Hypokalemia Syndrome i n

Cattle
Nicolas Sattlera, Gilles Fecteaub,*

KEYWORDS
 Bovine  Hypokalemia  Recumbency  Electrolytes  Anorexia  Potassium

KEY POINTS
 Risk factors for hypokalemia syndrome include the early lactation period, anorexia, and
repeated administration of isoflupredone.
 Treatment includes basic supportive care for recumbent animals and aggressive potas-
sium replacement therapy.
 Prognosis is guarded for recumbent cattle and worsens if hypokalemic myopathy or com-
plications of recumbency occur.

INTRODUCTION

Total body potassium depletion leads to muscle weakness and may or may not be
associated with low plasma potassium concentration (hypokalemia). More often, hy-
pokalemia is observed on a serum biochemistry profile in animals without potassium
depletion (potassium redistribution). The clinical significance of hypokalemia cannot
be ascertained without considering the other electrolytes as well as the acid-base sta-
tus. Moreover, the physical examination and complete history dictate whether inter-
vention is necessary.

NORMAL POTASSIUM BALANCE

Potassium is mostly intracellular. Serum potassium concentration is a poor indicator of

the potassium status of the animal. Determination of intracellular potassium concen-
tration in erythrocytes or muscle cells is a more accurate way to assess potassium
depletion, but with current technology it is not clinically feasible in most cases.1,2
The concentration of potassium in plasma depends on external potassium balance
and internal potassium balance. External potassium balance refers to potassium

The authors have nothing to disclose.

a
Service Vétérinaire Saint-Vallier, 400 montée de la station, Saint-Vallier, Québec, G0R3J0
Canada; b Clinical Sciences Department, Faculté de Médecine Vétérinaire, Université de Mon-
tréal, Saint-Hyacinthe, Québec J2S 7C6, Canada
* Corresponding author.
E-mail address: gilles.fecteau@umontreal.ca

Vet Clin Food Anim 30 (2014) 351–357

http://dx.doi.org/10.1016/j.cvfa.2014.04.004 vetfood.theclinics.com
0749-0720/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
352 Sattler & Fecteau

intake and absorption from the gastrointestinal (GI) tract, and potassium excretion by
the kidneys. The primary source of potassium is the forage portion of the normal
ruminant diet. An animal with a normal appetite usually has a normal serum potas-
sium concentration. Almost all ingested potassium (more than 300 g per day for a
600-kg cow) is absorbed and reaches the intracellular fluid compartment. Because
they have a forage-based diet, lactating dairy cows may eat more than 10 times their
daily potassium requirement. For this reason, cattle have renal excretory mecha-
nisms that are well developed to eliminate the excess potassium load from the
body. When intake is interrupted, the excretory mechanisms may not respond rapidly
enough to avoid potassium depletion. Cows with partial and/or total anorexia fre-
quently have moderate hypokalemia. This hypokalemia is not coupled with clinical
signs of weakness. Other abnormalities such as diarrhea, third space loss, and alka-
losis can exacerbate potassium loss from the intracellular and extracellular fluid
compartments.
Some corticosteroids with mineralocorticoid effects are known to lead to hypoka-
lemia (eg, isoflupredone acetate) by increasing potassium excretion in the kidneys.
Diuretic drugs (eg, furosemide) may also contribute to renal potassium loss. Following
relief of a urinary obstruction, a diuretic phase occurs and may lead to significant
potassium loss.
Internal potassium balance refers to the distribution of potassium between the intra-
cellular fluid (ICF) compartment and extracellular fluid (ECF) compartment. Acid-base
balance has a significant effect on the distribution of potassium between these com-
partments, with acidosis causing the movement of potassium from the ICF to the ECF
and resulting in hyperkalemia, and alkalosis causing potassium movement in the other
direction resulting in hypokalemia. Insulin also facilitates the movement of potassium
from the ECF to the ICF. Therefore, the administration of dextrose or insulin may result
in hypokalemia or an amelioration of hyperkalemia if it exists.

THE CLINICAL SYNDROME

Introduction
Hypokalemia syndrome has been reported.3–6 Lactating dairy cows as well as younger
animals may develop the disease. At present, except for animals treated with repeated
isoflupredone acetate administrations, the exact determinants causing hypokalemia
syndrome remain uncertain.

