How to manage hyperkalemia caused by Lisinopril (angiotensin-converting enzyme inhibitor)?

Management of Hyperkalemia Caused by Lisinopril

Adding an SGLT2 inhibitor while continuing lisinopril at a lower dose is the most effective strategy for managing hyperkalemia in patients on ACE inhibitors while maintaining cardio-renal protection. 1

Pathophysiology and Risk Assessment

Lisinopril, an ACE inhibitor, causes hyperkalemia by:

• Decreasing aldosterone production
• Reducing renal potassium excretion
• Promoting potassium retention, especially in patients with impaired renal function

Risk factors for hyperkalemia with lisinopril include:

• Renal dysfunction (eGFR <60 ml/min/1.73m²)
• Diabetes mellitus
• Heart failure
• Advanced age
• Concomitant use of potassium-sparing diuretics or potassium supplements
• Higher doses of lisinopril 2

Management Algorithm

Step 1: Assess Severity of Hyperkalemia

• Mild: 5.0-5.5 mmol/L
• Moderate: 5.6-6.5 mmol/L
• Severe: >6.5 mmol/L 3

Step 2: Acute Management (for Moderate to Severe Hyperkalemia)

1. For severe hyperkalemia (>6.5 mmol/L) with ECG changes:

   • Administer IV calcium gluconate 10% solution (15-30 mL) to stabilize cardiac membranes
   • Give insulin with glucose (10 units regular insulin IV with 50 mL of 25% dextrose)
   • Consider sodium bicarbonate if metabolic acidosis is present
   • Temporarily discontinue lisinopril 3

2. For moderate hyperkalemia (5.6-6.5 mmol/L):

   • Reduce lisinopril dose
   • Consider potassium binders
   • Monitor potassium levels closely 1, 3

Step 3: Long-term Management Strategies

Option A: Preferred Approach

• Add an SGLT2 inhibitor while continuing lisinopril at a lower dose 1
  • SGLT2 inhibitors reduce the risk of serious hyperkalemia (HR 0.84; 95% CI, 0.76-0.93)
  • This approach maintains cardio-renal protection while reducing hyperkalemia risk

Option B: Alternative Approaches

1. Switch to sacubitril/valsartan

   • Associated with lower rates of severe hyperkalemia compared to ACE inhibitors (HR 1.37; 95% CI, 1.06-1.76 for enalapril vs. sacubitril/valsartan) 1

2. Use potassium binders

   • Patiromer has been shown to reduce hyperkalemia rates (HR 0.63; 95% CI, 0.45-0.87) when used with RAAS inhibitors 1, 3
   • Options include:
     • Sodium zirconium cyclosilicate (SZC): Faster onset (1 hour), more selective for potassium
     • Patiromer: Onset of 7 hours, no sodium content (beneficial in heart failure) 3

3. Careful rechallenge with lower dose lisinopril

   • Over 80% of patients can tolerate RAAS inhibitors even after an episode of hyperkalemia 1

Step 4: Monitoring Protocol

• Check potassium and renal function within 1-2 weeks of initiating or changing ACE inhibitor dose 1
• Monitor potassium levels at least monthly for the first 3 months, then every 3 months thereafter 1
• More frequent monitoring for high-risk patients (CKD, heart failure, diabetes) 3

Additional Considerations

Lifestyle Modifications

• Counsel patients to avoid high-potassium foods
• Discontinue potassium supplements
• Avoid NSAIDs which can worsen hyperkalemia 1, 3
• Maintain adequate hydration 3

Common Pitfalls to Avoid

1. Complete discontinuation of RAAS inhibitors without attempting dose reduction

   • Discontinuing RAAS inhibitors is associated with poorer clinical outcomes 1
   • Only 22% of heart failure patients achieve recommended ACE inhibitor doses 1

2. Failure to monitor potassium levels

   • Potassium should be checked within 2-3 days and again at 7 days after initiating an aldosterone antagonist 1

3. Overlooking drug interactions

   • Potassium-sparing diuretics, NSAIDs, and potassium supplements can increase hyperkalemia risk 4

4. Ignoring renal function

   • ACE inhibitors can cause changes in renal function, especially in older adults 1, 4
   • Monitor creatinine and eGFR alongside potassium levels

By following this algorithm, clinicians can effectively manage hyperkalemia while maintaining the cardio-renal benefits of RAAS inhibitor therapy in most patients.