AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Potassium homeostasis

Potassium, the most abundant intracellular cation, is essential for the life of the organism. Potassium is obtained through the diet, and common potassium-rich foods include meats, beans, fruits, and potatoes.

Gastrointestinal absorption is complete, resulting in daily excess intake of approximately 1 mEq/kg/d (60-100 mEq). Ninety percent of this excess is excreted through the kidneys, and 10% is excreted through the gut. Potassium homeostasis is maintained predominantly through the regulation of renal excretion. The most important site of regulation is the collecting duct, where aldosterone receptors are present.

Excretion is increased by (1) aldosterone, (2) high sodium delivery to the collecting duct (eg, diuretics), (3) high urine flow (eg, osmotic diuresis), (4) high serum potassium level, and (5) delivery of negatively charged ions to the collecting duct (eg, bicarbonate).

Excretion is decreased by (1) absence or relative deficiency of aldosterone, (2) low sodium delivery to the collecting duct, (3) low urine flow, (4) low serum potassium level, and (5) renal failure.

Kidneys adapt to acute and chronic alterations in potassium intake. When potassium intake is chronically high, potassium excretion likewise is increased. In the absence of potassium intake, obligatory renal losses are 10-15 mEq/d. Thus, chronic losses occur in the absence of any ingested potassium. The kidney maintains a central role in the maintenance of potassium homeostasis, even in the setting of chronic renal failure. Renal adaptive mechanisms allow the kidneys to maintain potassium homeostasis until the glomerular filtration rate drops to less than 15-20 mL/min. Additionally, in the presence of renal failure, the proportion of potassium excreted through the gut increases. The colon is the major site of gut regulation of potassium excretion. Therefore, potassium levels can remain relatively normal under stable conditions, even with advanced renal insufficiency. However, as renal function worsens, the kidneys may not be capable of handling an acute potassium load.

Serum potassium level

Potassium is predominantly an intracellular cation; therefore, serum potassium levels can be a very poor indicator of total body stores. Because potassium moves easily across cell membranes, serum potassium levels reflect movement of potassium between intracellular and extracellular fluid compartments as well as total body potassium homeostasis. Several factors regulate the distribution of potassium between the intracellular and extracellular space, as follows.

Glycoregulatory hormones: (1) Insulin enhances potassium entry into cells, and (2) glucagon impairs potassium entry into cells.

Adrenergic stimuli: (1) Beta-adrenergic stimuli enhance potassium entry into cells, and (2) alpha-adrenergic stimuli impair potassium entry into cells.

pH: (1) Alkalosis enhances potassium entry into cells, and (2) acidosis impairs potassium entry into cells.

An acute increase in osmolality causes potassium to exit from cells.

An acute cell/tissue breakdown releases potassium into extracellular space.

Pathophysiology

Hypokalemia can occur due to one of 3 pathogenetic mechanisms.

The first is deficient intake. Poor potassium intake alone is an uncommon cause of hypokalemia but occasionally can be seen in very elderly individuals unable to cook for themselves or unable to chew or swallow well. Over time, such individuals can accumulate a significant potassium deficit. Another clinical situation where hypokalemia may occur due to poor intake is in patients receiving total parenteral nutrition (TPN), where potassium supplementation may be inadequate for a prolonged period of time.

The second is increased excretion. Increased excretion of potassium, especially coupled with poor intake, is the most common cause of hypokalemia. The most common mechanisms leading to increased renal potassium losses include enhanced sodium delivery to the collecting duct, as with diuretics; mineralocorticoid excess, as with primary or secondary hyperaldosteronism; or increased urine flow, as with an osmotic diuresis.

Gastrointestinal losses, most commonly from diarrhea, also are common causes of hypokalemia. Vomiting is a common cause of hypokalemia, but the pathogenesis of the hypokalemia is complex. Gastric fluid itself contains little potassium, approximately 10 mEq/L. However, vomiting produces volume depletion and metabolic alkalosis. These 2 processes are accompanied by increased renal potassium excretion. Volume depletion leads to secondary hyperaldosteronism, which, in turn, leads to enhanced cortical collecting tubule secretion of potassium in response to enhanced sodium reabsorption. Metabolic alkalosis also increases collecting tubule potassium secretion due to the decreased availability of hydrogen ions for secretion in response to sodium reabsorption.

The third is due to a shift from extracellular to intracellular space. This pathogenetic mechanism also often accompanies increased excretion, leading to a potentiation of the hypokalemic effect of excessive loss. Intracellular shifts of potassium often are episodic and frequently are self-limited, for example, with acute insulin therapy for hyperglycemia.

Regardless of the cause, hypokalemia produces similar signs and symptoms. Because potassium is overwhelmingly an intracellular cation and because a variety of factors can regulate the actual serum potassium concentration, an individual can incur very substantial potassium losses without exhibiting frank hypokalemia. Conversely, hypokalemia does not always reflect a true deficit in total body potassium stores.