Risk Factors
Lactating dairy cows less than 60 days in milk seem to be at greatest risk. Systemic
illness causing anorexia of several days’ duration is a risk factor.4 Repeated systemic
or intramammary administration of isoflupredone acetate can cause the syndrome.
The mineralocorticoid activity of isoflupredone acetate disturbs both the internal
and external potassium balance.7 Repeated doses can reduce serum potassium con-
centration by 70%.8 Food-restricted dairy cattle receiving repeated doses of isoflupre-
done acetate developed the syndrome in an experimental model.9 Following the label
directions concerning dose and duration seems to be important. Although it is a less
potent mineralocorticoid, use of dexamethasone was also reported as a potential
cause in some cases.4,6
Multiple treatments of dextrose and insulin are also reported to be associated with
the syndrome.3–6 In young animals, the repeated administration of isoflupredone
acetate to treat pneumonia and intravenous (IV) fluid administration have been
reported to initiate the syndrome.4
 Hypokalemia Syndrome in Cattle 353

Clinical Signs
In most cases, a primary disease was diagnosed and treated by either the owner or a
veterinarian before the generalized weakness or recumbency developed. The identifi-
cation of the concomitant disease is essential and should not be overlooked because
it influences the recovery and prognosis. Some patients are presented with an
obscure GI problem: anorexia, little to no feces, reluctance to move, and rapid return
to recumbency after stimulation to get up, mimicking colic. In most cases, the animal
rapidly becomes incapable of getting up and severe paresis develops. This constella-
tion of signs creates some confusion in the management of the case; specifically,
whether surgery is indicated.
After the initial phase of stiffness and tendency to lie down, most animals develop
the following clinical signs:
 Severe apparent depression (generalized weakness with little resistance to any
manipulations)
 Lack of tone of most muscle groups (tail tone to tongue tone are reduced)
 Tachycardia
 Abnormal neck posture (S-shaped neck) (Fig. 1)
 Recumbency
 GI stasis (forestomach and intestine) so no ruminal motility and little if any feces

Fig. 1. Typical (or classic) S-shape position of the neck of a cow with hypokalemia. The neck
muscle tone is so weak that the head cannot be held straight.
354 Sattler & Fecteau

In our experience, 2 types of recumbent animals may be observed. Some are weak
to the point of being unable to rise but do not have severe generalized rhabdomyoly-
sis, whereas others have severe rhabdomyolysis even in the non–weight-bearing mus-
cle groups. The patients with severe rhabdomyolysis recuperate slower, even after the
serum potassium value returns to normal. The increase in creatine kinase and aspar-
tate aminotransferase are more pronounced in the second group.
The generalized weakness often prevents the animal from reaching for food or
water, and it is common to observe a cow eating her grain if her head is placed in
the feed bucket. Perhaps an apparent lack of appetite can be explained by the inability
to reach the feed rather than anorexia. The position of the head is worth describing in
more detail. There is a complete inability to keep the head in a straight position. The
neck is carried in an S-shaped posture. Lack of muscle tone allows easy movement
of the head. Sometimes it is possible to position the head and neck in their normal
straight position, but inevitably the head eventually falls to one side or the other.
The first few cases of hypokalemia syndrome diagnosed by the authors were initially
suspected to have cervical subluxation because of this awkward positioning of the
neck. This condition may be observed in the standing animal immediately before
recumbency occurs or in the recumbent patient. Cardiac dysrhythmias may also be
noted (ventricular tachycardia, accelerated escape ventricular rhythm, or atrial
fibrillation).4

