Internal Medicine Nephrology


Hypokalemia ECG
ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval - common findings in hypokalemia.

Introduction – Hypokalemia

Hypokalemia (S-Potassium <3.5 mmol/l) occurs in approximately 20% of hospitalized patients and between 10% and 40% of patients treated with outpatient diuretics.

Hospitalized patients with hypokalemia have higher mortality rates than those with normokalemia. A large proportion of patients with hypokalemia are discharged from hospitals with residual electrolyte imbalances.

Mild hypokalaemia eliminates the treatment benefits that would otherwise be achieved by thiazide therapy in hypertension. The diagnostics and treatment of hypokalaemia should be included in the metabolic follow-up of patients with hypertension and other cardiovascular diseases. Prospective population studies have shown that the intake of potassium-rich fruits and vegetables is associated with lower blood pressure.

Hypokalemia increases the risk of arrhythmia in patients with digitalis treatment, ischemic heart disease and left ventricular dysfunction. Hypokalemia in these patient groups should be prevented with drugs if the patients are taking diuretics.

Gastrointestinal causes of hypokalaemia are usually evident in the overall clinical picture.

Drug treatment should always be suspected as a cause of hypokalemia.

Concomitant hypertension causes suspicion of underlying causes of hypertension such as hyperaldosteronism or renal artery stenosis. However, it should be noted that many cases of primary aldosteronism do not present with hypokalemia.

Low age in patients with hypokalemia may indicate rare genetic conditions.


I) Medications are by far the most common cause of hypokalemia.

– Increased renal K+ losses:

  • Diuretics – most common
  • Other medications:
    – Mineral corticoids (fludrocortisone in Florinef) and some glucocorticoids (hydrocortisone, prednisolone, prednisone).
    – Penicillin and related antibiotics in high parenteral doses, aminoglycosides.
    – Certain cytostatic drugs and fungicides in high doses that cause Mg2+ loss.

– Increased extra-intracellular transport of K+:

  • Beta-2 agonists
  • Theophylline
  • Verapamil intoxication
  • Insulin (overdose)

– Potassium loss from the intestine:

  • laxatives

II) Gastrointestinal causes

– With volume loss and metabolic alkalosis:

  • Vomiting, feeding tube (primary chloride loss)
  • Overuse of laxatives

– Along with metabolic acidosis:

  • Diarrhea (adenomas, Zollinger-Ellison syndrome, infectious gastroenteritis, short bowel syndrome, cytostatic drugs, VIPoma)
  • Ureterosigmoidostomy

III) Renal causes

– Hypokalemia with metabolic acidosis:

  • Renal tubular acidosis
  • Postobstructive uropathy
  • Diuretic phase of acute tubular necrosis
  • Chronic pyelonephritis

– Hypokalemia with metabolic alkalosis:

  • Diuretics
  • Primary aldosteronism and secondary hyperaldosteronism as a result of malignant hypertension, renovascular hypertension. Note, that patients with essential hypertension and vomiting or diarrhea are included in this group.
  • High levels of glucocorticoids such as in Cushing’s syndrome or cortisone treatment (hydrocortisone, prednisolone)
  • Increased aldosterone production without hypertension: Bartter’s syndrome, Gitelmans syndrome.
    – Bartter syndrome presents with hypokalemia, hypochloremia, normal/low serum magnesium, high aldosterone and renin and high or normal calcium excretion in urine.
    – Gitelman’s syndrome has hypokalemia, hypochloremia, low serum magnesium, high aldosterone and renin, and low urinary calcium excretion.

IV) Hypokalemia and concomitant hypertension

  • Primary hyperaldosteronism
    – Idiopathic aldosteronism (hyperplasia), aldosterone-producing adrenal gland adenoma, adrenal gland cancer .
  • Renovascular hypertension (renal artery stenosis)
  • Malignant hypertension
  • High levels of glucocorticoids
    – Cushing’s syndrome
    – Glucocorticoid treatment – which also has a mineral corticoid effect (hydrocortisone, prednisolone, prednisone)
  • Low or normal aldosterone levels
    – Regular intake of licorice (lowest daily dose not known)
    – Rare enzyme abnormalities: Apparent mineral corticoid excess (AME), Glucocorticoid suppressible aldosteronism (GSA).
    – Genetic renal tubular defects (Liddle’s syndrome)
  • Patients with diuretic-treated essential hypertension and/or vomiting or diarrhea.

V) Other causes that should be considered

  • Magnesium deficiency
  • Acute leukemia
  • Hyperthyroidism
  • Prolonged uncontrolled hyperglycemia
    – May lead to severely reduced potassium deposits but with normal serum potassium concentration which manifests itself first when correcting metabolic acidosis.

Symptoms and Clinical Findings – Hypokalemia

The occurrence of symptoms of hypokalaemia is linked to how quickly serum potassium has dropped and the current serum concentration. Thus, a patient with severe but prolonged hypokalemia may not have many symptoms.

  • 3.0-3.5 mmol / l: Often nonspecific or no symptoms. Patients with underlying heart disease and patients treated with digitalis are at increased risk of arrhythmia.
  • 2.5-3.0 mmol / l: General weakness, fatigue, apathy, anorexia, nausea, constipation, subileus/ileus and decreased tendon reflexes.
  • <2.5 mmol / l: Muscle necrosis and at lower concentration, progressive ascending paralysis may occur.

ECG changes. Initially, decreased T-wave amplitude, T-wave inversion, U-wave formation, decreased ST distance and supraventricular and ventricular tachyarrhythmia occur.

