Consider whether it is appropriate to treat the hypercalcaemia

• There may be situations when treatment is not considered appropriate, for example when the person has advanced cancer and is not suffering distressing or unpleasant symptoms as a result of hypercalcaemia [Kovacs et al, 1995]. There is no evidence that treatment of hypercalcaemia affects overall mortality, unless the primary cancer is treatable [Kovacs et al, 1995].
• However, treatment can alleviate distressing symptoms and improve quality of life [Kovacs et al, 1995; Heys et al, 1998; Ralston et al, 2004], returning the person to their pre-hypercalcaemic state within 3–4 days. Hypercalcaemia may reduce the pain threshold in people with cancer [Heys et al, 1998]. Furthermore, bisphosphonates reduce bone pain and the risk of pathological fractures, and calcitonin may have similar beneficial effects [Kovacs et al, 1995]. Because median survival is 2 months, treatment may be considered worthwhile [Regnard and Dean, 2010].
• The information that treatment may not be appropriate if the person was deteriorating rapidly (day-by-day) before they developed hypercalcaemia is based on the opinion of a CKS expert reviewer.

Management of symptomatic, or moderate or severe hypercalcaemia

• These recommendations are based on expert opinion from narrative reviews.
• For people with symptomatic hypercalcaemia or severe hypercalcaemia (adjusted serum calcium concentration greater than 3.4 mmol/L), there is consistent expert opinion from narrative reviews [Kovacs et al, 1995; Bushinsky and Monk, 1998; Heys et al, 1998; Carroll and Schade, 2003; Weiss-Guillet et al, 2003; Ralston et al, 2004; Smellie et al, 2008] and a textbook [Regnard and Dean, 2010] that immediate intravenous fluids and bisphosphonates are required, although definitions of 'severe' hypercalcaemia and the thresholds for admission vary slightly.
• For people with asymptomatic, moderate hypercalcaemia (adjusted serum calcium concentration 3.0–3.4 mmol/L), there is no consensus in the published literature on the appropriate management.
• Narrative reviews on the management of hypercalcaemia from any cause recommend oral rehydration (if possible) and non-urgent administration of intravenous bisphosphonates for this group [Bilezikian, 1993; Bushinsky and Monk, 1998; Carroll and Schade, 2003; Smellie et al, 2008].
• However, a textbook and narrative reviews specifically about the management of cancer-associated hypercalcaemia recommend immediate treatment with intravenous fluids and bisphosphonates [DTB, 1990; Weiss-Guillet et al, 2003; Ralston et al, 2004; Regnard and Dean, 2010].
• Admission (if appropriate) is recommended on the basis of expert opinion from a narrative review that calcium levels tend to increase faster in people with cancer-associated hypercalcaemia than in people with other causes of hypercalcaemia (for example primary hyperparathyroidism) [Ralston, 1994]. Because the likelihood of symptoms is related to the rate of onset of hypercalcaemia [Ralston, 1992; Bushinsky and Monk, 1998; Weiss-Guillet et al, 2003; Stewart, 2005], people with cancer are more likely to become symptomatic at lower levels of serum calcium. Furthermore, the serum calcium level is more likely to increase further, and lead to greater risk of harm, if it is not treated urgently.

Management of asymptomatic, mild hypercalcaemia

• There is also no clear consensus in the literature on the appropriate management of people with cancer-associated, asymptomatic, mild hypercalcaemia.
• Most authors recommend non-urgent treatment with intravenous bisphosphonates and oral fluids only for people without symptoms who have an adjusted serum calcium concentration 3.0 mmol/L or less [DTB, 1990; Bilezikian, 1993; Bushinsky and Monk, 1998; Heys et al, 1998; Carroll and Schade, 2003; Smellie et al, 2008]. However, lower thresholds for urgent treatment, at adjusted serum calcium concentrations of 2.7–2.9 mmol/L, are recommended in a guideline on the management of multiple myeloma [Smith, 2005], a narrative review [Ralston et al, 2004], and a textbook [Regnard and Dean, 2010].
• Because of the lack of a clear consensus, CKS recommends seeking immediate specialist advice.

Management if immediate admission is not necessary

• The recommendation to maintain good hydration by drinking 3–4 L of fluid per day (provided there are no contraindications) is based on expert opinion from a narrative review [DTB, 1990].
• The recommendation to reassure the person that it is not necessary to adopt a low calcium diet is based on expert opinion from narrative review [DTB, 1990; Kovacs et al, 1995]. This is because intestinal absorption of calcium is usually reduced.
• In the absence of any published evidence or opinion, the recommendation to advise the person to immediately report any symptoms of hypercalcaemia is based on what CKS considers to be good clinical practice.
• The recommendation to encourage mobilization is based on expert opinion from a narrative review that mobilization will help to prevent the generalized bone resorptive state (and so exacerbation of hypercalcaemia) that results from inactivity and bed rest [Kovacs et al, 1995].
• The recommendation to advise the person to avoid any medications or vitamin supplements that could worsen hypercalcaemia is based on expert opinion from a narrative review [Kovacs et al, 1995].

This information is based on evidence from a systematic review of bisphosphonates for hypercalcaemia due to cancer [Saunders et al, 2004], a guideline on the management of multiple myeloma [Smith et al, 2005], narrative reviews [DTB, 1990; Ralston, 1994; Kovacs et al, 1995; Heys et al, 1998; Deftos, 2002; LeGrand et al, 2008], a textbook [Regnard and Dean, 2010], and two case reports [Walker et al, 1996]. In addition, several CKS expert reviewers stated that management of the underlying cancer is a key treatment for hypercalcaemia.