Hypokalemia is a pathological state in which serum potassium is lower than the lowest normal physiological concentration. It is an electrolyte disorder caused by many diseases. If it is not treated promptly and effectively or due to improper medication, it may lead to aggravation of the patient's condition or even sudden death.Potassium supplementation is therefore an important aspect of fluid therapy in hospitalized animals, especially in severe cases.

Physiology of Potassium 

Under normal circumstances, red blood cells are constantly growing and undergoing apoptosis, and their production rate is equal to the apoptosis rate, thereby maintaining a dynamic balance of the number of red blood cells in the blood.

Hypokalemia is evaluated based on the serum potassium concentration of 3.6mmol/L:

Mild hypokalemia: 3~3.6mmol/L;

Moderate hypokalemia: 2.5~3mmol/L;

Severe hypokalemia: <2.5mmol/L;

Potassium is the main cation that maintains cell physiological activity. It plays an important role in maintaining the normal operation of nerve and muscle cells (including cardiomyocytes) and maintaining normal cell resting membrane potential. Therefore, understand the role of potassium in generating resting membrane potential, It is crucial to understand the importance of potassium supplementation in hypokalemic states.

Most of the potassium in the body (about 98%) is located inside the cells. The intracellular concentration is about 140mEqL and the extracellular concentration is 4mEqL. This normal relationship is maintained by the Na/K-ATPase mechanism of the cell membrane in a ratio of 3:2 Pumping sodium ions out of the cell and potassium ions into the cell creates a concentration gradient that causes potassium to flow out of the cell.

Since the cell membrane is impermeable to most intracellular anions, a net potential difference will be generated on the cell membrane when potassium efflux occurs, and this potential difference or resting cell membrane potential has a significant impact on the action potential of excited tissues (i.e. cardiac muscle, skeletal muscle, nerves) The production is crucial.Hypokalemia will cause an increase in the concentration difference across cell membranes, leading to a more negative resting membrane potential and cell hyperpolarization, leading to muscle weakness, electrocardiogram abnormalities, and arrhythmias.

Therefore, although the absolute amount of potassium is important, the ratio of intracellular to extracellular potassium concentration may be more important when considering the clinical significance of hypokalemia.

Causes of hypokalemia

Normal potassium concentrations are balanced by intake (i.e., diet) and output (about 90 to 95% via the kidneys, the remainder via the gastrointestinal tract). Another aspect of potassium balance is the normal distribution of potassium between cells and extracellular fluid. Distribution, at the cellular level, potassium balance is mainly affected by the upregulation of the Na/K-ATPase mechanism stimulated by insulin and 6-2 epinephrine.

In addition, the acid-base status also affects potassium distribution. Acidosis usually causes potassium to move extracellularly, while alkalosis causes potassium to move intracellularly.

Causes of hypokalemia can be divided into three broad categories:

·Potassium deficiency hypokalemia: reduced intake of potassium-containing foods (cannot be the only cause), excessive gastrointestinal/renal losses;

·Transferred hypokalemia: transfer of extracellular potassium into cells causing a decrease in serum potassium;

·Dilutional hypokalemia: excessive extracellular fluid, increased blood volume, and relatively reduced serum potassium concentration;

Specific causes of hypokalemia included in the 5th edition of Small Animal Internal Medicine

Generally speaking, the extracellular (that is, plasma) potassium concentration reflects the total potassium stores in the body, but in some cases this is not always the case.

When considering causes of hypokalemia, it is critical to distinguish systemic potassium deficiency from hypokalemia measured extracellularly (or in the plasma).

Systemic potassium deficiency: usually the result of excessive loss from the kidneys and gastrointestinal tract, such as various renal diseases, other conditions that can cause primary/secondary polyuria, and various gastrointestinal diseases.

plasma hypokalemia is detectable, often due to increased potassium transport from extracellular to intracellular fluid, including alkalemia, drugs, or conditions (eg, Xylitol, oral hypoglycemic agents, refeeding syndrome), catecholamines (stimulatory consequences of beta-2 agonists), hypothermia, albuterol overdose, thyrotoxicosis, barium toxicity, and hypokalemic periodic paralysis in Maine Coon cats.

