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Hypercalcaemia

Introduction

Hypercalcaemia is a raised level of corrected calcium * in the blood. It is the commonest life-threatening metabolic disorder in cancer patients, most frequently occurring in myeloma, breast, renal, lung and thyroid cancers however, 20% of patients with hypercalcaemia do not have bone metastases.

Assessment

Signs and symptoms

  • Common symptoms include malaise, weakness, anorexia, thirst, nausea, constipation and polyuria
  • Severe symptoms include nausea, vomiting, ileus, delirium, seizures, drowsiness and coma
  • Pain can be precipitated or exacerbated by hypercalcaemia
  • Onset of symptoms raising clinical suspicion should be investigated. Bloods should be checked for urea and electrolytes (U&Es), estimated glomerular filtration rate (eGFR), liver function tests (LFT’s) and calcium.

Points to consider prior to treatment

  • First episode or long interval since previous episode
  • Patient reports good quality of life prior to episode               
  • Multi-disciplinary team expectation is that treatment will have durable effect             
  • Patient is willing and able to have intravenous treatment and blood tests
  • Treatment may not be appropriate in a dying patient at the end of life – seek advice.

 

Management

Bisphosphonates and duration of action

 

zoledronic acid

disodium pamidronate

Intravenous (IV) dose

4mg

30 to 90mg

Onset of effect

<4 days

<3 days

Maximum effect

4 to 7 days

5 to 7 days

Duration of effect

4 weeks

2.5 weeks

 

* Corrected calcium = Measured calcium +0.022 x (40 - serum albumin g/l)

 Treatment

  • The aim of treatment is to improve symptoms and reduce corrected calcium * level to within the normal range
  • Normal corrected calcium value * 2.12 to 2.62mmol/l (locally defined ranges will apply)
  • IV fluid replacement and IV bisphosphonates are treatments of choice
  • The choice of bisphosphonate may be determined by local policy (such as disodium pamidronate/zoledronic acid). Refer to local formulary
  • To reduce risk of renal toxicity from bisphosphonate treatment, consider withholding medication that affects the renal function (eg non-steroidal anti-inflammatory drugs, diuretics, thiazide diuretics, angiotensin-converting enzyme inhibitors).

 

Practice Points

  • If the patient is asymptomatic with corrected calcium * between 2.62 mmol/l and <2.8 mmol/l, rehydrate with fluids and review as per Table 1
  • Explain signs, symptoms and treatment options to the patient, family and carers
  • Not all symptoms resolve after treatment. This may be due to other cause(s) or underlying disseminated disease
  • Bisphosphonates may cause mild flu-like symptoms
  • Bisphosphonates are implicated risk factors in osteonecrosis of the jaw, osteonecrosis of the auditory canal and atypical fractures 
  • Where possible, patients should have regular dental checks and avoid invasive dental procedures whilst on treatment
  • The severity of symptoms is related to the rate of increase; not the level of corrected calcium *
  • The speed of recurrence may signify a poor prognosis
  • Review current treatments for underlying disease
  • Untreated severe hypercalcaemia can be fatal.

 

Hypercalcaemia - figure 1

 

Table 1 - Bisphosphonate treatment for Hypercalcaemia

Corrected calcium* (mmol/l)

Drug & Dose

Diluent and maximum infusion rate

 

disodium pamidronate

 

2.62 to 3.0

15mg to 30mg

500ml NaCl 0.9% over > 60 minutes

3.0 to 3.5

60mg

500ml NaCl 0.9% over > 60 minutes

3.5 to 4.0

90mg

500ml NaCl 0.9% over > 90 minutes

>4.0

90mg

500ml NaCl 0.9% over > 90 minutes

 

zoledronic acid

 

>3.00

4mg

100ml NaCl 0.9% over 15 minutes

If corrected calcium >3.0mmol/l, some units routinely give pamidronate 90mg as a higher dose.   

 

Reduced doses in renal impairment

Disodium pamidronate in renal impairment, seek advice

  • eGFR >30ml/min: Minimum infusion period 90 minutes, maximum infusion rate 20mg/hour: consider dose reduction.
  • eGFR <30ml/min: avoid except in life threatening hypercalcaemia where specialist advice should be sought to determine if benefit outweighs risk.

 Zoledronic acid in renal impairment

  • Patients with tumour induced hypercalcaemia  (TIH) and deteriorating renal function should be appropriately assessed to determine if the potential benefit of treatment with zoledronic acid outweighs the possible risk.
  • After 24 - 48 hours of rehydration, consider a single IV dose of zoledronic acid 4 mg in 100 ml sodium chloride 0.9% over ≥ 15 minutes. N.B Dose alteration may not be needed in mild to moderate renal impairment in patients with TIH( i.e. eGFR >30ml/min)
  • Avoid if eGFR <30ml/min, see Summary of Product Characteristics (www.medicines.org.uk) for further details.

Resources

Guidelines

  • Scottish Intercollegiate Guidelines Network (2008). Guideline 106:Control of pain in adults with cancer. SIGN: Edinburgh; www.sign.ac.uk/pdf/SIGN106.pdf

Patient and professional website resources

Textbooks

  • Oxford Textbook of Palliative Medicine.  4th Edition  2010  Management of Hypercalcaemia CH 10.10 p1015-1017
  • Symptom Management in Advanced Cancer 4th edition 2009 Hypercalcaemia Ch 6 p215-219Twycross Wilcock and Toller
  • Palliative Care Formulary 4th edition (PCF4) 2011 Endocrine system and immunomodulation p469-479
  • British National Formulary 65 (BNF) 2013 6.6.2 Bisphosphonates and other drugs affecting bone metabolismp491-495