• Hyperkalaemia refers to a state of high serum potassium (K+), typically > 5.5 mmol/L.
  • Potassium is split between intracellular (98%, ~150 mmol/L K+ concentration) and extracellular (2%, ~4-5 mmol/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 (~100 mmol/L/day). To maintain extracellular K+ levels (~4-5 mmol/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 hyperkalaemia to occur there are then three possibilities.
    • Potassium shifting out of cells and into the blood,
    • Decreased excretion of potassium
    • Increased intake of potassium

Internal potassium imbalance

  • Acidosis: In this scenario the blood becomes too acidic, meaning there is a surplus of hydrogen ions circulating in the blood, which in turn leads to a lowered blood pH level. The body then shifts hydrogen ions in the blood intracellularly to increase the blood pH which results in the exchange of potassium ions for hydrogen ions, precipitating hyperkalaemia. It is important to note that hyperkalaemia does not always result from acidotic states though. In respiratory acidosis, due to carbon being lipid soluble, it shifts intracellularly without any need for potassium exchange. Comparably, in metabolic acidosis due to excess organic acids, protons can enter cells with the organic anion. Again, there is no need for potassium exchange.
  • Insulin deficiency: Insulin not only stimulates uptake of glucose, but also activates the Na+-K+-ATPase, inducing an influx of potassium. In the case of type 1 diabetics, after a meal (especially including K+ rich foods such as leafy greens, root vegetables or bananas) the lack of insulin can lead to enough potassium remaining in the bloodstream to cause hyperkalaemia.
  • Cell lysis: Due to 98% of potassium existing intracellularly, when a substantial number of cells die, significant amounts of potassium are liberated, potentially generating hyperkalaemia. Situations where this can occur include burns, during chemotherapy, rhabdomyolysis (eg: from crush injury or overexertion), or the natural breakdown of skeletal muscle (eg: long-term hospitalisation of immobile patients such as in ICU).
  • Other causes: of extracellular potassium shifting include hyperosmolarity where there is an elevated relative extracellular osmolarity which can draw water out of the cell. This inflates the intracellular K+ concentration and it’s associated gradient, forcing K+ out of the cell and into the interstitium and blood. Furthermore, manipulation of catecholamine concentrations can generate extracellular potassium shifting through effects on the sympathetic nervous system. Beta 2 antagonists (eg: propranolol) stimulate the sodium-potassium pump causing K+ to exit the cell. Concurrently, alpha 2 agonists (eg: clonidine) act via calcium-dependent channels to force K+ out of the cell.

Decreased excretion

  • Aldosterone deficiency: Excretion of potassium is handled by the principal cells of the distal convoluted tubule (DCT). Aldosterone increases the amount of sodium and potassium channels, and sodium-potassium pumps present on the principal cells. As more sodium is moved from the DCT into the blood, potassium is in turn pumped into the cell in exchange. However, in cases where there is a lack of aldosterone, such as adrenal insufficiency or hypoaldosteronism, sodium cannot move as freely. This can cause a resultant lowered potassium secretion by the kidneys, leading to hyperkalaemia.
  • The actions of drugs such as ACE Inhibitors, ARBs, ATII receptor antagonists and K+-sparing diuretics: These pharmaceuticals all reduce the effectiveness of aldosterone, thereby instigating decreased resorption of sodium, and lowering excretion of potassium.
  • Acute Kidney Injury (AKI): can result in a significant decrease in glomerular filtration rate (GFR), oliguria and hyperkalaemia. In cases of AKI, the kidney attempts to retain salt and water leading to minimal water or sodium present in the lumen by the time the filtrate passes into the DCT. The relative deficiency of water engenders a high luminal potassium concentration. Moreover, less sodium present at the DCT means less passing into the principal cell and out into the blood. Therefore, less potassium is pumped into the cell in exchange, inducing hyperkalaemia.

Increased intake

  • Excessive intake: of potassium can be a cause hyperkalaemia. However, this would usually entail particularly rapid and excessive infusion of potassium (eg: IV fluid therapy), rather than eating a surfeit of bananas.


  • The symptoms of hyperkalaemia are generally proportionately correlated to both the magnitude and duration of the potassium surplus. Typically, clinical manifestations are absent <6 mmol/L of serum potassium unless the increase 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, hyperkalaemia can have gastrointestinal, nervous system, cardiac, and respiratory effects.
  • Gastrointestinal sequelae can include nausea, vomiting and diarrhoea.
  • Effects on the nervous system can manifest as ascending muscle weakness/paralysis progressing from the legs to the trunk/arms. Decreased tendon reflexes are often noted. Can proceed to flaccid paralysis.
  • Cardiovascular consequences can be severe, including conduction abnormalities, eg: bradycardia, ventricular tachycardia (VT)/ventricular fibrillation (VF), asystole and sudden death.
  • Respiratory muscle weakness is a rare, though serious, complication of hyperkalaemia.


