Updated and modified 2016

Abstract

Veterinarians have been advised that energy content of electrolytes should be one of the major determinants to decide which brand of electrolyte to recommend to farmers for treatment of calves with scours (Schouten 2005). The basis upon which veterinarians choose to use high energy electrolytes is important and requires reviewing.
The opportunity to provide calves with higher energy to reduce weight loss while recovering from scours includes

  • use of high energy electrolyte formulations
  • maintenance of feeding of milk to sick calves

The merit of high energy formulations (compared with isotonic electrolytes) also needs to compare recovery times, amount of electrolytes, ease of management, or the possible impact of secondary infections on mortality rates. Let alone the relative costs. An understanding of the underlying physiological responses of infections on the normal development and functioning of the various intestinal compartments is also required.

Milk feeding has been shown to maintain weight. But that this was achieved with a significant increase in labour either in management of milk volumes, or the provision of extra tube feeding with electrolytes (for rehydration). High energy (hypertonic) electrolytes may not be optimal for the fastest rate of re-hydration.

Energy alone does not determine the ‘ideal’ electrolyte.
This review is aimed to report on criteria defining differences between electrolytes.

Part One: High Energy Electrolytes
Part Two: Milk Feeding for Recovering Calves
Part Three: Nutrients for Recovering Calves

Part One

High Energy Electrolytes

In 2005, Schouten stated, “I suspect that increasing the dextrose/glucose (energy) level of the presently available commercial electrolyte formulations could be beneficial to the scouring calf.” From this statement and a data table on kcal levels, sodium, potassium and chloride levels, Schouten then concludes that “an informed choice of an appropriate product can be made.”
The addition of more energy to an electrolyte though, shifts the foundation of the electrolyte from an isotonic to a hypertonic solution and the differences and outcomes from these two solutions has not been resolved (Naylor 1999).

table-1

Table1: Electrolytes registered as veterinary medicines on the New Zealand market: Highlighting features other than Energy

Notes:

(1):    Claims are for faster rehydration. In fact stomach emptying is slower for hypertonic though the net effect
is for glucose responses to occur at similar rates.

(2):    Hypertonic is invariably higher energy (dextrose). Claims are based on higher energy,
but it seems to be at slower rates of rehydration. Hypertonic may also have higher levels of sodium.

Revive (Schouten)

Energy 338 kcal
Sodium 6.77 g/2L
Potassium 2.42 g/2L
Chloride 7.30 g/2l

Enervade (Pauling – pers comm)
Energy 186 kcal
Sodium 3.66 g/2L
Potassium 0.98 g/2L
Chloride 4.12 g/2L

(3):    Fermentation products (soluble fibre and prebiotics) i.e.to n-butyrate claim made to assist with further
fluid and sodium absorption in the colon.

(4):   G Glycine;  A Alanine.

Tonicity of the Solution

There is a lack of published literature studying the use of isotonic versus hypertonic solutions for the treatment of rehydration of naturally scouring calves (with infectious scours), particularly where there is simply the addition of more glucose to an isotonic electrolyte formulation.
Levy (1990) reports on the effects of iso-osmolar and hyperosmolar solutions in normal calves.

Individual authors sometimes comment that they recommend isotonic or high energy, but these opinions frequently appear to be without data to support their view. Or they fail to recognise the difference in dehydration associated with chemically induced diarrhoea, and that associated with secretory or mal-absorption infectious agents.

There has been a comprehensive review in infant electrolyte formulations examining the relative merits of isotonic versus hypotonic electrolytes (Hahn et al 2001). And the history of the development of rehydration solutions in infants (with cholera) in the developing countries in Asia suggests hypertonic solutions have defined limits (Ruxin 1994).

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Table 2: Definitions of Tonicity

This review suggests apart from kilocalories there are several other benchmarks that identify differences between products (see Table 3).

