Adult-Gerontology Acute Care Practice Guidelines
Definition
A.Serum total calcium greater than 10.2 mg/dL (corrected for low albumin; see Box 5.2).
Incidence
A.Hypercalcemia is a relatively common abnormality that is usually mild in presentation.
B.Approximately 90% of cases of hypercalcemia may be caused by some type of malignancy or hyperparathyroidism.
C.Other causes may be from vitamin D deficiencies or kidney transplantation.
Pathogenesis
A.Calcium is controlled by three major hormones: Parathyroid, calcitonin, and vitamin D.
B.Dysregulation in these hormones can lead to hypercalcemia.
C.Calcium is tightly regulated in the bloodstream; therefore, even mild cases of hypercalcemia are concerning and should be investigated for possible malignancy.
Predisposing Factors
A.Women over the age of 50.
B.Patients taking excessive calcium or vitamin D supplements.
C.Cancer.
D.Genetics.
E.Immobility may contribute to release of calcium.
F.Lithium.
Subjective Data
A.Common complaints/symptoms.
1.Gastrointestinal, including nausea, vomiting, and constipation.
2.Anorexia.
3.Fatigue and lethargy.
4.Confusion.
5.Severe hypercalcemia.
a.Cardiac effects, including bradycardia or arrhythmias with EKG changes.
b.Volume depletion secondary to polyuria and hypercalcemia-induced natriuresis.
c.Possible acute renal failure if severe and prolonged.
6.Chronic hypercalcemia: Possible nephrolithiasis, systemic calcifications (e.g., vascular), and renal failure.
Physical Examination
A.Volume status.
B.Cardiac examination.
C.Neurological examination.
D.Reflexes.
E.Musculoskeletal examination.
Diagnostic Tests
A.Serum calcium and phosphorus.
B.25-hydroxyvitamin D.
C.Intact parathyroid hormone (PTH).
D.Creatinine, blood urea nitrogen (BUN).
E.Protein electrophoresis and immunofixation (serum and urine).
F.Thyroid-stimulating hormone (TSH).
G.EKG.
Differential Diagnosis
A.Malignancy: Local osteolytic hypercalcemia, or hematological malignancies.
B.Hyperparathyroidism: Primary, secondary, and tertiary.
C.Paget’s disease.
D.Milk-alkali syndrome.
E.Thyrotoxicosis.
F.Granulomatous diseases (such as sarcoidosis and tuberculosis).
G.Immobilization.
H.Medication-induced.
1.Vitamin A and D overdose/toxicity.
2.Parenteral nutrition.
3.Thiazide diuretics.
4.Lithium.
5.Estrogens, antiestrogens, and androgens.
6.Calcium supplements and calcium-containing phosphorus binders.
I.Impaired renal function (chronic kidney disease [CKD] or acute kidney injury [AKI])—usually due to clearance of drugs.
BOX 5.2
Calcium in Humans
•Normal total serum calcium is 8.6 to 10.2 mg/dL.
•Normal ionized serum calcium is 1.12 to 1.3 mmol/L.
•Extracellular calcium is found in three forms.
○40% of calcium in serum is protein-bound, primarily to albumin.
○50% is free (ionized or unbound) calcium.
○10% is complexed (i.e., calcium citrate).
•Total serum calcium underestimates active calcium.
○Ionized or unbound calcium is the biologically active form.
○Correct serum calcium in hypoalbuminemic patients for actual total calcium.
■Corrected calcium = serum total calcium + (0.8 × [4 – serum albumin concentration]).
•99% of total body calcium is found in bones.
•PTH and vitamin D regulate serum calcium.
•Physiologic functions.
○Bone metabolism.
○Electrophysiology of cardiac and smooth muscle.
○Coagulation.
○Endocrine and exocrine secretory functions.
•Phosphorus and calcium directly affect each other.
○Elevated phosphorus binds to ionized calcium, decreasing unbound, active calcium.
○Maintain the optimal relationship between calcium and phosphorous.
■For bone health.
■To prevent vascular and soft tissue calcifications.
•Calcium is an inotrope if given at accelerated doses (due to its effects on cardiac and smooth muscle).
•Calcium is critical to the coagulation cascade; thus, low calcium or blocking calcium can lead to bleeding.
PTH, parathyroid hormone.
Evaluation and Management Plan
A.Goal: To correct the underlying cause of hypercalcemia and prevent complications of hypercalcemia.
B.Step 1—Treat symptoms.
