Hyperkalemia: Comprehensive Management Guide
Definition and Classification
Hyperkalemia is defined as serum potassium >5.0 mEq/L and is classified by severity: mild (5.0-5.9 mEq/L), moderate (6.0-6.4 mEq/L), and severe (≥6.5 mEq/L). 1, 2
- This classification directly guides treatment intensity and urgency 1
- ECG changes mandate immediate treatment regardless of the absolute potassium value 1, 2
- Symptoms are often nonspecific, making ECG and laboratory confirmation essential 2
Anatomy and Physiology
- Extracellular potassium represents only 1-2% of total body potassium, but its concentration critically affects cardiac and skeletal muscle depolarization 3
- The kidneys are the primary regulators of potassium homeostasis, and impaired renal excretion is the dominant cause of sustained hyperkalemia 2
- Hyperkalemia causes depolarizing effects on the heart, shortening action potentials and increasing the risk of fatal arrhythmias 2
- A U-shaped curve exists between serum potassium and mortality, with both hyperkalemia and hypokalemia associated with adverse outcomes 2
Etiology and Pathophysiology
Hyperkalemia develops through three primary mechanisms: impaired renal potassium excretion (most common), transcellular shift from intracellular to extracellular space, and excessive potassium intake in the setting of impaired renal function. 2
High-Risk Populations
- Chronic kidney disease (CKD), heart failure, diabetes mellitus, and history of prior hyperkalemia 1, 2
- Renal failure is a predisposing factor in 75% of hyperkalemia cases 3
Medication-Induced Causes (50% of cases)
- RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) 1, 2
- Potassium-sparing diuretics (spironolactone, amiloride, triamterene) 2
- NSAIDs (attenuate diuretic effects and impair renal potassium excretion) 2
- Trimethoprim, heparin, beta-blockers 2
- The triple combination of ACE inhibitor + ARB + MRA is NOT recommended due to excessive hyperkalemia risk 2
Other Contributing Factors
- Potassium supplements and "low-salt" substitutes (high potassium content) 2
- Metabolic acidosis (stimulates potassium release from cells) 2
Signs and Symptoms
- Symptoms are typically nonspecific and unreliable for diagnosis 2, 4
- Cardiac manifestations are the most serious: arrhythmias, cardiac arrest 1
- Neuromuscular dysfunction can occur when severe 4
- ECG changes are the critical clinical indicator but can be highly variable and less sensitive than laboratory tests 2
ECG Changes (in order of severity)
- Peaked T waves (earliest finding) 2
- Flattened P waves 2
- Prolonged PR interval 2
- Widened QRS complexes 2
- Absent or atypical ECG changes do not exclude the necessity for immediate intervention 5
Diagnosis and Evaluation
Initial Assessment
- First priority: exclude pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique by repeating measurement with appropriate technique or arterial sampling 2, 6
- Obtain ECG immediately—ECG changes mandate urgent treatment regardless of potassium value 1, 2
- Assess kidney function (eGFR) and identify risk factors 2
Laboratory Evaluation
- Serum potassium level (venous or arterial) 2
- Basic metabolic panel (assess for concurrent metabolic acidosis: pH <7.35, bicarbonate <22 mEq/L) 2
- Renal function tests 2
- In leukemic patients, check both plasma and serum potassium to identify reverse pseudohyperkalemia 6
Medication Review
- Review all medications: RAAS inhibitors, NSAIDs, potassium-sparing diuretics, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes 2
Interventions and Treatments
The treatment algorithm for acute hyperkalemia involves three sequential steps: (1) cardiac membrane stabilization, (2) shifting potassium into cells, and (3) eliminating potassium from the body. 1, 5, 3
