ORIGINAL

Hetastarch and Hetastarch + 7.2% NaCl solution in the treatment of hypovolemic diarrheic calves

Hetastarch y Hetastarch + solucián de NaCl al 7.2%(p/v) en el tratamiento de terneros diarreicos hipovolémicos

Mehmet Çagri Karakurum,¹* Ph.D, Metin Koray Albay,¹ Ph.D, , Şima Şahinduran,¹ Ph.D, Kenan Sezer,¹ Ph.D, Ramazan Yildiz,¹ Ph.D, Necmettin Sarp Sevgisunar,¹ DVM.

¹Mehmet Akif Ersoy University, Faculty of Veterinary Medicine, Department of Internal Medicine, Burdur, Turkey.

*Correspondence: mckarakurum@hotmail.com

Received: August 2015; Accepted: January 2016.

Objective. In this study, it was aimed to compare the effectiveness of Hydroxyethyl Starch (HTS), HTS +7.2% NaCl combination and Ringer Lactate solutions in the treatment of hypovolemic calves with diarrhea. Materials and methods. A total of 21 holstein calves (12 female, 9 male, weighted 28-52 kg), at the age of 0-30 days, were enrolled in the present study. The calves were randomly divided into 3 groups. Calves in the first group received HTS (10 mL / kg), calves in the second group received Hydroxyethyl starch + 7.2% NaCl combination (4 mL/kg) and calves in the third group were treated with lactated Ringer's solution (32 mL/kg) intravenously. Calves in each group were administered with oral rehydration solution immediately, and at 8th and 16th hours after intravenous applications. Clinical examinations and laboratory findings were obtained at 0 hour, 30th minutes, 1st, 2nd, 4th, 12th and 24th hours respectively. Results. Calves in all groups achieved clinical remission with a positive response to treatment and there was no statistically significant difference in the vast majority of the variables examined, although dehydration, capillary refill time, mental status and pulse quality were better in hydroxyethyl starch group and especially in hydroxyethyl starch + 7.2% NaCl group than those of Ringer’s lactate group (p<0.05). Conclusions. In the present study, treatment of hypovolemic calves with diarrhea especially with Hydroxyethyl starch and Hydroxyethyl starch + 7.2% NaCl combination along with oral fluid therapy with the electrolyte solution was considered to be practical and effective.

Key words: Calf diarrhea, hypovolemia, hydroxyethyl starch, hydroxyethyl starch + 7.2% NaCl (Source: CAB).

RESUMEN

Objetivo. En este estudio, que tuvo como objetivo comparar la eficacia de hidroxietil almidán (HEM), HEM + 7.2% en combinacián con NaCl y soluciones lactato de Ringer en el tratamiento de los terneros hipovolémicos con diarrea. Materiales y métodos. Un total de 21 terneros Holstein (12 hembras, 9 machos, con pesos entre 28-52 kg) y edad de 0-30 días, fueron consideradas en el presente estudio. Los terneros fueron divididos aleatoriamente en 3 grupos. Terneros en el primer grupo recibieron HEM (10 ml/kg), los terneros en el segundo grupo recibieron almidán + combinacián hidroxietil 7.2% de NaCl (4 ml/kg) y terneros en el tercer grupo fueron tratados con solucián lactato de Ringer (32 ml/kg) por vía intravenosa. A los terneros en cada grupo se les administrá solucián de rehidratacián oral inmediatamente después, y las ocho y a las 16 horas después de las aplicaciones intravenosas. Los exámenes clínicos y de laboratorio se obtuvieron a las 0 h, 30 minutos, 1, 2, 4, 12 y 24 de horas respectivamente. Resultados. Los terneros en todos los grupos alcanzaron la remisián clínica con una respuesta positiva al tratamiento y no hubo diferencia estadísticamente significativa en la mayoría de las variables examinadas; a pesar de la deshidratacián, el tiempo de llenado capilar, el estado mental y la calidad de pulso fueron mejores en el grupo tratado con hidroxietil almidán y especialmente en hidroxietil almidán + 7.2% NaCl que los del grupo de lactato de Ringer (p<0.05). Conclusiones. En el presente estudio, el tratamiento de los terneros con diarrea hipovolémicos especialmente con hidroxietil almidán y almidán + 7.2% NaCl combinacián hidroxietil junto con la terapia de fluido oral con la solucián de electrolito fue considerado práctico y eficaz.

