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 initial treatment being hydration with intravenous normal saline at 200-300 mL/hour, followed by loop diuretics and other therapies as needed, as recommended by the NCCN guidelines 1.

Treatment Approach

The treatment of hypercalcemia depends on its severity and underlying cause. For mild hypercalcemia, adequate hydration with oral fluids may be sufficient. However, for moderate to severe hypercalcemia, more aggressive treatment is required.

• Intravenous normal saline at 200-300 mL/hour is the initial treatment to increase calcium excretion.
• Loop diuretics like furosemide 20-40 mg IV can be used after rehydration to further enhance calcium elimination.
• Bisphosphonates such as zoledronic acid 4 mg IV or pamidronate 60-90 mg IV are effective for hypercalcemia related to malignancy or bone resorption, with effects lasting 2-4 weeks.
• Calcitonin 4-8 IU/kg subcutaneously every 12 hours provides rapid but short-term calcium reduction.
• For severe cases, hemodialysis may be necessary.
• Cinacalcet 30-90 mg daily can help in hyperparathyroidism.

Monitoring and Definitive Treatment

Ongoing monitoring of calcium levels, renal function, and electrolytes is essential during treatment, as aggressive fluid administration can cause electrolyte imbalances and volume overload in patients with heart or kidney disease. The definitive treatment addresses the underlying cause, such as parathyroidectomy for primary hyperparathyroidism or treating malignancy, as supported by the Kidney Disease: Improving Global Outcomes 2017 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 of hypercalciemia should be started with hydration 3, 4, 5, 6, 7.
• Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 3, 5, 6.
• Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia 3, 4, 5.
• For long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonate is typically required 3, 4, 5, 6, 7.
• Among intravenous bisphosphonates, zoledronic acid or pamidronate are the agents of choice 3, 4, 5, 6, 7.
• Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases 3, 4, 5, 6.
• Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure 3, 5, 6.

Treatment Options

The following treatment options are available for hypercalciemia:

• Hydration and loop diuretics for mild cases 3, 5, 6
• Calcitonin and bisphosphonates for severe cases 3, 4, 5, 6, 7
• Glucocorticoids for hypercalcemia due to lymphoma or granulomatous diseases 3, 4, 5, 6
• Dialysis for severe hypercalcemia with kidney failure 3, 5, 6
• Parathyroidectomy for primary hyperparathyroidism 6

Underlying Cause

The underlying cause of hypercalcemia should be identified and treated:

• Primary hyperparathyroidism: parathyroidectomy or observation with monitoring 6
• Malignancy: anti-tumor therapy 5, 6
• Granulomatous diseases: glucocorticoids 3, 4, 5, 6
• Other causes: treatment of the underlying condition 5, 6