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Alternative Benchmarks for Electrolyte Formulation

Various other nutrients or supplements can also be considered as possible requirements of recovering calves. Naylor has reviewed many of the technical merits of various components and proposed many of the following components and their ratios.

table3

Stomach Emptying

The physiological response to hyperosmotic fluids in the stomach is to slow stomach emptying (Bell & Mostaghni 1975, Leon et al 1995). While this is desirable for food and nutrient intake, with a dehydrated calf this is not the primary objective. So just how severe is this slower emptying, and could it impact on calf recovery? The dehydrated calf is at risk with significant aspects of shock, acidosis, hypovolaemia, hypothermia developing, and at the tissue level with risk of hypo-perfusion, ischaemia and permeability damage with secondary infections.

Based on the different targets for fluid therapy in a scouring calf between re-hydration and the nutrient support, it is apparent that there can be a considerable difference in the rate of rehydration between hypo-/isotonic versus hypertonic fluids.

In studies in the horse stomach emptying is affected when fluids are at 628mOsm (cf 314mMol). The rate of stomach emptying of isotonic fluid may be further enhanced by bicarbonate content (Bell & Mostaghni, 1975). The emptying rate is also not affected much by lactose, but is affected by glucose. The neuro-transmitters involved are based in the duodenum (Bell & Mostaghni, 1975).

In studies in calves results from two glutamine formulated products, with one at 775mMol/L do not compare favourably with a solution at 415 mMol/L (Naylor et al 1997). It is possible that the differences are due to significant hypertonicity.

Hyperosmotic fluid

The potential for direct adverse effects of hyper-osmotic fluids on intestinal cells when the intestine is already under infectious insults is not routinely considered. The known effect of infections in the inflamed and ‘leaky’ intestinal wall on tissue ischaemia, the damage to the paracellular tight junctions may also be adversely affected by this hyper-osmotic environment. Cell cultures under such influence of hyper-osmotic fluids show cellular death (Verschoor et al). Milk mixed with electrolytes is considered to be hypertonic and cells in tissue culture die within 3 – 4 days. Isotonic fluid leads to maintenance of the barrier and survival; with glutamine associated with accelerated recovery.

The use of hypo-osmolar electrolytes in children have been examined in a meta-analysis of published reports (review Hahn et al 2001). Treatment of non-cholera scours in children is often in undernourished, and severely dehydrated infants. Recommendations by the WHO are now tending towards lower (hypo-osmolal < approx 270mEqui/litre) strength re-hydration solutions, with lower sodium (down to 60mMol/litre compared with 90mMol/litre). These hypotonic solutions prevent the inclusion of high amounts of glucose. It was also found that rice-starch based formulations are not as useful as glucose for non-cholera causes of dehydration. But, as rice is often the only carbohydrate that is available, its use should be promoted. Levels of glucose proposed for these hypotonic fluids include reductions of carbohydrates to approximately 75mMol/litre (40g dextrose in 2 litres is 111 mMol/litre i.e. 25% reduction in glucose content). Hence the WHO trend is to decrease dextrose, and not increase it (Bhan 2003).

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In studies in pigs (Argenzio et al, 1990) with artificially induced cryptosporidiosis, examination of the effects of isotonic, and hyperosmal solutions were compared in samples of infected and uninfected sections of the jejunum and ileum. It was found that hyperosmal solution adversely affected the absorption in the jejunum irrespective of it having been affected by infection. Isotonic fluid (without glucose) resulted in net absorption irrespective of the presence of infection. Only a moderate change to villus structure was observed. Glucose (maintaining isotonicity) increased the absorption in infected and uninfected jejunum by a factor of 4 in both groups (infected and uninfected).

However in the normal ileum net absorption of Na or water was glucose dependent. Infection reduced Na glucose dependent solute and water absorption, markedly reducing their absorption. In an infected ileum there is a loss of glucose dependent sodium absorption pathway. The ileum was also the area most severely affected by cryptosporidiosis with villi loss. Fluid and absorption is reduced by ½ to 2/3 respectively in the infected ileum compared with normal uninfected ileum.

