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Hypercalcemia

Hypercalcemia

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Hypercalcemia

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  1. Hypercalcemia Carol S. Viele RN MS Clinical Nurse Specialist Hematology-Onc-BMT UCSF

  2. Objectives • At the completion of this presentation the participant will be able to: • Describe 2 side effects of hypercalcemia • Define 2 agents utilized to treat hypercalcemia • Describe at least 2 nursing interventions for hypercalcemia

  3. Prevalence • Most common metabolic complication of cancer • 10-20% of all cancer patients per year will be diagnosed with hypercalcemia

  4. Associated Malignancies • Lung-35% ( NSCL)- 15% occurrence • Breast- 40-50% • Multiple Myeloma-20-40% • Head and Neck-6% • Genitourinary-6% • Other/Unknown primary-15%

  5. Mechanism of Calcium Regulation • Bone formation and resorption (99%) in bone • GI absorption • Urinary excretion

  6. Hypercalcemia in Cancer • Due to increased bone resorption and release of calcium from bone • Three mechanisms • Osteolytic metastases with local release of cytokines • Tumor secretion of parathyroid hormone-related protein • Tumor production of calcitriol

  7. Hormonal Control • Parathyroid hormone- released from the parathyroid in response to a drop in calcium, acts directly on bone by stimulating osteoclast formation and inhibiting osteoblasts • Vitamin D (1,25-dihydroxycholecalciferol)-increase calcium and phosphorous absorption from the intestinal mucosa • Calcitonin-reduces calcium release into circulation as a result of bone resorption

  8. Pathogenesis of Skeletal Metastases tumour cell activatd TGFß IL-6 IL-1 IL-6 TNF TGF EGF Imune cell PGs PTHrP cathepsins IL-1, TNF GM-CSF osteoblast OIF/OAF osteoclast mineralized bone

  9. Osteolytic Metastases • Osteolytic mets are the result of direct induction of local osteolysis by the tumor cells • Breast and Non–small cell lung • In Breast cancer adminstration of estrogen and antiestrogen Tamoxifen) can lead to hypercalcemia • Cytokines play a major role • Tumor necrosis factor • Interleukin-1

  10. Osteoclast Activating Factors • Multiple Myeloma can release these factors by tumor cells • Cytokines active in osteoclastic activity • Interleukin-1-beta • Lymphotoxin • Tumor necrosis factor • IL-6 • Macrophage colony stimulating factor • Macrophage inflammatory protein • Vascular cell adhesion molecule-1 • Hepatocyte growth factor ( This is produced by myeloma cells in culture)

  11. Pathogenesis of Skeletal Metastases tumour cell activatd TGFß IL-6 IL-1 IL-6 TNF TGF EGF Imune cell PGs PTHrP cathepsins IL-1, TNF GM-CSF osteoblast OIF/OAF osteoclast mineralized bone

  12. Clinical Manifestations • Dehydration • Polydipsia • Polyuria • Gastointestinal • Anorexia • Nausea/Vomiting • Constipation • Abdominal pain

  13. Clinical Manifestations • Bone pain • Pathologic fracture • Weakness • Lethargy • Hyporeflexia • Depression

  14. Clinical Manifestations • Stupor • Coma • Confusion • Visual disturbances • Apathy • Restlessness

  15. Clinical Manifestations • Genitourinary • Polyuria • Polydipsia • Nocturia • Calcium nephropathy • Hypercalciuria • Nephrolithiasis

  16. Clinical Manifestations • Cardiovascular • Hypertension • Bradycardia • Cardiac arrhythmias • Cardiac arrest • Heart block • Digitalis sensitivity

  17. Diagnosis • Laboratory tests • Ionized calcium or free calcium is the physiologically active form of calcium circulating in the blood • 50% of serum calcium is ionized • Results < 1.30

  18. Diagnosis • Normal serum calcium 9-11mg/dl • Hypercalcemia can be estimated via a formula: • Corrected Ca (mg/dl) = Ca divided by 4 minus albumin(gm/dl) times ) 0.8

  19. Medical Management • Mild hypercalcemia • Calcium < 12 • Asymptomatic • Therapy • Activity • Avoid salt restriction • Discontinue thiazide diuretics

  20. Medical Management • Moderate to severe hypercalcemia • Moderate 12-13 mg/dl • Severe >13.5 mg/dl • Therapy • Rehydration • Diuretics- Furosemide • Discontinue thiazide diuretics

  21. Medical Management • Antiresorptive therapy • Calcitonin • Bisphosphonates • Etidronate-Didronel • Pamidronate- Aredia • Zoledronic acid- Zometa • Ibandronate- Boniva • Risedronate- Actonel

  22. Mechanism of action of Bisphosphonates inhibit osteoclast formation, migration and osteolytic activity, promote apoptosis modulate signalling from osteoblasts to osteoclasts local release during bone resorption concentrated in newly mineralizing bone and under osteoclasts

  23. Current Therapeutic Approaches for Skeletal Complications ofMalignancies • Radiotherapy • Endocrine therapy • Chemotherapy • Orthopedic interventions • Analgesia • Bisphosphonates1 • Treatment of choice in hypercalcaemia of malignancy (HCM) • Potent inhibitors of pathologic bone resorption • Effective therapy for skeletal complications of bone metastases 1. Body JJ, et al. J Clin Oncol. 1998.

  24. Zoledronic Acid—Mechanisms of Action • Zoledronic acid reduces bone resorption by potently inhibiting osteoclast hyperactivity • Proposed mechanisms of action include: • Functional suppression of mature osteoclast1 • Inhibition of osteoclast maturation2 • Inhibition of osteoclast recruitment to the site2 • Reduction in the production of cytokines, eg, IL-1, IL-63 • Inhibition of tumour-cell invasion and adhesion to bone matrix4,5 1. Green J, et al. J Bone Miner Res. 1994. 2. Evans CE, Braidman IP. J Bone Miner Res. 1994. 3. Derenne S, et al. J Bone Miner Res. 1999. 4. Boissier S, et al. Cancer Res. 2000.5. Marion G, et al. Bone. 1998.

  25. Overall Safety Conclusions • ZOMETA (4 mg) via 15-minute infusion is safe and well tolerated, with a safety profile comparable to that of pamidronate (90 mg) via 2-hour infusion, including renal tolerability • Similar overall safety profile to that of other intravenous bisphosphonates • Laboratory abnormalities (grade 3 and 4) were similar for ZOMETA and placebo

  26. Efficacy • Zoledronic acid is the only bisphosphonate to be proven effective across tumor types in patients with both lytic and blastic bone lesions

  27. Nursing Management • Education • Patient • Significant others • Rehydration • I&O • Weights • Activity • Encourage ambulation

  28. Nursing Management • Safety • Falls prevention • Do not allow patient to overstress bones • Do not pull on arms or legs • Have patient report all bone pain • Be very gentle when assisting patient • Use assistive devices • Safety assessment for home via PT/Home Health

  29. Nursing Management • Decrease anxiety • Education

  30. References • Jensen, G., “Hypercalcema of Malignancy” in Oncology Nursing Secrets, R Gates and R Fink (eds), Philadelphia: Hanley and Belfus, 2008,523-526 • Paines, H., “How to manage metabolic emergencies”, ContempOncol, 3 (9), 54-57, 1993 • 2009 UpToDate, ‘Treatment of Hypercalcemia’ www.http://UPTODATE accessed 7/9/09