Normal range: adjusted calcium 2.1–2.6 mmol/L

The majority of calcium circulates bound to albumin, but a small amount is present as the physiologically active “ionised” calcium. The adjusted calcium or “ionised” calcium should be used when the patient has a low albumin.

Corrected calcium (mmol/L) = measured calcium + (0.02 x [40-albumin g/l]).

Occurs in about 10–20% of patients affected by cancer. It is generally indicative of a poorer prognosis in solid tumours.

Symptoms and signs:

Confusion, drowsiness, nausea and vomiting, thirst, polyuria, constipation, lethargy, bradycardia, myoclonus, seizures and coma.

Severity of symptoms are not necessarily indicative of the level of hypercalcaemia.

Generally when managing hypercalcaemia, an adjusted calcium level greater than 3.0 should be treated whether the patient is symptomatic or not.

Treatment:

It is important to carefully balance the benefits versus burdens of treating hypercalcaemia in a patient with advanced disease, considering the care setting, previous history of hypercalcaemia and patient preferences.

Treatment includes IV rehydration and use of intravenous bisphosphonates.

Bisphosphonates start to take effect after 48 hours to lower serum calcium, however the maximum effect may not be seen for 5 to 7 days. Bisphosphonates therefore may not be indicated in a patient whose estimated prognosis is very short.

Discontinue any calcium, vitamin D or vitamin A supplements.

Review and consider discontinuing any drugs which may affect renal blood flow e.g. NSAIDs, diuretics, ACE inhibitors, Angiotensin II receptor antagonists.

Renal function and albumin should be checked prior to giving infusion. In renal failure consult product literature for dosing guidance.

Recent studies have shown zoledronic acid to be superior to pamidronate in terms of more rapid onset and longer duration of action but please refer to your local policy for guidance.

Ensure the patient is appropriately hydrated before giving a bisphosphonate (e.g 1–3 litres of parenteral sodium chloride 0.9%) volume and rate should be adjusted according to age and other co-morbidities.

Depending on local policy pamidronate or zoledronic acid is used:

Either:

Disodium pamidronate IV infused at a rate not exceeding 1 mg/min (see manufacturer’s guidance for patients with renal impairment):

However one systematic review of bisphosphonate use4 states that 90mg pamidronate may be given irrespective of the initial calcium level, in order to increase the likelihood of successful and sustained normocalcaemia.

Or:

Zoledronic acid IV 4mg in 100 mL 0.9% saline infused over 15 minutes at least (see manufacturer’s guidance for patients with renal impairment)

Repeated infusions of bisphosphonates carry an increased risk of developing osteonecrosis of the jaw (rare before 4 months of treatment). Patients should avoid invasive dental procedures while receiving ongoing bisphosphonate therapy.

Monitoring

Repeat calcium levels are best monitored at 5–7 days post infusion as it takes this length of time for the bisphosphonate to have reached its maximum effect. It is advisable to recheck the calcium level when patient experiences symptoms or every 3-4 weeks.

Management of resistant / recurrent hypercalcaemia

• For resistant hypercalcaemia (hypercalcaemia not responding to initial bisphosphonate therapy at appropriate dose) seek specialist palliative care advice.
• Recurrent hypercalcaemia, that has recurred within a short time (e.g. 1 to 2 weeks) after previous appropriate treatment may represent advancing disease and may be less likely to respond to further treatment. If required, a further dose can be administered at 5–7 days. Seek specialist palliative care advice.