Frequency

United States

In the general population, data are difficult to estimate; however, probably fewer than 1% of people on no medications have a serum potassium level of lower than 3.5 mEq/L. Potassium intake varies according to age, sex, ethnic background, and socioeconomic status. Whether these differences in intake produce different degrees of hypokalemia or different sensitivities to hypokalemic insults is not known. Up to 21% of hospitalized patients have serum potassium levels lower than 3.5 mEq/L, with 5% of patients achieving potassium levels lower than 3 mEq/L. Of elderly patients, 5% demonstrate potassium levels lower than 3 mEq/L.

• In patients on non–potassium-sparing diuretics, hypokalemia is present in 20-50%. African Americans and females are more susceptible. Risk is enhanced by concomitant illness such as heart failure or nephrotic syndrome.
• Other groups with a high incidence of hypokalemia include individuals with eating disorders, published incidence ranging from 4.6% (Greenfeld, 1995) to 19.7% (Miller, 2005) in an outpatient setting; patients with AIDS, of which 23.1% of hospitalized patients are hypokalemic; and patients with alcoholism, where the incidence of hypokalemia in the inpatient setting is reportedly as high as 12.6% (Elisaf, 2002) and is likely due to a hypomagnesemia-induced decrease in tubular reabsorption of potassium. A relatively new and emerging group of individuals who are at high risk for hypokalemia are patients who have undergone bariatric surgery (Al-Momen, 2005).

Mortality/Morbidity

• Hypokalemia generally is associated with higher morbidity and mortality, especially due to cardiac arrhythmias or sudden cardiac death. However, an independent contribution of hypokalemia to increased morbidity/mortality has not been conclusively established.
• Patients who develop hypokalemia often have multiple medical problems, making the separation and quantitation of the contribution by hypokalemia, per se, difficult. For further details, see Complications.

Race

• Some suggestion is observed of increased frequency of diuretic-induced hypokalemia in African Americans. The higher frequency of hypokalemia in this group may be due to the lower intake of potassium among African American men (approximately 25 mEq/d) than in their white counterparts (70-100 mEq/d).

Sex

• Some suggestion also is observed of increased frequency of diuretic-induced hypokalemia in women.

Age

• With age, frequency increases, due to increased use of diuretics and poor diet, which often is low in potassium.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Symptoms are nonspecific and predominantly are related to muscular or cardiac function.
• • Weakness and fatigue are the most common complaints. The muscular weakness that occurs with hypokalemia can manifest in protean ways, ie, dyspnea, constipation or abdominal distention, or exercise intolerance. Rarely, muscle weakness progresses to frank paralysis.
  
  
  
  • Occasionally, a patient may complain of worsening diabetes control or polyuria due to a recent onset of hyperglycemia or nephrogenic diabetes insipidus.
  
  
  
  • The patient also may complain of palpitations.
  
  
  
  • With severe hypokalemia or total body potassium deficits, muscle cramps and pain can occur with rhabdomyolysis.
• When the diagnosis of hypokalemia is discovered, investigate potential pathophysiologic mechanisms.
• • Poor intake may result from the following:
    
    
    • Eating disorders
    
    
    
    • Dental problems
    
    
    
    • Poverty
       
  • Increased excretion may be due to the following:
    
    
    • Medications, including diuretics, AIDS therapy, or antibiotics
    
    
    
    • Polyuria
    
    
    
    • Vomiting or diarrhea
       
  • Shift of potassium into the intracellular space may occur due to the following:
    
    
    • Recurrent episodes of paralysis
    
    
    
    • Use of high doses of insulin
    
    
    
    • High-dose beta agonist therapy (eg, for chronic obstructive pulmonary disease)

Physical

• Vital signs generally are normal, except for occasional tachycardia or tachypnea due to respiratory muscle weakness.
• • Hypertension may be a clue to primary hyperaldosteronism, renal artery stenosis, licorice ingestion, or the more unusual forms of genetically transmitted hypertensive syndromes such as congenital adrenal hyperplasia, glucocorticoid remediable hypertension, or Liddle syndrome.
  • Relative hypotension should suggest occult laxative use, diuretic use, bulimia, or one of the unusual tubular disorders such as Bartter syndrome or Gitelman syndrome (see Bartter Syndrome). Bear in mind that occult diuretic use is far more common than either congenital tubular disorder and is, in fact, also called "pseudo Bartter."

• Muscle weakness and flaccid paralysis may be present.
• Patients may have depressed or absent deep-tendon reflexes.

Causes

Pathophysiologic mechanisms include poor intake, increased excretion, or a shift of potassium from the extracellular to the intracellular space. Mechanisms causing increased excretion are the most common. Singly, poor intake or an intracellular shift is a distinctly uncommon cause. Often, several disorders are present simultaneously.

