Hypokalemia in children

INTRODUCTION — Hypokalemia is defined as a serum or plasma potassium that is less than the normal value. Most reference laboratories establish the lower pediatric limit of normal serum potassium between 3 and 3.5 mEq/L. However, symptoms are unlikely to occur in most healthy children until serum potassium is below 3 mEq/L.

The etiology, clinical findings, diagnosis, evaluation, and management of pediatric hypokalemia are reviewed here. Hypokalemia in adults is discussed separately. (See "Clinical manifestations and treatment of hypokalemia in adults" and "Causes of hypokalemia in adults" and "Evaluation of the adult patient with hypokalemia".)

EPIDEMIOLOGY — Hypokalemia is relatively common among hospitalized pediatric patients, especially those who are critically ill [1-3]. In one study of 667 children cared for in a single-center pediatric intensive care unit in the United States during the calendar year 2006, 40 percent of the patients had a serum potassium level below 3.5 mEq/L [1]. This included patients with severe hypokalemia, defined as potassium level less than 2.5 mEq/L (4 percent); moderate hypokalemia, defined as potassium level 2.5 to less than 3 mEq/L (12 percent); and mild hypokalemia, defined as potassium level from 3 to less than 3.5 mEq/L (24 percent). Hypokalemia was associated with diagnoses of cardiac disease, kidney failure, or shock [1].

In resource-limited countries, severe hypokalemia (potassium level <2.5 mEq/L) is often observed in children with diarrhea and severe acute malnutrition and is associated with an increased risk of mortality [4].

POTASSIUM BALANCE AND LEVELS

Definition — Potassium is primarily an intracellular cation with cells containing approximately 98 percent of total body potassium. Hypokalemia is defined as serum level below the normal value, which is usually defined as 3.5 mEq/L, although the threshold varies with age (table 1). Degrees of hypokalemia are defined as following:

●Severe hypokalemia – Potassium level less than 2.5 mEq/L

●Moderate hypokalemia – Potassium level between 2.5 and 3 mEq/L

●Mild hypokalemia – Potassium level between 3 and 3.5 mEq/L

Homeostatic mechanisms — Homeostatic mechanisms regulate potassium balance in order to maintain high intracellular levels required for cellular functions (metabolism and growth), and low extracellular concentration to preserve the steep concentration gradient across the cell membrane needed for nerve excitation and muscle contraction. In children, positive potassium balance is needed for growth, whereas in adults, homeostasis is directed towards a zero potassium balance.

After a bolus of potassium intake, normal physiologic processes preserve the intra- and extracellular balance via intracellular potassium movement, which is regulated by cell membrane Na-K-ATPase (mediated by insulin, and alpha- and beta-2 adrenergic agonists), and urinary potassium excretion (primarily mediated by aldosterone). Although normal serum and plasma potassium concentrations in children and adolescents are similar to levels in adults, infants have a higher normal range of potassium because of their reduced urinary potassium excretion, which is caused by their relatively increased aldosterone insensitivity and decreased glomerular filtration rate (table 1). (See "Causes and evaluation of hyperkalemia in adults", section on 'Brief review of potassium physiology'.)

Pathogenesis of hypokalemia — Hypokalemia in children is caused by derangements of the homeostatic mechanisms that normally regulate potassium balance, which are the same as those that occur in adults. Understanding the underlying physiology is helpful in the diagnostic evaluation and treatment of children with hypokalemia.

Pediatric hypokalemia is due to one or a combination of the following mechanisms:

●Decreased potassium intake

●Increased intracellular movement of potassium

●Excessive loss of potassium via the gastrointestinal (GI) tract, kidney, or skin

CAUSES — In the following sections, the causes of pediatric hypokalemia are classified based on the underlying pathophysiologic process (table 2).

Decreased intake — Decreased intake alone is unlikely to cause hypokalemia in healthy children. However, prolonged decreased intake (eg, malnutrition or anorexia) in combination with increased potassium losses via the kidney or gastrointestinal (GI) tract can lead to significant potassium depletion.

Increased intracellular uptake — As noted above, the normal distribution of potassium between cells and the extracellular fluid is primarily maintained by the Na-K-ATPase pump in the cell membrane. Increased activity of the Na-K-ATPase pump and/or alterations in other potassium transport pathways can result in transient hypokalemia due to increased potassium entry into cells from the extracellular space.

●Alkalosis – Either respiratory or metabolic alkalosis can be associated with hypokalemia. In this setting, intracellular potassium movement is promoted to maintain electroneutrality as hydrogen ions exit the cell in response to the increase in extracellular pH. In general, serum potassium concentration falls by less than 0.4 mEq/L for every 0.1 unit rise in pH.

