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January 2025 — this is a new CKS topic. A literature review was performed in September 2024. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

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Additional information on causes of hypokalaemia

Medications

• Medications can affect the blood potassium concentration through a number of mechanisms. The most common medications associated with hypokalaemia include [SPS, 2024]:
  • Thiazide, thiazide-like, and loop diuretics — diuretic therapy is a common cause of hypokalaemia, affecting up to approximately 50% of those using these diuretics [Lin, 2021].
    • Thiazide, thiazide-like, and loop diuretics work by inhibiting renal sodium resorption, which increases sodium and water excretion in urine. The increased sodium delivery to the distal nephron results in compensatory mechanisms which cause potassium loss due to increased sodium-potassium exchange. The increased water loss triggers aldosterone release (through activation of the renin-angiotensin-aldosterone system) which promotes potassium excretion in exchange for sodium retention [BMJ Best Practice, 2022].
    • The risk of diuretic-induced hypokalaemia is related to the dosage of the drug, and may be higher in women and in black people [Lin, 2021].
    • A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac dysrhythmias can increase the risk of cardiovascular events and mortality [Lin, 2021].
    • Thiazide and thiazide-like diuretics include bendroflumethiazide, chlortalidone, hydrochlorothiazide, indapamide, metolazone, and xipamide [BNF, 2024].
    • Loop diuretics include bumetanide, furosemide and torsemide [BNF, 2024].
  • Acetazolamide — inhibition of carbonic anhydrase subsequently inhibits sodium and bicarbonate reabsorption in the proximal tubule thereby resulting in an increased distal delivery of sodium and bicarbonate, resulting in potassium wasting [Unwin, 2011].
  • Amphotericin B, cisplatin, and carboplatin — cause renal magnesium wasting [Daly, 2013]. The mechanism by which this results in hypokalaemia is uncertain [BMJ Best Practice, 2022], but the hypomagnesaemia may decrease the activity of the magnesium-dependent, sodium-potassium-ATPase pump in the renal nephron resulting in a decreased potassium reabsorption and renal potassium wasting [Daly, 2013].
  • Aminoglycoside antibiotics — use has been associated with hypokalaemia, hypomagnesemia, and hypocalcaemia. The mechanisms by which aminoglycosides alter renal tubular function are unknown [Scoglio, 2021].
  • Antipsychotics — clozapine, olanzapine, risperidone, and quetiapine use has been associated with hypokalaemia. The mechanism by which antipsychotics result in hypokalaemia is unclear, but may be related to antipsychotic induced hypercatecholaemia (which induces the intracellular shift of potassium) [Yang, 2018].
  • Beta-agonists such as salbutamol and adrenaline — beta adrenergic agents stimulate the sodium-potassium-ATPase pump and induce the intracellular movement of potassium [Daly, 2013].
  • Beta-lactam antibiotics such as penicillins, cephalosporins, or carbapenems — use results in non-reabsorbable anions in the nephron which creates a negative gradient on the inner side of the cortical collecting duct leading to increased renal potassium excretion [Jansen, 2024].
  • Corticosteroids — affect potassium homeostasis through several mechanisms including an indirect effect on the sodium-potassium-ATPase pump, which induces the intracellular movement of potassium. They also induce insulin resistance leading to hyperglycaemia and hyperinsulinemia, which favours an intracellular shift of potassium and increase renal potassium excretion by their mineralocorticoid effect [Shin, 2021].
  • Insulins — Insulin stimulates cellular uptake of glucose which in turn stimulates potassium cellular uptake [Daly, 2013].
  • Laxative use (particularly chronic or misuse) — increases gastrointestinal losses [BMJ Best Practice, 2022].
  • Xanthines such as theophylline and aminophylline — induce the intracellular movement of potassium [Veltri, 2015].

Hypomagnesaemia

• More than 50% of clinically significant hypokalaemia has concomitant magnesium deficiency [Kardalas, 2018].
• The mechanism by which hypomagnesaemia results in hypokalaemia is uncertain [BMJ Best Practice, 2022], but hypomagnesaemia may decrease the activity of the magnesium-dependent, sodium-potassium-ATPase pump in the renal nephron resulting in a decreased potassium reabsorption and renal potassium wasting [Daly, 2013].
• Concurrent hypokalaemia and hypomagnesaemia is most frequently observed in individuals receiving loop or thiazide diuretics [Kardalas, 2018].
• Hypokalaemia associated with hypomagnesaemia is often refractory to treatment with potassium, and therefore necessitates the initial correction of the magnesium deficiency [Kardalas, 2018; BMJ Best Practice, 2022].

