What are the causes and management of hyperkalemia?

Hyperkalemia: Etiology and Management

Hyperkalemia is primarily caused by impaired renal excretion, medication effects, transcellular shifts, or excessive potassium intake, and requires immediate treatment with potassium binders such as patiromer (starting at 8.4g daily) for moderate cases, along with addressing the underlying cause. 1

Etiology of Hyperkalemia

Impaired Renal Excretion

• Renal failure: Both acute and chronic kidney disease (particularly CKD stage 4 with eGFR <30 mL/min/1.73 m²) 1, 2
• Hypoaldosteronism: Including hyporeninemic hypoaldosteronism 3, 2
• Adrenal insufficiency: Resulting in decreased aldosterone production 3

Medication-Induced Hyperkalemia

• RAAS inhibitors: ACE inhibitors, ARBs, direct renin inhibitors 4
• Potassium-sparing diuretics: Spironolactone, eplerenone, amiloride, triamterene 4
• NSAIDs: Reduce renal blood flow and decrease potassium excretion 4
• Calcineurin inhibitors: Tacrolimus, cyclosporine 4
• Heparin and derivatives: Suppress aldosterone production 4
• Trimethoprim and pentamidine: Block distal tubule sodium channels 4
• Beta-blockers: Impair cellular potassium uptake 4

Transcellular Shifts

• Acidosis: Causes potassium to shift from intracellular to extracellular space 3
• Tissue breakdown: Rhabdomyolysis, tumor lysis syndrome, hemolysis 3
• Insulin deficiency: Reduces cellular potassium uptake 3
• Medications: Suxamethonium, beta-blockers, calcium channel blockers, mannitol 4

Excessive Intake

• Potassium supplements: Oral or intravenous administration 4
• Salt substitutes: Often contain potassium chloride 4
• Blood transfusions: Particularly with older stored blood 3

Clinical Manifestations

ECG Changes by Potassium Level

Potassium Level	ECG Changes
5.5-6.5 mmol/L	Peaked/tented T waves (early sign)
6.5-7.5 mmol/L	Prolonged PR interval, flattened P waves
7.0-8.0 mmol/L	Widened QRS, deep S waves
>10 mmol/L	Sinusoidal pattern, VF, asystole, or PEA
[1]

Other Symptoms

• Neuromuscular: Muscle weakness, paralysis, paresthesias 5
• Cardiac: Arrhythmias, conduction abnormalities 5

Management of Hyperkalemia

Acute Management

1. Cardiac membrane stabilization:

   • Calcium gluconate 10% solution, 15-30 mL IV (onset: 1-3 minutes, duration: 30-60 minutes) 1

2. Intracellular potassium shift:

   • Insulin with glucose: 10 units regular insulin IV with 50 mL of 25% dextrose (onset: 15-30 minutes, duration: 1-2 hours) 1
   • Inhaled beta-agonists: 10-20 mg nebulized over 15 minutes (onset: 15-30 minutes, duration: 2-4 hours) 1
   • Sodium bicarbonate: 50 mEq IV over 5 minutes (onset: 15-30 minutes, duration: 1-2 hours) 1

3. Potassium elimination:

   • IV furosemide if renal function permits 1
   • Potassium binders (see table below) 1
   • Dialysis for severe cases, especially with end-stage renal disease or severe renal impairment 5

Potassium Binders

Agent	Starting Dose	Onset	Key Considerations
Patiromer (Veltassa)	8.4g once daily	7 hours	Separate from other medications by 3 hours; no sodium content
Sodium zirconium cyclosilicate (Lokelma)	5-10g once daily	1 hour	Contains sodium (400mg per 5g); more rapid onset
Sodium polystyrene sulfonate	15-30g 1-4 times daily	Variable	Avoid chronic use due to GI side effects; high sodium content
[1]

Chronic Management

1. Medication review and adjustment:

   • Reduce or discontinue medications causing hyperkalemia 1
   • Consider alternative medications when possible 4

2. Dietary modifications:

   • Limit potassium intake to <40 mg/kg/day 1
   • Avoid high-potassium foods: processed foods, bananas, oranges, potatoes, tomatoes, legumes, yogurt, chocolate 1
   • Sodium restriction (<2g/day) 1

3. Ongoing monitoring:

   • Regular serum potassium monitoring (within 3-4 days of starting treatment) 1
   • Serial ECGs for moderate to severe hyperkalemia 1

4. Nephrology referral:

   • Essential for CKD stage 4 (eGFR <30 mL/min/1.73 m²) 1
   • Improves outcomes and may delay dialysis 1

5. Correction of associated electrolyte imbalances:

   • Correct magnesium deficiency before potassium correction 1
   • Address sodium/water depletion to reduce hyperaldosteronism 1

Special Considerations

Adaptation in Chronic Kidney Disease

• Patients with CKD adapt by increasing K+ excretion per nephron and transferring K+ more rapidly into cells 2
• However, these adaptive responses have limitations, and hyperkalemia may still occur with increased K+ loads 2

Pitfalls to Avoid

• Failure to recognize medication-induced hyperkalemia: RAAS inhibitors are the most common cause 4
• Overlooking hypomagnesemia: Must be corrected before potassium correction 1
• Sodium polystyrene sulfonate: Associated with serious gastrointestinal adverse effects; avoid chronic use 1, 5
• Overcorrection leading to hypokalemia: Regular monitoring is essential 1

Emerging Treatments

• Newer potassium binders (patiromer and sodium zirconium cyclosilicate) are more effective and have fewer side effects than traditional options 6, 5
• Balancing the benefits of RAAS inhibitors while mitigating hyperkalemia is crucial for optimal treatment of underlying conditions 6