• Poor intake
  
  
  • Eating disorders - Anorexia, bulimia, starvation, pica, and alcoholism
  
  
  
  • Dental problems - Inability to chew or swallow
  
  
  
  • Poverty - Lack of food, ie, "tea-and-toast" diet of elderly individuals
  
  
  
  • Hospitalization - Potassium-poor TPN
     
• Increased excretion
  
  
  
  
  • Endogenous mineralocorticoid excess
    
    
    • Cushing disease
    
    
    
    • Primary hyperaldosteronism, most commonly due to adenoma or bilateral adrenal hyperplasia
    
    
    
    • Secondary hyperaldosteronism due to volume depletion, congestive heart failure, cirrhosis, or vomiting
    
    
    
    • Adrenocortical carcinoma
    
    
    
    • Tumor that is producing adrenocorticotropic hormone
    
    
    
    • Congenital disorders - Congenital adrenal hyperplasia (11-beta hydroxylase or 17-alpha hydroxylase deficiency) or glucocorticoid-remediable hypertension
       
  • Hyperreninism due to renal artery stenosis
  
  
  
  • Exogenous mineralocorticoid excess
    
    
    • Steroid therapy for immunosuppression
    
    
    
    • Glycyrrhizic  acid -  Inhibits 11-beta hydroxysteroid dehydrogenase; contained in licorice and Chinese herbal preparations
    
    
    
    • Renal tubular disorders - Type I and type II renal tubular acidosis
    
    
    
    • Hypomagnesemia
  • Congenital disorders
    
    
    • Bartter syndrome: This is a group of autosomal-recessive disorders characterized by hypokalemic metabolic alkalosis and hypotension. Mutations in 6 different renal tubular proteins in the loop of Henle have been discovered in individuals with clinical Bartter syndrome (Bichet and Fujiwara, 2004; Naesens, 2004). They are the NaKCl (NKCC2) transporter; the ROMK1 potassium channel; the chloride channel CLCKa either alone or in combination with the chloride channel CLCKb; the calcium sensing receptor; and barttin, a protein required for the surface expression of the chloride channels. The most severe cases present antenatally or neonatally with profound volume depletion and hypokalemia. Less severe cases present in childhood or early adulthood with persistent hypokalemic metabolic alkalosis that is resistant to replacement therapy. Type IV, a variant to the classic Bartter syndrome, is associated with sensorineural hearing loss.
    
    
    
    • Gitelman syndrome: This is an autosomal-recessive disorder characterized by hypokalemic metabolic alkalosis and low blood pressure. It is caused by a defect in the thiazide-sensitive sodium chloride transporter in the distal tubule. Compared to Bartter syndrome, it generally is milder, presents later, and is complicated by hypomagnesemia. In contrast, patients with Bartter syndrome generally do not develop hypomagnesemia. Hypocalciuria is also frequently found in Gitelman syndrome, while the patients with Bartter syndrome are more likely to have increased urinary calcium excretion.
    
    
    
    • Liddle syndrome: This syndrome is an autosomal-recessive disorder characterized by a mutation in the epithelial sodium channel in the aldosterone-sensitive portion of the nephron, leading to unregulated sodium reabsorption, hypokalemic metabolic alkalosis, and severe hypertension.
       
  • Osmotic diuresis: Mannitol and hyperglycemia can cause osmotic diuresis.
  
  
  
  • Increased gastrointestinal losses: Losses can result from diarrhea or small intestine drainage.
  
  
  
  • Diuretics (carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics): Increased collecting duct permeability or increased gradient for potassium secretion can result in losses.
  
  
  
  • Some penicillins
  
  
  
  • Exogenous bicarbonate ingestion
  
  
  
  • Amphotericin B
  
  
  
  • Gentamicin
  
  
  
  • Cisplatin
• Shift of potassium from extracellular to intracellular space
  
  
  • Alkalosis, metabolic or respiratory
  
  
  
  • Insulin administration or glucose administration: This stimulates insulin release.
  
  
  
  • Intensive beta-adrenergic stimulation
  
  
  
  • Hypokalemic periodic paralysis is a rare disorder with recurrent periods of hypokalemic paralysis between periods of normal serum potassium levels.  In most cases, it is due to an abnormality in the alpha 1 subunit of the dihydropyridine-sensitive calcium channel in the skeletal muscle.  How a defect in a calcium channel produces hypokalemic paralysis is not well understood.
  
  
  
  • Thyrotoxic periodic paralysis is an acquired form of hypokalemic periodic paralysis and is most common in Asian males.  The mechanism by which hyperthyroidism produces hypokalemic paralysis is not yet understood, but theories include increased Na-K-ATPase activity, which has been found in patients with both thyrotoxicosis and paralysis. 
  
  
  
  • Refeeding: This is observed in prolonged starvation, eating disorders, and alcoholism.

