How to manage hypercalcemia?

Management of Hypercalcemia

The most effective approach to bringing down blood calcium levels is to start with aggressive IV fluid resuscitation with normal saline, followed by bisphosphonate therapy, with zoledronic acid 4 mg IV over 15 minutes being the preferred first-line treatment. 1

Initial Assessment and Stabilization

• Calculate corrected calcium: Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] to accurately diagnose and monitor hypercalcemia 1
• Obtain laboratory evaluation including:
  • Complete blood count
  • Urinalysis
  • Thyroid-stimulating hormone (TSH)
  • Liver function tests
  • Serum concentrations of intact parathyroid hormone (iPTH)
  • Parathyroid hormone-related protein (PTHrP)
  • Vitamin D metabolites
  • Calcium, albumin, magnesium, and phosphorus 1

Treatment Algorithm

1. Aggressive Hydration

• Administer IV normal saline at 200-300 mL/hour initially 1
• Target urine output >3 L/day 1
• Continue hydration until patient is euvolemic and hypercalcemia improves

2. Bisphosphonate Therapy

• Zoledronic acid 4 mg IV over 15 minutes is the preferred first-line treatment due to:
  • Higher complete response rate
  • Longer duration of action compared to other bisphosphonates 1
• Important safety note: Administration of zoledronic acid over 5 minutes increases risk of renal toxicity; always administer over 15 minutes 2
• Adjust dosing based on creatinine clearance to minimize renal toxicity 1

3. Additional Pharmacologic Options

• For immediate short-term management of severe symptomatic hypercalcemia:

  • Calcitonin provides rapid but short-lived effect 1, 3
  • Can be combined with bisphosphonates for enhanced effect 4

• For refractory hypercalcemia or in patients with severe renal impairment:

  • Denosumab is recommended over bisphosphonates 1, 5

• For specific causes:

  • Glucocorticoids for vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 3
  • Loop diuretics to enhance calcium excretion, but only after adequate hydration 1

Special Considerations

Renal Function

• Avoid nephrotoxic drugs in patients with renal impairment 1
• Consider plasma exchange in patients with rapidly progressive renal failure 1
• For patients with kidney failure, denosumab and dialysis may be indicated 6

Medication-Induced Hypercalcemia

• Discontinue offending agents such as:
  • Thiazide diuretics
  • Calcium supplements
  • Vitamin D or A supplements 1

Monitoring

• Regularly assess serum calcium, phosphate, magnesium, and renal function 1
• Monitor for hypocalcemia after treatment, especially with denosumab 1
• For patients with cardiac disease, optimize heart failure management 1

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia 1
• Failing to correct calcium for albumin 1
• Inadequate hydration before bisphosphonate administration 1
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia 1
• Administering bisphosphonates too rapidly (increases renal toxicity) 1, 2
• Failing to monitor for hypocalcemia after treatment 1

By following this structured approach, hypercalcemia can be effectively managed while addressing the underlying cause and minimizing complications.