In children with metabolic alkalosis, there is also an increased loss of urinary potassium. This is due to a rise in plasma bicarbonate concentration, resulting in a filtered bicarbonate load above its reabsorptive threshold, which leads to increased distal delivery of sodium bicarbonate. At the distal tubule, sodium is exchanged for potassium, causing the increased loss in urinary potassium. (See 'Increased distal delivery of sodium and water' below.)

●Increased insulin activity – Insulin promotes intracellular potassium movement by increasing the activity of the Na-K-ATPase pump and is used therapeutically to treat severe hyperkalemia [5]. In particular, insulin administration in children with diabetic ketoacidosis results in a fall in serum potassium due to the increased insulin-mediated intracellular movement of potassium. One small study also reported that insulin increased renal potassium excretion [6]. (See "Diabetic ketoacidosis in children: Treatment and complications", section on 'Serum potassium'.)

Hypokalemia due to insulin-mediated potassium transcellular movement can also be seen in the refeeding syndrome after prolonged starvation or in children and adolescents with eating disorders [7]. (See "Anorexia nervosa in adults and adolescents: The refeeding syndrome", section on 'Pathogenesis and clinical features' and "Poor weight gain in children younger than two years in resource-abundant settings: Management", section on 'Prevention of nutritional recovery syndrome'.)

●Elevated beta-adrenergic activity – Nonselective (eg, isoproterenol and epinephrine) and selective (eg, albuterol and terbutaline) beta-adrenergic agents promote intracellular movement of potassium by increasing Na-K-ATPase pump activity. The use of these agents in children can decrease serum potassium levels and, in some cases, result in hypokalemia [8,9]. (See "Acute asthma exacerbations in children younger than 12 years: Inpatient management", section on 'Laboratory studies'.)

●Hypokalemic periodic paralysis – Hypokalemic periodic paralysis is a rare neuromuscular condition that presents with sudden episodes of severe muscle weakness associated with hypokalemia. In these patients, the potassium level can drop rapidly to below 2 mEq/L. Symptoms may be triggered by events associated with increased adrenergic tone, such as exercise, stress, and high-carbohydrate meals.

Hypokalemic periodic paralysis is due to defects in muscle calcium and sodium channels. Most cases are hereditary and are primarily associated with a mutation in the gene that codes for the alpha-1 subunit of the dihydropyridine-sensitive calcium channel in skeletal muscle. These patients typically present in late childhood or adolescence. Acquired cases have been reported in patients with hyperthyroidism (referred to as thyrotoxic periodic paralysis) and typically present in older patients between 20 and 30 years of age. (See "Hypokalemic periodic paralysis" and "Thyrotoxic periodic paralysis".)

●Other drugs (besides beta-adrenergic agonists)

•Heavy metals – Barium toxicity is a rare cause of hypokalemia, caused by blockade of potassium channels limiting their efflux from cells. Barium salts are found in fireworks and rodent toxins [10,11]. Barium sulfate is the formulation used in radiographic procedures and is not absorbed from the gut. Cesium has been reported as a rare cause of hypokalemia in adults due to its use as an alternative therapy for cancer but has not been reported in children [12].

•Antipsychotic drugs – Hypokalemia has been reported in association with the use of risperidone and quetiapine in adults. Given the increasing use of this medication in children and adolescents, a high index of suspicion should be present in children with hypokalemia or cardiac arrhythmias who are prescribed these medications. (See "Causes of hypokalemia in adults", section on 'Antipsychotic drugs'.)

•Chloroquine intoxication is an uncommon cause of severe hypokalemia in children due to intracellular movement of potassium [13-16].

Gastrointestinal losses — GI losses are the most common cause of hypokalemia in children. In particular, diarrheal potassium content (20 to 50 mEq/L) is relatively high compared with other body fluids [17]. In resource-limited countries, acute diarrhea with hypokalemia is associated with an increased risk of death [4,18]. (See "Approach to the child with acute diarrhea in resource-limited settings", section on 'Fluid and electrolytes'.)

In contrast, upper GI losses (eg, vomiting, nasogastric drainage) are initially minimal as the potassium content is relatively low (5 to 10 mEq/L). However, the loss of gastric secretions results in metabolic alkalosis that leads to increased urinary potassium losses. As noted above, metabolic alkalosis leads to increased distal delivery of sodium bicarbonate, which in combination with hypovolemia-induced hyperaldosteronism results in enhanced potassium excretion as potassium is exchanged for sodium. (See 'Increased distal delivery of sodium and water' below.)