WORKUP

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urine potassium: This test is of vital importance because it establishes the pathophysiologic mechanism and, thus, helps formulate the differential diagnosis.
  
  
  • A spot urine potassium measurement is, for obvious reasons, the easiest and most commonly obtained test. Low urine potassium (<20 mEq/L) suggests poor intake, a shift into the intracellular space, or gastrointestinal loss. High urine potassium (>40 mEq/L) suggests renal loss.
  
  
  
  • A spot urine sodium and osmolality test obtained simultaneously with a spot urine potassium test can help refine the interpretation of the urine potassium level. A low urine sodium level (<20 mEq/L) with a high urine potassium level suggests the presence of secondary hyperaldosteronism. If the urine osmolality is high (>700 mOsm/kg), then the absolute value of the urine potassium concentration can be misleading and can suggest that the kidneys are wasting potassium.
    
    
    • For example, suppose the serum potassium level is 3 mEq/L and the urine potassium level is 60 mEq/L. The high urine potassium level would suggest renal potassium loss. However, the final concentration of potassium in the urine is dependent not only on the quantity of potassium secreted in response to sodium reabsorption, but also on the concentration of the urine.
    
    
    
    • In the above example, if urine osmolality is 300 mOsm/kg, ie, not concentrated relative to serum, then a measured urine potassium of 60 mEq/L indeed suggests renal potassium loss. However, if the urine osmolality is 1200 mOsm/kg, ie, concentrated 4-fold relative to serum, then the potassium concentration in the urine, in the absence of urinary concentration due to water reabsorption, is 15 mEq/L, ie, very low.
    
    
    
    • The conclusion would then be that the kidneys are not responsible for the low serum potassium.
       
  • To account for the potentially confounding effect of urine concentration on the interpretation of the urine potassium concentration, a calculation called the transtubular potassium gradient (TTKG) has been developed (West, 1986; Weinstein, 2001). This test, in effect, back-calculates what the serum-to-tubular fluid ratio of potassium would be at the level of the cortical collecting tubule, where potassium is secreted before urine concentration has occurred. Performing this test requires measuring serum and urine potassium levels and osmolality according to the following equation:
    
    TTKG = (Urine potassium X serum osm )/(serum potassium X urine osm)

  A value less than 3 suggests that the kidney is not wasting excessive potassium, while a value greater than 7 suggests a significant renal loss. This test cannot be applied when the urine osmolality is less than the serum osmolality.

• Urine potassium in 24 h: While more cumbersome to obtain, a 24-hour urine measurement of potassium excretion yields more precise data on exactly how much potassium is being lost through renal excretion.
  
  
  • Because the kidneys are able to conserve potassium up to approximately 10-15 mEq/d, a value of less than 20 mEq/24-hour urine specimen suggests appropriate renal conservation of potassium, while values above that indicate some degree of renal wasting.
  
  
  
  
  • To ensure that a full and accurate 24-hour urine sample has been collected, urine creatinine should be measured simultaneously.




• Basic metabolic profile: Measure electrolytes, BUN, and creatinine.



• Serum sodium level
  
  
  • Low serum sodium suggests thiazide diuretic use or marked volume depletion from gastrointestinal losses.
  
  
  
  
  • High serum sodium might suggest that nephrogenic diabetes insipidus has occurred secondary to hypokalemia. This could indicate that the hypokalemia is a long-standing problem. A high serum sodium level also might suggest the presence of primary hyperaldosteronism, especially if hypertension also is present.




• Serum bicarbonate level
  
  
  • A low serum bicarbonate level might suggest renal tubular acidosis, diarrhea, or the use of carbonic anhydrase inhibitors.
  
  
  
  
  • A high serum bicarbonate level is consistent with either primary hyperaldosteronism or secondary hyperaldosteronism. Causes of secondary hyperaldosteronism could be exogenous prednisone therapy, vomiting, or the use of thiazide or loop diuretics. A high serum bicarbonate level is also consistent with Bartter, Gitelman, or Liddle syndrome.
  
  
• Hyperglycemia might suggest that the hypokalemia has been of sufficient severity and duration to impair glucose tolerance.



• Creatine kinase: Occasionally, hypokalemia will be of sufficient severity to produce not only muscle weakness but also frank rhabdomyolysis. This most often occurs in the setting of alcoholism, where total body potassium stores may be quite low due to prolonged periods of poor intake. Severe rhabdomyolysis can lead to renal failure and subsequent severe hyperkalemia.



• Magnesium: Often, severe hypokalemia is associated with significant magnesium losses and cannot be corrected unless the hypomagnesemia is corrected.



• Algorithm for evaluation of hypokalemia: Complete history and physical examination can reveal the cause in most cases, negating the need for extensive testing.
  