  • Investigations for suspected hyperkalaemia involve an electrocardiogram (ECG) to investigate potential cardiotoxicity and laboratory tests to determine the optimum choice of therapy.
  • ECG changes: initially consist of peaked T waves and shortened QT intervals (K+ 5.5-6.5 mmol/L) and can progress to flattening then loss of the P wave (K+ 6.5-7.5 mmol/l), a widening QRS interval (K+ >7.5 mmol/L), and can terminate in a sinusoidal (sine) wave, VT or VF (K+ >8.0 mmol/L).
  • Whilst any potassium abnormalities should be confirmed via a supplementary serum sample. In cases of obvious hyperkalaemia (ECG changes/consistent history) this should not delay treatment.
  • ECG monitoring should continue until serum potassium values are brought back within desirable parameters and any cardiotoxicity is managed.
  • Laboratory tests: to optimise treatment include a full blood count (FBC) to check for normocytic normochromic anaemia; venous blood gas (VBG) to investigate a metabolic acidosis and confirm K+ concentration; kidney function tests (GFR/serum creatinine/creatinine clearance) to exclude an AKI; determination of volume status to enhance kidney function; investigation of adrenal insufficiency; evaluation of glucose; and measurement of digoxin levels (in the appropriate context).


  • Treatment of hyperkalaemia varies according to the clinical context and degree of urgency. Emergency treatment is intravenous, although in less exigent circumstances oral treatment can be an option.
  • First-line emergency treatment: of any life-threatening hyperkalaemia (unless associated with digoxin toxicity) is IV calcium gluconate 0.22 mmol/L over 2-3 minutes into a large vein.
  • Calcium lessens the membrane depolarisation of severe hyperkalaemia whilst not lowering serum K+.
  • Effects of IV calcium gluconate are transitory and may require repeat dosing within 30-60 minutes.
  • Concurrent with IV calcium gluconate, any volume depletion should be corrected to optimise kidney function
  • First-line treatment in cases of metabolic acidosis associated with volume depletion: is IV sodium bicarbonate 8.4% 50ml over 5-10 minutes. IV sodium bicarbonate may require repeat dosing within 60-120 minutes.
  • Fluid replacement therapy may need to be maintained with sodium chloride 0.9%.
  • In cases of severe hyperkalaemia associated with chronic kidney failure: insulin and glucose therapy is advised. This avoids the contraindicated effects of a sodium load whilst reducing serum K+ by 0.5-1.5 mmol/L over 30 minutes. Treatment consists of IV insulin 10 units short-acting bolus PLUS EITHER IV glucose 50% 50ml over 5 minutes OR IV glucose 10% 250ml over 10 minutes.
  • Hypoglycaemia must be excluded prior to glucose administration lest severe refractory hypoglycaemia be realised if glucose is given in the context of adrenal insufficiency. Blood glucose must be measured before treatment, then every 30 minutes for 2 hours, then every hour for the next 4 hours (total of 6 hours post-treatment).
  • In non-emergency situations: potassium can be exchanged for calcium or sodium in the bowel lumen via use of a polystyrene sulfonate resin taking several hours for effect.
  • If using a sodium exchange resin (eg: Resonium A), dosage is sodium polystyrene sulfonate 15g (suspended in 45-60ml water) orally, 3-4 times daily OR sodium polystyrene sulfonate 30-50g (suspended in 150ml water or 10% glucose) rectally as a retention enema, daily. Each gram of resin eliminates ~1 mmol of sodium whilst discharging ~2-3 mmol of sodium. This decreases the serum K+ concentration by 0.5-1mmol/L over 1-6 hours.
  • When excess sodium load is undesirable, a calcium exchange resin may be used. Treatment comprises calcium polystyrene sulfonate 15g (suspended in 45-60ml water) orally, 3-4 times daily OR calcium polystyrene sulfonate 30-50g (suspended in 150ml water or 10% glucose) rectally as a retention enema, daily. Calcium exchange resins should be avoided in the hypercalcaemic patient. All ion exchange resins should be ceased when serum K+ concentration is <5 mmol/l.

Additional considerations

  • In cases of hyperkalaemia caused by primary adrenal insufficiency or hypoaldosteronism: the main treatment is corticoseteroid replacement. Insulin should be avoided.
  • Digoxin toxicity/chronic digoxin accumulation: can worsen if conventional treatments are administered. Digoxin-specific antibody (Fab) fragments should be given in tandem with reducing serum potassium.
  • A medication review: is universally warranted in suspected hyperkalaemia. Any drugs which can precipitate or intensify hyperkalaemia should be aborted. Medication induced hyperkalaemia is particularly prevalent with impaired kidney function.
  • Certain patients are at higher risk of hypoglycaemia or adverse events in the case of hypoglycemia: (eg: starting anaesthesia or during ambulance transfer). In such cases, alternatively, a glucose infusion may be started after the initial insulin-glucose therapy. Treatment comprises IV glucose infusion at 75-100ml/hour.

By Adam George


Chan, B. S., & Buckley, N. A. (2014). Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clinical Toxicology, 52(8), 824–836.

Desai, R., Marshall, T., & Ryan, J. (2022). Hyperkalemia | Osmosis. Osmosis. Retrieved January 2, 2023, from

Emergency Care Institute (ECI). (2022, October 11). Potassium – hyperkalaemia. Emergency Care Institute (ECI). Retrieved January 2, 2023, from

Gulland, A. (2017). Sixty seconds on . . . potassium. BMJ.

Simon, L. V., Hashmi , M. F., & Farrell, M. W. (2022). Hyperkalemia. National Center for Biotechnology Information. Retrieved January 2, 2023, from