What is the appropriate workup and initial management for hyperkalemia?

Hyperkalemia Workup and Initial Management

Immediate Assessment: Verify and Classify

The first step is to confirm true hyperkalemia by repeating the measurement with proper technique or arterial sampling to exclude pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique. 1

• Obtain a 12-lead ECG immediately regardless of the potassium level, as ECG changes (peaked T waves, flattened P waves, prolonged PR interval, widened QRS) indicate urgent treatment need even before laboratory confirmation 1, 2
• Classify severity: mild (5.0-5.9 mEq/L), moderate (6.0-6.4 mEq/L), or severe (≥6.5 mEq/L) 1
• ECG findings can be highly variable and less sensitive than laboratory tests, but their presence mandates immediate intervention 1

Initial Laboratory Workup

Order a complete metabolic panel, complete blood count, urinalysis, and venous blood gas to identify the underlying cause and assess for concurrent metabolic acidosis. 1

• Check serum creatinine and eGFR to evaluate renal function 1
• Measure serum magnesium, calcium, and glucose 1
• Assess acid-base status (pH < 7.35 and bicarbonate < 22 mEq/L indicates metabolic acidosis) 1
• Review medication list for contributing agents: ACE inhibitors, ARBs, MRAs, NSAIDs, beta-blockers, trimethoprim, heparin, potassium supplements, and salt substitutes 1, 3

Acute Management Algorithm

For Severe Hyperkalemia (≥6.5 mEq/L) or ANY ECG Changes:

1. Cardiac Membrane Stabilization (FIRST-LINE, IMMEDIATE):

• Administer IV calcium gluconate 10% (15-30 mL over 2-5 minutes) OR calcium chloride 10% (5-10 mL over 2-5 minutes) with continuous cardiac monitoring 1, 2
• Onset: 1-3 minutes; duration: 30-60 minutes 1
• Repeat dose if no ECG improvement within 5-10 minutes 1
• Calcium does NOT lower potassium—it only temporarily stabilizes the cardiac membrane 1

2. Intracellular Potassium Shift (ADMINISTER SIMULTANEOUSLY):

• Insulin-glucose: 10 units regular insulin IV with 25g dextrose (50 mL D50W); lowers K+ by 0.5-1.2 mEq/L within 30-60 minutes, lasts 4-6 hours 1, 2
• Nebulized albuterol: 10-20 mg in 4 mL over 10-15 minutes; lowers K+ by 0.5-1.0 mEq/L within 30 minutes, lasts 2-4 hours; can repeat every 2 hours 1, 2
• Sodium bicarbonate: 50 mEq IV over 5 minutes ONLY if metabolic acidosis present (pH < 7.35, bicarbonate < 22 mEq/L); onset 30-60 minutes 1, 2

3. Definitive Potassium Removal (WITHIN HOURS):

• Loop diuretics: Furosemide 40-80 mg IV if eGFR > 30 mL/min and non-oliguric 1, 2
• Hemodialysis: Most reliable method for severe hyperkalemia; absolute indications include K+ > 6.5 mEq/L unresponsive to medical therapy, oliguria/anuria, ESRD, ongoing K+ release (tumor lysis, rhabdomyolysis), eGFR < 15 mL/min, or persistent ECG changes 1, 2, 3
• CRRT preferred over intermittent hemodialysis in hemodynamically unstable patients 1

For Moderate Hyperkalemia (6.0-6.4 mEq/L) WITHOUT ECG Changes:

• Administer insulin-glucose and albuterol as above 1
• Hold RAAS inhibitors temporarily 1
• Initiate potassium binder therapy (see below) 1
• Monitor potassium every 2-4 hours until stable 1

For Mild Hyperkalemia (5.0-5.9 mEq/L):

• Do NOT initiate acute interventions (calcium, insulin, albuterol) unless ECG changes or symptoms present 1
• Review and eliminate contributing medications 1
• Initiate potassium binder if on RAAS inhibitors 1

