New Trends in the Treatment of Hypokalemia in Cows

Abstract

Of all the mineral cations, potassium (K) is an essential nutrient for animals, and it is the third most common mineral in the body. Potassium has a role in maintaining normal cardiac and renal function, neuronal transmission, muscular contraction, and acid-base balance. The main thrust of this chapter is to review the physiology, pathology, pharmacology, occurrence, etiology, clinical signs of hypokalemia and its diagnostic and therapeutic approach in cows. The ambulatory measures to minimize the agony and preventive strategies to reduce the incidence of hypokalemia were discussed. Beside the potassium salt therapy, the inclusion of Taurine in the therapeutic regime was rational and to be appreciated.

1. Introduction

The main cation in intracellular fluid is potassium. It is essential for controlling osmotic pressure, maintaining acid-base balance, transmitting nerve impulses, contracting muscles, especially the heart muscle, and performing several cell membrane tasks as a component of the sodium-potassium pump. Additionally, necessary for glycogenesis, potassium facilitates the conversion of adenosine triphosphate to pyruvic acid by transferring phosphate. Potassium is also essential for many fundamental cellular enzymatic processes, including protein synthesis, amino acid absorption, and glucose metabolism [1, 2].

Alterations in the equilibrium between intracellular and extracellular potassium can result in hyperkalemia or hypokalemia despite the unaltered total body potassium content. Internal potassium balance is most typically impacted by disturbances in the acid-base balance [3, 4, 5]. The transport of hydrogen ions into the cells counteracts the elevated concentration of hydrogen ions in the extracellular fluid that results from metabolic acidosis. To maintain electro-neutrality, potassium ions must exit the intracellular compartment, which raises the concentration of potassium in plasma. Similar to this, potassium may be redistributed from the extracellular to the intracellular compartment in metabolic alkalosis, leading to hypokalemia [3, 5]. Maintaining the resting membrane potential depends on the ratio of extracellular to intracellular potassium [1]. Recently, isoflupredone acetate was administered intramuscularly to lactating dairy cows in conjunction with ketosis to cause a state of severe muscle weakness, recumbency, and hypokalemia [6]. Theileriosis, recumbency, traumatic reticulo-peritonitis, excessive use of isoflupredone acetate in the treatment of ketosis, excessive bicarbonate administration in the treatment of ruminal lactic acidosis, ileus, botulism, and abomasal displacement were the main causes of hypokalemia [7]. The parenteral administration of dextrose or insulin may result in hypokalemia [8].

Animal cells contain potassium as the primary cation (positive ion), whereas sodium is the primary cation outside of animal cells. The membrane potential, which is the differential in electric potential between the inside and exterior of cells, is caused by the concentration differences of these charged particles. Ion pumps in the cell membrane regulate the potassium and sodium levels in the membrane. An action potential, or “spike” of electrical discharge, can be produced by the cell thanks to the potential in the cell membrane that potassium and sodium ions cause. For bodily processes including neurotransmission, muscle contraction, and heart function, cells must be able to generate electrical discharge. In addition, potassium is a necessary mineral for controlling blood pressure, acidity levels, and water balance [9].

It is well knowledge that potassium homeostasis and acid-base balance are related. Generally speaking, hypokalaemia (lower blood pH) is linked to lower plasma potassium concentration, whereas acidaemia (lower blood pH) is linked to higher plasma potassium concentration (hyperkalaemia) [10].

The objective of this chapter is to describe the pathophysiology, diagnosis and therapy through intravenous and/or oral route (powder and bolus) of potassium formulations. A further aim is to demonstrate the role of taurine in potassium homeostasis and measures to prevent hypokalemia in the cows.

1.1 Absorption and excretion

In the rat, Rajendran and Geoffrey [11] noted that despite the colon’s great potential for K+ secretion and absorption, its function in preserving K+ homeostasis is frequently disregarded. For a long time, it was believed that the main processes for K+ absorption in the colons of humans and animals were solvent drag and/or passive diffusion. Nonetheless, it is now evident that electro neutral K+ absorption in the animal colon is mediated by apical H+, K+-ATPase, in conjunction with basolateral K+-Cl− co-transport and/or K+ and Cl− channels functioning in tandem. The rat colon’s K+ absorption is indicative of both ouabain-sensitive and -insensitive apical H+, K+-ATPase activities. H+, K+-ATPases that are ouabain-sensitive and -insensitive found in crypt cells and surface cells, respectively. Colonic H+, K+-ATPase is made up of the subunits α (HKCα) and β (HKCβ), which when co-expressed in HEK293 cells that show ouabain-insensitive H+, K+-ATPase activity; in Xenopus oocytes. On the other hand, HKCα co-expressed with the gastric β-subunit shows ouabain sensitive H+, K+-ATPase activity. Apical H+, K+-ATPase activity, HKCα specific mRNA and protein expression, and K+ absorption are all improved by aldosterone. Conversely, apical K+ channels that work in tandem with the baso-lateral Na+-K+-2Cl− co-transporter induce active K+ secretion [11].

