How to manage hyperkalemia in patients on angiotensin II receptor blockers (sartans)?

Management of Hyperkalemia in Patients on Sartans (ARBs)

Do not discontinue sartans (ARBs) in patients who develop hyperkalemia—instead, initiate newer potassium binders (patiromer or sodium zirconium cyclosilicate) to maintain these life-saving medications that reduce mortality and morbidity in cardiovascular and renal disease. 1

Initial Assessment and Severity Classification

Before treating, exclude pseudo-hyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique by repeating the measurement with appropriate technique or arterial sampling. 2, 1

Classify hyperkalemia severity: 2, 1

• Mild: 5.0-5.5 mEq/L
• Moderate: 5.5-6.0 mEq/L
• Severe: ≥6.5 mEq/L or any ECG changes (peaked T waves, flattened P waves, prolonged PR interval, widened QRS)

Obtain an ECG immediately, but do not rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests. 1 ECG changes indicate urgent treatment regardless of potassium level. 1

Management Algorithm Based on Potassium Level

For K+ 5.0-6.5 mEq/L (Mild to Moderate)

Maintain the sartan and initiate a potassium-lowering agent rather than discontinuing RAAS inhibitor therapy. 1 The European Society of Cardiology explicitly recommends this approach because sartans provide proven mortality benefit in heart failure, hypertension, coronary disease, and chronic kidney disease. 2, 1

Step 1: Review and eliminate contributing medications 1

• Stop NSAIDs immediately 1
• Discontinue potassium supplements and salt substitutes 1
• Hold trimethoprim, heparin if possible 1
• Reduce or stop potassium-sparing diuretics (spironolactone, amiloride, triamterene) 2
• Consider stopping beta-blockers if not essential 2

Step 2: Optimize diuretic therapy 1

• Add loop diuretics (furosemide 40-80 mg daily) or thiazide diuretics to increase urinary potassium excretion if adequate renal function present (eGFR >30 mL/min) 1, 3
• Co-administration of loop or thiazide diuretics is specifically recommended when combining sartans with aldosterone antagonists to reduce hyperkalemia risk 3

Step 3: Initiate newer potassium binders 1

Choose one of the following FDA-approved agents:

• Patiromer (Veltassa): Start 8.4 g once daily with food, titrate up to 25.2 g daily based on potassium levels; onset of action ~7 hours 2, 1

  • Maintains normokalemia for up to 12 months in patients with diabetes, CKD, and heart failure on RAAS inhibitors 2
  • In the AMBER trial, 86% of patients remained on spironolactone with patiromer vs 66% with placebo 2

• Sodium zirconium cyclosilicate (SZC/Lokelma): 10 g three times daily for 48 hours (correction phase), then 5-15 g once daily for maintenance; onset of action ~1 hour 2, 1

  • Reduces serum potassium within 1 hour and is effective for both acute (≥5.8 mEq/L) and chronic management 1
  • In HARMONIZE trial, 93% of patients maintained K+ ≤5.1 mEq/L across 11 months 2

Avoid sodium polystyrene sulfonate (Kayexalate)—it has delayed onset of action and carries risk of bowel necrosis. 1

For K+ >6.5 mEq/L (Severe)

Temporarily discontinue or reduce the sartan dose until K+ <5.0 mEq/L, then reinitiate with concurrent potassium binder therapy. 1, 4

Acute management sequence: 1, 4, 5

1. Cardiac membrane stabilization (within 1-3 minutes):

   • Calcium gluconate 10%: 15-30 mL IV over 2-5 minutes, OR
   • Calcium chloride 10%: 5-10 mL IV over 2-5 minutes (use central line when possible to avoid tissue injury from extravasation) 4, 5
   • Effects are temporary (30-60 minutes) and do not lower potassium 1

