American Journal of Animal and Veterinary Sciences

Review General Aspect and Current Fluid Therapy in Cattle with Digestive Diseases

1José-Ramiro González-Montaña, 2María-José Martin and 1Pilar Alonso

1Medicine, Surgery and Anatomy Veterinary Department, Veterinary Faculty, University of León, 24071 León, Spain 2Department of Animal Science, University of Lleida, 25198, Lleida, Spain

Article history Abstract: Digestive disorders therapy, both in calves and adult animals Received: 01-04-2017 depends on the correction of dehydration, academia and the removal of D- Revised: 18-05-2017 lactate from the blood and it is possible to do it by means of fluid therapy. Accepted: 30-06-2017 To do this, it is necessary to evaluate the dehydration of the animals and to

evaluate some clinical signs that allow to suspect acid-base and electrolytes Corresponding Author: José-Ramiro González- modifications in blood. The exact determination of these alterations, even a Montaña field level, by means of portable auto analyzers allow a fluid therapy Medicine, Surgery and adapted to each animal. Academia, with accumulation of D-lactate in the Anatomy Veterinary blood, seems to be one of the most important factors in the pathogenesis of Department, Veterinary systemic signs of neurological dysfunction, including ataxia, weakness and Faculty, University of León, reduction of food intake in several digestive diseases in ruminants. Also 24071 León, Spain reviewed are the products available in the market frequently used in the E-mail: [email protected] fluid therapy of these diseases, with their main indications and disadvantages. Finally, we review the main digestive pathologies that suffered from ruminants, especially diarrhea in calves, with their treatment.

Keywords: Fluid Therapy, Ruminant, Digestive Disorders, Acidosis

Introduction Intravenous (IV) therapy are likely partly responsible for the reduction in mortality rates. While the use of fluid therapy (oral or parenteral) This article does not have the commitment to review is widespread in pets, in farm animals its use is much the matter in depth, but it will try to give some general less frequent. This is mainly due to two reasons, first aspects of fluid therapy in ruminants, mainly trying to practical difficulty to perfuse large volumes of liquid raise a practical approach and bring these concepts to the under field conditions (fluids are administered in on- particularities to take into account the digestive process farm) and second the high cost, not so much in the affecting these animals. We must not forget that some cost of the fluids but in the cost of their application by diseases, such as ruminal acidosis and diarrhea in calves professional veterinary surgeons (Grove-White, 1994) are major causes of mortality in ruminants (Naylor et al ., which in many cases exceeds the value of the animals. 2006) and that the positive resolution of the pathology Although parenteral administration and especially the depends not only on the etiological treatment but also difficulty in slow and prolonged intravenous infusions is on the adequate restoration of fluid and electrolytes in another noteworthy feature, currently the availability of the dehydrated animal. commercial products which are suited to the veterinary General Plan of Fluid Therapy in Ruminants practice and the greater dedication to the clinic in Factors to Consider ruminants, compel a review of the therapeutic approach in various intestinal diseases that require fluid therapy, The physiological state in the animal organism bringing it closer to that which takes place in the clinic depends on the balance of fluids and electrolytes and of small animals and in humans. this, in turn, depends on an external balance, represented Before discussing the current state of fluid therapy, by the relationship between the mechanisms it is appropriate to recognize how advances in fluid intake/absorption and removal/secretion; and an inner therapy have improved the outcome for survival in balance, related to the distribution of fluids between different livestock diseases. In recent years, it has compartments body (intracellular and extracellular fluid, increased the survival in neonatal calves, lambs and in which is subdivided in plasma, interstitial fluid/lymph adult cows. Probably improvements in oral and and transcellular fluid) (Lisboa, 2004).

© 2017 José-Ramiro González-Montaña, María-José Martin and Pilar Alonso. This open access article is distributed under a Creative Commons Attribution (CC-BY) 3.0 license. José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

−1 −1 The general objectives of the fluid therapy are 1. To 100 mL kg in young animals and 150 mL kg in new replace lost fluids and correct existing electrolyte born animals, it depends significantly on the animal’s imbalances, 2. To cover the animal's needs in fluid age (Lisboa, 2004; Rejas et al ., 2001). maintenance and electrolytes and 3. To solve the acid- Volume of Maintenance (ml) = (50-150 base disturbances that have occurred (Rejas and Alonso, −1 2008; Grove-White, 1994). In ruminants, with a mL ) x BW (body weight, kg) gastrointestinal disease, the goals of fluid therapy, in addition to the aforementioned objectives (to correct the Volume of Expected Losses deficit fluid, the electrolyte imbalance and the acid-base Takes into account the volume that continues to be imbalances) should be aimed at reducing concentrations lost throughout the day of the treatment. It is difficult to of D-lactate (Naylor et al ., 2006; Grove-White, 1994). measure; it is an estimated amount and therefore with a On the other hand, in the dehydrated animals, it is relatively wide margin of mistake and it is only possible important to restore the hydro-sodium balance, which in those diseases in which the loss is visible (diarrhea helps the implementation of the homeostatic mechanisms and polyuria). It is impossible to estimate in cases of of the body, particularly the kidney. We mustn’t forget fluid abduction (abomasal dilatation, intestinal that if the kidneys are adequately perfused they are obstruction, etc.), so the technical difficulties cause this able to control mild to moderate acidosis and alkalosis volume to be, in some cases, ignored (Lisboa, 2004). (Rejas and Alonso, 2008). Assess the Degree of Dehydration Evaluation and Success in fluid therapy depends on the proper choice of the volume to perfuse, the route of administration, the Diagnosis of Acidosis rate of infusion, the type of fluid administered and the Therefore, to calculate the amount of fluids to be duration of the treatment (Lisboa, 2004; Naylor et al ., administered and regardless of the infusion line, the first 2006; Rejas and Alonso, 2008). step is to assess the degree of dehydration, which will calculate the volume of replacement. Calculating Total Fluid Requirements The key for ruminant clinic as is being able to decide To calculate the total amount of fluids to be whether the fluid therapy is necessary in sick calves, administered 3 different volumes must be taken into based more on the clinical examination rather than on the consideration: 1. Volume replacement, which is the laboratory values. The most important clinical amount of lost fluid, which are valued based on the parameters to guide decision-making in fluid therapy is degree of dehydration, 2. Daily maintenance needs or obtained from the evaluation of the hydration status volume maintenance, 3. Volume of expected losses (perhaps it would be better to say the degree of (mainly via faeces) (Rejas et al ., 2001; Lisboa, 2004; dehydration) and the functioning of the Central Nervous Rejas and Alonso, 2008): System (CNS) (Smith and Berchtold, 2014). Competence to assess hydration status is one of the Volume of Replacement critical points and often the calculation of the appropriate Is one that corrects the fluid deficit in the animal volume of fluids for treatment depends on the judgment (with a small margin of error). It is calculated by of the clinician to accurately establish the degree of multiplying the estimated dehydration (in percent) by dehydration that the sick animal show. This judgment is body weight (in kilograms) and ideally should be based on the identification of a series of signs, some replaced quickly. It should be recalculated every 24 h of subjective and therefore are not always quantifiable treatment. It is calculated by the following formula: criteria. The error can be reduced considerably when a (Lisboa, 2004; Smith and Berchtold, 2014). specific set of symptoms is evaluated instead of one of them in particular (Lisboa, 2004). Another possibility, Replacement Volume (L) = Body Weight though not always possible in the buiatrics, is to measure (kg) x Dehydration Degree (%) hematocrit and plasma protein concentration; this makes it possible to calculate with less chance of error the degree Volume of Maintenance of dehydration. The increase in the value of the Takes into account the daily rate of replacement of corpuscular volume (hematocrit) and the plasma protein liquid (or water) in the body and varies with the age of concentration would be indicative of laboratory findings the patient. The volume is calculated from a number of and could confirm dehydration (Lisboa, 2004). formulas; mainly depending on the affected species and The degree of dehydration can be assessed on clinical its age and to be administered within 24 h of treatment. grounds using signs such as the sinking of the eye Therefore, unlike the volume substitution, the (enophthalmos) and skin tenting, mainly the elasticity of administration is slow and should be divided throughout the skin over the neck and thorax, by the color and the day (Lisboa, 2004; Rejas et al ., 2001). In cattle it dryness of the membranes mucous membranes (Table varies from 50 mL kg −1 body weight per day in adults, to 1 and 2) (Rejas et al ., 2001; Naylor et al ., 2006;

112 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Grove-White, 1994; Smith, 2009). The bulging of the Hypovolemic Shock (12% BW) skin on the eyelid is a reliable indicator of dehydration (Constable et al ., 1998; Naylor et al ., 2006). According Coma, decubitus lateral permanent, loss of appetite (reflex suction absent), lack of skin elasticity (up to 20"), to Smith and Berchtold (2014), the degree of dry mucous with a whitish or bluish colour, enophthalmos is the best predictor of dehydration in enophthalmos marked, tachycardia or bradycardia, calves, followed by skin elasticity in the neck and arrhythmia, thready pulse, hypothermia and cold chest. In contrast to Rejas and Alonso (2008), in extremities, CRT> 8" (Lisboa, 2004; Smith, 2009). addition to the degree of hydration, the eye position Silanikove (1991) cites some goat's dehydration within the orbit depends on the amount of body fat, so around 20% (range 16-22%) of their initial mass and the in the case of cachectic animals or those with chronic goats always restored their initial mass (+1 kg) when diarrhea it is recommended the use of the cervical fold given access to water. as the most reliable indicator of the degree of Guidelines for estimating dehydration are shown in hydration (Rejas and Alonso, 2008). Constable (2003) Table 1 and 2. recommends multiplying the ocular collapse (in mm) by The severity of acidosis cannot be determined on 1.7 to estimate the degree of dehydration. In clinically clinical ground, nor is it related to the degree of sick calves is important to assess the hydration status dehydration present (Grove-White, 1994). along with other clinical signs, among which it should be The evaluation and diagnosis of acidosis from taken into account the ability of the calf to suckle, the clinical signs is common in bovine veterinary severity of CNS depression and if it can stand up (degree practice. The accuracy of predicting the degree of of weakness) Smith and Berchtold (2014). The set of acidosis taking into account the clinical signs has symptoms indicated, are more visible in young animals varied between studies. Clinical signs of neurological and are specially identified and characterized in calves depression weakness, ataxia and decreased reflexes in affected by diarrhea (Lisboa, 2004). threatening situations and for breastfeeding and the However, in Naylor et al . (2006)’s opinion many of panicular reflex) are highly correlated with the severity the older schemes used to assess dehydration have of metabolic acidosis in calves without dehydration. Also in overemphasized the severity of dehydration, as has been diarrheic calves, signs of CNS depression, the ability to shown in multiple clinical trials. stand and the suction force correlate well with In practical terms, it is considered that below 5% of metabolic acidosis (Smith and Berchtold, 2014). The dehydration there are no clinical signs and above 12% degree of enophthalmos and peripheral skin there is a risk of death. Based on this, you can categorize temperature are important and obvious signs that in mild dehydration (5-8%), moderate (8-10%) and determine whether or not IV fluid therapy is severe (> 10%). indicated; however, they do not correlate with the degree of acidosis (Smith and Berchtold, 2014). Mild Dehydration (5 to 8% of BW) While dehydration should be assessed from clinical signs as indicated above, the acid-base status can, however, The animal shows discreet apathy, remains standing, be simply and quickly measured using an analyser it maintains its thirst and appetite (i.e., the sucking reflex), it has decreased skin elasticity (2-4"), with pink apparatus. Today this equipment is portable and not too hardly sticky mucous, Capillary Refill Time (CRT) is 2- expensive equipment (Grove-White, 1994), it measures the 3" (Lisboa, 2004; Smith, 2009). total carbon dioxide (tCO 2) from a blood sample, it is important to remember that the main source of carbon Moderate Dehydration (8 to 10% BW) dioxide continues to be the plasma bicarbonate. Blood gases and acid-base status are ideally determined with a portable Show severe apathy, they prefer sternal recumbency gas analyser blood, such as i-STAT System (Abbott Point (although they can get up unassisted), with anorexia (the of Care Inc., Princeton, NJ) (Smith and Berchtold, 2014). sucking reflex is still present), with low skin elasticity However, sometimes these laboratory analysers are (5"), it has dry red sticky mucus, with a retraction of the expensive, are not available for clinical veterinarians and eyeball (enophthalmos), tachycardia and weak and therefore are not used in most clinical cases. regular pulse, cold extremities and discreetly CRT: 4-5" Experimental studies using IV diuretics and orally (Lisboa, 2004; Smith, 2009). administered sucrose shows that calves can suffer Severe Dehydration (10 to 12% BW) dehydration of at least 14% loss of body weight without becoming deeply depressed or lose the ability to stand or Depression, sternal recumbency permanent, loss of appetite (lack of sucking reflex), very low skin elasticity suck. As in naturally occurring diarrhea, most fluid loss (6-10") and dry red mucous membranes, marked is from the extracellular space. Despite the severe dehydration there were only minor changes in blood pH; enophthalmos, cold extremities, hypothermia, −1 tachycardia and thready pulse and CRT = 6-8" (Lisboa, levels of L-lactate increased from 1.1 to 2.8 mmol L 2004; Smith, 2009). (Constable et al ., 1998).

