How should hyperkalemia be managed, including cardiac stabilization, intracellular potassium shifting, potassium removal, and correction of underlying causes?

Hyperkalemia Management

Immediate Assessment and Classification

For any patient with hyperkalemia, obtain an ECG immediately—ECG changes (peaked T waves, flattened P waves, prolonged PR interval, widened QRS) indicate urgent need for treatment regardless of the exact potassium value. 1

Classification System

• Mild hyperkalemia: 5.0–5.9 mEq/L 1
• Moderate hyperkalemia: 6.0–6.4 mEq/L 1
• Severe hyperkalemia: ≥6.5 mEq/L 1

Any hyperkalemia with ECG changes or potassium >6.0 mEq/L requires hospital admission regardless of symptoms. 2 The presence of ECG abnormalities indicates life-threatening cardiac instability even when potassium levels appear only moderately elevated. 1

Before initiating treatment, verify this is not pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique by repeating the measurement with proper arterial sampling or technique. 1

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Emergency Management of Severe Hyperkalemia (≥6.5 mEq/L or ECG Changes)

Step 1: Cardiac Membrane Stabilization (Onset 1–3 Minutes)

Administer IV calcium gluconate 10% (15–30 mL) over 2–5 minutes immediately if potassium ≥6.5 mEq/L OR any ECG changes are present. 1 Calcium does NOT lower potassium—it only stabilizes cardiac membranes temporarily for 30–60 minutes. 1

• If no ECG improvement within 5–10 minutes, repeat the same dose of calcium gluconate 15–30 mL IV over 2–5 minutes. 1
• Alternatively, use calcium chloride 10% (5–10 mL) over 2–5 minutes if central venous access is available, as it is more potent. 1
• Critical pitfall: Never delay calcium administration while waiting for repeat potassium levels if ECG changes are present—ECG changes indicate urgent need regardless of the exact potassium value. 1

Step 2: Shift Potassium Intracellularly (Onset 15–30 Minutes)

Administer all three agents together for maximum effect:

• Insulin + glucose: 10 units regular insulin IV with 25 g dextrose (50 mL D50W). 1 This lowers potassium by 0.5–1.2 mEq/L within 30–60 minutes, with effects lasting 4–6 hours. 1

  • Critical pitfall: Never give insulin without glucose—hypoglycemia can be life-threatening. 1
  • Monitor glucose closely; patients with low baseline glucose, no diabetes, female sex, and altered renal function are at higher risk of hypoglycemia. 1

• Nebulized albuterol: 10–20 mg in 4 mL over 10–15 minutes. 1 This provides an additional 0.5–1.0 mEq/L reduction and can be repeated every 2 hours if needed. 1

• Sodium bicarbonate: 50 mEq IV over 5 minutes ONLY if metabolic acidosis is present (pH <7.35, bicarbonate <22 mEq/L). 1 Bicarbonate is ineffective without acidosis and wastes time. 1 Effects take 30–60 minutes to manifest. 1

Remember: Calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body. 1 Rebound hyperkalemia commonly occurs 2–4 hours after these effects wear off. 1

Step 3: Remove Potassium from the Body

Choose based on renal function and clinical context:

• Loop diuretics: Furosemide 40–80 mg IV increases renal potassium excretion if adequate kidney function exists (eGFR >30 mL/min) and urine output is sufficient. 1

• Hemodialysis: The most reliable and effective method for severe hyperkalemia. 1 Absolute indications include: 1

  • Potassium >6.5 mEq/L unresponsive to medical therapy
  • Oliguria or anuria
  • End-stage renal disease
  • Ongoing potassium release (tumor lysis syndrome, rhabdomyolysis)
  • Severe renal impairment (eGFR <15 mL/min)
  • Persistent ECG changes despite medical management

• Avoid sodium polystyrene sulfonate (Kayexalate): This agent has significant limitations including delayed onset, risk of bowel necrosis and colonic ischemia, and lack of efficacy data for acute management. 1

Step 4: Medication Management During Acute Episode

Immediately discontinue or hold: 1

• RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) when potassium >6.5 mEq/L
• NSAIDs
• Potassium-sparing diuretics (spironolactone, amiloride, triamterene)
• Trimethoprim
• Heparin
• Beta-blockers
• Potassium supplements and salt substitutes

Step 5: Monitoring Protocol

• Recheck potassium 1–2 hours after insulin/glucose or albuterol administration. 2
• Subsequently monitor every 2–4 hours during the acute treatment phase until stable. 2
• Continuous cardiac monitoring is mandatory during and after calcium administration. 1
• Monitor for rebound hyperkalemia 4–6 hours post-dialysis, especially in patients with severe initial hyperkalemia (>6.5 mEq/L) or ongoing potassium release. 1