  
  • Urine potassium level less than 20 mEq/L suggests gastrointestinal loss, poor intake, or shift of potassium into cells. Question the patient regarding (1) diarrhea and use of laxatives; (2) diet and TPN contents; and (3) the use of insulin, excessive bicarbonate supplements, and episodic weakness.
  
  
  
  
  • A urine potassium level higher than 40 mEq/L suggests renal loss.
    
    
    
    
    • Examine the patient's medication list. Question the patient regarding the use of diuretics.
    
    
    
    
    • Look at the acid-base balance; alkalosis suggests vomiting, Bartter syndrome, Gitelman syndrome, diuretic abuse, or mineralocorticoid excess. Acidosis suggests renal tubular acidosis types I or II or Fanconi syndrome (as is observed with paraproteinemias, amphotericin use, gentamicin use, or glue sniffing [toluene abuse]).
    
    
    
    
    • Measure the magnesium level; if low, correct it before attempting to correct the potassium level.
    
    
    
    
    • Measure the patient's blood pressure. Elevated blood pressure suggests primary hyperaldosteronism, Cushing syndrome, congenital adrenal hyperplasia, glucocorticoid-remediable hypertension, renal artery stenosis, or Liddle syndrome. Low blood pressure suggests diuretic abuse or a renal tubular disorder such as Bartter syndrome, Gitelman syndrome, or renal tubular acidosis.
    
    
  • If the urine potassium level is higher than 20 mEq/L but lower than 40 mEq/L, calculate the TTKG.
    
    
    • A TTKG of less than 3 suggests that renal loss is not a cause of hypokalemia.
    
    
    
    • A TTKG greater than 7 suggests mineralocorticoid excess.
    
    
    
    • A middle value may indicate a mixed disorder.

Imaging Studies

• Imaging techniques are not used as first-line studies. See Other Tests.

Other Tests

• Perform an ECG to determine whether the hypokalemia is affecting cardiac function or to detect digoxin toxicity. ECG may show atrial or ventricular tachyarrhythmias, decreased amplitude of the P wave, or appearance of a U wave.



• In most cases, the cause of hypokalemia is apparent from the history and physical examination and is confirmed by the measurement of urine potassium. By far the most common causes are losses due to diuretics or gastrointestinal disorders. Depending on history, physical examination findings, clinical impressions, and urine potassium results, the following tests may be appropriate, but they should not be first-line tests unless the clinical index of suspicion for the disorder is high.
• • Diuretic screen in urine and/or serum
  
  
  
  • Serum renin, aldosterone, and cortisol
  
  
  
  • 24-hour urine aldosterone, cortisol, sodium, and potassium
  
  
  
  • Pituitary imaging to evaluate for Cushing syndrome
  
  
  
  • Adrenal imaging to evaluate for adenoma
  
  
  
  • Renal angiogram to evaluate for renal artery stenosis
  
  
  
  • Enzyme assays for 17-beta hydroxylase deficiency

TREATMENT

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Orient medical care toward 4 different aims: (1) decreasing potassium losses, (2) replenishing potassium stores, (3) evaluating for potential toxicities, and (4) determining the cause to prevent future episodes.

• In treating hypokalemia, the first step is to identify and stop ongoing losses of potassium.
• • Discontinue diuretics/laxatives.
  
  
  
  • Use potassium-sparing diuretics if diuretic therapy is required (eg, severe heart failure).
  
  
  
  • Treat diarrhea or vomiting.
  
  
  
  • Use H2 blockers to decrease nasogastric suction losses.
  
  
  
  • Control hyperglycemia if glycosuria is present.
  
  
  
• Repletion of potassium losses is the second step.
• • As a first approximation, for every decrease in serum potassium of 1 mEq/L, the potassium deficit is approximately 200-400 mEq. However, bear in mind that many factors in addition to the total body potassium stores contribute to the serum potassium concentration. Therefore, this calculation could either overestimate or underestimate the true potassium deficit.
  
  
  
  • Oral potassium is absorbed readily. Relatively large doses can be given safely. Oral administration is limited by patient tolerance because some individuals develop nausea or even gastrointestinal ulceration with enteral potassium formulations.
  
  
  
  • Intravenous potassium is less well tolerated because it can be highly irritating to veins and can be given only in relatively small doses, generally 10 mEq/h. Under close cardiac supervision in emergent circumstances, as much as 40 mEq/h can be administered through a central line.
  
  
  
  • Oral and parenteral potassium can be used safely simultaneously.
  
  
  
  • Take ongoing potassium losses into consideration by measuring the volume and potassium concentration of body fluid losses.
  
  
  
  • If the patient is severely hypokalemic, avoid glucose-containing parenteral fluids to prevent an insulin-induced shift of potassium into the cells.
  
  
  
  • If the patient is acidotic, correct the potassium first to prevent an alkali-induced shift of potassium into the cells.
  
  
  
  • Replete magnesium if low.
  
