Disorders of potassium homeostasis are frequently encountered and associated with a wide range of diseases. Moderate to severe hyper- and hypokalaemia can have immediately life-threatening consequences and ER clinicians must be adept at rapid recognition and correction of dyskalaemias.

Review of Normal Potassium Homeostasis

Potassium is the major intracellular cation and is located predominantly in skeletal myocytes.^1,2 Normal extracellular and intracellular potassium concentrations are approximately 4 mmol/L, and 140 mmol/L, respectively. The concentration gradient between the intracellular and extracellular space is maintained by the active Na⁺-K⁺-ATPase pump that transports potassium into the cell and sodium out of the cell.³ Potassium regulation must adapt to both the addition of potassium to the extracellular compartment by oral potassium intake in the diet or parenteral administration in intravenous fluids in hospitalized patients.³ Two mechanisms are of great importance in maintaining a normal serum potassium concentration, 1) the distribution of potassium between the intra- and extracellular fluid compartment (internal potassium balance), and 2) the renal excretion of excess potassium (external potassium balance).³ Abnormalities in serum potassium concentrations can, therefore, arise from abnormal potassium intake or generation, disturbances in internal potassium balance, or from abnormal potassium excretion.³

Hypokalaemia

Definition and Etiology

Normal serum potassium values for dogs and cats are expected to range from 3.5 mmol/L to 5.5 mmol/L and hypokalaemia is defined as serum potassium concentrations less than 3.5 mmol/L.^1,2 An abnormality in any of the processes of potassium homeostasis can lead to hypokalaemia and the three general causes for hypokalaemia include 1) decreased daily potassium intake, 2) disorders of internal potassium balance (increased intracellular shift of potassium), and 3) disorders of external potassium balance (increased renal and more rarely, gastrointestinal potassium losses).^1,2,4

Due to increased renal potassium reabsorption in states of low serum potassium, decreased dietary intake alone is unlikely to lead to significant hypokalaemia.^1,4 Administration of intravenous fluids with a potassium deficient isotonic crystalloid, however, can lead to iatrogenic hypokalaemia.¹ An increased flux of potassium into cells can be observed with metabolic or respiratory alkalosis, refeeding syndrome, periodic hypokalaemic paralysis, hypothermia, rattle snake envenomation, or activation of the Na⁺-K⁺-ATPase pump due to increased insulin or catecholamine levels, beta adrenergic agonist therapy or toxicosis.^1,5-10 Increased gastrointestinal and urinary losses are the most important causes of hypokalaemia due to increased potassium loss and can be seen secondary to vomiting, diarrhoea, chronic kidney disease, diuretic administration, and several endocrinopathies.^1,2

Symptoms

Symptoms of hypokalaemia are generally not seen until potassium concentrations reach 3.0 mmol/L to 2.5 mmol/L.⁴ Hypokalaemia can affect multiple cellular functions, and acid-base balance, glucose metabolism, neuromuscular function, cardiovascular, and renal function can be impaired.^1,2,4 Acute potassium depletion can, therefore, lead to metabolic acidosis, hyperglycaemia, polyuria, polydipsia, decreased renal concentration ability, profound skeletal muscle weakness, as well as cardiac arrhythmias.^1,4,11-14

In cats specifically, hypokalaemic myopathy frequently manifests as ventroflexion of the neck and head. In severe cases of hypokalaemia, respiratory muscle fatigue can require ventilatory support until the hypokalaemia and polymyopathy have resolved.¹⁵ A variety of electrocardiographic (ECG) changes and cardiac arrhythmias have been observed in hypokalaemic dogs and cats but are less predictable than in hyperkalaemia. They can include atrial and ventricular tachyarrhythmias, ST segment depression, decreased amplitude of T waves, prolongation of the QT interval, and the appearance of U waves.^1,16,17

Treatment

Potassium deficits should be corrected, but immediate correction of the full deficit commonly is not urgent. Potassium replacement can generally be performed enterally or parenterally.