1.Use aggressive volume resuscitation with intravenous (IV) normal saline 0.9% (200–500 mL/hr) in patients with volume depletion and normal heart and kidney function.
2.Manage cardiac effects: EKG changes and hypotension or hypertension.
3.Replace phosphorus if hypophosphatemia is present.
C.Step 2—Treat hypercalcemia and identify the underlying cause.
1.Discontinue all vitamin D and calcium (oral and intravenous).
2.Acute, severe hypercalcemia.
a.Give loop diuretics (such as furosemide 40–100 mg IV), once volume resuscitation has taken place, to increase renal calcium excretion and avoid volume overload.
b.Possibly arrange for hemodialysis in patients with renal dysfunction.
3.Mild or asymptomatic hypercalcemia. Some therapies may also be beneficial in combination with severe hypercalcemia management.
a.Calcitonin.
i.Rapid onset of action but with short-term effectiveness (<48 hours) due to tachyphylaxis.
ii.Can be used in initial treatment of severe hypercalcemia along with intravenous hydration.
iii.Increases renal excretion and decreases osteoclast-mediated bone resorption of calcium.
iv.Dose: 4 to 8 units/kg IV or intramuscularly (IM) every 12 hours.
b.Glucocorticoids.
i.Useful in patients with granulomatous disorders or lymphoma.
ii.Decreases calcitriol production, which subsequently lowers intestinal calcium absorption.
iii.Sample regimens: Prednisone 20–60 mg/day PO or hydrocortisone 200 mg/day IV.
c.Bisphosphonates.
i.Examples: Pamidronate and zoledronate.
ii.Potent inhibitors of osteoclast-mediated bone resorption frequently used in hypercalcemia of malignancy.
iii.Due to delayed onset of action, limited role in severe, acute hypercalcemia.
d.Cinacalcet or etelcalcetide.
i.Indication: For outpatient management of primary hyperparathyroidism and secondary hyperparathyroidism of renal origin.
ii.Mimics the effects of calcium (calcimimetic) by binding to the calcium-sensing receptor on the parathyroid gland, thus reducing PTH and serum calcium.
iii.Dosing.
1)Cinacalcet: Initially at 30 mg one to two times daily to max of 180 mg/day.
2)Etelcalcetide: Initial dosing 5 mg three times weekly IV (after dialysis) to a maximum of 15 mg three times weekly IV (after dialysis).
e.Denosumab.
i.Indicated for hypercalcemia of malignancy.
ii.Delayed onset of action.
iii.Binds to receptor activator of nuclear factor-kappa ligand (RANKL), leading to decreased bone resorption.
iv.Given subcutaneously every 4 weeks with additional doses during the first month of treatment.
D.Step 3—Treat other electrolyte and acid–base disorders.
Follow-Up
A.Hypercalcemia can lead to osteoporosis, kidney stones or failure, nervous system disorders, and arrhythmias.
B.Follow-up of calcium levels is essential to prevent adverse outcomes.
Consultation/Referral
A.Patients should be referred to the appropriate service to treat the underlying disorder.
B.Oncology may be needed for patients with cancer.
C.Endocrine can be consulted for hormonal disorders contributing to hypercalcemia.
D.Nephrology should be consulted if there is renal involvement.
Special/Geriatric Considerations
A.Geriatric patients may be at increased risk due to immobility and dehydration.
B.Sitting or lying for long periods of time can cause calcium to leak into the bloodstream.
C.Severe dehydration can also transiently increase calcium concentration secondary to hypovolemia.
D.Hypercalcemia can contribute to arrhythmias that further put geriatric patients at risk for adverse events.
Bibliography
Kraft, M. D., Btaiche, I. F., Sacks, G. S., & Kudsk, K. A. (2005, August). Treatment of electrolyte disorders in adult patients in the intensive care unit. American Journal of Health System Pharmacy, 62(16), 1663–1682. doi:10.2146/ajhp040300
Moe, S. M., & Daoud, J. R. (2004). Disorders of mineral metabolism: Calcium, phosphorous, and magnesium. In D. S. Gipson, M. A. Perazella, & M. Tonelli (Eds.), National kidney foundation’s primer on kidney diseases (6th ed., pp. 100–112). Philadelphia, PA: Elsevier Saunders.
Shane, E. (2018, August 13). Diagnostic approach to hypercalcemia. In J. E. Mulder (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia
Shane, E., & Berenson, J. R. (2017). Treatment of hypercalcemia. In J. E. Mulder (Ed.), UpToDate. Retreived from https://www.uptodate.com/contents/treatment-of-hypercalcemia