Treatment can provide marked improvement of distressing symptoms. Polyuria, polydipsia, central nervous system symptoms, nausea, vomiting, and constipation are more likely to be managed successfully than are anorexia, malaise, and fatigue. Pain control may be improved for some patients who achieve normocalcemia.[Level of evidence: III] Effective calcium-lowering therapy usually improves symptoms, enhances the quality of life, and may allow patients to be managed in a subacute, ambulatory, or home care setting.
After normocalcemia is achieved, serum calcium should be monitored serially, with the frequency determined by anticipated duration of response to any particular hypocalcemic regimen.
Mild hypercalcemia is defined as corrected total serum calcium level lower than 12 mg/dL (<6 mEq/L or 3.0 mmol/L).
Hydration followed by observation is a treatment option. This option should be considered for asymptomatic patients who are about to be treated for tumors that are likely to respond to antineoplastic treatment (e.g., lymphoma, breast cancer, ovarian cancer, head and neck carcinoma, and multiple myeloma).
In symptomatic patients or when tumor response to therapy is expected to occur slowly, therapy for hypercalcemia should be implemented to manage symptoms and stabilize patients' metabolic states. Additional ancillary interventions should be directed toward controlling nausea and vomiting, encouraging mobility, noting febrile episodes, and the minimal use of sedating medications.
Moderate to Severe Hypercalcemia
Moderate to severe hypercalcemia is defined as corrected total serum calcium equal to 12 to 14 mg/dL (6–7 mEq/L or 3.0–3.5 mmol/L).
Rehydration is the essential first step in treating moderate or severe hypercalcemia. Although fewer than 30% of patients achieve normocalcemia with hydration alone, replenishing extracellular fluid, restoring intravascular volume, and saline diuresis are fundamental to initial therapy. Adequate rehydration may require 3,000 to 6,000 mL of 0.9% sodium chloride for injection (normal saline) within the first 24 hours to restore fluid volume. Restoring normal extracellular fluid volume will increase daily urinary calcium excretion by 100 to 300 mg. Clinical improvement in mental status and nausea and vomiting is usually apparent within 24 hours for most patients; however, rehydration is a temporizing intervention. If definitive cytoreductive therapies (surgery, radiation, or chemotherapy) are not forthcoming, hypocalcemic agents must be used to achieve long-term control.
Thiazide diuretics increase renal tubular calcium absorption and may exacerbate hypercalcemia. Thus, thiazide diuretics are contraindicated in hypercalcemia patients. Loop diuretics (e.g., furosemide, bumetanide, and ethacrynic acid) induce hypercalciuria by inhibiting calcium reabsorption in the ascending limb of the loop of Henle, but they should not be administered until fluid volume is restored. Otherwise, loop diuretics can exacerbate fluid loss, further reducing calcium clearance. Because sodium and calcium clearance are closely linked during osmotic diuresis, loop diuretics will depress the proximal tubular resorptive mechanisms for calcium, increasing calcium excretion to 400 to 800 mg per day.