Medication Management During Acute Episode

Hold immediately when K+ > 6.5 mEq/L: 1

• RAAS inhibitors (ACE-I, ARBs, MRAs)
• NSAIDs
• Potassium-sparing diuretics
• Trimethoprim
• Heparin
• Beta-blockers
• Potassium supplements and salt substitutes

Chronic Hyperkalemia Management

The goal is to maintain RAAS inhibitors using potassium binders rather than permanently discontinuing these life-saving medications. 1

Potassium Binder Selection:

Binder	Regimen	Onset	Key Points
Sodium zirconium cyclosilicate (SZC/Lokelma)	10g TID × 48h, then 5-15g daily	~1 hour	Suitable for urgent scenarios; reduces K+ within 1 hour [1]
Patiromer (Veltassa)	8.4g daily with food, titrate to 25.2g	~7 hours	Separate from other meds by ≥3 hours; for sub-acute/chronic control [1]
Sodium polystyrene sulfonate (Kayexalate)	AVOID	Variable	Risk of bowel necrosis, colonic ischemia, limited efficacy [1,4]

RAAS Inhibitor Management Strategy:

For K+ 5.0-6.5 mEq/L on RAAS inhibitors: 1

• Initiate approved K+-lowering agent (patiromer or SZC)
• Maintain RAAS inhibitor therapy unless alternative treatable cause identified
• These agents provide mortality benefit in cardiovascular and renal disease

For K+ > 6.5 mEq/L: 1

• Discontinue or reduce RAAS inhibitor temporarily
• Initiate K+-lowering agent when K+ > 5.0 mEq/L
• Restart RAAS inhibitor at lower dose once K+ < 5.0 mEq/L with concurrent binder therapy

Monitoring Protocol

Acute Phase: 1

• Recheck K+ 1-2 hours after insulin/glucose or beta-agonist therapy
• Continue every 2-4 hours until stable
• Repeat ECG to confirm resolution of cardiac changes

Post-Acute Phase: 1

• Check K+ within 1 week after starting or escalating RAAS inhibitors
• Reassess 7-10 days after initiating potassium binder
• Individualize frequency based on eGFR, heart failure, diabetes, or prior hyperkalemia episodes

Dietary Considerations

Limit foods rich in bioavailable potassium, especially processed foods, and avoid salt substitutes containing potassium. 1

• Evidence linking dietary potassium to serum levels is limited; a potassium-rich diet has cardiovascular benefits 1
• Focus dietary restriction on nonplant sources of K+ rather than blanket restriction 5
• Avoid herbal supplements that raise K+: alfalfa, dandelion, horsetail, nettle 1

Critical Pitfalls to Avoid

Never delay calcium administration while awaiting repeat potassium levels when ECG changes are present—ECG changes indicate urgent need regardless of the exact potassium value. 1

• Never give insulin without glucose; hypoglycemia can be fatal 1
• Recognize that calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 1, 2
• Do NOT use sodium bicarbonate without documented metabolic acidosis (pH < 7.35, bicarbonate < 22 mEq/L)—it is ineffective and wastes time 1, 2
• Do NOT permanently discontinue RAAS inhibitors; use potassium binders to maintain these agents 1
• Do NOT rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 1

Special Populations

CKD Stage 4-5: 1

• Optimal K+ range is broader: 3.3-5.5 mEq/L
• Patients tolerate higher K+ levels due to compensatory mechanisms
• Maintain target K+ 4.0-5.0 mEq/L to minimize mortality risk

Heart Failure: 1

• Both hypokalemia and hyperkalemia increase mortality risk
• Target K+ strictly 4.0-5.0 mEq/L
• Consider aldosterone antagonists for mortality benefit while using binders to control K+

Dialysis Patients: 6

• Target pre-dialysis K+ 4.0-5.5 mEq/L
• SZC 10g once daily on non-dialysis days preferred
• Monitor for rebound hyperkalemia 4-6 hours post-dialysis