastarch immediately and significantly (P < 0.01) decreased both serum total protein and albumin concentrations for 96 hours (with the exception of total protein concentration at the 1-hour time point, which was decreased but not significantly). Serum total protein and albumin concentrations were substantially lower than findings when horses were administered plasma. Infusion of hetastarch did not significantly alter plasma total solids concentration from baseline.

Figure 3—
Figure 3—

Mean ± SEM serum total protein concentration in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. Data collection ceased at 96 hours after infusion. See Figures 1 and 2 for key.

Citation: American Journal of Veterinary Research 77, 7; 10.2460/ajvr.77.7.708

Figure 4—
Figure 4—

Mean ± SEM serum albumin concentration in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. Data collection ceased at 96 hours after infusion. See Figures 1 and 2 for key.

Citation: American Journal of Veterinary Research 77, 7; 10.2460/ajvr.77.7.708

Prothrombin and partial thromboplastin times

Among the 6 horses, prothrombin times prior to the 2 treatments were comparable (10.4 ± 0.3 seconds and 10.2 ± 0.3 seconds for the hetastarch and plasma infusions, respectively). Infusion with hetastarch and plasma had no significant effect on prothrombin time at 2 hours (11.3 ± 0.5 seconds and 10.7 ± 0.4 seconds, respectively) or 8 hours (11.4 ± 0.5 seconds and 10.9 ± 0.5 seconds, respectively), compared with baseline. However, prothrombin time was slightly greater than the laboratory reference interval of 8.2 to 11.0 seconds at both time points (exceeding the upper reference limit by 0.3 and 0.4 seconds at 2 and 8 hours, respectively). Similarly, among the 6 horses, partial thromboplastin times prior to the 2 treatments were comparable (30.0 ± 1.4 seconds and 29.0 ± 1.5 seconds for the hetastarch and plasma infusions, respectively). Administration of hetastarch or plasma had no significant effect at 2 hours after infusion (30.0 ± 1.8 seconds and 30.0 ± 1.6 seconds, respectively). Freezing of samples collected 8 hours after infusion for measurement of partial thromboplastin time resulted in unacceptable processing artifacts, and the data were subsequently discarded.

Demeanor, heart rate, and rectal temperature

Infusion with hetastarch induced no notable change in demeanor, heart rate, or rectal temperature in any horse. In 1 horse, infusion with plasma resulted in mild to moderate signs of abdominal pain, which commenced at approximately 110 minutes after infusion and were characterized by anxiety, pawing, tachycardia (heart rate, 56 beats/min), and transient recumbency. As a result, the horse was treated with flunixin meglumine (1.1 mg/kg, IV, once) and diphenhydramine (1 mg/kg, IV, once) with prompt resolution of clinical signs. Infusion with plasma was associated with a slight but significant (P < 0.05) increase in mean heart rate, which commenced 30 minutes after infusion (data not shown). Mean heart rate before the plasma infusion was 37 ± 1 beats/min; after 30 minutes of infusion, mean heart rate increased up to 42 ± 3 beats/min, with significant (P < 0.05) differences from baseline recorded at 30, 60, and 70 minutes after infusion. Mean rectal temperature of the horses before both infusions was 37.8 ± 0.1°C, and remained ≤ 37.8°C throughout each experimental period. Values for both heart rate and rectal temperature remained within commonly accepted reference intervals for all horses with the exception of mild transient tachycardia in the horse with signs of abdominal pain.

Discussion

Intravenous administration of commercial equine plasma or hetastarch (10 mL/kg) resulted in mild and equivalent increases in pCOP for up to 48 hours, indicating comparable efficacy of these substances for increasing pCOP in healthy adult horses. The increase in pCOP (from baseline) observed in horses after hetastarch infusion in the present study was in concordance with previously reported findings in healthy ponies and horses10,12 as well as in hypo proteinemic horses.17 However, the duration of effect of 10 mL of hetastarch/kg on pCOP is potentially shorter in healthy horses than in healthy ponies, suggesting an effect of breed or body size on hetastarch dynamics in equids.10,12

