Art & science | endocrine disease
Diagnosis and management of patients with hypercalcaemia Jennie Walker discusses the signs, symptoms and treatment of this common, yet potentially life-threatening, condition Correspondence [email protected] Jennie Walker is clinical educator for musculoskeletal and neurosciences, Queen’s Medical Centre, Division of Orthopaedic Trauma and Sports Medicine, Nottingham Date of submission February 1 2015 Date of acceptance March 16 2015 Peer review This article has been subject to double-blind review and has been checked using antiplagiarism software Author guidelines journals.rcni.com/r/ nop-author-guidelines
Abstract Hypercalcaemia is a common biochemical abnormality in the blood that can be caused by malignancy, hyperparathyroidism, medications or underlying medical conditions. Initial signs and symptoms are often vague, however, if someone has severe hypercalcaemia it is treated as an emergency, requiring prompt management to prevent life-threatening complications such as dehydration, cardiac arrhythmias or coma. Understanding the pathophysiology, signs and symptoms of hypercalcaemia enables effective diagnosis and holistic management of the patient with complex health needs. Keywords Biochemical abnormalities, cancer, dehydration, endocrine disease, hypercalcaemia, hyperparathyroidism ONE OF the most common biochemical abnormalities in the body is elevated calcium levels in the blood, which is referred to as hypercalcaemia (Strachan and Newell-Price 2014). Although common (Grandjean and McMullen 2010), it can be potentially life threatening due to its effects on the kidneys, heart and brain (Clinical Knowledge Summaries (CKS) 2014). Sometimes patients are asymptomatic and abnormalities are discovered incidentally, through routine blood tests or investigations for other medical conditions. Hypercalcaemia can also present as an acute emergency, or more subtly, with chronic problems such as musculoskeletal aches and pains. Raised calcium levels may be caused by excessive calcium release, increased intestinal absorption or decreased renal excretion and may indicate other disease processes.
22 May 2015 | Volume 27 | Number 4
Prevalence and causes Data on the prevalence of hypercalcaemia in the general non-hospitalised population are scarce (CKS 2014), although Dark and Razak (2014) report an approximate prevalence of 15-20 cases per 100,000 people. Primary hyperparathyroidism and cancer account for around 90% of cases (CKS 2014). Primary hyperparathyroidism is the excessive secretion of parathyroid hormone (PTH), which is often caused by a parathyroid adenoma, although it may also be due to multiple endocrine neoplasia (Strachan and Newell-Price 2014). Primary hyperparathyroidism occurs in around 25 per 100,000 people in the general population and in 75 per 100,000 hospitalised patients (Green 2014). These figures are based on data from the US. While hyperparathyroidism is the most common cause of hypercalcaemia in outpatient settings, malignancy is the most common cause in hospitalised patients (Fenech and Turner 2013). Malignancy-associated hypercalcaemia occurs in between 20 and 30% of patients during the course of the disease (Green 2014). Most episodes of malignancy-associated hypercalcaemia occur with advanced disease and patients typically have a poor prognosis with up to 50% 30-day mortality (Green 2014). Patients who are particularly at risk of developing hypercalcaemia from metastatic disease include those with squamous cell lung cancer, breast cancer and multiple myeloma (Foulkes 2010, CKS 2014), although hypercalcaemia can also occur in other malignancies with or without bone metastases (Seccareccia 2010). Less common causes of elevated calcium include granulomatous disease, for example, sarcoidosis and tuberculosis; renal failure; Addison’s disease; thyrotoxicosis; dehydration; chronic liver disease; and immobilisation in people with Paget’s disease (CKS 2014, Green 2014). NURSING OLDER PEOPLE
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Thiazide diuretic use is also known to predispose to hypercalcaemia because it increases renal tubular reabsorption of calcium (Ahmad et al 2015). Familial hypocalciuric hypercalcaemia is a rare autosomal disorder that is caused by mutations in the calcium-sensing receptor gene (Christensen et al 2011). Although initial management of patients with hypercalcaemia will follow a standardised approach, the causes need to be considered carefully as the management of underlying pathology will differ significantly. Hypercalcaemia can be classified as mild, moderate or severe based on serum calcium concentration (CKS 2014), although serum calcium levels do not always correlate with the severity of symptoms (Smellie et al 2008). While symptoms tend to be progressive, patient response to raised calcium levels is variable and not all patients will experience all of the signs and symptoms (Foulkes 2010).
