What is the recommended stepwise approach to managing hyperkalemia, including indications for calcium gluconate, insulin with dextrose, albuterol, sodium bicarbonate, loop diuretics, potassium binders, and dialysis?

Approach to Hyperkalemia

For acute hyperkalemia with ECG changes or potassium ≥6.5 mEq/L, immediately administer IV calcium gluconate 15-30 mL over 2-5 minutes to stabilize the cardiac membrane, followed simultaneously by insulin 10 units IV with 25g dextrose and nebulized albuterol 10-20 mg to shift potassium intracellularly, then initiate definitive potassium removal with hemodialysis (most effective), loop diuretics if adequate renal function exists, or newer potassium binders (patiromer or sodium zirconium cyclosilicate) for subacute management. 1

Immediate Assessment and Risk Stratification

Verify the potassium level by repeating measurement with proper technique or arterial sampling to exclude pseudohyperkalemia from hemolysis or improper blood collection. 1 Classify severity as mild (5.0-5.9 mEq/L), moderate (6.0-6.4 mEq/L), or severe (≥6.5 mEq/L). 1

Obtain a 12-lead ECG immediately regardless of potassium level, as ECG changes indicate urgent treatment need even when laboratory values are pending. 1 Look for peaked T waves (>5.5 mEq/L), flattened P waves and prolonged PR interval (6.0-6.4 mEq/L), widened QRS complex (>6.5 mEq/L), or sine-wave pattern/ventricular arrhythmias (≥7-8 mEq/L). 1 Do not delay treatment while awaiting repeat laboratory confirmation if ECG changes are present—ECG abnormalities mandate immediate intervention. 1, 2

Step 1: Cardiac Membrane Stabilization (Onset 1-3 Minutes)

Administer IV calcium gluconate 10% (15-30 mL) over 2-5 minutes for any patient with ECG changes or potassium ≥6.5 mEq/L. 1 Alternatively, use calcium chloride 10% (5-10 mL) if central venous access is available, as it is more potent. 1 The protective effect begins within 1-3 minutes but lasts only 30-60 minutes. 1

Repeat the calcium dose if no ECG improvement within 5-10 minutes. 1 Maintain continuous cardiac monitoring during and after administration. 1 Critical caveat: Calcium does NOT lower serum potassium—it only temporarily protects the heart from arrhythmias. 1, 3 Never administer calcium through the same IV line as sodium bicarbonate, as precipitation will occur. 4

In patients with tumor lysis syndrome and elevated phosphate levels, use calcium cautiously as it increases the risk of calcium-phosphate precipitation in tissues. 4

Step 2: Intracellular Potassium Shift (Onset 15-30 Minutes)

Administer all three agents together for maximum effect:

Insulin-Glucose Therapy

Give 10 units regular insulin IV push with 25g dextrose (50 mL D50W) to lower potassium by 0.5-1.2 mEq/L within 30-60 minutes, with effects lasting 4-6 hours. 1 Never give insulin without glucose—hypoglycemia can be fatal. 1 Monitor blood glucose closely, as patients with low baseline glucose, no diabetes history, female sex, or altered renal function are at higher risk of hypoglycemia. 1

The dose can be repeated every 4-6 hours if hyperkalemia persists, with careful monitoring of potassium and glucose levels every 2-4 hours. 1 Verify that potassium is not below 3.3 mEq/L before administering insulin. 1

Beta-Agonist Therapy

Deliver nebulized albuterol 10-20 mg in 4 mL over 10-15 minutes to lower potassium by 0.5-1.0 mEq/L within 30 minutes, with duration of 2-4 hours. 1 This can be repeated every 2 hours if needed. 1 The combination of insulin-glucose plus albuterol produces greater potassium reduction than either agent alone. 1

Sodium Bicarbonate (ONLY with Metabolic Acidosis)

Administer 50 mEq IV over 5 minutes ONLY when arterial pH <7.35 and bicarbonate <22 mEq/L. 1 Sodium bicarbonate is ineffective without documented acidosis and should not be used as monotherapy for hyperkalemia. 1 The onset of action is slower (30-60 minutes) compared with insulin or beta-agonists. 1

Common pitfall: Do not use sodium bicarbonate without documented metabolic acidosis—it wastes time and provides no benefit. 1

Step 3: Definitive Potassium Removal (Within Hours)

Hemodialysis (Most Effective)

Hemodialysis is the most reliable and effective method for severe hyperkalemia, especially in patients with oliguria, end-stage renal disease, or refractory hyperkalemia despite medical management. 1 Absolute indications include:

• Serum potassium >6.5 mEq/L unresponsive to medical therapy 1
• Oliguria or anuria 1
• End-stage renal disease 1
• Ongoing potassium release (tumor lysis syndrome, rhabdomyolysis) 1
• Severe renal impairment (eGFR <15 mL/min) 1
• Persistent ECG changes despite medical management 1

In hemodynamically unstable patients, continuous renal replacement therapy (CRRT) is preferred over intermittent hemodialysis to minimize rapid fluid shifts and reduce intradialytic hypotension risk. 1