Mineralocorticoid receptor activation

• Excessive activation of epithelial cell mineralocorticoid receptors in the distal tubule and collecting duct of the kidney, colonic mucosa, and sweat glands promotes renal sodium and water reabsorption, resulting in a consequential potassium loss [Ekman, 2024].
• Numerous conditions and exogenous agents can induce mineralocorticoid excess. These include:
  • Primary aldosteronism — characterised by excessive aldosterone secretion from the adrenal zona glomerulosa. Aldosterone subsequently binds to mineralocorticoid receptors in epithelial cells [Ekman, 2024].
    • Primary aldosteronism may be indicated by the presence of oedema, hypertension, or metabolic alkalosis [Emmett, 2020; BMJ Best Practice, 2022].
    • Hypokalaemia may be present in 28% of people with primary aldosteronism [Ekman, 2024].
  • Hypercortisolaemia — characterized by excessive serum cortisol concentrations, which occur due to dysregulation in the hypothalamic-pituitary-adrenal axis or due to exogenous steroid use.
    • Results in symptoms of weight gain/obesity, muscle weakness, and mood alterations [Khan, 2024].
    • Hypokalaemia results from excess cortisol-mediated activation of mineralocorticoid receptors, leading to increased urinary potassium excretion and renal potassium wasting. Additionally, metabolic alkalosis secondary to cortisol excess further exacerbates hypokalaemia [Khan, 2024].
    • Ectopic adrenocorticotrophic hormone (ACTH) secretion by a non-pituitary tumour can be a rare cause of hypercortisolaemia [Larose, 2023].
  • Chronic liquorice ingestion — mineralocorticoid receptors bind to cortisol and aldosterone with equal affinity. An enzyme expressed in aldosterone-specific tissues (11 beta-hydroxysteroid dehydrogenase type 2) converts active cortisol to inactive cortisone and prevents the inappropriate activation of mineralocorticoid receptors by cortisol. An ingredient found in liquorice (glycyrrhizin) inhibits the activity of this enzyme, allowing the unopposed activation of mineralocorticoid receptors by cortisol, leading to features of mineralocorticoid excess [McHugh, 2021].
    • Likely an uncommon cause of apparent mineralocorticoid excess.
  • Alcoholism — in addition to a decreased potassium intake due to poor diet and increased gastrointestinal losses through vomiting or diarrhoea, chronic alcohol intake may also increase aldosterone secretion resulting in mineralocorticoid receptor activation [BMJ Best Practice, 2022].
  • Geller syndrome — a very rare autosomal dominant disease which produces a mutation in the mineralocorticoid receptor that ultimately causes hypokalaemia and hypertension during pregnancy [Hindosh, 2022].
    
    • Occurs due to an agonistic effect of progesterone on the mutated mineralocorticoid receptor.
    • Usually resolves post-partum.
    • Distinctive from other causes of mineralocorticoid excess as it will present without elevated renin or aldosterone levels.
  • Gitelman syndrome — a rare autosomal recessive disease characterized by hypokalaemic metabolic alkalosis, impaired urinary concentrating capacity (causing polyuria) and secondary hyperaldosteronism without hypertension [Stimson, 2018; Palazzo, 2022].
    • Produces hypokalaemia due to the genetically-determined functional impairment of sodium chloride and magnesium transporters, which decreases reabsorption in the distal convoluted tubule, resulting in salt wasting and polyuria, thereby raising aldosterone secretion [Knoers, 2008].
    • Usually presents in early infancy with failure to thrive.
  • Bartter syndrome — a rare autosomal recessive disease characterized by hypokalaemic metabolic alkalosis, impaired urinary concentrating capacity (causing polyuria) and secondary hyperaldosteronism without hypertension [Palazzo, 2022].
    • Produces hypokalaemia through a similar mechanism as Gitelman syndrome (see above), but with the functional impairment affecting the sodium chloride transporter in the thick ascending loop of Henle [Palazzo, 2022].

Other inherited disorders which cause potassium wasting

• A positive family history for any of the following in people with hypokalaemia should raise suspicions about these conditions:
  • Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST) syndrome — an autosomal dominant disorder caused by mutations in a gene which encodes a potassium channel on the basolateral side of the distal renal tubule. The loss of function mutation impairs the sodium-potassium-ATPase causing salt wasting and stimulation of the RAAS system axis resulting in further potassium excretion [Zieg, 2016].
  • Liddle syndrome — an autosomal dominant disease caused by a gain-of-function mutation which alters the structure of the epithelial sodium channel subunit. The altered subunit delays the degradation of the sodium channel thereby increasing its expression, leading to excessive sodium and water reabsorption, which ultimately results in potassium excretion. Metabolic alkalosis is usually present in patients who present with hypertension and hypokalaemia [Zieg, 2016].