1.2 Causes of hypokalemia

1.2.1 Lactation stress

In the lactating cow, 75% of potassium elimination is via the urine, 13% in feces and 12% in the milk Table 1 [12]. In the hypokalemic cow, this may be concentrated in the first 45 days of lactation [13] or 60 days [6]. In general, the younger cow seems to be more at risk than older cows [14].

Serial number	Disorders	Causes	References
1	Physiological or metabolic	Lactational stress, summer stress	[6, 12, 13, 14, 15, 16]
2	Pathological	Left displaced abomasum, right displaced abomasum, abomasal volvulus, abomasal impaction, clinical mastitis, dystocia, retained placenta, and hepatic lipidosis,; prolonge anorexia, diarrohea	[7, 17, 18, 19, 20]
3	Induced	Frequent administration of cortisones with minerlocoticoid activity, calcium, mifex, calcium, borogluconate, dextrose, insulin, bicarbonates	[7, 8]

Table 1.

Showing causes of hypokalemia.

Large milk producers have lower mean serum potassium concentrations than small milk producers [15]. These high milk producers are also more likely to experience hypokalemia during the early stages of lactation due to increased potassium loss in milk and a noticeable negative energy balance [16].

1.2.2 Summer stress

Nutritionists discovered a link between heat stress and potassium loss, with cows that stayed in the shade losing five times less potassium than the group of cows that had no shade. Heat-stressed cows also ate less during the daytime, thus also reducing their potassium intake [21].

1.2.3 Frequent administration calcium magnesium phosphite

The authors observed that the infusion of Calcium 1.86% w/v (as Calcium Gluconate I.P.) in (Miphocal or Mifex brands), Anhydrous Dextrose I.P. 20% w/v and Magnesium Hypophosphite 5.0% w/v were indiscriminately administered by para veterinarians to cure downers to more than 25 cows, resulted in 22.5–3 mM of potassium and 2 mM of calcium per liter respectively.

Tamer and Chandra Deep [17] report the development of hypocalcemia and hyperkalemia attributable to magnesium infusion in a pre-eclamptic human patient (Table 1).

1.2.4 Pathology

A nursing dairy cow with left or right displaced abomasum, abomasal volvulus, abomasal impaction, clinical mastitis, dystocia, retained placenta, and hepatic lipidosis is likely to have hypokalemia, which is defined as serum or plasma potassium concentration < 3.9 mEq/L [17, 18, 19]. In cows, hypokalemia is frequently seen as a result of prolonged anorexia and other main gastrointestinal and urinary system disorders [20, 22].

1.2.5 Clinical signs of hypokalemia

Following their initial period of rigidity and disinclination to move, the majority of animals exhibit the following clinical symptoms:

1. Depression characterized by a lack of resistance to manipulation and generalized weakness.

2. Diminished muscle tone in different parts of the body from tail to tongue.

3. Bradycardia.

4. An unusual neck alignment (an S-shaped neck) (Figure 1).

5. Recumbency.

6. Generalized intestinal and stomach stasis, resulting in minimal defecation and ruminal atony.

Figure 1.

Showing hypokalemic cow (photo courtesy—Dr. Manjunath, Mangalore).

2. Diagnosis of hypokalemia

Confirming a hypokalemia diagnosis requires serum biochemical investigation. A prompt and precise diagnosis is necessary to save the recumbent cowl, determine the prognosis, and choose the dosage and method of potassium chloride administration. Serum potassium levels below 2.5 mM/L indicate severe hypokalemia, which will cause most cows to be less alert, recumbent. Moderate hypokalemia is indicated by a serum potassium content of 2.5–3.5 mM/L. Some of these cows also are recumbent, and reduced gut motility. Serum potassium concentrations can be measured, but measurements of sodium, chloride, calcium, and phosphorus concentrations as well as serum CK and AST activity may be y useful in deciding the drug therapy. Aciduria can occur when the potassium concentration in the urine drops [13].

