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Course: Oncology Nursing

Topic: Nursing Management of

Oncological Emergency- Hypercalcemia of Malignancy

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Module Goals

Learners will be able to:

Explain the underlying pathophysiology of Hypercalcemia of Malignancy.
Describe the scope of the problem including the incidence, etiology and risk factors for this oncologic emergency.
List the clinical manifestations that are associated with this emergency situation.
Explain the nursing assessment including relevant diagnostic tests.
Characterize the nursing interventions and supportive care important to address this problem in a timely and effective manner.

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Hypercalcemia of Malignancy (HCM)

“Hyper- High”, “Calcemia- level of calcium”
Serum calcium level is more than 10.5 mg/dl (2.63 mmol/L)
Affects 10-30% of patient with cancer
Found in patient with advanced cancer
Common in patient with multiple myeloma and breast cancer, squamous cell carcinomas of the head or neck, lung, kidney, or cervix
Symptoms vary
Usually severely symptomatic

Klemencic, 2019

Mirrakhimov, 2015

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Why Hypercalcemia of Malignancy (HCM) is Alarming?

Serious neoplastic syndrome
High prevalence in cancer patients
Poor prognosis: 50% with HCM may not survive more than 30 days
Rapid identification and treatment is key
33% of the cases still do not receive first line therapy i.e. bisphosphonate
Practitioners lack up-to-date knowledge of evidence based treatment

Klemencic, 2019

Mirrakhimov, 2015

Contact info: info@nursesinternational.org

Practitioners need to be aware of how management options and suggested treatments have evolved over the past 5 to 10 years.

Many hospitalized HCM patient did not receive appropriate treatment and 33% did not receive bisphosphonate which is first line of therapy (Wright and colleagues, 2015). It was also found that health care providers are not updated with the treatment that has evolved over past 5-10 years. About 27% of the patient frequently received steroid therapy despite the fact that this is only truly indicated in the setting of vitamin D–secreting lymphomas. In addition to that, patient were being treated with medications like thiazide diuretics, lithium which are contraindicated to HCM. It was also seen that the treatment rarely follow the guidelines in treating the HCM patient in hospital settings.

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Pathophysiology of HCM

The causes are multiple:

Humoral HCM: 80% of all cases
Osteolytic HCM: 20% of all cases
Ectopic Hyperparathyroidism &
Vitamin D-secreting Lymphomas: Less than 1% of all cases

Klemencic, 2019

Mirrakhimov, 2015

Contact info: info@nursesinternational.org

Feldenzer & Sarno (2018).

There causes of HCM, including humoral HCM, osteolytic HCM, ectopic hyperparathyroidism, and vitamin D–secreting lymphomas

Humoral HCM is the most common cause of HCM which affects approximately 80% of HCM cases. Malignant tumors secreting parathyroid hormones-related protein (acts like parathyroid hormones) cause humoral HCM. Once parathyroid hormone- related protein increases, it leads to rise in osteocal activities . Such increased osteocal activities will destruct or sissolute the bone and release the calcium in the bloodstream. Humoral HCM is typically associated with renal, ovarian, breast, and squamous cell cancers as well as human T-cell lymphotropic virus (HTLV)–associated lymphoma
Osteolytic HCM is the second most common cause of HCM which affects 20% of HCM cases. It is caused when when malignant cells in bone marrow also produces excessive calcium and releases in the bloodstream. The osteocal activities are stimulated due to the inflammatory response of the malignant cells. This type of HCM is frequently seen in malignancies with bone metastasis as well as breast cancer and multiple myeloma.
The last two types of HCM (i.e. Ectopic hyperparathyroidism and Vitamin D secreting lymphomas) are rare and account for less than 1% of HCM cases. Vitamin D–secreting lymphomas increases the intestinal absorption of calcium and decreases renal calcium excretion.
Ectopic hyperparathyroidism causes increased secretion of PTH and acts nearly the same as Parathyroid hormones- related protein for causing increased serum calcium level in the body. Small cell lung cancer and adenocarcinomas are most commonly associated with ectopic hyperparathyroidism

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Risk Factors of HCM

Humoral HCM: renal, ovarian, breast, and squamous cell cancers as well as human T-cell lymphotropic virus (HTLV)–associated lymphoma.
Osteolytic HCM: malignancies with bone metastasis as well as breast cancer and multiple myeloma.
Ectopic Hyperparathyroidism: Small cell lung cancer and adenocarcinomas.
Vitamin D-secreting Lymphomas: Lymphomas.

Mirrakhimov, 2015

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Clinical Manifestations

Cardiovascular System: Arrhythmias, ventricular tachycardias, shortened ST segments and QT intervals, depressed ST segments, widened T waves, prolonged PR and QRS intervals, and cardiac arrest.
Gastrointestinal system: Anorexia, constipation, nausea, vomiting, weight loss, pancreatitis or peptic ulcer disease.
Renal System: Nephrolithiasis and chronic renal failure.
Neurological and Musculoskeletal Systems: Anxiety, depression, cognitive dysfunction, weakness, fatigue,confusion, stupor, coma.
Other signs and symptoms: Pruritus, generalized abdominal pain, and bone pain.

