Pediatric Hypokalemia

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Background

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.

Pathophysiology

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,[1] 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,[2] 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.[3]

Epidemiology

Mortality/Morbidity

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

Morbidity/mortality

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.

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 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:

Race

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.

Sex

No known sex predilection has been noted.

Age

Viral 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.

History

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

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.

Causes

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

Acute causes of potassium depletion include the following:

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

Other recognizable causes of hypokalemia include the following:

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

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

Drugs that may commonly cause hypokalemia include the following:

Laboratory Studies

The following studies are indicated in patients with hypokalemia:

Imaging Studies

Magnetic resonance imaging

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 ECG changes may be helpful if present, their absence should not be taken as reassurance of normal cardiac conduction.[12] The ECG in hypokalemia may appear normal or may have only subtle findings immediately before clinically significant dysrhythmias.

ECG findings may include the following (see the image below):

During therapy, monitor for changes associated with overcorrection and hyperkalemia, including a prolonged QRS, peaked T waves, bradyarrhythmia, sinus node dysfunction, and asystole.

Medical Care

Note the following:

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.

Transfer

Patients with severe or symptomatic hypokalemia require transfer to an ICU for intravenous potassium supplementation and continuous electrocardiographic monitoring.

Surgical Care

Except for excision of tumors leading to hypokalemia, management is nonsurgical.

Consultations

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.

Diet

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.

Activity

Patients with hypokalemic periodic paralysis may need to modify exercise regimens to avoid periods of strenuous exercise.

Patients at risk of 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.

Medication Summary

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.

Potassium chloride (also citrate, acetate, bicarbonate, gluconate)

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.

Class Summary

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.

Further Outpatient Care

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.

Inpatient & Outpatient Medications

Other than potassium supplementation as described above, no additional medications are required.

If current medications are responsible for hypokalemia, substitution of potassium-sparing alternatives may help reduce degree of hypokalemia and may help minimize requirements for potassium supplementation.

Deterrence/Prevention

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.

Patient Education

Patients 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.

Author

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

Disclosure: Nothing to disclose.