113 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Table 1. Clinical signs for guide to assessment of fluid losses in the calves Skin tent Mucous Dehydration Demeanor Eyeball recession duration (sec) membranes Extremities < 5% Normal None < 2 Moist, pink Temperate 6-8% (mild) Slightly depressed Slight, 1-3 mm 3-5 Dry -Temperate at ± Cold 8-10% (moderate) Depressed Moderate, 4-5 mm 6-7 Dry ± Cold at cold 10-12% (severe) Comatose Severe, 6-7 mm 8-10 Very Dry Cold > 12% Comatose/dead Severe, 8-12 mm > 10 Very Dry Cold

Table 2. Clinical assessment of dehydration in cows (Rejas et al ., 2001), * some calves may lose up to 16% BW (Naylor et al ., 2006) Dehydration (% loss BW) Clinical signs 0-5% Not detectable 6-7% Mild enophthalmos Persistence skinfold (3-5 sec.) Dry mucous 8-9% Hollow eyes Persistence skinfold (6-10 sec.) Sticky mucous 10-12% Deep-set eyes in the orbits Skin fold indefinite persistence (> 15 sec.) Dry mucous Clearly depression 12-15% Marked signs of shock Impending death

By contrast, a case study of naturally occurring rehydration (Rejas et al ., 2001; Rejas and Alonso, 2008). severe calf diarrhea showed that most deeply depressed However, if dehydration is severe (> 8%) it is calves were involuntary lateral decubitus with and had mandatory the intravenous route, supplemented in an average level of 7.5% dehydration; and only a few some cases with oral rehydration. It is necessary to calves were more than 14% dehydrated (Naylor, 1999). note that very dehydrated calves often do not suck and The discrepancy between the degree of dehydration have ileus, delaying the absorption of oral liquids commonly seen in the field and the maximum amount of (Rainger and Dart, 2006; Rejas and Alonso, 2008). dehydration that a calf can support reflects the influence Also for signs of shock (poor perfusion) require the of other factors working along with dehydration to limit use of the intravenous route; while signs such as life. For example, many calves are also acidotic enophthalmos, mucous dryness or increased duration of the dehydrated and this combination is likely to be more skinfold only indicate dehydration. Signs include lethal than dehydration alone (Naylor et al ., 2006). hypothermia, coldness of limbs, ears and tail, decubitus, Dehydration is a common feature of ruminal acidosis tachycardia, weak pulse, increased capillary refill time, pale in calves (Halimi et al ., 1991; Gentile et al ., 2004). In mucous, CNS depression, whether or not they can stand acidosis and the dehydration syndrome the clinical signs (degree of weakness) and absence of sucking reflex indicate of dehydration are not present. However, serum that the animal is shocked or even about to go into shock creatinine concentrations may be elevated suggesting (Rejas and Alonso, 2008; Smith and Berchtold, 2014). renal failure. This may be secondary to mild hypovolemia Oral Rehydration and decreased renal blood flow (Kasari and Naylor, 1986; Naylor et al ., 2006). Parenteral fluid therapy should be set up for any animal with an imbalance in fluid, electrolytes or Choice of Route And Rate of Administration Orally acid-base and for those in which oral fluid therapy is or Parenterally? unlikely to be effective. However if oral hydration is set up from the beginning, before any deficits and Orally or Parenterally? imbalances become too severe, this treatment is highly The level of dehydration indicates the way to apply effective in most cases of calves with diarrhea. the fluid therapy. In diarrheic young animals, when However, it will be totally ineffective in recumbent or dehydration does not exceed 8% and there is adequate comatose calves, as they are likely to be suffering tissue perfusion, the oral route may be sufficient. These from shock or severe acidosis. Parenteral fluid therapy cases, with mild dehydration (<6%) or moderate is also indicated in diarrheic calves, which (between 6 and 8%) with intestinal motility and intact progressively worsen despite adequate oral treatment intestinal epithelium, are candidates for enteral (Rainger and Dart, 2006; Grove-White, 1994).

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The oral route is the best solution for Oral fluids and electrolytes should be administered administrating a rehydrating solution when the calf by the animal sucking them from a teat or by a retains the sucking reflex which rules out significant flexible catheter inserted through the oesophagus dehydration (Alonso et al ., 2001; McClure, 2001; (Alonso et al ., 2008b). Another possibility, applied in Rainger and Dart, 2006; Smith, 2009; Meganck et al ., on-farm situations is to administer the solution by a 2014). This also has other advantages as the solution can bottle, made of glass or hard plastic, partially inserted in be administered by the farmer avoiding early degrees of the mouth of the animal and allowing the animal to severe dehydration, a large quantity of rehydrating swallow slowly. This technique must be done carefully solution may be rapidly administered without the risk of because it may cause pneumonia by aspiration. The oral side effects, it is possible to administer high amounts of route is absolutely contraindicated in cases of the potassium without toxic risk; and even in most cases retention of fluids in the digestive tract (Lisboa, 2004). they are cheaper than intravenous solutions (Rejas et al ., The oral route is absolutely contraindicated in cases of 2001; Alonso et al ., 2008a). They also have some liquids retention in the digestive tract (Lisboa, 2004). drawbacks, since they are not suitable in animals whose It is not recommended the administration of more intestinal mucosa is much deteriorated, exacerbating than 2 litres each time, because the distended diarrhea if they do not absorb glucose; and they are not abomasum and rumen reflux occurs. If you need to valid in animals with severe signs of dehydration give larger amounts they must be given at intervals of (Alonso et al ., 2008b). 2 h (Alonso et al ., 2008a). It is important to increase Oral rehydration, as in parenteral, aims to correct the number of administrations to encourage the animal metabolic acidosis, restore blood volume, restore to drink more fluids (Rejas and Alonso, 2008). There electrolyte balance and provide energy (Rejas et al ., is no exact rate for fluid therapy. In general, the maximum 2001). Clinical studies with children and calves have amount of oral fluid for a 50 kg diarrheic calf in a 24 h demonstrated that duration of diarrhea is shortened and period is 8 litres divided into at least 4 feeds of 2 litres or weight loss is reduced if oral nutrition is maintained less (Naylor et al ., 2006; Rejas and Alonso, 2008). As (McClure, 2001; Grove-White, 1994). While a few years large amounts of milk may predispose to acidosis, ago it was recommended not to administer milk to small shots of approximately one litre are diarrheic calf during the first 48-72 h of therapy with recommended (Rejas and Alonso, 2008). Parenteral oral rehydration solutions (Alonso et al ., 2008a; fluids and oral rehydration solutions should be at body Rejas and Alonso, 2008), as this would allow the temperature (Rejas et al ., 2001). gastrointestinal tract to heal and reduce undigested food Parenterally in the intestinal lumen, causing osmotic diarrhea (Rainger and Dart, 2006; Rejas and Alonso, 2008). There are four routes for parenteral administration: Currently, it is recommended that the intake of milk (1) Intravenous, (2) Intraperitoneal, (3) Subcutaneous (whether natural or milk replacers) be continued at all and (4) Intraosseous (Constable, 2003). The choice of times; as milk feeding supplemented with oral one or the other depends on how hurt the animal is and rehydration solutions, for the treatment of diarrhea, does the practical possibilities for therapy. not cause nor worsen the disease, also these animals that Intravenously drink milk gain more weight (Rejas and Alonso, 2008; Smith, 2009) and the negative energy balance causes The fluid intravenous therapy is the only permissible cachexia, which cause harm to the patient by way when the degree of dehydration is more than 8% compromising the growth of enterocytes and the immune (Rejas et al ., 2001; Alonso et al ., 2008b). The parenteral function (Rejas and Alonso, 2008). Keeping a full diet of route, especially the intravenous route, with rapid −1 milk along with some amount of oral rehydration infusion (10 to 20 mL kg BW/h) volume replacement solutions, greater than or equal to the estimated amount is always necessary in cases of severe dehydration and of fluid lost through faeces, is the best choice to manage hypovolemic shock. Even moderate dehydration the diarrhea (Rejas and Alonso, 2008). In Smith (2009) intravenous administration may be necessary in opinion's, calves should be maintained on their full milk depressed calves without a sucking reflex (Lisboa, 2004). diet plus oral electrolytes when possible; if calves are Ideally, the volume replacement can be infused more depressed and refuse to suckle, milk can be withheld for rapidly than other volumes. In hypovolemic shock forced −1 one feeding (12 h) and a hypertonic oral electrolyte infusions of 40 mL kg body weight/h may be required. If product substituted, but the milk feeding should always be possible, intravenous therapy should be administered for resumed within 12 h. In some cases, the problem is the about 6 or 8 h; until the calf is able to stand up, be alert acceptance of oral rehydration solutions for the calf, and has a sucking reflex; at this stage you can switch to an sometimes even slightly hiporexic. Limiting the amount of oral rehydration (Rejas and Alonso, 2008). The milk makes the calf is hungry and more willing to accept maintenance volume and estimated losses can be infused oral rehydration solutions (Rejas and Alonso, 2008). at a rate of 2 to 5 mL kg −1 body weight/h during 24 h of

115 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 treatment (Lisboa, 2004), i.e., it is divided in 2 to 4 Setting up a Fluid Line administrations during the day. While most calves can be treated on the farm, it is Subcutaneous preferable to hospitalize all those cases requiring intravenous therapy (Grove-White, 1994). Intravenous Subcutaneous rehydration can be replaced in some administration of large volumes of solutions requires cases of orally route. Absorption takes place in the intravenous catheterization and periodic monitoring of following 4-6 h after injection, but this requires that the flow rate and application devices. the degree of dehydration is less than 8%. If however, There are many descriptions of the technique for dehydration is greater than 8% reabsorption is much intravenous catheterization (jugular and auricular veins) slower as a result of peripheral vasoconstriction and for administering fluids. Catheterization is best (Alonso et al ., 2001). This route may be associated performed with the calf sedated, in lateral recumbency, with intravenous administration in cases of severe with its legs tightly tied up. The jugular vein is located dehydration, especially when potassium is provided and a small incision (2.5 cm) is made to expose the vein. (Alonso et al ., 2001). A 3 inch and 14 gauge catheter is placed in the vein and The effectiveness of subcutaneous fluid sutured in place. It is customary to place a three-way tap administration have not been evaluated in experimentally dehydrated neonatal or adult ruminants. Except calcium and sutured in place at two or three points, ensuring its and magnesium solutions, which are used to treat attachment to the calf. The three-way tap enables blood hypocalcemia and hypomagnesemia, fluids rarely sampling and an easy administration of other additional administered subcutaneously in ruminants because drugs (Grove-White, 1994). absorption rate is suspected to be slow (Constable, It is often difficult to maintain a catheter and a flow 2003). The solutions to be applied should be isotonic rate, as a result of changes in the animal's position solutions of electrolytes and glucose (5%) which can be (lateral recumbency, standing, rotating the neck, etc.) administered up to 80 mL kg −1 at different points of altering the hydrostatic pressure gradient and because application (up to 20 mL kg −1 per application) movement can lead to tangling of the fluid line. Even (Alonso et al ., 2008a). Constable (2003) suggests that, sometimes the animals themselves, especially in young to facilitate absorption, can be added hyaluronidase can animals, lick and nibble the fluid-administration line, be added the solution (150 U/L solution), but it has not especially when intravenous fluids are administered on been given its safety and efficacy. farms situations (Constable, 2003). It is advisable to administer a long-acting antibiotic to minimize the risk Intraperitoneally of thrombophlebitis (Grove-White, 1994). The effectiveness of intraperitoneal fluid administrations have not been evaluated in dehydrated Solutions for Parenteral Use neonatal or adult ruminants. Although intraperitoneal Parenteral fluid therapy: Sterile crystalloid solutions fluid has been used in dehydrated calves, this route is not are used. These balanced polyionic solutions, preferably recommended because of the possible alteration of the isotonic, i.e., with an osmolality close to the plasma provide peritoneal absorption in these types of calves and the risk electrolytes and even precursors, allowing simultaneous of peritoneal adhesions. The safe administration of plasma correction of imbalances in water, electrolyte and acid-base to neonatal calves through a catheter inserted in the (Lisboa, 2004; Rejas et al ., 2001). paralumbar fossa has been reported (Constable, 2003). Commercial products are derived from human line, In dehydrated goats, intraperitoneal hydration packaged in bottles of 500 mL−1 and 1000. The most showed that a higher proportion of water was retained in frequently used are: comparison with central rehydration and this was related to a more effective kidney retention mechanism (lower • Saline (0.9% NaCl) isotonic and provides Na + and Cl − glomerular filtration rate and higher tubular • Ringer's solution: Isotonic and provides Na +, Cl −, K + reabsorption); plus higher proportions of water were and Ca 2+ retained in the rumen and thirst saturation was more • Ringer lactate solution: Isotonic and provides Na +, effective (Silanikove, 1991). Cl −, K +, Ca 2+ and lactate • Intraosseous Glucosaline solution (5% glucose and 0.9% NaCl): Hypertonic and provides Na + and Cl − It is unlikely that the intraosseous route is needed in ruminants, because of their large size and easy accessible These solutions are suitable for the correction of veins for catheterization (Constable, 2003). Contrary to dehydration, hyponatremia, hypochloremia, potassium what happens in carnivores and birds, there seems to be loss and metabolic alkalosis (Lisboa, 2004). no reports of intraosseous fluid administration in The correction of metabolic acidosis requires the use ruminants (Constable, 2003). of sodium bicarbonate. In the case of ruminants,