The effect of equine plasma infusion on pCOP and other variables in healthy horses does not appear to have been previously reported. In the present study, infusion of 10 mL of plasma/kg induced an increase in pCOP that was comparable to that induced by an equivalent volume of hetastarch. However, it should be recognized that the primary determinant of the oncotic pressure of plasma is albumin, a molecule that can rapidly distribute throughout the extracellular fluid compartment and migrate into the interstitium.18 These characteristics potentially complicate the ability to elicit predictable changes in pCOP via administration of plasma to individual horses. Furthermore, in horses with disease conditions that promote extravasation of albumin, it is possible that plasma transfusion might have negligible efficacy in improving pCOP, compared with the effects of hydroxyethylated starch products.4,5,19,20 However, to the authors' knowledge, direct comparison of the effects of infusions of hydroxyethylated starch products and plasma has yet to be performed in systemically compromised or hypoproteinemic horses, and the specific benefits and disadvantages of administration of each colloid type must be considered when determining appropriate treatment for individual equids.

In addition to providing albumin and oncotic support, plasma transfusion is specifically indicated when there is an established need for immunoglobulins, coagulation factors, antithrombin, or specific antibodies.4,5,19 Hetastarch (600/0.75) has the advantages of lower cost, higher oncotic pressure, greater persistence within the vasculature with repeated administration and in the face of capillary leakage, and, on the basis of the results of the present study, possibly a more profound volume expanding effect, compared with the effects of equine plasma.5,9,20 Furthermore, the potential for adverse allergic reactions in response to a transfusion is likely lower for hetastarch than it is for plasma.7,17,21,22 However, an issue associated with administration of hetastarch is a detrimental effect on hemostasis, and it is also not recommended for administration to humans with risk of acute renal injury or severe sepsis.11,23,24 Tetrastarch (6% hetastarch [130/0.4]) is a more recently available starch product that has lower molecular weight and molar substitution than 6% hetastarch (600/0.75).12,25 Compared with other colloids, the purported advantages of this newer product include equivalent or superior hemodynamic effects with reduced risks of renal injury and impaired hemostasis, thereby permitting administration of much higher doses.8,9 Tetrastarch administration to healthy horses increases central venous pressure and pCOP in a manner comparable to hetastarch, with minor effects on specific hemostatic variables.11,12,25 Finally, the possibility of a synergistic effect resulting from combination of plasma and hetastarch does not appear to have been investigated. Anecdotally, combination of colloid products is commonly practiced in equine medicine, and although it remains to be proven, this approach may facilitate oncotic pressure support while concurrently minimizing expense.

Administration of hetastarch induces substantial changes in commonly monitored clinicopathologic variables in ponies, horses, and llamas, which is largely attributable to the dilutional effects of volume expansion.10,13,16 This phenomenon was observed in the present study, with infusion of hetastarch resulting in significant decreases in Hct, blood hemoglobin concentration, and chemically analyzed serum total protein and albumin concentrations for 72 to 120 hours. Although infusion of plasma also resulted in decrements in Hct and blood hemoglobin concentration, the observed changes were much less profound and resolved within 24 hours. Although these differences possibly indicate that the capacity for volume expansion of hetastarch is superior to that of commercial equine plasma when administered at comparable doses, the profound dilutional effects of even a relatively modest dose of hetastarch (600/0.75) may complicate serial monitoring of specific clinicopathologic variables in treated horses. In horses, the dilutional effects may be less profound and persistent following tetrastarch administration, compared with hetastarch administration, despite comparable effects of the 2 products on colloid osmotic pressure.12 Hydroxyethyl starch administration has been previously shown to increase central venous pressure and arterial pressures in healthy horses12; however, advanced cardiovascular monitoring was not performed in the present study and the effect of hetastarch infusion, compared with plasma infusion, on measured cardiovascular variables in the study horses cannot be determined.

With regard to impaired hemostasis associated with administration of hetastarch products, influences other than dilutional effects include decreases in von Willebrand factor concentration and activity, decreases in plasma factor VIII concentration, and impaired platelet function.8,11,26 In the present study, hemostasis was minimally assessed via measurement of coagulation times and platelet count, and administration of 10 mL of hetastarch/kg had minimal impact on these variables, consistent with previous study results.10,12 Although assessment of coagulation status via dynamic viscoelastic coagulometry was not performed in the present study, such in vitro assessment of equine blood diluted to a level comparable to that expected to result from an infusion of hetastarch (10 mL/kg) has demonstrated minimal effects on hemostasis.11 Nonetheless, prudence dictates that hydroxyethyl starch products, and particularly those with higher molecular weights, should be used judiciously in perioperative situations or in horses with diagnosed or suspected coagulation disorders to reduce the possibility of exacerbating impaired hemostasis. Equine plasma, therefore, likely represents the most appropriate colloid treatment option in those situations. However, it is also unknown whether concurrent administration of equine plasma may reduce or neutralize reported adverse effects of hydroxyethyl starch administration on hemostatic variables.