Alkalosis

• Metabolic alkalosis may result from chloride depletion due to vomiting or nasogastric suction [Kardalas, 2018; Krogager, 2021; Kim, 2023].
• Metabolic or respiratory alkalosis (elevation in the extracellular pH) promotes the intracellular shift of potassium [BMJ Best Practice, 2022].
• The mechanism involves the movement of cellular hydrogen ions into the extracellular space to decrease the elevated pH, which results in the intracellular movement of potassium to maintain the electroneutrality [BMJ Best Practice, 2022].

Diabetic ketoacidosis or hyperosmolar hyperglycaemic state

• Produces marked potassium loss [BMJ Best Practice, 2022].
• Hyperosmolar hyperglycaemic state is most common in older people with type 2 diabetes [BMJ Best Practice, 2022].
• A history of diabetes should prompt suspicion of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS) [BMJ Best Practice, 2022].
• DKA is suggested by a history of polyuria, fatigue, weight loss, nocturia, and a rapid deterioration in clinical state (with nausea, abdominal pain, and vomiting) [BMJ Best Practice, 2022].
• DKA and HHS result in emesis and osmotic diuresis leading to secondary hyperaldosteronism, both of which cause hypokalaemia [Davis, 2016]. 
  • Serum concentrations of potassium can be elevated due to the acidosis and insulin deficiency, which contributes to an extracellular shift of potassium (but the total body potassium will be decreased, and the serum concentration will fall rapidly with administration of insulin which will drive an intracellular shift of potassium) [BMJ Best Practice, 2022]. 

Villous adenoma or vasoactive intestinal peptide secreting tumour

• A suspicion of these conditions should be prompted by a history of:
  • Colon polyps, haematochezia, diarrhoea, constipation, and flatulence — villous adenoma [BMJ Best Practice, 2022].
  • Abdominal pain, flushing, lethargy, nausea, vomiting, muscle weakness, and muscle cramps, associated with weight loss and an abdominal mass  — vasoactive intestinal peptide secreting tumour (VIPoma)[BMJ Best Practice, 2022].
• Both villous adenoma and VIPoma result in refractory watery diarrhoea which increases gastrointestinal potassium losses [Bains, 2019; Cidon, 2022].

Pheochromocytoma

• Pheochromocytomas are rare chromaffin cell tumours originating in the adrenal medulla that are associated with catecholamine production [Farrugia, 2019].
• Hypokalaemia may occur as a complication of pheochromocytoma due to catecholamines promoting potassium entry into the cells by increasing activity of the sodium-potassium-ATPase pump [BMJ Best Practice, 2022].

Thyrotoxicosis and hyperthyroid periodic paralysis 

• Hyperthyroid periodic paralysis (HPP) is characterised by acute paralytic attacks and hypokalaemia in association with hyperthyroidism [Neki, 2016; Zieg, 2016].
  • HPP is a rare but potentially lethal manifestation of hyperthyroidism, which mainly affects young (20–40 years old) Asian males, and typically presents following a high carbohydrate content meal, during or immediately after a strenuous exercise, and in the early morning [Neki, 2016; BMJ Best Practice, 2022].
  • Symptoms resolve promptly with correction of hypokalaemia [Neki, 2016].
  • HPP should be suspected when there is a family history of the disorder or when the symptoms occur in combination with manifestations of hyperthyroidism [BMJ Best Practice, 2022].
• HPP occurs due to an intracellular shift of potassium, caused by increased activity of the sodium-potassium-ATPase pump which is augmented by insulin excess, increased adrenergic response and high circulating levels of thyroid hormones [Neki, 2016; Zieg, 2016; BMJ Best Practice, 2022].

Basis for recommendation

These recommendations are based on the British Medical Journal Best Practice guidelines Assessment of Hypokalaemia [BMJ Best Practice, 2022], and expert opinion in narrative review articles [Jensen, 2015; Kardalas, 2018; Krogager, 2021; Lin, 2021; Kim, 2023; Brown, 2023].

Severity of hypokalaemia

• Hypokalaemia can be an incidental finding on routine blood tests [Jensen, 2015].
• Although the severity of hypokalaemia symptoms tends to be proportionate to the degree and duration of serum potassium reduction [Kardalas, 2018], this correlation is not always present [Kim, 2023].
• Symptoms generally do not present unless the serum potassium concentration is below 3.0 mEq/L (3.0 mmol/L), unless it falls rapidly or the patient has a predisposing risk factor for dysrhythmia [Kardalas, 2018].
• Conditions which cause hypokalaemia result in varying degrees of clinical severity depending on duration and the presence of concurrent medical conditions [BMJ Best Practice, 2022].
• Gastrointestinal or urinary loss are the most likely mechanisms to result in severe hypokalaemia [BMJ Best Practice, 2022].

