Hyperkalemia Management in Patients on ACE Inhibitors or ARBs
Step 1: Confirm True Hyperkalemia and Assess Severity
Immediately rule out pseudohyperkalemia by repeating the measurement with proper blood sampling technique (avoid prolonged tourniquet use, fist clenching, or hemolysis), as these can falsely elevate potassium levels 1. If the repeat value confirms hyperkalemia, classify severity: mild (5.0–5.5 mEq/L), moderate (5.5–6.0 mEq/L), or severe (≥6.0 mEq/L) 1, 2.
Obtain a 12-lead ECG immediately to assess for cardiac toxicity (peaked T waves, flattened P waves, prolonged PR interval, widened QRS complex), as ECG changes indicate urgent need for treatment regardless of the exact potassium value 1, 2, 3.
Step 2: Emergency Management (If K⁺ ≥6.0 mEq/L or ECG Changes Present)
Cardiac Membrane Stabilization (First-Line, Immediate)
Administer IV calcium gluconate 10% (15–30 mL over 2–5 minutes) or calcium chloride 10% (5–10 mL over 2–5 minutes) to protect against arrhythmias 1, 2, 3. This works within 1–3 minutes but lasts only 30–60 minutes and does not lower potassium 1, 2. Repeat the dose if ECG does not improve within 5–10 minutes 2, 3.
Shift Potassium Intracellularly (Administer Simultaneously)
- Insulin + Glucose: Give 10 units regular insulin IV with 25 g dextrose (50 mL D50W) to lower potassium by 0.5–1.2 mEq/L within 30–60 minutes, lasting 4–6 hours 1, 2, 3.
- Nebulized Albuterol: Administer 10–20 mg in 4 mL over 10–15 minutes to reduce potassium by 0.5–1.0 mEq/L within 30 minutes, lasting 2–4 hours 1, 2, 3.
- Sodium Bicarbonate (only if metabolic acidosis present): Give 50 mEq IV over 5 minutes only when pH <7.35 and bicarbonate <22 mEq/L 1, 2, 3. It is ineffective without acidosis 2.
Remove Potassium from the Body
- Loop Diuretics: Administer furosemide 40–80 mg IV if eGFR >30 mL/min and the patient is non-oliguric 1, 2, 3.
- Hemodialysis: The most effective method for severe hyperkalemia, especially in patients with oliguria, ESRD, or refractory hyperkalemia despite medical therapy 1, 2, 3. Indications include K⁺ >6.5 mEq/L unresponsive to treatment, oliguria/anuria, ongoing potassium release (tumor lysis, rhabdomyolysis), or persistent ECG changes 2, 3.
Step 3: Medication Management During Acute Episode
Immediately hold or reduce the following medications when K⁺ >6.5 mEq/L 1, 2, 3:
- ACE inhibitors or ARBs (temporarily discontinue or reduce dose by 50%) 1, 2
- Mineralocorticoid receptor antagonists (spironolactone, eplerenone) 1, 2, 3
- Potassium-sparing diuretics (amiloride, triamterene) 1, 2
- NSAIDs 1, 2, 3
- Trimethoprim-containing antibiotics 1, 2
- Potassium supplements and salt substitutes 1, 2, 3
- Beta-blockers (if contributing) 1, 2
- Heparin 1, 2
Step 4: Chronic/Recurrent Hyperkalemia Management (K⁺ 5.0–6.5 mEq/L)
Do NOT Permanently Discontinue ACE Inhibitors or ARBs
Maintain RAAS inhibitor therapy using potassium-lowering agents rather than discontinuing these life-saving medications, as they provide mortality benefit in cardiovascular disease, heart failure, and proteinuric CKD 1, 2, 3. Discontinuing RAAS inhibitors leads to worse cardiovascular and renal outcomes 2, 3.
Initiate Potassium Binders (Preferred Strategy)
For patients with K⁺ 5.0–6.5 mEq/L on RAAS inhibitors, initiate a potassium binder while maintaining RAAS inhibitor therapy 1, 2, 3:
Sodium Zirconium Cyclosilicate (SZC/Lokelma): Start 10 g three times daily for 48 hours, then 5–15 g once daily for maintenance 1, 2, 4. Onset of action is ~1 hour, making it suitable for more urgent scenarios 1, 2, 4. For hemodialysis patients, start 5 g once daily on non-dialysis days (or 10 g if K⁺ >6.5 mEq/L) 2, 4.
Patiromer (Veltassa): Start 8.4 g once daily with food, titrated up to 25.2 g daily based on potassium response 1, 2. Onset of action is ~7 hours 1, 2. Separate from other oral medications by at least 3 hours to avoid reduced absorption 2, 4.