Pathophysiology Calcium is present in the intracellular and extracellular fluids, although most of the body’s calcium content is found in bone and calcified cartilage. Calcium is important for effective working of the cells and muscle contraction, neurotransmission and bone formation. Serum calcium levels are normally maintained in the
therapeutic range by the PTH, 1,25-dihydroxy vitamin D3 (calcitriol) and calcitonin (Grandjean and McMullen 2010). PTH and calcitriol are important physiological regulators of calcium homeostasis, while calcitonin plays a modest role (Sargent and Smith 2010). Although these regulators are useful in preventing hypocalcaemia, they are less effective in controlling hypercalcaemia (Sargent and Smith 2010). The actions of PTH, calcitriol and calcitonin are outlined in Table 1. In normal circumstances bone is continuously resorbed (removed) by osteoclasts and replaced with new bone created by osteoblasts. For hypercalcaemia to develop, the normal calcium regulation system must be overwhelmed by an excess of PTH, calcitriol or a huge calcium load (Green 2014). In patients with malignancy, tumour cells can release proteins and cytokines that stimulate osteoclasts and enhance bone resorption, which results in calcium being released into the blood and increasing calcium levels (Sargent and Smith 2010). Diagnosis is made by measuring total serum calcium and adjusting for serum albumin. It is important to correct for albumin levels because total calcium values underestimate levels of ionised calcium (Seccareccia 2010). Mild hypercalcaemia is an adjusted serum calcium concentration of 2.65-3.00mmol/L. Moderate is 3.01-3.40mmol/L and severe is greater
Table 1 Actions of parathyroid hormone, calcitriol and calcitonin Hormone
Target organ
Actions
Effect
Parathyroid hormone
Bone
■ Stimulates osteoclastic bone resorption ■ Stimulates renal tubule calcium reabsorption
Raised calcium
Kidney
■ Inhibits renal tubule phosphate reabsorption ■ Stimulates renal 1a-hydroxylase conversion of 25-hydroxy vitamin D (calcifediol) to 1,25-dihydroxy vitamin D3 (calcitriol)
Lowered phosphate
Gut
■ Increases calcium and phosphate absorption
Raised calcium, lowered phosphate
■ Increases bone resorption ■ Enhances bone mineralisation
Raised calcium
Kidney
■ Increases renal calcium reabsorption
Raised calcium
Bone
■ Inhibits osteoclastic bone resorption
Lowered calcium
Kidney
■ Promotes renal calcium and phosphate excretion
Lowered calcium and phosphate
Calcitriol (1,25-dihydroxy Bone vitamin D3)
Calcitonin
(Sargent and Smith 2010)
NURSING OLDER PEOPLE
May 2015 | Volume 27 | Number 4 23
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Art & science | endocrine acute care disease than 3.40mmol/L (CKS 2014). Plain X-rays can show bone abnormalities such as demineralisation, bone cysts, fractures or bony metastases.
Signs and symptoms Signs and symptoms of the condition are often diverse and non-specific (CKS 2014). Common features include musculoskeletal pain and weakness, drowsiness, confusion, nausea, vomiting, polyuria, polydipsia and dehydration (Dark and Razak 2014). As many early symptoms are non-specific, the cause may mistakenly be presumed to be due to other health concerns or treatments such as radiotherapy or chemotherapy (Foulkes 2010). If diagnosis and treatment of hypercalcaemia is delayed the number and severity of symptoms the patient experiences can increase. Common signs and symptoms are listed in Box 1. Renal calculi (kidney stones) may develop due to raised serum calcium and if hypercalcaemia is long-standing, calcium may also be deposited in the soft tissues, for example, chondrocalcinosis and nephrocalcinosis, and trigger diverse clinical presentations depending on the areas affected. Many people with chronic hypercalcaemia remain asymptomatic, particularly when the condition is mild (CKS 2014). However, prompt detection and management are important. The extent of symptoms experienced is typically related to severity and rate Box 1 Common signs and symptoms of patients with hypercalcaemia ■ Bone pain ■ Muscle weakness ■ Joint/bone and muscle aches ■ Fatigue ■ Impaired concentration and memory ■ Depression ■ Altered levels of consciousness: drowsiness, delirium, seizures and/or coma ■ Anxiety ■ Nausea and vomiting ■ Anorexia ■ Constipation ■ Abdominal pain ■ Polyuria ■ Polydipsia ■ Dehydration ■ Renal colic due to kidney stone (nephrolithiasis) ■ Hypertension ■ Shortened QT interval on electrocardiogram ■ Cardiac arrhythmias (Sargent and Smith 2010, Clinical Knowledge Summaries 2014, Strachan and Newell-Price 2014)
24 May 2015 | Volume 27 | Number 4
of onset (CKS 2014). If symptoms are not recognised and treated in a timely fashion, the patient may become progressively unwell and may require admission to hospital (Foulkes 2010). Progressive cardiac dysfunction and renal failure can develop if hypercalcaemia is not managed appropriately (Karthikeyan et al 2006) and cardiac arrhythmias, cardiac arrest or coma may occur. When a diagnosis has been confirmed, the next step is to determine the cause. Initial investigation is directed at malignancy and hyperparathyroidism, the most common causes (Green 2014). Investigations may include urinalysis, renal function and serum electrolytes to assess for chronic kidney disease and liver function tests to exclude chronic liver failure (CKS 2014). It is also useful to assess PTH and phosphate levels to help determine the cause. A review of the patient’s medical history may highlight other potential underlying causes, such as sarcoidosis. Serum and urine protein electrophoresis, including tests for Bence-Jones protein, should also be considered to check for myeloma (CKS 2014). If the cause is unknown, referring the patient to the endocrinology team should be considered.
