DESCRIPTION

• The normal extracellular fluid concentration of potassium is typically 3.5 to 4.8 mEq/L.
• Serum potassium concentration of greater than 5.5 mEq/L is hyperkalemia.

PATHOPHYSIOLOGY

• Hyperkalemia creates a steady subthreshold depolarization of the cell, which inactivates sodium channels essential to the production of action potentials and thereby prevents myocardial contraction.
• Even small increases in extracellular potassium cause excitable cells, especially in the heart, to partially depolarize.
• Hemolysis of drawn blood, tight tourniquet, leukocytosis, or thrombocytosis may cause elevated levels of K+ in a sample of blood that are not elevated in the patient.
• The pathophysiology is closely tied to causes of hyperkalemia, including:
  • Pseudohyperkalemia
  • Impaired excretion
  • Effective circulating volume depletion
  • Renal failure
  • Pharmacologic intervention
    • Potassium-sparing diuretics
    • Prostaglandin synthesis inhibitors (ibuprofen and ketorolac)
    • angiotensin-converting enzyme (ACE) inhibitors
    • Trimethoprim-sulfamethozaxole
    • Pentamidine
    • Heparin
    • Digitalis
    • Aldosterone resistance/hypoaldosteronism
    • Addison's disease, sickle cell anemia, systemic lupus erythematosus, kidney transplant, amyloidosis, obstructive uropathy/tubulointerstitial disease, or type IV distal renal tubular acidosis
• Increased entry of K+ into the serum caused by hemolysis/rhabdomyolysis, potassium-rich foods or supplements, trauma, or tumor lysis syndrome
• Shifts of potassium from intracellular to extracellular fluid caused by digitalis intoxication, acidemia (especially nonanion gap metabolic acidosis), insulin deficiency, muscle overuse injury from agitation or straining, or hyperosmolality

EPIDEMIOLOGY

• True hyperkalemia is uncommon outside of the setting of renal failure, although it is associated with severe poisonings (e.g., digoxin).
• Hyperkalemia in the setting of decreased renal function is usually accompanied by an excess intake of potassium or by a pharmacologic intervention with potassium-sparing diuretics, beta-receptor blockers, or ACE inhibitors.

RISK FACTORS

• Acute or chronic renal failure
• Diabetes mellitus
• Pharmacologic interventions
• Myopathy or trauma
• Malignant disease

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• RISK FACTORS

DIFFERENTIAL DIAGNOSIS

• Common toxicologic causes of hyperkalemia include digoxin intoxication and acidemia or rhabdomyolysis from any source (e.g., sympathomimetic toxicity and seizures).
• Common nontoxicologic causes include pseudohyperkalemia or renal failure from any cause.

SIGNS AND SYMPTOMS

• Hyperkalemia primarily causes cardiac conduction abnormalities that may quickly deteriorate to ventricular fibrillation.
• ECG changes with hyperkalemia, especially with a widened QRS complex, constitute a medical emergency.
• Physical signs may help reveal the poison involved when they occur in a patient with hyperkalemia.

Vital Signs

Hypotension and bradycardia are common in severe cases.

HEENT

Blurred vision and colored halos may indicate digitalis toxicity.

Cardiovascular

• ECG effects range from a peaked T wave, decreased R wave, prolonged P-R interval, through a widened QRS complex, and degenerating into a sine wave in the most severe form.
• High-grade atrioventricular block may indicate digoxin or beta-blocker toxicity.
• Sudden ventricular fibrillation or cardiac arrest is possible at any stage.

Gastrointestinal

Nausea and vomiting suggest digitalis toxicity.

Renal

Renal function tests often reveal transient or chronic renal insufficiency.

Fluids and Electrolytes

Hyperkalemia must be present for a diagnosis.

Musculoskeletal

Weakness progresses to paralysis in severe cases.

Neurologic

Paresthesia and decreased deep tendon reflexes may be present.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum electrolytes, BUN, and creatinine are needed to determine hyperkalemia and assess renal function.
• Pseudohyperkalemia must be excluded.
  • A second sample may exclude hemolysis due to blood draw technique.
  • True hyperkalemia is usually associated with other abnormal laboratory values.
  • True hyperkalemia exists if serum and plasma values for potassium differ by less than 0.2 mEq/L.
• CBC is needed to determine whether hemolysis, leukocytosis, or thrombocytosis could be the cause of pseudohyperkalemia.
• ECG and continuous monitoring are needed; any changes in the ECG, especially QRS widening, constitute a medical emergency.
• A serum creatine kinase assay is needed to determine the contribution of muscle injury.