Symptoms of hypokalaemia

• Many people with hypokalaemia are often asymptomatic, particularly with mild hypokalaemia (serum concentration 3.0 to 3.4 mmol/L) which has developed slowly in a person without risk factors for dysrhythmia [Kardalas, 2018; Lin, 2021; BMJ Best Practice, 2022].
• Symptoms in people with mild hypokalaemia are often due to the underlying cause of the hypokalaemia, rather than the hypokalaemia itself [Kardalas, 2018; BMJ Best Practice, 2022].
• Details on the symptoms typically experienced in people with hypokalaemia is provided in guidelines [BMJ Best Practice, 2022] and expert opinion in narrative review articles [Kardalas, 2018; Krogager, 2021; Lin, 2021].
• Recommendations on the red flag symptoms which should prompt an acute referral to secondary care are based on guidelines [BMJ Best Practice, 2022] and expert opinion in narrative review articles [Kardalas, 2018; Krogager, 2021; Kim, 2023].
• Severe muscle weakness:
  • Provided the hypokalaemia develops slowly, it does not usually occur at potassium concentrations greater than 2.5 mmol/L [BMJ Best Practice, 2022].
  • Weakness usually begins with the lower extremities, progresses to the torso and upper extremities, and can result in paralysis [BMJ Best Practice, 2022].
  • Respiratory muscle weakness can sometimes be severe enough to result in respiratory failure and death [BMJ Best Practice, 2022].
  • Gastrointestinal muscles weakness can result in ileus and its associated symptoms of distension, anorexia, nausea, and vomiting [BMJ Best Practice, 2022].
  • Cramps, paraesthesia, tetany, muscle tenderness, and atrophy can also occur [BMJ Best Practice, 2022].
  • Urgent potassium replacement is required in all cases [BMJ Best Practice, 2022].
• Cardiac dysrhythmias:
  • Cardiac dysrhythmias represent the most serious complication of hypokalaemia, particularly in people with underlying heart disease or treated with digoxin or anti-arrhythmic drugs (class I and II) [Krogager, 2021], increased beta-adrenergic activity, magnesium depletion or those with coronary ischaemia [BMJ Best Practice, 2022].
  • Hypokalaemia prolongs the action potential duration increasing the QT interval, it also increases QT dispersion, slows intracardiac conduction, and induces abnormal pacemaker activity (including early afterdepolarizations [trigger dysrhythmias]) [Krogager, 2021].
  • Hypokalaemia has been associated with a number of dysrhythmias including sinus bradycardia, premature atrial and ventricular beats, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation [BMJ Best Practice, 2022].
  • Hypokalaemia produces different ECG abnormalities at different concentrations [Krogager, 2021]:
    • Between 3.0 and 3.5 mmol/L it can cause flattening or inversion of the T waves.
    • Between 2.5 and 3.0 mmol/L it can cause significant Q-T interval prolongation, U waves, decreased amplitude of the P-wave, T-wave flattening, ST-interval depression (0.5 mm) atrioventricular block (PR-interval prolongation) and ventricular extrasystoles.
    • Less than 2.5 mmol/L can cause atrial fibrillation, multifocal atrial tachycardias, premature atrial and ventricular contractions, bradycardia, Torsade de Pointes ventricular fibrillation, syncope, sudden cardiac death and hear failure.
  • Hypokalaemia in patients with congestive heart failure or myocardial infarction is associated with an increased likelihood of ventricular tachycardia or fibrillation [Kim, 2023].
• Renal abnormalities:
  • Hypokalaemic nephropathy can occur with chronic hypokalaemia, which impairs renal urine concentration mechanisms to produce symptoms of nocturia, polyuria and polydipsia, and increases renal ammonia production and bicarbonate reabsorption [BMJ Best Practice, 2022].

Rare complications of hypokalaemia

• Hypokalaemic periodic paralysis is a potentially fatal complication of muscle weakness. It is often precipitated by exercise, stress, an excessively large carbohydrate meal, or conditions associated with increased release of adrenaline, cortisol, aldosterone, or insulin [BMJ Best Practice, 2022].
• Thyrotoxic periodic paralysis is characterised by hypokalaemia, flaccid paralysis, and thyrotoxicosis, and can result in hypercapnic respiratory failure and ventricular fibrillation [BMJ Best Practice, 2022].
• Prolonged hypokalaemia can result in cardiac dysrhythmias, renal injury and rhabdomyolysis, and people with co-morbidities are at risk of experiencing more severe symptoms, [Kardalas, 2018; Krogager, 2021; BMJ Best Practice, 2022; Brown, 2023].

How do I interpret investigation results?

Discussion with a secondary care specialist may aid the interpretation of investigation results.