116 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 including lactate (base precursor), it has minimal The solutions aim is to promote correct dehydration, potential alkalizing. The concentration of a lactate hyponatremia, hypochloremia, potassium loss and Ringer's solution is small and is a racemic mixture, metabolic acidosis. Its ionic composition obeys the therefore the ability to metabolize D-lactate is negligible. − principle of maximum efficiency in the absorption of NaHCO 3 solution at 1.3% is ideal and isotonic, but, sodium and therefore water by the enterocytes. The curiously not marketed. Commercially the following −1 presence of glucose and glycine increase this efficiency, concentrations are: 3, 5, 7.5, 8.4 and 10%, in 250 mL due to the existence of absorption mechanisms as co- bottles 10 mL ampoules to 8.4% are easily found on the transport of Na +/glucose and Na +/amino acids market and can be diluted in 155 mL (15½ ampoules) in −1 (Constable et al ., 2001; McClure, 2001). Osmolarity 845 mL of sterile distilled water to generate a desired close to that of plasma or slightly above, also contributes 1L of isotonic solution (Lisboa, 2004). to increased efficiency of absorption (Lisboa, 2004). The magnitude of metabolic acidosis is variable and The ingredients used to prepare these solutions must be does not necessarily correlate with the severity of water cheap and easy to acquire (NaCl, KCl, NaHCO 3 or sodium imbalance, this is particularly true in cases of ruminal citrate and dextrose); and they can be stored as a powder in lactic acidosis. The correct assessment of the state of packets ready to be diluted in water (Lisboa, 2004). acidosis is obtained only by the blood gas test. Only The World Health Organization (WHO) has from the known value of Base Deficit (BD) would it be recommended, since the 70s, a rehydration solution with − −1 possible to accurately calculate the amount of HCO 3 the following ionic composition: 90 mmol L of Na, 80 −1 −1 −1 − suitable for correction, using the following formula: mmol L Cl, 20 mmol L of K, 30 mmol L of HCO 3 (Lisboa, 2004): and 100 mmol L−1 of dextrose, with osmolarity of 320 mOsm L−1 (Lisboa, 2004). Later, in 1986, WHO has − HCO3− deficit (mEq) = BD (mEq/L) x BW(kg) replaced HCO 3 for citrate (base precursor) to increase − x 0.5 1 g of NaHCO 3 equals 12mEqHCO 3 their shelf life. Another solution that has been used with satisfactory Unable to perform a blood gas analysis, which is results in calves is composed of 2.5 g of NaCl, 1.5 g KCl, common for a veterinarian who operates on the farm, 5 g NaHCO 3 and 28 g dextrose diluted in 1 litre of water. one can estimate the degree of acidosis based on The preparation is simple. The NaHCO 3 may be replaced subjective criteria; i.e., based on the severity of by 5 g of sodium acetate. The final osmolarity is 390 depression, assuming a margin of error. A value of 10 mOsm L−1) (Lisboa, 2004). In adult ruminants the mEq/L estimated could be accepted as reasonable for following solution has been recommended: 160 g NaCl, diarrheal calves with moderate to severe dehydration, as −1 20 g KCl, 10 g of CaCl 2 and 300 mL of propylene glycol well as for cattle with ruminal lactic acidosis depressed, diluted in 20 L of water. It should be noted that this but still standing (Lisboa, 2004). solution does not allow the correction of acidosis, since Intravenous fluids are usually given through a both bicarbonate as base precursors are metabolized in the catheter in the jugular vein or auricular (ear). Catheterization of the auricular vein in calves described rumen microbial fermentation process (Lisboa, 2004). in detail previously (Smith and Berchtold, 2014). Glucose (or lactose) in oral fluid mixtures is present only to aid in sodium and water absorption, it is a totally Solutions for Oral Use inadequate energy source for calves (Constable et al ., For practical reasons and especially under on-farm 2001; McClure, 2001; Grove-White, 1994). conditions, prolonged intravenous infusions are rarely Rate of Fluid Administration performed in ruminants; because of the need for monitoring and complications with maintaining the There is no exact rule for administration of fluid integrity of the infusion system (catheters, equipment, therapy. The key to deciding the rate at which to extenders and bottles). These limiting factors have administer fluids must be the response to treatment, this served as a great stimulus for oral hydration. In fact, oral is the best guide to assess the required amount of liquid hydration with appropriate solutions can be considered, (Grove-White, 1994). Although clinical signs, such as at present, the option of choice for the treatment of the sinking of the eye and skin tenting, are indicative that diarrheic calves due to their effectiveness, convenience a calf is dehydrated, they can be notoriously inaccurate and low cost (Rejas et al ., 2001; Lisboa, 2004; Sen et al ., concerning the measurement of hematocrit and plasma 2009; Smith, 2009). proteins (Grove-White, 1994). The use of portable Multiple products have been reported for use orally analyzers can be of great value to evaluate the acid-base in veterinary medicine, mainly oriented towards the changes during therapy and can also help decisions to be treatment of diarrheal calves (Alonso et al ., 2001; made regarding the composition of intravenous fluid Lisboa, 2004; Sen et al ., 2009; Smith, 2009; used and the quantity, particularly in the severely Meganck et al ., 2014). acidotic but minimally dehydrated calves in which there

117 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 are no clear signs other than weakness and collapse It has been found that a high rate of infusion fluid (Grove-White, 1994). for intravenous administration of 80 ml kg −1 h does At this point we should distinguish two types of not cause significant hypertension over hydration. situations: 1. Hospitalized animals, in which fluid may This rate is equivalent to a maximum volume of liquid be infused intravenously for many h; and 2. Individuals of 2.8 L −1 h for a 35 kg calf or 3.8 L −1 h for a 47 kg in the stable, in which the intravenous fluid has to be calf, severely dehydrated. No higher rhythms are administered quickly (Rejas and Alonso, 2008). recommended (Smith and Berchtold, 2014), since The recommended rate, particularly IV infusion, is studies in sheep and healthy cats indicate that fluid −1 from 20 to 40 mL kg h. The usual aim is to correct overload occurs at delivery rates of about 90 mL kg−1 dehydration in about 6 to 8 h and then gradually for periods longer than one h (Naylor et al ., 2006). administer the remaining fluids required for maintenance Some sick calves with hypoproteinemia or increased and ongoing losses (Naylor et al ., 2006). vascular permeability are likely to be more susceptible Usually half the estimated fluids and electrolyte to volume overload (Naylor et al ., 2006). deficits must be corrected in the first 6 h and the In practice, very rapid rates of intravenous fluid −1 remainder for the next 18 h in order to complete 24 h. infusion, 100 mL kg h can be used for short periods of However it is possible and often beneficial, to proceed time (no more than 20 min) in the initial resuscitation of more rapidly (Grove-White, 1994); and an initial speed calves with severe dehydration. The aim of this high fluid delivery of up to 80 ml kg −1 h can be used safely, initial rate of infusion is to rapidly improve circulation administering up to 2 litres during the first 30 min of by restoring blood volume (Naylor et al ., 2006). Based therapy and the remainder more slowly over the on plasma volume of 7.2% of body weight fluid subsequent 24 to 48 h. A shocked calf with severe administration at this speed will increase plasma volume dehydration may need between 5 to 20 litres of liquid by almost 50% (Naylor et al ., 2006). over 24 to 48 h (Grove-White, 1994). Prognosis and Therapy Duration Alternatively, during the first day and in hospitalized animals, the fluid therapy is divided into 3 periods. As previously stated, clinical signs such as the During the first three h half the existing losses should be ability to stand up, the intensity of suction, the loss of administered (half the degree of dehydration) and correct the blinking reflex and the age of diarrheal calves are at least half of the existing acidosis. Thus, in less than essential to determine whether the treatment with three h, the calf will have a mild dehydration and mild fluids is functioning properly. Urination in 30 to 60 acidosis. During the next 5 h, until 8 h, the rest of lost min after therapy, improved mental state and fluids (rest of the degree of dehydration) were hydration and the most important, restoration of the administered, correcting the rest of acidosis, although a sucking reflex should be supervised in treatment mild acidosis can be corrected by renal function if you responses (Smith and Berchtold, 2014). have liquids and electrolytes. At this point it is Decubitus calves must stand up for a few h after fluid convenient to start managing solutions to replace therapy. If the sucking reflex does not return after IV potassium losses, once the hyperkalemia secondary to therapy, other diseases such as septicemia, omphalitis, or acidosis has been corrected. According to the patient, pneumonia should be ruled out (Smith and Berchtold, this rehydration can be intravenously or orally with oral 2014) and it would be advisable to check the acid-base rehydration solution. Between 8 and 24 h, daily −1 −1 status of the animal, especially in calves (adding maintenance needs (50-70 mL kg ) and estimated bicarbonate and even potassium). It is necessary to note that future losses (1-4 L) are administered, usually orally determining a possible acidosis in the farm is difficult and (Rejas and Alonso, 2008). −1 costly and the administration of alkalizing is done without Often slower infusion rates (30 to 50 mL kg h) are any laboratory data, which influences the clinical response used to prevent overhydration and pulmonary edema. to fluid therapy (Smith and Berchtold, 2014). −1 Therefore at a speed of 30 to 40 mL kg h, a calf of 40 The length of hospitalization varies, but generally kg with 10% dehydration can be rehydrated in less than speaking the calves are discharged after 48 to 72 h, at 3 to 4 h and also the volumes of liquids daily which time they will be able to suckle and drink fluids −1 maintenance (80 to 100 mL kg ) and continuing losses orally. As in all diseases of calves, the immune status of up to 7 litres per day need to be added in order to of the calf is of great importance in relation to the calculate daily fluid necessities. Rates of 30 mL kg −1 for prognosis (Grove-White, 1994). As a rule, those a number of h produce no toxic side effects (Bjorling and calves with a very low immunoglobulin level die Rawlings, 1983; Broaddus et al ., 1990; Gottardo et al ., despite treatment (Grove-White, 1994). 2002). However, if the calf can suck after initial The prognosis for calves with longstanding resuscitation the required fluids can be administered orally diarrhea is also poor, in part because they will have a to reduce costs and labour (Smith and Berchtold, 2014). very serious negative energy balance despite the fact