Treatment How the patient is treated for hypercalcaemia depends on calcium levels, clinical presentation and underlying cause (Green 2014). The goal of therapy is to treat hypercalcaemia and subsequently manage the underlying cause. Patients with severe hypercalcaemia or those who are acutely symptomatic should be admitted to hospital urgently for treatment. It is important to liaise with the oncology team for patients with malignant hypercalcaemia because management of the underlying cancer can reduce further incidents. There is no clear consensus about how to manage patients with cancer-associated mild hypercalcaemia or who are asymptomatic, so specialist advice should be sought (CKS 2014). However, they should be advised to avoid thiazide diuretics, dehydration, high-calcium diet and prolonged bed rest or inactivity (Shane and Berenson 2014). Oral bisphosphonates may also be considered as maintenance therapy. The initial goals of treatment are to stabilise the patient and reduce calcium levels through rehydration and decreasing bone resorption (Ahmad et al 2015). In the acutely unwell patient it is important to assess and maintain the airway, breathing and circulation, with regular assessment of respiratory rate, oxygen saturations, blood pressure, pulse and fluid balance. If the patient is taking any medication that may contribute to hypercalcaemia, NURSING OLDER PEOPLE
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for example calcium supplements or thiazide diuretics, it should be stopped or reduced if appropriate (CKS 2014). Patients should be rehydrated with intravenous (IV) saline 0.9% to improve renal function and increase urinary excretion of calcium (Dark and Razak 2014). Hydration is needed as many patients are dehydrated as a result of nausea, vomiting or renal impairment. IV infusion is typically between four and six litres in 24 hours (Society for Endocrinology 2013), although this depends on calcium levels and previous hydration status. Renal and cardiovascular status of older patients should be assessed to prevent fluid overload during this period, particularly when there is known pre-existing renal and cardiovascular compromise. Loop diuretics, for example, furosemide, are no longer routinely used to reduce serum calcium levels, although may still be considered if fluid overload develops (Society for Endocrinology 2013). When the patient is adequately rehydrated, IV bisphosphonates can be administered to inhibit osteoclast activity in the bone (Green 2014). As osteoblast functions are not affected by bisphosphonates, calcium levels usually reduce rapidly. Slower infusion rates and/or reduced doses may be considered where there is renal impairment (Society for Endocrinology 2013). Commonly used bisphosphonates include zoledronic acid, pamidronate or ibandronic acid (Society for Endocrinology 2013). Calcitonin also acts rapidly to increase calcium excretion and reduce bone resorption (Dark and Razak 2014), and may be considered if bisphosphonates are not suitable or offer a poor response (Society for Endocrinology 2013). Denosumab, a monoclonal antibody, may also be considered as a treatment option in patients with hypercalcaemia of malignancy (Hu et al 2014). Haemodialysis may be used in life-threatening hypercalcaemia (Crowley and Gittoes 2013). Calcium levels need to be carefully monitored throughout treatment as hypocalcaemia may be induced. Second-line treatments for hypercalcaemia include glucocorticoids to inhibit calcitriol production in lymphoma or other granulomatous diseases, or calcimimetics in patients with hypercalcaemia due to primary hyperparathyroidism, parathyroid carcinoma or renal failure (Society for Endocrinology 2013). In some instances treatment of hypercalcaemia may not be appropriate, for example, for patients with advanced cancer who are not experiencing distressing or unpleasant symptoms (Seccareccia 2010, CKS 2014). When patients are terminally ill the focus of care shifts from curative intent to NURSING OLDER PEOPLE
a supportive approach, particularly where lifespan is relatively short. The focus in these circumstances is therefore on the relief of suffering rather than continued intense investigations or treatment. This can be a difficult concept for the family to understand, especially if there have been repeated episodes of hypercalcaemia throughout the patient’s journey. It is therefore important that in palliative circumstances the patient and family are aware of the concerted effort to control symptoms, and any concerns that the family may have are discussed in an open manner.