 

Conclusion:

(particularly for cryptosporidiosis)

Recommendation on the type of electrolyte for the purpose of rehydration:

  • There is an assumption that fluid absorption is of prime concern in dehydrated animals.Data is not
    presented on the effect of glucose on absorption when in a hypertonic solution.
  •  Without further data, it may (or may not) be contra-indicated.
  •  A hyperosmolar solution adversely affects jejunum fluid (Na+ and water) absorption.
  • When cryptosporidiosis is present the glucose dependent Na+ absorption (and passive water absorption)
    will be affected in the lower intestine,
  • It is therefore reasonable to maintain maximum fluid absorption in the jejunum.
  • An isotonic solution containing glucose is recommended.
Self Regulation of Electrolyte Intake

It is reported (Ruxin 1994) that infants suffering from dehydration will self regulate the amount of isotonic electrolytes they require. The same principle for calves would ensure that calves achieve rapid rehydration. One suggestion is to offer both fresh water and also electrolytes separately to recovering calves (e.g. at night), allowing calves to choose.

Palatability of electrolyte solutions

Trials have shown that 2 – 3 gm/kg glucose in solutions is optimal for preferred acceptance by most normal calves. Marginal decrease in preference effects are reported in %ages of calves finding high glucose solutions palatable eg 80-150 g per 2 litres. (Goatcher & Church, 1970). Trials also report that sweetness is the preferred taste receptor that calves respond to (c.f. bitter for the goat, and salt in sheep). There are distinct taste responses associated with some alkalinizing agents, such as bitter for acetate (Martindale), and saline taste with citrate (Martindale). No taste responses are reported for sodium bicarbonate. There have not been any reports on the palatability of different solutions. Farmers report that they notice differences, with their preferred option being solutions for higher palatability for ease and convenience. Seaweed is reported to provide a more preferred option in sick calves (unpublished data).

Part Two: Milk Feeding for Recovering Calves

Milk Feeding

Garthwaite et al. (1994) examined options of treatment of calves with diarrhea primarily associated with cryptosporidiosis. This data has been used to promote high energy and maintenance of milk feeding. While mention is made of the benefits to weight gain while on milk, the effect on management of these sick calves is not simple when whole volume milk feeding is followed. Early milk (even when split into 3 feeds) led to increased tubing of electrolytes in the first 24 hours of re-hydration, with 4/14 calves refusing electrolytes and requiring tubing of electrolytes. And in the first 2 days this strategy also led to milk rejection as well (8/14 calves).

This applied only to calves offered full complements of milk volume. By comparison a smaller volume of milk (25% of their daily requirement) separate from electrolytes (Group B) did not lead to rejection of any re-hydration fluids (Garthwaite et al 1994).

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Treatments A and B were given in two equal feedings at 8 AM and 3 PM;

Ttreatment C was given in three equal feedings at 8 AM, 3 PM, and 8 PM. Milk – milk replacer. ORS

Fig 1: The average body weights of calves during therapy for diarrhea. Day 1 weights were taken before starting therapy (Garthwaite et al 1994).

Heath et al (1989) studied the effects of tube feeding of milk, offering full milk diets and withholding milk feeds for a period of 10 days. Signs of depression were associated with the benefits obtained with forced tube feeding if the goal of weight gains were to be pursued. Ultimately the calf was the best indicator when the gut was in a state of freedom of discomfort. The relationship of gut discomfort and gastric emptying is discussed further by Bell and Mostagni (1983).

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In summary for ease of management, milk should be offered in small volumes to avoid the additional labour inputs of tubing with electrolytes. Irrespective of which strategy is used, the volume of milk offered in the first few days of recovery does need to be managed with individual calf-feeding indicated. In a 1999 review by Naylor, smaller volumes of milk are recommended for calves in recovery.

The effect of diarrhea on the energy digestibility of milk has been calculated as being reduced by 31% (Youanes & Herdt, 1987). The loss of digestibility was related mainly to loss of fat absorption.

Fat digestion is adversely affected because of reduced chylomicron formation. There was also a lack of rise in blood glucose levels after lactose ingestion compared with normal calves. The loss of carbohydrate absorption is reflected by rises of lactate in faeces. This suggests that this loss of digestibility of lactose in the small intestine from reduced lactase activity as a result of infection (esp. rotavirus and also cryptosporidiosis) enables fermentable carbohydrate to reach the large intestine.

