What is the stepwise management of hypercalcemia?

Stepwise Management of Hypercalcemia

The management of hypercalcemia should follow a systematic approach based on severity, with initial hydration using normal saline followed by bisphosphonates (preferably zoledronic acid) for moderate to severe cases. 1

Assessment and Classification

• Severity classification:

  • Mild: >5.0 to <5.5 mEq/L (>10.0 to <11.0 mg/dL)
  • Moderate: 5.5 to 6.0 mEq/L (11.0 to 12.0 mg/dL)
  • Severe: >6.0 mEq/L (>12.0 mg/dL or >3.0 mmol/L) 1, 2

• Diagnostic evaluation should include:

  • Serum calcium (ionized if available)
  • Intact PTH, PTHrP
  • 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D
  • Albumin (for corrected calcium calculation)
  • Magnesium and phosphorus levels 1

Step 1: Hydration

• Mild hypercalcemia: Oral hydration may be effective 1

• Moderate to severe hypercalcemia:

  • Rehydrate with IV crystalloid fluids (normal saline) not containing calcium
  • Target: Restore extracellular volume and improve renal calcium excretion
  • Rate: Typically 200-300 mL/hour initially, adjusted based on cardiovascular status 1
  • Continue until patient is euvolemic 2

Step 2: Loop Diuretics

• Administer only after correction of intravascular volume (never in dehydrated patients)
• Furosemide: Promotes calciuresis
• Dosing: As needed based on volume status
• Monitor: Electrolytes (especially potassium and magnesium) 1

Step 3: Bisphosphonates

• First-line pharmacologic therapy for moderate to severe hypercalcemia
• Preferred agent: Zoledronic acid 4 mg IV over 15 minutes 1
  • Reserve 8 mg dose for relapsed or refractory cases 1
• Alternative: Pamidronate 90 mg IV over 2 hours 1, 3
• Onset: 24-48 hours
• Duration: 2-4 weeks
• Monitor renal function before and during treatment 1
• Contraindicated in severe renal impairment 3

Step 4: Additional Therapies for Refractory Cases

• Calcitonin:

  • Rapid onset (2-4 hours) but short duration
  • Dose: 4-8 IU/kg SC/IM every 6-12 hours
  • Useful as adjunct while waiting for bisphosphonates to take effect
  • Tachyphylaxis limits use beyond 48-72 hours 4, 5

• Denosumab:

  • For bisphosphonate-refractory hypercalcemia
  • Particularly useful in renal impairment
  • Dose: 120 mg SC
  • Monitor for hypocalcemia after treatment 1

• Glucocorticoids:

  • Effective primarily for hypercalcemia due to:
    • Vitamin D intoxication
    • Granulomatous disorders (sarcoidosis)
    • Some lymphomas
  • Dose: Prednisone 40-60 mg/day 1, 4

• Dialysis:

  • Reserved for severe hypercalcemia with renal failure
  • Use calcium-free or low-calcium dialysate 4, 5

Special Considerations

• Malignancy-related hypercalcemia:

  • Most common in squamous cell lung cancer and multiple myeloma
  • Poorer prognosis (median survival ~1 month after discovery) 1
  • More aggressive hydration and earlier bisphosphonate use recommended

• Monitoring:

  • Serum calcium: Daily until normalized, then weekly
  • Renal function: Before and during bisphosphonate therapy
  • Hydration status: Continuously during IV fluid administration

• Common pitfalls:

  • Administering loop diuretics before adequate hydration
  • Delaying bisphosphonate therapy (should be started early)
  • Failing to monitor for renal dysfunction with bisphosphonates
  • Overlooking magnesium deficiency which can worsen hypercalcemia
  • Not addressing the underlying cause 6, 5

Remember that definitive treatment requires addressing the underlying cause of hypercalcemia, particularly in malignancy-related cases where treating the primary disease is essential for long-term control.