Hyperkalemia Management
For patients with hyperkalemia, particularly those with kidney disease or heart failure, the treatment approach depends critically on potassium level, ECG findings, and clinical context—with immediate cardiac membrane stabilization for severe cases (K+ >6.5 mEq/L or ECG changes), followed by intracellular potassium shifting, and definitive removal strategies, while aggressively maintaining RAAS inhibitors using newer potassium binders rather than discontinuing these life-saving medications. 1, 2
Classification and Initial Assessment
Severity Classification
- Mild hyperkalemia: 5.0-5.5 mEq/L 2
- Moderate hyperkalemia: 5.5-6.0 mEq/L (some guidelines use 6.0-6.4 mEq/L) 2, 3
- Severe hyperkalemia: >6.0 mEq/L (some guidelines use ≥6.5 mEq/L) 2, 3
Rule Out Pseudohyperkalemia First
- Repeat measurement with proper blood sampling technique if hemolysis, prolonged tourniquet application, or fist clenching suspected 2, 4
- Consider arterial sampling for confirmation if pseudohyperkalemia remains a concern 2, 4
Obtain ECG Immediately
- Look for peaked T waves, flattened P waves, prolonged PR interval, widened QRS complexes 2
- Critical caveat: ECG changes are highly variable and less sensitive than laboratory tests—absent ECG findings do NOT exclude the need for urgent treatment 2, 5
- Any ECG changes indicate urgent treatment regardless of the exact potassium value 2, 3
Acute Management Algorithm
Step 1: Cardiac Membrane Stabilization (If K+ >6.5 mEq/L OR Any ECG Changes)
Administer IV calcium immediately—this is the first priority to prevent fatal arrhythmias. 2, 3
- Calcium gluconate (10%): 15-30 mL IV over 2-5 minutes 2
- OR Calcium chloride (10%): 5-10 mL IV over 2-5 minutes (preferred for central access; avoid peripherally due to tissue injury risk) 2
- Onset: 1-3 minutes 2
- Duration: 30-60 minutes (temporary only) 2
- Repeat dosing: If no ECG improvement within 5-10 minutes, give second dose of 15-30 mL 2
- Continuous cardiac monitoring mandatory during and after administration 2
Critical pitfall: Calcium does NOT lower potassium—it only stabilizes cardiac membranes temporarily. 2 You must simultaneously initiate potassium-lowering therapies. 2
Special consideration: In patients with elevated phosphate levels (tumor lysis syndrome), use calcium cautiously due to calcium-phosphate precipitation risk. 2
Step 2: Shift Potassium Intracellularly (All Three Agents Together for Maximum Effect)
Give all three simultaneously for severe hyperkalemia: 2
Insulin + Glucose (First-Line)
- Regular insulin: 10 units IV bolus 2
- With 25g dextrose (50 mL of 50% dextrose or equivalent) 2, 5
- Onset: 15-30 minutes 2
- Duration: 4-6 hours 2
- Can be repeated every 4-6 hours if hyperkalemia persists, with careful glucose and potassium monitoring 2
- Monitor for hypoglycemia: Check glucose every 30-60 minutes initially, especially in patients with low baseline glucose, no diabetes, female sex, or altered renal function 2
Critical pitfall: Never give insulin without glucose—hypoglycemia can be life-threatening. 2
Nebulized Beta-2 Agonist (Adjunctive)
- Albuterol: 10-20 mg in 4 mL nebulized over 10 minutes 2
- Onset: 15-30 minutes 2
- Duration: 2-4 hours 2
- Provides additive effect when combined with insulin 2
Sodium Bicarbonate (ONLY If Metabolic Acidosis Present)
- Indication: pH <7.35, bicarbonate <22 mEq/L 2
- Dose: 50 mEq IV over 5 minutes 2
- Onset: 30-60 minutes 2
- Mechanism: Promotes potassium excretion through increased distal sodium delivery and counters acidosis-induced potassium release 2
Critical pitfall: Do NOT use sodium bicarbonate without metabolic acidosis—it is ineffective and wastes time. 2 Never administer through the same IV line as calcium (precipitation will occur). 2
Step 3: Remove Potassium from the Body
Loop Diuretics (If Adequate Renal Function)
- Furosemide: 40-80 mg IV 2
- Increases renal potassium excretion by stimulating flow to renal collecting ducts 2
- Should be titrated to maintain euvolemia, not primarily for potassium management 1, 2
Hemodialysis (Most Effective Method)
- Indications: 2
- Severe hyperkalemia unresponsive to medical management
- Oliguria or end-stage renal disease
- Rapid deterioration of kidney function
- Most reliable and effective method for potassium removal 2
- Monitor for rebound hyperkalemia 4-6 hours post-dialysis as intracellular potassium redistributes 2
Potassium Binders (For Definitive Removal)
See chronic management section below for detailed dosing.