Results of the present study indicated that 6% hetastarch (600/0.75) or commercial equine plasma administered at a dose of 10 mL/kg over a period of 3 hours generated a mild, prompt, and comparable increase in pCOP for 48 hours in healthy adult mares. Whether the effects of these treatments in systemically compromised or hypoproteinemic horses are similarly comparable is worthy of investigation, as is the potential for synergistic benefit from administration of different colloid products in combination in horses.

Acknowledgments

Presented in abstract form at the Veterinary Emergency and Critical Care Society meeting, San Antonio, Tex, September 2012.

ABBREVIATIONS

pCOP

Plasma colloid osmotic pressure

Footnotes

a.

Abbocath-T radiopaque teflon catheter, Hospira Inc, Lake Forest, Ill.

b.

Hespan, 6% hetastarch in 0.9% sodium chloride injection, B Braun Medical Inc, Evanston, Ill.

c.

Equine plasma, Mg Biologics, Ames, Iowa.

d.

Wescor 4420 colloid osmometer, Wescor Inc, Logan, Utah.

e.

Fibrosystem, Becton-Dickinson, Cockeysville, Md.

f.

Veterinary Diagnostic Laboratory, Oregon State University, Corvallis, Ore.

g.

Advia 120 hematology system, Siemens Healthcare Diagnostics, Deerfield, Ill.

h.

Roche/Hitachi 917 automatic analyzer, Roche Diagnostics Corp, Indianapolis, Ind.

i.

PC SAS, Version 9.2, SAS Institute Inc, Cary, NC.

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  • 14. Wendt-Hornickle EL, Snyder LBC, Tang R, et al. The effects of lactated Ringer's solution (LRS) or LRS and 6% hetastarch on the colloid osmotic pressure, total protein and osmolality in healthy horses under general anesthesia. Vet Anaesth Analg 2011; 38: 336343.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Pantaleon LG, Furr MO, McKenzie HC II, et al. Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endotoxemia in anesthetized horses. J Vet Intern Med 2006; 20: 14221428.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Carney KR, McKenzie EC, Mosley CA, et al. Evaluation of the effect of hetastarch and lactated Ringer's solution on plasma colloid osmotic pressure in healthy llamas. J Am Vet Med Assoc 2011; 238: 768777.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Bellezzo F, Kuhnmuench T, Hackett ES. The effect of colloid formulation on colloid osmotic pressure in horses with naturally occurring gastrointestinal disease. BMC Vet Res 2014; 10 (suppl 1): S8.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Hall JE, Guyton AC. The microcirculation and lymphatic system: capillary fluid exchange, interstitial fluid, and lymph flow. In: Hall JE, Guyton AC, eds. Textbook of medical physiology. 12th ed. Philadelphia: Saunders Elsevier, 2011:177–189.

    • Search Google Scholar
    • Export Citation
  • 19. Rudloff E, Kirby R. The critical need for colloids: selecting the right colloid. Compend Contin Educ Pract Vet 1997; 19: 811826.

  • 20. Marx G, Cobas Meyer M, Schuerholz T, et al. Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage. Intensive Care Med 2002; 28: 629635.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Wilson EM, Holcombe SJ, Lamar A, et al. Incidence of transfusion reactions and retention of procoagulant and anticoagulant factor activities in equine plasma. J Vet Intern Med 2009; 23: 323328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Hardefeldt LY, Keuler N, Peek SF. Incidence of transfusion reactions to commercial equine plasma. J Vet Emerg Crit Care 2010; 20: 421425.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev 2013; 23: 7.

    • Search Google Scholar
    • Export Citation
  • 24. Reinhart K, Perner A, Sprung CL, et al. Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. Intensive Care Med 2012; 38: 368383.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Viljoen A, Page PC, Fosgate GT, et al. Coagulation, oncotic and haemodilutional effects of a third-generation hydroxyethyl starch (130/0.4) solution in horses. Equine Vet J 2014; 46: 739744.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis. Anesthesiology 2005; 103: 654660.

Contributor Notes

Address correspondence to Dr. McKenzie (erica.mckenzie@oregonstate.edu).

