Download Hypercalcemia Lecture Notes

Hypercalcemia
Carol S. Viele RN MS
Clinical Nurse Specialist
Hematology-Onc-BMT
UCSF
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
Prevalence
Most common metabolic complication of
cancer
10-20% of all cancer patients per year will
be diagnosed with hypercalcemia
Associated Malignancies
Lung-35% ( NSCL)- 15% occurrence
Breast- 40-50%
Multiple Myeloma-20-40%
Head and Neck-6%
Genitourinary-6%
Other/Unknown primary-15%
Mechanism of Calcium Regulation
Bone formation and resorption (99%) in
bone
GI absorption
Urinary excretion
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 hormonerelated protein
– Tumor production of calcitriol
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
Pathogenesis of Skeletal
Metastases
tumour
cell
activatd
TGFß
IL-6
IL-1
IL-6
TNF
TGF
EGF
PGs
PTHrP
cathepsins
Imune
cell
IL-1,
TNF
GM-CSF
osteoblast
OIF /
OAF
osteoclast
mineralized bone
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
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)
Pathogenesis of Skeletal
Metastases
tumour
cell
activatd
TGFß
IL-6
IL-1
IL-6
TNF
TGF
EGF
PGs
PTHrP
cathepsins
Imune
cell
IL-1,
TNF
GM-CSF
osteoblast
OIF /
OAF
osteoclast
mineralized bone
Clinical Manifestations
Dehydration
Polydipsia
Polyuria
Gastointestinal
– Anorexia
– Nausea/Vomiting
– Constipation
– Abdominal pain
Clinical Manifestations
Bone pain
Pathologic fracture
Weakness
Lethargy
Hyporeflexia
Depression
Clinical Manifestations
Stupor
Coma
Confusion
Visual disturbances
Apathy
Restlessness
Clinical Manifestations
Genitourinary
–Polyuria
–Polydipsia
–Nocturia
–Calcium nephropathy
–Hypercalciuria
–Nephrolithiasis
Clinical Manifestations
Cardiovascular
– Hypertension
– Bradycardia
– Cardiac arrhythmias
– Cardiac arrest
– Heart block
– Digitalis sensitivity
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
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
Medical Management
Mild hypercalcemia
–Calcium < 12
–Asymptomatic
–Therapy
Activity
Avoid salt restriction
Discontinue thiazide diuretics
Medical Management
Moderate to severe hypercalcemia
– Moderate 12-13 mg/dl
– Severe >13.5 mg/dl
Therapy
– Rehydration
– Diuretics- Furosemide
– Discontinue thiazide diuretics
Medical Management
Antiresorptive therapy
–Calcitonin
–Bisphosphonates
Etidronate-Didronel
Pamidronate- Aredia
Zoledronic acid- Zometa
Ibandronate- Boniva
Risedronate- Actonel
Mechanism of action of
Bisphosphonates
inhibit osteoclast
formation, migration and
osteolytic activity,
promote apoptosis
local release
during bone
resorption
modulate signalling
from osteoblasts to
osteoclasts
concentrated in
newly mineralizing
bone and under
osteoclasts
Current Therapeutic Approaches for
Skeletal Complications of Malignancies
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.
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, IL1, 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.
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
Efficacy
Zoledronic acid is the only
bisphosphonate to be proven effective
across tumor types in patients with both
lytic and blastic bone lesions
Nursing Management
Education
– Patient
– Significant others
Rehydration
– I&O
– Weights
Activity
– Encourage ambulation
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
Nursing Management
Decrease anxiety
Education
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”, Contemp Oncol, 3 (9), 54-57,
1993
2009 UpToDate, ‘Treatment of Hypercalcemia’
www.http://UPTODATE accessed 7/9/09