Mirrakhimov, 2015

Contact info: info@nursesinternational.org

Feldenzer & Sarno (2018).

Signs and symptoms of hypercalcemia depend upon the level of calcium in the body and the rate calcium level is rising. The signs and symptoms varies as per the severity. Hypercalcemia of malignancy usually occurs more acutely and effects more severely compared to other causes of hypercalcemia.

The signs and symptoms of hypercalcemia include

Stones: Nephrolithiasis
Bones: Bone pain
Moans: Abdominal Moans nausea, vomiting, weight loss, peptic ulcer diseases, pancreatitis
Groans: Psychic Groans includes anxiety, depression, cognitive dysfunction.

Cardiovascular System: The cardiovascular system of a person suffering from HCM will have arrythmias, ventricular tachycardias, shortened ST segments and QT intervals, depressed ST segments, widened T waves, prolonged PR and QRS intervals, and cardiac arrest.

Gastrointestinal system: The signs and symptoms depends upon the degree of hypercalcemia. If it is mild, common signs and symptoms include anorexia and constipation. And if it is higher degrees of hypercalcemia, signs and symptoms may include nausea, vomiting, weight loss (if chronic), and even pancreatitis or peptic ulcer disease.

Renal System: HCM may cause nephrogenic diabetes insipidus (Causes polyuria, renal vasoconstriction, and distal renal tubular acidosis, often resulting in acute kidney injury and significant dehydration). If it is chronic hypercalcemia, nephrolithiasis and chronic renal failure can also occur.

Neurological and Musculoskeletal Systems: The signs and symptoms include, anxiety, depression, cognitive dysfunction, lethargy, weakness, fatigue, hyporeflexia, confusion, stupor, and in the most severe cases, coma. It may also cause irreversible leukoencephalopathy syndrome, which presents with headaches, seizures, and subcortical edema on imaging.

Other signs and symptoms: Pruritus, generalized abdominal pain, and bone pain.

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Diagnostic Flowchart on the Work-up of Hypercalcemia

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Hypercalcemia can be diagnosed clinically with serum calcium level. Once it is confirmed, the pathophysiological cause has to be ruled out so that the treatment can be determined accordingly (pathophysiology impacts the treatment and management).

It is advised to confirm elevated serum calcium with a repeat test (ionized calcium). Nevertheless, if the serum calcium level is moderate to severely higher, it is advised to start the treatment while waiting for the result.

Sometimes hyperparathyroidism, dehydration can cause hypercalcemia therefore it has to be ruled out before confirming HCM. . If PTH is normal then it is more likely that HCM is present. If the serum PTH level is decreased or low normal, HCM is the likely diagnosis and checking a serum PTHrP level should be considered for further evaluation.

If the laboratory finding shows the PTHrP level elevated, then it is more likely that humoral HCM is the cause. However, if the laboratory finding shows the normal or low level of PTHrP, the next step is to look for bony metastatic disease, checking the vitamin D level (Elevated vitamin D levels could be due to underlying lymphomas)

Finally, if laboratory results shows normal values of PTH, PTHrP, and vitamin D, other causes of hypercalcemia (certain medications like thiazide diuretics, corticosteroids, lithium, Vitamin A or vitamin D over supplementation, renal failure) must be considered.

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Management of Hypercalcemia

Aggressive rehydration: Normal Saline
Bisphosphonates: Reduces osteocal activities
Denosumab: Prevents skeletal related events, osteoporosis
Other treatment choices:

Calcitonin
Corticosteroids
Cinacalcet (Sensipar)

Klemencic, 2019; Mirrakhimov, 2015

Contact info: info@nursesinternational.org

Feldenzer & Sarno (2018),

Aggressive rehydration:

Aggressive rehydration with IV fluids like normal saline (bolus followed by maintenance dose to maintain urine output of 100/150 ml per hour) is given to manage the hypercalcemia patient. Usually hypercalcemia patient presents with dehydration due to nausea, vomiting, anorexia. due to less fluid in the body, kidney function decrease and excretion of calcium via urine is also decreased.

Bisphosphonates:

Bisphosphonates are drugs that are found to be safe and effective to the patient suffering from HCM. This drug binds with the bone and prevent/reduce osteocal activities (which is responsible for releasing calcium in the blood). Along with the aggressive rehydration, IV bisphosphonate treatment should be started to treat HCM. However, there are some side effects of bisphosphonate use. The most common are fever and flu-like symptoms, mild bone aches and pains. There is also a risk of nephrotoxic acute tubular necrosis (in patients who have advanced cancer or have been previously treated with bisphosphonates, and with concurrent use of nonsteroidal anti-inflammatory drugs. Due to this risk, experts recommend careful use of bisphosphonates if patients have pre-existing kidney injuries or a decrease in renal function. Zoledronic acid (second generation bisphosphonates) is generally contraindicated in patients with a creatinine clearance (CrCl) of less than 30 mL/min.

