What is the initial step in managing hypercalcemic crisis: intravenous administration of steroids, calcitonin, saline, furosemide, or mithramycin (plicamycin)?

From the Guidelines

The initial step in management of a hypercalcemic crisis is intravenous saline (option c). When faced with a hypercalcemic crisis, aggressive volume expansion with isotonic saline should be started immediately at rates of 200-300 mL/hour, adjusted based on the patient's cardiovascular status. This approach works because most patients with hypercalcemia are volume depleted, and rehydration helps dilute serum calcium levels while increasing renal calcium excretion. Saline infusion enhances calcium clearance by inhibiting calcium reabsorption in the proximal tubule and loop of Henle. Only after adequate rehydration should other therapies like furosemide (which promotes calciuresis), calcitonin (which inhibits bone resorption), bisphosphonates, or other agents be considered. While steroids and mithramycin may be useful in specific causes of hypercalcemia, they are not the first-line treatment for the acute management of hypercalcemic crisis. Careful monitoring of fluid status, electrolytes, and renal function is essential during treatment, as highlighted in the NCCN guidelines 1.

Key points to consider in the management of hypercalcemic crisis include:

• Aggressive hydration with intravenous saline to correct volume depletion and enhance renal calcium excretion
• Monitoring of fluid status, electrolytes, and renal function to avoid complications
• Consideration of other therapies such as furosemide, calcitonin, and bisphosphonates after adequate rehydration
• Avoidance of nephrotoxic medications and correction of metabolic abnormalities, as recommended in the NCCN guidelines 1
• The use of bisphosphonates, such as zoledronic acid, which is preferred by the NCCN MM Panel members for the treatment of hypercalcemia 1

From the FDA Drug Label

1. 2 Treatment of Hypercalcemia Calcitonin-salmon injection is indicated for the early treatment of hypercalcemic emergencies, along with other appropriate agents, when a rapid decrease in serum calcium is required, until more specific treatment of the underlying disease can be accomplished It may also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents.

The initial step in management of a hypercalcemic crisis is intravenous saline, as it is mentioned that calcitonin-salmon injection may be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids.

• The use of calcitonin is recommended for the early treatment of hypercalcemic emergencies, but it is not the initial step.
• Intravenous fluids, specifically saline, is the initial step in managing hypercalcemic crisis. 2

From the Research

Initial Management of Hypercalcemic Crisis

The initial step in managing a hypercalcemic crisis involves several key interventions. The primary goal is to restore normovolemia, enhance renal excretion of calcium, and reduce calcium levels.

• The first step is to administer intravenous saline to restore fluid volume and enhance renal function 3, 4, 5, 6, 7.
• Other treatment options, such as calcitonin, bisphosphonates, glucocorticoids, and loop diuretics, may be considered in addition to saline therapy 3, 4, 5, 6, 7.
• Furosemide may be used to enhance calcium excretion, but it is not the initial step in management 4, 5.
• Mithramycin is rarely used due to its potential toxicity 4.
• Steroids may be used in specific cases, such as vitamin D intoxication or granulomatous disorders 6.

Key Considerations

It is essential to identify and treat the underlying cause of hypercalcemia, whether it be primary hyperparathyroidism, malignancy, or another condition 3, 4, 5, 6, 7.

• Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation may be considered for refractory hypercalcemic crises 3, 7.
• The choice of treatment depends on the severity of hypercalcemia, the presence of acute kidney injury, and the underlying cause of hypercalcemia 4, 5, 6, 7.