118 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 that they may be receiving oral fluids containing particles per kilogram of solution and is expressed as glucose (Meganck et al ., 2014). mOsm/kg of solution. Osmolarity expresses the level of concentration of various solutions components, defined Source of Fluids Fluid Composition as the number of particles per litre of solution and is Although there are many preparations that can be expressed as mOsm/L of solution. The correct term in used in fluid therapy to be found on the market either plasma and extracellular fluid is osmolarity, since oral or parenteral, only a few are used in routine practice. osmoles are dissolved in water only and not throughout The fluids are categorized on the basis of their physical the volume of the solution; it has a certain volume nature (crystalloid or colloid) and osmolarity (hypo- occupied by the solutes. However, we know that usually osmotic, iso-osmotic, or hyperosmotic) (Table 4). the difference between one and another way of Isosmotic or slightly hypo-osmotic crystalloid solutions expressing and preparing a solution is minimal; and most commonly are administered parenterally, although therefore can mOsm/kg or mOsm/L can be used under specific circumstances hyperosmotic crystalloid interchangeably, but in other cases the difference is large solutions or iso-osmotic colloid solutions are preferred and it is recommended to use mOsm/kg. One kg of (Constable, 2003). plasma approaches 1 L plasma; therefore osmolarity can A crystalloid is a substance that forms a true solution be easily calculated from the concentration of and is capable of being crystallized. NaCl is the classic electrolytes in the fluid solution. Onekg (1 L) of plasma crystalloid because there as a crystal and also dissolves has two components, 70 g protein and 930 g of water and completely when is placed in water. As crystalloid plasma. Accordingly, normal plasma osmolality in solutions on the market are Ringer’s solution, lactated ruminants is approximately 285 mOsm kg −1 and may Ringer’s solution, acetated Ringer’s solution, 0.9% increase by drinking water (osmolality >285 mOsm kg −1) sodium chloride (NaCl), 7.2% NaCl (hypertonic saline), or by increasing the excretion of free water (osmolality 1.3% sodium bicarbonate (NaHCO 3), 8% NaHCO 3, <285 mOsm kg −1). An osmolality of 285 mOsm kg −1 is calcium gluconate and 50% dextrose (Constable, 2003). equivalent to a plasma water osmolarity of 306 mOsm Solutions crystalloid and especially those containing L−1 ([285 mOsm/kg]/[0.93 L kg −1]) (Constable, 2003). sodium, are indicated in hypovolemia, but are The normal plasma osmolality for ruminants is 306 contraindicated in congestive heart failure and in animals −1 mOsm L , therefore we can define the solutions used in with severe hypoalbuminemia (Constable, 2003), −1 because sodium retention can aggravate heart disease fluid therapy as iso-osmolar (300 to 312 mOsm L ), hyperosmolar (> 312 mOsm L−1) and hypo-osmolar and because sodium decreased plasma albumin; and −1 therefore oncotic pressure, resulting in movement of (<300 mOsm L ) (Constable, 2003, 561). Using this fluid into the interstitial spaces and exacerbating tissue classification, it is clear that some routinely used oedema (Constable, 2003). crystalloid solutions are hypo-osmotic; in particular, −1 A colloid is a substance that is too large to pass lactated Ringer's solution (275 mOsm L ) is slightly −1 through a semi permeable membrane. Examples of hypo-osmotic and 5% dextrose (250 mOsm L ) is colloid solutions administered to ruminants are whole moderately hypo-osmotic, although after glucose blood, plasma, dextrans, hydroxyethyl starches and metabolism, 5% dextrose becomes a markedly hypo- gelatins (Constable, 2003). Intravenous colloid therapy is osmotic solution (Constable, 2003). Ringer's solution, based on the premise that the large molecular size of 0.9% NaCl and 1.3% NaHCO 3 therefore are considered colloids ensures their retention within the intravascular iso-osmotic solutions because they distribute in plasma space. Consequently, intravascular volume expansion is water and an osmolarity of 309, 308 and 310 mOsm L−1, greater and of longer duration when colloids, rather than has been calculated, respectively, (Constable, 2003). crystalloids are infused (Hughes, 2001). Colloid Because of hemolysis induced hypo-osmolarity fluids solutions are excellent for sustained expansion of plasma parenterally administered fluids should be iso-osmotic or volume, while are contraindicated in congestive heart hyperosmotic (Constable, 2003). failure and in the presence of oliguric or anuric renal failure (Constable, 2003). Colloids represent a therapeutic 0.9% Sodium Chloride Solution modality with specific indications, contraindications, benefits and risks. In comparison, balanced electrolyte Isotonic saline, also called physiological saline, is an solutions are relatively safe, inexpensive and iso-osmotic solution that little used in the routine therapy physiological. The high cost of some colloidal solutions of sick ruminants because ruminants often develop restrains the use versus crystalloid fluid administration in hypocalcemia and hypokalemia when suffering from many clinical situations (Hughes, 2001). lack of appetite. The 0.9% NaCl is used in cleansing To understand some aspects of the fluids used in fluid wounds, in surgical procedures and as a vehicle for other therapy two terms must be understood: osmolality and electrolytes and dextrose. It is a slightly acidifying osmolarity. Osmolality is the number of dissolved solution (Constable, 2003).

119 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Ringer’s Solution RLS, since acetate is metabolized more rapidly, therefore alkalinization is faster. Ringer's solution is a balanced, polyionic, non In addition, acetate exacerbates not D-lactic acidosis, alkalizing, iso-osmotic, crystalloid solution containing + + 2+ − present in most calves with diarrhea (Constable, 2003; physiological concentrations of Na , K , Ca and Cl . Smith and Berchtold, 2014). Commercial formulations Ringer's solution is the standard intravenous fluid for of acetated Ringer's solution containing gluconate; which adult ruminants because these animals tend to become like the D-lactate it is metabolized poorly by calves (and alkalemic when they suffer from lack of appetite possibly also by adults ruminant) (Constable, 2003; (Constable, 2003). Like the 0.9% NaCl solution is Smith and Berchtold, 2014). slightly acidifying solution (Constable, 2003). Iso-Osmotic Sodium Bicarbonate (1.3% NaHCO 3 Lactated Ringer’s Solution Solution) Ringer's lactate (frequently abbreviated as LRS), is Iso-osmotic sodium bicarbonate solution (1.3% 275 mOsm L−1; it is a crystalloid, balanced solution, NaHCO 3) is an alkalinizing iso-osmotic crystalloid polyionic, alkalizing, iso-osmotic containing physiological + + 2+ − solution, considered a strong alkalizing fluid, that is used concentrations of Na , K , Ca , Cl and lactate. to treat severe acidemia (indicated whenever blood pH < It is used to correct dehydration and mild electrolyte 7.20 due to metabolic acidosis). imbalance in ruminants, because the lactate is Sodium bicarbonate has proved more effective than predominantly metabolized to bicarbonate ion, which other bicarbonate precursors (such as lactate or acetate) can increase blood pH. Because accurate lactate or other synthetic bases (Smith and Berchtold, 2014), metabolism to produce the alkalizing effect, it is because bicarbonate does not have to be metabolized by considered to have weak alkalizing or slow capacity and the liver to exercise alkalizing effect in the blood it is not recommended for ruminants with severe (Constable, 2003; Smith and Berchtold, 2014). This acidemia (Constable, 2003; Smith and Berchtold, 2014). solution is alkalizing, since bicarbonate is combined and A possible disadvantage of the commercially + eliminates H ions producing CO 2 and water. available LRSis that lactate is an equimolar racemic Isotonic sodium bicarbonate solution (1.3%) can be mixture of L-lactate and D-lactate, so its use should be easily prepared by adding sodium bicarbonate (NaHCO 3) avoided in severely acidemic calves, since it can increase in sterile water (or distilled) at 13 g per litre (155 mEq/L − the concentrations of D-lactate (Constable, 2003; Smith HCO 3 ) (Constable, 2003). The amount of isotonic and Berchtold, 2014). In healthy animals the L-lactate is bicarbonate necessary to correct acidemia is calculated rapidly metabolized, while ruminant tissues have based on total concentration of CO 2 in blood, or the negligible activity D-lactate dehydrogenase, whereby the bicarbonate concentration, the value of excess base; and excretion of D-lactate is done primarily through the urine generally ranges between 2 and 5 L, based on the weight of (Constable, 2003). Therefore solutions of DL-lactate (as the calf and the severity of acidosis. Although there are found in lactated Ringers solution) in ruminants have rules to calculate bicarbonate needs (Smith and Berchtold, about half of the alkalizing ability than in solutions of L- 2014), a simple estimate is to administer isotonic sodium lactate only (Constable, 2003; Smith and Berchtold, bicarbonate solution for approximately 10% of the body 2014). Lactate Ringer's solution is used routinely, in weight over a period of several h (for example 4 L for a calf some cases by custom, although in patients, neonatal and of 40 kg) (Constable, 2003; Smith and Berchtold, 2014). adult ruminants, concentrations may be increased in Bicarbonate should not be used for the treatment of blood lactate; so it would be counterproductive to add severe respiratory acidosis, because the additional carbon lactate to these animals. dioxide (CO 2) generated may worsen respiratory acidosis (Constable, 2003). Acetated Ringer’s Solution 7.2% Sodium Chloride (Hypertonic Saline) Acetated Ringer's solution is similar to the RLS; but −1 it contains acetate instead of containing lactate. It is a This hypertonic saline solution (2460 mOsm L ) is balanced crystalloid, polyionic, alkalizing, hypoosmotic recommended for rapid expansion of plasma volume of solution, with 294 mOsm L−1. Commercially available severely dehydrated ruminants and its combination with formulations of this solution containing physiological oral electrolyte solutions or large volumes of LRS. + + 2+ − concentrations of Na , K , Mg , Cl acetate (CH 3COO) Therefore it can be very effective in resuscitating and gluconate (CH 2 (OH) {CH (OH)} 4COO) (Constable, severely dehydrated calves, being less expensive and 2003; Sen et al ., 2009; Smith and Berchtold, 2014). easier to administer (Smith and Berchtold, 2014). It is It is also considered a weak or slow alkalizing fluid recommended to administer this hypertonic saline at 4 to and must manage large quantities must be administered 5 mL kg −1 intravenously for 4 to 5 min (1 mL kg −1 min) to correct dehydration in calves with diarrhea. This (Constable, 2003; Smith and Berchtold, 2014). Faster acetated Ringer's solution, is theoretically better than the administration can cause hemodynamic collapse due to

120 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 vasodilation and decreased cardiac contractility, while D-Lactic Acidosis in Ruminants slower administration does not provide significant advantages compared to crystalloid solutions iso-osmotic Diarrhea, ruminal acidosis (in so-called ruminal (Constable, 2003). As with large volumes NaCl 0.9% drinkers) and acidosis without dehydration syndrome are small amounts of hypertonic saline consistently induce the main causes of morbidity and mortality in new-born mild acidosis (Constable, 2003), although the decrease in calves. For years we have known that adult ruminants, pH after administration of hypertonic saline is less than with acute ruminal acidosis, D-lactic acidosis develop after rumen overload and that increasing concentrations 0.08 units and disappears rapidly with time. Therefore, of D-lactate are responsible for most of the systemic the effect of hypertonic saline in the acid-base balance is acidemia, which occurs in calves called "syndrome clinically inconsequential (Constable, 2003). Hypertonic saline is also indicated for the treatment acidosis-without-dehydration'' and in cases of diarrhea in of hyperkalemia in calves (Smith and Berthold, 2014). calves with a significant dehydration (Berchtold, 2009). The importance of lactate and especially the isomer D- 8.4% Sodium Bicarbonate lactate in the path physiology of various gastrointestinal diseases in ruminants has expanded in recent years with The Hypertonic Sodium Bicarbonate (HSB), several clinical and experimental studies. Therefore, we commercially available as 8.4% solution, contains sodium think it is appropriate to review some aspects of the bicarbonate 1 mEq mL −1 and a total osmolarity of 2000 −1 importance of D-lactic acid for the development of mOsm L (Smith and Berchtold, 2014; Constable, 2003, clinical signs and therapy for the treatment of these 564). It’s used for the correction of severe acidosis and syndromes (Gentile et al ., 2004; Lorenz et al ., 2005; dehydration in ruminants, especially calves with diarrhea Naylor et al ., 2006; Gentile et al ., 2008). (Walker et al ., 1998; Constable, 2003; Smith and As indicated above the objectives of fluid therapy in Berchtold, 2014). ruminants, especially in calves with gastrointestinal It’s recommended for rapid alkalization in presence − disease, they are to correct dehydration, to correct the of severe acidemia (pH <7.2), providing 1 mEqHCO 3 acidemia; and the special aspect of reducing D-lactate per ml of solution, which facilitates the calculation of the concentrations. We should take this value as less than 1 volume to be administered. mmol L−1 (Naylor et al ., 2006). The rate of intravenous administration of 8.4% It is known that in calves with enteritis and diarrhea, −1 NaHCO 3 should not exceed 1 ml kg min (Constable, dehydration is a contributing factor to the CNS 2003). Theoretically, the product must generate an depression. However, this alone would not be able to osmotic movement of water and electrolytes from the produce the profound depression which is observed in gastrointestinal tract into extracellular space, similar to a some diarrheic calves (Walker et al ., 1998; Constable, hypertonic saline (Smith and Berchtold, 2014). However 2003). Given the ability of D-lactate to produce the HSB should not be used in diarrheic calves that have profound weakness, ataxia and CNS depression and concurrent respiratory diseases; as these calves may not considering that there is an increase of D-lactate in be able to effectively exhale excess CO 2 generated calves with severe diarrhea, it seems likely that the D- (Smith and Berchtold, 2014). lactate is partly responsible for these clinical signs (Walker et al ., 1998; Meganck et al ., 2014). 5% Dextrose As indicated elsewhere in this article the ruminants, This solution, abbreviated D5W, has 250 mOsm L−1, especially calves more than a week old, show a high but plasma osmolality decreases as glucose is production of lactic acid. Both isomers, D- and L-lactate, metabolized, leaving the water free (Constable, 2003, are produced in the gastrointestinal tract of ruminants by 564). It is the only non-alkalizing fluid that is generally bacterial metabolism of carbohydrates without any used in neonatal ruminants. Dextrose is often added to harmful consequence for the animal (Berchtold, 2009). other solutions, from 5 to 10% to offset the negative In adult cattle the fermentation of large amounts of carbohydrates induces an increase in the concentration of energy balance in diarrheic calves, whether or not organic acids which leads to a decrease in pH showing hypoglycemia (Smith and Berchtold, 2014). intraruminal, which favours the overgrowth of certain Because 5% dextrose solution has no sodium to expand bacteria (which are capable of producing large quantities the extracellular volume, its only application in of D- and L-lactate (Dirksen et al., 2005; Berchtold, ruminants is to provide free water (Constable, 2003; 2009; Smith, 2009). A similar effect occurs in calves Smith and Berchtold, 2014). with diarrhea; increased production of D- and L-lactate, In practice to provide energy and rehydrate the new- −1 probably due to villus atrophy, malabsorption of born, add 25 to 50 g of dextrose or 50 to 100 mL of a nutrients and increased intestinal fermentation by solution of 50% dextrose to 1 litre of LRS or isotonic bacteria present in the intestine (Berchtold, 2009). Both sodium bicarbonate to make a slightly hypertonic isomers (D- and L- lactate) are absorbed through the solution (Smith and Berchtold, 2014). blood (Berchtold, 2009).