Increased urine levels as tubules lose the ability to concentrate urine. Thus, hypokalemia itself can produce hypovolemia which in turn stimulates the renin-angiotensin-aldosterone system which further increases the potassium losses.

Clinical Evaluation and Lab Testing – Hypokalemia

Extrarenal causes are often easy to identify clinically. The exception may be laxatives of abuse or voluntary vomiting.

In the presence of ECG abnormalities and serum potassium concentration <3.0 mmol/l, treatment, and diagnostic procedures should be started at the same time.

  • Evaluate volume status clinically (general condition, peripheral edema, skin turgor) and blood pressure.
  • Review medication list
  • Check blood gas (pH and bicarbonate)
  • Tests of renal function (serum creatinine, urea) and serum chloride concentration.
  • “Spot” urine. Potassium concentrations> 20 mmol/l in concomitant hypokalemia indicate renal potassium loss.
  • 24-hour urine collection for potassium testing. If 24 hours of excretion <20 mmol, renal loss is unlikely, while >60 mmol supports renal potassium losses.
  • Other directed lab testing depending on clinical status and directed history.
  • In the case of hypertension, further investigation should be carried out:

    – Plasma aldosterone: renin ratio if concomitant hypertension. Samples can be taken after a few minutes of rest and during ongoing antihypertensive and cardiac medication, but not spironolactone, eplerenone, and amiloride. High ratios indicate primary aldosteronism, low ratios indicate secondary hyperaldosteronism or renovascular hypertension, while low levels of both aldosterone and renin suggest other underlying causes such as Cushing’s syndrome, excessive licorice intake or renal tubular causes. Reference values ​​for aldosterone, renin, and aldosterone: renin ratio are laboratory dependent.

    – Renal artery Doppler to check for renovascular hypertension.
  • Investigate if serum potassium levels have been taken previously. If previous serum potassium has always been low, a genetic cause should be suspected.

Treatment – Hypokalemia

I) Prevention:

In patients with diuretic therapy, potassium replacement should be considered. Note that treatment with potassium-sparing diuretics is the most common cause of severe hyperkalemia where the known risk factors are: renal impairment and diabetes mellitus. Regular monitoring is necessary and its frequency is dependent on age, underlying disease, concomitant treatment with other drugs such as ACE inhibitors, Angiotensin II receptor inhibitors, NSAIDs, etc.

Patients with digitalis treatment, left ventricular dysfunction, ischemic heart disease and concomitant diuretic therapy should be on regular serum potassium monitoring.

Preventive treatment can be given in the form of:

  • Potassium-sparing diuretics

    – Spironolactone – an aldosterone receptor blocker (Aldactone, Spironolactone Nycomed, Spironolactone, Pfizer)

    – Eplerenone – an aldosterone receptor blocker (Inspra)

    – Amiloride (Amiloferm, Amiloride Mylan, Moduretic, Normorix, Sparkal)

    – Combinations of Hydrochlorothiazide and Amiloride (Amiloferm, Moduretic, Normorix, Sparkal)
  • Potassium chloride tablets (Kaleorid, prolonged-release tablet 750 mg). The usual preventive dose is about 20 mmol K+ per day (1500 mg of potassium chloride)
  • Potassium citrate solution (Kajos , Oral solution 33 mg (0.85 mmol) K + / ml) – cheap but with poor taste which can impair compliance with treatment.
  • Dietary advice is a harmless and good way to prevent hypokalaemia. However, note that dietary treatment is an ineffective way of treating hypokalaemia with concomitant chloride losses (diuretics, vomiting, etc.) since potassium in the diet is primarily bound to phosphate.

II) Acute treatment:

– In the case of ECG abnormalities and/or serum potassium concentration <3.0 mmol/l.

– In simultaneous digitalis treatment or documented arrhythmia.

  • Iv potassium infusion (eg Addex Potassium). Heart rhythm monitoring should be done especially in individuals with concomitant heart disease (see above). The infusion should be administered by infusion pump. The triple maintenance dose is about 5 mmol per hour. A dose higher than 20 mmol per hour should preferably not be given. The serum potassium concentration should be monitored at least once a day, depending on the potassium dose and arrhythmia.
  • In diuretic- or diarrhea-induced severe hypokalemia, there is a presumed simultaneous magnesium deficiency that can increase arrhythmia propensity and make it difficult to correct the hypokalemia. A daily dose of 20 mmol Mg2+ (500 mg) can be used in the treatment of mild magnesium deficiency (Emgesan 250mg, Magnesium Recip 120 mg, solution AddexMagnesium 10mmol/10ml). Serum concentration of Mg2+ is not considered reliable when diagnosing magnesium deficiency.
  • In concomitant chloride losses and/or volume losses, the renal potassium excretion increase further. Thus, in diuretic-induced hypokalemia and in chloride losses caused by vomiting, or ventricular tubes, with concomitant metabolic alkalosis, aggressive volume substitution as well as potassium and chloride (eg Addex Potassium chloride) should be given .

III) Non-acute potassium substitution is preferred if possible.

  • Double or triple replacement dose may be given until serum potassium concentration exceeds 3.0 mmol/l or 3.5 mmol/l if risk of arrhythmia is present.
  • After acute treatment, 5-7 days of treatment with at least 1500 mg of potassium chloride per day should be considered to ensure that the total amount of potassium is restored.
  • Consider continuing preventative treatment as above.

IV) Investigation of underlying cause/disease.

Further Reading