Increased urinary losses — Urinary potassium excretion is primarily due to secretion of potassium in the distal nephron by the principal cells in the connecting tubule and cortical collecting tubule. In the distal tubule, sodium is reabsorbed under the influence of mineralocorticoids (primarily aldosterone) and potassium is exchanged to preserve electroneutrality. Increased urinary potassium loss contributing to hypokalemia is typically due to one or both of the following mechanisms:

●Increased delivery of sodium and water to the distal nephron

●Increased mineralocorticoid activity

Increased distal delivery of sodium and water — In children, the following conditions are associated with urinary potassium losses leading to lower serum potassium as a result of increased distal delivery of sodium.

●Diuretics – Diuretic therapy (loop and thiazide diuretics) impairs sodium reabsorption in more proximal nephron segments leading to distal delivery of sodium. In addition, volume depletion leads to increased aldosterone activity.

●Nonreabsorbable ions – Nonreabsorbable anions are accompanied by sodium, resulting in distal delivery of sodium, which is exchanged with potassium. Pediatric settings in which the presence of nonreabsorbable anions results in increased distal delivery of sodium include excess filtered bicarbonate in patients with excessive vomiting or with proximal (type 2) renal tubular acidosis (RTA), beta-hydroxybutyrate in patients with diabetic ketoacidosis, and hippurate following toluene abuse (glue sniffing). (See 'Gastrointestinal losses' above and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Serum potassium' and "Inhalant misuse in children and adolescents", section on 'Hypokalemia'.)

●Osmotic diuresis – Osmotic diuresis can also result in increased distal delivery of sodium, resulting in hypokalemia. This is most commonly seen in children with diabetic ketoacidosis who have glucose osmotic diuresis due to glycosuria because the filtered load exceeds the proximal tubular reabsorptive capacity. Administration of mannitol is a less frequent cause of hypokalemia due to osmotic diuresis. Hypovolemia may also result from osmotic diuresis if there is inadequate fluid replacement, which leads to increased aldosterone activity and enhanced distal potassium secretion. (See 'Increased mineralocorticoid activity' below.)

●Genetic tubular disorders – Bartter and Gitelman syndromes are autosomal recessive diseases that are caused by mutations in genes encoding tubular transport proteins involved in sodium reabsorption. In these patients, sodium absorption is disrupted leading to increased distal delivery of sodium, resulting in metabolic alkalosis and hypokalemia, similarly to findings seen in patients who receive chronic diuretic therapy. In addition, the volume depletion leads to increased levels of renin and aldosterone, which further enhances urinary potassium losses. (See "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations".)

●Tubular injury – Tubular injury due to tubulointerstitial diseases or cisplatin results in decreased sodium reabsorption in more proximal nephron segments, leading to distal delivery of sodium, where potassium is exchanged for sodium. In one small case series of pediatric patients, tubulopathy due to cisplatin, which resulted in reduced potassium, persisted for months to years following completion of chemotherapy [19]. (See "Cisplatin nephrotoxicity", section on 'Salt wasting'.)

Renal tubular acidosis — In distal (type 1) RTA, increased urinary potassium loss is due to enhanced potassium secretion needed to maintain electroneutrality because of the impaired distal acidification (ie, defective secretion of protons) (table 3). In addition, tubular cellular membrane permeability is also increased, leading to potassium loss into the lumen along with protons. In proximal (type 2) RTA, as noted above, urinary potassium loss is due to increased distal delivery of sodium bicarbonate due to the reduced proximal tubule's absorptive capacity for bicarbonate. (See "Etiology and clinical manifestations of renal tubular acidosis in infants and children" and 'Increased distal delivery of sodium and water' above.)

Increased mineralocorticoid activity — Increased mineralocorticoid activity enhances potassium urinary excretion.

●Hypovolemia – In children, the most common cause of increased mineralocorticoid activity is secretion of aldosterone (hyperaldosteronism) in response to volume depletion.

●Other etiologies – Other pediatric causes of increased mineralocorticoid activity are rare and include:

•Aldosterone-secreting adenomas. (See "Pathophysiology and clinical features of primary aldosteronism", section on 'Pathophysiology' and "Diagnosis of primary aldosteronism".)

•Glucocorticoid remediable aldosteronism (GRA) is an autosomal dominant disorder due to a fusion of the promoter of the gene encoding aldosterone synthase in the adrenal zona fasciculata (involved in cortisol synthesis) with the coding region of the related gene in the zona glomerulosa (involved in aldosterone synthesis). This mutation increases the production of aldosterone, which can be suppressed by glucocorticoid administration. GRA typically presents with hypertension before 21 years of age. The potassium level is normal in the majority of patients, and, if hypokalemia is present, it is usually mild. (See "Familial hyperaldosteronism", section on 'Familial hyperaldosteronism type I (FH type I) or glucocorticoid-remediable aldosteronism (GRA)'.)

•Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder due to mutations of the gene that encodes 11-beta-hydroxysteroid dehydrogenase type 2 isoform, which normally breaks down cortisol to cortisone. This genetic defect results in increased levels of renal cortisol, which binds to the mineralocorticoid receptor. AME typically presents in infancy or early childhood with severe hypertension, failure to thrive, and muscle weakness due to hypokalemia. Chronic ingestion of licorice containing glycyrrhetinic acid has a similar effect. (See "Apparent mineralocorticoid excess syndromes (including chronic licorice ingestion)".)

•Although the most common form of congenital adrenal hyperplasia (21-hydroxylase deficiency) leads to decreased aldosterone synthesis and hyperkalemia, other rarer forms of congenital adrenal hyperplasia are associated with increased mineralocorticoid synthesis and hypokalemia. These include 17-alpha-hydroxylase deficiency, which presents with hypertension, hypokalemia, and hypogonadism at puberty, and 11-beta-hydroxylase deficiency, which presents in neonates with virilization, hypertension, and hypokalemia. (See "Uncommon congenital adrenal hyperplasias", section on 'CYP17A1 deficiencies' and "Uncommon congenital adrenal hyperplasias", section on '11-beta-hydroxylase deficiency'.)

Other causes of urinary loss

●Amphotericin B nephrotoxicity — Amphotericin B causes hypokalemia by disrupting cellular membranes and increasing membrane permeability. Potassium flows down its concentration gradient out of tubular epithelial cells into the lumen. A large study in adults comparing conventional amphotericin with the liposomal form found a significant reduction in hypokalemia from 11.6 to 6.7 percent [20]. A review of children outside of the neonatal period receiving amphotericin found hypokalemia to be present in 47 percent of those measured but none of those receiving liposomal amphotericin [21]. (See "Amphotericin B nephrotoxicity".)

●Liddle syndrome – Liddle syndrome is caused by an autosomal dominant gain-of-function mutation in subunits of the epithelial sodium channel that presents in childhood as hereditary hypokalemic metabolic alkalosis and hypertension. This genetic disorder has similar findings to AME. (See "Genetic disorders of the collecting tubule sodium channel: Liddle syndrome and pseudohypoaldosteronism type 1".)

Cystic fibrosis and skin losses — Electrolyte abnormalities including hypokalemia have been reported in patients with cystic fibrosis [22]. For children with cystic fibrosis who are not identified by newborn screening, hypochloremia, hypokalemia, and metabolic alkalosis may present in young children less than 2.5 years of age with volume depletion.

CLINICAL MANIFESTATIONS — Clinical manifestations vary depending on the severity and acuity of hypokalemia. Symptoms generally do not become manifest until the serum potassium is below 3 mEq/L unless there is a rapid significant fall in serum potassium.

Clinical findings include:

●Muscle weakness and paralysis

●Cardiac arrhythmias and electrocardiogram (ECG) changes

●Polyuria due to impaired urinary concentrating ability

Neuromuscular and cardiac symptoms induced by hypokalemia are related to alterations in the generation of the action potential, which is dependent on the transcellular potassium gradient. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Pathogenesis of symptoms'.)

Muscular weakness — Hypokalemia can induce skeletal muscle weakness and, in some severe cases, paralysis. Patients are generally asymptomatic until the potassium drops below 2.5 mEq/L or at higher levels if there is a sudden precipitous drop in potassium. Muscle weakness typically starts in the proximal muscles of the lower extremities and progresses upwards to the trunk and upper extremities. As the potassium drops below 2 mEq/L, severe weakness progresses, involving respiratory muscles, which may result in respiratory failure and death.

Hypokalemia can also induce smooth muscle weakness, which is manifested as ileus [23]. Affected patients may complain of abdominal distension, anorexia, nausea, vomiting, and/or constipation.

In addition to causing muscle weakness, severe potassium depletion (serum potassium less than 2.5 mEq/L) can lead to muscle cramps and/or fasciculations, rhabdomyolysis, and myoglobinuria. A potential diagnostic problem is that the release of potassium from the cells with rhabdomyolysis can mask the severity of the underlying hypokalemia with misleading values of normal or high serum/plasma values. (See "Rhabdomyolysis: Epidemiology and etiology" and "Rhabdomyolysis: Epidemiology and etiology", section on 'Electrolyte disorders'.)

Cardiac findings — Hypokalemia may adversely affect the cardiac conduction, resulting in arrhythmias including premature atrial and ventricular complex beats, sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation. Hypokalemia is also associated with characteristic ECG changes including PR prolongation, flattening of T waves, and ST depression. With more profound hypokalemia, U waves can emerge after the T waves, as best seen in the precordial leads (waveform 1) [23,24]. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Cardiac arrhythmias and ECG abnormalities'.)