Parenteral administration of potassium solutions (e.g., potassium chloride, potassium phosphate) is indicated in patients with moderate (2.5 mmol/L to 3.4 mmol/L) to severe (<2.5 mmol/L) hypokalaemia.^1,2 The rate of intravenous potassium administration should generally not exceed 0.5 mmol/kg/h to avoid potential life threatening effects of iatrogenic hyperkalaemia.¹ Guidelines for potassium supplementation based on degree of hypokalaemia are provided below:

Table 1. Guidelines for intravenous potassium supplementation in dogs and cats 35

Patients that present in shock or dehydrated should be resuscitated or rehydrated prior to potassium repletion. Only in severely hypokalaemic animals should potassium substitution be started at the time of rehydration. Similarly, the administration of sodium bicarbonate and insulin to patients in diabetic ketoacidosis should be delayed until rehydration is achieved and serum potassium levels are >3.5 mmol/L as sudden correction of acidaemia and insulin replacement can worsen hypokalaemia by enhancing intracellular potassium shifts.^2,4 In a subset of hypokalaemic patients, simultaneous correction of magnesium deficits is likely to allow for more rapid and thorough correction of potassium deficit.¹⁸ When supplementing flexible intravenous fluid bags, extreme care must be taken to sufficiently mix the content of the bag to avoid inadvertent administration of fluids containing life threateningly high potassium concentrations.¹⁹

Oral potassium most commonly is administered in the form of potassium gluconate powder or tablets with food. The recommended dose is 0.5 mmol/kg body weight orally once to twice daily and should be titrated to effect.²⁰ Oral potassium substitution is limited to patients experiencing mild hypokalaemia (serum potassium concentration >3.4 mmol/L) and patients that voluntarily intake food or can be fed by oesophageal or gastroenteral feeding tubes.

Hyperkalaemia

Definition and Etiology

Hyperkalaemia is defined as serum potassium concentrations that exceed 5.5 mmol/L and can be life threatening at concentrations greater than 7.5 mmol/L.¹ As outlined above, potassium intake occurs orally, by intravenous infusion, or by increased potassium release from intracellular sites. Initially, most excess potassium is taken up and transiently stored intracellularly and then excreted primarily by the kidneys.³ Therefore, an abnormality in any process of potassium intake or generation, translocation from cells into extracellular fluid, or decreased renal excretion can lead to hyperkalaemia.³

Hyperkalaemia occurs more commonly due to excessive potassium supplementation in intravenous fluids than with increased oral intake. Renal potassium excretion is usually so efficient that an increase in potassium intake alone will not cause hyperkalaemia in a normal subject.¹ For hyperkalaemia to develop, urinary excretion of potassium must be reduced and prerenal (e.g., decreased effective circulating volume), renal (e.g., acute or chronic renal disease, hypoaldosteronism), and postrenal diseases (e.g., ureteral obstruction, urethral obstruction, uroabdomen) are the most common causes for persistent hyperkalaemia in companion animals.^1,3

Transcellular shift of potassium out of cells is a common cause of hyperkalaemia and can be seen secondary to accumulation of uraemic acids, respiratory acidosis, hydrogen chloride, or calcium chloride infusions.^2,21,22 Release of potassium from the intracellular space can occur when the rate of tissue breakdown is increased such as in severe exercise, trauma, heat stroke, administration of cytotoxic agents, or radiation therapy to patients with malignant lymphoma (tumour lysis syndrome), and during spontaneous reperfusion of the limbs or following treatment with thrombolytic agents in cats that suffer from aortic thromboembolism.^23-32

Symptoms

The clinical manifestations of hyperkalaemia are limited to skeletal muscle weakness and abnormal cardiac conduction and reflect the physiologic effect of potassium on resting membrane potential and membrane excitability.^1,21 Skeletal muscle weakness can develop when serum potassium concentration exceeds 8.0 mmol/L.¹ Severe hyperkalaemia can lead to atrial standstill, bradycardia, and ventricular asystole due to impaired membrane excitability of the cardiac conduction system.²¹ Rarely, wide complex tachycardia can be seen in cats with severe hyperkalaemia.³³

