What is the treatment protocol for inpatient hyperkalemia?

Inpatient Hyperkalemia Treatment Protocol

For severe hyperkalemia (≥6.5 mEq/L) or any ECG changes, immediately administer intravenous calcium for cardiac membrane stabilization, followed by insulin with glucose and nebulized beta-agonists to shift potassium intracellularly, then initiate definitive potassium removal strategies including loop diuretics or hemodialysis. 1, 2, 3

Severity Classification and Initial Assessment

• Mild hyperkalemia: 5.0-5.9 mEq/L 1, 2, 3
• Moderate hyperkalemia: 6.0-6.4 mEq/L 1, 2, 3
• Severe hyperkalemia: ≥6.5 mEq/L (life-threatening emergency) 1, 2, 3

Critical first step: Exclude pseudohyperkalemia from hemolysis, repeated fist clenching, or improper phlebotomy technique by repeating the measurement with appropriate technique or arterial sampling before initiating aggressive treatment. 2, 3

ECG changes mandate urgent treatment regardless of potassium level, including peaked T waves, flattened P waves, prolonged PR interval, and widened QRS complexes. 1, 2, 3 However, ECG findings are highly variable and less sensitive than laboratory values—do not rely solely on ECG. 2

Step 1: Cardiac Membrane Stabilization (Immediate - Within 1-3 Minutes)

Calcium chloride is preferred over calcium gluconate because it provides a more rapid increase in ionized calcium concentration, making it more effective in critically ill patients. 1, 3

• Calcium chloride (10%): 5-10 mL (500-1000 mg) IV over 2-5 minutes 1, 3
• Alternative - Calcium gluconate (10%): 15-30 mL IV over 2-5 minutes 1, 3

Key considerations:

• Effects begin within 1-3 minutes but are temporary (30-60 minutes) 1, 2, 3
• Calcium does NOT lower serum potassium—it only protects against arrhythmias 1, 3
• Administer through central venous catheter when possible, as extravasation through peripheral IV may cause severe skin and soft tissue injury 1
• Monitor heart rate during administration and stop if symptomatic bradycardia occurs 1

Step 2: Shift Potassium Into Cells (Onset 15-30 Minutes, Duration 4-6 Hours)

Administer all three therapies simultaneously for maximum effect:

Insulin with Glucose (Most Effective)

• Standard dose: 10 units regular insulin IV with 25g glucose (50 mL of D50W) over 15-30 minutes 1, 2, 3
• Can be repeated every 4-6 hours if hyperkalemia persists or recurs 2
• Monitor serum potassium and glucose every 2-4 hours after administration 2
• Critical: Verify potassium is not below 3.3 mEq/L before administering insulin 2
• High-risk patients for hypoglycemia: low baseline glucose, no diabetes history, female sex, altered renal function 2

Nebulized Beta-2 Agonists

• Albuterol: 10-20 mg nebulized over 15 minutes 1, 2, 3
• Reduces serum potassium by approximately 0.5-1.0 mEq/L 1, 3
• Effects last 4-6 hours 1, 3

Sodium Bicarbonate (ONLY if Metabolic Acidosis Present)

• Indication: Use ONLY in patients with concurrent metabolic acidosis (pH < 7.35, bicarbonate < 22 mEq/L) 1, 2
• Dose: 50 mEq IV over 5 minutes 1
• Effects take 30-60 minutes to manifest 2
• Do NOT use in patients without metabolic acidosis—it is only indicated when acidosis is present 2

Critical warning: These measures provide only transient effects (1-4 hours), and rebound hyperkalemia can occur after 2 hours. 1 Definitive potassium removal must be initiated simultaneously.

Step 3: Eliminate Potassium From Body (Definitive Treatment)

For Patients with Adequate Renal Function

• Loop diuretics: Furosemide 40-80 mg IV to increase urinary potassium excretion 1, 2, 3
• Effective only in patients with adequate kidney function 1, 3

For Severe or Refractory Cases

• Hemodialysis is the most effective and reliable method for severe hyperkalemia, especially in patients with renal failure, oliguria, or cases unresponsive to medical management 1, 2, 3, 4

Potassium Binders (NOT for Emergency Use)

Sodium polystyrene sulfonate (Kayexalate) has significant limitations:

• FDA indication: Treatment of hyperkalemia, but NOT for emergency use due to delayed onset of action 5
• Dose: 15-50 g orally or rectally 1, 3, 5
• Major concerns: Never undergone rigorous placebo-controlled trials to prove efficacy and safety; prolonged use associated with severe gastrointestinal side effects including bowel necrosis 6
• Should be avoided for acute management 6

Newer potassium binders are safer alternatives:

• Patiromer (Veltassa) and sodium zirconium cyclosilicate (SZC/ZS-9) are FDA-approved, more effective, and safer than traditional cation exchange resins 6, 1, 3
• Both increase fecal potassium excretion and have been shown to normalize elevated potassium levels and prevent recurrences in patients on RAAS inhibitors 6

Management of Hyperkalemia in Patients on RAAS Inhibitors

The European Society of Cardiology provides specific guidance for maintaining life-saving RAAS inhibitor therapy 6, 2, 3:

Potassium 5.0-6.5 mEq/L on RAAS Inhibitors

• Initiate approved potassium-lowering agent (patiromer or SZC) 6, 2, 3
• Maintain RAAS inhibitor therapy unless alternative treatable etiology identified 6, 2, 3
• Monitor potassium levels closely 6, 2, 3
• If not on maximal tolerated dose, up-titrate RAAS inhibitor once potassium <5.0 mEq/L 6

Potassium >6.5 mEq/L on RAAS Inhibitors

• Discontinue or reduce RAAS inhibitor temporarily 6, 2, 3
• Initiate potassium-lowering agent when levels >5.0 mEq/L 6, 2, 3
• Monitor potassium levels closely 6, 2, 3

Rationale: In patients with cardiovascular disease on RAAS inhibitors, maintaining these life-saving medications by using potassium binders is preferable to discontinuing therapy, as RAAS inhibitors reduce mortality and morbidity. 6, 2

Monitoring Protocol

• Check potassium within 1 week of starting or escalating RAAS inhibitors 2
• Reassess potassium 7-10 days after starting or increasing RAAS inhibitor doses 2
• More frequent monitoring required in high-risk patients with history of hyperkalemia, chronic kidney disease, diabetes, or heart failure 2
• After acute treatment: Monitor potassium every 2-4 hours initially 2

Common Pitfalls to Avoid

• Do not rely solely on ECG findings—they are highly variable and less sensitive than laboratory tests 2
• Do not use sodium bicarbonate without metabolic acidosis—it is only indicated when acidosis is present 2
• Always administer glucose with insulin to prevent hypoglycemia 2
• Remember that calcium, insulin, and beta-agonists do not remove potassium—they only temporize, requiring definitive removal strategies 2
• Do not use sodium polystyrene sulfonate for emergency treatment due to delayed onset and risk of bowel necrosis 6, 5
• Avoid down-titration or discontinuation of RAAS inhibitors when possible, as these drugs improve outcomes in heart failure and proteinuric kidney disease 4

Medication Review

Identify and address contributing medications 2:

• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists
• NSAIDs
• Beta-blockers
• Potassium-sparing diuretics
• Trimethoprim, pentamidine
• Heparin

Team Approach

Optimal management involves cardiologists, nephrologists, primary care physicians, nurses, pharmacists, social workers, and dietitians working collaboratively. 2