What is the management and treatment of hyperkalemia?

Hyperkalemia: Comprehensive Clinical Guide

Definition and Classification

Hyperkalemia is defined as serum potassium >5.0 mEq/L and represents a potentially life-threatening electrolyte emergency requiring immediate recognition and treatment. 1

Classification by severity: 1, 2

• Mild: 5.0-5.9 mEq/L
• Moderate: 6.0-6.4 mEq/L
• Severe: ≥6.5 mEq/L (life-threatening)

Critical caveat: ECG changes (peaked T waves, flattened P waves, prolonged PR interval, widened QRS) mandate urgent treatment regardless of the absolute potassium value. 1 However, absent or atypical ECG changes do NOT exclude the need for immediate intervention—ECG findings are highly variable and less sensitive than laboratory values. 2, 3

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Anatomy and Physiology

The kidneys are the primary regulators of potassium homeostasis, with impaired renal excretion being the dominant cause of sustained hyperkalemia. 2 Only 1-2% of total body potassium exists in the extracellular space, but this concentration is critical for cardiac and neuromuscular function. 4

Three primary mechanisms cause hyperkalemia: 2

• Impaired renal potassium excretion (most common)
• Transcellular shift from intracellular to extracellular space
• Excessive potassium intake in the setting of impaired renal function

Cardiac effects: Hyperkalemia causes depolarization of cardiac membranes, shortening action potentials and increasing the risk of fatal arrhythmias. 2 A U-shaped mortality curve exists—both hyperkalemia and hypokalemia are associated with adverse outcomes. 2

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Etiology and Pathophysiology

High-risk populations: 5, 2

• Chronic kidney disease (CKD)—present in 75% of hyperkalemia cases 4
• Heart failure
• Diabetes mellitus
• History of prior hyperkalemia

Medication-induced hyperkalemia (contributes to 50% of cases): 2, 4

• RAAS inhibitors: ACE inhibitors, ARBs, mineralocorticoid receptor antagonists (MRAs)
• Potassium-sparing diuretics: Spironolactone, amiloride, triamterene
• NSAIDs: Impair renal potassium excretion and attenuate diuretic effects
• Other: Trimethoprim, heparin, beta-blockers, potassium supplements, salt substitutes

The triple combination of ACE inhibitor + ARB + MRA is absolutely contraindicated due to excessive hyperkalemia risk. 2

Important: Most cases are multifactorial, involving both impaired renal function and contributing medications. 4

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Signs and Symptoms

Symptoms are typically nonspecific, making ECG and laboratory confirmation essential. 2 Patients may be entirely asymptomatic until life-threatening arrhythmias occur. 6

When present, symptoms include: 6

• Muscle weakness
• Paresthesias
• Palpitations
• Nausea

ECG changes (in order of severity): 1, 2

1. Peaked T waves (earliest finding)
2. Flattened P waves
3. Prolonged PR interval
4. Widened QRS complex
5. Sine wave pattern (pre-arrest)
6. Ventricular fibrillation/asystole

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Diagnosis and Evaluation

Step 1: Exclude Pseudohyperkalemia

Before initiating aggressive treatment, exclude pseudohyperkalemia from hemolysis, repeated fist clenching, or improper phlebotomy technique. 1, 7 Repeat measurement with appropriate technique or obtain arterial sample if suspicion exists. 1

Pseudohyperkalemia is increasingly seen in: 7

• Severe leukocytosis
• Thrombocytosis
• Hemolyzed specimens

Step 2: Obtain ECG Immediately

An ECG must be obtained immediately in all patients with potassium >6.0 mEq/L or any symptomatic patient. 1, 3 ECG changes indicate the need for emergent cardiac membrane stabilization. 1

Step 3: Assess Renal Function and Risk Factors

Check eGFR and identify contributing factors: 2

• CKD stage
• Diabetes
• Heart failure
• Current medications (especially RAAS inhibitors, NSAIDs, potassium-sparing diuretics)
• Recent medication changes
• Dietary potassium intake (including salt substitutes)

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Interventions and Treatments

ACUTE HYPERKALEMIA MANAGEMENT

The treatment algorithm follows three sequential steps, with all interventions initiated simultaneously in severe cases (K+ ≥6.5 mEq/L or ECG changes): 1

STEP 1: Cardiac Membrane Stabilization (Immediate—within 1-3 minutes)

Administer IV calcium FIRST if K+ ≥6.5 mEq/L OR any ECG changes are present: 1, 2

Preferred: Calcium chloride 10%: 5-10 mL (500-1000 mg) IV over 2-5 minutes 1

• Provides more rapid increase in ionized calcium than calcium gluconate 1
• Must be given through central line when possible—peripheral extravasation causes severe tissue injury 1