• Details from the history and observations from the examination, along with results of the initial investigations are likely to identify a suspected cause of hypokalaemia. 
• Where further tests have been performed:
  • Urine potassium — a concentration less than 15 mmol/L in a random sample suggests non-renal loss, whereas urine potassium greater than 15 mmol/L in a random sample suggests renal loss of potassium.
  • Aldosterone and renin — elevated with hypochloraemia in people with Gitelman or Bartter syndrome.
• Acid-base status can help distinguish possible causes of hypokalaemia.
• Where urinary potassium indicates non-renal causes (urinary potassium concentration less than 15 mmol/L in a random sample):
  • Hypokalaemia with metabolic acidosis may be due to:
    • Chronic laxative use or misuse.
    • Villous adenoma.
    • Gastrointestinal endocrinopathies such as vasoactive intestinal peptide secreting tumour (VIPoma).
  • Hypokalaemia with metabolic alkalosis may be due to:
    • Vomiting.
    • Diuretic use.
    • Chronic laxative use or misuse (occurs in some people rather than acidosis as typically expected — hypokalaemia impairs intestinal chloride reabsorption, which subsequently decreases intestinal lumen chloride-bicarbonate exchange, thereby raising the blood bicarbonate concentration).
• Where urinary potassium indicates renal causes (urinary potassium concentration greater than15 mmol/L in a random sample):
  
  • Hypokalaemia with metabolic acidosis may be due to:
    • Diabetic ketoacidosis.
    • Type 1 (distal) or type 2 (proximal) renal tubular acidosis.
    • Salt-wasting nephropathies.
  • Hypokalaemia with metabolic alkalosis in a person with high blood pressure may be due to:
    • Diuretic use.
    • Renovascular disease.
    • Mineralocorticoid excess due to primary aldosteronism.
    • Hypokalaemic periodic paralysis — suspect where there is a family history.
  • Hypokalaemia with metabolic alkalosis in a person who does not have high blood pressure may be due to:
    
    • Vomiting (may be indicated by a urine chloride concentration less than 15 mmol/L, with a urine pH greater than 7.0, and higher levels of urinary sodium and potassium).
    • Diuretic use.
    • Gitelman or Bartter syndrome.

Basis for recommendation

These recommendations are based on guidelines from the British Medical Journal Best Practice Assessment of Hypokalaemia [BMJ Best Practice, 2022], the Royal Children's Hospital Melbourne Hypokalaemia [RCHM, 2024] and the Specialist Pharmacy Service Treating acute hypokalaemia in adults [SPS, 2024], and expert opinion in narrative review articles [Unwin, 2011; Kardalas, 2018; Krogager, 2021; Kim, 2023; Piner, 2023].

Refer people with severe hypokalaemia or people who are symptomatic

• Urgent potassium replacement is required in people with severe hypokalaemia (serum potassium less than 2.5 mmol/L [less than 2.5 mEq/L]) or in patients who are symptomatic [Kardalas, 2018; Krogager, 2021; BMJ Best Practice, 2022; Kim, 2023; Piner, 2023].
• The degree of hypokalaemia does not always correlate with the severity of symptoms [Kim, 2023].

Taking a detailed history and performing a physical examination to identify the underlying cause

• These recommendations are based the British Medical Journal Best Practice guidelines [BMJ Best Practice, 2022], the Royal Children's Hospital Melbourne Clinical Practice Guidelines: Hypokalaemia [RCHM, 2024], and expert opinion in narrative review articles [Kardalas, 2018; Krogager, 2021; Kim, 2023; Piner, 2023].
• It is important to identify concurrent medical conditions and medication use as caution is required when replacing potassium in people with conditions such as anuric patients or chronic kidney disease, or those using medicines such as diuretics for heart failure [BMJ Best Practice, 2022].
• Electrocardiography (ECG) should be performed when hypokalaemia is identified to help determine the urgency of treatment [Kim, 2023].
• The underlying cause of hypokalaemia is usually apparent after obtaining a detailed medical history and physical examination [Kardalas, 2018].

Laboratory investigations

• Recommendations on the laboratory investigations which should be used to guide the assessment of hypokalaemia and help identify its cause are based the British Medical Journal Best Practice guidelines [BMJ Best Practice, 2022], the Royal Children's Hospital Melbourne Clinical Practice Guidelines: Hypokalaemia [RCHM, 2024], and expert opinion in narrative review articles [Kardalas, 2018; Krogager, 2021; Kim, 2023].
• Optimum treatment of hypokalaemia requires that the cause be established and the underlying disorder alleviated [Unwin, 2011].
• The recommendation to repeat the serum potassium measurement to exclude a spurious hypokalaemia is based on recommendations provided in guidelines [BMJ Best Practice, 2022; RCHM, 2024] and expert opinion in a narrative review article [Kim, 2023].
• Urine electrolytes should be determined in order to differentiate between renal and non-renal causes of hypokalaemia [Krogager, 2021; Kim, 2023].
  • The most accurate method for evaluating urinary potassium excretion is a 24-hour timed urine potassium collection. A more practical approach is calculation of the urine potassium-to-creatinine ratio from a spot urine specimen; a ratio greater than 1.5 mEq per mmol (13 mEq per g) is indicative of renal potassium wasting.
  • However, considerable intraindividual variability has been described for spot urine test results meaning this investigation may have a low specificity for identifying renal causes of hypokalaemia.
• Other specific investigations may be required in secondary care when there is suspicion of:
  • Aldosterone-producing adrenal adenoma — aldosterone suppression test.
  • Cushing's syndrome — urinary free cortisol level, low-dose dexamethasone suppression test, evening salivary cortisol levels, and dexamethasone-corticotrophin-releasing hormone test.
  • Mineralocorticoid, glucocorticoid or catecholamine excess — CT scan of the adrenal glands (may also require MRI of pituitary gland).
  • Central diabetes or diabetes insipidus — water restriction test.
  • Cystic fibrosis — sweat chloride test.

