What is the management pathway for hyperkalemia?

Hyperkalemia Management Pathway

Hyperkalemia management follows a severity-based algorithm: immediately stabilize the cardiac membrane with IV calcium for severe cases (K+ ≥6.5 mEq/L) or any ECG changes, shift potassium intracellularly with insulin/glucose and albuterol, then remove potassium from the body using diuretics, potassium binders, or dialysis, while addressing the underlying cause. 1

Initial Assessment

Verify true hyperkalemia by excluding pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique—repeat the measurement with appropriate technique or arterial sampling before initiating treatment 1, 2

Classify severity immediately: 1

• Mild: 5.0-5.9 mEq/L
• Moderate: 6.0-6.4 mEq/L
• Severe: ≥6.5 mEq/L

Obtain ECG immediately to assess for peaked T waves, flattened P waves, prolonged PR interval, or widened QRS complexes—these findings mandate urgent treatment regardless of potassium level, though ECG changes are highly variable and less sensitive than laboratory values 1, 2

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Acute Management Algorithm (K+ ≥6.5 mEq/L OR Any ECG Changes)

Step 1: Cardiac Membrane Stabilization (FIRST-LINE)

Administer IV calcium gluconate 10% solution: 15-30 mL (1.5-3 grams) IV over 2-5 minutes to stabilize cardiac membranes and prevent life-threatening arrhythmias 1, 2, 3

• Effects begin within 1-3 minutes but are temporary (30-60 minutes) and do NOT reduce total body potassium 1, 2
• Repeat dosing may be necessary if no ECG improvement within 5-10 minutes 1
• Continuous cardiac monitoring is mandatory during and after administration 1
• Alternative: Calcium chloride 10%: 5-10 mL IV over 2-5 minutes (preferred for central access) 1

Critical pitfall: In malignant hyperthermia with hyperkalemia, use calcium only in extremis as it may contribute to calcium overload of the myoplasm 1

Step 2: Intracellular Potassium Shift (Give All Three Together)

Administer all three agents simultaneously for maximum effect: 1

1. Insulin 10 units regular IV + 25g dextrose (D50W) 1, 3

   • Onset: 15-30 minutes, duration: 4-6 hours 1
   • Can be repeated every 4-6 hours if hyperkalemia persists, monitoring potassium every 2-4 hours and glucose to avoid hypoglycemia 1
   • Never give insulin without glucose—hypoglycemia can be life-threatening 1
   • Verify potassium is not below 3.3 mEq/L before administering 1

2. Nebulized albuterol 10-20 mg in 4 mL 1, 3

   • Onset: 15-30 minutes, duration: 2-4 hours 1
   • Augments insulin effects 1

3. Sodium bicarbonate 50 mEq IV over 5 minutes ONLY if metabolic acidosis present (pH <7.35, bicarbonate <22 mEq/L) 1, 2

   • Onset: 30-60 minutes 1
   • Do NOT use without metabolic acidosis—it is ineffective and wastes time 1
   • Promotes potassium excretion through increased distal sodium delivery 1

Critical pitfall: Remember that calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 1

Step 3: Potassium Removal from Body

Choose based on renal function and clinical context: 1

For adequate kidney function:

• Loop diuretics (furosemide 40-80 mg IV) to increase renal potassium excretion 1, 3
• Titrate to maintain euvolemia, not primarily for potassium management 1

For severe cases, renal failure, or refractory hyperkalemia:

• Hemodialysis is the most effective and reliable method for potassium removal 1, 3, 4
• Reserved for severe hyperkalemia unresponsive to medical management, oliguria, or end-stage renal disease 1

Step 4: Medication Review During Acute Episode

Temporarily discontinue or reduce at K+ ≥6.5 mEq/L: 1

• RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid antagonists)
• NSAIDs
• Potassium-sparing diuretics (spironolactone, amiloride, triamterene)
• Trimethoprim
• Heparin
• Beta-blockers
• Potassium supplements and salt substitutes

Critical pitfall: Never permanently discontinue RAAS inhibitors in patients with cardiovascular disease or proteinuric CKD—they provide mortality benefit and slow disease progression 1

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Moderate Hyperkalemia Management (K+ 6.0-6.4 mEq/L, No ECG Changes)

Treat with insulin/glucose and albuterol to shift potassium intracellularly, plus calcium IV if ECG changes develop: 1

For potassium elimination: 1

• Loop diuretics if adequate renal function
• Initiate potassium binder for long-term management:
  • Patiromer (Veltassa): 8.4g once daily with food, titrated up to 25.2g daily (onset ~7 hours) 1, 5
  • Sodium zirconium cyclosilicate (SZC/Lokelma): 10g three times daily for 48 hours, then 5-15g once daily (onset ~1 hour) 1, 5

Maintain RAAS inhibitors using potassium binders rather than discontinuing these life-saving medications 1

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Mild Hyperkalemia Management (K+ 5.0-5.9 mEq/L, No ECG Changes)

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

Management strategy: 1

1. Review and eliminate contributing medications:

   • NSAIDs, potassium supplements, salt substitutes
   • Consider adjusting (not discontinuing) RAAS inhibitors if no cardiovascular indication

