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, gastrointestinal (GI), and cardiac conduction abnormalities.
Hypokalemia is generally defined in children as a serum potassium level of less than 3.5 mEq/L, 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, in association with long-term diuretic or laxative use, chronic diarrhea, hypomagnesemia, and 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.
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]
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]
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:
Drugs associated with magnesium depletion, such as aminoglycosides, amphotericin B, and cisplatin
In a study of adolescents who engaged in binge drinking, Pistritto et al found the development of hypokalemia and disruption of the acid-base balance to be common. Hypokalemia was particularly prevalent in those adolescents with normal acid-base equilibrium or metabolic acidosis. However, the study indicated that binge drinking only rarely affects glucose, sodium, and calcium levels.[15]
Hypokalemia is uncommon in the general pediatric population of developed countries but is frequently present in pediatric patients who are critically ill.[16, 17] It is considerably more common in developing countries, owing to malnutrition and diarrheal illnesses.[18]
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 GI infections tend to be more common in infants and younger children. Younger children with emesis or diarrhea are at an increased risk for 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.
A retrospective cohort study by Heydenrych found that in hospitalized children under age 5 years with severe, acute malnutrition (SAM), hypokalemia, as well as hypophosphatemia, hyponatremia, and other morbidities, was more prevalent on admission in those who later developed refeeding syndrome in the hospital during treatment. Indeed, of children with SAM who were tested for hypokalemia on admission, 90.0% who later developed refeeding syndrome had hypokalemia, compared with 36.3% of those who did not develop refeeding syndrome.[19]
Mortality is rare in hypokalemia, except when severe or occurring 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
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.
Hypokalemia due to excessive loss is usually accompanied by a history of GI loss (emesis or diarrhea), urinary output, or sweating. This may be exacerbated by inadequate oral intake.
Query about current or recent treatment with medications and herbal products (especially natural licorice), including insulin, albuterol or other beta2-sympathomimetics, corticosteroids, diuretics, laxatives, enemas, or bowel-prep solutions. A complete and up-to-date medication and supplement list is essential, especially if the patient is taking new medications or may have had medication substitutions.
The patient may have had similar episodes in the past. Familial historical data may include surgery for pituitary or adrenal tumors or acute intermittent episodes of paralysis, with or without association with hyperthyroidism.
Physical examination findings may frequently be within the reference range. Occasionally, muscle weakness is evident.
Cardiac arrhythmias and acute respiratory failure from muscle paralysis are life-threatening complications that require immediate diagnosis.
Cardiovascular examination findings may also be within normal limits. Occasionally, tachycardia with irregular beats may be heard. Severe hypokalemia may manifest as bradycardia with cardiovascular collapse.
Hypoactive bowel sounds may suggest hypokalemic gastric hypomotility or ileus.
The following studies are indicated in patients with hypokalemia:
Serum electrolyte tests - Screen for concurrent electrolyte abnormalities, which may affect treatment
Blood gas analysis - Assess acid-base status; alkalosis may induce hypokalemia, and treatment of acidosis may worsen existing hypokalemia
Drug screen (serum or urine) - Amphetamines and other sympathomimetic stimulants can cause hypokalemia; other drugs that can cause hypokalemia include verapamil (with overdose), theophylline, amphotericin B, aminoglycosides, and cisplatin.
Serum adrenocorticotropic hormone (ACTH), cortisol, renin activity, and aldosterone tests - Evaluate for suspected Cushing, Conn, or adrenal hyperplasia syndromes, including 11-beta-hydroxylase deficiency.
Simultaneous serum insulin and C-peptide tests - Because hyperinsulinism can cause transient hypokalemia, elevated serum insulin without appropriately elevated C-peptide suggests exogenous insulin administration, which may represent factitious disorder imposed on another (Munchausen by proxy).
Perform brain magnetic resonance imaging (MRI) if a brain or pituitary tumor is suspected as a cause of hypercortisolism.
Ultrasonography and computed tomography scanning
Perform abdominal ultrasonography or computed tomography (CT) scanning if an adrenal tumor or hyperplasia is suspected.
Electrocardiography
Although electrocardiographic changes may be helpful if present, their absence should not be taken as reassurance of normal cardiac conduction.[20] The electrocardiogram (ECG) in hypokalemia may appear normal or may have only subtle findings immediately before clinically significant dysrhythmias.
Electrocardiographic findings may include the following (see the image below):
Ventricular dysrhythmia
Prolongation of QT interval
ST-segment depression
T-wave flattening
Appearance of U waves
View Image
Prominent U waves after T waves in hypokalemia.
During therapy, monitor for changes associated with overcorrection and hyperkalemia, including a prolonged QRS, peaked T waves, bradyarrhythmia, sinus node dysfunction, and asystole.
Other than potassium supplementation, no medications are required.