Nursing management As patients often present with symptoms that may be vague, or which may mimic the side effects of other treatments, nurses should have a high index of suspicion of hypercalcaemia in those with predisposing pathology or who are known to have chronic hypercalcaemia. It is also imperative that advanced nurse practitioners are vigilant in identifying abnormal test results and aware of appropriate follow-up actions (Grandjean and McMullen 2010). Effective education of patients who are at risk of hypercalcaemia will help them and their families to be aware of the warning signs. This will enable families to seek assistance promptly, which will lead to prompt diagnosis and starting appropriate treatment (Gabriel 2012). As many older people have multiple comorbidities, it is important to encourage them to describe every symptom, no matter how trivial it may seem, to enable a comprehensive approach to be adopted. Hypercalcaemia may signify advancing disease in patients with malignancy, or metastatic disease, which may have many emotional and psychological implications for them and their families. Good communication skills and involvement of relevant members of the multidisciplinary team will enable effective assessment and management of actual or potential problems. Online resources such as patient information leaflets written by Cancer Research UK (www.cancerresearchuk.org) or Macmillan Cancer Support (www.macmillan.org.uk) may also be useful to aid communication and provide support and further information for patients who are coping with the physical and emotional effects of cancer. Where patients and family members are finding it difficult to cope with disease progression, it is often helpful to discuss care with the oncology team, so that appropriate help can be put in place. Patients with advanced cancer may develop changes in their mental status as a result of medical conditions such as hypercalcaemia. May 2015 | Volume 27 | Number 4 25
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Art & science | endocrine disease Regular assessments of mental status will enable prompt detection of delirium or other changes in cognitive status. Although the tools and systems may differ between healthcare providers and clinical environments, the main factors to assess include (Waller and Caroline 2000): ■ Consciousness, alertness and ability to concentrate. ■ Orientation to time, place and person. ■ Activity – quiet/agitated. ■ Thought – logical reasoning, delusions, hallucinations and cognitive function. ■ Memory. In severe cases of hypercalcaemia, the patient will require close monitoring of vital signs and cardiac status. Careful monitoring of hydration status is required, not only because of the initial risk of dehydration, but also because those with renal or cardiac insufficiencies are at risk of fluid overload (hypervolaemia) from the saline infusion (Shane and Berenson 2014). Nurses should be vigilant for patients developing oedema or dyspnoea (shortness of breath) as these may indicate hypervolaemia. Part of the nurse’s role is to support patients receiving treatment and to manage other side effects of hypercalcaemia, such as nausea and constipation, in conjunction with the medical team. This requires an individualised and holistic approach, particularly due to the often complex pre-existing comorbidities of older patients. IV bisphosphonates are generally well tolerated, although patients may experience flu-like symptoms as a side effect (Shane and Berenson 2014).
Patients with mildly elevated calcium levels who are being managed in community settings need general advice to ensure they maintain adequate fluid intake – at least six to eight glasses of water a day – to minimise the risk of nephrolithiasis (Shane and Berenson 2014) and maintain normal dietary intake of calcium and vitamin D (Fenech and Turner 2013). Restriction of dietary calcium is not advocated as a preventative strategy because it may lead to malnutrition. Referral to the dietetics team should be made if dietary advice is required. Where possible it is important to encourage ambulation to minimise bone resorption and other risks of immobilisation such as deep vein thrombosis. Regular monitoring of serum calcium levels and follow-up assessments are required to ensure that no further complications develop.
Conclusion Hypercalcaemia is a relatively common biochemical abnormality that can have a significant effect on the health and wellbeing of older people in acute hospital and community settings. Understanding the pathophysiology, signs and symptoms will permit effective diagnosis and timely management. Nurses should be aware of at-risk population groups, so they can work with them to educate, support and identify symptoms. Nurses play an important role in the assessment and management of patients with hypercalcaemia, who often have other complex healthcare needs.
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Conflict of interest None declared
References Ahmad S, Kuraganti G, Steenkamp D (2015) Hypercalcemic crisis: a clinical review. The American Journal of Medicine. 128, 3, 239-245.
Fenech M, Turner J (2013) Hypercalcaemia and primary hyperparathyroidism. Medicine. 41, 10, 573-576.
Christensen S, Nissen P, Vestergaard P et al (2011) Familial hypocalciuric hypercalcaemia: a review. Current Opinion in Endocrinology, Diabetes, and Obesity. 18, 6, 359-370.
Foulkes M (2010) Nursing management of common oncological emergencies. Nursing Standard. 24, 41, 49-56.
Clinical Knowledge Summaries (2014) Hypercalcaemia. http://cks.nice.org.uk/ hypercalcaemia#!topicsummary (Last accessed: March 25 2015.) Crowley R, Gittoes N (2013) How to approach hypercalcaemia. Clinical Medicine. 13, 3, 287-290. Dark C, Razak A (2014) Oncology. In Walker B, Colledge N, Ralston S et al (Eds) Davidson’s Principles & Practice of Medicine. 22nd edition. Churchill Livingstone Elsevier, Edinburgh.
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Gabriel J (2012) Acute oncological emergencies. Nursing Standard. 27, 4, 35-41.
Hu M, Glezerman I, Leboulleux S et al (2014) Denosumab for treatment of hypercalcemia of malignancy. The Journal of Clinical Endocrinology and Metabolism. 99, 9, 3144-3152. Karthikeyan V, Khan J, Lip G (2006) Hypercalcemia and the cardiovascular system. Heart and Metabolism. 30, 25-29.