121 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

In healthy animals L-lactate is rapidly metabolized, correction of acidosis or preventing acidemia, enhance while ruminant tissues have negligible activity D-lactate survival of diarrheic calves (Booth and Naylor, 1987; dehydrogenase, whereby the removal of D-lactate is done Naylor et al ., 2006). Although the mechanism is unclear, primarily through excretion in the urine (Constable, 2003; it is possible that the correction of academia simply accelerates the removal of D-lactate from the body Berchtold, 2009; Meganck et al ., 2014). Therefore, (Naylor et al ., 2006). metabolic acidosis that develops is mainly caused by CSF pH falls more slowly than blood pH and some time increasing concentrations of D-lactate (Naylor et al ., 2006; is required before the effects of acidemia (Naylor et al ., Berchtold, 2009). Since the D-lactate also only be removed 2006) are fully noticed. Acidemia also affects the efficiently by the kidneys, dehydration may have an indirect intracellular and extracellular potassium concentrations role in the increased toxicity of D-lactate (Ewaschuk et al ., and acidosis favors the movement of potassium from the 2004; Naylor et al ., 2006). cells into serum. These alterations in potassium levels Relative Contribution of Dehydration, Acidemia predispose to the development of cardiac arrhythmias and D-Lactic Acid to Clinical Signs in and cause weakness or even death (Naylor et al ., 2006). Gastrointestinal Disease In ruminal acidosis in adult cattle is likely that the Calves with gastrointestinal disorders may show relative contributions of dehydration, acidemia and D- signs of neurological dysfunction, including ataxia, lactate are similar to those of diarrheic calves weakness and reduced food intake. These systemic signs (Naylor et al ., 2006). are collectively referred to as malaise and may be the Correction of Acidosis in Ruminants result of dehydration, acidosis, endotoxemia or sepsis. Therefore the accumulation of D-lactate in blood seems We know that the simple fluid replacement without to be one of the most important factors in the alkalizing is not effective in the treatment of diarrhea in pathogenesis of systemic signs of weakness and CNS calves. Therefore, to achieve the correction of acidosis, depression in calves with gastrointestinal disease; playing a major role in the development of malaise in sodium bicarbonate is the treatment of choice for its sick calves and even in its death (Kasari and Naylor, immediate action on acid-base balance (Alonso et al ., 1986; Lorenz et al ., 2005; Naylor et al ., 2006; 2001; 2008b). Sodium bicarbonate is an effective Trefz et al., 2012a; Meganck et al ., 2014). alkalizing agent; a fact that has been empirically No obvious correlation between the serum levels demonstrated in blind, randomized, controlled studies in of D-lactate and dehydration. Variations in behaviour, diarrheic calves and calves with acidosis and dehydration posture and palpebral reflex are more closely syndrome (Kasari and Naylor, 1986; Booth and Naylor, correlated with elevations of saerum D-lactate 1987; Naylor et al ., 2006; Smith, 2009; Trefz et al ., 2012a). concentrations than with decreases in base excess. Bicarbonate can be given IV as an isotonic or However, impairment of a good sucking reflex is more related to the degree of dehydration than it hypertonic solution. In the field it is more practical to reflects acidosis (Meganck et al ., 2014). use a hypertonic compared with an isotonic solution. There are even researches showing that the D-lactate Rapid IV administration of an 8.4% bicarbonate −1 produced these clinical signs when it is administered formulation at 5-10 mL kg provided an effective and experimentally at calves (Lorenz et al . 2005; Naylor et al ., safe method to improve acid–base abnormalities 2006). In general, this suggests that the D-lactate is (Meganck et al ., 2014). responsible for most of the clinical signs in calves with The infusion of bicarbonate must be done with acidosis and without dehydration syndromes. The D- caution, since overdosing intravenously may cause a rise lactate easily penetrates the space of Cerebrospinal Fluid in PCO 2 which translates clinically hyperventilation (to (CSF) -with concentrations similar to serum- and it is + remove the CO 2 produced), an excess of Na thought than the loss of fighting reflex threat, the (hypernatremia) which causes hyperosmolarity and blinking reflex, the panicular reflex and the ability to − extracellular alkalosis (HCO 3 excess ions) accompanied stand are highly correlated with the concentration D- by cardiac arrhythmia and increased tissue needs oxygen lactate in the CSF (Naylor et al ., 2006; Berchtold, 2009). Interestingly, losses of the reflex of suckle correlates causing a secondary hyperlactatemia. poorly with the concentration of D-lactate and, unlike The base deficit is the most useful parameter to other reflexes, correlates well with the degree of quantify metabolic acidosis and it allows to quantify acidemia. (Gentile et al ., 2004; 2008; Lorenz et al ., the therapeutic requirements of bicarbonate in sick 2005; Naylor et al ., 2006; Lorenz, 2009; Trefz et al ., calves. In this case, the amount of sodium required to 2012b; Meganck et al ., 2014). The role of acidemia is correct metabolic acidosis is given by the formula: less clear and several experiments documented that the (Naylor et al ., 2006; Meganck et al ., 2014).

122 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Sodium Bicarbonate Requirement, mmol = concerns that it increases the pH of the abomasum and Body weight, Kg x Base Deficit x Vd thereby facilitates the entry of pathogens into the intestinal tract. Bicarbonate and citrate also interfere with the Where Vd is the volume of distribution of bicarbonate coagulation of milk, which is a concern in lactating calves and has been experimentally determined in healthy calves, (Naylor et al ., 2006). Although Meganck et al . (2014) in calves with diarrhea and calves with acidosis without concluded, that feeding with products containing dehydration syndrome (Kasari and Naylor, 1986). bicarbonate or citrate does not affect milk clotting in Although in practice; a value of Vd = 0.5 is used, it vivo and disagrees with general recommendations to may range from 0.45 to 0.75, depending on the plasma not feed with these products concurrently with or proteins and phosphate buffering systems between calves short before/after cow’s milk to calves. and on differences in the degree of intracellular acidosis Although sodium bicarbonate is the agent of choice for (Naylor et al ., 2006; Meganck et al ., 2014). correction IV of acidemia, other alkalizing sodium salts If a serum bicarbonate is available, bicarbonate precursors of bicarbonate are also used; but they do not have their drawbacks in over dosage, which are both source requirements can be calculated from the bicarbonatemia, − of HCO 3 and energy, including L-sodium lactate and using the following formula with a Vd of 0.6 (to sodium acetate (Kasari and Naylor, 1986; Alonso et al ., compensate for buffering by non-bicarbonate systems) 2001; Naylor et al ., 2006; Alonso et al ., 2008a; Smith, (Suzuki et al ., 2002; Naylor et al ., 2006). 2009; Meganck et al ., 2014). Sodium lactate has a

progressive alkalizing effect, provided they have Sodium Bicarbonate Requirement, mmol = obtained the integrity of liver function, which is rare in Body Weight, kg x (30-Patient Bicarbonate) an affected calf with severe diarrhea. Thus, the x Vd application of a solution containing lactate, whose D- isomer is not physiological and therefore is not Normally the correction of acidosis requires 1 to 4 L −1 metabolized or if so very slowly, it is contraindicated in (25 to 100 mL kg ) of an isotonic solution of sodium an hypovolemic calf (Alonso et al ., 2008b). Seems that bicarbonate (1.3%), administered intravenously over sodium acetate oral solutions are more effective in about 4 to 8 h (Suzuki et al ., 2002; Naylor et al ., 2006). expanding the plasma volume than sodium bicarbonate It is possible that this rapid correction produces a oral solutions, although there was considerable calf-to- paradoxical CSF acidosis. In severely acidotic calves calf variability (Sen et al ., 2009). Nevertheless, clinically treated with sodium bicarbonate, a residual depression may important differences in the resuscitative response of oral appear that requires 12 to 18 h to resolve. This may be due replacement therapy with solutions (300 or 150 mmol to the correction of acidosis in the CSF, the clearance of D- −1 L ) of sodium acetate or sodium bicarbonate were not lactate or some other factor (Naylor et al ., 2006). identified (Sen et al ., 2009). Sodium acetate has the Hypertonic solutions of sodium bicarbonate (8.4%) advantage of metabolizing faster in the liver and other have been tested in new-born calves, with experimentally −1 tissues (unlike lactate), it also has the advantage of induced respiratory acidosis at doses of 5 mL kg for 5 vasodilator effects, allowing irrigation of peripheral and min, with satisfactory results (Naylor et al ., 2006; splanchnic tissues (Alonso et al ., 2008a; Smith, 2009). Berchtold, 2009). Although some diarrheic calves show Several important questions still need to be answered normonatremia, others are hyponatremic and others are about the correction of D-lactic acidosis. One of the severely hypernatremic, therefore hypertonic sodium more important is whether or not correction of acidemia bicarbonate should be used cautiously in calves unless speeds the clearance of D-lactate. Conventional IV fluid the serum sodium concentration has been measured therapy with saline and sodium bicarbonate given in (Naylor et al ., 2006). accordance with the preceding principles has been shown Oral acidemia correction can be achieved with electrolyte solutions containing bicarbonate, acetate, to rapidly correct hyper D-lactatemia in diarrheic calves citrate or other metabolizable bases. Bicarbonate, (Ewaschuk et al ., 2006). This is also associated with the administered orally, is not directly effective, it is first excretion of D-lactate in urine (Ewaschuk et al ., 2006). neutralized by the acidity of the abomasum. Systemic In a controlled trial in calves with the acidosis without alkalinization occurs when pumps protons abomasal dehydration syndrome sodium bicarbonate was more regenerate abomasal acid, with an equal addition of effective than an equal volume of saline in correcting bicarbonate to the systemic circulation. Since oral CNS depression suggesting that sodium bicarbonate electrolyte therapy is only recommended for calves not therapy helps speed removal of D-lactate (Kasari and Naylor, 1986; Naylor et al ., 2006). severely compromised, the metabolism of bases such as + acetate is unlikely to deteriorate. In a trial with an oral As mentioned earlier, bicarbonate losses or H gains are electrolyte solution containing acetate, it was slightly likely to be ongoing and considerably more bicarbonate more effective than an identical solution containing may be required than at first calculated. This is especially bicarbonate in correcting acidemia. Generally, true in older calves, where acidosis is due in part to the bicarbonate is avoided in oral electrolyte solutions due to production of acids in the colon (Grove-White, 1994). In