Kidney manifestations — Prolonged hypokalemia can cause kidney dysfunction, particularly impaired concentrating ability that presents as polyuria and/or polydipsia. (See "Hypokalemia-induced kidney dysfunction".)

DIAGNOSIS — The diagnosis of hypokalemia is made by the detection of a plasma or serum potassium level that is below the normal range, usually 3.5 mEq/L. In infants, the normal range of potassium is greater than in older children and adults because of their reduced urinary potassium excretion (table 1). In many instances, the diagnosis is made incidentally when plasma or serum electrolytes are obtained during an evaluation for another condition, especially in children with levels between 3 and 3.5 mEq/L, whereas levels below 3 mEq/L are more often associated with clinical signs and symptoms.

It is important to note that potassium levels may vary by measurement technique. Normal values are typically based on measurements from central hospital automated blood biochemistry autoanalyzers. In intensive care unit and emergency department settings, there is increasing utilization of point-of-care testing blood chemistry analyzers that allow rapid and accurate assessment of potassium levels from whole blood samples, with results that are similar to those found with blood gas analyzers [25]. However, one study in children reported potassium levels were lower by a mean difference of 0.4 mEq/L when measured by blood gas analyzers compared with values obtained from the central laboratory [26]. These differing results may be due to the use of different blood gas analyzers. Clinicians should be aware of these differences in their own institutions before interpreting potassium measurements based on blood gas results.

Of note, serum or plasma potassium is not reflective of total potassium stores, as 98 percent of potassium is intracellular. Settings in which there is a transcellular movement of potassium into the cell can lead to the false assumption of total body potassium depletion. This may lead to unnecessary potassium repletion rather than correcting the underlying cause of increased intracellular potassium uptake (eg, alkalosis or administration of insulin). Conversely, a normal or elevated potassium level in a setting of potassium movement out of the cell (eg, diabetic ketoacidosis) may mask true total body potassium depletion.

EVALUATION TO DETERMINE UNDERLYING ETIOLOGY — Because severe hypokalemia is a potentially life-threatening condition, initial management takes precedence over any diagnostic evaluation. The urgency and type of intervention are based on the magnitude of the potassium deficit and presence of symptoms.

History — The history often clearly points to the underlying etiology, and there is little need for further extensive diagnostic evaluation.

Historical clues include the following:

●Acute gastrointestinal (GI) illness with diarrhea or vomiting is the most common cause of hypokalemia in otherwise healthy children.

●Decreased dietary potassium intake is typically not the main cause of hypokalemia but may be an exacerbating factor, particularly in children with acute GI illness and potassium loss. (See 'Decreased intake' above.)

●The use of medications that may promote intracellular potassium uptake (adrenergic agents [albuterol] or exogenous insulin) or increase renal potassium excretion (eg, diuretics). (See 'Causes' above.)

●A positive family history of periodic paralysis or muscle weakness is suggestive of a genetic form of periodic paralysis. (See "Hypokalemic periodic paralysis".)

●A diagnosis of thyrotoxic periodic paralysis should be considered in any patient with concomitant or preceding symptoms of hyperthyroidism (weight loss, heat intolerance, tremor, palpitations, anxiety, increased frequency of bowel movements, and shortness of breath). (See "Thyrotoxic periodic paralysis".)

●History of recurrent hypokalemia is suggestive of an underlying chronic pathologic condition, which warrants further evaluation.

Physical examination — Once hypokalemia has been discerned, the initial physical assessment should include the following:

●Cardiac rate and rhythm by auscultation to screen for arrhythmias.

●Muscle strength and tone.

●Reflexes.

●Evaluation of the effective circulating volume and respiratory status. These factors influence initial management strategies and can prove useful in clarifying acid-base and volume balance in children with unclear origin of their hypokalemia.

Laboratory studies — In symptomatic cases or if there is any concern for a cardiac arrhythmia, an electrocardiogram (ECG) should be performed and treatment should be immediately started to address any clinically significant findings.

In the child with relatively mild hypokalemia with a history of present illness that suggests a clear etiology such as viral GI illness or diuretic therapy, there is little utility to an extensive laboratory evaluation.

If the cause of hypokalemia is uncertain, laboratory evaluation initially focuses on assessing whether or not there is excessive renal potassium loss (table 4 and algorithm 1).

Urinary potassium excretion — The most common pediatric cause of increased urinary potassium excretion is hypovolemia, which results in increased mineralocorticoid activity due to secretion of aldosterone (hyperaldosteronism). In these children, hypokalemia and increased urinary potassium renal excretion resolve with fluid and potassium repletion. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)

Other causes of excessive renal potassium losses are less common and are also less likely to have rapid improvement to a normal potassium level with replacement therapy. In addition, unless the underlying etiology is addressed (eg, chronic diuretic therapy or renal tubular acidosis [RTA]), potassium levels will usually fall again, once supplementation is withdrawn. (See 'Increased urinary losses' above and "Clinical manifestations and treatment of hypokalemia in adults", section on 'Ongoing losses and the steady state'.)