STEP 1: Cardiac Membrane Stabilization (Onset: 1-3 minutes, Duration: 30-60 minutes)
Administer IV calcium immediately if potassium ≥6.5 mEq/L OR any ECG changes are present. 1, 2
- Calcium chloride (10%): 5-10 mL IV over 2-5 minutes (preferred for central access) 1, 2
- Calcium gluconate (10%): 15-30 mL IV over 2-5 minutes (preferred for peripheral access) 1, 2
- Continuous cardiac monitoring is mandatory during and for 5-10 minutes after administration 2
- If no ECG improvement within 5-10 minutes, repeat the dose 2
- Pediatric dosing: 100-200 mg/kg/dose via slow infusion with ECG monitoring 2
Critical Caveats:
- Calcium does NOT lower serum potassium—it only stabilizes cardiac membranes temporarily 2, 3
- Never administer calcium through the same IV line as sodium bicarbonate (precipitation will occur) 2
- In patients with elevated phosphate levels, use calcium cautiously due to calcium-phosphate precipitation risk 2
- In malignant hyperthermia with hyperkalemia, calcium should only be used in extremis due to myoplasmic calcium overload risk 2
STEP 2: Shift Potassium Into Cells (Onset: 15-30 minutes, Duration: 4-6 hours)
Insulin with glucose is the most reliable agent for shifting potassium into cells. 1, 3
Insulin/Glucose Protocol
- Standard dose: 10 units regular insulin IV + 25g glucose (50 mL D50W) 1, 2
- Some protocols recommend 0.1 units/kg (approximately 5-7 units in adults) 2
- Verify potassium is not below 3.3 mEq/L before administering insulin 2
- Monitor glucose and potassium every 2-4 hours after administration 2
- Can be repeated every 4-6 hours as needed for persistent or recurrent hyperkalemia 2
- High-risk patients for hypoglycemia: low baseline glucose, no diabetes history, female sex, altered renal function 2
Beta-2 Agonist (Albuterol/Salbutamol)
- Nebulized albuterol 10-20 mg in 4 mL over 10-15 minutes 2, 5
- Can be used alone or to augment insulin effect 3
- Onset: 15-30 minutes, Duration: 2-4 hours 2
- Intravenous salbutamol (5 mcg/kg over 15 minutes) is effective and safe in pediatric patients 7
Sodium Bicarbonate (ONLY if metabolic acidosis present)
- Indication: ONLY for hyperkalemic patients with concurrent metabolic acidosis (pH <7.35, bicarbonate <22 mEq/L) 2, 5
- Dose: 50 mEq IV over 5 minutes 2
- Onset: 30-60 minutes 2
- Do NOT use in patients without metabolic acidosis—it is ineffective and wastes time 2, 3
- Mechanism: promotes potassium excretion through increased distal sodium delivery and counters acidosis-induced potassium release 2
Combination Therapy for Severe Hyperkalemia:
- Give all three agents together for maximum effect: insulin + glucose, nebulized albuterol, and sodium bicarbonate (if acidosis present) 2
STEP 3: Eliminate Potassium From the Body
Loop Diuretics (for patients with adequate renal function)
- Furosemide 40-80 mg IV 1, 2
- Promotes urinary potassium excretion by stimulating flow to renal collecting ducts 2
- Titrate to maintain euvolemia, not primarily for potassium management 2
Hemodialysis (most effective method)
- Indications: severe hyperkalemia unresponsive to medical management, oliguria, or end-stage renal disease 2, 3
- Rapidly and reliably removes potassium 2, 3
- Monitor for rebound hyperkalemia within 4-6 hours post-dialysis as intracellular potassium redistributes 2
Potassium Binders
Newer potassium binders (Sodium Zirconium Cyclosilicate and Patiromer) are preferred for subacute and chronic management, offering faster onset and higher efficacy. 1, 2
Sodium Zirconium Cyclosilicate (SZC/Lokelma)
- FDA-approved for treatment of hyperkalemia in adults 8
- Limitation: Should NOT be used as emergency treatment for life-threatening hyperkalemia due to delayed onset of action 8
- Acute phase: 10g three times daily for 48 hours 2
- Maintenance: 5-15g once daily 2