Alternative: Calcium gluconate 10%: 15-30 mL IV over 2-5 minutes 1

• Safer for peripheral IV access 1
• Requires larger volume to achieve equivalent effect 1

Critical points about calcium: 1, 2

• Onset: 1-3 minutes
• Duration: 30-60 minutes (temporary only)
• Does NOT lower serum potassium—only stabilizes cardiac membranes
• Monitor heart rate continuously; stop if symptomatic bradycardia occurs 1
• If no ECG improvement within 5-10 minutes, repeat the dose 2
• Never administer through same IV line as sodium bicarbonate (causes precipitation) 2

Pediatric dosing: 20 mg/kg (0.2 mL/kg of 10% calcium chloride) over 5-10 minutes with continuous ECG monitoring 1

STEP 2: Shift Potassium into Cells (Onset 15-30 minutes, Duration 4-6 hours)

Give all three agents together for maximum effect in severe hyperkalemia: 2

1. Insulin with Glucose (most reliable agent): 1, 4

• Standard dose: 10 units regular insulin IV + 25g glucose (50 mL D50W) over 15-30 minutes
• Alternative: 100 mL D25W provides 25g glucose 1
• Pediatric: 0.1 units/kg insulin + 200 mg/kg dextrose as D10W 1
• Monitor glucose every 2-4 hours to prevent hypoglycemia 2
• Can be repeated every 4-6 hours if hyperkalemia persists 2
• High-risk for hypoglycemia: Low baseline glucose, no diabetes, female sex, impaired renal function 2

2. Nebulized Beta-2 Agonist: 1

• Albuterol: 10-20 mg in 4 mL nebulized over 15 minutes
• Salbutamol: 5 mcg/kg over 15 minutes (alternative, especially in pediatrics) 8
• Can be used alone or to augment insulin effect 4
• Reduces potassium by approximately 0.5-1.0 mEq/L 1
• Side effect: Slight increase in heart rate 8

3. Sodium Bicarbonate (ONLY if metabolic acidosis present): 1, 2

• Dose: 50 mEq IV over 5 minutes
• Indication: pH <7.35, bicarbonate <22 mEq/L
• Mechanism: Counters acidosis-induced potassium release; increases distal sodium delivery to promote renal excretion 1
• Onset: 30-60 minutes (slower than insulin/albuterol) 2
• Do NOT use without metabolic acidosis—it is ineffective and wastes time 2, 4

Critical warning about temporary measures: Insulin/glucose and albuterol provide only transient effects lasting 1-4 hours, and rebound hyperkalemia can occur after 2 hours. 1 Definitive potassium removal must be initiated simultaneously. 1

STEP 3: Eliminate Potassium from Body (Definitive Treatment)

Choose method based on renal function, severity, and clinical context: 1, 2

1. Loop Diuretics (if adequate renal function): 1, 2

• Furosemide: 40-80 mg IV
• Increases renal potassium excretion by stimulating flow to collecting ducts 2
• Effective only with eGFR >30 mL/min 2
• Titrate to maintain euvolemia, not primarily for potassium management 2

2. Newer Potassium Binders (preferred for subacute/chronic management): 1, 2

Sodium Zirconium Cyclosilicate (SZC/Lokelma): 2, 9

• Acute phase: 10g PO three times daily for 48 hours
• Maintenance: 5-15g once daily
• Onset: ~1 hour (fastest oral agent)
• Mechanism: Exchanges hydrogen and sodium for potassium
• Limitation: Not for emergency treatment of life-threatening hyperkalemia due to delayed onset 9
• Side effect: Monitor for edema (sodium content) 2

Patiromer (Veltassa): 2, 10

• Starting dose: 8.4g once daily with food
• Titration: Up to 25.2g daily based on response
• Onset: ~7 hours
• Mechanism: Exchanges calcium for potassium in colon
• Administration: Separate from other medications by ≥3 hours 2
• Limitation: Not for emergency treatment due to delayed onset 10
• Side effects: Hypomagnesemia (monitor magnesium levels), hypercalcemia 2

3. Sodium Polystyrene Sulfonate (Kayexalate)—AVOID: 1, 2

• Dose: 15-50g orally or rectally with sorbitol
• Significant limitations: Delayed onset, variable efficacy, risk of bowel necrosis and serious GI injury 1, 2
• Should be avoided in favor of newer binders 1, 2

4. Hemodialysis (most effective method): 1, 2

• Indications: 2
  • Severe hyperkalemia unresponsive to medical management
  • Oliguria or anuria
  • End-stage renal disease
  • Ongoing potassium release (tumor lysis syndrome, rhabdomyolysis)
• Rapidly and reliably removes potassium 4
• Monitor for rebound hyperkalemia within 4-6 hours post-dialysis 2