Palabras clave: Almidán hidroxietil almidán hidroxietil + 7.2% de NaCl, diarrea, hipovolemia, terneros (Fuente:CAB).

Calf diarrhea is one of the most important health problem and a major source for cause of economic losses in calf husbandry (1,2). Diarrhea leads to severe dehydration and imbalances in acid-base and electrolyte status in neonatal calf. Oral electrolyte fluid administration is recommended for the treatment of moderately dehydrated diarrheic calves; indeed IV infusion of fluids is necessary for severely dehydrated calves (3,4). Administration of large volumes of isotonic solutions is time consuming and expensive. To avoid these disadvantages use of colloid+ hypertonic saline combination along with oral electrolyte fluid administration are recommended in the treatment of neonatal calf diarrhea (2,5,6).

Hydroxyethyl starch (HTS) is a high molecular weight (average molecular weight = 450.000 dalton) glucose polymer produced chemically from amylopectin. Enzymatic degradation by α-amylase in blood increases the plasma volume. It is commercially available as 6% Hetastarch in 0.9% NaCl solution. At this concentration, it is hyperoncotic and iso-ismotic. HTS is a natural polysaccharide and rapidly hydrolyzed by amylase. In dogs when given at 25 mL/kg, increases plasma volume 1.37 times the volume infused. Intravascular persistence is also comparable with dextran 70. After 24 h of injection 38% of hetastarch remaining intravascular compared with 19% of dextran. Most HES molecules may persist in the body for 2−7 days. In dogs up to 100 mL/kg dose was reported to be nontoxic and non-allergic. To the present author’s knowledge there are no reports of hetastarch in the use of ruminants (3,7).

The aim of the present study was to evaluate the effectiveness of hetastarch alone and in combination with HSS in the treatment of hypovolemic calves with naturally occurring diarrhea.

MATERIALS AND METHODS

The method of this study was modified from a prior study (6).

Location of study. This study was performed in Burdur province, which is located in south-west of Turkey; it is located between 37.43°N and 30.17°E, with an altitude level 950 m above sea level. Burdur province homes one of the highest populations of cattle in country. Burdur has a continental Mediterranean climate with cold, snowy winters and hot, long and dry summers. The average temperature was between 3.9°C and 25°C, 51.2% relative humidity, with an annual precipitation average of 440 mm.

Animal material. This study was conducted on 21 hypovolemic diarrheic calves (12 female, 9 male, weighted 32-46 kg, 0-30 day of age) in Burdur province between 2012 January- 2013 June. Bacterial, viral or parasitic etiology was not the subject of the study. Calves with coexisting diseases such as arthritis, omphalitis and pneumonia were exclude from the study. Also blood gas work findings did not taken into account. Calves were allocated to the three groups as 123, 321, 231, 213, 312 randomly. Calves were hospitalize individually in a private room in the hospitalization area of veterinary teaching hospital. Informed written consent was obtain from all of the calves owners.

Calves were chose according to the presence of dehydration (distance between medial canthus and eyeball more than 4 mm, showing 8% dehydration or more).

After decision for inclusion to the study each calf weighted and an 18 gauge catheter replaced to the V. jugularis. Blood specimen collections and treatment applications were done through this catheter. Catheters were wash at each sampling.

Clinical examination and collection of specimens. Clinical examinations and blood collections (for hematology, biochemistry and blood gas work) of all calves were perform before and at ½, 1, 2, 4, 12, 24 h after the treatment.

Clinical examinations. Body temperature, pulse, respiration rates, peripheral pulse quality, capillary refill time, dehydration degrees and mental status of each calf were exanimated at above mentioned times.

Mental status, peripheral pulse quality and fecal consistency were evaluated and numerically scores as adopted from previous studies.

For the evaluation of mental status, scoring method (0= Normal, 1= Mild depression, does not suckle vigorously, 2= moderate depression and poor suckling, 3= severe depression, recumbent and no suckle reflex), as reported by Walker et al (2) was used.