Pathophysiology
Because most of the total body potassium is intracellular,10 plasma concentration is
not as important as the gradient between the potassium concentrations of the ICF
and ECF compartments, which is the determinant of the resting cellular membrane
potential and plays a role in the formation and transmission of action potentials.11
This gradient explains why animals may be observed with weakness in the absence
of severe rhabdomyolysis. However, structural damage associated with potassium
depletion has also been reported in cattle.3–5,12 This structural damage most likely
occurs in the group of patients observed with severe rhabdomyolysis. As far as the
authors know and according to other investigators, there is no clear explanation for
the distribution of animals into one category or the other.3,4
The changes in cardiac electrical activity associated with hypokalemia could be
explained by one or more of the following phenomena: hyperpolarization of the
cardiac cell resulting in spontaneous automatic activity, slow conduction caused by
the increased difference between resting membrane potential and threshold potential,
increased action potential duration as a result of slow repolarization, depressed fast
responses because of higher membrane potential when a slow repolarizing cell is
stimulated, slow responses in fibers normally showing fast responses, and conduction
block.13 In addition to electrical abnormalities, if muscle cell necrosis occurs, cardiac
dysrhythmia could become even more likely. However, muscle lesions compatible
with hypokalemic myopathy (muscular necrosis) have not been consistently docu-
mented in the reported hypokalemia syndrome of cattle.3–6

Differential Diagnosis
In the early stages of the condition, hypokalemia syndrome could be confused with GI
problems such as acute abdomen: intestinal ileus and intussusception or musculo-
skeletal/neurologic problems such as cervical trauma, luxations, osteomyelitis or
neoplasia, vertebral malformations, fractures, and torticollis. A complete history and
thorough physical examination help rule out the other possibilities mentioned earlier.
Other conditions to rule out when the animal is presented recumbent are
 Hypokalemia Syndrome in Cattle 355

hypocalcemia, botulism, and tick paralysis. It is important to consider hypokalemia

syndrome as a differential diagnosis in recumbent postpartum cows because
administration of calcium solution intravenously to normocalcemic cows carries a sub-
stantial risk.

Clinical Pathology and Ancillary Tests

Serum biochemistry profile is helpful in the management of hypokalemic cattle. How-
ever, there is no consensus on the lower threshold for potassium below which the
diagnosis is confirmed. The lower threshold limit is usually stated to be 2.2 to
2.5 mmol/L. The degree of increase of creatine phosphokinase and other muscle
enzymes suggests whether the muscle damage is related to the primary problem
(hypokalemia) or to secondary (recumbency-associated) muscle damage. Concomi-
tant acid-base derangements vary from severe metabolic hypochloremic alkalosis
to metabolic acidosis in severe advanced cases.3 Hypophosphatemia has been
observed in 25% to 40% of cases but the significance of this finding remains to be
shown.3–5
Lumbar muscle biopsy (between L2 and L5) on a living patient or sampling during
postmortem examination helps to differentiate primary hypokalemic myopathy from
secondary myopathy caused by recumbency.
Fractional urinary excretion of potassium (FEk) has been used to provide insight into
the pathophysiology of hypokalemia syndrome. In one study, FEk remained in the
normal to high range despite a documented severe hypokalemia 12 to 24 hours before
clinical signs appeared. FEk from 55% to 128% have been reported in 5 hypokalemia
cases.5 The normal range of FEk for early lactating cattle has been reported to be
26.9% to 120%.14
A method of determining both the internal and external potassium balances simul-
taneously in dairy cows has been presented.3

Treatment
Nonspecific treatment
Any concomitant or preexisting problems should be addressed appropriately. Good
nursing care appropriate for any down cow should be in place and emphasized. Of
particular importance is keeping feed and water easily accessible to the cow at all
times. Dairy cows should be milked regularly and turned from one side to the other.
Any device helping the animal to get up is useful, but the timing is important. Prema-
ture attempts may aggravate or cause a musculoskeletal problem because weak
animals are prone to injury (lack of muscle tone). Use of a flotation tank (Aquacow
Rise System) is of great value once the serum potassium concentration has returned
to the normal range.

Specific treatment
If serious complications arise during the animal’s recumbency, even if normal potas-
sium status is restored, the complicating problem may result in the death of the animal.
Good nursing care is critical to the recovery of hypokalemic patients. Specific treat-
ment is intended to address potassium depletion. Potassium chloride supplementation
administered orally is the preferred method. The optimal total amount to administer
daily remains to be defined, but the authors have used 60 to 100 g/100 kg of body
weight per day. However, most investigators recommend a lower dose (250 g per
cow per day). When IV potassium chloride is administered, the rate should not exceed
0.5 mEq of K1/kg/h. Serum potassium should be monitored daily to allow adjustment of
356 Sattler & Fecteau

the treatment regimen. Treatment is usually necessary for 3 to 5 days.3–5 It is probably

safe to continue some supplementation until the appetite has returned to 100%.