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Management of Moderate Hyperkalemia (6.0–6.4 mEq/L)

If ECG changes are present, treat as severe hyperkalemia above. 1 If no ECG changes:

Treatment Algorithm

• Obtain ECG immediately to assess for cardiac effects. 2

• Shift potassium intracellularly: 1

  • Insulin 10 units IV + 25 g dextrose
  • Nebulized albuterol 10–20 mg in 4 mL
  • Sodium bicarbonate 50 mEq IV over 5 minutes ONLY if metabolic acidosis present

• Initiate potassium removal: 1

  • Loop diuretics (furosemide 40–80 mg IV) if adequate renal function
  • Consider hemodialysis if refractory or severe renal impairment

• For long-term potassium elimination, initiate a potassium binder: 1

  • Sodium zirconium cyclosilicate (SZC/Lokelma): 10 g three times daily for 48 hours, then 5–15 g once daily for maintenance. Onset of action ~1 hour. 1
  • Patiromer (Veltassa): 8.4 g once daily with food, titrated up to 25.2 g daily. Onset of action ~7 hours. 1 Separate from other oral medications by at least 3 hours. 1

Medication Adjustment

• Do NOT permanently discontinue RAAS inhibitors in patients with cardiovascular disease or proteinuric CKD—these provide mortality benefit. 1
• Temporarily hold or reduce RAAS inhibitors until potassium <5.0 mEq/L, then restart at lower dose with concurrent potassium binder therapy. 1
• Review and eliminate contributing medications: NSAIDs, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes. 1

Monitoring

• Recheck potassium within 24–48 hours after initial interventions. 2
• Monitor potassium and renal function within 7–10 days after initiating potassium binder or adjusting RAAS inhibitor dose. 1

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Management of Mild Hyperkalemia (5.0–5.9 mEq/L)

Do NOT initiate acute interventions (calcium, insulin, albuterol) for mild hyperkalemia without ECG changes or symptoms. 1

Initial Steps

• Obtain ECG to rule out cardiac effects. 2
• Verify not pseudohyperkalemia by repeating measurement with proper technique. 1
• Review medications: 1
  • RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists)
  • NSAIDs
  • Potassium-sparing diuretics
  • Trimethoprim-sulfamethoxazole (especially in patients on RAAS inhibitors—this combination dramatically amplifies hyperkalemia risk) 1
  • Heparin
  • Beta-blockers
  • Potassium supplements and salt substitutes

Treatment Algorithm Based on Clinical Context

For patients on RAAS inhibitors with potassium 5.0–6.5 mEq/L: 1

• Initiate a potassium binder (patiromer or SZC) while maintaining RAAS inhibitor therapy unless an alternative treatable cause is identified. 1
• This approach enables continuation of life-saving cardiovascular medications. 1

For patients with adequate renal function:

• Consider loop diuretics (furosemide 40–80 mg daily) to enhance urinary potassium excretion. 1

Dietary modifications:

• Restrict potassium intake to <3 g/day. 2
• Avoid high-potassium foods: bananas, oranges, melons, potatoes, tomato products, salt substitutes, legumes, chocolate, yogurt. 2
• However, evidence linking dietary potassium intake to serum levels is limited, and potassium-rich diets provide cardiovascular benefits including blood pressure reduction. 1 Stringent dietary restrictions may not be necessary in patients receiving potassium binder therapy. 1

Monitoring Protocol

• Recheck potassium within 1 week of starting or escalating RAAS inhibitors. 1
• Reassess 7–10 days after initiating potassium binder therapy. 1
• Individualize monitoring frequency based on comorbidities (CKD, diabetes, heart failure) and medications. 1
• High-risk patients with history of hyperkalemia require more frequent checks. 1

When to Escalate Care

Immediate hospital referral if: 2

• Potassium rises above 6.0 mEq/L on repeat testing
• ECG changes develop
• Patient develops symptoms (muscle weakness, paresthesia)
• Rapid deterioration of kidney function

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Special Population: Patients on Spironolactone + RAAS Inhibitor

For patients on spironolactone plus losartan (or other RAAS inhibitor) with potassium >5.5 mEq/L: 2

• Reduce spironolactone dose by 50% (e.g., 25 mg → 12.5 mg daily). 2
• Do NOT discontinue spironolactone unless potassium >6.0 mEq/L or ECG changes appear—premature cessation removes the proven mortality benefit. 2
• Discontinue any potassium-containing dietary supplements immediately. 2

Monitoring after dose reduction: 2

• Recheck potassium and creatinine in 2–3 days
• Perform 7-day follow-up potassium test to confirm downward trend
• If stable, monitor monthly for first 3 months, then every 3 months thereafter