- Onset of action: ~1 hour 2
- Mechanism: exchanges hydrogen and sodium for potassium 2
- First-line agent for hemodialysis patients: 5g once daily on non-dialysis days, adjust weekly in 5g increments 2
- Monitor for edema due to sodium content 2
Patiromer (Veltassa)
- FDA-approved for treatment of hyperkalemia in adults and pediatric patients ≥12 years 9
- Limitation: Should NOT be used as emergency treatment for life-threatening hyperkalemia due to delayed onset of action 9
- Starting dose: 8.4g once daily with food 2
- Titrate up to 25.2g daily based on potassium levels 2
- Onset of action: ~7 hours 2
- Mechanism: exchanges calcium for potassium in the colon 2
- Separate from other oral medications by at least 3 hours 2
- Monitor magnesium levels (causes hypomagnesemia and hypercalcemia) 2
- For each 1 mEq/L increase in serum magnesium, serum potassium increases by 1.07 mEq/L 2
Sodium Polystyrene Sulfonate (Kayexalate) - AVOID
- Significant limitations: delayed onset of action, risk of bowel necrosis, and lack of efficacy data 2
- Associated with intestinal ischemia, colonic necrosis, and doubling of risk for serious gastrointestinal adverse events 2
- Should be avoided for acute management and in hemodialysis patients 2
Treatment Algorithms by Severity
Mild Hyperkalemia (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. 2
- Review and eliminate contributing medications: NSAIDs, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes 2
- Consider loop diuretics (furosemide) if adequate renal function present 2
- For patients on RAAS inhibitors with K+ 5.0-5.9 mEq/L: initiate potassium binder (patiromer or SZC) and maintain RAAS inhibitor therapy 2
- Check potassium within 1 week 2
Moderate Hyperkalemia (6.0-6.4 mEq/L)
- If ECG changes present: administer IV calcium immediately 2
- Shift potassium into cells:
- Eliminate potassium:
- For patients on RAAS inhibitors: maintain therapy and add potassium binder 2
- Monitor potassium every 2-4 hours initially 2
Severe Hyperkalemia (≥6.5 mEq/L)
Administer IV calcium immediately if potassium ≥6.5 mEq/L OR any ECG changes are present. 2
Cardiac membrane stabilization:
Shift potassium into cells (give all together for maximum effect):
Eliminate potassium:
Medication management:
After acute resolution (K+ <5.5 mEq/L):
Chronic Hyperkalemia Management
The primary goal is maintaining life-saving RAAS inhibitor therapy by using potassium-lowering agents rather than discontinuing these medications. 2
Medication Optimization
- For patients on RAAS inhibitors with K+ 5.0-6.5 mEq/L: initiate potassium binder (patiromer or SZC) and maintain RAAS inhibitor therapy 2
- For patients on RAAS inhibitors with K+ >6.5 mEq/L: temporarily discontinue or reduce RAAS inhibitor, initiate potassium binder, restart RAAS inhibitor at lower dose once K+ <5.0 mEq/L 2
- Eliminate or reduce contributing medications: NSAIDs, trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes 2
- Optimize diuretic therapy with loop or thiazide diuretics 2
Monitoring Protocol
- Check potassium within 1 week of starting or escalating RAAS inhibitors 2
- Reassess 7-10 days after initiating potassium binder therapy 2
- Individualize monitoring frequency based on eGFR, heart failure, diabetes, or history of hyperkalemia 2
- High-risk patients require more frequent monitoring 2
Dietary Considerations
- Evidence linking dietary potassium intake to serum potassium is limited 2
- A potassium-rich diet has multiple health benefits, including blood pressure reduction 2
- Newer potassium binders may allow for less restrictive dietary potassium restrictions 2
- Avoid potassium supplements and salt substitutes 2
Special Populations
Chronic Kidney Disease (CKD)
