Hypokalemia

Hypokalemia is defined as a plasma potassium level of less than 3.5 mEq/L in children, and is frequently present in critically ill pediatric patients. As the most abundant intracellular cation, potassium is necessary for the maintenance of normal charge difference between intracellular and extracellular environments. Integral to normal cellular function, potassium homeostasis is tightly regulated by specific ion-exchange pumps (primarily by a cellular, membrane-bound, sodium-potassium ATP-ase). 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 occur due to chronic 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 beta-2 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 in a patient with underlying heart disease requiring digoxin therapy, following cardiac surgery, or when accompanied by arrhythmia.

• Short-term morbidity is common, including 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 (hyperaldosteronism), Cushing syndrome, and familial hypokalemic paralysis. In addition, 2-8% of Asians with hyperthyroidism develop significant hypokalemia and hypokalemic paralysis.

Sex:

• No known gender differences exist.

Age:

• Viral gastrointestinal infections tend to be more common in infants and younger children. With emesis or diarrhea, younger children are at higher risk to the development of hypokalemia, due to the fact that gastrointestinal loss represents relatively larger fluid and electrolyte loss than in older, children and adults.

• Insulin-dependent diabetes mellitus resulting 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, are less common causes of hypokalemia in the pediatric patient. Periodic hypokalemic paralysis may initially present in childhood or young adulthood precipitated by rest after strenuous exercise, physical or metabolic stress (including exposure to cold, and alcohol ingestion), a high-carbohydrate meal, or exposure to exogenous insulin or epinephrine. Hypokalemia resulting from hyperthyroidism is generally observed in adults.

History:

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

• Inquire about current or recent treatment with medications including insulin, albuterol or other beta2-symptathomimetics, corticosteroids, diuretics, or laxatives.

• Similar episodes in the past. Familial historical data should include acute, intermittent episodes of paralysis, with or without association with hyperthyroidism, or surgery for pituitary or adrenal tumors.

Physical:

• The physical exam may frequently be within normal limits. Occasionally, muscle weakness is evident.

• Life threatening complications which require immediate diagnosis are acute respiratory failure from muscle paralysis and cardiac arrhythmias.

• The cardiovascular exam 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 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 the manifestation of excessive potassium shifts from the extracellular to the intracellular space, as seen with the following:

• Alkalosis

• Insulin

• Catecholamines

• Sympathomimetics

• Hypothermia

• Other recognizable causes of hypokalemia include the following:

• Renal tubular disorders such as Bartter and Gitelman syndromes

• Classic feature of type I or classic distal tubular acidosis

• Periodic hypokalemic paralysis

• Hyperaldosteronism

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

• Cystic fibrosis with hyperaldosteronism from severe chloride and volume depletion

• Cushing syndrome

• Exogenous steroid administration

• Other Conditions which may cause hypokalemia:

• Drugs: theophylline, verapamil overdose, high-dose penicillin, ampicillin, carbenicillin and those associated with magnesium depletion, such as aminoglycosides, amphotericin B and cisplatin

• Other conditions: acute myelogenous monomyeloblastic or lymphoblastic leukemia

Lab Studies:

• Serum electrolytes: Screen for concurrent electrolyte abnormalities, which may affect treatment.

• Blood gas

• Assess acid-base status.

• Alkalosis may induce hypokalemia, and treatment of acidosis may worsen existing hypokalemia.

• Electrocardiogram

• 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 prior to 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 over-correction and hyperkalemia including prolonged QRS, peaked T waves, bradyarrhythmia, sinus node dysfunction, and asystole.

• Drug screen (serum or urine)

• Amphetamines and other sympathomimetic stimulants can cause hypokalemia.

• Other drugs that can cause hypokalemia include verapamil overdose, theophylline, amphotericin B, aminoglycosides, and cisplatin.

• Serum ACTH, cortisol, renin activity, aldosterone

• Evaluate for suspected Cushing, Conn, or adrenal hyperplasia syndromes, which include 11-beta-hydroxylase deficiency.

Imaging Studies:

• Magnetic resonance imaging (MRI)

• Obtain a brain MRI if a brain or pituitary tumor is suspected as a cause of hypercortisolism.

• Ultrasound and computed tomography (CT)

• Obtain abdominal ultrasound or CT if adrenal tumor or hyperplasia is suspected.

Other Tests:

• Simultaneous serum insulin and C-peptide

• Since hyperinsulinism can cause transient hypokalemia, elevated serum insulin without appropriately elevated C-peptide suggests exogenous insulin administration, which may represent Munchausen by proxy syndrome.

Medical Care:

• Treatment depends on severity and etiology.

• Unlike hyponatremia, in which total body sodium deficit can be readily estimated, serum potassium may not reflect total body stores accurately. Indeed, during diabetic ketoacidosis, serum potassium levels are usually initially elevated even in the face of severe, total body potassium depletion. 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 intravenous potassium solution.

Surgical Care:

• Except for excision of tumors leading to hypokalemia, management is non-surgical.

Consultations:

• After resolution, consultation with an endocrinologist, geneticist or specialist in metabolic disease may be necessary to diagnose and treat 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 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.

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 may be treated with enteral potassium supplements. Symptomatic or severe hypokalemia should be corrected with intravenous potassium preparations.

Further Outpatient Care:

• Patients should receive follow-up medical care for home management if the condition is expected to persist beyond inpatient care.

• 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:

• The patient should be transferred to ICU for severe or symptomatic hypokalemia 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 over-treatment must be emphasized in discharge teaching.

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

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

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 based on a falsely low serum potassium value due to sampling or lab error (or failing to treat a patient with symptoms due to actual hypokalemia based on a falsely elevated serum potassium value due to sampling or lab error)