Hypokalaemia

Most cases are the result of either diuretic consumption or loss of GI fluids through persistent vomiting, chronic diarrhoea or laxative abuse. With vomiting, the cause is not mainly direct loss of potassium but that of chloride causing high levels of aldosterone and inhibiting potassium reabsorption from the kidney tubules. In diarrhoea, loss of bicarbonate may cause metabolic acidosis which causes a shift of potassium into the cells so that serum concentration may not reflect total potassium levels.

The commonest congenital cause of hypokalaemia is Gitelman's syndrome associated with impaired renal tubular ion transport due to a mutation in the Na⁺/Cl^– cotransporter gene.² Bartter syndrome is closely related but presents in infancy with failure to thrive and is due to a mutation in the Cl^– channel gene.

Common problem, particularly amongst some subgroups of the population. For example, 2.5% population aged over 75 years in a Swedish study (strongly associated with use of thiazides or combination diuretics),³ 20.6% British adults receiving thiazides⁴ and 19.7% anorexics in an outpatient setting.⁵ Risk of developing hypokalaemia is increased by concomitant illness, particularly heart failure, alcoholism and nephrotic syndrome.

• Mild forms are generally asymptomatic. In more severe condition symptoms (ie K⁺ <3.0 mmol/l) include:
  • Lassitude
  • Generalised weakness and muscle pain (due to rhabdomyolysis)⁶
  • Constipation
  At K⁺ <2.5 mmol/l, serious neuromuscular problems emerge including:
  • Paralysis
  • Paraesthesia
  • Tetany
• Suspect from clinical context, eg diuretics, copious vomiting, prolonged diarrhoea. Patient may conceal their abuse of diuretics or laxatives and self-induced vomiting.
• Gitelman's syndrome typically presents early in adulthood with hypotension, alkalosis and salt wasting together hypomagnesaemia, hypocalciuria and hypermagnesuria. Clinical signs include salt craving, cramps, muscle weakness and aches, fatigue, generalised weakness and dizziness, nocturia and polydipsia.
• ECG changes - when K⁺ <3.0 mmol/l the ECG often demonstrates flat T waves, ST depression, QT interval prolongation and prominent U waves. Ventricular arrhythmias such as premature ventricular contractions, torsades de pointes, ventricular tachycardia and ventricular fibrillation can also occur.⁷

Urine tests

• Urinary potassium - where low suggests poor intake, shift into the intracellular space or GI loss. Where high, suggests renal loss.
• Urinary sodium - low urinary sodium combined with high urinary potassium suggests secondary hyppoaldosteronism.
• Urinary osmolality - needed to interpret urinary potassium levels.

Blood tests

• U and Es - where serum sodium is low, suggests thiazide use or marked volume depletion
• Serum bicarbonate
• Serum glucose
• Creatine kinase
• Serum magnesium - low serum magnesium often accompanies hypokalaemia and needs to be corrected to enable recovery of serum potassium

ECG

To determine whether the hypokalemia is affecting cardiac function or to detect digoxin toxicity.
Additional tests may be required if clinical suspicion of a particular underlying disorder is high. For example:

• Diuretic screen in urine and/or serum
• Serum renin, aldosterone, and cortisol
• 24-hour urine aldosterone, cortisol, sodium, and potassium
• Pituitary imaging to evaluate Cushing syndrome
• Adrenal imaging
• Renal angiogram to exclude renal artery stenosis

The management of hypokalaemia is almost always by potassium replacement. The amount of supplementation required depends on the severity of the hypokalaemia. Urgency of replacement is also guided by severity and other medical problems (eg recent MI, digoxin use). Each 0.3 mmol/l reduction in serum level reflects 100 mmol/l deficit in body stores in most cases. So, for example, a patient with a serum potassium of 2.6 mmol/l, will require at least 300 mmol of potassium to correct the deficit.
Potassium replacement can be oral (dietary or with supplements) or intravenously:

• Normal diet contains significant amounts of potassium but is usually as phosphates and will be ineffective in replenishing body potassium in common causes unless adequate chloride is also supplied. Foods containing high potassium include bananas, potatoes and chocolate.
• Potassium supplements - usually given as potassium chloride (eg Sando-K®, Slow-K®) 40-120 mmol/day in divided doses. Potassium phosphate can be used for patients with combined potassium and phosphate depletion (eg in liver cirrhosis or DKA) and potassium bicarbonate is suitable for patients with potassium depletion and metabolic acidosis (eg distal renal tubular acidosis)
• Intravenous replacement - with severe hypokalaemia (where serum potassium is less than 2.6 mmol/l), potassium chloride (KCl) can be infused via a peripheral line. KCl concentration should not exceed 40 mmol/l (60 mmol/l in an emergency) and the rate should not exceed 20 mmol/h. Never bolus KCl as it can cause fatal arrhythmias. In an emergency, IV KCl can be administered via a central line but requires continuous cardiac monitoring.

Gitelman's syndrome is treated with potassium and magnesium supplementation and NSAIDs.
Counselling and psychiatric referral is appropriate for the diuretic or laxative abuse/self-induced vomiting associated with bulimia.

• Cardiac arrhythmias and sudden cardiac death¹⁰ (those with congestive cardiac failure, underlying IHD, on digoxin or aggressive therapy for hyperglycaemia in diabetic ketoacidosis are most vulnerable)
• Muscle weakness, flaccid paralysis, rhabdomyolysis
• Abnormal renal function including nephrogenic diabetes insipidus, metabolic alkalosis (due to enhanced bicarbonate absorption) and enhanced renal chloride excretion
• Ileus
• Contributes to the development of hepatic encephalopathy in cirrhosis
• Chronic hypokalaemia is a factor in the development of hypertension

It is seldom necessary to use potassium supplementation with low dose diuretics used as antihypertensives. However, if potassium salts are used to prevent hypokalaemia, approximately 25-50 mmol/day in divided oral doses is usual. Smaller doses should be used if there is danger of renal insufficiency, especially in the elderly. Potassium salts can cause nausea and vomiting, so poor concordance is common. Replacing thiazide or loop diuretic with potassium-sparing ones such as spironolactone or amiloride is frequently preferable. Potassium salts are better given as a liquid or effervescent preparation as the non-effervescent tablets can cause severe oesophageal and gastric irritation. Long-term oral potassium supplementation requires careful monitoring.