Concurrent hypomagnesaemia

• It is important to determine whether there is concurrent hypomagnesaemia (less than 0.75 mmol/L) as hypokalaemia can often only be corrected once the magnesium has been corrected [BMJ Best Practice, 2022].
  • Hypomagnesaemia can lead to increased urinary potassium loss, but the underlying mechanism for this effect is uncertain [BMJ Best Practice, 2022].
  • Hypokalaemia can therefore often only be corrected once the magnesium deficit has been addressed [BMJ Best Practice, 2022].
• Hypomagnesaemia can predispose people treated with medications which prolong the QT interval to torsades de pointes [BMJ Best Practice, 2022].

Interpretation of investigation results

• Recommendations on how to interpret investigation results are based the British Medical Journal Best Practice guidelines [BMJ Best Practice, 2022] and expert opinion in narrative review articles [Kardalas, 2018].
• There is no strict correlation between measured potassium concentrations and total body potassium stores. In chronic hypokalaemia, a potassium deficit of 200–400 mmol is required to lower the potassium concentration by 1 mmol/L. This estimate is valid in states of acid-base equilibrium, but in diabetic ketoacidosis, the potassium concentration can be normal or even elevated despite having a marked potassium deficit due to urinary or gastrointestinal losses [BMJ Best Practice, 2022].

Basis for recommendation

These recommendations are based on the British Medical Journal Best Practice guidelines Assessment of Hypokalaemia [BMJ Best Practice, 2022], the Royal Children's Hospital Melbourne Clinical Practice Guidelines: Hypokalaemia [RCHM, 2024], and expert opinion in narrative review articles [Daly, 2013; Kardalas, 2018; Krogager, 2021; Kim, 2023; Thayakaran, 2024].

When should I admit or refer a person with hypokalaemia?

• Immediately admit the person to hospital if they:
  • Have severe hypokalaemia (less than 2.5 mmol/L).
  • Are symptomatic, particularly those with dysrhythmias, paralysis, respiratory failure, or severe weakness,
  • Have clinical signs of hypovolaemia, thyrotoxic crisis, hypokalaemic periodic paralysis, metabolic acidosis/alkalosis, hyperosmolar hyperglycaemic state, or diabetic ketoacidosis.
  • Have severe (less than 0.5 mmol/L) or symptomatic hypomagnesaemia.
• Discuss with a specialist about the need for admission or referral If the person is asymptomatic but has moderate hypokalaemia (2.5–2.9 mmol/L).
• Discuss the need for referral with an appropriate specialist where the person has a concurrent medical condition which predisposes to an increased risk of poor outcome, including:
  • Cardiac disease — increased risk of fatal dysrhythmias. See the CKS topic on Heart failure - chronic for more information.
  • Renal disease — increased hospitalization and mortality, and progression of chronic kidney disease. See the CKS topic on Chronic kidney disease for more information.
  • Hepatic disease — people with a history of cirrhosis are at an increased risk of hepatic encephalopathy. See the CKS topic on Cirrhosis for more information.
• Arrange an urgent suspected cancer pathway referral if malignant disease is suspected as the cause of hypokalaemia.
• Refer to an appropriate specialist, with the urgency depending on clinical judgement, where the cause of hypokalaemia is not clear.

How should I manage a person with hypokalaemia in primary care?

Primary care management is appropriate for those with mild (3.0–3.4 mmol/L) or moderate (2.5–2.9 mmol/L) hypokalaemia who do not require referral to secondary care, following discussion with a specialist.