- Maintain RAAS inhibitors aggressively in proteinuric CKD using potassium binders, as these drugs slow CKD progression 2
- Optimal potassium range is broader in advanced CKD: 3.3-5.5 mEq/L for stage 4-5 CKD versus 3.5-5.0 mEq/L for stage 1-2 CKD 2
- Target predialysis potassium of 4.0-5.5 mEq/L to minimize mortality risk 2
- Patients with advanced CKD tolerate higher potassium levels due to compensatory mechanisms 2
Hemodialysis Patients
- Sodium Zirconium Cyclosilicate (SZC) is the first-line agent: 5g once daily on non-dialysis days, adjust weekly in 5g increments 2
- Patiromer is second-line: 8.4g once daily with food, titrate up to 16.8g or 25.2g daily 2
- Avoid sodium polystyrene sulfonate (SPS/Kayexalate) due to serious safety concerns including fatal gastrointestinal injury 2
- Monitor for rebound hyperkalemia within 4-6 hours post-dialysis 2
- Consider adjusting dialysate potassium concentration (typically 2.0-3.0 mEq/L) based on predialysis levels 2
Cardiovascular Disease
- Patients on RAAS inhibitors require careful monitoring of potassium levels, with assessment 7-10 days after starting or increasing doses 2
- Do NOT permanently discontinue RAAS inhibitors—use potassium binders to maintain these life-saving medications 2
Pediatric Patients
- Intravenous salbutamol (5 mcg/kg over 15 minutes) is effective, rapid, safe, and predictable for treating acute hyperkalemia in children of any age 7
- Calcium gluconate dosing: 100-200 mg/kg/dose via slow infusion with ECG monitoring 2
- Patiromer is FDA-approved for pediatric patients ≥12 years 9
Potential Complications
Treatment-Related Complications
- Hypoglycemia from insulin administration 1, 2
- Rebound hyperkalemia after temporizing measures wear off 1, 4
- Hypokalemia from overtreatment 1, 2
- Hypomagnesemia and hypercalcemia from patiromer 2
- Edema from sodium content in SZC 2
- Gastrointestinal injury from sodium polystyrene sulfonate 2
Cardiac Complications
- Ventricular arrhythmias and cardiac arrest are the most serious consequences 1
- Fatal arrhythmias can occur with severe hyperkalemia 4, 3
Relevant Red Flags and CVICU Tips
Critical Red Flags
- ECG changes mandate immediate treatment regardless of potassium value 1, 2
- Absent or atypical ECG changes do not exclude the necessity for immediate intervention 5
- Do NOT rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 2
- Potassium ≥6.5 mEq/L requires immediate calcium administration 2
CVICU-Specific Tips
- Never delay treatment while waiting for repeat lab confirmation if ECG changes are present 2
- Calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 2
- Failure to initiate concurrent potassium-lowering therapies will result in recurrent life-threatening arrhythmias within 30-60 minutes 2
- Never give insulin without glucose—hypoglycemia can be life-threatening 2
- Never use sodium bicarbonate without metabolic acidosis—it is ineffective 2
- Combination therapy (insulin + albuterol + bicarbonate if acidosis) provides maximum effect for severe hyperkalemia 2
- Monitor glucose and potassium every 2-4 hours after initial treatment 2
- Patients with severe initial hyperkalemia (>6.5 mEq/L) or ongoing potassium release (tumor lysis syndrome, rhabdomyolysis) require more frequent monitoring 2
Common Pitfalls to Avoid
- Do NOT discontinue RAAS inhibitors permanently—they provide mortality benefit and slow disease progression 2
- Do NOT use sodium polystyrene sulfonate (Kayexalate) for acute management or in hemodialysis patients 2
- Do NOT administer calcium through the same IV line as sodium bicarbonate 2
- Do NOT forget to separate patiromer from other oral medications by at least 3 hours 2
- Do NOT overlook pseudohyperkalemia from hemolysis or poor phlebotomy technique 2, 6
- Do NOT forget to monitor magnesium levels in patients on patiromer 2