AUTHOR INFORMATION

Section 1 of 11

Authored by Michael Verive, Program Director, Department of Pediatric Critical Care, Advocate Hope Children's Hospital

Coauthored by David Jaimovich, MD, Section Chief, Division of Critical Care, Hope Children's Hospital, Assistant Professor Pediatrics, Assistant Professor, Department of Pediatrics, University of Illinois at Chicago

Michael Verive, is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Medical Association, and Society of Critical Care Medicine

Edited by G Patricia Cantwell, MD, Associate Clinical Professor, Department of Pediatrics, Miller School of Medicine, University of Miami; Director of Pediatric Critical Care Medicine, Jackson Children's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Barry 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; Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Associate Professor, Department of Clinical Pediatrics, State University of New York at Stony Brook; and Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center

Author's Email:	Michael Verive
Editor's Email:	G Patricia Cantwell, MD

eMedicine Journal, February 12 2007, VOLUME 8, Number 2

INTRODUCTION

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Background: Hypokalemia is defined as a plasma potassium level of less than 3.5 mEq/L in children. It is frequently present in pediatric patients who are critically ill. 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 tightly regulated by specific ion-exchange pumps, primarily by cellular, membrane-bound, sodium-potassium adenosine triphosphatase (ATPase) pumps. Derangements of potassium regulation often lead to neuromuscular, gastrointestinal, and cardiac conduction abnormalities.

Pathophysiology: Hypokalemia may be due to a total body deficit of potassium, which may result from long-term inadequate intake, long-term diuretic or laxative use, and chronic diarrhea, hypomagnesemia, or hyperhidrosis. Acute causes of potassium depletion include diabetic ketoacidosis, severe gastrointestinal losses from 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, sympathomimetics, and hypothermia. Other recognizable causes include renal tubular disorders, such as distal renal tubular acidosis, Bartter and Gitelman syndromes, periodic hypokalemic paralysis, hyperthyroidism, administration of beta2-adrenergic agents, 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.

Mortality/Morbidity:

• Mortality is rare, except when hypokalemia is severe or occurs following cardiac surgery, when accompanied by arrhythmia, or in a patient who has underlying heart disease and requires digoxin therapy.

• Short-term morbidity is common and may include gastrointestinal 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.

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 exists.

Age:

• Viral gastrointestinal 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 gastrointestinal loss is relatively higher than that 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 and Conn syndromes, 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 epinephrine. Hypokalemia resulting from hyperthyroidism is generally observed in adults.

CLINICAL

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History:

• Hypokalemia due to excessive loss is usually accompanied by a history of gastrointestinal loss (emesis or diarrhea), urinary output, or sweating. This may be exacerbated by inadequate oral intake.



• Query about current or recent treatment with medications, including insulin, albuterol or other beta2-sympathomimetics, corticosteroids, diuretics, laxatives, enemas, or bowel-prep solutions.



• 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 normal limits. 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:


• • Prolonged diuretic use
  
  
  
  • Inadequate potassium intake
  
  
  
  • Laxative use
  
  
  
  • Diarrhea
  
  
  
  • Hyperhidrosis
  
  
  
  • Hypomagnesemia
  
  
  
• Acute causes of potassium depletion include the following:


• • Diabetic ketoacidosis
  
  
  
  • Severe gastrointestinal losses from vomiting and diarrhea
  
  
  
  • Dialysis and diuretic therapy
  
  
  
• 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

  • Hypothermia



• Other recognizable causes of hypokalemia include the following:
  • Renal tubular disorders, such as Bartter and Gitelman syndromes

  • Type I or classic distal tubular acidosis

  • Periodic hypokalemic paralysis

  • Hyperaldosteronism



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



• Drugs that may cause hypokalemia include the following:


• • Theophylline

  • Verapamil (with overdose)

  • High-dose penicillin

  • Ampicillin

  • Carbenicillin

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

DIFFERENTIALS

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Hyperthyroidism

WORKUP

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Lab Studies:

• 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 Munchausen by proxy syndrome.

Imaging Studies:

• Magnetic resonance imaging (MRI): Obtain a brain MRI if a brain or pituitary tumor is suspected as a cause of hypercortisolism.



• Ultrasonography and computed tomography (CT): Obtain an abdominal ultrasonogram or CT scan if an adrenal tumor or hyperplasia is suspected.

Other Tests:

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


• • Ventricular dysrhythmia
  
  
  
  • Prolongation of QT interval
  
  
  
  • ST-segment depression
  
  
  
  • T-wave flattening
  
  
  
  • Appearance of U waves
  
  
  
  • During therapy, monitor for changes associated with overcorrection and hyperkalemia, including a prolonged QRS, peaked T waves, bradyarrhythmia, sinus node dysfunction, and asystole.
  
