What are the causes and treatment of hyperkalemia?

Causes and Treatment of Hyperkalemia

Hyperkalemia requires immediate recognition and treatment based on severity, with life-threatening cases demanding rapid intervention to stabilize cardiac membranes, shift potassium intracellularly, and ultimately remove excess potassium from the body. 1

Definition and Classification

• Hyperkalemia: Serum potassium (K+) > 5.0 mmol/L
• Severity classification:
  • Mild: >5.0 to <5.5 mmol/L
  • Moderate: 5.5 to 6.0 mmol/L
  • Severe: >6.0 mmol/L 1

Common Causes

1. Decreased Renal Excretion

• Acute or chronic kidney disease
• Hypoaldosteronism (including hyporeninemic hypoaldosteronism in diabetic nephropathy)
• Medications affecting potassium excretion:
  • Renin-angiotensin-aldosterone system inhibitors (RAASi):
    • ACE inhibitors
    • Angiotensin receptor blockers (ARBs)
    • Mineralocorticoid receptor antagonists (MRAs) like spironolactone
    • Direct renin inhibitors (aliskiren)
  • Potassium-sparing diuretics (triamterene, amiloride)
  • NSAIDs
  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Trimethoprim-sulfamethoxazole
  • Heparin
  • Beta-blockers 1

2. Increased Potassium Intake/Administration

• Potassium supplements
• Salt substitutes
• High-potassium foods (bananas, melons, orange juice)
• Stored blood products
• Herbal supplements (alfalfa, dandelion, noni juice, etc.) 1

3. Transcellular Shifts (Movement from Intracellular to Extracellular Space)

• Metabolic acidosis
• Insulin deficiency
• Hyperglycemia
• Cell lysis (rhabdomyolysis, tumor lysis syndrome, hemolysis)
• Medications (digitalis, beta-blockers) 1, 2

Clinical Manifestations

• ECG changes (progression as K+ rises):
  • Peaked T waves (earliest sign)
  • Flattened or absent P waves
  • Prolonged PR interval
  • Widened QRS complex
  • Sine-wave pattern (pre-arrest)
• Neuromuscular symptoms:
  • Muscle weakness
  • Paresthesias
  • Flaccid paralysis
  • Respiratory difficulties 1

Treatment Approach

Acute Life-Threatening Hyperkalemia (K+ >6.0 mmol/L with ECG changes)

1. Cardiac Membrane Stabilization (acts within 1-3 minutes):

   • Calcium chloride 10%: 5-10 mL (500-1000 mg) IV over 2-5 minutes, OR
   • Calcium gluconate 10%: 15-30 mL IV over 2-5 minutes
   • May repeat if no effect observed within 5-10 minutes 1

2. Shift Potassium Into Cells (acts within 30 minutes):

   • Insulin with glucose: 10 units regular insulin IV with 25g glucose (50 mL of D50W) over 15-30 minutes
   • Nebulized beta-2 agonists: albuterol 10-20 mg nebulized over 15 minutes
   • Sodium bicarbonate: 50 mEq IV over 5 minutes (primarily if metabolic acidosis present) 1

3. Promote Potassium Excretion:

   • Loop diuretics: furosemide 40-80 mg IV (if renal function adequate)
   • Cation exchange resins: sodium polystyrene sulfonate (Kayexalate) 15-50g orally or rectally with sorbitol
   • Hemodialysis (most effective method for severe cases or renal failure) 1

Chronic Hyperkalemia Management

1. Identify and address underlying causes:

   • Review and modify medications contributing to hyperkalemia
   • Treat underlying conditions (renal failure, acidosis, etc.)

2. Pharmacologic management:

   • Loop or thiazide diuretics to enhance renal K+ excretion
   • Newer potassium binders:
     • Patiromer sorbitex calcium
     • Sodium zirconium cyclosilicate
   • Fludrocortisone in aldosterone deficiency (caution with fluid retention) 1

3. RAASi management:

   • Avoid discontinuation if possible due to mortality benefits
   • Consider dose reduction rather than discontinuation
   • Add potassium binders to maintain RAASi therapy 1, 3

Important Caveats

• Sodium polystyrene sulfonate is not for emergency treatment of life-threatening hyperkalemia due to its delayed onset of action 4
• Insulin/glucose, albuterol, and bicarbonate provide only temporary benefit (1-4 hours), with potential for rebound hyperkalemia after 2 hours 1
• ECG findings can be variable and may not always correlate with serum potassium levels 1
• Patients with cardiovascular disease and chronic kidney disease are at highest risk for recurrent hyperkalemia (50% have ≥2 recurrences within 1 year) 1
• Monitoring serum K+ is crucial, especially 7-10 days after starting or increasing doses of RAASi medications 1