Urinary potassium excretion is assessed using spot urine samples obtained concomitantly with serum chemistries (table 4). Although 24-hour urine collections will give the most accurate picture of renal potassium handling, these are difficult to perform in many children and delay establishment of a diagnosis.

●Spot urinary potassium – Random urinary potassium levels <15 to 20 mmol/L in a patient with serum potassium level <3 mmol/L generally suggest that the hypokalemia is caused by GI losses, poor intake, cellular shift, or diuretic use rather than urinary losses. Substantially higher levels suggest excessive renal potassium losses.

Random urinary potassium levels are sometimes misleading because spot values are influenced by water excretion at that time. In states of polyuria, spot urinary potassium levels may be lower than if urine output were normal. In states of decreased urine flow, random levels may appear >20 mmol/L even though overall daily potassium excretion is being appropriately conserved.

●Urine potassium-to-creatinine ratio – Calculating the potassium-to-creatinine ratio in a spot urine sample helps to correct for any variations in urine volume in patients with stable glomerular filtration rate. A urine potassium-to-creatinine ratio <13 mEq/g creatinine (<1.5 mEq/mmol creatinine) suggests that the hypokalemia is due to GI losses, poor intake, cellular shift, or diuretic use rather than urinary losses. Ratios >13 mEq/g creatinine suggest that the hypokalemia is caused by pathologic urinary losses either due to increased mineralocorticoid activity or tubular dysfunction. (See "Evaluation of the adult patient with hypokalemia", section on 'Urine potassium-to-creatinine ratio'.)

Further evaluation — For those children with hypokalemia and excessive urinary potassium excretion without an apparent etiology, further evaluation is warranted and is based on the presence or absence of an elevated blood pressure (algorithm 1).

●For hypertensive patients, plasma renin and aldosterone are obtained.

•Low renin and high aldosterone levels are suggestive of primary hyperaldosteronism (adrenal abnormalities). Metabolic alkalosis is also observed in these patients.

•Low renin and low aldosterone are suggestive of one of the following:

-Increased activity of another mineralocorticoid that is not aldosterone (eg, apparent mineralocorticoid excess [AME] and some forms of congenital adrenal hyperplasia) (see 'Increased mineralocorticoid activity' above)

-Liddle syndrome due to enhanced sodium tubular resorption (see "Genetic disorders of the collecting tubule sodium channel: Liddle syndrome and pseudohypoaldosteronism type 1")

●For normotensive patients, evaluation focuses on the acid-base status of the patient as determined by venous pH and serum electrolytes (table 5).

•For patients with metabolic acidosis, diagnostic possibilities include types I and II RTA and diabetic ketoacidosis.

•For patients with metabolic alkalosis, diagnostic possibilities include chronic diuretic use, persistent vomiting, and the genetic tubulopathies of Bartter and Gitelman syndromes. Measurement of urinary chloride concentration may be helpful in differentiating among these disorders.

-Urinary chloride concentration is normal in Bartter or Gitelman syndromes (see "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations")

-Urinary chloride concentration is low in patients with vomiting

-Urinary chloride concentration is variable with diuretic therapy, depending on whether tubular function is still responsive to diuretic activity

•In patients who have no underlying acid-base disorders, diagnostic possibilities include magnesium depletion or osmotic diuresis. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Hypokalemia'.)

●Although genetic testing can be performed for the rare genetic potassium-wasting disorders of Bartter, Gitelman, and Liddle syndromes, other clinical findings that are suggestive of these diagnoses should be present prior to genetic testing. These entities are discussed in greater detail separately. (See "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations" and "Genetic disorders of the collecting tubule sodium channel: Liddle syndrome and pseudohypoaldosteronism type 1".)

MANAGEMENT

Overview — The acuity and degree of the hypokalemia influence the clinical approach to therapy. The goals of therapy are to prevent or treat life-threatening complications (arrhythmias, paralysis, rhabdomyolysis, and diaphragmatic weakness) associated with severe hypokalemia, replace the potassium deficit, and correct the underlying cause. The urgency of therapy depends on the severity of hypokalemia and the rate of decline in serum potassium concentration. Lower-grade hypokalemia (serum/plasma potassium between 2.5 and 3 mEq/L) or chronic hypokalemia at lower levels tend to be better tolerated by the patient and are less likely to require urgent interventions.

The management of pediatric hypokalemia includes:

●Ascertaining the need for potassium replacement.

●Identifying and, if possible, treating the underlying cause of hypokalemia (eg, hypomagnesemia).