  
  

TREATMENT

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Medical Care:

• Treatment depends on severity and etiology.



• 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 usually are 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.



• Transient, asymptomatic, or mild hypokalemia may resolve spontaneously or may be treated with enteral potassium supplements.



• Symptomatic or severe hypokalemia should be corrected with a solution of intravenous potassium.

Surgical Care:

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

Consultations:

• After resolution, consultation with an endocrinologist, 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.

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, which may have aldosteronelike activity) may also be necessary for high-risk individuals.

MEDICATION

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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.

Drug Category: Potassium supplements -- These 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.

Drug Name	Potassium chloride (also citrate, acetate, bicarbonate, gluconate) -- 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.
Adult Dose	IV replacement: 10-40 mEq IV infused over 2-3 h; not to exceed 40 mEq/h; may repeat q3-4h prn; modify infusion rate for specific requirements PO supplementation: 50-100 mEq/d PO divided bid/tid or qd as SR formulation; larger doses may be needed in severe depletion to replenish potassium body storage
Pediatric Dose	Usual dose for potassium replacement: 0.5-1 mEq/kg IV; not to exceed 30-40 mEq/dose Not to exceed 0.3-0.5 mEq/kg/h for noncritical hypokalemia; however, this rate may be inadequate in life-threatening hypokalemia Infusion rates: >0.5 mEq/kg/h can be delivered but requires ECG monitoring to detect potentially fatal arrhythmia, especially ventricular dysrhythmia, because it can rapidly lead to cardiac arrest Oral supplementation is based on body weight, ranging from 2-4 mEq/kg/d PO in divided doses to avoid gastric distress
Contraindications	Undiluted IV administration; hyperkalemia, renal failure, conditions in which potassium retention is present, oliguria or azotemia, crush syndrome, severe hemolytic reactions, anuria, and adrenocortical insufficiency Acidosis (alkaline forms of potassium such as potassium bicarbonate, citrate, acetate, or gluconate can be used in the face of metabolic acidosis)
Interactions	Coadministration with drugs that elevate potassium (eg, potassium-sparing diuretics, ACE inhibitors) may cause severe hyperkalemia; hypokalemia may result in digoxin toxicity in patients taking digoxin; caution if discontinuing potassium administration in patients taking digoxin
Pregnancy	A - Safe in pregnancy
Precautions	Do not infuse rapidly; high plasma concentrations of potassium may cause death due to cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels; monitor potassium replacement therapy whenever possible by means of continuous or serial ECG; IV potassium must be diluted before administration, when a concentration >40 mEq/L is infused, local pain and phlebitis also may follow Solid potassium supplements can produce or aggravate gastric ulcers and can produce strictures or stenotic lesions; patients with a predisposition to these lesions should use liquid formulations GI complaints, including nausea, stomach pain, vomiting, and flatulence, are some of the more common adverse drug reactions with the oral preparations Closely monitor potassium levels to avoid hyperkalemia

FOLLOW-UP

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Further Inpatient Care:

• After the initial phase of 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.

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.

In/Out Patient Meds:

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

Transfer:

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

Complications:

• Hyperkalemia from excessive potassium replacement



• Cardiac dysrhythmia



• Gastric erosions



• Strictures

Prognosis:

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

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 excellent patient education resources, visit eMedicine’s Endocrine System Center. Also, see eMedicine’s patient education article Low Potassium.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Failure to adequately communicate the risks of treatment



• Failure to appropriately monitor patients receiving potassium supplementation for complications, especially patients with renal failure or patients receiving potassium-sparing diuretics or angiotensin-converting enzyme inhibitors



• Failure to follow serum potassium and other electrolyte concentrations during or after therapy



• Treating a patient on the basis of a low serum potassium value that is false because of a sampling or laboratory error (or failing to treat a patient with symptoms of actual hypokalemia because of an elevated serum potassium value that is false because of a sampling or laboratory error)

TEST QUESTIONS

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CME Question 1: Which of the following does not cause hypokalemia?

A: Diuretic therapy
B: Excessive calcium administration
C: Prolonged diarrhea
D: Emesis
E: None of the above

The correct answer is B: Although calcium administration is essential in the treatment of hyperkalemia, it does not cause hypokalemia. The other answers are all common causes for hypokalemia.

CME Question 2: Why is intravenous therapy for severe or symptomatic hypokalemia preferred over enteral supplementation?