Recommended Tests

• A digoxin level may be needed to evaluate cardiac glycoside toxicity.
• Urine electrolytes, osmolality, and a 24-hour urine K+ excretion test are recommended to determine whether abnormal renal handling is responsible for the disorder. (Extrarenal hyperkalemia is associated with renal excretion of more than 200 mEq/day of potassium.)
• Determining morning serum cortisol levels is a useful first step to rule out Addison's disease in a case of mild elevation in potassium, hypotension, and hyponatremia.
• A cortrosyn stimulation test should be considered if cortisol levels are low.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• It is necessary to determine the urgency of the situation by evaluating the potassium level and performing an ECG; any ECG changes mandate immediate therapy, as does a true K+ level greater than 7.5 mEq/L.
  • Immediate therapy usually consists of an intravenous calcium infusion, followed by glucose/insulin, sodium bicarbonate, or beta-receptor agonist.
• If the total body load of potassium is increased (rather than shifted from an intracellular to extracellular location), sodium polysterene sulfonate (Kayexelate) is also administered to remove excess potassium from the body.
• Internal shifts in K+ are assessed by evaluating the patient for acidemia, digitalis, adrenergic agents, or hyperosmolar state.
• The state of renal potassium excretion should be assessed by presence of renal failure, hypoaldosteronism, K+sparing diuretics or ACE inhibitors.
• The rate of potassium entry into serum should be assessed by the presence of muscle injury, overdose with potassium supplements, intravenous infusion rate supplemental potassium, dietary intake, or use of salt substitutes.

SEVERE HYPERKALEMIA (EMERGENCY TREATMENT)

Hyperkalemia in the setting of ECG changes, especially a widened QRS complex, or serum levels greater than 7.5 mEq/L, is considered a medical emergency. In severe cases, intervention should begin with immediate calcium administration, followed by administration of glucose and insulin or sodium bicarbonate, or both.

• Calcium chloride is administered first because it has the most rapid onset of action.
  • Available as a 10% solution, the adult dose is 5 ml intravenously over 5 minutes during continuous ECG monitoring, repeated in 5 to 6 minutes as occasion requires; the pediatric dose is 0.2 to 0.3 ml (20-30 mg/kg/dose) up to 5 ml using the same infusion technique.
  • Calcium should be avoided if digoxin toxicity is possible because calcium may increase the cardiac toxicity of cardiac glycosides.
• Glucose and insulin. This regimen redistributes potassium into the cell.
  • Regular insulin 10 units, and 25 g of dextrose (1 ampule of D₅₀) should be administered immediately by intravenous push.
  • Onset of action occurs in 15 to 30 minutes.
• beta-receptor agonists. Like glucose/insulin, beta-receptor agonists redistribute potassium into the cell.
  • Onset of action occurs in 15 to 30 minutes.
  • A large dose of an immediately available nebulized form (e.g., albuterol 10 mg nebulizer) should be used in addition to other measures.
• Sodium bicarbonate also redistributes potassium into cells. The adult dose is 2 ampules (88-100 mEq) by intravenous push every 1 to 2 hours as guided by potassium level; the pediatric dose is 1 to 2 mEq/kg.
• Following the above measures and if the total body stores of potassium are increased, sodium polystyrene sulfonate (Kayexelate) or hemodialysis should be used to increase potassium elimination.
  • Sodium polystyrene sulfonate (Kayexelate) is an ion exchange resin used to enhance the gastrointestinal excretion of potassium. Its onset of action is 2 to 12 hours.
  • Because it may cause anorexia, nausea, vomiting, and constipation, a suspension in 70% sorbitol (5 g resin/20 ml suspension) is used.
  • The patient should be given 20 to 40 ml orally four times daily, or until the serum K+ is less than 5.5 mEq/L. A maintenance dose of 20 ml may be given orally two or three times daily if further treatment is needed.
  • It also may be administered as a retention enema.
• Dialysis. Although dialysis effectively removes excess potassium from the body and is essential in patients with acute renal failure or end-stage renal failure, the process takes time to set up and should not be used alone under emergency situations.

DIGITALIS TOXICITY

• Digoxin immune Fab is indicated for ventricular dysrhythmia, hyperkalemia above 5.5 mEq/L, significant ingestion (more than 10 mg in adults, more than 4 mg in children), or when patient is unresponsive to conventional therapy.
• The use of calcium to treat hyperkalemia in the setting of digitalis intoxication may exacerbate the toxic effects of the cardiac glycosides.

MILD TO MODERATE HYPERKALEMIA (NONEMERGENCY)

• In hyperkalemia that does not constitute a medical emergency, management is focused on treating the cause of excess hyperkalemia.
• In a low-K+ diet, salt substitutes should be avoided.
• Drugs that may cause hyperkalemia should be discontinued.
• Sodium polystyrene sulfonate (Kayexelate) therapy may be used as described earlier.
• Other causes of hyperkalemia should be evaluated and treated, such as aldosterone resistance, hypoaldosteronism, or Addison's disease.

Section Outline:

• SEVERE HYPERKALEMIA (EMERGENCY TREATMENT)
• DIGITALIS TOXICITY
• MILD TO MODERATE HYPERKALEMIA (NONEMERGENCY)

• Hyperkalemia should be monitored with serial electrolyte determinations, ECG, and cardiac monitoring.
• The patient should be evaluated to determine the cause of hyperkalemia; the evaluation should include drugs, diet, comorbidity, and endocrine causes.

• Pseudohyperkalemia must be differentiated from true hyperkalemia.
• True hyperkalemia is usually associated with more than one abnormal laboratory value.

Poisoning by agents primarily affecting blood constituents.

See Also: SECTION III, Digoxin Immune Fab chapter, and SECTION IV, beta-Receptor Blockers, and Digoxin and Cardiac Glycosides chapters.

RECOMMENDED READING

Mandal AK. Hypokalemia and hyperkalemia. Med Clin North Am 1997;81:611-639.

Authors: Nirmal K. Veeramachaneni and Charles B. Cairns

Reviewer: Katherine M. Hurlbut