• Ensure the serum potassium measurement has been repeated to exclude spurious hypokalaemia and a rapidly decreasing serum potassium concentration (which will require admission to hospital).
• If the person has an acute illness that is causing the hypokalaemia, treat the underlying problem and recheck the serum potassium concentration after 2 weeks, or sooner based on clinical judgement.
• If the person is taking a medication that may be contributing to the hypokalaemia, stop the medication if appropriate and recheck the serum potassium concentration after 2 weeks, or sooner based on clinical judgement.
  • Consider switching diuretics such as thiazides or frusemide for potassium-sparing diuretics such as amiloride, eplerenone, or spironolactone. See the CKS topic on Hypertension for more information.
  • If the person is taking a medication that cannot be stopped, contact their appropriate specialist to discuss whether to stop the medication, monitor the serum potassium concentration, or refer to an endocrinologist.
  • If the serum potassium concentration remains low after stopping the medication, assess for another underlying cause or refer the person to an endocrinologist.
• If a poor diet is suspected of contributing to the hypokalaemia, recommend increasing dietary sources of potassium and recheck the serum potassium concentration after 2 weeks, or sooner based on clinical judgement.
  • Dietary sources of potassium include tomato, green and leafy vegetables (such as spinach and broccoli), potatoes, white mushrooms, nuts, seeds, legumes (such as lima beans, pumpkin seeds, and pistachios), and fruit (particularly bananas, oranges, watermelon, apricots, raisins, and pineapple).
  • A healthier diet, which involves lowering salt intake and increasing intake of vegetables and fruits, helps to reduce blood pressure as well as prevent hypokalaemia.
  • Be aware that increasing dietary potassium is inadequate for correcting non-dietary causes of hypokalaemia.
  • Recheck the serum potassium concentration after 2 weeks, or sooner based on clinical judgement.
• Consider oral potassium replacement, based on clinical judgment:
  • Where hypokalaemia is thought to be due to increased losses or poor intake, consider correcting hypokalaemia with oral potassium chloride. See the prescribing information for more information, including dosing recommendations.
  • Perform repeat serum potassium concentration 3–4 days after initiation, and titrate supplementation according to the response.
    • A serum potassium concentration greater than 3.5 mmol/L should be aimed for in healthy people.
    • A serum potassium concentration of at least 4.0 should be aimed for in people with hypertension, cardiac dysrhythmias, and chronic heart failure.
  • Where hypokalaemia is thought to be due to redistribution of potassium, correction of the underlying cause may be sufficient to correct the hypokalaemia, whereas correction with oral potassium supplementation could result in rebound hyperkalaemia.
    • Discussion with an endocrinologist may be beneficial where potassium redistribution is the suspected cause of hypokalaemia.
  • Where doubt exists as to the cause of hypokalaemia or oral potassium cannot be tolerated, the person should be referred to an endocrinologist.
• Hypokalaemia and hypomagnesaemia often co-exist, and the treatment of hypokalaemia is unlikely to be successful without correction of hypomagnesaemia.
  • People with mild and asymptomatic hypomagnesaemia can be managed in primary care.
  • Correct hypomagnesaemia with oral magnesium supplementation, see the prescribing information for more information, including dosing recommendations.
    • Caution is recommended in people with pre-existing diarrhoea, high output stoma or fistula, as oral supplementation may result in further gastrointestinal irritation and diarrhoea.

What dose and preparation of potassium chloride should be used?

• Adults:
  • The recommended dose is 2g to 4 g (24 mmol to 48 mmol) daily in divided doses.
  • The Specialist Pharmacy Service recommends:
    • 24 mmol of potassium up to 2 to 3 times a day in people with mild hypokalaemia.
    • 24 mmol to 36mmol of potassium up to 3 to 4 times a day in people with moderate hypokalaemia.
• Children and neonates:
  • 1 mmol/k to 2 mmol/kg daily, with a usual maximum dose of 50 mmol. The total daily dose can be given in divided doses of 0.5 to 1 mmol/kg twice daily, or over 3 divided doses.
• Available preparations:
  • Potassium chloride and potassium bicarbonate 600 mg/400 mg effervescent tablets (Sando-K®) provide 12 mmol potassium per tablet.
  • Potassium chloride modified release 600 mg tablets (PotaChlor® and Aad K®) provide 8 mmol potassium per tablet.
    • Potassium salts are preferably given as an effervescent preparation rather than a modified-release tablet, as modified-release preparations can cause nausea and vomiting resulting in poor compliance.
• Regular monitoring of serum potassium concentration is required for all people using oral potassium chloride preparations.

[BNF, 2024; BNFC, 2024; RCHM, 2024; SPS, 2024]

What are the contraindications and cautions with oral potassium chloride?