Chronic Hyperkalemia Management
Critical Principle: Maintain RAAS Inhibitors
Do NOT permanently discontinue RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) in patients with cardiovascular disease, heart failure, or proteinuric CKD—these provide mortality benefit and slow disease progression. 1, 2, 3 Instead, use potassium binders to enable continuation of these life-saving medications. 1, 2
Medication Management Algorithm
For K+ 5.0-6.5 mEq/L on RAAS Inhibitors:
- Initiate approved potassium-lowering agent (patiromer or sodium zirconium cyclosilicate) 2
- Maintain RAAS inhibitor therapy unless alternative treatable cause identified 2
- Review and eliminate/reduce contributing medications: NSAIDs, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes 2, 3
For K+ >6.5 mEq/L on RAAS Inhibitors:
- Temporarily discontinue or reduce RAAS inhibitor dose by 50% 2, 3
- Initiate potassium-lowering agent 2
- Restart RAAS inhibitor at lower dose once K+ <5.0-5.5 mEq/L with concurrent potassium binder therapy 2, 3
Newer Potassium Binders (Preferred Agents)
Sodium Zirconium Cyclosilicate (SZC/Lokelma) - First-Line for Urgent Scenarios
- Mechanism: Highly selective potassium binding, exchanges hydrogen and sodium for potassium 2
- Onset: ~1 hour (fastest acting) 2, 6
- Dosing: 2, 6
- Acute phase: 10g three times daily for 48 hours
- Maintenance: 5-15g once daily (typically 5-10g)
- Adjust weekly in 5g increments based on predialysis potassium for hemodialysis patients 2
- Efficacy: Reduces serum potassium within 1 hour of single 10g dose 2
- Monitoring: Watch for edema due to sodium content 2
Patiromer (Veltassa) - First-Line for Chronic Management
- Mechanism: Exchanges calcium for potassium in the colon 2, 6
- Onset: ~7 hours 2, 6
- Dosing: 2, 6
- Starting dose: 8.4g once daily with food
- Titration: Up to 16.8g or 25.2g daily based on response
- Adjust dose weekly based on potassium levels
- Drug interactions: Separate from other oral medications by at least 3 hours (especially ciprofloxacin, levothyroxine, metformin) 2, 6
- Monitoring: Check magnesium levels (can cause hypomagnesemia and hypercalcemia) 2
- Efficacy: Mean potassium reduction of 0.65-0.97 mEq/L at 4 weeks 2
Clinical trial evidence: In the DIAMOND trial, patiromer with high-dose RAAS inhibitor therapy reduced hyperkalemia rates (K+ >5.5 mmol/L) by 37% compared to placebo (HR 0.63,95% CI 0.45-0.87). 1 In PEARL-HF, patiromer enabled 86% of patients to remain on spironolactone 50mg daily versus 66% with placebo. 2
Avoid Sodium Polystyrene Sulfonate (Kayexalate)
Do NOT use sodium polystyrene sulfonate for acute or chronic management. 2
- Delayed onset of action (hours to days) 2
- Limited efficacy data 2
- Associated with intestinal ischemia, colonic necrosis, and doubling of serious GI adverse events 2, 7
Additional Strategies for Chronic Management
SGLT2 Inhibitors (Protective Effect)
- Reduce risk of serious hyperkalemia in patients with type 2 diabetes, high cardiovascular risk, or CKD (HR 0.84,95% CI 0.76-0.93) 1
- Effect consistent across subgroups taking RAAS inhibitors and MRAs 1
- Opportunity for simultaneous introduction/reintroduction of GDMT components 1
ARNi (Sacubitril/Valsartan) vs. ACE Inhibitors
- In PARADIGM-HF, sacubitril/valsartan associated with lower severe hyperkalemia rates compared to enalapril in HFrEF patients on MRAs (HR 0.73,95% CI 0.58-0.94) 1
Loop Diuretics
- Optimize diuretic therapy to increase urinary potassium excretion 2
- Furosemide 40-80 mg daily if adequate renal function present 2
- Titrate to maintain euvolemia, not primarily for potassium management 1, 2
