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By James L. Lewis, III, MD

Hypokalemia is serum K concentration < 3.5 mEq/L caused by a deficit in total body K stores or abnormal movement of K into cells. The most common causes are excess losses from the kidneys or GI tract. Clinical features include muscle weakness and polyuria; cardiac hyperexcitability may occur with severe hypokalemia. Diagnosis is by serum measurement. Treatment is giving K and managing the cause.


Hypokalemia can be caused by decreased intake of K but is usually caused by excessive losses of K in the urine or from the GI tract.

GI tract losses

Abnormal GI K losses occur in all of the following:

  • Chronic diarrhea, including chronic laxative abuse and bowel diversion

  • Clay (bentonite) ingestion, which binds K and greatly decreases absorption

  • Vomiting

  • Protracted gastric suction (which removes volume and HCl, causing the kidneys to excrete HCO3 and, to electrically balance lost HCO3, K)

  • Rarely, villous adenoma of the colon, which causes massive K secretion

GI K losses may be compounded by concomitant renal K losses due to metabolic alkalosis and stimulation of aldosterone due to volume depletion.

Intracellular shift

The transcellular shift of K into cells may also cause hypokalemia. This shift can occur in any of the following:

  • Glycogenesis during TPN or enteral hyperalimentation (stimulating insulin release)

  • After administration of insulin

  • Stimulation of the sympathetic nervous system, particularly with β2-agonists (eg, albuterol, terbutaline), which may increase cellular K uptake

  • Thyrotoxicosis (occasionally) due to excessive β-sympathetic stimulation (hypokalemic thyrotoxic periodic paralysis)

  • Familial periodic paralysis

Familial periodic paralysis (see page Familial Periodic Paralysis) is a rare autosomal dominant disorder characterized by transient episodes of profound hypokalemia thought to be due to sudden abnormal shifts of K into cells. Episodes frequently involve varying degrees of paralysis. They are typically precipitated by a large carbohydrate meal or strenuous exercise.

Renal losses

Various disorders can increase renal K excretion. Excess mineralocorticoid effect can directly increase K secretion by the distal nephrons and occurs in any of the following:

  • Adrenal steroid excess that is due to Cushing syndrome, primary hyperaldosteronism, rare renin-secreting tumors, glucocorticoid-remediable aldosteronism (a rare inherited disorder involving abnormal aldosterone metabolism), and congenital adrenal hyperplasia.

  • Ingestion of substances such as glycyrrhizin (present in natural licorice and used in the manufacture of chewing tobacco), which inhibits the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSDH), preventing the conversion of cortisol, which has some mineralocorticoid activity, to cortisone, which does not, resulting in high circulating concentrations of cortisol and renal K wasting.

  • Bartter syndrome, an uncommon genetic disorder that is characterized by renal K and Na wasting, excessive production of renin and aldosterone, and normotension. Bartter syndrome (see also Bartter Syndrome and Gitelman Syndrome) is caused by mutations in a loop diuretic–sensitive ion transport mechanism in the loop of Henle.

  • Gitelman syndrome is an uncommon genetic disorder characterized by renal K and Na wasting, excessive production of renin and aldosterone, and normotension. Gitelman syndrome is caused by loss of function mutations in a thiazide-sensitive ion transport mechanism in the distal nephron.

Liddle syndrome (see also Liddle Syndrome) is a rare autosomal dominant disorder characterized by severe hypertension and hypokalemia. Liddle syndrome is caused by unrestrained Na reabsorption in the distal nephron due to one of several mutations found in genes encoding for epithelial Na channel subunits. Inappropriately high reabsorption of Na results in both hypertension and renal K wasting.

Renal K wasting can also be caused by numerous congenital and acquired renal tubular diseases, such as the renal tubular acidoses and Fanconi syndrome, an unusual syndrome resulting in renal wasting of K, glucose, phosphate, uric acid, and amino acids.

Hypomagnesemia is a common correlate of hypokalemia. Much of this correlation is attributable to common underlying causes (ie, diuretics, diarrhea), but hypomagnesemia itself may also result in increased renal K losses.


Diuretics are by far the most commonly used drugs that cause hypokalemia. K-wasting diuretics that block Na reabsorption proximal to the distal nephron include

  • Thiazides

  • Loop diuretics

  • Osmotic diuretics

By inducing diarrhea, laxatives, especially when abused, can cause hypokalemia. Surreptitious diuretic or laxative use or both is a frequent cause of persistent hypokalemia, particularly among patients preoccupied with weight loss and among health care practitioners with access to prescription drugs.

Other drugs that can cause hypokalemia include

  • Amphotericin B

  • Antipseudomonal penicillins (eg, carbenicillin)

  • Penicillin in high doses

  • Theophylline (both acute and chronic intoxication)

Symptoms and Signs

Mild hypokalemia (serum K 3 to 3.5 mEq/L) rarely causes symptoms. Serum K < 3 mEq/L generally causes muscle weakness and may lead to paralysis and respiratory failure. Other muscular dysfunction includes cramping, fasciculations, paralytic ileus, hypoventilation, hypotension, tetany, and rhabdomyolysis. Persistent hypokalemia can impair renal concentrating ability, causing polyuria with secondary polydipsia.


  • Serum K measurement

  • ECG

  • When the mechanism not evident clinically, 24-h urinary K excretion and serum Mg concentration

Hypokalemia (serum K < 3.5 mEq/L) may be found on routine serum electrolyte measurement. It should be suspected in patients with typical changes on an ECG or who have muscular symptoms and risk factors and confirmed by blood testing.


