• Hypokalaemia simply means low blood potassium (K+).
  • Mild hypokalaemia refers to a serum potassium concentration of under 3.5mmol/L
  • Severe hypokalaemia indicates less than 2.5mmol/L of potassium in the blood.
  • Potassium is split between intracellular (98%, ~150mmol/L K+ concentration) and extracellular (2%, ~4-5mmol/L concentration) compartments.
  • Potassium ions are the main intracellular cation and carry an electrical charge. They establish an electrochemical gradient across the cell membrane known as the internal potassium balance. This is maintained via sodium-potassium pumps (Na+-K+-ATPase) and is critical in establishing the resting membrane potential of all muscles throughout the body.
  • There is also the body’s external potassium balance to be considered. Extracellular potassium is delivered via dietary intake (~100mmol/L/day). To maintain extracellular K+ levels (~4-5mmol/L) the vast majority of dietary potassium requires excretion. This is predominantly handled by the kidneys, with excess potassium being filtered through the glomeruli, passed through the renal tubules, and excreted in the urine.


  • For hypokalaemia to occur there are then two possibilities. Either there is an internal imbalance with excessive intracellular shifting of potassium, or an external imbalance whereby the kidneys excrete too much potassium.

Internal potassium imbalance

  • Alkalosis: In this scenario the blood becomes too alkaline, meaning there is a deficiency of hydrogen ions circulating in the blood, which in turn leads to a raised blood pH level. The body then releases intracellular hydrogen ions to lower the blood pH which results in the exchange of hydrogen ions for potassium ions, precipitating hypokalaemia.
  • Insulin administration: Insulin not only stimulates uptake of glucose, but also the activity of the sodium-hydrogen antiporter on the cell membrane, causing sodium to enter the cell. This in turn activates Na+-K+-ATPase, inducing an influx of potassium. In the case of type 1 diabetics who rely on exogenous insulin this can generate hypokalaemia. Cases of prolonged total parenteral nutrition can similarly lead to hypokalaemia via glycogenesis provoking inordinate insulin release.
  • Other causes: of intracellular potassium shifting include stimulation of the sympathetic nervous system, notably with beta 2 agonists (eg: salbutamol) and alpha 2 antagonists (eg: mirtazapine), and thyrotoxicosis which also causes disproportionate sympathetic stimulation.

External potassium imbalance

  • Mineralocorticoid effects or the actions of drugs such as diuretics (loop, thiazide and osmotic), laxatives or penicillin: These factors instigate increased resorption of sodium, and elevated excretion of potassium. Mineralocorticoids initially boost intracellular potassium concentrations via stimulation of Na+-K+-ATPase leading to a transient hyperkalaemia. This is then counteracted via sodium resorption across the cell membrane which increases electronegativity and shifts the electrochemical gradient in favour of potassium excretion, causing hypokalaemia.
  • Gastrointestinal loss: must also be considered in the hypokalaemic patient as external potassium imbalance can also result from chronic diarrhoea or villous adenoma of the colon.
  • NB: hypomagnesemia must always be considered in cases of hypokalaemia. Concomitant magnesium deficiency (usually due to loop or thiazide diuretic usage) is highly prevalent, can intensify hypokalaemia, and hypokalaemia coinciding with hypomagnesemia is frequently refractive to treatment with potassium.


  • The symptoms of hypokalaemia are generally proportionately correlated to both the magnitude and duration of the potassium deficiency. Typically, symptoms are absent until serum potassium falls below 3mmol/L unless the decrease in potassium concentration is particularly rapid or there are intensifying factors such as predisposition to arrhythmias.
  • Symptoms can range from non-existent to fatal cardiac arrhythmias. Systematically, hypokalaemia can have renal, nervous system, cardiac, gastrointestinal, and respiratory effects.
  • Renal sequelae include metabolic acidosis, rhabdomyolysis, diabetes insipidus and tubular interstitial nephritis.
  • Effects on the nervous system can manifest as leg cramps, weakness, paresis and ascending paralysis.
  • Cardiovascular consequences comprise arrhythmias and heart failure.
  • Constipation and intestinal paralysis are another potential complication of hypokalaemia, as is respiratory failure.


  • Investigations for suspected hypokalaemia involve an electrocardiogram (ECG) and laboratory tests to confirm the diagnosis and exclude any potential concurrent electrolyte abnormalities.
  • ECG changes: initially consist of T wave flattening or inversion and can progress to include increased P wave amplitude, PR interval prolongation, long QT intervals, prominent U waves, and widespread ST depression.
  • Laboratory tests: include a comprehensive metabolic panel; renal function tests (EUC); serum potassium, calcium, magnesium (CMP) and phosphate analysis; arterial or venous blood gas measurement (ABG/VBG); and urinary potassium assessment via either spot or 24-hour urine collection. Any abnormal serum potassium findings should be confirmed with repeat serum potassium testing.


  • Treatment of hypokalaemia varies according to the clinical context and degree of urgency. As with any electrolyte abnormality, restorative therapy may be ineffective without correction of the underlying mechanism driving the imbalance. Generally, treatment is either oral or intravenous.
  • Orally: 1200-3600mg sustained release potassium chloride daily in divided doses can be given, with dosage adjusted according to response. If a patient has difficulty swallowing, then an effervescent formulation of 548-1096mg of potassium dissolved in water may be administered 2-3 times daily.
  • Intravenous treatment: is necessary in three specific instances. When oral therapy is not possible; in cases of severe hypokalaemia with concurrent muscle paralysis; and when cardiac rhythm disturbances indicative of hypokalaemia are present on ECG.
  • Intravenous correction of hypokalaemia via rapid infusion carries the risk of fatal hyperkalaemia and as such the rate of infusion must not exceed 10 mmol/hour.
  • NB this may be increased in monitored settings under specialist supervision
  • Due to the potential for local venous irritation causing cardiac arrhythmias, concentration of potassium delivered through a peripheral vein must not exceed 40 mmol/L. It is recommended to give 20-40 mmol/L of potassium chloride via premixed infusion bags at the appropriate 3-12 hourly rate.
  • Throughout potassium replacement both continuous ECG monitoring and 2 hourly serum potassium concentration should be performed.

Additional considerations

  • Low muscle mass: in cachectic patients inflates the risk of overcorrection and consequent hyperkalaemia.
  • Diuretic drug abuse: diuretic dosage should be reduced gradually along with restriction of water and sodium intake to avoid considerable fluid retention.
  • Mineralocorticoid excess: causing hypokalaemia (such as in primary hyperaldosteronism) requires sodium intake restriction to achieve effective potassium repletion.
  • Avoid solutions containing dextrose: as these can increase insulin secretion and exacerbate the hypokalaemia.
  • Finally, it cannot be overstated that potassium supplementation will remain ineffective if there is a concurrent hypomagnesemia. This must be treated prior to potassium correction.


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