Dietary Modifications (Nuanced Approach)
- Evidence linking dietary potassium intake to serum levels is limited 2
- Potassium-rich diet provides cardiovascular benefits including blood pressure reduction 2
- Focus on reducing nonplant sources of potassium rather than stringent restriction 8
- Avoid high-potassium salt substitutes 2, 3
- Newer potassium binders may allow less restrictive dietary potassium restrictions 2
Monitoring Protocol
Timing of Potassium Checks
- Within 1 week of starting or escalating RAAS inhibitors 2
- Reassess 7-10 days after initiating potassium binder therapy 2
- Within 2-4 hours after initial emergency interventions 2
- Within 24-48 hours after medication adjustments 2
- Every 2-4 hours initially for severe hyperkalemia (>6.5 mEq/L) or ongoing potassium release (tumor lysis syndrome, rhabdomyolysis) 2
High-Risk Patients Requiring More Frequent Monitoring
- Chronic kidney disease (especially eGFR <60 mL/min) 2, 4
- Heart failure 2, 4
- Diabetes mellitus 2, 4
- History of hyperkalemia 2
- Advanced age 4
Concurrent Monitoring
- Renal function (creatinine, eGFR) with every potassium check 2
- Magnesium levels in patients on patiromer 2
- Glucose levels every 30-60 minutes after insulin administration 2
Special Populations
Advanced CKD (Stage 4-5)
- 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 2
- Patients tolerate higher potassium levels due to compensatory mechanisms 2
- Target predialysis potassium of 4.0-5.5 mEq/L to minimize mortality risk 2
- Maintain RAAS inhibitors aggressively using potassium binders in proteinuric CKD, as these drugs slow CKD progression 2
Heart Failure
- Up to 40% of heart failure patients on RAAS inhibitors develop hyperkalemia 4
- Withdrawal of GDMT associated with poorer clinical outcomes 1
- Consider SGLT2 inhibitors and ARNi to reduce hyperkalemia risk while optimizing GDMT 1
Hemodialysis Patients
- First-line: Sodium zirconium cyclosilicate 5g once daily on non-dialysis days, adjust weekly in 5g increments 2
- Second-line: Patiromer 8.4g once daily with food, titrate up to 16.8-25.2g daily 2
- Avoid sodium polystyrene sulfonate due to serious safety concerns 2
- Consider adjusting dialysate potassium concentration (typically 2.0-3.0 mEq/L) based on predialysis levels 2
Critical Pitfalls to Avoid
Do NOT rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 2
Do NOT delay treatment while waiting for repeat lab confirmation if ECG changes are present—ECG changes indicate urgent need regardless of exact potassium value 2
Do NOT use sodium bicarbonate in patients without metabolic acidosis—it is only indicated when acidosis is present 2
Do NOT give insulin without glucose—hypoglycemia can be life-threatening 2
Remember that calcium, insulin, and beta-agonists do NOT remove potassium from the body—they only temporize 2 Failure to initiate concurrent potassium removal strategies will result in recurrent life-threatening arrhythmias within 30-60 minutes. 2
Do NOT permanently discontinue beneficial RAAS inhibitors—dose reduction plus potassium binders is preferred to maintain mortality and morbidity benefits in heart failure and CKD 2, 3
Do NOT overlook pseudohyperkalemia from hemolysis or improper blood sampling 2, 4
Do NOT use sodium polystyrene sulfonate for acute or chronic management due to delayed onset, limited efficacy, and risk of bowel necrosis 2
Monitor closely for hypokalemia in patients on potassium binders—hypokalemia may be even more dangerous than hyperkalemia 2
Do NOT ignore the need for magnesium monitoring in patients on patiromer (for each 1 mEq/L increase in serum magnesium, serum potassium increases by 1.07 mEq/L) 2