  
  
  • Tailor treatment to the individual patient. For example, if diuretics cannot be discontinued due to an underlying disorder such as congestive heart failure, institute potassium-sparing therapies such as a low-sodium diet, potassium-sparing diuretics, ACE inhibitors, and angiotensin receptor blockers. The low-sodium diet and potassium-sparing diuretics limit the amount of sodium reabsorbed at the cortical collecting tubule, thus limiting the amount of potassium secreted. ACE inhibitors and angiotensin receptor blockers inhibit the release of aldosterone, thus blocking the kaliuretic effects of that hormone.
  
  
  
• Monitor for toxicity of hypokalemia. Generally, the toxicity of hypokalemia is cardiac in nature. Monitor the patient if evidence of cardiac arrhythmias is observed, and institute very aggressive replacement parenterally under monitored conditions.



• Determine the underlying cause to treat and prevent further episodes.
• • Again, history and physical examination findings clarify the cause in the vast majority of cases.
  
  
  
  • Look for clues to the etiology.
    
    
    • Urine potassium concentration
    
    
    
    • Presence of hypertension or hypotension
    
    
    
    • Acid-base disturbances
    
    
    
    • Family history
    
    
    
    • Tooth erosion; melanosis coli; obsession with body image; high-risk behaviors such as cheerleading, wrestling, or modeling; or evidence of alcohol abuse
       
  • Tailor the workup to the individual patient if the cause is not completely apparent.
  
  
  

Surgical Care

Generally, hypokalemia is a medical, not a surgical, condition. Surgical intervention is required only after determining that the etiology requires it. Etiologies that may require surgery include the following:

• Renal artery stenosis
• Adrenal adenoma
• Intestinal obstruction producing massive vomiting
• Villous adenoma

Consultations

The following consultations may be appropriate, depending on the clinical findings:

• Renal specialist for evaluation of unexplained urinary potassium losses suggested to be secondary to a tubular disorder



• Endocrinologist if Cushing syndrome, primary hyperaldosteronism, glucocorticoid-remediable hypertension, or congenital adrenal hyperplasia is suggested



• Psychiatrist for alcoholism or eating disorders



• Surgeon (see Surgical Care)

Diet

In general, a low-sodium and high-potassium diet is appropriate.

Activity

Unless the patient has severe underlying cardiac disease, no restrictions are necessary. Instruct patients to discontinue exercise if muscle pain or cramps develop because this may herald hypokalemia significant enough to produce rhabdomyolysis.

MEDICATION

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to correct the deficiency.

Drug Category: Electrolytes

Oral or parenteral therapy for potassium replacement.

Drug Category: Angiotensin-converting enzyme inhibitors

Inhibit production of aldosterone and decrease renal potassium losses. All the drugs in this category work in the same way. Differences are in the duration of action and the ability to inhibit locally produced and circulating ACE.

Drug Category: Potassium-sparing diuretics

Excellent adjunct therapy when ongoing renal losses are anticipated. May be used in conjunction with thiazide or loop diuretics.

Drug Category: Angiotensin II receptor blockers

These agents competitively inhibit the ability of angiotensin II to interact with and stimulate angiotensin II receptors. This action results in decreased aldosterone secretion and, consequently, decreased renal potassium excretion.

Drug Category: Selective aldosterone blockers

These agents selectively block aldosterone binding at mineralocorticoid receptors.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Further inpatient care consists of monitoring serum potassium levels and adjusting supplements. Once a cause has been determined for hypokalemia and the condition has been treated as per the diagnosis, ensuring that treatment plans are adequate is imperative. Recall that potassium can shift in and out of cells under several influences. Therefore, several determinations of serum potassium level after presumably adequate replacement are indicated to ensure that serum potassium levels achieve normalcy.



• After potassium has been replenished, checking again for several days to determine whether potassium has stabilized or has started falling again is equally important. For example, if an individual presents with nausea and vomiting and hypokalemia, the physician might understandably attribute the hypokalemia to the nausea and vomiting. However, if after replenishment, the patient once again develops hypokalemia without nausea and vomiting, then considering other possible causes of hypokalemia is necessary. Additionally, if a need for ongoing potassium supplementation is anticipated for the patient (eg, a patient on long-term diuresis for hypertension), then ensuring that the prescribed daily potassium supplement is adequate to maintain a normal serum potassium level is important.



• Evaluate for more unusual secondary causes. If an unusual cause of hypokalemia is suggested, due to either specific clinical features or failing to observe a response to the initial therapy, evaluation can at least begin while the patient is hospitalized. However, evaluation often can be completed in an outpatient setting.
• • If occult diuretic or laxative use is suspected, establishing proof of this is best accomplished in the hospital, with patients in a relatively controlled environment. In this setting, 24-hour urine measurements of sodium and potassium excretion, measurement of serum potassium at frequent intervals, and supervision of intake and output are possible. Ongoing potassium losses in the face of a negative urine and serum screen for diuretics suggest another diagnosis.
  