Grandjean C, McMullen P (2010) Hypercalcemia: what constitutes reasonable follow-up? The Journal for Nurse Practitioners. 6, 9, 691-693.
Sargent J, Smith O (2010) Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders. British Journal of Haematology. 149, 4, 465-477.
Green T (2014) Hypercalcemia in Emergency Medicine. http://emedicine.medscape.com/ article/766373-overview (Last accessed: March 25 2015.)
Seccareccia D (2010) Cancer-related hypercalcemia. Canadian Family Physician. 56, 3, 244-246.
Smellie W, Vanderpump M, Fraser W et al (2008) Best practice in primary care pathology: review 11. Journal of Clinical Pathology. 61, 4, 410-418. Society for Endocrinology (2013) Acute Hypercalcaemia: Emergency Endocrine Guidance. Society for Endocrinology, Bristol. Strachan M, Newell-Price J (2014) Endocrine disease. In Walker B, Colledge N, Ralston S et al (Eds) Davidson’s Principles & Practice of Medicine. 22nd edition. Churchill Livingstone Elsevier, Edinburgh. Waller A, Caroline N (2000) Handbook of Palliative Care in Cancer. Second edition. Butterworth-Heinemann, Oxford.
Shane E, Berenson J (2014) Treatment of Hypercalcemia. tinyurl.com/q9povw3 (Last accessed: March 31 2015.)
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Diagnosis and management of patients with hypercalcaemia Jennie Walker discusses the signs, symptoms and treatment of this common, yet potentially life-threatening, condition Correspondence [email protected] Jennie Walker is clinical educator for musculoskeletal and neurosciences, Queen’s Medical Centre, Division of Orthopaedic Trauma and Sports Medicine, Nottingham Date of submission February 1 2015 Date of acceptance March 16 2015 Peer review This article has been subject to double-blind review and has been checked using antiplagiarism software Author guidelines journals.rcni.com/r/ nop-author-guidelines
Abstract Hypercalcaemia is a common biochemical abnormality in the blood that can be caused by malignancy, hyperparathyroidism, medications or underlying medical conditions. Initial signs and symptoms are often vague, however, if someone has severe hypercalcaemia it is treated as an emergency, requiring prompt management to prevent life-threatening complications such as dehydration, cardiac arrhythmias or coma. Understanding the pathophysiology, signs and symptoms of hypercalcaemia enables effective diagnosis and holistic management of the patient with complex health needs. Keywords Biochemical abnormalities, cancer, dehydration, endocrine disease, hypercalcaemia, hyperparathyroidism ONE OF the most common biochemical abnormalities in the body is elevated calcium levels in the blood, which is referred to as hypercalcaemia (Strachan and Newell-Price 2014). Although common (Grandjean and McMullen 2010), it can be potentially life threatening due to its effects on the kidneys, heart and brain (Clinical Knowledge Summaries (CKS) 2014). Sometimes patients are asymptomatic and abnormalities are discovered incidentally, through routine blood tests or investigations for other medical conditions. Hypercalcaemia can also present as an acute emergency, or more subtly, with chronic problems such as musculoskeletal aches and pains. Raised calcium levels may be caused by excessive calcium release, increased intestinal absorption or decreased renal excretion and may indicate other disease processes.
22 May 2015 | Volume 27 | Number 4
Prevalence and causes Data on the prevalence of hypercalcaemia in the general non-hospitalised population are scarce (CKS 2014), although Dark and Razak (2014) report an approximate prevalence of 15-20 cases per 100,000 people. Primary hyperparathyroidism and cancer account for around 90% of cases (CKS 2014). Primary hyperparathyroidism is the excessive secretion of parathyroid hormone (PTH), which is often caused by a parathyroid adenoma, although it may also be due to multiple endocrine neoplasia (Strachan and Newell-Price 2014). Primary hyperparathyroidism occurs in around 25 per 100,000 people in the general population and in 75 per 100,000 hospitalised patients (Green 2014). These figures are based on data from the US. While hyperparathyroidism is the most common cause of hypercalcaemia in outpatient settings, malignancy is the most common cause in hospitalised patients (Fenech and Turner 2013). Malignancy-associated hypercalcaemia occurs in between 20 and 30% of patients during the course of the disease (Green 2014). Most episodes of malignancy-associated hypercalcaemia occur with advanced disease and patients typically have a poor prognosis with up to 50% 30-day mortality (Green 2014). Patients who are particularly at risk of developing hypercalcaemia from metastatic disease include those with squamous cell lung cancer, breast cancer and multiple myeloma (Foulkes 2010, CKS 2014), although hypercalcaemia can also occur in other malignancies with or without bone metastases (Seccareccia 2010). Less common causes of elevated calcium include granulomatous disease, for example, sarcoidosis and tuberculosis; renal failure; Addison’s disease; thyrotoxicosis; dehydration; chronic liver disease; and immobilisation in people with Paget’s disease (CKS 2014, Green 2014). NURSING OLDER PEOPLE
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Thiazide diuretic use is also known to predispose to hypercalcaemia because it increases renal tubular reabsorption of calcium (Ahmad et al 2015). Familial hypocalciuric hypercalcaemia is a rare autosomal disorder that is caused by mutations in the calcium-sensing receptor gene (Christensen et al 2011). Although initial management of patients with hypercalcaemia will follow a standardised approach, the causes need to be considered carefully as the management of underlying pathology will differ significantly. Hypercalcaemia can be classified as mild, moderate or severe based on serum calcium concentration (CKS 2014), although serum calcium levels do not always correlate with the severity of symptoms (Smellie et al 2008). While symptoms tend to be progressive, patient response to raised calcium levels is variable and not all patients will experience all of the signs and symptoms (Foulkes 2010).