Hence in the early stages of an infection, milk may not provide the assumed energy as in a normal calf. Any theoretical effort to replace energy to levels of that of a normal calf may be misleading, as being unobtainable, or impracticable.

Timing and management of milk re-introduction

Electrolytes are used to re-hydrate, and correct acid-base imbalances. For this reason calves should not have milk withheld for any reason other than the need to re-hydrate with fluids.

And as faecal consistency is considered not to be a measure of recovery from scours (Brooks et al 1966) it is therefore appropriate not to wait for faecal consistency to return to normal before offering milk feeds.

For this reason so long as a calf is not dehydrated and it is prepared to drink milk, milk is the preferred option for energy. The lateral (cf dorsoventral angle – vertical fold) tenting of the neck skin and observing the return to normal position is the preferred method of testing for dehydration.

However, force feeding of milk is inappropriate and leads to extended periods of discomfort and lengthy periods of ongoing tubing (refer Pauling 2005). So voluntary milk is preferred, though timing and amounts offered require to be practical.

The Amounts of Milk

In the acutely affected clinically affected calf, normal volumes of milk (Garthwaite et al, 1994) and even when given at 50% of normal volume (Heath et al, 1989), there can be loss of voluntary intake.

On the other hand, any calf which is fasted (i.e food withheld with an appetite) has been shown to have an appetite which is 50% greater than maintenance, (Mylrea, 1966), and it takes approx. 3 – 4 days to rebalance intake against requirements. Trials have also confirmed that feeding milk can lead to loss of appetite which may even be an acceptable physiological response to overfeeding (Mylrea 1966). Cafeteria systems may encourage strong drinkers (compared with slow drinkers) to take higher volumes of milk.

Summary
  • Maintenance of fluid hydration as well as feeding can be achieved with alternating fluids and milk once a calf is successfully re-hydrated.
  • The volumes of milk need to be lower than normal full milk volumes.

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Part Three:Nutrients for Recovering Calves

Nutrients for Recovering Calves
Technical Aspects of Electrolyte Formulation

Cabohydrate Form: Food digestion of reducing substances (carbohydrates such as glucose requiring the enzyme lactase for activity) occurs predominantly in the upper small intestine. The majority of solutes and passive water absorption occurs in the lower small intestine. Absorption of fluids is glucose and/or amino-acid dependant. When infant diarrhoea cereals (rice starch) are added to electrolytes there is a reduction of faecal volumes from 18 – 36% (non-cholera v cholera origin diarrhoeas). This additional absorption occurs in the colon based on fermentation of fermentable carbohydrates to n-butyrate.

Pathological changes associated with some infections may lead to different requirements in an electrolyte formulation. Rotavirus is especially affecting the upper small intestine and responsible for a mal-adsorption diarrhea, whereas cryptosporidiosis affects the lower small intestine and is a secretory and mal-absorptive diarrhea. In infants, the ideal electrolyte formulations are not found to be equivalent when measuring outcomes for secretory (mainly cholera) compared with mal-adsorptive (rotavirus and cryptosporidial) diarrhoeas (Bahn 2003).

This should serve as an indication that calf scours with a secretory component (i.e. some mixed infections – and especially those with cryptosporidiosis), may not respond equivalently to different electrolyte formulations compared to malabsorptive causes of diarrhoea (rotavirus). Rotavirus has also been shown to produce secretory stimulating enterotoxin (Ball et al 1996). There are greater effects on acid-base balances for the higher small intestinal infections with rotavirus, compared with lower small intestinal infections with cryptosporidiosis where dehydration from mal-absorption dominates the clinical signs.

Energy of electrolytes has been indicated in terms of kcal, and typically this is derived from the addition of dextrose (glucose). This simply defines one aspect of energy without regard to specific energy requirements of tissue type, and irrespective of tissues specifically affected by infectious agents. Frequently amino-acids are added as an alternative source for intestinal Na+ energy dependent activity; though even these alternative amino-acid pathways may be affected in cryptosporidiosis (Topouchian et al 2001).