123 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 these cases, applying fluid with bicarbonate is beneficial, Pathophysiology of Disorders provided that the acid-base status has been previously measured and during therapy. Grove-White (1994) Alteration of secretion and absorption mechanisms recommends the addition of 400 to 800 mmol of sodium are essential in the pathophysiology of diarrhea. The bicarbonate to 5 litres of fluid, being safe and effective in continuous flow of water and electrolytes through the severely acidotic calves. intestinal mucosa, either through absorption or secretion, may be altered in greater or lesser degrees by the causes Major Digestive Diseases and their Treatment by that provoke diarrhea (Zurita et al ., 1987; McClure, Fluid Therapy 2001; Meganck et al ., 2014). Regardless of origin, most calves with diarrhea show an increased number of Most electrolyte imbalances are due to a net loss of coliform bacteria in the small intestine (bacterial electrolytes caused by diseases of the digestive system. overgrowth), which contributes to morphological Sweating, bleeding wounds from burns, excessive damage of the intestinal mucosa and may result in salivation and vomiting are also accompanied by loss of electrolytes, but are unimportant in ruminant animals increased susceptibility to bacteremia. Metabolic (Dirksen et al ., 2005; Radostits et al ., 2007). acidosis is a frequent consequence of gastrointestinal disease and is in calves with dehydration and in Neonatal Diarrhea in Calves clinically sick calves, with minimal or no signs of dehydration, the so-called ''acidosis-without-dehydration While diarrheal diseases can appear at any age in syndrome'' (Berchtold, 2009; Meganck et al ., 2014). ruminants, it is in young animals, calves, lambs and kids, Dehydration causes diarrheain calf with a significant where neonatal diarrhea is the most common cause of decrease in extracellular volume, which is of particular death, being a major cause of economic losses to the importance at the level of plasma compartment livestock industry (Smith and Berchtold, 2014). (hypovolemia) and a slight increase in intercellular Diarrhea in new-born calves remains the leading volume. During diarrhea, there is a loss of sodium, cause of morbidity and mortality (Berchtold, 2009). It is potassium, chloride and bicarbonate faeces, with a a complex disease that occurs predominantly during the decrease in plasma sodium concentration; resulting in first weeks of life, with multiple causes among which extracellular hypoosmotic fluid (hyponatremia), which include viruses (rotavirus, coronavirus), bacteria makes water pass to the intracellular space, increasing its (Escherichia coli, Salmonella sp.), protozoa volume (Rejas and Alonso, 2008). A calf with diarrhea (Cryptosporidium parvum, Eimeria sp .) or errors in has water loss up to 100 mL kg −1 body weight (4000- feeding and management (Radostits et al ., 2007; 5000 mL−1) (Alonso et al ., 2008a). Contrary to what one Berchtold, 2009). might think, hyponatremia is observed rather than Regardless of the pathogen or the mechanism hypernatremia, this is due to water retention by the involved, this disease is characterized by increased loss kidneys that occurs in response to Ant Diuretic Hormone of electrolytes and water in the faeces of calves and often (ADH), released as a result of hypovolemia. ADH and decreases milk intake (Smith and Berchtold, 2014). thirsty, regulates the plasma sodium concentration, so Regardless of the cause, it is necessary to establish a that changes in serum sodium variations indicate water treatment protocol that includes antibiotics (although the rather than sodium. Sodium loss is primarily origin is not initially bacterial, diarrheal stool favour the extracellular, plasma sodium drop causes the flow of growth of a large number of pathogens), anti-toxic, anti- water into the intracellular space, decreasing parasitic and especially correct dehydration and reverse extracellular volume (Rejas and Alonso, 2008); also the the acid-base and electrolyte changes produced. intracellular environment may be affected because of This process causes dehydration, strong acidosis, + + electrolyte abnormalities (usually decreased sodium, metabolic acidosis producing a Na /H exchange chlorides, increased or decreased potassium and to a between the intracellular and extracellular spaces (Alonso et al ., 2008b). Also, the loss of bicarbonates as lesser extent magnesium), increased levels of D-lactate − and a negative energy balance (by anorexia and HCO 3 takes increased production of H+ ions, causing malabsorption of nutrients). extracellular acidosis and intracellular subsequently Therefore, diarrhea is by far the most common (Alonso et al ., 2008a). indication for fluid therapy in neonatal calves (Alonso et al ., From the metabolic point of view, the acidosis is the 2001; Smith and Berchtold, 2014). It is necessary to note most important disorder, along with dehydration are the that acidosis is the most important disorderin calves that triggers that provoke the fatal evolution of the process this along with dehydration, are the triggers that cause (Alonso et al ., 2001). Several factors predispose animals the fatal evolution of the process (Alonso et al ., 2008b); with diarrhea to metabolic acidosis. Among them we can however there is the possibility of finding clinically ill mention 1. Excessive loss of bicarbonate in the faeces, 2. calves with minimal or no signs of dehydration, the so- Dehydration, leading to hypovolemia and low perfusion called ''acidosis-without-dehydration-syndrome" in tissues, 3. Anaerobic metabolism at a muscular level, (Berchtold, 2009). which causes increased production of lactic acid, 4. Acid

124 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 production of abnormal intestinal flora (dysbiosis) and potassium loss associated with hyperkalemia, disturbs 5. Low renal perfusion, leading to a decreased the functioning of the heart and skeletal muscles, causing + − excretion of H and lower production of HCO 3 , the weakness, lethargy, arrhythmia and bradycardia − kidney is the largest body forming HCO 3 (Rejas et al ., (Alonso et al ., 2008a) and the electrocardiogram little 2001; Alonso et al ., 2008b). amplitude level and absence of the P wave is observed An important discovery was that metabolic (Alonso et al ., 2008b). acidosis in diarrheic calves varies during the first There is also a hypoglycemia due to both anorexia weeks of life. This has been pointed out that and the lack of intestinal absorption. The increase of metabolic acidosis is less severe during the first week uremia, present in many animals, is a consequence of of life, than in diarrheic calves older than 8 days increased catabolism and decreased urine output. The (Naylor et al ., 2006; Smith and Berchtold, 2014). Those elevation of uremia seems to be one of the earliest calves over 1 week of life can produce high levels of plasmatic variables in diarrhea in young ruminants. So organic acids in the large intestine, as a result of bacterial much so, that Fayet and Overwater, consider that the growth, so these calves often suffer more severe acidosis. assessment of uremia, chloremia and hematocrit allow a Subsequent studies confirmed that in calves with diarrhea prognosis to be issued and estimate the effectiveness of over 1 week old, base deficit usually was almost twice that the treatment (Alonso et al ., 2008a). in calves with diarrhea occurring during the first week of Fluid Therapy in Diarrhea of Calves life (Meganck et al ., 2014; Smith and Berchtold, 2014). These patients show signs of mental depression, Fluid therapy is perhaps the most important aspect in the weakness and anorexia, which may result from therapy of calves with diarrhea, as the most common cause dehydration, acidemia, endotoxaemia or sepsis, of death is dehydration and acidosis. There are multiple although there is evidence that the isomer D-lactate studies that certify that the prevention and correction of plays an important role in its development. Recent these alterations significantly improves the survival of these studies have linked the degree of depression of calves animals. Therefore the objectives are: 1. Correct with increasing concentration of D-lactate instead of dehydration and electrolyte imbalances, 2. Correct acid- only the severity of acidosis or dehydration (Naylor et al ., base deficits (reduce levels of D-lactate), 3. Provide 2006; Berchtold, 2009; Lorenz et al ., 2005; Meganck et al ., nutritional support and 4. Remove and/or prevent possible 2014; Smith and Berchtold, 2014). Derivatives bacteremia (Smith and Berchtold, 2014). Three of these clinical signs of increasing concentrations of D-lactate goals are covered by fluid therapy (Alonso et al ., 2008b; and its relation to predicting acidemia in calves are Berchtold, 2009; Smith and Berchtold, 2014). described elsewhere in this chapter. Restitution of water and electrolytes should be The D-lactate is primarily responsible for the acidosis initiated early and without waiting for the onset of of individuals with severe diarrhea, since cells symptoms of dehydration. The amount of fluids to be metabolize lactate with difficulty; it accumulates in the administered should be calculated from the degree of blood faster than the L-isomer (Lorenz et al ., 2005; dehydration, maintenance needs and losses that could Rejas and Alonso, 2008; Meganck et al ., 2014). occur in the near future. The amount of liquid to be Acidosis is also important; as it affects intra- and perfused, as well as the rate and the route of extracellular concentrations of potassium, favouring the administration is noted in a previous section. The movement of potassium from the cells into the conditions in which calves with diarrhea are and extracellular fluid and causing hyperkalemia. Although especially their clinical signs or blood measurements, will significant loss of potassium with faeces occur in calves be considered in order to opt for one or the other infusion with diarrhea and that their intake is reduced, these line; and for the right kind of fluids for the disease. animals can have a normal or elevated serum potassium. Oral hydration is an easy method of execution, Hyperkalemia is attached to the phenomenon of economic, widespread, with good results and does not uncompensated metabolic acidosis and H+ ions penetrate require special training of staff (Zurita et al ., 1987). into the intracellular compartment and cause the output There are multiple oral preparations in the market, of K + ions into the extracellular sector to maintain generally in powder form to be dissolved in water, electro-neutrality (Alonso et al ., 2008a). Moreover, containing sodium, potassium, chloride and glucose. hypovolemia favours greater loss of potassium via the Sometimes citrates and glycine are added to facilitate the kidneys, caused by aldosterone (Rejas and Alonso, absorption of electrolyte. The presence of glucose 2008). Therefore, kalemia does not reflect the real deficit of represents an energy intake, but can only meet a fraction potassium in a calf with diarrhea. Thus diarrheic calf with of the energy required by the calf (Meganck et al ., 2014). severe dehydration and acidosis uncompensated, has a Although there is considerable controversy regarding negative level of potassium, although hyperkalemia appears the use of breast milk and milk replacers in diarrheic and potassium intake is necessary (Alonso et al ., 2008b). calves, several studies recommend maintaining the Potassium loss is difficult to assess clinically; intracellular milk supply, sometimes supplemented with oral

125 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131 rehydration solutions, because it improves the energy Although there are four routes for parenteral balance of the calf and facilitates the recovery of the administration: intravenous, subcutaneous, intestinal mucosa (Zurita et al ., 1987; McClure, 2001; intraperitoneal and intraosseous (Constable, 2003); the Alonso et al ., 2008a; 2008b; Smith, 2009; Meganck et al ., first two are used in bovine clinical and to choose one or 2014). The administration of liquids is easy when the calf the other depends on the degree of involvement of the is standing and alert, however weakened animals and/or animal and practical possibilities for therapy. Nor is prostrated represent a significant risk. It is important to there an exact rule for administration of fluid; treatment avoid rapid administration because of the possibility of response being the best guide to assess the amount of deriving liquid to the airway, therefore bottle-feeding, liquid needed to perfuse (Grove-White, 1994). The esophageal probes, or bottles partially introduced in the recommended infusion rate is 20 to 40 mL g−1 h, trying mouth, are often used. to correct dehydration in about 6 to 8 h and then It is recommended to administer quantities of less gradually the remaining fluids administered required for than two litres each time to prevent gastric distention and maintenance and expected losses (Naylor et al ., 2006); reflux into rumen. Thus recommended intakes are but especially in heavily affected animals can be separated by at least 2 h and at least 3-4 times a day; increased infusion rate. This and other aspects have been which favoursa greater intake of liquid by the animal. A listed in the relevant chapter. positive development of clinical signs should be seen within 48 h and once the animal restarts voluntary water Ruminal Acidosis/Lactic Acidosis for Ruminal intake, it is interesting to reduce the volume of Overload rehydration solutions, administered orally. Parenteral hydration should be considered in valuable The clinical symptoms vary depending on the animals, or calves with a severe clinical profile. Its main duration and volume of production of lactic acid, ranging advantages are the rapid distribution of water and from a temporary loss of appetite to severe electrolytes, greater choice of more complete solutions gastrointestinal symptoms, with significant involvement and a faster clinical response. The most commonly used of the general condition (Dirksen et al ., 2005). The solutions are isotonic solution of 5% glucose, which disease occurs as a result of excessive consumption of provides energy and water, Lactate Ringer's solution, which food or rations rich in carbohydrates easily digestible, it is able to cover -albeit minimally- the sodium, potassium, especially starch and/or sugars, simultaneously with a bicarbonate deficits and mild acidosis (Zurita et al ., 1987). poor amount of fiber (Lisboa, 2004; Dirksen et al ., 2005). Lactate Ringer's solution, which is able to cover -even In rare cases, it can be told that recently the animal has minimally- the deficit sodium, potassium, bicarbonate escaped, has had access and has ingested a large quantity and mild acidosis (Zurita et al ., 1987). In more severe of such food (Lisboa, 2004; Dirksen et al ., 2005). cases be necessary to use alkalizing solutions, as Lactic acid is generated in excess as a final product indicated in this article. of altered rumen microbial fermentation. These carbohydrates which are easily digestible cause a Alkalizing fluids are the right choice for IV significant production of volatile fatty acids, especially rehydration of calves with diarrhea and dehydration. lactic acid, which causes a significant drop in ruminal Currently, sodium bicarbonate is recommended for this pH. The lactic acid concentration rises above 100 mmol treatment solution. Sodium bicarbonate (either hypertonic −1 −1 L , reaching in extreme cases above 300 mmol L , or isotonic) quickly corrects both acidosis and dehydration synthesized lactic acid (L and D isomers). Both isomers and restores normal cell function (Smith and Berchtold, are physiological metabolites of ruminal content and 2014). In Müller's opinion, the sodium gluconate is even can be checked in a diet with coarse food. ineffective in correcting acidemia and a solution containing sodium bicarbonate is much more effective in The production of either isomer is determined in alkalinizing diarrheic calves with strong ion acidosis many cases for food and microorganisms in the rumen, than a solution with sodium gluconate (Müller et al ., so ruminal pH changes may alter the microbial flora 2012). When the calf's sucking reflex is restored, additional significantly and therefore their concentrations vary. treatment may be administered orally (Smith and Berchtold, Thus D-lactic isomer increases during acidosis, from 2014). The age of the calf should be taken into account 20% at pH 6 up to 50% at pH 5 (Dirksen et al ., 2005). when assessing the severity of acidosis and to determine This is of great importance, because the D-lactic acid is the requirements of bicarbonate in diarrheal calves. metabolized in an inferior form; and therefore more Acidosis may be present in sick calves with diarrhea, slowly than the L-isomer and that its elimination is with or without dehydration, who cannot stand, they are primarily by renal excretion (Dirksen et al ., 2005). lying or unstable, listless or in a coma, with incomplete When ruminal acidosis is severe, it ends up or absent palpebral reflex. Also, if the sucking reflex is causing an acid-base systemic imbalance, absent or weak, or calf is chewing erratically rather than characterized by hyperlactataemia, since a large sucking normally, D-lactic acidosis may be present in amount of lactic acid is absorbed (Lisboa, 2004; these animals (Smith and Berchtold, 2014). Dirksen et al ., 2005; Radostits et al ., 2007;

