Hypokalaemia

Essentials

• Hypokalaemia denotes a state where the concentration of potassium in the plasma and the entire extracellular space is lower than 3.3 mmol/l.
• Hypokalaemia is detected in 20% of hospitalised patients. Hypokalaemia is only mild in most cases.
• Severe hypokalaemia is present in 5% of hospitalised patients; plasma potassium concentration being below 2.5 mmol/l. Then emergency assessment and treatment are usually necessary.
• In primary health care, hypokalaemia is detected in 10-40% of patients using diuretics.
• Identifying the cause of hypokalaemia is essential for selecting appropriate treatment.

Potassium homeostasis

• The plasma potassium level is regulated by shifting potassium between extracellular and intracellular spaces and through maintaining a balance between potassium intake and renal excretion.
• Insulin and catecholamines regulate the entry of potassium into the intracellular space through stimulating the Na+/K+-ATPase enzyme on the cell membrane. An infusion of insulin and a strong adrenergic stimulation will, therefore, lead to hypokalaemia.
• Aldosterone and other mineralocorticoids affect the body's potassium stores through regulating the excretion of potassium in the urine by activating the epithelial sodium channels in the renal tubules.
• An excessive amount of mineralocorticoids will lead to hypokalaemia and their deficiency to hyperkalaemia.
• A feedback system operates between plasma potassium concentration and aldosterone secretion; hyperkalaemia stimulates the secretion of aldosterone whereas hypokalaemia prevents its secretion.
• The effect of aldosterone on the distal renal tubule is regulated by the amount of sodium delivered to the distal tubule and the acid-base balance. Low sodium delivery will suppress the kaliuretic effect of aldosterone.
• The most common cause of hypokalaemia is the loss of potassium through the digestive tract or the use of diuretics.
• It is important to identify hypokalaemia associated with hypertension, and consequently to suspect secondary hypertension and inappropriate activation of mineralocorticoid receptors.

Causes of hypokalaemia

• Insufficient intake of dietary potassium is rarely the cause of hypokalaemia and is only possible where the daily intake is less than 1 g.
  • Anorexia nervosa
  • Chronic malnourishment
• Excessive sweating or extensive burns may lead to loss of potassium through skin.
• Often the condition in is caused by a mixture of several mechanisms.

Recognition

• Hypokalaemia is diagnosed by determining the plasma potassium concentration
• Hypokalaemia-induced ECG changes include T wave flattening and inversion, ST segment depression and the appearance of a U wave.

Symptoms

• Hypokalaemia causes muscle weakness, asthenia, constipation, polyuria and loss of appetite
• Muscular symptoms appear when plasma potassium concentration falls below 2.5 mmol/l
• Hypokalaemia of an abrupt onset may cause frank paralysis
• Hypokalaemia increases the risk of cardiac arrhythmias (extrasystoles, conduction defects, tachyarrhythmias), especially in coronary heart disease, heart failure and in patients using digoxin.
• Glucose control is impaired, since insulin excretion from beta cells is reduced and insulin resistance increases.

Diagnosis

• Ask the patient about
  • use of diuretics, glucocorticoids, laxatives and other drugs that cause hypokalaemia
  • liquorice consumption
  • gastrointestinal symptoms (diarrhoea, vomiting).
• Physical examination
  • Blood pressure
  • Appearance
  • Nutritional state
  • Tooth erosion
• First line investigations: acid-base balance, plasma potassium, sodium, chloride, ionised calcium, magnesium, creatinine
• ECG
• For differential diagnosis it is essential to establish whether the patient is hypertensive or normotensive.
  • The differential diagnosis of hypokalaemia in a normotensive patient must include the evaluation of renal chloride excretion.
  • The differential diagnosis in hypertensive patients concentrates on the results of renin and aldosterone assays.
• If the cause of hypokalaemia cannot be ascertained, further investigations are indicated:
  • 24 hour urine sodium, potassium, chloride and magnesium
  • plasma renin activity and serum aldosterone
  • 1 mg overnight dexamethasone suppression test, salivary cortisol test or 24 hour urine cortisol, if Cushing syndrome Cushing's Syndrome is suspected
  • urine pH.
• A urine drug screen may be appropriate in order to diagnose surreptitious diuretic use.
• Alkalosis as such will maintain kaliuresis despite existing hypokalaemia.

Treatment

• The mainstay of treatment is discontinuation of drugs that reduce blood potassium concentration and the correction of potassium deficiency and possible magnesium deficiency.
• The extent of potassium deficiency cannot be accurately assessed from the plasma potassium concentration. As a rule of thumb it may be considered that when potassium stores diminish by 100 mmol the plasma potassium concentration falls 0.3 mmol/l. If plasma potassium is 2.5 mmol/l, the body's potassium deficiency is at least 300 mmol.
• Potassium deficiency is primarily corrected by administering 2-6 g potassium chloride by mouth. The daily dose is 25-80 mmol (1 g = 13 mmol).
• The maximum hourly dose of intravenous potassium is 20 mmol, which would increase plasma potassium concentration by 1 mmol/l in the absence of ongoing potassium loss. In alkalosis some of the potassium administered is excreted in the urine, and the actual effect is, therefore, smaller.
• Potassium is infused in a peripheral vein as a glucose solution (HASH(0x2fd0288) 40 mmol/l); the solution infused in a central vein may be stronger.
• The rapid correction of severe hypokalaemia requires continuous ECG monitoring, measurements of plasma potassium concentrations every 2-4 hours, and it is carried out in a unit with appropriate monitoring capacity.
• Fluids containing glucose or administration of insulin may initially worsen the hypokalaemia as potassium is shifted into the intracellular space.
• For the same reason, correction of metabolic acidosis by bicarbonate or treatment with a beta₂-agonist is safest to start only when the potassium concentration is HASH(0x2fcfe80) 3 mmol/l.
• Hypomagnesaemia is corrected by administering magnesium sulphate 40-60 mmol/day by infusion or as an oral preparation containing magnesium 0.5-1.5 mmol/kg/day.
• Drug therapies tailored according to the underlying disease in hypokalaemia are for example
  • spironolactone or eplerenone (inhibition of mineralocorticoid effect)
  • metyrapone or ketoconazole (hypercortisolism)
  • amiloride or triamterene (Liddle syndrome).

References

• Medford-Davis L, Rafique Z. Derangements of potassium. Emerg Med Clin North Am 2014;32(2):329-47. [PubMed]