Because many medications (particularly loop diuretics, mineralocorticoids, catecholamines, methylxanthines, alkalinizing agents) may be responsible for hypokalemia, eliminating or reducing the doses of these medications may be helpful in preventing or minimizing hypokalemia.
If current medications are responsible for hypokalemia, substitution of potassium-sparing alternatives may help to reduce degree of hypokalemia and may help to minimize requirements for potassium supplementation.
If the condition is expected to persist beyond inpatient care, patients should receive follow-up medical care for home treatment. Additional medical follow-up must be obtained for associated medical conditions.
Patients with severe or symptomatic hypokalemia require transfer to an intensive care unit (ICU) for intravenous potassium supplementation and continuous electrocardiographic monitoring.
Except for excision of tumors leading to hypokalemia, management is nonsurgical.
The treatment of hypokalemia depends on severity and etiology. Note the following:
Unlike hyponatremia, in which the total body sodium deficit can be readily estimated, serum potassium may not accurately reflect total body stores; indeed, during diabetic ketoacidosis, serum potassium levels are usually initially elevated, even in the face of severe depletion of total body potassium; correction of acidosis in diabetic ketoacidosis may cause a precipitous drop in serum potassium levels
Treatment of hypokalemia should be directed at the etiology of hypokalemia as well as its correction, as treatment of hypokalemia carries with it a significant risk of iatrogenic hyperkalemia
Transient, asymptomatic, or mild hypokalemia may spontaneously resolve or may be treated with enteral potassium supplements
Symptomatic or severe hypokalemia should be corrected with a solution of intravenous potassium
Whenever practical, treatment of hypokalemia should be performed in a monitored setting, with medications and personnel available to intervene in the event that treatment results in symptomatic hyperkalemia.
After the initial phase of hypokalemia therapy is completed, focus further inpatient care on matching potassium intake to losses, periodic testing of serum potassium levels, and electrocardiographic monitoring for hypokalemia or hyperkalemia due to therapy.
Alleviation of aggravating conditions, simplification of medication administration, and patient education form the basis of ongoing patient health and safety.
In a multicenter phase 2B study, Lemonnier et al found evidence that bumetanide improves the core symptoms of autism spectrum disorder (ASD) in children but that one of the most frequent adverse events is hypokalemia. Eighty-eight patients with ASD (2-18 years old) were divided into four age groups and randomized to receive bumetanide (0.5, 1.0, or 2.0 mg twice daily) or placebo for 3 months. The adverse event of hypokalemia occurred primarily at the start of the treatment at the 1.0 and 2.0 mg twice-daily doses, and it improved gradually with the intake of oral potassium supplements.[21]
After resolution, consultation with subspecialists (including, but not limited to, endocrinologist, nephrologist, pulmonologist, gastroenterologist, geneticist, or specialist in metabolic disease) may be necessary to diagnose and manage predisposing conditions.
Consultation with a dietitian may be helpful in cases of hypokalemia due to inadequate dietary intake.
Consultation with mental health professionals may be necessary for ongoing treatment of hypokalemia secondary to anorexia and/or bulimia.
Dietary modification may be necessary for patients with excessive potassium losses (eg, diuretic or laxative use) or patients with hypokalemia who are at increased risk, such as those receiving digoxin.
Avoidance of specific foods (eg, licorice) may also be necessary for high-risk individuals.[5]
Patients with hypokalemic periodic paralysis may need to modify exercise regimens to avoid periods of strenuous exercise.
Patients at risk for hypokalemia from sweat losses should have adequate potassium and fluid available during activities likely to result in significant sweating and should be given anticipatory guidance regarding symptoms of hypokalemia.
Medical therapy is aimed at potassium supplementation by the enteral (ie, oral or through feeding tubes) or parenteral route. Transient, asymptomatic, or mild hypokalemia may resolve spontaneously, or it may be treated using enteral potassium supplements. Symptomatic or severe hypokalemia should be corrected with intravenous potassium preparations.
Clinical Context:
Potassium chloride is the preferred salt for patients with preexisting alkalosis. First choice for IV therapy. Essential for transmission of nerve impulses, contraction of cardiac muscle, and maintenance of intracellular tonicity, skeletal and smooth muscles, and normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss, or because of low intake. Depletion may result from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, vomiting, or inadequate replacement during prolonged parenteral nutrition.
These agents are used to restore body potassium storage. Electrolytes are used to correct disturbances in fluid and electrolyte homoeostasis or acid-base balance and to reestablish osmotic equilibrium of specific ions.
Michael J Verive, MD, FAAP, Pediatrician, UP Health System Portage
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Barry J Evans, MD, Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin
Disclosure: Nothing to disclose.
Additional Contributors
G Patricia Cantwell, MD, FCCM, Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami Leonard M Miller School of Medicine/ Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Director, Palliative Care Team, Holtz Children's Hospital; Medical Manager, FEMA, South Florida Urban Search and Rescue, Task Force 2
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