2.1 Strides in the estimation of serum and blood potassium

2.1.1 Potentiometric direct measurement

Since the development of commercially available electrodes for sodium and potassium ions and electrodes selective for univalent cations over a decade ago, the determination of sodium and potassium in biological fluids has been the subject of substantial research (Table 2). This electrode, a glass electrode that is sodium ion selective, and a reference electrode are all included in a small-volume cell. Since a potassium ion specific electrode is the gold standard for clinical potassium measurements and can be miniaturized for small blood volumes, can be used to measure potassium in the blood sample. Anantibiotic, valinomycin, selectively binds potassium and it, is pumped into a membrane inside the ion specific electrode. When valinomycin comes in contact with a potassium-containing solution, potassium binds to it, creating a potential difference relative to a reference and building up a charge. Thus, by measuring this voltage, one would be able to ascertain the potassium concentration in a sample solution. Potassium is relatively low in concentration, thus amplification of the signal will be necessary to successfully detect it at clinically relevant concentration [23].

Serial number	Design	Principle	References
1	Potentiometric direct measurement	Valinomycin, selectively binds potassium and it, is pumped into a membrane inside the ion specific electrode. When valinomycin comes in contact with a potassium-containing solution, potassium binds to it, creating a potential difference relative to a reference and building up a charge	[23]
2	Turbid-metric	Potassium is precipitated using sodium tetraphenylborate. The turbidity is measured with spectrophotometer	[24]
3	Smartphone-enabled quantification of potassium in the blood plasma	Turbid metric principle	[25]
4	Equipment-free detection of K+	Microfluidic paper-based analytical devices	[26]

Table 2.

Showing various diagnostic techniques’.

2.1.2 Rapid quantitative turbid-metric spot test analysis of potassium in the blood serum

The market offers a quantitative turbid metric spot test method for determining potassium concentration in the blood serum. Potassium is precipitated using sodium tetraphenylborate, a traditional analytical reagent, in basic media. Using a micro-turbid metric cell created for this purpose, the turbidity is measured directly in this solution without any additional dilution. The buffer and the solution of the analytical reagent were combined with the blood serum. At 700 nm, the turbidity is measured with a spectrophotometer in the working concentration range, the calibration curve is a straight line with a correlation coefficient of 0.9998. The analytical outcomes achieved using this technique is in contrast those obtained using an electrode that selectively use ionized potassium ions [24].

2.1.3 Smartphone-enabled quantification of potassium in the blood plasma

A novel technique for measuring the K+ concentration, [K+], in the blood plasma using an optical attachment that was specially made for a smartphone. Turbidity is the basis for the development of the approach. Measurement of blood plasma solutions using sodium tetraphenylborate, a recognized reagent that cause potassium to precipitate. A unique image-processing technique is used to analyze the photo taken with a smartphone camera. This allows the data to be converted from RGB to HSV color space and the mean value of the light-intensity component (V) to be calculated. Photographs of blood plasma with varying K+ concentrations analyzed show a relationship between V and [K+]. The outcome with those obtained using an ion-selective electrode device and atomic absorption spectroscopy, the method’s correctness is verified. When employing the treated blood plasma calibration, the method’s accuracy was within ±0.18 mM and precision was within ±0.27 mM in the [K+] range of 1.5–7.5 mM. Good correlation was observed between the data collected by the smartphone approach and the ion-selective electrode device in spike test conducted on a fresh blood plasma. The method’s inexpensive cost and smartphone integration make it advantageous for measuring [K+] on demand and in remote locations with restricted hospital access [25].

2.1.4 Equipment-free K+ detection on microfluidic paper-based analytical devices using ionic dye in ion-selective capillary sensor

A microfluidic paper-based analytical device (μPAD) is linked to an ion-selective capillary sensor to enable remote potassium ion (K+) analysis. The concept is based on two sequential steps: first, the analyte ion is selectively substituted with an ionic dye, and this dye is subsequently detected in a distance-based paper readout. To perform the first step, the capillary sensor holds the polyvinyl chloride membrane film layer in place after it has been plasticized with dioctylsebacate. This layer has potassium ionophorevalinomycin on its inner wall, a lipophilic cation-exchanger, and the ionic indicator Thioflavin T (ThT) dye. When the sample is introduced into the film membrane, K+ in the aqueous sample solution is quantitatively removed, and ThT is substituted. This solution was placed onto the inlet region of a μPAD to flow the ThT down a channel formed by wax printing, resulting in the electrostatic binding of ThT to the cellulose carboxylic groups, converting the ion exchange signal into a distance-based analysis. The starting K+ concentration This solution was applied to the μPAD’s intake region, allowing ThT to flow through a channel created by wax printing. ThT then electrostatically bound to the carboxylic groups in cellulose, transforming the ion exchange signal into a distance-based analysis. The initial K+ concentration determines the quantity of ThT in the aqueous solution after ion-exchange; hence, the sample K+ concentration is reflected in the distance of the ThT-colored area. An identifiable response in the K+ concentration range of 1–6 mM was generated by the ion exchange process when it was operated in what is referred to as a “exhaustive sensing mode,” which is not achievable with the traditional optode sensing mode. Because there are no hydrogen ions present, the equilibrium competition of the capillary sensor is entirely pH-independent, in contrast to conventional optodes that have a pH-sensitive signal. Studies using mixed and separate solutions have shown that K+ has extremely high selectivity over Na+ and Ca2+ [26].