• Do not prescribe oral potassium chloride to people with:
  • Plasma-potassium concentration above 5 mmol/L.
  • Uncontrolled Addison's disease.
  • Severe renal impairment.
  • Crush injury.
  • Acute dehydration.
• Prescribe oral potassium chloride with caution to:
  • The elderly.
  • People with cardiac disease, myotonia congenita, or severe haemolysis.
  • People with mild or moderate renal impairment  — smaller doses must be used to reduce the risk of hyperkalaemia.
  • People using potassium-sparing diuretics, angiotensin-converting enzyme (ACE) Inhibitors or angiotensin II receptor blockers (ARBs) — risk of hyperkalaemia. 
  • People with hiatus hernia or a history of peptic ulcer or intestinal stricture (for modified-release preparations).
  • People with hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency — be aware some preparations may contain sucrose (these preparations are contraindicated in such cases).

[BNF, 2024; BNFC, 2024; EMC, 2024]

What adverse effects are associated with oral potassium chloride?

• Adverse effects include:
  • Rebound hyperkalaemia — symptoms are typically expected to be minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre.
    • Symptoms include paraesthesia of the extremities, listlessness, mental confusion, weakness, paralysis, hypotension, cardiac arrhythmias, heart block, and cardiac arrest.
  • Gastrointestinal effects, such as abdominal cramps, diarrhoea, nausea, and vomiting — gastrointestinal effects may be reduced by taking the medication with or after food.

[BNF, 2024; BNFC, 2024; EMC, 2024]

What drug interactions are associated with oral potassium chloride?

• Concurrent use of the following medications with potassium chloride can increase the possibility of hyperkalaemia:
  • Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
  • Beta-blockers.
  • Calcineurin inhibitors (CNIs) such as ciclosporin, tacrolimus, and cyclosporine.
  • Heparin and low molecular weight heparins (LMWHs).
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclo-oxygenase (COX)-2 specific NSAIDs.
  • Other potassium salts.
  • Potassium-sparing diuretics.
  • Pentamidine.
  • Suxamethonium.
  • Tolvaptan.
  • Trimethoprim.

[BNF, 2024; BNFC, 2024; EMC, 2024]

What dose and preparation of oral magnesium should be used?

Magnesium aspartate

• Adults:
  • 10 mmol to 20 mmol per day.
• Children:
  • Aged 2–3 years — 5 mmol once daily.
  • Aged 4–9 years — 5 mmol to 10 mmol once daily.
  • Aged 10–17 years — 10 mmol once daily.
• Available preparations:
  • Magnesium aspartate 243 mg oral powder sachets (AsparMag® and Magnaspartate®) provide 10 mmol magnesium per sachet.
• Regular monitoring of the serum magnesium concentration is required for all people using oral magnesium aspartate preparations.

Magnesium citrate

• Adults:
  • 4 mmol to 8 mmol three times per day.
• Children:
  • Aged 12–17 years — 4 mmol three times per day.
• Available preparations:
  • Magnesium citrate 97.2 mg tablets provide 4 mmol magnesium per tablet.
• Regular monitoring of the serum magnesium concentration is required for all people using oral magnesium citrate preparations.

[BNF, 2024; BNFC, 2024]

What are the contraindications and cautions with oral magnesium supplements?

• Do not prescribe oral magnesium to people with:
  • Disorders of cardiac conduction.
  • Severe renal impairment (glomerular filtration rate less than 30 ml/min/1.73 m²).
• Prescribe oral magnesium with cation to people with:
  • Hyperphosphataemia — be aware some preparations may contain phosphate (these preparations are contraindicated in such cases).
  • Hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency — be aware some preparations may contain sucrose (these preparations are contraindicated in such cases). 
  • Extensive bowel resection — absorption may be reduced.

[BNF, 2024; BNFC, 2024; EMC, 2021; EMC, 2022; EMC, 2023]

What adverse effects are associated with oral magnesium supplements?

• Uncommon adverse effects include diarrhoea or soft faeces (likelihood increases with higher doses).
• Rare or very rare adverse effects include fatigue (likelihood increases with prolonged use).
• Other adverse effects include gastrointestinal irritation and rebound hypermagnesaemia.
• Where side effects occur, consider interrupting treatment and restarting at a reduced dose.

[BNF, 2024; BNFC, 2024; EMC, 2021; EMC, 2022; EMC, 2023]

What drug interactions are associated with oral magnesium supplements?

• Magnesium and other medicinal products may mutually impair absorption, a time interval of 2–4 hours should generally be applied where possible.
• Concurrent use of the following medications may result in increased magnesium losses, necessitating a dose adjustment:
  • Aminoglycoside antibiotics, cisplatin, and ciclosporin A.
  • Diuretics including thiazide and furosemide.
  • EGF-receptor antagonists such as cetuximab and erlotinib.
  • Proton pump inhibitors such as omeprazole and pantoprazole.
• Other specific drug interactions include:
  • Baloxavir marboxil — concentration of the active metabolite may be decreased by concurrent oral magnesium use.

[BNF, 2024; BNFC, 2024; EMC, 2021; EMC, 2022; EMC, 2023]