Treatment

The most appropriate treatment of hyperkalaemia is dependent on the degree of hyperkalaemia, the timeframe of onset, and the underlying cause. An ECG should be performed in every patient with moderate to severe hyperkalaemia as rapid onset of even moderate hyperkalaemia can cause cardiac arrhythmias.^1,2 Animals capable of normal urine potassium excretion (i.e., with normal urine output) and without clinical signs associated with hyperkalaemia in the range of 5.5 mmol/L to 6.5 mmol/L might not require immediate treatment, however, exogenous potassium administration should be discontinued and the cause for the hyperkalaemia investigated.¹ Potassium free (e.g., 0.9% NaCl) or potassium deficient fluids (e.g., lactated Ringer’s) can be administered to patients with normal urinary output to promote diuresis and may be sufficient to decrease serum potassium concentrations to normal ranges. The goals of treatment of patients suffering from severe hyperkalaemia or exhibiting clinical signs associated with hyperkalaemia is aimed at restoring the resting membrane potential of cells, normalizing cardiac action potential conduction velocities, and ultimately lowering the serum potassium concentration. Ten percent (10%) calcium gluconate antagonizes the effect of hyperkalaemia on myocardial resting membrane potential, but will not lower the potassium concentration.¹ Regular insulin with dextrose to prevent hypoglycaemia or the sole administration of dextrose solutions to increase endogenous insulin levels, sodium bicarbonate, and beta adrenergic agonists can all be successfully used to decrease serum potassium concentrations by promoting increased intracellular shifts of potassium.^2,34 A summary of treatments for life threatening hyperkalaemia is provided below.

Table 2. Treatment of severe hyperkalaemia^1,2,34

References

1.  DiBartola SP, DeMorais HA. Disorders of potassium: hypokalemia and hyperkalemia. In: DiBartola SP, ed. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice, 4th ed. St. Louis, MO: Elsevier Saunders; 2012.

2.  Riordan LL, Schaer M. Potassium disorders. In: Silverstein DC, Hopper K, eds. Small Animal Critical Care Medicine. St. Louis, MO: Elsevier Saunders; 2015.

3.  Rose BD, Post TW, eds. Potassium homeostasis. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. New York, NY: McGraw-Hill, Medical Pub. Division; 2001.

4.  Rose BD, Post TW, eds. Hypokalemia. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. New York, NY: McGraw-Hill, Medical Pub. Division; 2001.

5.  Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 1981;71(3):456–467.

6.  Armitage-Chan EA, O’Toole T, Chan DL. Management of prolonged food deprivation, hypothermia, and refeeding syndrome in a cat. J Vet Emerg Crit Care. 2006;16(s1):S34–41.

7.  Julius TM, Kaelble MK, Leech EB, Boyle KL, Strandberg EJ, Clare MC. Retrospective evaluation of neurotoxic rattlesnake envenomation in dogs and cats: 34 cases (2005–2010): Neurotoxic rattlesnake envenomation in dogs and cats. J Vet Emerg Crit Care. 2012;22(4):460–469.

8.  Malik R, Musca FJ, Gunew MN, Menrath VH, Simpson C, Culvenor J, et al. Periodic hypokalaemic polymyopathy in Burmese and closely related cats: A review including the latest genetic data. J Feline Med Surg. 2015;17(5):417–426.

9.  Matos MJ, Jenni S, Fischer N, Bienz H, Glaus MT. Myokardschädigung und paroxysmale ventrikuläre tachykardie bei einem hund nach albuterolintoxikation. Schweiz Arch Für Tierheilkd. 2012;154(7):302–305.

10.  McCown JL, Lechner ES, Cooke KL. Suspected albuterol toxicosis in a dog. J Am Vet Med Assoc. 2008;232(8):1168–1171.

11.  Garella S, Chang B, Kahn S. Alterations of hydrogen ion homeostasis in pure potassium depletion: studies in rats and dogs during the recovery phase. J Lab Clin Med. 1979;93(2):321–331.

12.  Dow SW, Fettman MJ, LeCouteur RA, Hamar DW. Potassium depletion in cats: renal and dietary influences. J Am Vet Med Assoc. 1987;191(12):1569–1575.

13.  Rowe JW, Tobin JD, Rosa RM, Andres R. Effect of experimental potassium deficiency on glucose and insulin metabolism. Metabolism. 1980;29(6):498–502.

14.  Bilbrey GL, Herbin L, Carter NW, Knochel JP. Skeletal muscle resting membrane potential in potassium deficiency. J Clin Invest. 1973;52(12):3011–3018.

15.  Hammond TN, Holm JL. Successful use of short-term mechanical ventilation to manage respiratory failure secondary to profound hypokalemia in a cat with hyperaldosteronism. J Vet Emerg Crit Care. 2008;18(5):517–525.