2. Shift potassium intracellularly (onset 15-30 minutes, duration 4-6 hours):

   • Regular insulin 10 units IV with 50 mL D50W (25g glucose) over 15-30 minutes 1, 4
   • Monitor glucose closely; administer glucose even if baseline glucose is elevated to prevent hypoglycemia 1
   • Can repeat every 4-6 hours if hyperkalemia persists, monitoring potassium every 2-4 hours 1
   • Nebulized albuterol 10-20 mg over 15 minutes as adjunctive therapy (lowers K+ by 0.5-1.0 mEq/L) 1, 4

3. Sodium bicarbonate ONLY if concurrent metabolic acidosis present (pH <7.35, bicarbonate <22 mEq/L):

   • Effects take 30-60 minutes to manifest 1
   • Do not use in patients without metabolic acidosis 1

4. Eliminate potassium from the body:

   • Furosemide 40-80 mg IV if adequate renal function (eGFR >30 mL/min) 1, 4
   • Hemodialysis is the most effective method for severe hyperkalemia, especially with renal failure, oliguria, or cases unresponsive to medical management 1

5. Initiate potassium binder:

   • Start SZC 10 g three times daily for rapid effect (onset 1 hour) 1

Monitoring Protocol

Check potassium within 1 week of starting or escalating sartan therapy. 1 This is critical because 37-40% of patients with stage 3 CKD develop hyperkalemia (K+ >5.0 mEq/L) within the first 2 months of initiating RAAS inhibitors. 6

Reassess potassium 7-10 days after initiating or adjusting potassium binder therapy. 1

Individualize monitoring frequency based on risk factors: 1

• Chronic kidney disease (especially eGFR <60 mL/min)
• Heart failure
• Diabetes mellitus
• Advanced age
• History of hyperkalemia
• Concurrent use of multiple RAAS inhibitors or aldosterone antagonists

For severe hyperkalemia, check potassium every 2-4 hours initially until stable below 5.5 mEq/L, with continuous cardiac monitoring for at least 6 hours or until K+ <6.0 mEq/L. 4

Special Considerations for Sartan + Aldosterone Antagonist Combination

The combination of sartans with spironolactone or other mineralocorticoid receptor antagonists (MRAs) increases hyperkalemia risk to 5-10% in patients with heart failure or CKD. 2 Life-threatening hyperkalemia has been reported with candesartan plus spironolactone and losartan plus spironolactone combinations. 3, 7

When combining sartans with MRAs: 3

• Assess trans-tubular potassium gradient (TTKG) and fractional excretion of potassium (FEK) before starting therapy to identify high-risk patients
• Co-administer thiazide or loop diuretics to reduce hyperkalemia risk
• Monitor potassium within 1 week, then at 1 and 2 months after initiating combination therapy 6

Dietary Considerations

Do not routinely restrict dietary potassium in patients on sartans—evidence linking dietary potassium intake to serum levels is limited, and potassium-rich diets provide cardiovascular benefits including blood pressure reduction. 1

Focus dietary restriction on reducing nonplant sources of potassium rather than eliminating fruits and vegetables. 8 Avoid potassium supplements and salt substitutes containing potassium chloride. 2, 1

Key Pitfalls to Avoid

• Do not discontinue sartans reflexively for mild-moderate hyperkalemia—use potassium binders to maintain these mortality-reducing medications 1
• Remember that calcium, insulin, and beta-agonists only temporize—they do not remove potassium from the body 1
• Do not use sodium bicarbonate without documented metabolic acidosis 1
• Always administer glucose with insulin to prevent hypoglycemia 1
• Do not rely solely on ECG findings—obtain laboratory confirmation 1
• Avoid sodium polystyrene sulfonate (Kayexalate) for acute management due to bowel necrosis risk 1

Reinitiating Sartan Therapy After Severe Hyperkalemia

Restart the sartan once K+ <5.0 mEq/L AND concurrent conditions (infection, acute kidney injury, volume depletion) are controlled. 4

Initiate a potassium binder (patiromer or SZC) concurrently when restarting the sartan to prevent recurrence. 1 Monitor potassium within 1 week of reinitiation. 1, 4