Sodium concentration:

Recent trial work suggests that there are major effects on the rate of influx v efflux of water, sodium, and glucose by changes in the mMol concentration of sodium. This work (rat model normal intestine) suggests that minor ingredients can play a significant role in rates of passage of each component and that low sodium (60mMol/litre) is preferable to 90mMol/litre. Sodium concentration interacts to have major effects on this rate of influx v efflux of glucose, and water.  Particular amino-acids, specifically arginine at very low concentrations can provide a significant enhancement in rates of influx over efflux and that this is also sensitive to sodium concentrations, with lower levels of sodium having higher ratios of influx/efflux (Wapnir et al, 1997).

Amino Acids

Alanine may compete with glucose for absorption enzymes. Therefore, when/or if alanine is absorbed preferentially to glucose this exchange may be disadvantageous, because the energy content is only 50% compared with glucose, and there is also a greater effect on osmolarity (Wapnir 2000). In one report, hypertonic ORS containing alanine reduced stool output by 42% although the episode of diarrhoea remained unchanged. This trial concluded that the ratio of alanine to glucose must be balanced (q Wapnir 2000).

In an experimental model (Kozar et al. 2004), the effects of alanine, glucose and glutamine were compared for their potential to protect the cytoskeleton and intestinal permeability. Glucose and glutamine both maintained ATP energy levels whereas alanine levels fell by 50%. Glutamine further maintained epithelial barrier cell function compared to glucose (Kozar et al 2004). In human infants with acute diarrhoea, glutamine taken orally (though not in an electrolyte formulation) had shorter and less severe diarrhoea. These infants also had less complicating infections of the urinary and respiratory tracts (Yalcin et al. 2004). This benefit has not been confirmed with trials in calves (Naylor et al, 1997). These trials were carried out with hypertonic electrolyte solutions which also did not have any bicarbonate as an alkalizing agent. The very high tonicity solution had more complications (n.s) in recovery than the two lower tonicity solutions (both still hypertonic.)

Examples of energy pathways dependent on specific sources include glutamine as the essential energy for lymphocytes and enterocytes. In studies in mice, arginine in specific low concentration has a benefit in improving rate of maturation of the enterocytes damaged by cryptosporidial infections

And in sections of rat intestine exposed to different amino-acids in isotonic (or hypotonic) electrolytes – alanyl-glutamine has demonstrated superior activity to glutamine in rat intestine in both electrolyte and water absorption (cholera toxin model) (Lima et al 2002). Glutamine is not stable to acid conditions (normal stomach conditions are typically pH 2 – 3), and currently no products contain the more expensive bipeptide alanyl-glutamine. Alanyl-glutamine may also have some indirect benefits as a precursor of the anti-oxidant glutathione (see below).

Glycine is reported to provide an enhanced absorption rate over the equivalent osmalarity glutamine solution.

The origin of this benefit may be the independent neutral amino-acid energy channel to glucose dependent pathways providing active sodium and passive water absorption.

In experimental animals comparing solutions 285 – 304mMol/L (Lima et al 2002), alanyl-glutamine provides an improved rate of water and sodium absorption over glutamine.

Fibre

It is claimed that by the addition of fibre to a diet, there is a beneficial effect by maintaining intestinal barrier function and preventing bacterial translocation even in the absence of oral nutrients (Spaeth et al 1990). All fibre is not equal however, with citrus pectin failing to providing benefits. However Kaolin and cellulose fibre does provide benefit. The effect of fibre are seen with changes to intestinal morphology, mucosal mass, and gut bacterial ecology.   Some soluble dietary fibre even though fermentable remains only partially fermentable (Fibersol-2), and has reported to also produce beneficial intestinal morphological changes. There are also significant affects on stomach emptying with fibres having a high viscosity. To maintain high rates of stomach emptying it is important that soluble dietary fibres do not affect the viscosity of the electrolyte solution. Fortunately there are complex carbohydrates that meet this objective. Soluble dietary fibres such as resistant maltodextrins do not adversely affect viscosity and maintain stomach emptying.