16.  Felkai F. Electrocardiographic signs in ventricular repolarization of experimentally induced hypokalaemia and appearance of the U-wave in dogs. Acta Vet Hung. 1985;33(3–4):221–228.

17.  Hanton G, Yvon A, Provost J-P, Racaud A, Doubovetzky M. Quantitative relationship between plasma potassium levels and QT interval in beagle dogs. Lab Anim. 2007;41(2):204–217.

18.  Hamill-Ruth RJ, McGory R. Magnesium repletion and its effect on potassium homeostasis in critically ill adults: Results of a double-blind, randomized, controlled trial. Crit Care Med. 1996;24(1):38–45.

19.  Hoehne SN, Hopper K, Epstein SE. Accuracy of potassium supplementation of fluids administered intravenously. J Vet Intern Med. 2015;29(3):834–839.

20.  Papich MG. Saunders Handbook of Veterinary Drugs: Small and Large Animal. Philadelphia, PA: Elsevier/Saunders; 2011.

21.  Rose BD, Post TW, eds. Hyperkalemia. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. New York, NY: McGraw-Hill, Medical Pub. Division; 2001.

22.  Abrams WB, Lewis DW, Bellet S. The effect of acidosis and alkalosis on the plasma potassium concentration and the electrocardiogram of normal and potassium depleted dogs. Am J Med Sci. 1951;122:506–515.

23.  Nickell JR, Shih A. Anesthesia case of the month. Administration of aged packed RBCs. J Am Vet Med Assoc. 2011;239(11):1429–1431.

24.  Borgeat K, Wright J, Garrod O, Payne JR, Fuentes VL. Arterial thromboembolism in 250 cats in general practice: 2004–2012. J Vet Intern Med. 2014;28(1):102–108.

25.  Calia CM, Hohenhaus AE, Fox PR, Meleo KA. Acute tumor lysis syndrome in a cat with lymphoma. J Vet Intern Med. 1996;10(6):409–411.

26.  Henry CJ, Lanevschi A, Marks SI, Beyer JC, Nitschelm SH, Barnes S. Acute lymphoblastic leukemia, hypercalcemia, and pseudohyperkalemia in a dog. J Am Vet Med Assoc. 1996;208(2):237–239.

27.  Fuentes VL. Arterial thromboembolism risks, realities and a rational first-line approach. J Feline Med Surg. 2012;14(7):459–470.

28.  Laing EJ, Fitzpatrick PJ, Binnington AG, Norris AM, Mosseri A, Rider WD, et al. Half-body radiotherapy in the treatment of canine lymphoma. J Vet Intern Med Am Coll Vet Intern Med. 1989;3(2):102–108.

29.  Schaafsma IA, van Emst MG, Kooistra HS, Verkleij CB, Peeters ME, Boer P, et al. Exercise-induced hyperkalemia in hypothyroid dogs. Domest Anim Endocrinol. 2002;22(2):113–125.

30.  Teichmann S, Turković V, Dörfelt R. Hitzschlag bei hunden in süddeutschland. Tierärztl prax kleintiere. 2014;42(4):213–222.

31.  Welch KM, Rozanski EA, Freeman LM, Rush JE. Prospective evaluation of tissue plasminogen activator in 11 cats with arterial thromboembolism⋆. J Feline Med Surg. 2010;12(2):122–128.

32.  Ookuma T, Miyasho K, Kashitani N, Beika N, Ishibashi N, Yamashita T, et al. The clinical relevance of plasma potassium abnormalities on admission in trauma patients: a retrospective observational study. J Intensive Care. 2015;3:37.

33.  Norman BC, Côté E, Barrett KA. Wide-complex tachycardia associated with severe hyperkalemia in three cats. J Feline Med Surg. 2006;8(6):372–378.

34.  Stafford JR, Bartges JW. A clinical review of pathophysiology, diagnosis, and treatment of uroabdomen in the dog and cat. J Vet Emerg Crit Care. 2013;23(2):216–229.

35.  Greene RW, Scott RC. Lower urinary tract disease. In: Ettinger SJ, ed. Textbook of Veterinary Internal Medicine. Philadelphia, PA: WB Saunders Co.; 1975.