Clinical features of hypokalemia

Most dogs and cats with mild to moderate hypokalemia have no clinical symptoms. Clinically, severe hypokalemia mainly affects the neuromuscular and cardiovascular systems.

Generalized muscle weakness is the most common symptom. In cats, the neck can be bent forward, the forelimbs are excessively extended, and the hindlimbs are abducted. They are more susceptible than dogs. It can also lead to respiratory muscle weakness and the need for assisted breathing.

The impact on the heart includes weakened myocardial contractility, reduced cardiac output, cardiac rhythm disorders, and the clinical manifestations are variable. It can only be diagnosed through electrocardiogram. The specific manifestations in electrocardiogram are:

Decreased T wave amplitude

·ST segment weakening

·QT interval prolongation

·U wave protrusion

·Arrhythmias (supraventricular/ventricular)

In addition, hypokalemia may reduce the clinical efficacy of Class I antiarrhythmic drugs.

Symptoms of other hypokalemia-related conditions include:

Hypokalemic nephropathy: chronic tubulointerstitial nephritis, impaired renal function and azotemia, polydipsia and polyuria, impaired concentrating ability;

Hypokalemic polymyopathy: increased serum CK activity and abnormal electromyography;

Paralytic ileus: abdominal distension, anorexia, vomiting, constipation;

Step-by-step diagnosis of hypokalemia

The key points for diagnosing hypokalemia are often summarized as asking the medical history and observing the clinical manifestations to see whether there is muscle weakness; decreased or absent tendon reflexes, nausea, vomiting and abdominal distension; testing whether the blood potassium concentration is lower than 3.6mmol/L; whether there is any electrocardiogram Abnormal changes include early T wave decrease, widening, biphasic or inversion, followed by ST segment decrease and U wave appearance. The following diagnostic ideas are available for reference:

Review current medication history:

Increased loss or decreased uptake via intracellular transfer

Consider the characteristics of individual animals：

Is this a young Maine Coon cat? It has been reported that in Maine Coon cats aged 4 to 12 months, there is a syndrome characterized by repeated episodes of limb muscle weakness, ventral neck laxity, elevated creatine kinase concentrations, and hypokalemia - hypokalemia. Hemorrhagic phase polymyopathy[1];

Is this a senior cat? Aldosterone-producing adrenal tumors due to hyperaldosteronism, which can further produce hypokalemia, can be considered in all older cats;

Does the animal have gastrointestinal symptoms or evidence of gastrointestinal disease (suggesting potassium loss)?

Is there a possibility of refeeding syndrome?

Does the animal have evidence of kidney disease?

What is the acid-base status?

If the medical history is unclear or if both gastrointestinal and renal disease are suspected, calculating the fractional excretion potassium (FEK) can help distinguish gastrointestinal losses from renal losses as follows:

FEK= (Uk/Sk) / (Ucr/Scr) x100%

in a study (adamsetal.1991)[2], the fek value of normal cats was 10.6+/-2.1%; in other words, if fek>10~12%, the kidneys are losing too much potassium; if fek< in 10~12%, the cause of hypokalemia is gastrointestinal loss and/or intracellular k+ translocation; in another study (dow et al. 1990) [3], normal cats fed a potassium-free diet, fek value will drop from 10%~12% to 3%~6%;

In potassium-deficient animals with normal renal function, a FEK of 6% should be considered normal, but the clinical utility of the FEK calculation may be limited by the fact that FEK does not correlate well with urinary potassium excretion over a 24-hour period;

Treatment of hypokalemia

In the treatment of hypokalemia, if acute hypokalemia occurs, emergency measures should be taken for treatment. For chronic hypokalemia, as long as the serum potassium is not less than 3mmol/L, the cause can be checked first and then treated accordingly. Treatment, the basic treatment principles are as follows:

·Treatment of the underlying disease requires identifying and addressing the underlying cause of hypokalemia;

·Complete correction of hypokalemia within one to two days may not be required;

·To correct hypokalemia in animals with hypophosphatemia, most commonly caused by diabetic ketoacidosis, potassium phosphate solution contains:potassium = 4.4mEq/ml, phosphate = 3mmol/ml. When using potassium phosphate to correct hypophosphatemia, serum potassium concentration must be considered. It is recommended to correct serum phosphorus at a rate of 0.03~0.12 mmo/kg/hr;

·Use potassium chloride to supplement potassium. If the dog or cat can take it orally, try to take it orally. Otherwise, supplement it through intravenous drip;

General rules for oral potassium supplementation:

Studies have found that oral KCI and KHCO3 are not well tolerated by cats, and potassium gluconate is recommended; dogs may require 2-44 mEq of potassium per day, depending on size.

