What is the composition of the hyperkalemia cocktail for a patient with acute kidney injury (AKI) and hyperkalemia?

The Hyperkalemia Cocktail

The "hyperkalemia cocktail" refers to the combination of intravenous calcium gluconate, insulin with glucose, and nebulized albuterol administered together for acute severe hyperkalemia (>6.5 mEq/L or with ECG changes). This three-drug regimen works through complementary mechanisms: calcium stabilizes cardiac membranes within 1-3 minutes, while insulin and albuterol shift potassium intracellularly within 15-30 minutes 1, 2.

Components and Dosing

1. IV Calcium Gluconate (First-Line)

• Administer 15-30 mL of 10% calcium gluconate IV over 2-5 minutes as the immediate priority when ECG changes are present (peaked T waves, widened QRS, prolonged PR interval) 1, 2.
• Onset of cardioprotective effects occurs within 1-3 minutes, but duration is only 30-60 minutes 1, 3.
• Critical caveat: Calcium does NOT lower serum potassium—it only temporarily stabilizes cardiac membranes 3, 2.
• If no ECG improvement within 5-10 minutes, repeat the dose of 15-30 mL IV over 2-5 minutes 1, 3.
• Continuous cardiac monitoring is mandatory during and after administration 3.

2. Insulin with Glucose (Intracellular Shift)

• Administer 10 units of regular insulin IV plus 25 grams dextrose (50 mL of 50% glucose) 2, 4.
• Redistributes potassium within 30-60 minutes with effects lasting 4-6 hours 1, 2.
• Never give insulin without glucose—hypoglycemia can be life-threatening 3.
• Monitor glucose levels closely, particularly in patients with low baseline glucose, no diabetes, female sex, or altered renal function 3.

3. Nebulized Albuterol (Adjunctive Intracellular Shift)

• Administer 10-20 mg albuterol in 4 mL via nebulizer 2, 4.
• Onset within 30 minutes with duration of 2-4 hours 3, 2.
• Produces comparable potassium-lowering effects to insulin-dextrose when used together 5.
• The maximal reduction is approximately 0.88-1.18 mEq/L occurring at 90-120 minutes 6, 5.

4. Sodium Bicarbonate (ONLY if Metabolic Acidosis Present)

• Administer 50 mEq IV over 5 minutes ONLY if concurrent metabolic acidosis is present (pH <7.35, bicarbonate <22 mEq/L) 1, 3, 2.
• Effects take 30-60 minutes to manifest 3.
• Do not use in patients without metabolic acidosis—it is ineffective and wastes time 3.
• Promotes potassium excretion through increased distal sodium delivery and counters acidosis-induced potassium release 1, 3.

Clinical Algorithm for Administration

Step 1: Verify Severity and ECG Changes

• Confirm hyperkalemia with ECG changes (peaked T waves, widened QRS, prolonged PR interval, or arrhythmias) 3.
• 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 3.

Step 2: Administer Calcium First

• Give 15-30 mL of 10% calcium gluconate IV over 2-5 minutes 2.
• Monitor ECG continuously for 5-10 minutes 3.
• If no improvement, give second dose of 15-30 mL IV over 2-5 minutes 3.

Step 3: Simultaneously Initiate Potassium-Lowering Therapies

• Give all three agents together for maximum effect: insulin 10 units regular IV + 25g dextrose, nebulized albuterol 10-20 mg in 4 mL, and sodium bicarbonate 50 mEq IV over 5 minutes ONLY if metabolic acidosis present 2, 4.
• This combination approach is favored as first choice among available options 4.

Step 4: Initiate Potassium Removal

• Choose method based on renal function and clinical context 3:
  • Loop diuretics (furosemide 40-80 mg IV) if adequate kidney function exists 3, 2
  • Newer potassium binders (patiromer or sodium zirconium cyclosilicate) for definitive treatment 2
  • Hemodialysis for severe cases unresponsive to medical management, oliguria, or end-stage renal disease 1, 3

Important Caveats

• Calcium, insulin, and beta-agonists are temporizing measures only—they do NOT remove potassium from the body 3, 2.
• Failure to initiate concurrent potassium-lowering therapies will result in recurrent life-threatening arrhythmias within 30-60 minutes 3.
• Never administer calcium through the same IV line as sodium bicarbonate—precipitation will occur 3.
• In patients with elevated phosphate levels, use calcium cautiously as it increases risk of calcium-phosphate precipitation in tissues 3.
• Beta-agonists can worsen hypokalemia after the acute episode resolves 7.

Medication Management During Acute Episode

• Temporarily discontinue or reduce RAAS inhibitors at K+ ≥6.5 mEq/L 3, 2.
• Review and hold: NSAIDs, potassium-sparing diuretics, trimethoprim, heparin, beta-blockers, potassium supplements, and salt substitutes 3, 2.

After Acute Resolution: Preventing Recurrence

• Initiate newer potassium binders (sodium zirconium cyclosilicate or patiromer) and restart RAAS inhibitors at lower dose once potassium <5.5 mEq/L, as they provide mortality benefit in cardiovascular and renal disease 3, 2.
• Monitor potassium levels every 2-4 hours during acute treatment phase until stabilized 7.