3. Various treatment options

3.1 Nonspecific treatment

Any concurrent or pre-existing ailment needs to be properly managed. A downer cow should receive good nursing care, be comfortable, and not be bothered. Maintaining the cow’s constant access to water and nutrition is especially crucial. Regular milking and turning from one side to the other is necessary for dairy cows. Any equipment that aids in the animal’s emergence is beneficial, but timing is crucial. Because weak animals are more likely to be injured due to a lack of muscle tone, premature attempts may exacerbate or even induce a musculoskeletal problem. After the serum potassium content returns to the normal level, using a flotation tank (Aqua cow Rise System) is quite beneficial [27].

3.2 Nursing the downer cow

Only when the cow has a good chance of recovering and there is a capable person nearby who is willing to dedicate the necessary time and energy to offer proper nursing care may a downed cow be nursed. The downer cow’s chances of recovering completely are increased with proper nursing, but this can be labour- and time-intensive. If you are unable to provide the cow proper nursing care, you should think about euthanizing it right away [28].

3.3 Guideline for tending to a downtrodden cow

1. Give the cow comfortable, clean, dry bedding so that when it tries to stand, it has a non-slip surface [28].

2. Ensure a steady supply of wholesome food and clean water,

3. Every 3–4 hours, move the cow from side to side.

4. Make sure the cow is periodically moved and that her weight is not always on one side if she is unable to switch sides on her own. She should also flex and lengthen her hind limbs each time.

5. Remove the milk by hand from the udder.

6. Consistently encourage the cow to stand; only use a lifting hoist equipment to help her do so.

7. Never let a cow dangle inside a hoisting mechanism [28].

3.4 Specific treatment

The severity of the hypokalemia should determine the oral or intravenous potassium therapy. It is crucial to keep in mind that a potassium deficiency be 200–400 mEq is represented by every 1 mEq/L reductions in serum potassium. Nevertheless, this computation may overestimate or underestimate the potassium shortage. Individuals with mild to moderate hypokalemia (potassium concentration of 2.5–3.5 mEq/L), may just require oral potassium replacement. If potassium levels are less than 2.5 mEq/L, intravenous potassium should be given, very slowly and call for the attendance of a veterinarian.

3.5 Injectable formulations

Potassium injections should never be given intravenously; instead, they should be diluted with 500 ml of regular saline injections, with a pace of between 0.1 and 0.2 mEq/kg/h being the ideal range. A maximum injection rate of 0.5 mEq/kg/h is recommended for intravenous supplementation; at replacement fluid flow rates, this translates to 20–40 mEq/L of fluid.

Dosage: The dose should be frequently adjusted for the animal, and continuous monitoring of plasma concentration should be performed. When the severity of hypokalemia is known, an administration regime is recommended:

1. Mild hypokalemia: serum concentration 3.0–3.5 K+ mEq/l | quantity of potassium chloride per kg/weight administered for 24 hours: 2–3 mEq.

2. Moderate hypokalemia: serum levels 2.5–3.0 K+ mEq/l | quantity of potassium chloride/kg/weight administered for 24 hours: 3–5 mEq.

3. Severe hypokalemia: serum concentration ≤ 2.5 K+ mEq/l | quantity of potassium chloride per kg/weight administered for 24 hours: 5–10 mEq.

If the serum potassium concentration is not known, 20–40 mEq/l potassium chloride should be added to the solution for intravenous perfusion.

One millimole is equivalent to one milli equivalent (mEq) or 39.1 milligram of potassium. Potassium chloride sterile aqueous solution is widely accessible in the market for this use, often at a concentration of 2 mEq K/mL. As an alternative, adding 1 g of KCI powder to fluids meant for intravenous delivery yields about 13 mEq of K+ [26].

3.6 Potassium chloride injection

Potassium chloride injection is available in the market globally as vials and ampoule potassium chloride concentrate is used for electrolyte and fluid replenishment. It must be diluted before use. Potassium chloride can rehydrate the cow and restore electrolyte balance. 10 ml and 20 ml single-dose vials are a administration & dosage: intravenous. Before being administered, it must be diluted with water or another acceptable fluid to the proper strength. Potassium chloride, 2 mEq (149 mg), is present in each milliliter of sterile aqueous solution available in the market.