Dr. Esser's present address is Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN 55108. Dr. McNitt's present address is DeKalb County Packing Co Inc, 20036 Webster Rd, DeKalb, IL 60115.

  • Figure 1—

    Mean ± SEM pCOP in 6 healthy adult horses before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or 6% hydroxyethyl starch (600/0.75) in saline (0.9% NaCl) solution (hetastarch [circles]) at a dose of 10 mL/kg in a crossover study. Each horse received each infusion at an interval of 18 months. Infusions were administered via constant drip over a 3-hour period through an IV catheter in the left jugular vein; blood samples were collected via that catheter before each infusion (baseline), immediately after each infusion was completed (0 hours), and at 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours after infusion. *At this time point after horses received the plasma infusion, the value differed significantly (P < 0.05) from baseline. †At this time point after horses received the hetastarch infusion, the value differed significantly (P < 0.05) from baseline.

  • Figure 2—

    Mean ± SEM Hct in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. ‡At this time point, values for each treatment differed significantly (P < 0.05). See Figure 1 for remainder of key.

  • Figure 3—

    Mean ± SEM serum total protein concentration in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. Data collection ceased at 96 hours after infusion. See Figures 1 and 2 for key.

  • Figure 4—

    Mean ± SEM serum albumin concentration in the 6 healthy adult horses in Figure 1 before, immediately after (0 hours), and at intervals after IV infusion of commercially available equine plasma (crosses) or hetastarch (circles) at a dose of 10 mL/kg in a crossover study. Data collection ceased at 96 hours after infusion. See Figures 1 and 2 for key.

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  • 3. Boscan P, Steffey EP. Plasma colloid osmotic pressure and total protein in horses during colic surgery. Vet Anaesth Analg 2007; 34: 408415.

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  • 13. Jones PA, Bain FT, Byars TD, et al. Effect of hydroxyethyl starch infusion on colloid oncotic pressure in hypoproteinemic horses. J Am Vet Med Assoc 2001; 218: 11301135.

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  • 14. Wendt-Hornickle EL, Snyder LBC, Tang R, et al. The effects of lactated Ringer's solution (LRS) or LRS and 6% hetastarch on the colloid osmotic pressure, total protein and osmolality in healthy horses under general anesthesia. Vet Anaesth Analg 2011; 38: 336343.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Pantaleon LG, Furr MO, McKenzie HC II, et al. Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endotoxemia in anesthetized horses. J Vet Intern Med 2006; 20: 14221428.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Carney KR, McKenzie EC, Mosley CA, et al. Evaluation of the effect of hetastarch and lactated Ringer's solution on plasma colloid osmotic pressure in healthy llamas. J Am Vet Med Assoc 2011; 238: 768777.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Bellezzo F, Kuhnmuench T, Hackett ES. The effect of colloid formulation on colloid osmotic pressure in horses with naturally occurring gastrointestinal disease. BMC Vet Res 2014; 10 (suppl 1): S8.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Hall JE, Guyton AC. The microcirculation and lymphatic system: capillary fluid exchange, interstitial fluid, and lymph flow. In: Hall JE, Guyton AC, eds. Textbook of medical physiology. 12th ed. Philadelphia: Saunders Elsevier, 2011:177–189.

    • Search Google Scholar
    • Export Citation
  • 19. Rudloff E, Kirby R. The critical need for colloids: selecting the right colloid. Compend Contin Educ Pract Vet 1997; 19: 811826.

  • 20. Marx G, Cobas Meyer M, Schuerholz T, et al. Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage. Intensive Care Med 2002; 28: 629635.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Wilson EM, Holcombe SJ, Lamar A, et al. Incidence of transfusion reactions and retention of procoagulant and anticoagulant factor activities in equine plasma. J Vet Intern Med 2009; 23: 323328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Hardefeldt LY, Keuler N, Peek SF. Incidence of transfusion reactions to commercial equine plasma. J Vet Emerg Crit Care 2010; 20: 421425.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev 2013; 23: 7.

    • Search Google Scholar
    • Export Citation
  • 24. Reinhart K, Perner A, Sprung CL, et al. Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. Intensive Care Med 2012; 38: 368383.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Viljoen A, Page PC, Fosgate GT, et al. Coagulation, oncotic and haemodilutional effects of a third-generation hydroxyethyl starch (130/0.4) solution in horses. Equine Vet J 2014; 46: 739744.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis. Anesthesiology 2005; 103: 654660.

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