In cats with hypokalemic nephropathy, the initial oral dose of potassium gluconate is 5 to 8 mEq/day given in two to three divided doses, while the maintenance dose can usually be reduced to 2 to 4 mEq/day.

Indications for parenteral potassium supplementation:

Moderate to severe hypokalemia (<3 mEq/L); animal requires hospitalization and cannot tolerate oral medications; animal receives easily potassium-replenishing intravenous fluids

Preparations available for parenteral use (USA) include:

·Potassium chloride solution: Contains 2mEq potassium per mL

·Potassium phosphate solution containing K2 HPO4 and KH2 PO4 (K=4.36mEqK/mL; phosphorus=3.003mmol/mL; osmotic pressure=5840mosm/kg)

General rules for parenteral potassium supplementation:

The potassium concentration in peripherally administered infusion fluids should generally not exceed 60 mEq/L because higher concentrations of potassium may cause peripheral venous pain and sclerosis (Rose et al., 1994) [4];

Parenteral fluids containing 35 mEqL can be safely used for subcutaneous administration (Finco et al. 1977)[5];

Animals with potassium supplements greater than 0.1~0.2 meq/kg/hr should monitor potassium ions every 4~6 hours;

Animals with potassium supplementation greater than 0.4 mEq/kg/hr should undergo ECG monitoring and potassium ion monitoring every 4 hours;

Generally speaking, potassium supplementation exceeding 0.5 mEq/kg/hr (maximum) is not recommended. There are some exceptions. In one study, potassium infusion rates as high as 0.9 mEq/kg/hr were safe in hypokalemic animals (Hamill et al., 1991) [6]. After adding potassium chloride to the soft infusion bag, it is important to mix thoroughly! Rates higher than 0.5 mEq/kg/hr should only be used in life-threatening hypokalemia when there is insufficient time for slow potassium replacement or during cardiopulmonary resuscitation (CPR).It is recommended to calculate potassium supplementation in mEq/kg/hr and then convert this value to the amount of potassium contained in one liter of intravenous fluid.

Prognosis of hypokalemia

The prognosis of hypokalemia mainly depends on the chance of curing the primary disease. In most cases, the potassium content in the body can return to normal levels after treatment of the primary disease and potassium supplementation. However, the primary disease of some affected pets cannot be cured, such as familial hypokalemic periodic paralysis, etc., and potassium supplementation can only be maintained regularly to maintain balance.

reference：

[1] Malik R, Musca FJ, Gunew MN, et al. Periodic hypokalaemic polymyopathy in Burmese and closely related cats:a review including the latest genetic data.JFeline Med Surg.2015;17(5):417-426.doi:10.1177/1098612X15581135;

[2] Adams LG, Polzin DG, Osborne CA, et al. Comparison of fractional excretion and 24-hour urinary excretion of sodium and potassium in clinically normal cats and cats with induced chronic renal failure. Am J Vet Res 1991;52:718;

[3] Dow SW, Fettman MJ, Smith KR, et al. Effects of dietary acidification and potassium depletion on acid-base balance, mineral metabolism and renal function in adult cats. J Nutr 1990;120:569;

[4] Rose BD. Hypokalemia.In: Rose BD,editor. Clinical physiology of acid-base and electrolyte disorders.New York:McGraw-Hill;1994.94.p.811;

[5] Finco DR. Fluid therapy. In: Kirk RW, editor. Current veterinary therapy VI. Philadelphia:WB Saunders; 1977.p.8.

[6] Hamill RJ, Robinson LM, Wexler HR, et al. Efficacy and safety of potassium infusion therapy in hypokalemic critically ill patients.Crit  Care Med 1991;19:694;