References

  1. Bevacqua JE. Diabetic ketoacidosis in the pediatric ICU. Crit Care Nurs Clin North Am. 2005 Dec. 17(4):341-7, x. [View Abstract]
  2. Kumar PS, Deenadayalan M, Janakiraman L, Vijayakumar M. Neonatal Bartter syndrome. Indian Pediatr. 2006 Aug. 43(8):735-7. [View Abstract]
  3. Johns C. Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars. CJEM. 2009 Jan. 11(1):94-6. [View Abstract]
  4. Gurakan F, Baysoy G, Wedenoja S, et al. Three cases of a rare disease, congenital chloride diarrhea, summons up the variation in the clinical course and significance of early diagnosis and adequate treatment in the prevention of intellectual disability. Turk J Pediatr. 2011 Mar-Apr. 53(2):194-8. [View Abstract]
  5. Patra S, Nadri G, Chowdhary H, Pemde HK, Singh V, Chandra J. Nephrogenic diabetes insipidus with idiopathic Fanconi's syndrome in a child who presented as vitamin D resistant rickets. Indian J Endocrinol Metab. 2011 Oct. 15(4):331-3. [View Abstract]
  6. Lumpaopong A, Kaewplang P, Watanaveeradej V, Thirakhupt P, Chamnanvanakij S, Srisuwan K, et al. Electrolyte disturbances and abnormal urine analysis in children with dengue infection. Southeast Asian J Trop Med Public Health. 2010 Jan. 41(1):72-6. [View Abstract]
  7. Bouthoorn SH, van der Ploeg T, van Erkel NE, van der Lely N. Alcohol intoxication among Dutch adolescents: acute medical complications in the years 2000-2010. Clin Pediatr (Phila). 2011 Mar. 50(3):244-51. [View Abstract]
  8. Bhattacharya M, Kapoor S. Quadriplegia due to Celiac Crisis with Hypokalemia As Initial Presentation of Celiac Disease: A Case Report. J Trop Pediatr. 2011 Apr 27. [View Abstract]
  9. Emiroglu M. Micafungin use in children. Expert Rev Anti Infect Ther. 2011 Sep. 9(9):821-34. [View Abstract]
  10. Zaki SA, Lad V. Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis. Indian J Pharmacol. 2011 Sep. 43(5):609-10. [View Abstract]
  11. Buchler M, Caillard S, Barbier S, et al. Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transplant. 2007 Nov. 7(11):2522-31. [View Abstract]
  12. [Guideline] Drew BJ, Califf RM, Funk M, et al. Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses. Circulation. 2004 Oct 26. 110(17):2721-46. [View Abstract]
  13. Clayton JA, Rodgers S, Blakey J, Avery A, Hall IP. Thiazide diuretic prescription and electrolyte abnormalities in primary care. Br J Clin Pharmacol. 2006 Jan. 61(1):87-95. [View Abstract]
  14. Dinleyici EC, Dogruel N, Acikalin MF, Tokar B, Oztelcan B, Ilhan H. An additional child case of an aldosterone-producing adenoma with an atypical presentation of peripheral paralysis due to hypokalemia. J Endocrinol Invest. 2007 Nov. 30(10):870-2. [View Abstract]
  15. Isbrucker RA, Burdock GA. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol. 2006 Dec. 46(3):167-92. [View Abstract]
  16. Jospe N, Forbes G. Fluids and electrolytes--clinical aspects. Pediatr Rev. 1996 Nov. 17(11):395-403; quiz 404. [View Abstract]
  17. Landau D. Potassium handling in health and disease: lessons from inherited tubulopathies. Pediatr Endocrinol Rev. 2004 Dec. 2(2):203-8. [View Abstract]
  18. Lucas da Silva PS, Iglesias SB, Waisberg J. Hypokalemic rhabdomyolysis in a child due to amphotericin B therapy. Eur J Pediatr. Feb. 166:169-71. [View Abstract]
  19. Lumpaopong A, Thirakhupt P, Srisuwan K, Chulamokha Y. Rare F311L CFTR gene mutation in a child presented with recurrent electrolyte abnormalities and metabolic alkalosis: case report. J Med Assoc Thai. 2009 May. 92(5):694-8. [View Abstract]
  20. Mueller PL, Jaimovich DG. Endocrine and metabolic emergencies. Handbook of Pediatric and Neonatal Transport Medicine. 1996. 265-92, 492.
  21. Parr JR, Salama A, Sebire P. A survey of consultant practice: intravenous salbutamol or aminophylline for acute severe childhood asthma and awareness of potential hypokalaemia. Eur J Pediatr. 2006 May. 165(5):323-5. [View Abstract]
  22. Rodriguez-Soriano J. Bartter and related syndromes: the puzzle is almost solved. Pediatr Nephrol. 1998 May. 12(4):315-27. [View Abstract]
  23. Rose BD. Introduction to disorders of potassium balance. Clinical Physiology of Acid-Base and Electrolyte Disorders. 1989. 715-56.
  24. Wiseman K. Index of suspicion. Case 3. Familial periodic paralysis. Pediatr Rev. 1997 Oct. 18(10):357, 359-60. [View Abstract]
  25. Wood EG, Lynch RE. Fluid and Electrolyte Balance. 1998. 703-22.
  26. Kumar R, Kumar P, Aneja S, Kumar V, Rehan HS. Safety and efficacy of low-osmolarity ORS vs. modified rehydration solution for malnourished children for treatment of children with severe acute malnutrition and diarrhea: a randomized controlled trial. J Trop Pediatr. 2015 Aug 27. [View Abstract]
  27. Seyberth HW. Pathophysiology and clinical presentations of salt-losing tubulopathies. Pediatr Nephrol. 2015 Jul 16. [View Abstract]
  28. Hartman S, Merkus P, Maseland M, Roovers L, van Setten P. Hypokalaemia in children with asthma treated with nebulised salbutamol. Arch Dis Child. 2015 Oct. 100(10):970-2. [View Abstract]

Prominent U waves after T waves in hypokalemia.

Prominent U waves after T waves in hypokalemia.