Peripheral pulse quality scoring was conducted from A.maxillaris externa by the method as reported by Şentürk (6): 1) = Difficult to palpate and count; 2) = Very weak but countable; 3)=Weak; 4) = Normal

Fecal consistency was scored as follows: 0=Normal, 1= mild diarrhea, 2= severe watery diarrhea.

Clinical dehydration severity were scored as 0=normal bright eyes, normal skin turgor and eye balls, 1= congested episcleral vessels, slightly decreased skin turgor and slightly retracted eye ball (distance between medial canthus and eyeball is 1- 3 mm), 2= dry oral mucosa, evident decrease in skin turgor, retracted eye ball (distance between medial canthus and eyeball is 4-6 mm), 3= cold nose and oral mucosa, marked decrease in skin turgor, well retracted eye ball (distance between medial canthus and eyeball is > 7 mm).

Hematological, biochemical examinations and blood-gas analyses. Hematological examinations (PCV, Hemoglobin, RBC and WBC) were performed by a hematology device (MS9 blood cell counter, Melet Schloesing Laboratories, Osny, France) immediately. Blood specimens for biochemical analyses were collected in tubes without anticoagulant and centrifuged at 3000 rpm, at 4°C for 10 min. Serum specimens were carefully harvest and stored at −20°C until use. Biochemical variables (Total Protein, BUN, Glucose, Creatinine and Phosphorus) were determined by an auto analyzer and commercial kits (VET TEST 8008, IDEXX Laboratories Inc., Westbrook, ME, USA). Venous blood gas analysis (pH, HCO₃, Base excess) and measurements of Na+, Cl-, K+ concentrations were done by using an automated gas analyzer in 10 minutes after blood withdrawal (Roche OPTI CCA blood gas analyzer, Roche, Mannheim, Germany).

Treatment. Calves were randomly llocated into three groups. Hetastarch (Varihes 6 % IV infüzyon solusyonu^®, 10 mL/kg IV) along with 50 mL/kg oral electrolyte solution (Baymix^®, Bayer) was administered to group I (HTS group) and Hetastarch + 7.2% NaCl (4 mL/kg IV) with oral electrolyte solution (50 mL/kg, PO) was administered to group II (HTS + 7.2% NaCl group). Hetastarch + 7.2 % NaCl solution was prepared by adding 32.6 g NaCl to 500 mL of 6% Hetastarch solution in 0.9% NaCl. Lactated Ringer’s solution (32 mL/kg, IV) with oral electrolyte solution (22 mL/kg, PO) was administered to group III (LR group). Oral electrolyte solution was readministered to each calf (50 mL/kg) at the 8th and 16th hours of the study. Additionally Ceftiofur sodium (Excenel^®, Pfizer, 2.2 mg/kg, SC, q12 h) was given to all calves. Calves that were unwilling to suckle were intubated.

Statistical analysis. General linear model (time, treatment with repeated measures on factor time) was use for comparison of continuous variables. Multiple pair-wise comparisons were done between or within groups, using Tukey test to compare means. Between groups, comparisons for each variable were made at each time point.

To assess non parametric data Kruskal Wallis test and Mann-Whitney U test was used. Comparisons for 0-hour value were made by Willcoxon test. p<.05 was deemed statistically significant. All statistical analysis was performed by using Minitab 16 statistical software.

RESULTS

Diarrhea led to hypovolemia, imbalance of acid-base status and metabolic disorders in all calves. All the calves were dehydrated 8% or more. Dehydration related hypovolemia resulted in increases in hematocrit, BUN, creatinine and capillary refill time. Metabolic acidosis was evident with a decrease in pH and HCO-₃ values and an increase in base excess. Pre and post-treatment clinical and laboratory data of groups are in tables 1,2,3.

Table 1. Results of physical examination

Table 2. Results of biochemical analyses

Table 3. Results of Blood gas work variables and Hematological analyses.