The role of the large intestine

Studies have shown that 60% of a standard electrolyte volume is excreted from failure of absorption (Naylor q. Guards & Tennant, 1986). The earlier separation of absorption between the small intestine and large intestine was shown to be false (Powell, q  Nafatalin 1990) with fluid in a normal large intestine absorbed through the activity of butyrate driven sodium absorption ‘with colonic crypts being the final arbiter of stool fluidity’

It has been proposed that non-digestible carbohydrates are the origins of butyrate, being fermented by saccharolytic bacteria present in the large intestine. Not all complex carbohydrates deliver the same proportions of n-butyrate (see Ramakrishna el al 2000).

This includes

  1. Resistant amylase starches (Ramakrishna et al 2000). The addition of resistant starch produced a significantly (p = 0.001) reduced period of diarrhoea compared with standard ORT for cholera. This was based on fermentable starch being reduced by 50% in transit through the large intestine, or the equivalent of 25g starch fermented per 2 litre dose of an isotonic electrolyte (327 mMol/L.).
  2. Resistant maltodextrins (e.g. Fibersol-2® – present in Enervade® and Kryptade®) See prebiotic carbohydrates below. Soluble dietary fibres differ in their effect on the recovery of damaged villus structure
  3. It is also possible that undigested simple monosaccharides and disaccharides (lactose) overflowing undigested from the small intestine will also be fermented and potentially provide similar n-butyrate benefits.

The different carbohydrates (e.g. lactose versus starches) delivered to the large intestine ferment producing different ratios of SCFAs (short chain fatty acids), and therefore differ in n-butyrate production.

The colon is the site of significant sodium and water absorption normally which is dependant on energy from n-butyrate specifically. This is potentially an important target for enhanced fluid and electrolyte absorption in dehydrated calves.

Prebiotic carbohydrates

The large intestinal cells are dependant on Short Chain Fatty Acids (SCFAs) derived from the bacterial fermentation either from the overflow of undigested carbohydrates (e.g lactose) or non-digestible but fermentable more complex carbohydrates (prebiotic carbohydrates, pectins and rice etc). This enables the normal fluid absorption to also occur from the large intestine, and the generation of higher levels of vitamins (mainly B vitamins) from bacterial fermentation. The bacterial population of the large intestine associated with diarrhoea washout frequently is significantly lower with luminal bacteria significantly more severely affected than mucosal populations. Repopulating the ecological balance can be achieved with certain (stomach-acid resistant) probiotic strains, (Allen et al 2003). Probiotics act in concert with the immune system to provide a wide spectrum of activity. Prebiotics such as fructooligosaccharides act through the promotion of the natural gut flora’s beneficial bacteria (Oli et al 1998). The presence of carbohydrates with specific stereotypic bonding induces multiplication of different populations of saccharolytic bacteria in the large bowel, and this occurs in the recovering animal with diarrhoea (Oli et al 1998).

Probiotics and recovery from rotavirus & cryptosporidiosis

Allen et al 2003 has reviewed published papers on probiotics and human infant diarrhoeas. They examine aetiology and probiotic strains used. All results have been subject to review before being admitted for analysis. Their conclusion is that some probiotics do provide a useful adjunct to some diarrhoeas, with certain provisos also reported.

A report by Casas & Dobrogosz (2000) examines and report on one probiotic strain Lactobacillus reuteri . This strain is also included in the report by Timmerman et al.(2002) with benefits to calf general health following a mix of probiotic strains.

The conclusions from these reports is summarized

  • Strain specificity to the host species may be important to obtain clinical benefits.
  • Some strains are only suitable as live organisms and therefore subject to issues of storage.
  • Acid resistance of these strains to enable passage to the intestine is important. Some human strains marketed for their probiotic benefits fail to pass effectively in sufficient numbers to provide any benefit (UK data- Consumer)
  • Some strains of organisms researched and developed exhibit a range of effects that differ between strains. L reuteri for example has some antibacterial factors (reuterin).
  • Some may provide a dominant and exert an exclusivity which decreases the pro-inflammatory effects of other natural flora strains (Christiansen et al, 2002).
  • Health benefits occur outside the immediate gut environment (Timmerman et al, 2005).
Seaweed and fibres

Nutritional components included in some electrolytes include seaweeds. They are a source of natural dietary fibre. Alginates found in seaweed also stimulate mucus cells to release mucin. Other dietary fibres such as pectin, or gum Arabic do not have this direct effect (Plaisancie 2006). This benefit is therefore different from that achieved by bacterial fermentation and the production of butyrate for cellular energy. Seaweeds are also high in certain aminoacids which are also important constituents of mucin (e.g. threonine), and they also potentially aid palatability (pers. comm.)