3.7 Potassium acetate injections Hospira, Inc.

Potassium acetate in water, sterile, nonpyrogenic, concentrated solution for injection is known as acetate injection, USP (2 mEq/mL). As an electrolyte replenisher, the fluid is given intravenously following dilution. It cannot be given without diluting it. Bicarbonate (HCO3▬) can also be generated from acetate (CH3COO▬), a source of hydrogen ion acceptors, through the liver’s metabolic conversion process. It has been demonstrated that this can happen quickly, even in cases of severe liver disease. Potassium acetate (196 mg/mL) yields 2 mEq of potassium (K+) and acetate (CH3COO▬) respectively. To alter the pH, acetic acid may be added to the solution. With a range of 5.5–8.0, the pH is 6.2. The specific gravity is 1.089 and the osmolar concentration is 4 mOsmol/mL (calculated). A maximum infusion rate of 1 mEq/kg/h is recommended [29, 30].

3.8 Oral formulation

According to Sweeney [31] oral potassium supplementation is better than intravenous since it is less expensive, easier to administer, and allows for higher doses to be given with fewer risk of side effects (Table 3). Given that potassium is needed in cattle with whole-body K depletion and chloride is needed in cattle with alkalaemia and pH-induced compartmental shift of K to the intracellular space, oral potassium chloride administration appears to offer the best salt formulation for treating cows with hypokalemia [14].

	Drug/s	Presentation	Dose	Remarks	References
1	Potassium 60 g	Powder	Two doses	Effective in mild to moderate hypokalemia	[19]
2	Potassium; chloride 60; sodium chloride 30	Solution	Sodium chloride 60 g; Potassium chloride 30	Both salts are dissolved in 15 liters of water and given as drench in mild hypokalemia	[31]
3	Potassium chloride 52 g	Bolus	One	Plasma potassium concentrations for all preparations increased within 30 minutes and the increase lasted for 12 hours.. The feed intake increased in 50% of cows within 2 hours after potassium application, which may contribute to the increase of plasma potassium concentration	[32]
4	Potassium propionate52	500 g gel	One
5	Potassium chloride powder52	Solution	One
6	Potassium acetate	10% solution	BID for daily for 1 days	Treatment continued till recovery	[29]
7	Potassium chloride: 51 wt.%; CaCl2 2H2O: 25 wt-%; Water: 15 wt.%	Bolus	One or two	In the moderate hypokalemic cow, a bolus administration resulted in reconstitution of mean and medium plasma potassium concentration to normal (reference range 3.5–5.0 mmol/l) within an hour following administration. In severe hypokalemia, one more bolus was given with no adverse effect	[33]
8	Dipotassium phosphate 100 g of phosphate 1 and 83 g of potassium	Bolus	two boluses once daily for a maximum of 3–5 days	Recovery within 3 days	[34]
	Potassium chloride 24 g; Sodium carbonate; Potassium carbonate; Taurine 6; Propylene glycol 200 ml	Powder and liquid	Both were together administered and repeated after 10 hours if necessary	Recovery within 3–12 hours’ stabilizes the potassium, provides energy palatable	[35]

Table 3.

Various oral treatment methods of hypokalemia.

3.9 Powder formulations

Since potassium chloride tastes bad when taken orally, giving cows access to it usually does not lead to enough voluntary consumption. Second, some of the advantages of supplementing may be offset by increased potassium excretion in the urine, which is linked to increased urine flow during intravenous replacement fluid administration. If a free-choice oral electrolyte solution consisting of 60 g sodium chloride and 30 g potassium chloride diluted in 15 L of water is made available to patients with minor cases of hypokalemia, it will be easily ingested and help correct the modest deficiency [31] Wittek et al. [32] conducted a comparative study on three oral potassium formulations and discovered that the cows treated for hypokalemia received 52 g of potassium in three different formulations: group B was given a potassium chloride bolus (released over 12 hours); group G was given potassium propionate gel (released over 2 hours); and group S was given potassium chloride solution (available immediately). They discovered that the amounts of potassium in plasma for all preparations rose in less than 30 minutes and continued to rise for 12 hours. Within two hours of the potassium administration, 50% of the cows’ feed intake increased, which could have contributed to the rise in plasma potassium content.

3.10 Potassium acetate

Narayana et al. [29] successfully treated the downer cows, creeper cow and cattle with leg weakness with Potassium acetate 10 g b.i.d. orally, and 10% solution 100 ml intravenously/day until signs of recovery which was in a week to a month.