A: Potassium is not adequately absorbed from the gastrointestinal mucosa.
B: Enteral potassium has to undergo "first-pass" effect in the liver to become biologically available.
C: When the enteral route is unavailable, or severe or symptomatic hypokalemia is present, intravenous supplementation can correct serum levels more rapidly.
D: Intravenous potassium is less expensive than enteral potassium.
E: None of the above

The correct answer is C: Transient, asymptomatic, or mild hypokalemia may resolve spontaneously and can be treated with enteral potassium supplements if this route is available. Symptomatic or severe hypokalemia should be corrected with intravenous potassium solutions.

Pearl Question 1 (T/F): Three common manifestations of hypokalemia include (1) muscle weakness, cramping, and/or fatigue, (2) QT-segment shortening and loss of normal U waves, and (3) gastrointestinal hypomotility and/or ileus.

The correct answer is False: The most common manifestations of hypokalemia include (1) muscle weakness, cramping, and/or fatigue, (2) cardiac conduction abnormalities (prolonged QT interval, U waves, ST-segment depression, ventricular dysrhythmias), and (3) gastrointestinal hypomotility or ileus.

Pearl Question 2 (T/F): As long as potassium supplementation is being given at a rate not exceeding 1 mEq/kg/h, no cardiovascular monitoring is required.

The correct answer is False: The usual dose of 0.5-1 mEq/kg in children (not to exceed 30-40 mEq/dose). The recommended replacement rate is 0.3-0.5 mEq/kg/h, but, with cardiac monitoring, potassium may given faster if needed. Continuous electrocardiographic monitoring for dysrhythmias should be considered in all cases.

Pearl Question 3 (T/F): A patient without significant medical history is admitted after an uneventful hernia repair. The patient is awake, alert, and in no apparent distress. Routine laboratory tests reveal levels of sodium at 154 mEq/dL, potassium at 1.1 mEq/dL, chloride at 125 mEq/dL, and bicarbonate at 5 mEq/dL. The continuous electrocardiographic monitor reveals normal sinus rhythm and rate, with normal QRS, T, and ST morphology. This patient requires immediate potassium replacement to avoid cardiac dysrhythmias.

The correct answer is False: The laboratory values listed probably represent a specimen drawn upstream of an intravenous solution of isotonic sodium chloride solution. A repeat specimen should be drawn from a separate isolated site and analyzed prior to instituting any potassium replacement.

Pearl Question 4 (T/F): During treatment of an infant admitted to the hospital with severe hypokalemia, the infant's heart rate decreases, the QRS complex is widens, and frequent abnormal ventricular beats begin to appear. These physiologic changes are likely due to excessive potassium supplementation.

The correct answer is True: All signs point to hyperkalemia; thus, the patient`s potassium replacement has been miscalculated or improperly mixed, or it is being given at too rapid an infusion rate. The infusion should be immediately discontinued, a serum potassium level should be drawn and sent for immediate analysis, and treatment for hyperkalemia should be strongly considered. Because the risk of hyperkalemia is always present during the treatment of hypokalemia, appropriate therapy to correct hyperkalemia should be made available for any patient receiving potassium supplementation.

BIBLIOGRAPHY

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• Bevacqua JE: Diabetic ketoacidosis in the pediatric ICU. Crit Care Nurs Clin North Am 2005 Dec; 17(4): 341-7, x[Medline].
• Clayton JA, Rodgers S, Blakely J, et al: Thiazide diuretic prescription and electrolyte abnormalities in primary care . Br J Clin Pharmacol 2006; 1: 87-95[Medline].
• Jospe N, Forbes G: Fluids and electrolytes--clinical aspects. Pediatr Rev 1996 Nov; 17(11): 395-403; quiz 404[Medline].
• Kumar PS, Deenadayalan M, Janakiraman L: Neonatal Bartter syndrome. Indian Pediatr 2006 Aug; 43(8): 735-7[Medline].
• Landau D: Potassium handling in health and disease: lessons from inherited tubulopathies. Pediatr Endocrinol Rev 2004 Dec; 2(2): 203-8[Medline].
• Mueller PL, Jaimovich DG: Endocrine and Metabolic Emergencies. Handbook of Pediatric and Neonatal Transport Medicine 1996; 265-292, 492.
• 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[Medline].
• Rodriguez-Soriano J: Bartter and related syndromes: the puzzle is almost solved. Pediatr Nephrol 1998 May; 12(4): 315-27[Medline].
• Rose BD: Introduction to Disorders of Potassium Balance. Clinical Physiology of Acid-Base and Electrolyte Disorders. 1989; 715-756.
• Wiseman K: Index of suspicion. Case 3. Familial periodic paralysis. Pediatr Rev 1997 Oct; 18(10): 357, 359-60[Medline].
• Wood EG, Lynch RE: Fluid and Electrolyte Balance. 1998; 703-22.

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