“49 years old man, no known medical illness, presented with lethargy for 3 weeks, loss of appetite for 2 weeks, and constipation for 3 days. At ED, noted corrected serum calcium 3.98 mmol/L”

Introduction

• Normal range of serum calcium: 2.1 – 2.65 mmol/L
• Severe hypercalcaemia = Serum calcium >3.5 mmol/L
• Acute therapy is warranted if serum calcium >3 mmol/L or severe symptoms
• Patients with severe hy[ercalcaemia are usually dehydrated during initial presentation

Investigations

(i) Initial investigations

• FBC, RP, Ca, Mg, PO4
• LFT (look for ALP level)
• Thyroid function test
• iPTH (intact parathyroid hormone)

(ii) Other investigations to be considered

• If suspect PTB / TB related hypercalcaemia: CXR, Sputum AFP x1, x2, x3; Sputum MTB GeneXpert
• If suspect malignancy (e.g. multiple myeloma): urine protein electrophoresis, serum protein electrophoresis, skeletal survey, full blood picture, tumour markers
• KUB X-rays, KUB USG e.g. if AKI not resolving despite on hydration — TRO obstructive uropathy

Acute therapy of severe hypercalcaemia

1) Hyperhydration

• Initially 300 – 500 mL normal saline over 1 hour, sometimes up to 10 – 20 mL/kg over 1 hour
• Followed by 3 – 4L (=6 – 8 pints) normal saline over 24 hours
• Correct electrolyte abnormality e.g. IV KCl maintenance / fast correction for hypokalaemia; IV MgSO4 for hypomagnesaemia

• Hyperhydration with 3 – 4L normal saline over 24 hours can be given for 2 – 3 days, depending on clinical response and assessment
  • The patient must be reassessed (e.g. after 24 hours of fluid) to determine whether fluid can be titrated down or maintained. Check input/output balance, RP, and electrolytes.
  • How much fluid to be given depends on patient’s hydration status (e.g. from IVC diameter & collapsibility; presence of GI loss, amount of oral intake, urine output; CVP monitoring if available), haemodynamic status (BP, HR), and whether patient having fluid restriction (e.g. CCF, ESRF)
• Normal saline helps to restore extracellular fluid (i.e. rehydrate the patient) and to promote calcium excretion (Na competitively inhibits renal tubular absorption of Ca)

2) Diuretics

• IV Frusemide 20 – 40 mg TDS

• DO NOT use thiazides which can reduce calcium excretion
• IV Frusemide helps to prevent fluid overload and to further promote calcium excretion

3) Bisphosphonates

Examples:

• Zoledronate (Zometa®): IV Zoledronate 4 mg over at least 15 minutes (agent of choice for malignancy-associated hypercalcaemia because it’s more potent and effective than pamidronate)
• Pamidronate: IV Pamidronate 30 mg / 60 mg / 90 mg in 1L normal saline over 4 – 6 hours.
  • Action starts after several days and lasts for weeks to months
  • Example dose: 30 mg for Ca <3 mmol/L, 60 mg for Ca 3 – 3.4 mmol/L, 90 mg for Ca >3.4 mmol/L)

• Useful especially if suspect hypercalcaemia due to malignancy. Bisphosphonates work by inhibiting bone resorption.
• Prescriber category: A* (must be discussed with specialist for initiation and dosage)
• Treatment can be repeated if hypercalcaemia recurs (usually after 2 – 3 weeks)

4) Treatment of underlying disease / cause

Further reading

• Sarawak Handbook of Medical Emergencies (4th edition)