3.11 Bolus formulations

3.11.1 The bolus formulation is easy to administer with a Balling gun and is easy to pack and transport

Wilhelm-Olany [33] conducted a trial with a following composition bolus with ingredients.

Potassium chloride: 51 wt.%

CaCl₂ 2H₂O: 25 wt.%

Water: 15 wt.%

Magnesium oxide: 9 wt.%.

There were 45–48 g of potassium per piece in the bolus formulation, or roughly 85–91 g of potassium chloride. Bolus is administered orally with a Balling gun. An hour after bolus injection, the mean and medium plasma potassium concentrations in the moderately hypokalemic cow were returned to normal (reference range 3.5–5.0 mmol/l). One extra bolus was administered in cases of severe hypokalemia with no negative consequences.

3.12 Kalitop (Resco Product, Belgium)

3.12.1 Each bolus contains 70 g of potassium

3.12.1.1 Dosage and administration

Two Kalitop bolus together in 1 application, and 2 boluses 12 hours later if necessary. Orally with the help of a bolus applicator or Balling gun.

3.12.1.2 Potassium Bolus (J Farm, Poland)

Potassium bolus for the dairy cow; includes 66 g of potassium in each bolus reduction of the risk of hypokalaemia.

Indications:

• A cow with prolonged inappetence (>2 days) after labour, especially with recurrent ketosis

• The cow receiving more than one injection of corticosteroid that have mineralocorticoid activity

Properties:

• rapid disintegration and assimilation

• reduction of the risk of hypokalemia

• counteraction of depression gastrointestinal tract motility and stimulation of appetite

• all ingredients are digestible

Composition:

Potassium chloride, magnesium stearate.

Instruction for proper use:

Give 1 bolus into the cow’s mouth by using applicator.

After 8–12 hours repeat the administration of 1 bolus, if needed.

Shelf life: 18 months from the manufacturing date.

Packaging: Each 150 g bolus is secured in a plastic tube. There are four boluses in one paper box.

3.12.1.3 K-Phos Boost Bolus

Since the symptoms of hypophosphatemia and hypokalemia are similar and manifest in the early postpartum period, Solvet Animal Health (Calgary, Alberta, Canada) has created a dipotassium phosphate (K₂PO₄) bolus called “K Phos-Boost” to treat both conditions. Dipotassium phosphate (K₂HPO₄) makes up each 230-gram K Phos-Boost Bolus (Solvet Animal Health, Calgary, Alberta, Canada), which provides 100 g of phosphate and 83 g of potassium per bolus. In the rumen, the bolus dissolves entirely in 30 minutes. For dairy cows lacking in potassium and phosphorus, the suggested published dose is 131 g of potassium and 198 g of phosphate per day for a period of 1–5 day. When cows ingest two boluses of dipotassium phosphate, they get 200 g of phosphate and 166 g of potassium daily. This is in good agreement with the daily dosage that have been published. Therefore, two boluses once daily for a maximum of 3–5 days is the recommended dose [34].

Dosage: Administer using the K-Phos Boost branded applicator. Give 2 boluses orally, once daily for up to 3 days. Allow access of water.

In severe hypokalemic cows with a serum potassium concentration of less than2.5 mmol/L one dose of intravenous injection followed after 12 hours by either oral powder or Bolus potassium formulation saved the cows from certain death [36].

The oral delivery of potassium chloride in solution through the use of a bottle or a drenching gun or a stomach tube may irritate the mucous membranes of the oral cavity and the esophagus as a result of its caustic action [37].

3.12.1.4 Nutri-Pot

It turned out that drenching the Nutri-Pot (A) and Nutri-Pot (B) mixture was a simple and secure process. In addition to acting as a lubricant and demulcent, propylene glycol supplied instant energy and facilitated the rapid absorption of potassium. Increased feed absorption and consequent milk production were linked to improvements in the clinical state [35].

Generally, hypokalemia in cows with anorexia and debility when oral formulations, replenish the serum potassium but do not provide sufficient energy for speedy recovery.

Higher or frequent oral dose is not recommended, because they can lead to osmotic diarrhea, excessive salivation, muscular tremors of the legs, and excitability. Hypokalemia is usually associated with acidosis. It was hypothesized that formulation that overcomes acidosis, provides energy, improves and stabilizes cell membranes and regulates osmosis will pave a way for a speedy recovery.

