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Hypercalcemia


- Discussion:
    - physical properties
    - state in body fluids
         - calcium is a necessary & important addition to cell membranes, giving strength to these structures and regulating permeability;
         - physiologic roles of calcium are well established;
         - abnormally low concentrations of Ca permit spontaneous discharges of both sensory & motor fibers in peripheral nerves, leading to tetany;
                - see depolarization and calcium regulation of muscle contraction;
    - w/ elevated levels, nerve impulses are blocked, leading to coma;
    - normal levels:
         - serum:    4.2-5.3 mEq/L or 8.5-10.5 mg/dL;
         - ionized:  2.24-2.46 mEq/L or 4.48-4.92 mg/dL
    - inciting causes of hypercalcemia
    - signs & symptoms
    - EKG changes
    - calcification of soft tissue


- Initial Management:
    - determine if the patient is symptomatic;
    - d/c all thiazide diuretics; (decr Ca excretion);
    - d/c Vit D and Calcium Supplements;
    - correct volume depletion / expand extracellular volume; (r/o CHF);
          - give NS 500 ml IV "wide open" (will dilute Ca/promote excretion)
          - pt may require upto 4-10 liters of NS per day, inorder to keep patient in volume expanded state;
          - when hypercalcemia is mild (serum Ca level, <3.00 mmol/liter), hydration with saline is often adequate, and most pts do not require drug therapy;
          - even when hypercalcemia is more severe, hydration w/ saline is first step in management;
    - establish diuresis > 2500 ml/day;
          - lasix 20-40 mg IV q2-4 hr (will increase Ca excretion);
    - severe hypercalcemia:
          - w/ life-threatening hyperCa (more than 4.00 mmol/l or more than 16 mg / dl), unequivocally symptomatic, or both, more specific therapy is required in addition to saline;
          - consider dialysis;
          - calcitonin
                 - in this situation, most rapid-acting osteoclast inhibitor, calcitonin, becomes a first-line drug;
                 - it has the advantage of being relatively rapid-acting and is given in single dose;
                 - since calcitonin alone is unlikely to reduce serum Ca concentration to normal, however, additional therapy should be considered;
                 - if there are no contraindications, such as renal or hepatic dysfunction, thrombocytopenia, or coagulopathy, mithramycin;


- Disuse Hypercalcemia:
    - immobilization can lead to significant decrease in bone formation (without affecting bone resorption);
    - the result is hypercalcemia;
    - these patients should be managed with either calcitonin or pamidronate


- Hypercalcemia Second to Malignancy: (metastatic bone disease);
    - corticosteroids:
          - prednisone 5-15 mg po qd;
          - hydrocortisone (solu-cortef) 40-60 mg iv qd in dd;
          - ref: High-dose Steroids for Neurotrauma – Another Thing to Watch 

    - indomethacin 50 mg po q8hr;
    - calcitonin
    - mithramycin:
          - 15-25 ug/kg IV in 1 lit of NS over 3-6 hrs;
          - onset of action in 24 hours;
          - agents that are nephrotoxic should be avoided if possible;
          - plicamycin (also called mithramycin) is not ideal agent for hypercalcemia in myeloma because it is directly toxic agent and it depends on the kidneys for excretion;
    - etidronate
    - pamidronate
    - clodronate



Drug Therapy -- Management of Acute Hypercalcemia.

Hypercalcemia and bone resorption in malignancy.