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 through improved glomerular filtration. Saline also blocks calcium reabsorption in the proximal tubule by inhibiting the sodium-calcium co-transporter. Only after adequate hydration has been established should other treatments like furosemide (which enhances calcium excretion), calcitonin (which inhibits bone resorption), bisphosphonates, or other medications be considered. Initiating treatment with medications other than saline could worsen dehydration and potentially lead to acute kidney injury, further complicating the hypercalcemic state. According to the NCCN guidelines 1, hydration is a crucial step in the management of hypercalcemia, and the use of bisphosphonates, steroids, and/or calcitonin is also recommended. However, the most recent and highest quality study 1 prioritizes hydration as the initial step, making intravenous saline the most appropriate choice.

Some key points to consider in the management of hypercalcemic crisis include:

• Aggressive volume expansion with isotonic saline
• Adjusting the rate of saline administration based on the patient's cardiovascular status
• Using furosemide, calcitonin, bisphosphonates, or other medications only after adequate hydration has been established
• Monitoring for potential complications such as acute kidney injury
• Considering the use of bisphosphonates, steroids, and/or calcitonin as recommended by the NCCN guidelines 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 inhibit osteoclastic bone resorption.

• Rehydration is crucial:
  • The use of intravenous normal saline is emphasized as the mainstay of therapy to restore fluid volume and enhance calcium excretion 3, 4, 5.
  • This approach is supported by the need to correct dehydration, which is a common complication of hypercalcemia.
• Other initial management strategies include:
  • The administration of loop diuretics like furosemide to increase calcium excretion once the patient is rehydrated 6, 4.
  • The use of calcitonin, which can help lower calcium levels quickly, although its use may be limited by tachyphylaxis 3, 6, 4.
  • Bisphosphonates are considered a cornerstone in the treatment of hypercalcemia, especially for long-term management, but their onset of action is slower compared to calcitonin 6, 7.
  • Glucocorticoids may be used in specific cases, such as vitamin D intoxication or granulomatous disorders 7.

Choice of Initial Intravenous Therapy

Given the options provided:

• Saline (c) is the correct initial intravenous therapy for hypercalcemic crisis, as it addresses dehydration and helps in enhancing renal excretion of calcium.
• Other options, while potentially part of the management plan, are not the initial step:
  • Steroids (a) may be used in specific scenarios but are not the first line.
  • Calcitonin (b) is effective but typically used after or alongside rehydration.
  • Furosemide (d) is used to enhance diuresis but only after adequate rehydration.
  • Mithramycin (e) is an older agent with significant side effects and is rarely used today.