Pediatric Hypokalemia

Potassium is the most abundant intracellular cation and is necessary for maintaining a normal charge difference between intracellular and extracellular environments. Potassium homeostasis is integral to normal cellular function and is tightly regulated by specific ion-exchange pumps, primarily by cellular, membrane-bound, sodium-potassium adenosine triphosphatase (ATPase) pumps. Derangements of potassium regulation may lead to neuromuscular, GI, and cardiac conduction abnormalities.

Hypokalemia is generally defined as a serum potassium level of less than 3.5 mEq/L in children, although exact values for reference ranges of serum potassium are age-dependent, and vary among laboratories. It is frequently present in pediatric patients who are critically ill and reflects a total body deficiency of potassium or, more commonly, reflects conditions that promote the shift of extracellular potassium into the intracellular space. ^[1]

Hypokalemia may be due to a total body deficiency of potassium, which may result from prolonged inadequate intake or excessive losses (including but not limited to, long-term diuretic or laxative use, and chronic diarrhea, hypomagnesemia, or hyperhidrosis). Acute causes of potassium depletion include diabetic ketoacidosis, ^[2] severe GI losses due to vomiting and diarrhea, dialysis, and diuretic therapy.

Hypokalemia may also be the manifestation of large potassium shifts from the extracellular to intracellular space, as seen with alkalosis, insulin, catecholamines (including albuterol and other commonly-used beta2-adrenergic agonists), sympathomimetics, and hypothermia.

Other recognizable causes include renal tubular disorders, such as distal renal tubular acidosis, Bartter syndrome, ^[3] and Gitelman syndrome, periodic hypokalemic paralysis, hyperthyroidism, and hyperaldosteronism.

Other mineralocorticoid excess states that may cause hypokalemia include cystic fibrosis (with hyperaldosteronism from severe chloride and volume depletion), Cushing syndrome, and exogenous steroid administration. Excessive natural licorice consumption can also cause or exacerbate potassium loss due to inhibition of 11-betahydoxysteroid dehydrogenase, which leads to elevated endogenous mineralocorticoid activity. ^{[4, 5]}

 

Hypokalemia may be due to a total body deficit of potassium, which may occur chronically with the following:

• Prolonged diuretic use

• Inadequate potassium intake

• Laxative use

• Diarrhea (including congenital chloride diarrhea) ^[6]

• Hyperhidrosis

• Hypomagnesemia

• Renal tubular losses (including Fanconi syndrome, ^[7] Bartter syndrome, Gitelman syndrome, and others)

• Dengue syndrome ^[8]

Acute causes of potassium depletion include the following:

• Diabetic ketoacidosis

• Severe GI losses from vomiting and diarrhea

• Dialysis and diuretic therapy

• Alcohol intoxication/overdose ^[9]

Hypokalemia may also be due to excessive potassium shifts from the extracellular to the intracellular space, as seen with the following:

• Alkalosis

• Insulin use

• Catecholamine use

• Sympathomimetic use

• Use of sodium bicarbonate, especially during therapeutic alkalinization (commonly used to treat salicylate and cyclic antidepressant overdoses, tumor lysis syndrome, rhabdomyolysis, etc)

• Use of sodium polystyrene sulfonate to treat transient hyperkalemia

• Hypothermia

Other recognizable causes of hypokalemia include the following:

• Renal tubular disorders, such as Bartter syndrome and Gitelman syndrome

• Type I or classic distal tubular acidosis

• Periodic hypokalemic paralysis

• Hyperaldosteronism

• Celiac disease ^[10]

Other states of mineralocorticoid excess that may cause hypokalemia include the following:

• Cystic fibrosis with hyperaldosteronism from severe chloride and volume depletion

• Cushing syndrome

• Exogenous steroid administration, including fludrocortisone ^[11] and other mineralocorticoids

• Excessive licorice consumption ^[4]

Other conditions that may cause hypokalemia include acute myelogenous, monomyeloblastic, or lymphoblastic leukemia.

Drugs that may commonly cause hypokalemia include the following:

• Furosemide, bumetanide, and other loop diuretics

• Methylxanthines (theophylline, aminophylline, caffeine)

• Verapamil (with overdose)

• Amphotericin B, micafungin ^[12]

• Quetiapine (particularly in overdose)

• Ampicillin, carbenicillin, high-dose penicillins ^[13]

• Sirolimus ^[14]

• Drugs associated with magnesium depletion, such as aminoglycosides, amphotericin B, and cisplatin

Incidence

Hypokalemia is uncommon in the general pediatric population of developed countries but is frequently present in pediatric patients who are critically ill. ^{[15, 16]} It is considerably more common in developing countries owing to malnutrition and diarrheal illnesses. ^[17]

Race-, sex-, and age-related demographics

Racial differences may be present in predisposing conditions such as Bartter syndrome, Gitelman syndrome, Conn syndrome (ie, hyperaldosteronism), Cushing syndrome, and familial hypokalemic paralysis. In addition, significant hypokalemia and hypokalemic paralysis develop in 2-8% of Asians with hyperthyroidism.

No known sex predilection has been noted.

Viral gastrointestinal (GI) infections tend to be more common in infants and younger children. Younger children with emesis or diarrhea are at an increased risk of hypokalemia because the depletion of fluid volume and electrolytes from GI loss is relatively higher than that found in older children and adults.

Insulin-dependent diabetes mellitus that results in diabetic ketoacidosis (with its inherent fluid and potassium loss) is more common in children. Excessive corticosteroid and mineralocorticoid secretion, as in Cushing syndrome and Conn syndrome, is a less common cause of hypokalemia in the pediatric patient. Periodic hypokalemic paralysis may appear in childhood or young adulthood, precipitated by rest after strenuous exercise, physical or metabolic stress (eg, exposure to cold, alcohol ingestion), a high-carbohydrate meal, or exposure to exogenous insulin or catecholamines (eg, epinephrine and albuterol). Hypokalemia due to hyperthyroidism is generally observed in adults.

With adequate control of potassium levels and resolution of any predisposing condition, the prognosis is excellent.

Morbidity/mortality

Short-term morbidity is common and may include GI hypomotility or ileus; cardiac dysrhythmia; QT prolongation; appearance of U waves that may mimic atrial flutter, T-wave flattening, or ST-segment depression; and muscle weakness or cramping.

Mortality is rare, except when hypokalemia is severe or occurs following cardiac surgery, when accompanied by arrhythmia, or in patients who have underlying heart disease and require digoxin therapy.

Mortality and morbidity can also be related to treatment for hypokalemia with potassium supplementation, particularly if potassium is given in large doses or rapidly. Because of the risk associated with potassium replacement, alleviation of the cause of hypokalemia may be preferable to treatment, especially if hypokalemia is mild, asymptomatic, or transient and is likely to resolve without treatment.

Complications

Complications of hypokalemia include the following:

• Hyperkalemia due to excessive/rapid potassium replacement

• Cardiac dysrhythmia

• Gastric erosions

• Strictures

Patients and their parents should be educated in terms of predisposing conditions. The importance and risks involved with potassium supplementation and the warning signs of hypokalemia or overtreatment must be emphasized upon discharge from the hospital.

Knowledge of cardiopulmonary resuscitation and education on timely access to emergency medical services may prevent morbidity or mortality.

Ongoing communication is essential for reducing the risks and in therapy, especially in patients with chronic conditions associated with hypokalemia.

For patient education resources, see the Thyroid and Metabolism Center, as well as Low Potassium.