What is the management for severe hypercalcemia?

Management of Severe Hypercalcemia (Calcium > 14 mg/dL)

The initial management of severe hypercalcemia requires aggressive IV fluid resuscitation with normal saline (200-300 mL/hour initially), followed by bisphosphonates as first-line pharmacological intervention. 1

Initial Emergency Management

1. Aggressive IV fluid resuscitation

   • Normal saline at 200-300 mL/hour initially
   • Target urine output > 3 L/day
   • Correct hypovolemia before using diuretics

2. First-line pharmacological therapy

   • Bisphosphonates: Zoledronic acid 4 mg IV over 15 minutes (preferred)
   • Alternative: Pamidronate IV if zoledronic acid unavailable

3. Immediate short-term management for symptomatic patients

   • Calcitonin can be used for rapid but temporary calcium reduction 2
   • Particularly useful while waiting for bisphosphonates to take effect

4. Loop diuretics

   • Add furosemide after adequate hydration is achieved
   • Enhances calcium excretion

Monitoring and Additional Management

• Monitor serum calcium, phosphate, magnesium, renal function, and electrolytes regularly
• Correct electrolyte deficiencies, particularly potassium and magnesium
• Albumin-corrected calcium calculation: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1

Alternative and Adjunctive Therapies

• For renal impairment or refractory hypercalcemia:

  • Denosumab is preferred in patients with severe renal impairment 1
  • Consider dialysis with calcium-free dialysate for severe cases with renal failure 3

• For specific etiologies:

  • Glucocorticoids for vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 4
  • Cinacalcet for selected cases of primary hyperparathyroidism when surgery is not possible 5

• Surgical management:

  • Parathyroidectomy for tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism) 6
  • Consider imaging of parathyroid glands with 99 Tc-Sestamibi scan, ultrasound, CT scan, or MRI prior to re-exploration parathyroid surgery 6

Common Pitfalls to Avoid

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

Long-term Management

• Identify and treat the underlying cause (90% of cases are due to primary hyperparathyroidism or malignancy) 4
• For patients with primary hyperparathyroidism who were receiving phosphate binders prior to surgery, this therapy may need to be discontinued or reduced based on serum phosphorus levels 6
• When oral intake is possible after acute management, patients may receive calcium carbonate 1-2g three times daily and calcitriol up to 2g/day, adjusted to maintain normal ionized calcium levels 6

Remember that severe hypercalcemia (>14 mg/dL) is a medical emergency that requires prompt intervention to prevent serious complications including confusion, somnolence, and coma 4.