 Other supplement targets

 

 Colostrum and milk

Milk is considered the ideal nutritional source for the immature digestive system to meet a calf’s needs. Quite separate from its nutritional benefits, milk contains features which may aid the recovery of the damage of the intestine and the recovery of normal function. This includes some components which stimulates the mucus activity from goblet cells (metabolism and secretion) with mucus acting as a local barrier to pathogenic invasion. It may reduce the attachment of various pathogens E coli to the enterocytes. Or it may reduce rotavirus replication (Juntenen at al 2001).

The components in milk affecting goblet cells include growth factors (EGF, TGF-β, and KGF) found in milk (and colostrum), and parts of the casein fraction specifically β-casomorphin. (Plaisancie 2006). Milk may also act through its effect on bacterial populations and their effect on the innate and acquired immune system.  EGF and its analogs are targeted for development as they have been shown to improve recovery by reducing inflammatory processes.

Management of infections
Anti-oxidants

There is a correlation between each of the following factors: (in animal models) (refer Doig et al, 1998)

Mucosal ischaemia (loss of blood flow)

Extent of the pathological injury to the mucosa

Severity of intestinal permeability

Severity of bacterial translocation

In order to advance treatment of the recovery of calves from intestinal infections including re-hydration with electrolytes, nutritional support including the use of targeted energy sources may improve treatment outcomes. These targeted sources may include supplements of anti-oxidants to reduce the increase in intestinal permeability (De Souza & Greene 2005). These anti-oxidants may act to limit cytokine activation, and reduce the central behavioural response to abdominal discomfort (see below) – leading to loss of appetite.

These may be further aided by

    1. Limiting further mucosal injury (by avoiding hypertonic fluids),
    2. Improving the rate of fluid re-hydration by minimizing fluid losses at the membrane (alanyl-glutamine).
      Alanyl-glutamine is a precursor of glutathione an important anti-oxidant for the intestinal and hepatic
      cells.
    3. Recognizing that the early severe insult from infections in spite of the above will in some calves lead
      to intestinal permeability changes, and
    4. Bacterial translocation will then become important. Recognizing the clinical signs of septicaemia
      becomes an important challenge separate from recognition of signs of de-hydration, hypothermia, and
      acidosis,
    5. Early re-hydration may be one of the most important ways to limit severe outcomes. (Early rehydration should be the fastest possible rehydration).
Antibiotics for recovery

Mixed infections in modeled infections of cryptosporidiosis and E coli show that mortality is highest in hypogammaglobulinaemic lambs challenged sequentially with both infections rather than one alone (La Ragione et al 2006). This is consistent with many reports that mixed infections have significantly more severe outcomes in mortality rates (Tzipori et al, 1983).

Weak calves not prepared to suckle or stand may also be at risk of secondary infections (Lofstedt 1999 ), which will contribute to mortality statistics especially if calves are also low gamma-globulinaemic. Differentiating severely acidotic calves, from calves at risk of secondary infections can be based on the presence of sternal recumbency/weakness, and a markedly reduced suckling reflexes. For a review see Lofstedt (1999).   Septicaemia is more severe is calves less than 5 days of age. Acidosis tends to be more severe in scouring calves over 8 days of age.

Rectal temperature is a useful guide to differentiate depressed acidotic calves from depressed septicaemic calves. A lower rectal temperature is more likely to be associated with depression and acidosis than associated with secondary infections (Naylor et al 1997). Depressed infected calves were more likely to be severely acidotic (Naylor et al 1997). And infected calves also grow at a slower rate than non-infected calves (Naylor et al 1997). Energy supplementation will not reduce mortality of these weak moribund calves. Nor will more energy treat these clinical infections or lead to recovery of growth rate. That is, high tonicity (i.e. high energy) in an electrolyte as reported by Naylor 1997 may result in higher mortality.

