What medications should be ruled out in a patient with hyperkalemia?

Medication Review in Hyperkalemia 6.4 mEq/L

In a patient with hyperkalemia of 6.4 mEq/L, immediately review and consider discontinuing or reducing RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists), NSAIDs, potassium-sparing diuretics, trimethoprim, heparin, beta-blockers, potassium supplements, and salt substitutes. 1

Priority Medications to Rule Out

RAAS Inhibitors (Highest Priority)

• ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (MRAs) are the most common culprits and should be temporarily reduced or held when potassium exceeds 6.0 mEq/L 2, 1
• The European Society of Cardiology specifically recommends discontinuing or reducing MRAs when potassium exceeds 6.0 mmol/L 3
• Do not permanently discontinue these medications—they provide mortality benefit in cardiovascular and renal disease; instead, temporarily hold them and restart at lower doses once potassium <5.0 mEq/L with concurrent potassium binder therapy 1
• The triple combination of ACE inhibitor + ARB + MRA is NOT recommended due to excessive hyperkalemia risk 2

NSAIDs (Second Priority)

• NSAIDs attenuate diuretic effects and impair renal potassium excretion 2, 1
• Avoid NSAIDs unless absolutely essential, including over-the-counter preparations 2
• NSAIDs are nephrotoxic and increase risk of both hyperkalemia and renal dysfunction 2

Potassium-Sparing Diuretics

• Amiloride and triamterene must be avoided when using MRAs 2
• These agents directly impair renal potassium excretion 4

Antimicrobials

• Trimethoprim impairs renal potassium excretion and should be reviewed 1
• Pentamidine can cause hyperkalemia through impaired renal excretion 4

Anticoagulants

• Heparin and derivatives suppress aldosterone secretion and contribute to hyperkalemia 1, 4
• This is a frequently overlooked cause in hospitalized patients 1

Beta-Blockers

• Beta-blockers promote transcellular potassium shift and should be reviewed 1, 4
• They impair cellular potassium uptake mechanisms 4

Potassium Supplements and Salt Substitutes

• Potassium supplements must be discontinued immediately 1
• "Low-salt" substitutes have high potassium content and should be avoided 2, 1
• Review all over-the-counter supplements that may contain potassium 1

Additional Medications to Consider

Calcineurin Inhibitors

• Tacrolimus and cyclosporine impair renal potassium excretion 4

Other Agents

• Mannitol can cause transcellular potassium shifts 4
• Suxamethonium promotes potassium release from cells 4
• Calcium channel blockers may alter transmembrane potassium movement 4

Critical Management Algorithm

For Potassium 6.0-6.4 mEq/L (Moderate Hyperkalemia):

1. Obtain ECG immediately to assess for peaked T waves, flattened P waves, prolonged PR interval, or widened QRS 1
2. If ECG changes present: Administer IV calcium gluconate 15-30 mL over 2-5 minutes for cardiac membrane stabilization 1
3. Review all medications above and eliminate or reduce contributing agents 1
4. Temporarily hold or reduce RAAS inhibitors until potassium <5.0 mEq/L 2, 1
5. Initiate potassium binder (patiromer 8.4g daily or sodium zirconium cyclosilicate 10g three times daily for 48 hours) 1
6. Recheck potassium within 24-48 hours after medication adjustments 1

After Acute Resolution:

• Restart RAAS inhibitors at lower dose once potassium <5.0 mEq/L with concurrent potassium binder therapy 1
• Monitor potassium within 7-10 days after restarting or adjusting RAAS inhibitor doses 1
• Continue potassium binder long-term to maintain RAAS inhibitor therapy in patients with cardiovascular disease or proteinuric CKD 1

Common Pitfalls to Avoid

• Never permanently discontinue RAAS inhibitors due to hyperkalemia—this leads to worse cardiovascular and renal outcomes 1
• Do not overlook heparin as a contributing factor in hospitalized patients 1
• Remember that dietary restriction alone is insufficient—medication review is essential 1
• Do not delay treatment while waiting for repeat labs if ECG changes are present 1