●Use of potassium-sparing diuretic therapy for patients with chronic renal wasting conditions, for which there is no treatment for the underlying disorder (Bartter or Gitelman syndrome).

●Electrocardiographic (ECG) monitoring for symptomatic children and those in whom there is a concern for cardiac arrhythmia.

●In patients receiving intravenous (IV) fluid, a saline without dextrose solution should be used for initial therapy since the administration of dextrose stimulates the release of insulin which drives extracellular potassium into the cells. This can lead to a transient 0.2 to 1.4 mEq/L reduction in the serum potassium concentration, particularly if the solution contains only 20 mEq/L of potassium [27,28]. The transient reduction in serum potassium can induce arrhythmias in susceptible patients.

Potassium supplementation

Determining need and timing — The urgency of potassium supplementation is dependent on the severity of hypokalemia based on the presence or absence of symptoms.

●In symptomatic patients (arrhythmias, marked muscle weakness, or paralysis), rapid potassium supplementation should be provided. In some cases, this requires IV administration of potassium chloride, particularly in those who are unable to take oral medications. In this setting, an infusion with a potassium concentration of no more than 40 mEq/L is given at a rate not to exceed 0.5 to 1 mEq/kg of body weight per hour. The goal is to raise the potassium level by 0.3 to 0.5 mEq/L. These patients require continuous ECG monitoring to detect changes due to hypokalemia and also possibly rebound hyperkalemia during replacement therapy. (See 'Clinical manifestations' above and "Causes, clinical manifestations, diagnosis, and evaluation of hyperkalemia in children", section on 'Cardiac conduction abnormalities'.)

●In asymptomatic patients with potassium levels less than 3 mEq/L, replacement of potassium stores is generally needed. Oral therapy is preferred, and IV supplementation should be reserved for those who are unable to take oral medications. The amount of replacement therapy is dependent on the cause of the hypokalemia, presence of any acid-base disorder, and ongoing excessive losses. In particular, supplementation may not be needed in patients whose hypokalemia was caused by transient cellular uptake (eg, limited exposure to beta-adrenergic agents or exogenous insulin), as correction of the underlying cause results in resolution of hypokalemia.

●In asymptomatic patients with acute hypokalemia and potassium levels between 3 and 3.5 mEq/L, correction of the underlying cause and dietary potassium are usually sufficient without the need for additional potassium supplementation. For those who are unable to take enteral potassium, the addition of a maintenance amount of potassium to IV fluids is usually sufficient.

●In asymptomatic patients with chronic hypokalemia, potassium supplementation may be needed, particularly if the underlying cause is not amenable to correction (eg, types I and II renal tubular acidosis [RTA]). (See "Treatment of distal (type 1) and proximal (type 2) renal tubular acidosis".)

Route — Potassium can be administered either enterally or IV. Whenever possible, potassium supplementation should be given enterally. Data in children cared for in a cardiac intensive care unit have shown that enteral administration has comparable efficacy and fewer side effects than IV administration [29].

The main concern about the use of IV potassium supplementation is the inadvertent administration of a large amount of potassium in a short period of time, resulting in hyperkalemia. Safety measures to prevent this complication include limiting the absolute amount of potassium in any single container or bag of fluid, as well as using an infusion pump. IV potassium administration is also associated with pain and phlebitis when administered through a peripheral vein, which can be minimized if the potassium content of the infusion is less than 20 mEq/L. Central venous access is needed if the potassium concentration exceeds 40 mEq/L.

Formulation — Potassium supplementation commonly comes in five preparations: potassium chloride, potassium phosphate, potassium acetate, potassium citrate-citric acid, and potassium bicarbonate.

●Potassium chloride tends to result in quicker potassium repletion per dose than phosphate or citrate [30] and is the most common pharmacologic supplement. It is also preferred in patients with concomitant hypochloremia or metabolic alkalosis.

●Potassium phosphate is often used in the setting of proximal tubule dysfunction, such as Fanconi syndrome or cystinosis, where there is loss of both potassium and phosphorus. It may be used preferentially in children with diabetic ketoacidosis with symptomatic hypophosphatemia.

●Potassium acetate is also commonly used in diabetic ketoacidosis, allowing for correction of hypokalemia as well as acidosis upon the metabolism of acetate to bicarbonate.

●Potassium citrate-citric acid or bicarbonate is generally used in children with hypokalemia and acidosis, as seen in types I and II RTA.

Magnesium depletion — Hypomagnesemia may accompany hypokalemia. Magnesium can be lost at the same time as potassium with gastrointestinal (GI) losses or with diuretic use. Hypomagnesemia can also promote renal potassium wasting directly in the distal tubule and can also prevent reabsorption of filtered potassium at the loop of Henle [24]. Magnesium supplementation may need to be considered in this setting, especially with difficulty correcting hypokalemia. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Hypokalemia'.)