In comparison with 0 hour value, the degree of dehydration started to decrease at 2^nd hour in HTS + 7.2% NaCl combination group, and at 4^th hour in HTS and LR group. There were no dehydration symptoms after 24 hours of treatment in HTS + 7.2% NaCl combination and HTS groups; however, dehydration symptoms were evident in LR group. Decrease in dehydration (Table 1) was significant at 12^th hour in HTS + 7.2% NaCl group when compared with HTS and LR group (p<0.05). There were varying degrees of mental status impairment in all calves and it was found to be associated with the severity of metabolic acidosis. Improvement in mental status seen in all groups after treatment however there were no differences between groups. But when compared to 0 hour, improvement started at 2^nd hour in HTS and HTS + 7.2% NaCl groups and at 4^th hour in LR group. Albeit there was no statistical differences between groups, according to us clinical improvement in mental status was better than others in HTS + 7.2% NaCl group. Capillary refill time was shortened in all groups after treatment. Shortening in CRT was statistically significant in 1^st hour in HTS + 7.2% NaCl combination and LR group and in 2^nd hour in HTS group. When compared between groups statistical difference was seen in 24 th hour and more prominent in HTS + 7.2% NaCl group (Figure 1).

Figure 1. Capillary refill time (CRT) in hypovolemic calves with diarrhea. Shortening in CRT was statistically significant in 1st hour in HTS + 7.2% NaCl combination and LR group and in 2nd hour in HTS group. When compared between groups statistical difference was seen in 24th hour and more prominent in HTS + 7.2% NaCl combination group.

Peripheral pulse quality was improve in groups after treatment and was found to be statistically different at 30th minute, 1^st, 2^nd, 4^th and 12^th hour between groups. Improvement was most notably seen in HTS and HTS + 7.2% NaCl combination groups. There were no significant differences in respiratory and pulse rates, fecal consistency.

Various degrees of metabolic acidosis were observed in groups at the beginning of the study. Group interaction was not observed in blood gas variables observed among group involved (Table 3). WBC, RBC counts and Hematocrit value was increased in all groups before treatment and decreased after the treatment. Hemoglobin value was decreased in all groups after treatment however no statistical differences were detected for Hematological variables.

There were no differences in total protein measurements between groups. When compared within groups there was difference in points of time in LR group. Increases in both BUN and creatinine were detected in all groups due to prerenal azotemia at 0 hour. However, they decreased after treatment and no differences were detected in all groups. Sodium concentrations were statistically significant between groups at 30^th minute and 1^st hour after treatment. When compared with HTS group increase in sodium value was evident in HTS + 7.2% NaCl combination and LR groups. There were no differences in chloride concentrations between groups but there was a difference in points of time in HTS group. Serum potassium concentration was high at 0 hour in all groups and they decreased after treatment and no statistical differences were detected. Glucose concentrations were increased when compared with 0 hour but no differences detected between groups. But statistical significance was present at all time points in HTS and LR group. Phosphorus concentrations were decreased when compared with 0 hour but no differences detected between groups. However, in HTS + 7.2% NaCl combination group decreases in phosphorus after treatment was statistically significant in points of time (Table 2). All the calves were survived.

DISCUSSION

The leading causes of calf deaths are related to complications of dehydration. Therefore normalization of hydration status with appropriate use of oral and intravenous fluids is an important factor of treatment (3,4). Calves that are dehydrated less than 6% may benefit from oral electrolyte fluids but calves that are 8% or more dehydrated calves must receive intravenous fluids (7). This study showed that intravenous administration of HTS and HTS + 7.2% NaCl solutions along with oral electrolyte solution are effective in the treatment of dehydration due to naturally occurring neonatal calf diarrhea. This finding is parallel to the findings of other reports used Dextran + 7.2% NaCl combination to compare with isotonic NaCl and LR solutions (2,6).

In hypooncotic situations, HES infusion has a great advantage over other colloids because the larger molecules remain intravascular, limiting pulmonary fluid flux. There is a risk of coagulopathy in the use of HTS as in other colloids (8). In this study no side effects was seen attributed to the use of hydroxyethyl starch in the calf. Although moist rales in 2 calves in HTS group seen at 12^th hour of the study, they were totally normal by auscultation at 24^th hour.