Monitor for rebound hyperkalemia within 4-6 hours post-dialysis as intracellular potassium redistributes to the extracellular space. 1 Check potassium levels every 2-4 hours initially in patients with severe initial hyperkalemia (>6.5 mEq/L) or ongoing potassium release. 1

Loop Diuretics (Renal Function Dependent)

Use IV furosemide 40-80 mg to increase renal potassium excretion in non-oliguric patients with eGFR >30 mL/min and adequate urine output. 1 Titrate to maintain euvolemia, not primarily for potassium management. 1

Potassium Binders (Subacute Management)

Sodium zirconium cyclosilicate (SZC/Lokelma) is preferred for urgent scenarios with onset of action in approximately 1 hour. 1, 5 For initial treatment, give 10g three times daily for 48 hours, then 5-15g once daily for maintenance. 1, 5 SZC reduces serum potassium within 1 hour of a single 10g dose. 1

Patiromer (Veltassa) has a slower onset (~7 hours) and is reserved for subacute or chronic management. 1 Start with 8.4g once daily with food, titrated up to 25.2g daily based on potassium levels. 1 Separate administration from other oral medications by at least 3 hours. 1

Avoid sodium polystyrene sulfonate (Kayexalate) due to delayed onset, limited efficacy data, and serious risk of bowel necrosis and colonic ischemia. 1, 6 It should not be used for acute management. 1

Step 4: Medication Management During Acute Episode

Hold the following medications immediately when potassium >6.5 mEq/L:

• RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists) 1
• NSAIDs 1
• Potassium-sparing diuretics 1
• Trimethoprim-containing agents 1
• Heparin 1
• Beta-blockers 1
• Potassium supplements and salt substitutes 1

After acute resolution, restart RAAS inhibitors at a lower dose once potassium <5.0 mEq/L. 1 Initiate a potassium binder (SZC or patiromer) to enable continuation of life-saving RAAS therapy, as these medications provide mortality benefit in cardiovascular and renal disease. 1

Chronic Hyperkalemia Management

For patients on RAAS inhibitors with potassium 5.0-6.5 mEq/L, initiate an approved potassium-lowering agent (patiromer or SZC) and maintain RAAS inhibitor therapy unless an alternative treatable etiology is identified. 1 Do not permanently discontinue RAAS inhibitors—use potassium binders to maintain these life-saving medications. 1

For patients with potassium >6.5 mEq/L, discontinue or reduce RAAS inhibitor temporarily and initiate a potassium binder when levels >5.0 mEq/L. 1

Monitoring Protocol

• Check potassium within 1 week of starting or escalating RAAS inhibitors 1
• Reassess 7-10 days after initiating potassium binder therapy 1
• Individualize monitoring frequency based on eGFR, heart failure, diabetes, or history of hyperkalemia 1
• For patients with advanced CKD (stage 4-5), the optimal potassium range is broader (3.3-5.5 mEq/L), but maintaining 4.0-5.0 mEq/L minimizes mortality risk 1

Dietary Management

Limit foods rich in bioavailable potassium, especially processed foods. 1 Avoid salt substitutes containing potassium and herbal supplements that raise potassium (alfalfa, dandelion, horsetail, nettle). 1 Evidence linking dietary potassium intake to serum levels is limited, and a potassium-rich diet has multiple health benefits, so dietary restriction should be approached cautiously. 1

Critical Pitfalls to Avoid

1. Do not delay calcium administration while awaiting repeat potassium levels when ECG changes are present 1
2. Never give insulin without glucose—hypoglycemia can be fatal 1
3. Do not rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 1
4. Do not use sodium bicarbonate without documented metabolic acidosis—it is ineffective and wastes time 1
5. Remember that calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 1
6. Do not permanently discontinue RAAS inhibitors—use potassium binders to maintain these agents 1

Special Populations

Diabetic Ketoacidosis

Add 20-30 mEq potassium (2/3 KCl and 1/3 KPO4) to each liter of IV fluid once potassium falls below 5.5 mEq/L with adequate urine output. 7 Delay insulin therapy if potassium <3.3 mEq/L until potassium is restored. 7

Tumor Lysis Syndrome

For symptomatic patients with potassium >7.0-7.5 mEq/L or widened QRS complex, use rapid-acting insulin (0.1 U/kg IV) with glucose (25% dextrose 2 mL/kg), sodium bicarbonate (1-2 mEq/kg IV push), and calcium gluconate (100-200 mg/kg/dose) via slow infusion with ECG monitoring. 4 Do not administer sodium bicarbonate and calcium through the same line. 4

Hemodialysis Patients

For chronic management, use sodium zirconium cyclosilicate 5g once daily on non-dialysis days, adjusting weekly in 5g increments based on predialysis potassium measurements to maintain 4.0-5.0 mEq/L. 1 Patiromer is an alternative at 8.4g once daily with food, separated from other medications by 3 hours. 1 Target predialysis potassium of 4.0-5.5 mEq/L to minimize mortality risk. 1