Prevention
Prevention is oriented toward supplementation of animals considered to be at risk.
Dairy cattle that are chronically anorectic and treated with isoflupredone acetate
and/or IV dextrose and insulin should received oral potassium supplementation. The
optimal dosage regimen to administer to a normal patient considered at risk is empiric,
but 100 g twice a day seems safe.

Prognosis
In 3 reports, the survival rates were 2 of 8,3 7 of 17,5 and 11 of 14.4 The survival rate in
retrospective studies is inconsistent because so many variables accounted for death
and/or euthanasia (duration of recumbency, severity of concomitant disease, pres-
ence of hypokalemic myopathy, and treatments received, as well as cost of treatment
in a particular hospital).1 Prevention of any complications associated with recumbency
is probably a major determinant in the outcome. The complexity of the disease and the
duration of the recovery phase warrant a guarded prognosis at best. The availability of
a flotation tank seems to be a significant positive prognostic factor.3–5

UNANSWERED QUESTIONS

A few important questions remain unanswered. The precise relationship between the
perturbations of internal versus external potassium balance in affected cattle is not
clear. The precipitating factor for some cattle to develop the severe rhabdomyolysis
is still not understood. The impact of excessive nutritional potassium on kidney
homeostasis should be investigated further. The optimal treatment regimen is also still
to be proved in a clinical trial.

REFERENCES

1. Johnson PJ, Goetz TE, Foreman JH, et al. Effect of whole-body potassium deple-
tion on plasma, erythrocyte, and middle gluteal muscle potassium concentration
of healthy, adult horses. Am J Vet Res 1991;52:1676–83.
2. Sattler N, Fecteau G, Couture Y, et al. Évaluation des équilibres potassiques chez
la vache laitière et étude de ses variations journalières et selon le stade de pro-
duction. Can Vet J 2001;42:107–15.
3. Sielman ES, Sweeney RW, Whitlock RH, et al. Hypokalemia syndrome in dairy
cows: 10 cases (1992–1996). J Am Vet Med Assoc 1997;210:240–3.
4. Sattler N, Fecteau G, Girard C, et al. Description of 14 cases of bovine hypoka-
laemia syndrome. Vet Rec 1998;143:503–7.
5. Peek SF, Divers TJ, Guard C, et al. Hypokalemia, muscle weakness and recum-
bency in dairy cattle. Vet Ther 2000;1:235–44.
6. Johns IC, Whitlock RH, Sweeney RW. Hypokalaemia as a cause of recumbency in
an adult dairy cow. Aust Vet J 2004;82:413–6.
7. Vita G, Bartolone S, Santoro M, et al. Hypokalemic myopathy in pseudohyperal-
dosteronism induced by fluoroprednisolone-containing nasal spray. Clin Neuro-
pathol 1987;6:80–5.
8. Neff AW, Connor AD, Bryan HS. Studies on 9a-fluoroprednisolone acetate, a new
synthetic corticosteroid for the treatment of bovine ketosis. J Dairy Sci 1960;43:
553–62.
 Hypokalemia Syndrome in Cattle 357

9. Sattler N, Fecteau G, Pare J. Experimental reproduction of the bovine hypokale-

mia syndrome [abstract]. J Vet Intern Med 2002;16:337.
10. Guyton AC, Hall JE. Transport of ions and molecules through the cell membrane.
In: Guyton AC, Hall JE, editors. Textbook of medical physiology. 9th edition. Phil-
adelphia: WB Saunders; 1996. p. 43–55.
11. Guyton AC, Hall JE. Membrane potentials and action potentials. In: Guyton AC,
Hall JE, editors. Textbook of medical physiology. 9th edition. Philadelphia: WB
Saunders; 1996. p. 57–72.
12. Lindeman RD. Hypokalemia: causes, consequences and correction. Am J Med
Sci 1976;272:5–17.
13. Commerford PJ, Lloyd EA. Arrhythmias in patients with drug toxicity, electrolyte
and endocrine disturbances. Med Clin North Am 1984;68:1051–78.
14. Fleming SA, Hunt EL, Brownie C, et al. Fractional excretion of electrolytes in
lactating dairy cows. Am J Vet Res 1992;53:222–4.