Nutri-pot that was presented in two parts [36] 50 g of powder part containing 12 g of elemental potassium and 4 gram bicarbonate sodium and potassium 6 gram of taurine and liquid part containing 200 ml propylene glycol), was conducted. In 84 clinical cases 40 without taurine and another 44 with taurine, at the veterinary hospital, during 2022–2023. In Rayachoti of Andhra Pradesh. The second dose was repeated if necessary. Taurine-enriched formulation group recovered and returned to normal milk within 3 days than the formulation without taurine took 5–7 days to return to normal milk [36].

Nutri-pot is the proprietary product of Instar Health care, Kadapa. The formulation provided sufficient energy, increased palatability, enhanced absorption, countered acidosis, lessened gastric irritation, stabilized membranes and balanced the influx and outflux of potassium in the cells of the heart muscle, and skeletal muscles of limbs and neck. The role of taurine in membrane function and stabilization has greatly increased the importance of dietary taurine. Taurine apparently, normalize the content of potassium and calcium ions in vivo and in vitro. The action of taurine appears 50 be membrane-based [38] as it has detoxifying, antioxidant, and membrane-stabilizing properties apparently due to its molecular structure [39, 40].

3.12.1.5 Role of taurine in the formulation

It is assumed that taurine-containing formulations may stabilize the translocation of potassium from intracellular to extracellular and vice versa, since hypokalemia is caused by abnormalities of potassium concentration in plasma and can result from changes in external potassium balance (intake vs. excretion) or internal potassium balance (intracellular to extracellular) [38].The antioxidant and metabolic enzyme activity were regulated by dietary K+ and taurine, which also reduced stress and balanced energy needs. The best growth performance, ionic homeostasis, and stress reduction were shown by GIFT tilapia fed a diet containing 0.5% taurine and 0.2% K+. This suggests that taurine plays a critical role in enhancing the wellbeing of fish raised in low-salinity, potassium-deficient water [41]. Taurine nutritional supplements enhance potassium ionic equilibrium [42, 43].

Evidence for the role of taurine in membrane function and stabilization exemplifies the potential importance of dietary taurine. It is said that most actions of taurine appear to be membrane-based because it has detoxifying, antioxidant, and membrane-stabilizing properties apparently due to its molecular structure. Taurine was shown to normalize the content of potassium and calcium ions in vivo and in vitro [38]. In excitable tissues, taurine (2-aminoethane sulfonic acid) is widely distributed. Its many physiological and pharmacological effects are little understood in terms of its underlying mechanisms. However, taurine’s physicochemical characteristics imply that it interacts with membrane phospholipids to change the characteristics of membrane-associated proteins as well as membrane functions like ion binding and conductance [37, 38, 39].

4. Prevention of hypokalemia

Early lactation cow can suffer from negative potassium balance due to greater potassium excretion, greater secretion of potassium in milk, and increased perspiration losses during heat stress. With the inclusion of a higher amount of potassium in the early lactation diet, some studies showed an increase in milk production, 3.5% fat corrected milk, and the milk fat, which was not associated with an increase in dry matter intake. Potassium supplementation in the form of potassium carbonate has also increased milk fat percentages, partly explained by reduced ruminal synthesis of bio-hydrogenation intermediates known to inhibit milk fat synthesis. The lowering of bio-hydrogenation intermediates that inhibit milk fat synthesis is likely mediated through the alkalizing effects of some potassium supplements to increase ruminal fluid pH(I) Harrison et al. [44] recommend formulating for 1.6% K, and to increase to1.8 to 2% for heat stress. Harrison [44] advised formulating for 1.6% K and raising to 1.8–2%. In order to help achieve a DCAD of >35 mEq/100 g of dry matter, sodium levels can be raised. The maximum amount of sodium in the dry matter ratio is 0.8%.

4.1 Potassium carbonate administration

In order to enhance the buffering capacity of rations, boost the supply of K during heat stress, and balance electrolytes in the ration for optimal lactational performance, potassium carbonate has been added to feed as a feed supplement. Potassium carbonate, however, can heat feed and induce caking. A novel product has been developed by Milk Specialties Global (Eden Prairie, MN), which used 204 g of bye pass fat to coat 68 g of potassium carbonate as a premix. According to Kayla et al.’s study [45], feeding the novel product to a milking Holstein dairy cow on a regular basis did not cause any palatability issues.

The effects of adding electrolyte and ascorbic acid to feed under heat stress in buffalo were investigated by Sunil Kumar et al. [46]. They added ascorbic acid polyphosphate at 10 g/animal/d, potassium carbonate at 12.5 g/animal/d, and sodium bicarbonate at 15 g/animal/d as supplements and noted a reduction in heat stress.