126 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Alonso et al ., 2008a). It is important to note that (Radostits et al ., 2007). In sheep and goats, therapeutic lactate is 10 times stronger than the volatile fatty acids, measures consisted of neutralization of acidity by oral so it exceeds the buffer capacity of the rumen fluid and and/or parenteral use of isotonic (1.3%) and hypertonic saliva (poorly produced if dehydration). Ruminal (5%) sodium bicarbonate with adequate fluid therapy acidosis also produces a progressive inhibition of motor (Tufani et al ., 2013). Thus, it has been used 5% sodium activity of the rumen, causing paralysis when the pH is bicarbonate solution at 10 mL kg −1, along with a about 5 (Alonso et al ., 2008b). Systemic lactic acidosis balanced electrolyte solution (100 mL kg −1) and 1.3% may eventually be accompanied by varying degrees of solution of sodium bicarbonate at 50 mL kg −1 in severe dehydration (Lisboa, 2004). Increasing the osmolarity of case, or isotonic sodium bicarbonate (1.3%), 50 mL kg −1 ruminal fluid additionally promotes a flow of water in intravenously in moderate cases (Tufani et al ., 2013). the light of organs, besides the lactic acid that is Because the gastrointestinal contents hyperosmolarity conveyed to the intestine causes an osmotic diarrhea, and enteric water loss through diarrhea, oral fluid supply which further aggravates dehydration and electrolyte does not serve to recover the lost fluids. Cattle that imbalance (Alonso et al ., 2008a). responds favorably to rumenotomy and the fluid has Treatment of Lactic Acidosis increased muscle strength, he begins to urinate after one h and try to remain standing after 6 to 12 h (Radostits et al ., In addition to multiple measures to empty the ruminal 2007). The general rule recommends to correct half of content, to modify the microbial flora, to restore the initial deficit of bicarbonate in the first 6 h and the intestinal motility and proventriculi and other supportive other half in the next 6-18 h. The bicarbonate deficit therapies must be balanced hemoconcentration and blood ranges between 12 and 20 mmol L−1 (Alonso et al ., acidosis (Tufani et al ., 2013; Dirksen et al ., 2005; 2001). We must also not forget that once the animal Alonso et al ., 2008b; Radostits et al ., 2007). Fresh recovers, the reuse of ruminal lactate provides an ruminal cud from slaughter house was collected and additional force of bicarbonate; thus the risk of overload transplanted into rumen (Tufani et al ., 2013). If the alkaline intensifies (Alonso et al ., 2001). overload is severe, it is necessary to empty the ruminal The criteria for calculating the intravenous infusion content either by rumenotomy or by siphoning. of bicarbonate as alkalizing would be given by the × Afterwards ruminal and metabolic acidosis will be formula: Deficit (mmol/L) 0.3 body weight (kg), where 0.3 is the extracellular space (equivalent to 30% corrected by alkalizing agents administered orally or −1 BW) and an infusion rate of 2.5 mmol kg BW/h parenterally, according to the symptoms (Tufani et al ., (Alonso et al ., 2008a). As an example for a cow with 2013; Radostits et al ., 2007). Alkalizing used in the −1 −1 500 kg, with a deficit of 15 mmol L , would require rumen are Mg salts (oxide or sulfate, 1 g kg ) or sodium × × −1 2250 mmol bicarbonate (15 0,3 500), equivalent about (0.5 g kg ) bicarbonate, in plenty of warm water by gavage 14 litres of bicarbonate 1.3% and about 2.25 litres of or by rumenotomy (Tufani et al ., 2013; Alonso et al ., bicarbonate 8.4% (Table 3). The recommended infusion 2008a). Alkalizing in rumen isn’t always recommended, rate is 2.5 mmol kg−1 BW/hour. because if the amount administered is not calculated correctly alkalosis can be caused (Alonso et al ., 2008b). Subclinical Ruminal Acidosis Animals that die in the first phase of the disease do so Subclinical ruminal acidosis is due to intensive primarily as a result of blood decompensated acidosis, production of volatile fatty acids with temporary hypovolemia, shock and disseminated intravascular increases lactic acid. The main causes are diets with high coagulation (Dirksen et al ., 2005, 398). Therefore to concentrations of easily fermentable carbohydrates or as achieve a positive evolution of the disease it is often a consequence of certain organic and metabolic diseases decisive to maintain fluid homeostasis and acid-base (Dirksen et al ., 2005). As a general rule, it does not balance; this is also very important because the excretion require fluid, nor orally nor parent rally. Correction of of lactic acid is mostly done by the kidney (Dirksen et al ., ruminal acidosis by administering alkalizing agents, with 2005). Whenever circumstances permit fluid replacement it should be done by a continuous plenty of warm water and orally as indicated above, is intravenous drip; it is suitable for the mixture of usually sufficient. The substances used are salts of Mg or physiological saline and sodium bicarbonate (NaCl sodium bicarbonate (Radostits et al ., 2007). 0.9%+ sodium bicarbonate, 1.4% = 4.5 g NaCl + 6.5 g Abomasal Displacement NaHCO 3/L) or only bicarbonate solutions at 1.4 or 5% (Dirksen et al ., 2005). Radostits et al . (2007) recommend The imbalance of fluid, electrolyte and acid-base is the treating systemic acidosis by intravenous solutions consequence of the difficulty of abomasal transit and sodium bicarbonate 5%, with a rate of 5 litres to an retention of liquids in the light of displaced abomasum, animal of 450 kg, for an initial period of 30 min. Then because emptying is prevented or delayed and the 1.3% sodium bicarbonate is administered at a rate of 150 resulting ions are continuously secreted and don´t undergo −1 ml kg BW, intravenously for the following 6-12 h the physiological process of intestinal resorption.

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Table 3. Severity of acidosis (Grove-White, 1994, 266).* rate of 4 to 6 l h. Metabolic alkalosis is corrected using equivalent to plasma bicarbonate sodium chloride solutions at different concentrations Severity of acidosis TCO 2* (mmol/L) (0.9, 3.6 and 7.2%), with no significant differences in Normal 24 (21-28) outcomes (Radostits et al ., 2007). Mild acidosis 16.5 -21.0 Acidifying solutions are isotonic solutions that Moderate acidosis 12-16 Severe acidosis 8-12 mainly consist of potassium chloride and ammonium Very severe acidosis < 8 chloride (108 g of potassium chloride +80 g of NH 4Cl in 20 L of water), providing a source of potassium and Therefore, the retention of large amounts of ions chloride to correct alkalosis. This solution can be 2+ + + − administered intravenously at a rate of 20L in 4 h to Ca , Na , H+, K and Cl occurs. This liquid is very rich − + 450 kg cows; followed by administration of a in Cl ions which combine with H ions secreted to + balanced electrolyte solution at dose of 100 to 150 mL generate HCl. For every H secreted inside the −1 − kg BW in a 24 h period. abomasum a ion HCO 3 it is generated and returned to The latter acidifying solution should be used the extracellular fluid compartment (Lisboa, 2004; carefully, it is necessary to make periodic blood Dirksen et al ., 2005; Radostits et al ., 2007; Alonso et al ., assessments and ideally every hour to prevent acidosis 2008b). Thus, dehydration is accompanied by metabolic (Radostits et al ., 2007). Treatment with oral electrolytes alkalosis, with hypochloremia and hypokalemia, is recommended primarily in the postoperative period possibly there hyperglycemia (Rejas et al ., 2001; Lisboa, (Radostits et al ., 2007). A mixture of NaCl (50 to 100 g), 2004; Dirksen et al ., 2005; Radostits et al ., 2007) and KCl (50 g) and NH 4Cl (50 to 100 g) is administered + even possible hypocalcemia (Dirksen et al ., 2005). K every 24 h; along with parenteral fluid if necessary. depletion is due to increased disposal in the urine, as a Supplementation with 50 g/day of NaCl may be compensatory mechanism renal alkalosis (exchange of H + continued until the cow returns to normal appetite retained or to maintain electrical neutrality for the (Radostits et al ., 2007). − −1 elimination of HCO 3 ) (Alonso et al ., 2008a). Sometimes, supplementation with 500 mL of 25% calcium borogluconate intravenously is Abomasal Displacement to the Left recommended, the rationale is that the administration Surgical correction through various techniques or of calcium enhances the motility of the abomasum procedures of dump, with or without restraint, to settle (Radostits et al ., 2007). a dystopia of abomasum with varying degrees of Abomasal Displacement to the Right, with or success. Treatment of secondary ketosis, without Torsion accompanying this digestive pathology, requires parenteral administration of dextrose and oral In displaced abomasum to the right, with much lower administration of sodium propionate or propylene glycol. prevalence, the condition described above is complicated In abomasal displacement to the left, may be varying by hypovolemic shock and end toxemic shock, due to degrees of dehydration, metabolic alkalosis, vascular compromise and areas of ischemic necrosis, hypokalemia, hypochloremia and (Radostits et al ., especially when there is torsion of the viscera. In these 2007); therefore ideally it makes blood valuations, situations and with the advancement of the process, although balanced electrolyte solutions containing lactic acidosis beats the original alkalosis (Lisboa, 2004). sodium, chloride, potassium, calcium and glucose intake It is recommended the examination of blood for is sufficient in most cases (Radostits et al ., 2007). alkalosis/acidosis determination to ensure the diagnosis and the possible evolution of the disease. In mild cases, with minimal systemic disorders, in Because of the retention of hydrochloric acid which a light hemoconcentration and metabolic alkalosis markedly increase blood parameters indicators of is observed, early treatment with fluids and electrolytes − alkalosis (pH, pCO 2, HCO 3 , positive BE), while orally or intravenously can give good results. Fluid clearly concentrations of chlorine and potassium therapy is essential to restore digestive motility, descend. Simultaneously hematocrit, hemoglobin and especially when the abomasum is distended for urea levels increase, indicating hem concentration and accumulation of fluid, requiring the transit of content limited function renal. In an advanced stage, alkalosis into the duodenum to be started in order for the is overwhelmed by a metabolic acidosis, which is − electrolytes which it contains to be absorbed. recognized by the drop in pH, pCO 2, HCO 3 , BE (<+5 It is recommended to mix 2 litres of physiological mmol L−1) in blood, whereas there is little change in saline +1 litre of isotonic solution of 1.1% KCl +1 litre the concentrations of chloride, potassium and urea of isotonic solution of 5% dextrose intravenously at a (Dirksen et al ., 2005).

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Table 4. Composition of the main crystalloid solutions used in fluid therapy. *[lactate] + + - − 2+ Na K Cl HCO 3 Glucose Ca Osmolalidad (mmol/l) (mmol/l) (mmol/l) (mmol/l) (g/l) (mmol/l) (mOsm/l) 0.9% NaCl 154 ─ 154 ─ ─ ─ 308 Ringer 147 4 155 ─ ─ 2.2 308 Ringer lactate 131 5.4 112 28* ─ 3.6 294 5% glucosaline 154 ─ 154 ─ 5 ─ 586 1.3% NaHCO 3 167 ─ ─ 167 ─ ─ 334 8.4% NaHCO 3 1000 ─ ─ 1000 ─ ─ 2000 18,5% KCl ─ 2480 2480 ─ ─ ─ 4936

Regarding the pre and postoperative therapy, if the duodenum and in that case neither metabolic alkalosis patient's general condition is markedly affected it can be nor dehydration occur (Radostits et al ., 2007). deduced, without a blood analysis, that hypovolemia, Washing the rumen, when it appears significantly metabolic alkalosis and other consequences have distended, not only relieves the pressure but also allows occurred resulting from the disorder in the greater ease for scanning the abdomen (Radostits et al ., gastrointestinal tract. These patients should receive 2007). Some animals respond adequately to the preoperatively several litres of intravenous physiological administration of fluids and electrolytes, in combination saline, which serves not only to bring the patient to an with oral administration of mineral oil (5 to 10 litres operable state, but to prevent a probable circulatory daily for 3 days) or docusate sodium (Radostits et al ., disorder that occurs during the replacement. For post- 2007). The use of a hypertonic saline 1.8% is effective operative treatment of severe cases it is advisable drip for correction of metabolic alkalosis hypochloremic infusion of physiological saline equivalent to 3%, experimentally induced in sheep and could be useful in maximum 5% (depending on state) of body weight in the cattle (Radostits et al ., 2007). first 24-48 h. In milder cases blood status is normalized in 24-48 h, without an intravenous infusion, as long as Intestinal Obstruction Dilation and Cecal Volvulus bowel function is resumed (Dirksen et al ., 2005). The cecal dilation primarily affects cattle milk yield Overload and Abomasal Dilatation during early lactation. Clinically it is characterized by In addition to the treatment for the primary disease, loss of appetite, decreased milk production, fewer stools, special importance to the parenteral fluid and correction detection of high-pitched sounds in the upper right flank of acid-base balance should be given. Hypertonic oral and the detection of the distended viscera on rectal rehydration solutions have the theoretical disadvantage examination. Intestinal obstruction is manifested clinically that they may create a transient dehydration after feeding with anorexia, abdominal pain, absence of stools, dark because the hypertonicity of abomasal fluid contents can faecal shedding with blood and mucus, dehydration with cause movement of water from the extracellular space acid-base imbalance and the death of the animal when no into the abomasum (Sen et al ., 2009). Successful results physical obstruction is properly resolved. Surgical with the following treatment have been obtained: correction is the only treatment in those animals in which Starting with intravenous drip of 1L of sodium chloride recovery is sought (Radostits et al ., 2007). 7.2%, followed by 20 L of physiological saline with 50 g Among the support measures it is of great L−1 glucose and 80 mmol of potassium chloride. On the importance that a fluid and electrolyte therapy adapted 2nd and 3rd day post-surgery it is recommended to apply to the degree of dehydration, be applied by continuous 10 L of physiological saline intravenous glucose drip and if not possible by repeated intravenous (Dirksen et al ., 2005; Smith, 2009). applications (Dirksen et al ., 2005). Physiological saline solutions with a possible addition of 10 to 20 Vagal Indigestion Syndrome mmol of potassium/L are suitable; usually it is achieved Vagal indigestion and other causes, mainly has its by applying half of the calculated according to the origin in two etiologies, vagus nerve injury and degree of dehydration in the term of 5 to 10 h; because reticulated adhesions. Following the functional with the restart of the intake passage absorption obstruction and distension an abomasal fluid retention processes help in normalizing (Dirksen et al ., 2005). occurs in this viscera and a backflow of its contents into Multiple electrolyte solutions with physiological saline the rumen leading to a ruminal chloride concentration are effective, even though the animal has metabolic >20 mmol L−1. Therefore you can observe varying degrees alkalosis with hypokalemia and hypochloremia of dehydration and metabolic alkalosis leading towards (Radostits et al ., 2007). The fluid and electrolytes hypochloremic and hypokalemia (Radostits et al ., 2007). intravenously are always needed in the postoperative In the previous stenosis the abomasal fluid can reach the period and may also be needed preoperatively.

