What is hyperkalemia?

What is Hyperkalemia?

Hyperkalemia is an elevated serum potassium concentration greater than 5.0 mEq/L (mmol/L), representing a potentially life-threatening electrolyte abnormality that can cause fatal cardiac arrhythmias and requires immediate recognition and treatment. 1

Definition and Classification

• Mild hyperkalemia: >5.0 to <5.5 mEq/L 2
• Moderate hyperkalemia: 5.5 to 6.0 mEq/L 2
• Severe hyperkalemia: >6.0 mEq/L 2

The American Heart Association uses these thresholds to guide treatment intensity, with severe hyperkalemia (>6.0 mEq/L) requiring hospital admission regardless of symptoms due to high risk of cardiac arrhythmias and sudden death. 2

Pathophysiology and Mechanisms

Potassium homeostasis is primarily maintained by the kidneys, which excrete excess potassium, though the gastrointestinal tract and other systems contribute to a lesser extent. 1 Hyperkalemia develops through three main mechanisms:

• Reduced renal excretion (most common in clinical practice, particularly in chronic kidney disease) 1, 3
• Transcellular shift of potassium from intracellular to extracellular space 3
• Excessive potassium intake (dietary or iatrogenic) 3

Hyperkalemia causes depolarization of cardiac cell membranes, shortening action potentials and dramatically increasing the risk of life-threatening arrhythmias. 1 Additional effects include neuromuscular dysfunction, metabolic acidosis, and suppression of renal ammoniagenesis. 1

High-Risk Populations

Patients at increased risk for developing hyperkalemia include those with:

• Chronic kidney disease (reduced potassium excretion capacity) 1, 2
• Heart failure (up to one-third develop hyperkalemia >5.0 mEq/L when on mineralocorticoid receptor antagonists) 2
• Diabetes mellitus (hyporeninemic hypoaldosteronism) 1, 2
• Advanced age (reduced renal function and polypharmacy) 4

Medication-Induced Hyperkalemia

Iatrogenic hyperkalemia from medications represents the most important cause in everyday clinical practice, with prevalence of 2-4% in general population but 10-55% in hospitalized patients. 4, 5 Key causative medications include:

• RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) - most common mechanism 4, 5
• Potassium-sparing diuretics (spironolactone, amiloride, triamterene) 4
• NSAIDs (reduce renal potassium excretion) 2, 5
• Trimethoprim-sulfamethoxazole 4
• Calcineurin inhibitors (cyclosporine, tacrolimus) 4, 5
• Heparin (suppresses aldosterone production) 4
• Beta-blockers (reduce renin release) 4, 5

Clinical Presentation

Hyperkalemia is often asymptomatic, especially in chronic cases, making laboratory detection critical. 4, 6 When symptoms occur, they include:

• Cardiac manifestations: Arrhythmias, cardiac arrest 4, 6
• Neuromuscular symptoms: Muscle weakness, paresthesias, paralysis 2, 6
• ECG changes: Peaked T waves, flattened P waves, prolonged PR interval, widened QRS complex 2, 4

Any hyperkalemia with ECG changes requires immediate hospital admission due to imminent risk of fatal arrhythmias. 2

Mortality and Morbidity

A U-shaped relationship exists between serum potassium and mortality, with both hyperkalemia and hypokalemia associated with adverse outcomes. 1 Hyperkalemia increases risk of:

• Cardiovascular mortality and morbidity 1
• Progression of chronic kidney disease 1
• Hospitalization 1

The exact potassium threshold for life-threatening complications remains controversial and varies based on individual comorbidities, rate of potassium rise, and presence of structural cardiac disease. 1, 7 Patients with chronic kidney disease may tolerate higher potassium levels due to compensatory mechanisms, with retrospective data showing stronger association between hyperkalemia and 1-day mortality in those with normal kidney function compared to CKD patients. 1

Diagnostic Considerations

Always rule out pseudohyperkalemia before initiating treatment, as hemolysis during blood collection, excessive fist clenching, or delayed specimen processing can falsely elevate potassium levels. 2, 4 Confirm with repeat measurement using proper phlebotomy technique. 2

Treatment Principles

Management strategies depend on severity and clinical context:

Severe Hyperkalemia (>6.0 mEq/L or with ECG changes)

Immediate treatment is required and should not be delayed while waiting for confirmatory laboratory values if clinical suspicion is high. 2

• Cardiac membrane stabilization: Calcium gluconate or calcium chloride (immediate effect) 2, 6
• Shift potassium intracellularly: Insulin with glucose, nebulized beta-2 agonists (onset 30-60 minutes) 2, 6
• Enhance elimination: Loop diuretics, potassium binders, hemodialysis 2, 6

Chronic/Recurrent Hyperkalemia Management

• Review and adjust causative medications rather than permanently discontinuing beneficial RAAS inhibitors 1, 2
• Consider newer potassium binders (patiromer, sodium zirconium cyclosilicate) to allow continuation of cardioprotective and renoprotective RAAS therapy 1, 8
• Dietary potassium restriction to <3 g/day 2, 4
• Regular monitoring of potassium levels, especially after medication changes 1, 2

Critical Pitfalls to Avoid

• Do not permanently discontinue RAAS inhibitors due to mild-moderate hyperkalemia; dose reduction plus potassium binders is preferred to maintain mortality and morbidity benefits in heart failure and CKD 2, 4
• Do not delay treatment of severe hyperkalemia while awaiting repeat laboratory confirmation 2
• Do not overlook ECG changes in patients with hyperkalemia 2, 4
• Do not ignore pseudohyperkalemia as a potential cause before initiating aggressive treatment 2, 4