4.2 Various Additives to minimize hypokalemia

4.2.1 Additional supplementation of potassium salts to animals at risk

Potassium must be given orally to the inoperant cow as part of the fluid and electrolyte treatment regimen. Supplementing animals deemed to be at risk is the focus of prevention. Oral potassium supplementation is recommended for dairy animals that are persistently anorectic and receiving treatment with isoflupredone acetate, intravenous dextrose, and insulin. While there is no definitive recommended dosage for a normal patient deemed at risk, 100 g twice a day appears to be a safe starting point [8].

4.2.2 Additional supplementation of propylene glycol

The easiest way to keep cows from developing hypokalemia is to make sure they are getting enough dry matter to eat. Propylene glycol supplementation in the early nursing cow diet enhanced energy status, reduced body weight loss, and had negligible effects on feed intake and milk production; nevertheless, it may have decreased the amount of protein and fat in the milk [35].

4.2.3 Additives to enhance the dry matter intake

Utilizing additives to balance rumen functioning: Few additions have a consistent effect on conditioning rumen functionality. This is due to the fact that every addition is dependent upon the circumstances established by the cow’s overall ration consumption as well as her physical and general health. Every additive must therefore be assessed using a methodology unique to each farm. Generally speaking, the most widely utilized additions are yeast, sodium bicarbonate, and yeast derivatives. Other, less common ones are clays, algae, probiotics, enzymes, and various salts. When receiving two or more cortisone injections with mineralo-corticoid action, one should always give an oral powder or bolus.

4.2.4 Iodised oil to combat the thermal stress

In case of hypokalemia occur during thermal stress, inject 5 ml containing 150 mg of iodisedoil, at brisket region for 3 consecutive days will overcome the thermal stress for 60 days without detrimental effect on thyroid [47].

4.3 Thermo CAD heat stress pack

ThermoCAD Heat Stress Pack, an Altech, Hubbard product in hot weather, 4–8 oz. per head per day as a top-dress, as part of a TMR, or as the grain portion of a dairy or beef diet. In addition, water and forage are required. Cattle in dairy and beef feedlots that are nursing should utilize the ThermoCAD Heat Stress Pack when the weather is warm and conducive to heat stress. Tasco (Ascophyllumnodosum) is a unique blend with minerals, vitamins, electrolytes, and feed additives called ThermoCad, which is intended to assist sustain dry matter intake and replace essential nutrients that are necessary for effective heat stress abatement.

5. Conclusion

“From the latest scientific findings presented in this chapter, the following most important conclusions can be drawn:

1. The cows with serum or plasma potassium concentrations less than 3.9 mEq/L are considered hypokalemia.

2. Hypokalemia can arise from induced, physiological, or pathological conditions.

3. Extended periods of anorexia, lying down, twitches in the muscles, melancholy, fluctuations in body temperature, and an odd neck posture (an S-shaped neck) are some of the prominent symptoms.

4. The turbid metric approach is a quick, simple, and cost-effective way to estimate serum potassium at the field level.

5. A maximum delivery rate of 0.5 mEq/kg/h is recommended for severe hypokalemia when serum concentration ≤ 2, 5 K+ mEq/parenteral injections; at replacement fluid flow rates, this often equates to 20–40 mEq/L of fluid.

6. Beside the potassium salt therapy, we emphasize the inclusion of Taurine in the therapeutic regime.

6. Future research and recommendation

As a cytoprotective molecule, taurine is involved in many different processes, including energy production, neuromodulation, calcium homeostasis, and osmoregulation. These processes supports the taurine’s anti-oxidant properties and the molecular mechanisms underlying its action in a variety of pathological conditions linked to oxidative stress. In fact, taurine shows promise as a treatment for conditions connected to the central nervous system, circulatory system, skeletal muscle, and metabolism. The multilayered characterization of taurine therapeutic targets with the use of next-generation sequencing will provide comprehensive insights into taurine’s prospective clinical applications [47, 48, 49].

It is worthwhile to research the inclusion of taurine in the oral and injectable potassium chloride formulations to lower the dosage and speed up the healing process of hypokalemia in the dairy cow.

Acknowledgments

Our profound gratitude to Dr. Santimalla Siva Reddy, Assistant Director, Veterinary Hospital, Rayachoti, India, for assessing Nutri-Pot in hypokalemic cows and sharing his research, and to Dr. Paranjyothikanni, Ph.D. Director, Bangalore Allergic Centre, Bangalore, for his invaluable suggestions in preparing this manuscript. For editing the script, I would like to thank Dr. K. Narayana, a retired professor of veterinary pharmacology at the veterinary college in Bangalore.

Declaration of interest

The writers affirm that there is not any conflict of interest that would be seen as compromising this review’s objectivity.