Denosumab:

Denosumab is a fully human monoclonal antibody that is used for the prevention of skeletal-related events in patients with solid tumor malignancies as well as osteoporosis. it has been recommended by FDA for the prevention of skeletal-related events among patients with multiple myeloma who have developed bone metastases.Denosumab is generally well tolerated by the patients and it has common side effects like arthralgia and mild dyspnea

Other Treatment Choice:

Calcitonin: Another choice in the management of HCM is the administration of calcitonin. Calcitonin inhibits all osteoclast activity as well as to prevent renal absorption of calcium . However, this medication is rapid acting and can cause hypocalcemia approximately 2 hours of administration. It is usually used in acute phase of hypercalcemia and used as bridging treatment until the effect of bisphosphonates are seen. The maintenance of calcitonin must be given every 6-8 hours to the patient suffering from hypercalcemia. Side effects of calcitonin are nausea, vomiting, and pain or irritation at the injection site.
Corticosteroids: Corticosteroids are the drug choice if a person has vitamin D–secreting tumors or lymphoma. This drug usually works by decreasing gastric absorption of calcium. It is slow acting and can take approximately 4 days to see a response. Hydrocortisone IV is generally initiated for 3-5 days. Side effects of corticosteroids includes peptic ulcer disease, hyperglycemia, hypertension, steroid-induced psychosis, peptic. It also increases the risk of tumor lysis syndrome.
Other emerging treatment of HCM are Cinacalcet (Sensipar) which acts by decreasing PTH production. This has been used successfully to treat HCM secondary to parathyroid carcinoma. It has less side effects like nausea, vomiting, and headaches.
Scientists are anticipating another model of treatment i.e. anti-PTHrP antibodies are currently being tested in animal models. This approach offers future hope for additional treatment options.

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What would the nurse do?

A patient who has been admitted in the unit with a diagnosis of HCM secondary to multiple myeloma. His K level is 9mEq/L and is being managed with aggressive rehydration and and IV Zoledronic acid. While reviewing his file you saw the patient’s kidney function test where creatinine clearance rate is 20ml/min.

What could be wrong with this diagnosis and treatment?
What is your role/responsibility as the nurse in caring for this patient?

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Nursing Assessment of HCM

Assess heart rate and rhythm
Assess polyuria, polydipsia, nephrolithiasis (seen in ultrasonography)
Assess muscle strength
Assess, mental status, level of consciousness
Assess patient’s ability to eat food
Assess the presence of nausea, vomiting or any abdominal pain
Assess the bowel sound, bowel movement pattern

Mirrakhimov, 2015

Contact info: info@nursesinternational.org

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Nursing Considerations:

Careful Monitoring
Careful consideration of management options
Continuous monitoring of the patient about the side effects and serum calcium level
Continuous monitoring of the patient’s level of consciousness
Watch for hypocalcemia
Prevent Hypercalcemia
Monitor patient's weight chart, food chart, and fluid chart
Encourage weight-bearing exercises

Mirrakhimov, 2015

Contact info: info@nursesinternational.org

Careful Monitoring: A patient should be carefully monitored for the clinical response during and after the treatment of HCM

Careful consideration of management options: Certain management options and treatment methods may be contraindicated for some patient. E.g. Patient with chronic kidney diseases or who has low creatinine clearance level should not be given Zoledronic acid (second generation bisphosphonates). Therefore, a complete medical history, proper examination and certain lab test has to be run before starting the treatment to the patient.

Continuous monitoring of the patient about the side effects and serum calcium level: A patient has to be continuously monitored who are in long term use of bisphosphonate as it may cause hypocalcemia. If that happens it has to be treated with Vitamin D supplement and calcium repletion and other supportive measures.

Monitor patient's weight chart food chart and fluid chart: In order to monitor patinet’s nurtion and weight loss plan.

Encourage weight-bearing exercises as tolerated unless contraindicated.

Other steps can be taken to prevent hypercalcemia: Ensure the patient discontinues oral calcium supplement, vitamin D supplement, calcitriol, thiazide diuretics or other form of medication that can contribute hypercalcemia.

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What Would the Nurse Do?

A 48 year old male diagnosed with adenocarcinoma has been receiving chemotherapy. He comes to the unit with the complaints of nausea and vomiting. He has not been able to keep anything down. On physical examination, the patient seems dehydrated. His lab test shows his potassium level to be 6mEq/L.

What is this patient’s most likely diagnosis?

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Red Flags

Confusion or any neurological changes
Known or suspected malignancy
Nausea, vomiting, dehydration, weight loss
Renal function deterioration
Recurrent renal calculi
Corrected serum calcium >3 mmol/L
Pancreatitis

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References:

Klemencic, S., & Perkins, J. (2019). Diagnosis and Management of Oncologic Emergencies. The Western Journal of Emergency Medicine, 20(2), 316–322. https://doi.org/10.5811/westjem.2018.12.37335

Mirrakhimov A. E. (2015). Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. North American Journal of Medical Sciences, 7(11), 483–493. https://doi.org/10.4103/1947-2714.170600

Contact info: info@nursesinternational.org

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