What seems to be indicated is a

  • bicarbonate isotonic electrolyte
  • aggressive attention to volume restoration
  • possibly by stomach tubing small volumes more frequently (to avoid abomasal overload into the rumen and secondary acidosis)

using pain relief (i.e NSAIDs – Meloxicam) to improve demeanor, and also suckling reflexes ( Todd et al 2007)

Antibiotics will be required. Though they may only assist some of calves. There is some clinical tests showing elevated urea may be indicate a poorer prognosis.  Antibiotic treatment of septicaemic calves (associated with diarrhoea) saved 60% of these calves when treated aggressively with both iv fluids, and also an antibiotic protocol (Thomas et al 2004). Superior activity was reported with the use of cefquinome with a once a day injection compared with gentamycin three times daily.

Targeting the neurotransmitter –tachykinin pathways

Calves with significant gastric discomfort associated with some infections may lose their appetite and the risk of prolonged milk deprivation exists if this appetite is not corrected.

The pathway for this activity is considered to be cytokine mediated.

Earlier return of normal gut function can now be achieved with Kryptade electrolyte for diarrhoea associated with cryptosporidiosis. Beta-cyclodextrin knocks out the oocysts, and it has been proposed that this reduces the replication cycle in the intestinal wall. It would be reasonable to assume that this reduces inflammatory pathways and allows return to appetite as a result of less discomfort (Hernandez et al 2007).

Refer to the review on probiotics in the treatment of rotavirus (Allen et al, 2003) to improve the rate of recovery.

Pain reduction can also occur by symptomatic treatment with Meloxicam (Todd et al 2007).   Substance P, one of the tachykinin gastro-intestinal neurotransmitters, is correlated with the signs of pain with cryptosporidiosis (Robinson et al 2003). Drugs are now available to directly medicate for the signs of discomfort by interfering with Substance P (a.i. maropitant – Pfizer). In vitro treatment of samples obtained from infected macaques with the Substance P receptor antagonist (aprepitant – Merck) completely reversed the increase in basal ion secretion and corrected the glucose malabsorption associated with cryptosporidiosis (Hernandez et al 2007).

Conclusions:
  • Early treatment will limit severity of ischaemia, permeability and secondary infections.
  • Isotonic fluids will have benefits over hypertonic solutions (high energy) for rehydration.
  • Use more complex nutritionally supplemented ORTs. Target the nutrient supplement for improved
    performance.
  • Be aware of the risks of secondary infections and the signs indicating their presence.

Treat calves not responding as rapidly as their peers with antibiotics.

  • Start milk feeding as soon as a calf is re-hydrated and there has been a return of appetite. Test
    calves gently to see if they will take milk.
  • Offer milk in smaller volumes as calves return to appetite approx. 25% of normal volumes – small
    volumes more frequently.
  • Alternate fluids and milk feeds until fully recovered.
  • Offer isotonic electrolytes ad lib once a calf is bright and rehydrated. They will self-select the
    volume required. Ensure fresh, clean water is available at all times.
  • For individual calf treatment for earlier recovery consider the newer drug groups of meloxicam or
    Substance P antagonists.

Note: Bruce Pauling is Managing Director for Professional Veterinary Distributors Ltd.
Enervade and Kryptade are trade names of Professional Veterinary Distributors Ltd. Fibersol-2 is a trade name of Matsutani Chemical Industry Co.
ENERVADE and KRYPTADE are registered pursuant to the ACVM Act 1997, A9610 and A9621   See www.foodsafety.org.nz for registration conditions

 

© Professional Veterinary Distributors Ltd., September 2007

References:

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First published
Pauling B. (2007) Energy & nutrient supplementation of calves with diarrhoea. Dairy Vets of NZVA. Newsletter Vol 25 (1)
Professional Veterinary Distributors Ltd. Titirangi. Auckland

Energy & nutrient supplementation of calves with diarrhoea