ECG should be done on patients with hypokalemia. Cardiac effects of hypokalemia are usually minimal until serum K concentrations are < 3 mEq/L. Hypokalemia causes sagging of the ST segment, depression of the T wave, and elevation of the U wave. With marked hypokalemia, the T wave becomes progressively smaller and the U wave becomes increasingly larger. Sometimes, a flat or positive T wave merges with a positive U wave, which may be confused with QT prolongation (see see Figure: ECG patterns in hypokalemia and hyperkalemia.). Hypokalemia may cause premature ventricular and atrial contractions, ventricular and atrial tachyarrhythmias, and 2nd- or 3rd-degree atrioventricular block. Such arrhythmias become more severe with increasingly severe hypokalemia; eventually, ventricular fibrillation may occur. Patients with significant preexisting heart disease and patients receiving digoxin are at risk of cardiac conduction abnormalities as a result of even mild hypokalemia.

Diagnosis of cause

The cause is usually apparent by history (particularly the drug history); when it is not, further investigation is warranted. After acidosis and other causes of intracellular K shift (increased β-adrenergic effect, hyperinsulinemia) have been eliminated, 24-h urinary K and serum Mg concentrations are measured. In hypokalemia, K secretion is normally < 15 mEq/L. Extrarenal (GI) K loss or decreased K ingestion is suspected in chronic unexplained hypokalemia when renal K secretion is < 15 mEq/L. Secretion of > 15 mEq/L suggests a renal cause for K loss. Unexplained hypokalemia with increased renal K secretion and hypertension suggests an aldosterone-secreting tumor or Liddle syndrome. Unexplained hypokalemia with increased renal K loss and normal BP suggests Bartter or Gitelman syndrome, but hypomagnesemia, surreptitious vomiting, and diuretic abuse are more common and should also be considered.

ECG patterns in hypokalemia and hyperkalemia.

(Serum K is in mEq/L.)


  • Oral K supplements

  • IV K supplements for severe hypokalemia or ongoing K losses

Many oral K supplements are available. Because high single doses can cause GI irritation and occasional bleeding, deficits are usually replaced in divided doses. Liquid KCl given orally elevates concentrations within 1 to 2 h but has a bitter taste and is tolerated particularly poorly in doses > 25 to 50 mEq. Wax-impregnated KCl preparations are safe and better tolerated. GI bleeding may be even less common with microencapsulated KCl preparations. Several of these preparations contain 8 or 10 mEq/capsule. Because a decrease in serum K of 1 mEq/L correlates with about a 200- to 400-mEq deficit in total body K stores, total deficit can be estimated and replaced over a number of days at 20 to 80 mEq/day.

When hypokalemia is severe (eg, with ECG changes or severe symptoms), is unresponsive to oral therapy, or occurs in hospitalized patients who are taking digoxin or who have significant heart disease or ongoing losses, K must be replaced IV. Because K solutions can irritate peripheral veins, the concentration should not exceed 40 mEq/L. The rate of correction of hypokalemia is limited because of the lag in K movement into cells. Routine infusion rates should not exceed 10 mEq/h. In hypokalemic-induced arrhythmia, IV KCl must be given more rapidly, usually through a central vein or using multiple peripheral veins simultaneously. Infusion of 40 mEq KCl/h can be undertaken but only with continuous cardiac monitoring and hourly serum K determinations. Glucose solutions are avoided because elevation in the serum insulin concentrations could result in transient worsening of hypokalemia.

Even when K deficits are severe, it is rarely necessary to give > 100 to 120 mEq of K in a 24-h period unless K loss continues. In K deficit with high serum K concentration, as in diabetic ketoacidosis, IV K is deferred until the serum K starts to fall. When hypokalemia occurs with hypomagnesemia, both the K and Mg deficiencies must be corrected to stop ongoing renal K wasting (see page Hypomagnesemia : Treatment).


Routine K replacement is not necessary in most patients receiving diuretics. However, serum K should be monitored during diuretic use when risk of hyperkalemia or of its complications is high. Risk is high in

  • Patients with decreased left ventricular function

  • Patients taking digoxin

  • Patients with diabetes (in whom insulin concentrations can fluctuate)

  • Patients with asthma who are taking β2-agonists

Triamterene 100 mg po once/day or spironolactone 25 mg po qid does not increase K excretion and may be useful in patients who become hypokalemic but must use diuretics. When hypokalemia develops, K supplementation, usually with oral KCl, is indicated.

Key Points

  • Hypokalemia can be caused by decreased intake of K but is usually caused by excessive losses of K in the urine or from the GI tract.

  • Clinical signs include muscle weakness, cramping, fasciculations, paralytic ileus, and when hypokalemia is severe, hypoventilation, and hypotension.

  • ECG changes typically occur when serum K is < 3 mEq/L, and include ST segment sagging, T wave depression, and U wave elevation. With marked hypokalemia, the T wave becomes progressively smaller and the U wave becomes increasingly larger.

  • Hypokalemia may cause premature ventricular and atrial contractions, ventricular and atrial tachyarrhythmias, and 2nd- or 3rd-degree atrioventricular block; eventually, ventricular fibrillation may occur.

  • Replace K orally,giving 20 to 80 mEq/day unless patients have ECG changes or severe symptoms.

  • For hypokalemic arrhythmia, give IV KCl through a central vein at a maximum of 40 mEq/h and only with continuous cardiac monitoring; routine IV infusion should be no more than 10 mEq/h.

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