Avoid sodium polystyrene sulfonate (Kayexalate) due to risk of bowel necrosis, colonic ischemia, and lack of efficacy data 1, 2, 3.
Restart RAAS Inhibitors at Lower Dose
Once potassium <5.0 mEq/L, restart the ACE inhibitor or ARB at a lower dose (reduce by 50%) with concurrent potassium binder therapy 1, 2, 3. For example, if the patient was on lisinopril 20 mg daily, restart at 10 mg daily 1, 2.
Optimize Diuretic Therapy
Add or increase loop diuretics (furosemide 40–80 mg daily) to enhance urinary potassium excretion if eGFR >30 mL/min 1, 2, 3. Thiazide diuretics can also be used 1, 2.
Dietary Modifications
Restrict potassium intake to <3 g/day (50–70 mmol/day) 3. Counsel patients to avoid high-potassium foods (bananas, oranges, potatoes, tomatoes, salt substitutes, legumes, chocolate, yogurt) and herbal supplements (alfalfa, dandelion, horsetail, nettle) 1, 2, 3.
Step 5: Monitoring Protocol
Acute Phase
- Recheck potassium 1–2 hours after insulin/glucose or albuterol administration 1, 2, 3.
- Continue monitoring every 2–4 hours until stable 1, 2, 3.
- Obtain repeat ECG to confirm resolution of cardiac changes 2, 3.
After Medication Adjustments
- Check potassium and renal function within 2–3 days and again at 7 days after initiating or adjusting RAAS inhibitors or potassium binders 1, 2, 3.
- Monitor monthly for the first 3 months, then every 3–6 months thereafter 1, 2, 3.
- For patients on potassium-sparing diuretics, check potassium every 5–7 days until values stabilize 1, 5.
High-Risk Patients (More Frequent Monitoring)
Individualize monitoring frequency based on 1, 2, 3:
- Chronic kidney disease (especially eGFR <45 mL/min) 1, 2, 6
- Heart failure 1, 2, 3
- Diabetes mellitus 1, 2, 7
- History of recurrent hyperkalemia 1, 2
- Concurrent use of multiple potassium-affecting medications 1, 2
Step 6: Special Populations
Hemodialysis Patients
For patients on chronic hemodialysis, administer potassium binders only on non-dialysis days 2, 4. Start SZC 5 g once daily on non-dialysis days (or 10 g if K⁺ >6.5 mEq/L) 2, 4. Target pre-dialysis potassium of 4.0–5.0 mEq/L 1, 2. Monitor potassium before and after each dialysis session 2. ACE inhibitors and ARBs do not significantly worsen hyperkalemia in hemodialysis patients with adequate dialysis 8, 9, but anuric patients require more cautious monitoring 9.
CKD Stage 3B–5 (Not on Dialysis)
Maintain RAAS inhibitors aggressively using potassium binders, as these drugs slow CKD progression 1, 2, 3. The optimal potassium range is broader in advanced CKD (3.3–5.5 mEq/L for stage 4–5 CKD) 1, 2, but maintaining 4.0–5.0 mEq/L minimizes mortality risk 1, 2.
Heart Failure Patients
Both hypokalemia and hyperkalemia increase mortality risk in heart failure; target potassium strictly between 4.0–5.0 mEq/L 1, 5, 2. If on mineralocorticoid receptor antagonists (spironolactone, eplerenone), reduce dose by 50% when K⁺ >5.5 mEq/L (e.g., spironolactone 25 mg → 12.5 mg daily) 1, 2, 3. Discontinue MRA only if K⁺ >6.0 mEq/L or ECG changes develop 1, 2, 3.
Critical Pitfalls to Avoid
- Do NOT delay calcium administration while awaiting repeat potassium levels if ECG changes are present 2, 3.
- Never give insulin without glucose—hypoglycemia can be fatal 2, 3.
- Do NOT use sodium bicarbonate without documented metabolic acidosis (pH <7.35, bicarbonate <22 mEq/L)—it is ineffective without acidosis 1, 2, 3.
- Do NOT permanently discontinue ACE inhibitors or ARBs due to hyperkalemia—use dose reduction plus potassium binders to maintain mortality and morbidity benefits 1, 2, 3.
- Recognize that calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 1, 2, 3. Rebound hyperkalemia occurs 2–4 hours after these therapies wear off 1, 2.
- Do NOT combine ACE inhibitors + ARBs + mineralocorticoid receptor antagonists (triple RAAS blockade)—this dramatically increases hyperkalemia risk 1, 5.
- Avoid NSAIDs entirely in patients on RAAS inhibitors, as they impair renal potassium excretion and increase hyperkalemia risk 1, 2, 3, 6.
- Monitor for hyperkalemia within the first week after initiating ARBs, as 52% of hyperkalaemic events occur within the first week 7. The highest frequency occurs on the first day 7.