Hyponatremia, hyperkalemia and hypercalcemia are quite common electrolyte disorders in neonatal calf diarrhea (1,4,9). Increases in serum sodium and chloride concentrations have been detected in endotoxemic calves in calves after hypertonic NaCl use (10). In this study, serum sodium concentrations were detected to be elevated in LR group and HTS + 7.2% NaCl combination at 30^th minute and 1^st hour after initiation of the treatment. There was no difference between groups after the 1^st hour. Also an increase was observed in chloride concentrations after treatment in all groups, but the chloride concentration of the HTS group was found to be lower than other groups. In the present study this effect was observed after 1^st hour of the treatment.

Increases in BUN and phosphorus in calves with diarrhea has been reported to be an indicator of renal failure usually depending on severity of dehydration (1,4). In this study, significant increases in BUN and creatinine variables were seen in all 3 groups. These variables decreased with the treatment however there was no statistically difference between groups. The normalization of the concentration of creatinine at 24th hour of the treatment had been interpreted in terms of correction of pre-renal failure. In this study, it was found that the serum phosphorus was high on 0 hour and observed to decrease after treatment, but there was no statistical significance between the groups. Within group evaluation showed a statistically significant decrease in HTS + 7.2% NaCl combination group after the treatment.

Hypoglycaemia is a significant complication of calf diarrhea (2,4). In the present study hypoglycemia was detected in the calves especially with prolonged starvation. However, serum glucose concentrations increased after treatment but there was no difference between groups. Within group evaluations showed statistical difference in HTS and LR group.

The half-life of intravenous isotonic fluids is less than the colloid + 7.2% NaCl solution. Hypertonic saline increases the osmolality and osmolarity of plasma and as a consequence fluid drawn from intracellular and interstitial space into the vessels and a rapid increase in the plasma volume and oxygen transport occurs (3,6,8,11). Also the colloids remain in vascular compartment providing normovolemia with a relatively small volume for a long time (3). In this study, decreased peripheral pulse quality and prolonged capillary refill time was detected due to dehydration. Treatment corrects the peripheral pulses quality and capillary refill time in the present study. When the capillary refill time evaluated it was found that the improvement of the HTS + 7.2% NaCl combination group was better than the other groups. Evaluations at the 24^th hour showed that improvements in HTS and HTS + 7.2% NaCl combination groups were found to be better than the LR group. Assessment of the peripheral pulse quality in all groups was significant especially in HTS and HTS + 7.2% NaCl combination group when compared to the LR group. The obtained data are consistent with the findings reported by Senturk 2003. This condition might be explained by the effects of hypertonic saline and colloid solutions in reducing edema in endothelial cells of blood vessels, decreasing vascular resistance by pre-capillary dilation and the effects explained in providing normovolemia (3,6).

Oral electrolyte solution involving colloid + hypertonic saline or just hypertonic saline was reported to reduce the dehydration by a rapid and sustained increase plasma volume (2,5,6,11). When evaluated the improvement in all groups to 0 hour; correction of dehydration in HTS + 7.2% NaCl combination group starts at 2nd hour, in HTS and LR group start at the 4th hour. However, signs of dehydration still observed at the 24th hour of treatment in LR group. No dehydration signs were present in HTS and HTS + 7.2% NaCl combination group after 24th hour of treatment (Table 1). Correction of dehydration was better at 12th hour of treatment in HTS + 7.2% NaCl combination than the HTS and LR groups when evaluated between groups (p<0.05).

There were no statistically significance detected in mental status of calves when between or within group comparisons made. When the assessment made to the 0 hour, improvement start at 2^nd hour in HTS and HTS + 7.2% NaCl groups and at 4th hour in LR group. Although there was no statistically difference between groups, present authors observed that clinically the best improvement was in HTS + 7.2% NaCl combination group. The suckling reflex is closely associated with base excess variables (2,6,11,12) and improvement in mental status was attributed to correction of dehydration and acid-base status.

In conclusion, Hydroxyethyl starch and Hydroxyethyl starch + 7.2% NaCl combination along with an oral electrolyte solution was found to be practical and effective of in the treatment of hypovolemic diarrheic calves.

This study was supported by Mehmet Akif Ersoy University Scientific Research Projects Commission. (Project No. 141-NAP-11)

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