How do you correct hypercalcemia (elevated calcium levels)?

From the Guidelines

Hypercalcemia should be treated based on its severity, underlying cause, and symptoms, with the goal of reducing calcium levels and alleviating symptoms, as recommended by the NCCN guidelines 1.

Treatment Approach

For mild hypercalcemia (calcium <12 mg/dL), adequate hydration with oral fluids may be sufficient.

• For moderate to severe hypercalcemia, intravenous normal saline at 200-300 mL/hour is the initial treatment to increase calcium excretion through the kidneys.
• Once the patient is hydrated, loop diuretics like furosemide (20-40 mg IV every 2-4 hours) can be added to enhance calcium excretion.

Medications

• For severe or symptomatic hypercalcemia, bisphosphonates such as zoledronic acid (4 mg IV over 15 minutes) or pamidronate (60-90 mg IV over 2-4 hours) are effective by inhibiting bone resorption, with effects lasting several weeks.
• Calcitonin (4-8 IU/kg SC/IM every 12 hours) works rapidly but has short-lived effects.
• Denosumab (120 mg SC) may be used in renal impairment when bisphosphonates are contraindicated.
• Glucocorticoids like prednisone (40-60 mg daily) are particularly effective for hypercalcemia caused by certain malignancies or granulomatous diseases.
• Cinacalcet (30-90 mg daily) is useful for hyperparathyroidism.

Monitoring and Underlying Cause

Treating the underlying cause, such as surgical removal of parathyroid adenomas or addressing malignancy, is crucial for long-term management. Regular monitoring of serum calcium, renal function, and electrolytes is essential during treatment, as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline update 1.

From the FDA Drug Label

Vigorous saline hydration alone may be sufficient for treating mild, asymptomatic hypercalcemia. In hypercalcemia associated with hemotologic malignancies, the use of glucocorticoid therapy may be helpful. The recommended dose of pamidronate disodium in moderate hypercalcemia (corrected serum calcium* of approximately 12 to 13.5 mg/dL) is 60 to 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours. The recommended dose of pamidronate disodium in severe hypercalcemia (corrected serum calcium* >13.5 mg/dL) is 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours.

Correction of Hypercalcemia:

• Mild, asymptomatic hypercalcemia: Vigorous saline hydration alone may be sufficient.
• Hypercalcemia associated with hemotologic malignancies: Glucocorticoid therapy may be helpful.
• Moderate hypercalcemia (corrected serum calcium 12-13.5 mg/dL): Pamidronate disodium 60-90 mg IV infusion over 2-24 hours.
• Severe hypercalcemia (corrected serum calcium >13.5 mg/dL): Pamidronate disodium 90 mg IV infusion over 2-24 hours. 2

From the Research

Correction of Hypercalciemia

The correction of hypercalciemia involves several steps and treatments, depending on the underlying cause and severity of the condition.

• Treatment should be started with hydration, as stated in the study 3.
• Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload, as mentioned in 3.
• Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia, according to 3 and 4.
• For long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonate is typically required, as stated in 3 and 4.
• Among intravenous bisphosphonates, zoledronic acid or pamidronate are the agents of choice, as mentioned in 3 and 5.
• Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases, as stated in 3 and 5.
• Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure, according to 3 and 5.

Treatment Options

Different treatment options are available for hypercalciemia, including:

• Hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate, for initial therapy of symptomatic or severe hypercalcemia, as mentioned in 5 and 6.
• Denosumab and dialysis for patients with kidney failure, as stated in 5.
• Glucocorticoids as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption, according to 5.
• Parathyroidectomy or observation with monitoring for asymptomatic primary hyperparathyroidism, as mentioned in 5.

Efficacy of Therapeutic Agents

The efficacy of different therapeutic agents in managing severe hypercalcaemia secondary to primary hyperparathyroidism has been studied, with results showing:

• Saline hydration decreases calcium levels, but normalization of calcium level does not occur in any patient, as stated in 6.
• Furosemide does not have a significant additional effect on calcium levels when compared with the effect of saline hydration alone, according to 6.
• Zoledronic acid is more potent and results in normalization of calcium levels in 60% of patients, as mentioned in 6.