2. Optimize diuretic therapy:

   • Loop or thiazide diuretics to promote urinary potassium excretion if adequate renal function 1

3. For patients requiring RAAS inhibitors (cardiovascular disease, proteinuric CKD):

   • Maintain RAAS inhibitor at current dose AND initiate approved potassium-lowering agent (patiromer or SZC) 1, 2
   • This approach preserves mortality benefit while controlling potassium 1

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Chronic Hyperkalemia Prevention

For Patients on RAAS Inhibitors

K+ 5.0-6.5 mEq/L: 1

• Initiate patiromer or SZC while maintaining RAAS inhibitor therapy unless alternative treatable cause identified
• Do NOT discontinue RAAS inhibitors—they provide mortality benefit in cardiovascular and renal disease 1

K+ >6.5 mEq/L: 1

• Temporarily discontinue or reduce RAAS inhibitor
• Initiate potassium-lowering agent
• Restart RAAS inhibitor at lower dose once K+ <5.0 mEq/L with concurrent potassium binder therapy 1

Potassium Binder Selection

Patiromer (Veltassa): 1, 5

• Starting dose: 8.4g once daily with food
• Titrate up to 25.2g daily based on potassium levels
• Onset: ~7 hours
• Separate from other oral medications by at least 3 hours
• Mechanism: Exchanges calcium for potassium in colon
• Monitor for hypomagnesemia and hypercalcemia

Sodium zirconium cyclosilicate (SZC/Lokelma): 1, 5

• Starting dose: 10g three times daily for 48 hours, then 5-15g once daily
• Onset: ~1 hour (suitable for more urgent scenarios)
• Mechanism: Exchanges hydrogen and sodium for potassium
• Monitor for edema due to sodium content

Avoid sodium polystyrene sulfonate (Kayexalate): 1, 2

• Delayed onset, limited efficacy
• Risk of bowel necrosis and fatal gastrointestinal injury
• Should NOT be used for acute management

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Monitoring Protocol

Initial monitoring: 1, 2

• Check potassium within 1 week of starting or escalating RAAS inhibitors
• Reassess 7-10 days after initiating potassium binder therapy
• Monitor potassium every 2-4 hours after acute interventions

Ongoing monitoring frequency based on risk factors: 1

• High-risk patients (CKD, heart failure, diabetes, history of hyperkalemia) require more frequent checks
• Standard: 1-2 weeks, 3 months, then every 6 months for stable patients on RAAS inhibitors
• Monitor magnesium levels in patients on patiromer to detect hypomagnesemia 1

Target potassium ranges: 1

• General population: 3.5-5.0 mEq/L
• Advanced CKD (stage 4-5): 3.3-5.5 mEq/L (broader range tolerated)
• Optimal target to minimize mortality: 4.0-5.0 mEq/L

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Special Populations

Hemodialysis Patients

Predialysis potassium management: 1

• Target predialysis potassium: 4.0-5.5 mEq/L to minimize mortality risk
• First-line: SZC 5g once daily on non-dialysis days, adjust weekly in 5g increments 1
• Second-line: Patiromer 8.4g once daily with food, titrate up to 16.8-25.2g daily 1
• Consider adjusting dialysate potassium concentration (typically 2.0-3.0 mEq/L) based on trends 1

Post-dialysis monitoring: 1

• Monitor for rebound hyperkalemia within 4-6 hours post-dialysis
• Check potassium every 2-4 hours initially for severe cases (>6.5 mEq/L)
• Obtain ECG if initial presentation included cardiac changes

CKD Patients (Not on Dialysis)

Maintain RAAS inhibitors aggressively in proteinuric CKD using potassium binders, as these drugs slow CKD progression 1

At K+ 6.2 mEq/L: 1

• Temporarily reduce or hold ACE inhibitor
• Restart at lower dose with concurrent potassium binder therapy
• Do NOT permanently discontinue—leads to worse cardiovascular and renal outcomes

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Critical Pitfalls to Avoid

1. Never delay treatment while waiting for repeat lab confirmation if ECG changes are present 1
2. Never use sodium bicarbonate without metabolic acidosis—it is ineffective and wastes time 1
3. Never give insulin without glucose—hypoglycemia can be life-threatening 1
4. Do not rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 1
5. Remember that calcium, insulin, and beta-agonists do NOT remove potassium from the body—they only temporize 1
6. Never permanently discontinue RAAS inhibitors in cardiovascular disease or proteinuric CKD—use potassium binders instead 1
7. Avoid the triple combination of ACE inhibitor + ARB + MRA—excessive hyperkalemia risk 1
8. Monitor closely for hypokalemia with potassium binders—may be even more dangerous than hyperkalemia 1

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Team Approach

Optimal chronic hyperkalemia management involves a multidisciplinary team: 1, 2

• Cardiologists and nephrologists for complex cases
• Primary care physicians for ongoing management
• Nurses for monitoring and patient education
• Pharmacists for medication reconciliation
• Dietitians for nutritional counseling (though dietary restriction alone is unlikely to resolve hyperkalemia) 1