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After obstruction of the small intestine caused by a Constable, P.D., 2003. Fluid and electrolyte therapy in hairball in 2 young beef calves, were administered of ruminants. Vet. Clin. North Am. Food Anim. 7.2 L of normal saline (0.9% NaCl), IV, over the first Pract., Philadelphia, 19: 557-597. 36 h, plus one liter of lactated Ringer’s solution and DOI: 10.1016/S0749-0720(03)00054-9 3.6 L of normal saline were given during the surgery Constable, P.D., E. Thomas and B. Boisrame, 2001. and for the next 24 h, with positive results Comparison of two oral electrolyte solutions for (Abutarbush and Radostits, 2004). the treatment of dehydrated calves with experimentally-induced diarrhea. Vet. J., 162: 129-140. Acknowledgement DOI: 10.1053/tvjl.2000.0553 Constable, P.D., P.G. Walker, D.E. Morin and We are grateful to Fiona Hickey for the linguistic J.H. Foreman, 1998. Clinical and laboratory revision of this paper. assessment of hydration status of neonatal calves with diarrhea. J. Am. Vet. Med. Assoc., 212: 991-996. Author’s Contributions Dirksen, G., H.D. Gründer and M.M. Stöber, 2005. Medicinainterna y Cirugía Del Bovino. 4th Edn., All authors equally contributed in this work. Inter-Médica, Buenos Aires, Argentina, pp: 1172. Ewaschuk, J.B., G.A. Zello and J.M. Naylor, 2006. Ethics Lactobacillus GG does not affect d-lactic acidosis in diarrheic calves, in a clinical setting. J. Vet. This review article is original and its contents have Internal Med., 20: 614-619. not been published before. No ethics issues are DOI: 10.1111/j.1939-1676.2006.tb02905.x concerned with the present article. Ewaschuk, J.B., J.M. Naylor and G.A. Zello, 2004. D- lactate production and excretion in diarrheic References calves. J. Vet. Internal Med., 18: 744-747. DOI: 10.1111/j.1939-1676.2004.tb02615.x Abutarbush, S.M. and O.M. Radostits, 2004. Obstruction Gentile, A., I. Lorenz, S. Sconza and W. Klee, 2008. of the small intestine caused by a hairball in 2 young Experimentally induced systemic hyperchloremic beef calves. Canad. Vet. J., 45: 324-325. acidosis in calves. J. Vet. Internal Med., 22: 190-195. Alonso, D., J. Ángel, R. López and Juan, 2008a. DOI: 10.1111/j.1939-1676.2008.0028.x Fluidoterapia práctica en rumiantes. RECVET- Gentile, A., S. Sconza, I. Lorenz, G. Otranto and Revista Electrónica de Clín. Vet., 3: 1-18. G. Rademacher et al ., 2004. D-Lactic acidosis in Alonso, D., J. Ángel, R. López and Juan, 2008b. calves as a consequence of experimentally induced ruminal acidosis. J. Vet. Med. Series A, 51: 64-70. Procesos entéricos en vacunos. RECVET-Revista DOI: 10.1111/j.1439-0442.2004.00600.x Electrónica de Clínica Vet., 3: 1-14. Gottardo, F., S. Mattiello, G. Cozzi, E. Canali and Alonso, D.A.J., L.E. Fidalgo Álvarez and J.R.G. Montaña, E. Scanziani et al ., 2002. The provision of drinking 2001. Fluidoterapia en Medicina de Rumiantes. In: water to veal calves for welfare purposes. J. Anim. Aplicaciones de Fluidos en Veterinaria, Rejas J., Sci., 80: 2362-2372. DOI:10.2527/2002.8092362x L.E. Fidalgo, A. Goicoa and J.R. González (Eds.), Grove-White, D., 1994. Fluid therapy the neonatal calf. Consulta de Difusión Veterinaria, Valencia, Spain, Practice, 16: 263-266. DOI: 10.1136/inpract.16.5.263 pp: 111-128. Halimi, M., S.I. Ahmed, M.T. Rai, 1991 . Studies on experimental ruminal acidosis in calves fed with Berchtold, J., 2009. Treatment of calf diarrhea: Intravenous ragi slurry: 5. Haematological changes. Mysore J. fluid therapy. Vet. Clin. North Am. Food Anim. Pract., Agric. Sci., 25: 236-238. 25: 73-99. DOI: 10.1016/j.cvfa.2008.10.001 Hughes, D., 2001. Fluid therapy with artificial Bjorling, D.E. and C.A. Rawlings, 1983. Relationship of colloids: Complications and controversies. Vet. intravenous administration of Ringer's lactate Anaesthesia Analgesia, 28: 111-118. solution to pulmonary edema in halothane- DOI: 10.1046/j.1467-2995.2001.00023.x anesthetized cats. Am. J. Vet. Res., 44: 1000-1006. Kasari, T.R. and J.M. Naylor, 1986. Further studies on Booth, A.J. and J.M. Naylor, 1987. Correction of metabolic the clinical features and clinic pathological findings acidosis in diarrheal calves by oral administration of of a syndrome of metabolic acidosis with minimal dehydration in neonatal calves. Canad. J. Vet. Res., electrolyte solutions with or without bicarbonate. J. 50: 502-508. Am. Vet. Med. Assoc., 191: 62-8. Lisboa, J.A.N., 2004. Fluidoterapia emruminantes: Uma Broaddus, V.C., J.P. Wiener-Kronish and N.C. Staub, abordagem prática. Proceedings of the Congresso 1990. Clearance of lung edema into the pleural Paulista de Medicina Veterinária, Conselho space of volume- loaded anesthetized sheep. J. Regional de Medicina Veterinária do Estado de São Applied. Physiol., 68: 2623-2630. Paulo, (ESP’ 04), Santos, Brasil, pp: 3-6.

130 José-Ramiro González-Montaña et al . / American Journal of Animal and Veterinary Sciences 2017, 12 (3): 111.131 DOI: 10.3844/ajavsp.2017.111.131

Lorenz, I., 2009. D-Lactic acidosis in calves. Vet. J., Sen, I., V. Altunok, M. Ok, A. Coskun and P.D. Constable, 179: 197-203. 2009. Efficacy of oral rehydration therapy solutions Lorenz, I., A. Gentile and W. Klee, 2005. Investigations containing sodium bicarbonate or sodium acetate of D-lactate metabolism and the clinical signs of D- for treatment of calves with naturally acquired lactataemia in calves. Vet. Record, 156: 412-415. diarrhea, moderate dehydration and strong ion DOI: 10.1136/vr.156.13.412 acidosis. J. Am. Vet. Med. Assoc., 234: 926-934. McClure, J.T., 2001. Oral fluid therapy for treatment of DOI: 10.2460/javma.234.7.926 neonatal diarrhea in calves. Vet. J., 162: 87-89. Silanikove, N., 1991. Effects of oral, intraperitoneal and DOI: 10.1053/tvjl.2001.0597 intrajugularrehydrations on water retention, rumen Meganck, V., G. Hoflack and G. Opsomer, 2014. volume, kidney function and thirst satiation in goats. Advances in prevention and therapy of neonatal Comparative Biochem. Physiol. Part A: Physiol., dairy calf diarrhea: A systematical review with 98: 253-258. emphasis on colostrum management and fluid Smith, G.W., 2009. Treatment of calf diarrhea: Oral fluid therapy. Acta Vet. Scandinavica, 56: 1-8. therapy. Vet. Clin. North Am. Food Anim. Pract., DOI: 10.1186/s13028-014-0075-x 25: 55-72. Müller, K.R., A. Gentile, W. Klee and P.D. Constable, Smith, G.W. and J. Berchtold, 2014. Fluid therapy in 2012. Importance of the effective strong ion difference calves. Vet. Clin. North Am. Food Anim. of an intravenous solution in the treatment of diarrheic Pract., 30: 409-427. calves with naturally acquired acidemia and strong ion DOI: 10.1016/j.cvfa.2014.04.002 (metabolic) acidosis. J. Vet. Internal Med., 26: Suzuki, K., T. Kato, G. Tsunoda, S. Iwabuchi and 674-683. DOI: 10.1111/j.1939-1676.2012.00917.x K. Asano et al ., 2002. Effect of intravenous infusion Naylor, J.M., 1999. Oral electrolyte therapy. Rev. Vet. of isotonic sodium bicarbonate solution on acidemic Clin. North Am. Food Anim. Pract., 15: 487-504. calves with diarrhea. J. Vet. Med. Sci., 64: 1173-1175. DOI: 10.1016/S0749-0720(15)30160-2 Trefz, F.M., A. Lorch, M. Feist, C. Sauter ‐Louis and Naylor, J.M., G.A. Zello and S. Abeysekara, 2006. I. Lorenz, 2012a. Metabolic acidosis in neonatal calf Advances in oral and intravenous fluid therapy of diarrhea-clinical findings and theoretical assessment of calves with gastrointestinal disease. Proceedings of a simple treatment protocol. J. Vet. Internal Med., 26: the 24th World Buiatrics Congress, (WBC’ 06), 162-170. DOI: 10.1111/j.1939-1676.2011.00848.x Nice, France, pp: 139-50. Trefz, F.M., A. Lorch, M. Feist, C. Sauter-Louis and Radostits, O.M., C.C. Gay, K.W. Hinchcliff and I. Lorenz, 2012b. Metabolic acidosis in neonatal calf P.D. Constable, 2007. Veterinary Medicine: A diarrhea-Clinical findings and theoretical assessment of Textbook of the Diseases of Cattle, Horses, Sheep, a simple treatment protocol. J. Vet. Internal Med., 26: Pigs and Goats. 10th Edn., WB Saunders, Philadelphia, 162-170. DOI: 10.1111/j.1939-1676.2011.00848.x USA, ISBN-10: 780702027772, pp: 2065. Tufani, N.A., D.M. Makhdoomi and A. Hafiz, 2013. Rainger, J. and A. Dart, 2006. Enteral fluid therapy in Rumen acidosis in small ruminants and its large animals. Australian Vet. J., 84: 447-451. therapeutic management. Iran. J. Applied Anim. DOI: 10.1111/j.1751-0813.2006.00072.x Sci., 3: 19-24. Rejas, L.J. and A.J.D. Alonso, 2008. Principios Walker, P.G., P.D. Constable, D.E. Morin, J.K. Drackley generales de fluidoterapia en rumiantes. RECVET- and J.H. Foreman et al ., 1998. A reliable, practical Revista Electrónica de Clín. Vet., 3: 1-15. and economical protocol for inducing diarrhea and Rejas, L.J., J.R.G. Montaña and F.P. Montaña, 2001. severe dehydration in the neonatal calf. Canad. J. Introducción a la Fluidoterapia. In: Aplicaciones de Vet. Res., 62: 205-213. Fluidosen Veterinaria, Rejas J., L.E. Fidalgo, A. Zurita, L., P. Smith and L. Zurich, 1987. Diarrea del Goicoa and J.R. González (Eds.), Consulta de terneroreciénnacido. Monografías de Med. Vet., Difusión Veterinaria, Valencia, Spain, pp: 53-64. 9: 1-16.

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