Potassium-sparing diuretics — Potassium supplementation by itself is less effective in tubulopathies such as Bartter or Gitelman syndromes, where there is ongoing renal wasting of potassium. Use of a potassium-sparing diuretic such as amiloride may attenuate these losses. (See "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations".)

Children with hyperaldosteronism may benefit from spironolactone or eplerenone therapy to reduce the urinary potassium effect of aldosterone. (See "Treatment of primary aldosteronism", section on 'First line: Mineralocorticoid receptor antagonists'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hypokalemia (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Hypokalemia is defined as a serum or plasma potassium level below the normal value, which is usually defined as 3.5 mEq/L. Normal serum potassium concentrations in children and adolescents are similar to levels in adults. However, infants have a higher normal range of potassium because of their reduced urinary potassium excretion, caused by their relatively increased aldosterone insensitivity and decreased glomerular filtration rate (table 1). (See 'Definition' above.)

●Causes – Pediatric hypokalemia is caused by derangements of the normal hemostatic mechanisms that regulate potassium balance and include the following (table 2):

•Decreased dietary potassium intake is unlikely to cause hypokalemia in healthy children. However, prolonged decreased intake can contribute to potassium depletion caused by other disorders.

•Intracellular potassium uptake results in transient hypokalemia. Increased potassium entry into the cells is promoted by the following conditions: alkalosis, increased insulin activity (eg, exogenous insulin administration) and beta-adrenergic activity (eg, albuterol administration), and hypokalemic periodic paralysis. (See 'Increased intracellular uptake' above.)

•Increased gastrointestinal (GI) loss is the most common cause of pediatric hypokalemia.

•Increased urinary losses is usually due to either increased delivery of sodium to the distal nephron in exchange for potassium (eg, diuretic therapy, genetic tubular disorders [Bartter and Gitelman syndromes], and osmotic diuresis) or increased mineralocorticoid activity (eg, hyperaldosteronism due to hypovolemia). (See 'Increased urinary losses' above.)

●Clinical manifestations – Clinical manifestations vary depending on the severity and acuity of hypokalemia. Symptoms generally do not become manifest until the serum potassium is below 3 mEq/L, unless there is a rapid significant fall in serum potassium. Clinical findings include muscle weakness and paralysis, cardiac arrhythmias and electrocardiogram (ECG) changes (waveform 1), and polyuria due to impaired urinary concentration. (See 'Clinical manifestations' above.)

●Diagnosis – The diagnosis of hypokalemia is made by the detection of a serum or plasma potassium level that is below the normal range of 3.5 mEq/L. In many instances, the diagnosis is made incidentally when serum or plasma electrolytes are obtained during an evaluation for another condition, especially in children with levels between 3 and 3.5 mEq/L, whereas levels below 3 mEq/L are more often associated with clinical signs and symptoms. (See 'Diagnosis' above.)

●Evaluation – After acute management of symptomatic severe hypokalemia, further evaluation focuses on determining the etiology as subsequent care is based on the underlying cause of hypokalemia. The assessment includes a focused history and physical examination. In most cases, the history is sufficient to determine the underlying cause. However, additional laboratory testing may be needed in patients in whom the diagnosis remains uncertain (algorithm 1). (See 'Evaluation to determine underlying etiology' above.)

●Management – The acuity and degree of the hypokalemia influence the clinical approach to therapy. The goals of therapy are to prevent or treat life-threatening complications (arrhythmias, paralysis, rhabdomyolysis, and diaphragmatic weakness) associated with severe hypokalemia, replace the potassium deficit, and correct the underlying cause. (See 'Management' above.)

•Severe or symptomatic – Patients with severe or symptomatic hypokalemia (arrhythmias, marked muscle weakness, or paralysis) require urgent potassium supplementation. For these patients, we recommend intravenous (IV) administration of potassium chloride, particularly in those who are unable to take oral medication (Grade 1B). In this setting, an infusion with a potassium concentration of no more than 40 mEq/L is given at a rate not to exceed 0.5 to 1 mEq/kg of body weight per hour. The goal is to raise the potassium level by 0.3 to 0.5 mEq/L. These patients require continuous ECG monitoring to detect changes due to hypokalemia and also possibly rebound hyperkalemia during replacement therapy. (See 'Determining need and timing' above.)

•Others – In asymptomatic patients, the need for potassium supplementation is based on the underlying cause and severity of hypokalemia. If potassium supplementation is needed, we recommend that oral potassium therapy be given (Grade 1B). The formulation of potassium is also dependent on the underlying condition. (See 'Formulation' above and 'Determining need and timing' above.)