How do I treat a patient with hypercalcemia?

Treatment of Hypercalcemia (Calcium 11.1 mg/dL) in a Skilled Nursing Facility

For a calcium level of 11.1 mg/dL in a skilled nursing facility, initiate IV normal saline hydration targeting urine output of 100-150 mL/hour, while simultaneously investigating the underlying cause by measuring intact PTH, and consider bisphosphonate therapy (zoledronic acid 4 mg IV over 15 minutes) if the patient is symptomatic or if the hypercalcemia persists despite hydration. 1

Initial Assessment and Diagnostic Workup

Before initiating treatment, obtain the following laboratory tests to determine the underlying etiology:

• Measure intact parathyroid hormone (iPTH) - this is the single most important test to distinguish PTH-dependent causes (primary hyperparathyroidism) from PTH-independent causes (malignancy, other) 1, 2
• Check albumin level to calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 [4 - Serum albumin (g/dL)] 3
• Measure serum creatinine, phosphorus, magnesium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D 1
• If PTH is suppressed (<20 pg/mL), check PTHrP to evaluate for malignancy-associated hypercalcemia 1, 2
• Obtain medication history specifically for thiazide diuretics, lithium, calcium supplements (>500 mg/day), and vitamin D supplements (>400 IU/day) 1

Important caveat: Measure ionized calcium if available to avoid pseudo-hypercalcemia from hemolysis or improper sampling 1

Treatment Algorithm

Step 1: Hydration (First-Line for All Patients)

• Administer IV normal saline aggressively to correct hypovolemia and promote calciuresis, targeting urine output of 100-150 mL/hour 1
• Vigorous saline hydration should be initiated promptly with an attempt to restore urine output to about 2 L/day 4, 5
• Monitor fluid status carefully to avoid overhydration, especially in patients with cardiac or renal insufficiency 1, 4
• Loop diuretics (furosemide) should only be used after volume repletion in patients with cardiac or renal insufficiency to prevent fluid overload - never before correcting hypovolemia 1, 5

Step 2: Bisphosphonate Therapy

For a calcium of 11.1 mg/dL, bisphosphonate therapy should be considered based on symptoms and response to hydration:

• Zoledronic acid 4 mg IV infused over no less than 15 minutes is the preferred bisphosphonate due to superior efficacy compared to pamidronate 1, 4, 2
• Alternative: Pamidronate IV if zoledronic acid is unavailable 1, 5
• Check serum creatinine before administration - dose adjustments are required for creatinine clearance <60 mL/min 4
• For CrCl 50-60 mL/min: reduce dose to 3.5 mg; for CrCl 40-49 mL/min: 3.3 mg; for CrCl 30-39 mL/min: 3.0 mg 4
• Do not use in severe renal impairment (CrCl <30 mL/min) - consider dialysis instead 1, 4

Timing consideration: Bisphosphonates take 2-4 days to achieve maximal effect, so they should be administered early even though the hypocalcemic action is delayed 6, 2

Step 3: Adjunctive Therapies (If Needed)

• Calcitonin 100 IU subcutaneously or intramuscularly provides rapid onset of action within hours but has limited efficacy and can be used as a bridge until bisphosphonates take effect 1, 7
• Corticosteroids (prednisone 1 mg/kg/day orally) are effective for hypercalcemia due to excessive intestinal calcium absorption, including vitamin D intoxication, granulomatous diseases (sarcoidosis), some lymphomas, and multiple myeloma 1, 2

Step 4: Monitoring and Follow-up

• Monitor serum calcium, renal function (creatinine), and electrolytes (potassium, magnesium) regularly to assess treatment effectiveness 1
• Correct any electrolyte deficiencies, particularly potassium and magnesium, as these play a role in the genesis of hypercalcemia 6
• If serum calcium does not normalize after initial bisphosphonate treatment, retreatment may be considered after a minimum of 7 days 4
• Renal function must be carefully monitored before each dose, and treatment should be withheld if renal deterioration occurs (increase of 0.5 mg/dL in normal baseline creatinine or 1.0 mg/dL in abnormal baseline) 4

Etiology-Specific Considerations

If Primary Hyperparathyroidism (Elevated or Normal PTH):

• For asymptomatic patients >50 years with calcium <1 mg above upper normal limit and no skeletal or kidney disease, observation may be appropriate 2
• Parathyroidectomy should be considered for younger patients, higher calcium levels, or evidence of skeletal/kidney involvement 2

If Malignancy-Associated (Suppressed PTH):

• Treat the underlying cancer when possible, as hypercalcemia of malignancy carries poor prognosis with median survival of approximately 1 month 1
• Continue bisphosphonate therapy for up to 2 years in patients with multiple myeloma or bone metastases 1

If Chronic Kidney Disease:

• Restrict calcium-based phosphate binders to avoid worsening hypercalcemia 1
• Consider hemodialysis with calcium-free or low-calcium dialysate for severe hypercalcemia complicated by renal insufficiency 1, 7

Critical Pitfalls to Avoid

• Never use loop diuretics before correcting hypovolemia - this worsens volume contraction and can paradoxically increase calcium 5, 6
• Do not exceed 4 mg dose of zoledronic acid - higher doses increase renal toxicity risk 4
• Avoid NSAIDs and IV contrast media in patients with renal impairment to prevent further kidney damage 1
• Do not restrict calcium intake excessively without medical supervision, as this can worsen bone disease in CKD patients 1
• Correct hypocalcemia before initiating bisphosphonate therapy and supplement with oral calcium 500 mg plus vitamin D 400 IU daily during treatment 1, 4
• Avoid sedatives and narcotic analgesics when possible, as they reduce activity and oral intake, potentially raising serum calcium 6

Special Considerations for Skilled Nursing Facility

• Encourage mobilization - getting patients out of bed to stand or walk reduces bone resorption 6
• Ensure adequate oral intake to prevent volume contraction 6
• Monitor for symptoms including polyuria, polydipsia, nausea, confusion, vomiting, and mental status changes 1