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CHRONIC/RECURRENT HYPERKALEMIA MANAGEMENT

The primary goal is maintaining life-saving RAAS inhibitor therapy while controlling potassium levels. 1, 2

Treatment Algorithm Based on Potassium Level:

Potassium 4.5-5.0 mEq/L: 1

• Initiate or uptitrate RAAS inhibitor therapy
• Monitor potassium closely (within 7-10 days) 2

Potassium 5.0-6.5 mEq/L (on RAAS inhibitors): 1, 2

• Initiate approved potassium-lowering agent (patiromer or SZC)
• Maintain RAAS inhibitor therapy (provides mortality benefit)
• Monitor potassium levels closely
• Eliminate contributing medications (NSAIDs, potassium supplements, salt substitutes)

Potassium >6.5 mEq/L (on RAAS inhibitors): 1, 2

• Temporarily discontinue or reduce RAAS inhibitor
• Initiate potassium-lowering agent
• Monitor potassium closely
• Restart RAAS inhibitor at lower dose once K+ <5.0 mEq/L with concurrent potassium binder 2

Medication Management:

Review and adjust contributing medications: 2

• Discontinue if possible: NSAIDs, trimethoprim, heparin, potassium supplements, salt substitutes
• Avoid: Amiloride and triamterene when using MRAs 2
• Never use: ACE inhibitor + ARB + MRA combination 2

Optimize diuretic therapy: 2

• Loop diuretics (furosemide 40-80 mg daily) or thiazide diuretics
• Promotes urinary potassium excretion
• Requires adequate renal function (eGFR >30 mL/min)

Fludrocortisone (use cautiously): 2

• Increases potassium excretion
• Risks: Fluid retention, hypertension, vascular injury
• Reserve for cases where other options exhausted 2

Monitoring Protocol:

Frequency based on risk factors: 5, 2

• High-risk patients (CKD, diabetes, heart failure, history of hyperkalemia, on RAAS inhibitors): Check within 1 week of starting/escalating RAAS inhibitors, then at 1-2 weeks, 3 months, then every 6 months
• After initiating potassium binder: Reassess at 7-10 days 2
• Post-dialysis patients with severe initial hyperkalemia: Every 2-4 hours initially due to rebound risk 2

Target potassium ranges: 2

• General population: 3.5-5.0 mEq/L
• Advanced CKD (stage 4-5): 3.3-5.5 mEq/L (broader range tolerated)
• Hemodialysis patients: Predialysis 4.0-5.5 mEq/L

Dietary Considerations:

Evidence indicates direct links between dietary potassium intake and serum potassium are limited, and potassium-rich diets provide cardiovascular benefits including blood pressure reduction. 2 Stringent dietary restrictions may not be necessary in patients receiving potassium binder therapy. 5, 2

However, avoid: 2

• Potassium supplements
• Salt substitutes (high potassium content)

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SPECIAL POPULATIONS

CKD Patients:

Maintain RAAS inhibitors aggressively in proteinuric CKD using potassium binders—these drugs slow CKD progression. 2 Patients with advanced CKD tolerate higher potassium levels (3.3-5.5 mEq/L) due to compensatory mechanisms. 2

For moderate hyperkalemia (6.0-6.4 mEq/L) with no ECG changes: 2

• Start loop diuretics (furosemide) if eGFR >30 mL/min
• Initiate potassium binder (patiromer or SZC)
• Temporarily reduce ACE inhibitor at K+ 6.2 mEq/L
• Restart at lower dose with concurrent binder once K+ <5.0 mEq/L

Dialysis is reserved for: 2

• Severe hyperkalemia unresponsive to medical management
• Oliguria or ESRD
• After other approaches have been instituted

Hemodialysis Patients:

First-line agent: Sodium Zirconium Cyclosilicate (SZC): 2

• Dose: 5g once daily on non-dialysis days
• Adjust weekly in 5g increments based on predialysis potassium
• Goal: Maintain predialysis K+ 4.0-5.0 mEq/L
• Advantage: Rapid onset (~1 hour), highly selective binding
• Monitor: Edema (sodium content)

Second-line agent: Patiromer: 2

• Dose: 8.4g once daily with food, separate from other meds by 3 hours
• Titrate to 16.8g or 25.2g based on response
• Monitor: Magnesium levels (causes hypomagnesemia)—for each 1 mEq/L increase in magnesium, potassium increases by 1.07 mEq/L 2

Avoid sodium polystyrene sulfonate (SPS/Kayexalate) due to serious safety concerns including fatal GI injury. 2

