What is the protocol for managing hypercalcemia?

From the Guidelines

Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate option. The management of hypercalcemia depends on its severity and underlying cause. For mild hypercalcemia, adequate hydration and treating the underlying cause may be sufficient. For moderate to severe hypercalcemia, aggressive IV fluid resuscitation with normal saline at 200-300 mL/hour should be initiated to promote calcium excretion, followed by loop diuretics like furosemide 20-40 mg IV after adequate hydration to enhance calcium excretion.

• Bisphosphonates, such as zoledronic acid 4 mg IV over 15 minutes, are first-line medications for hypercalcemia of malignancy, as recommended by the NCCN guidelines 1.
• Calcitonin can provide rapid but short-term calcium reduction at 4 IU/kg SC/IM every 12 hours.
• For refractory cases, consider denosumab 120 mg SC, glucocorticoids (prednisone 40-60 mg daily for 10 days), or dialysis for severe cases with renal failure.
• Ongoing management should include monitoring serum calcium, phosphate, and renal function every 6-12 hours initially, addressing the underlying cause, maintaining hydration, and restricting dietary calcium. The NCCN guidelines also recommend careful assessment of fluid status to avoid hypervolemia, especially in patients with oliguria renal failure 1. Additionally, institutions differ in their use of plasmapheresis for adjunctive treatment of renal dysfunction, and erythropoietin therapy may be considered for anemic patients, especially those with renal failure 1.

From the FDA Drug Label

In humoral hypercalcemia, osteoclasts are activated and bone resorption is stimulated by factors such as parathyroid hormone-related protein, which are elaborated by the tumor and circulate systemically. Reducing excessive bone resorption and maintaining adequate fluid administration are, therefore, essential to the management of hypercalcemia of malignancy Patients who have hypercalcemia of malignancy can generally be divided into two groups according to the pathophysiologic mechanism involved: humoral hypercalcemia and hypercalcemia due to tumor invasion of bone

The hypercalcemia protocol involves reducing excessive bone resorption and maintaining adequate fluid administration.

• Key steps in managing hypercalcemia of malignancy include:
  • Reducing bone resorption
  • Maintaining adequate fluid administration
• Types of hypercalcemia include:
  • Humoral hypercalcemia
  • Hypercalcemia due to tumor invasion of bone 2

From the Research

Hypercalcemia Protocol

• Hypercalcemia is a condition that affects approximately 1% of the worldwide population, with mild hypercalcemia being usually asymptomatic, but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people 3.
• Severe hypercalcemia can cause nausea, vomiting, dehydration, confusion, somnolence, and coma, and is typically treated with hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 4.
• The underlying cause of hypercalcemia should be identified and treated, with primary hyperparathyroidism (PHPT) and malignancy being responsible for greater than 90% of all cases of hypercalcemia 3, 4.

Diagnosis and Treatment

• Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, distinguishing PTH-dependent from PTH-independent causes 3.
• In patients with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level indicates another cause 3.
• Treatment of hypercalcemia should be started with hydration, and loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 4.
• Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia, and for long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonate is typically required 4.
• Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases, and dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure 4.

Management of Severe Hypercalcaemia

• Severe hypercalcaemia is a life-threatening condition that should be managed urgently, with saline hydration, furosemide, and zoledronic acid being commonly used therapeutic agents 5.
• However, the use of furosemide in the management of hypercalcemia is not recommended, as there is limited evidence to support its effectiveness, and bisphosphonates are a more effective treatment option 6.
• Zoledronic acid has been shown to be more potent than saline hydration and furosemide in reducing serum calcium levels in patients with severe hypercalcaemia secondary to PHPT 5.