Pathophysiology Calcium is present in the intracellular and extracellular fluids, although most of the body’s calcium content is found in bone and calcified cartilage. Calcium is important for effective working of the cells and muscle contraction, neurotransmission and bone formation. Serum calcium levels are normally maintained in the
therapeutic range by the PTH, 1,25-dihydroxy vitamin D3 (calcitriol) and calcitonin (Grandjean and McMullen 2010). PTH and calcitriol are important physiological regulators of calcium homeostasis, while calcitonin plays a modest role (Sargent and Smith 2010). Although these regulators are useful in preventing hypocalcaemia, they are less effective in controlling hypercalcaemia (Sargent and Smith 2010). The actions of PTH, calcitriol and calcitonin are outlined in Table 1. In normal circumstances bone is continuously resorbed (removed) by osteoclasts and replaced with new bone created by osteoblasts. For hypercalcaemia to develop, the normal calcium regulation system must be overwhelmed by an excess of PTH, calcitriol or a huge calcium load (Green 2014). In patients with malignancy, tumour cells can release proteins and cytokines that stimulate osteoclasts and enhance bone resorption, which results in calcium being released into the blood and increasing calcium levels (Sargent and Smith 2010). Diagnosis is made by measuring total serum calcium and adjusting for serum albumin. It is important to correct for albumin levels because total calcium values underestimate levels of ionised calcium (Seccareccia 2010). Mild hypercalcaemia is an adjusted serum calcium concentration of 2.65-3.00mmol/L. Moderate is 3.01-3.40mmol/L and severe is greater
Table 1 Actions of parathyroid hormone, calcitriol and calcitonin Hormone
Target organ
Actions
Effect
Parathyroid hormone
Bone
■ Stimulates osteoclastic bone resorption ■ Stimulates renal tubule calcium reabsorption
Raised calcium
Kidney
■ Inhibits renal tubule phosphate reabsorption ■ Stimulates renal 1a-hydroxylase conversion of 25-hydroxy vitamin D (calcifediol) to 1,25-dihydroxy vitamin D3 (calcitriol)
Lowered phosphate
Gut
■ Increases calcium and phosphate absorption
Raised calcium, lowered phosphate
■ Increases bone resorption ■ Enhances bone mineralisation
Raised calcium
Kidney
■ Increases renal calcium reabsorption
Raised calcium
Bone
■ Inhibits osteoclastic bone resorption
Lowered calcium
Kidney
■ Promotes renal calcium and phosphate excretion
Lowered calcium and phosphate
Calcitriol (1,25-dihydroxy Bone vitamin D3)
Calcitonin
(Sargent and Smith 2010)
NURSING OLDER PEOPLE
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Art & science | endocrine acute care disease than 3.40mmol/L (CKS 2014). Plain X-rays can show bone abnormalities such as demineralisation, bone cysts, fractures or bony metastases.