Dialysate adjustment: 2

• Standard: 2.0-3.0 mEq/L potassium
• For recurrent severe hyperkalemia: Lower to 2.0 mEq/L
• Monitor for intradialytic arrhythmias with lower concentrations

Post-Dialysis Management:

Monitor for rebound hyperkalemia within 4-6 hours as intracellular potassium redistributes. 2 Obtain ECG if initial presentation included cardiac changes to document resolution. 2

Initiate chronic prevention: 2

• Start potassium binder (SZC or patiromer)
• Target predialysis K+ 4.0-5.5 mEq/L
• Restart RAAS inhibitors at lower dose once K+ <5.5 mEq/L (provides mortality benefit)

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Potential Complications

Cardiac complications (most serious): 2, 6

• Ventricular arrhythmias
• Cardiac arrest
• Sudden death

Treatment-related complications: 2

• Hypoglycemia: From insulin administration without adequate glucose
• Rebound hyperkalemia: After temporary measures wear off (2-6 hours)
• Hypokalemia: From overcorrection
• Tissue necrosis: From calcium chloride extravasation
• GI injury: From sodium polystyrene sulfonate
• Hypomagnesemia: From patiromer
• Edema: From SZC (sodium content)

Complications of discontinuing RAAS inhibitors: 2

• Worse cardiovascular outcomes
• Accelerated CKD progression
• Increased mortality in heart failure

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Relevant Red Flags and CVICU Tips

Critical Red Flags:

1. ECG changes mandate immediate treatment regardless of potassium value 1, 3

• Do NOT wait for repeat lab confirmation if ECG changes present 2
• Absent ECG changes do NOT exclude need for intervention 3

2. Never delay calcium administration in severe hyperkalemia with ECG changes 2

• Calcium is the ONLY intervention that protects against immediate arrhythmic death
• All other measures take 15-60 minutes to work

3. Rebound hyperkalemia is common and dangerous 1

• Occurs 2-6 hours after temporary measures
• Must initiate definitive potassium removal simultaneously with temporizing measures
• Monitor closely, especially post-dialysis patients

4. Hypoglycemia from insulin can be life-threatening 2

• Never give insulin without glucose
• Monitor glucose every 2-4 hours
• High-risk: Low baseline glucose, no diabetes, female, renal impairment

CVICU-Specific Tips:

Cardiac membrane stabilization: 1, 2

• Calcium chloride preferred over calcium gluconate in critically ill patients (more rapid ionized calcium increase)
• Give through central line when possible
• Monitor continuously during administration
• Repeat dose if no ECG improvement in 5-10 minutes
• Effects last only 30-60 minutes—must initiate other therapies simultaneously

Combination therapy for severe hyperkalemia: 2

• Give insulin + glucose + albuterol + calcium together for maximum effect
• Add sodium bicarbonate ONLY if pH <7.35
• Do NOT use bicarbonate without acidosis—wastes time

Medication reconciliation is critical: 2

• Review ALL medications on admission
• Hold NSAIDs, potassium supplements, salt substitutes immediately
• Temporarily reduce/hold RAAS inhibitors if K+ >6.5 mEq/L
• Never permanently discontinue RAAS inhibitors—restart with binder once stable

Monitoring intensity: 2

• Severe hyperkalemia (>6.5 mEq/L): Check K+ every 2-4 hours initially
• After insulin/glucose: Check glucose every 2-4 hours
• Post-dialysis: Check K+ at 2,4, and 6 hours for rebound
• On patiromer: Check magnesium levels

Hemodialysis indications in ICU: 2

• Severe hyperkalemia unresponsive to medical therapy
• Ongoing potassium release (tumor lysis, rhabdomyolysis)
• Oliguria/anuria
• Need for rapid, reliable potassium removal

Common pitfalls to avoid: 2

• Relying solely on ECG findings (they are variable and insensitive)
• Using sodium bicarbonate without metabolic acidosis
• Giving insulin without glucose
• Thinking calcium/insulin/albuterol remove potassium (they only temporize)
• Permanently discontinuing RAAS inhibitors (leads to worse outcomes)
• Using sodium polystyrene sulfonate (risk of bowel necrosis)
• Failing to initiate definitive removal while using temporary measures

Team approach: 2

• Involve nephrology early for severe/recurrent cases
• Coordinate with cardiology for patients on RAAS inhibitors
• Engage pharmacy for medication reconciliation and binder dosing
• Consider dietitian consultation for long-term management

Optimal potassium target in ICU: 2

• General: 4.0-5.0 mEq/L minimizes mortality
• Advanced CKD: 3.3-5.5 mEq/L acceptable
• Avoid overcorrection—hypokalemia may be more dangerous than mild hyperkalemia