  
  
  • If patients are hypertensive, then the next steps would be determining serum renin activity and aldosterone and cortisol levels; obtaining a 24-hour urine measurement for aldosterone, cortisol, sodium, and potassium; initiating a captopril renal scan to investigate the possibility of renal artery stenosis; and performing a CT scan of the abdomen to investigate for a possible adrenal adenoma. A high cortisol level suggests Cushing disease. Evaluate for pituitary or adrenal causes. If renin and aldosterone levels are both elevated, this points more strongly to renal artery stenosis.
  
  
  
  • If the index of suspicion is high enough, then perform a renal arteriogram and renal vein renin determination to look for significant renal artery stenosis as a cause of hypertension and hypokalemia. A high aldosterone level with low renin activity suggests primary hyperaldosteronism. If the patient is hypertensive but the aldosterone level is low, this suggests one of the more unusual congenital forms of hypertension, such as Liddle syndrome, where a mutation in the epithelial sodium channel produces uncontrollable sodium reabsorption or glucocorticoid-remediable hypertension. This scenario also could be produced by licorice ingestion or ingestion of a steroid with mineralocorticoid activity, such as prednisone or fludrocortisone.
  
  
  
  • If patients are not hypertensive but have hypokalemic metabolic alkalosis, then possibilities include Bartter syndrome or Gitelman syndrome if diuretic use and bulimia have been excluded. If patients have metabolic acidosis, the most common cause is diarrhea. If this is not present, then the most likely possibility is a distal renal tubular acidosis, as might be seen with amyloid or amphotericin use or with glue sniffing.
  
  
  

Further Outpatient Care

• For otherwise healthy patients undergoing what appears to be an acute episode causing hypokalemia, such as severe diarrhea, no further follow-up care is required.
• For patients who are likely to develop hypokalemia again (eg, on diuretic therapy), periodic monitoring of serum potassium levels is essential. If not performed during hospitalization, then outpatient follow-up care with tests such as 24-hour urine cortisol and aldosterone is acceptable.

In/Out Patient Meds

• Oral potassium chloride
• • This should be given as indicated. Maintain the patient, if necessary, on a fixed regimen.
  • Potassium chloride is absorbed easily and can be given several times per day if needed, especially if high-dose diuretic therapy is required.

• Potassium-sparing diuretics
• • Generally, use potassium-sparing diuretics only in patients with normal renal function who are prone to significant hypokalemia.
  • Some evidence indicates that spironolactone is particularly useful in patients with cirrhosis and patients with heart failure. Exercise caution in using potassium-sparing diuretics in either of these populations. Frequent determination of potassium levels is mandatory.
  • Often, individuals with cirrhosis or congestive heart failure have subtle decreases in renal function that might not be apparent based on routine lab work. In addition, patients with heart failure often are treated with ACE inhibitors, another class of drugs that inhibits renal potassium excretion.
  • The combination of mild renal insufficiency, an ACE inhibitor, a potassium-sparing diuretic, and a potassium supplement can very easily result in life-threatening hyperkalemia. Although these combinations can be used, frequent follow-up care is necessary.

• Angiotensin-converting enzyme inhibitors
• • ACE inhibitors have gained significantly in popularity due to demonstration of their tolerability and benefit in a variety of disease conditions. These drugs are amazingly well tolerated by large groups of individuals.

  • Cough is the most common complaint, but other types of adverse effects commonly seen with other antihypertensives, such as exercise intolerance, fatigue, dry mouth, impotence, and drowsiness, are not reported as commonly.

  • In particular, these drugs have demonstrable clinical benefit for the treatment of hypertension, congestive heart failure, and a variety of kidney diseases, including diabetic nephropathy.

  • The combination of ACE inhibitors with thiazide or loop diuretics is excellent because they ameliorate some of the hypokalemia that can occur with diuretic use.

  • Nonetheless, the provisos listed regarding potassium-sparing diuretics apply here. In patients with renal insufficiency and on potassium supplements or potassium-sparing diuretics, use of ACE inhibitors can lead to lethal hyperkalemia.

Transfer

• Transfer generally is not required unless patients experience untreatable cardiac arrhythmias, digoxin toxicity, or paralysis and no facilities are available for monitoring. In general, even severe hypokalemia can be treated successfully in most medical centers.

Deterrence/Prevention

• Some authors advocate the routine use of potassium supplementation in patients with congestive heart failure. Undoubtedly, most patients will require potassium supplementation because they will be taking loop diuretics. However, recall the caveats concerning the use of potassium supplements, ACE inhibitors, and potassium-sparing diuretics in patients with subclinical renal failure.

Complications

• Cardiovascular complications are clinically the most important harbingers of significant morbidity or mortality from hypokalemia.
• • Although hypokalemia has been implicated in the development of both atrial arrhythmias and ventricular arrhythmias, ventricular arrhythmias have received the most attention. Increased susceptibility to cardiac arrhythmias is observed with hypokalemia in the following settings.
    