Signs and symptoms Signs and symptoms of the condition are often diverse and non-specific (CKS 2014). Common features include musculoskeletal pain and weakness, drowsiness, confusion, nausea, vomiting, polyuria, polydipsia and dehydration (Dark and Razak 2014). As many early symptoms are non-specific, the cause may mistakenly be presumed to be due to other health concerns or treatments such as radiotherapy or chemotherapy (Foulkes 2010). If diagnosis and treatment of hypercalcaemia is delayed the number and severity of symptoms the patient experiences can increase. Common signs and symptoms are listed in Box 1. Renal calculi (kidney stones) may develop due to raised serum calcium and if hypercalcaemia is long-standing, calcium may also be deposited in the soft tissues, for example, chondrocalcinosis and nephrocalcinosis, and trigger diverse clinical presentations depending on the areas affected. Many people with chronic hypercalcaemia remain asymptomatic, particularly when the condition is mild (CKS 2014). However, prompt detection and management are important. The extent of symptoms experienced is typically related to severity and rate Box 1 Common signs and symptoms of patients with hypercalcaemia ■ Bone pain ■ Muscle weakness ■ Joint/bone and muscle aches ■ Fatigue ■ Impaired concentration and memory ■ Depression ■ Altered levels of consciousness: drowsiness, delirium, seizures and/or coma ■ Anxiety ■ Nausea and vomiting ■ Anorexia ■ Constipation ■ Abdominal pain ■ Polyuria ■ Polydipsia ■ Dehydration ■ Renal colic due to kidney stone (nephrolithiasis) ■ Hypertension ■ Shortened QT interval on electrocardiogram ■ Cardiac arrhythmias (Sargent and Smith 2010, Clinical Knowledge Summaries 2014, Strachan and Newell-Price 2014)
24 May 2015 | Volume 27 | Number 4
of onset (CKS 2014). If symptoms are not recognised and treated in a timely fashion, the patient may become progressively unwell and may require admission to hospital (Foulkes 2010). Progressive cardiac dysfunction and renal failure can develop if hypercalcaemia is not managed appropriately (Karthikeyan et al 2006) and cardiac arrhythmias, cardiac arrest or coma may occur. When a diagnosis has been confirmed, the next step is to determine the cause. Initial investigation is directed at malignancy and hyperparathyroidism, the most common causes (Green 2014). Investigations may include urinalysis, renal function and serum electrolytes to assess for chronic kidney disease and liver function tests to exclude chronic liver failure (CKS 2014). It is also useful to assess PTH and phosphate levels to help determine the cause. A review of the patient’s medical history may highlight other potential underlying causes, such as sarcoidosis. Serum and urine protein electrophoresis, including tests for Bence-Jones protein, should also be considered to check for myeloma (CKS 2014). If the cause is unknown, referring the patient to the endocrinology team should be considered.
Treatment How the patient is treated for hypercalcaemia depends on calcium levels, clinical presentation and underlying cause (Green 2014). The goal of therapy is to treat hypercalcaemia and subsequently manage the underlying cause. Patients with severe hypercalcaemia or those who are acutely symptomatic should be admitted to hospital urgently for treatment. It is important to liaise with the oncology team for patients with malignant hypercalcaemia because management of the underlying cancer can reduce further incidents. There is no clear consensus about how to manage patients with cancer-associated mild hypercalcaemia or who are asymptomatic, so specialist advice should be sought (CKS 2014). However, they should be advised to avoid thiazide diuretics, dehydration, high-calcium diet and prolonged bed rest or inactivity (Shane and Berenson 2014). Oral bisphosphonates may also be considered as maintenance therapy. The initial goals of treatment are to stabilise the patient and reduce calcium levels through rehydration and decreasing bone resorption (Ahmad et al 2015). In the acutely unwell patient it is important to assess and maintain the airway, breathing and circulation, with regular assessment of respiratory rate, oxygen saturations, blood pressure, pulse and fluid balance. If the patient is taking any medication that may contribute to hypercalcaemia, NURSING OLDER PEOPLE
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for example calcium supplements or thiazide diuretics, it should be stopped or reduced if appropriate (CKS 2014). Patients should be rehydrated with intravenous (IV) saline 0.9% to improve renal function and increase urinary excretion of calcium (Dark and Razak 2014). Hydration is needed as many patients are dehydrated as a result of nausea, vomiting or renal impairment. IV infusion is typically between four and six litres in 24 hours (Society for Endocrinology 2013), although this depends on calcium levels and previous hydration status. Renal and cardiovascular status of older patients should be assessed to prevent fluid overload during this period, particularly when there is known pre-existing renal and cardiovascular compromise. Loop diuretics, for example, furosemide, are no longer routinely used to reduce serum calcium levels, although may still be considered if fluid overload develops (Society for Endocrinology 2013). When the patient is adequately rehydrated, IV bisphosphonates can be administered to inhibit osteoclast activity in the bone (Green 2014). As osteoblast functions are not affected by bisphosphonates, calcium levels usually reduce rapidly. Slower infusion rates and/or reduced doses may be considered where there is renal impairment (Society for Endocrinology 2013). Commonly used bisphosphonates include zoledronic acid, pamidronate or ibandronic acid (Society for Endocrinology 2013). Calcitonin also acts rapidly to increase calcium excretion and reduce bone resorption (Dark and Razak 2014), and may be considered if bisphosphonates are not suitable or offer a poor response (Society for Endocrinology 2013). Denosumab, a monoclonal antibody, may also be considered as a treatment option in patients with hypercalcaemia of malignancy (Hu et al 2014). Haemodialysis may be used in life-threatening hypercalcaemia (Crowley and Gittoes 2013). Calcium levels need to be carefully monitored throughout treatment as hypocalcaemia may be induced. Second-line treatments for hypercalcaemia include glucocorticoids to inhibit calcitriol production in lymphoma or other granulomatous diseases, or calcimimetics in patients with hypercalcaemia due to primary hyperparathyroidism, parathyroid carcinoma or renal failure (Society for Endocrinology 2013). In some instances treatment of hypercalcaemia may not be appropriate, for example, for patients with advanced cancer who are not experiencing distressing or unpleasant symptoms (Seccareccia 2010, CKS 2014). When patients are terminally ill the focus of care shifts from curative intent to NURSING OLDER PEOPLE
a supportive approach, particularly where lifespan is relatively short. The focus in these circumstances is therefore on the relief of suffering rather than continued intense investigations or treatment. This can be a difficult concept for the family to understand, especially if there have been repeated episodes of hypercalcaemia throughout the patient’s journey. It is therefore important that in palliative circumstances the patient and family are aware of the concerted effort to control symptoms, and any concerns that the family may have are discussed in an open manner.