Criteria for temporary discontinuation of spironolactone: 2

• Potassium >6.0 mEq/L
• ECG abnormalities
• Creatinine >2.5 mg/dL
• Development of diarrhea or dehydration

Critical pitfall: Do not stop both spironolactone and losartan simultaneously—the combination provides significant mortality advantage in heart failure. 2 Dose reduction with adjunct potassium binders is preferred. 2

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Chronic Hyperkalemia Management

Maintain RAAS Inhibitors Using Potassium Binders

The European Society of Cardiology recommends maintaining life-saving RAAS inhibitor therapy in patients with hyperkalemia by using potassium-lowering agents. 1

For patients on RAAS inhibitors with potassium 5.0–6.5 mEq/L: 1

• Initiate patiromer or SZC while maintaining RAAS inhibitor therapy unless alternative treatable cause identified

For patients on RAAS inhibitors with potassium >6.5 mEq/L: 1

• Temporarily discontinue or reduce RAAS inhibitor
• Initiate potassium binder
• Restart RAAS inhibitor at lower dose once potassium <5.0 mEq/L with concurrent potassium binder

Potassium Binder Selection and Dosing

Sodium zirconium cyclosilicate (SZC/Lokelma): 1

• Acute phase: 10 g three times daily for 48 hours
• Maintenance: 5–15 g once daily
• Onset: ~1 hour
• Advantages: Rapid onset suitable for urgent scenarios; may improve metabolic acidosis
• Monitoring: Watch for edema due to sodium content

Patiromer (Veltassa): 1

• Starting dose: 8.4 g once daily with food
• Titration: Up to 25.2 g daily based on potassium response
• Onset: ~7 hours
• Administration: Separate from other oral medications by at least 3 hours (except amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, warfarin—no separation needed) 1
• Monitoring: Check magnesium levels regularly (patiromer causes hypomagnesemia and hypercalcemia) 1

Indications for starting patiromer: 1

• Mild hyperkalemia (5.0–5.9 mEq/L) in patients requiring RAAS inhibitor continuation
• When initiating or uptitrating spironolactone in heart failure patients with baseline potassium 4.3–5.1 mEq/L and CKD (prevents hyperkalemia development)
• Moderate hyperkalemia (6.0–6.4 mEq/L) in diabetic kidney disease patients

Optimize Diuretic Therapy

• Loop or thiazide diuretics promote urinary potassium excretion by stimulating flow to renal collecting ducts. 1
• Furosemide 40–80 mg daily if adequate renal function present (eGFR >30 mL/min). 1
• Titrate to maintain euvolemia, not primarily for potassium management. 1

Special Considerations in CKD

For patients with CKD stages 4–5: 1

• Optimal potassium range is broader: 3.3–5.5 mEq/L for stage 4–5 CKD versus 3.5–5.0 mEq/L for stage 1–2 CKD
• Maintain RAAS inhibitors aggressively using potassium binders—these drugs slow CKD progression and provide mortality benefit
• Target predialysis potassium of 4.0–5.5 mEq/L to minimize mortality risk

For hemodialysis patients: 1

• First-line: SZC 5 g once daily on non-dialysis days, adjust weekly in 5 g increments to maintain predialysis potassium 4.0–5.0 mEq/L
• Second-line: Patiromer 8.4 g once daily with food, titrate up to 16.8 g or 25.2 g daily
• Avoid sodium polystyrene sulfonate due to serious safety concerns including fatal gastrointestinal injury
• Consider adjusting dialysate potassium concentration (typically 2.0–3.0 mEq/L) based on predialysis levels

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Common Pitfalls to Avoid

• Do NOT rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests. 1
• Do NOT use sodium bicarbonate in patients without metabolic acidosis—it is only indicated when acidosis is present. 1
• Ensure glucose is administered with insulin to prevent hypoglycemia. 1
• Remember that calcium, insulin, and beta-agonists do NOT remove potassium from the body—they only temporize. 1
• Do NOT delay treatment while waiting for repeat lab confirmation if ECG changes are present. 1
• Do NOT permanently discontinue beneficial RAAS inhibitors due to hyperkalemia—dose reduction plus potassium binders is preferred to maintain mortality and morbidity benefits in heart failure and CKD. 1
• Do NOT ignore the 5.5 mEq/L threshold for dose reduction in patients on spironolactone—waiting until 6.0 mEq/L increases arrhythmia risk. 2
• Failure to monitor potassium within 2–3 days after spironolactone dose adjustment is a common error that can allow dangerous potassium accumulation. 2

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Team Approach

Optimal chronic hyperkalemia management involves a multidisciplinary team including cardiologists, nephrologists, primary care physicians, nurses, pharmacists, social workers, and dietitians. 1 Educational initiatives on newer potassium binders are needed to improve long-term outcomes. 1