    
    • Congestive heart failure
    
    
    
    • Underlying ischemic heart disease/acute myocardial ischemia
    
    
    
    • Aggressive therapy for hyperglycemia, such as with diabetic ketoacidosis
    
    
    
    • Digitalis therapy
       
  • Low potassium intake has been implicated as a risk factor for the development of hypertension and/or hypertensive end-organ damage.
  
  
  
  • Hypokalemia leads to altered vascular reactivity, likely due to the effects of potassium depletion on the expression of adrenergic receptors, angiotensin receptors, and mediators of vascular relaxation. The result is enhanced vasoconstriction and impaired relaxation, which may play a role in the development of diverse clinical sequelae, such as ischemic central nervous system events or rhabdomyolysis.
  
  
  
• Muscle weakness, depression of the deep-tendon reflexes, and even flaccid paralysis can complicate hypokalemia. Rhabdomyolysis can be provoked, especially with vigorous exercise.



• Abnormalities of renal function often accompany acute or chronic hypokalemia.
• • This may include nephrogenic diabetes insipidus.
  
  
  
  • It also may include metabolic alkalosis due to impaired bicarbonate excretion and enhanced ammonia genesis.
  
  
  
  • Another may be cystic degeneration and interstitial scarring.
  
  
  
• Hypokalemia decreases gut motility, leading to or exacerbating an ileus.



• Hypokalemia also is a contributory factor in the development of hepatic encephalopathy in the setting of cirrhosis.



• Hypokalemia has a dual effect on glucose regulation.
• • Hypokalemia decreases insulin release.
  
  
  
  • It also decreases peripheral insulin sensitivity.
  
  
  
• Hypokalemia has widespread actions in many organ systems, which, over time, result in cardiovascular disease.
  
  
  • Hypokalemia or potassium deficiency contributes to the development of hypertension.
  
  
  
  • Altered glucose metabolism due to impaired insulin release and peripheral sensitivity leads to altered lipid metabolism and endothelial cell dysfunction, increasing the risk of overt atherosclerosis.
  
  
  
  • The combined endothelial and vascular smooth-muscle cell dysfunction enhances vasoconstriction, increasing the likelihood of end-organ ischemia.
  
  
  
  • Treatment of hypertension with diuretics without due attention to potassium homeostasis exacerbates the development of end-organ damage by fueling the metabolic abnormalities.
  
  
  
  • These patients are then at higher risk for lethal hypokalemia under stress conditions such as myocardial infarction, septic shock, or diabetic ketoacidosis.

Prognosis

• The prognosis for hypokalemia depends entirely on the underlying cause. An acute episode due to diarrhea has an excellent prognosis. Hypokalemia due to a congenital disorder such as Bartter syndrome has a poor to nonexistent potential for successful treatment.

Patient Education

• Instruct patients on symptoms of hypokalemia or hyperkalemia.
• • Palpitations or notable cardiac arrhythmias
  • Muscle weakness
  • Increasing difficulty with diabetes control
  • Polyuria

• Instruct patients on the effects of medications, specifically, which of their drugs will produce serum potassium abnormalities in either direction. For example, tell patients to discontinue diuretics if nausea and vomiting or diarrhea occurs and to call the physician if such gastrointestinal losses persist. Depending on patients' underlying disease or diseases, sudden fluid losses can result in either hypokalemia or hyperkalemia if diuretics, potassium supplements, or antihypertensives are continued.
• Instruct patients on diet. High sodium intake tends to enhance renal potassium losses. Therefore, instruct patients about a low-sodium, high-potassium diet.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Low Potassium.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• ECG monitoring is imperative for severe hypokalemia (<2 mg/dL in otherwise healthy individuals or <3 mg/dL in patients with known or suspected cardiac disease). With a sudden shift of potassium into the cells (eg, with insulin therapy for diabetic ketoacidosis), even individuals with healthy hearts can develop lethal arrhythmias. Continuously monitor patients on digoxin or those with digoxin toxicity.
• Cases of suspected inadequate intake as a cause of hypokalemia generally indicate abuse by self or others. Consider psychiatric evaluation for suspected alcoholism or an eating disorder. Consider referral to abuse authorities if neglect (particularly in the case of an elderly person) or intentional child abuse is suspected.
• Remember that the combination of potassium supplements, ACE inhibitors, angiotensin receptor blockers, and potassium-sparing diuretics has the potential to produce severe hyperkalemia. Patients taking drugs that can alter serum potassium levels require periodic follow-up care. The greater the number of medical problems and the greater the number of drugs, the more frequent the follow-up care should be. Failure to check potassium levels after alteration of 1 of these drugs could allow the patient to develop a lethal complication.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Mar 20, 2007