Nursing management As patients often present with symptoms that may be vague, or which may mimic the side effects of other treatments, nurses should have a high index of suspicion of hypercalcaemia in those with predisposing pathology or who are known to have chronic hypercalcaemia. It is also imperative that advanced nurse practitioners are vigilant in identifying abnormal test results and aware of appropriate follow-up actions (Grandjean and McMullen 2010). Effective education of patients who are at risk of hypercalcaemia will help them and their families to be aware of the warning signs. This will enable families to seek assistance promptly, which will lead to prompt diagnosis and starting appropriate treatment (Gabriel 2012). As many older people have multiple comorbidities, it is important to encourage them to describe every symptom, no matter how trivial it may seem, to enable a comprehensive approach to be adopted. Hypercalcaemia may signify advancing disease in patients with malignancy, or metastatic disease, which may have many emotional and psychological implications for them and their families. Good communication skills and involvement of relevant members of the multidisciplinary team will enable effective assessment and management of actual or potential problems. Online resources such as patient information leaflets written by Cancer Research UK (www.cancerresearchuk.org) or Macmillan Cancer Support (www.macmillan.org.uk) may also be useful to aid communication and provide support and further information for patients who are coping with the physical and emotional effects of cancer. Where patients and family members are finding it difficult to cope with disease progression, it is often helpful to discuss care with the oncology team, so that appropriate help can be put in place. Patients with advanced cancer may develop changes in their mental status as a result of medical conditions such as hypercalcaemia. May 2015 | Volume 27 | Number 4 25
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Art & science | endocrine disease Regular assessments of mental status will enable prompt detection of delirium or other changes in cognitive status. Although the tools and systems may differ between healthcare providers and clinical environments, the main factors to assess include (Waller and Caroline 2000): ■ Consciousness, alertness and ability to concentrate. ■ Orientation to time, place and person. ■ Activity – quiet/agitated. ■ Thought – logical reasoning, delusions, hallucinations and cognitive function. ■ Memory. In severe cases of hypercalcaemia, the patient will require close monitoring of vital signs and cardiac status. Careful monitoring of hydration status is required, not only because of the initial risk of dehydration, but also because those with renal or cardiac insufficiencies are at risk of fluid overload (hypervolaemia) from the saline infusion (Shane and Berenson 2014). Nurses should be vigilant for patients developing oedema or dyspnoea (shortness of breath) as these may indicate hypervolaemia. Part of the nurse’s role is to support patients receiving treatment and to manage other side effects of hypercalcaemia, such as nausea and constipation, in conjunction with the medical team. This requires an individualised and holistic approach, particularly due to the often complex pre-existing comorbidities of older patients. IV bisphosphonates are generally well tolerated, although patients may experience flu-like symptoms as a side effect (Shane and Berenson 2014).
Patients with mildly elevated calcium levels who are being managed in community settings need general advice to ensure they maintain adequate fluid intake – at least six to eight glasses of water a day – to minimise the risk of nephrolithiasis (Shane and Berenson 2014) and maintain normal dietary intake of calcium and vitamin D (Fenech and Turner 2013). Restriction of dietary calcium is not advocated as a preventative strategy because it may lead to malnutrition. Referral to the dietetics team should be made if dietary advice is required. Where possible it is important to encourage ambulation to minimise bone resorption and other risks of immobilisation such as deep vein thrombosis. Regular monitoring of serum calcium levels and follow-up assessments are required to ensure that no further complications develop.
Conclusion Hypercalcaemia is a relatively common biochemical abnormality that can have a significant effect on the health and wellbeing of older people in acute hospital and community settings. Understanding the pathophysiology, signs and symptoms will permit effective diagnosis and timely management. Nurses should be aware of at-risk population groups, so they can work with them to educate, support and identify symptoms. Nurses play an important role in the assessment and management of patients with hypercalcaemia, who often have other complex healthcare needs.
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Conflict of interest None declared
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