Hypocalcaemia is defined as a total calcium < 2.1 mmol/L (adjusted for albumin).
Causes
- Decreased entry of calcium into circulation
- Hypoparathyroidism
- Vitamin D deficiency
- Hypomagnesaemia (the presence of hypomagnesaemia can cause hypocalcaemia by interfering with the secretion and action of PTH)
- PTH resistance, or pseudohypoparathyroidism
- Increased loss of calcium from the circulation
- 'Hungry bone syndrome' (seen after parathyroidectomy or thyroidectomy)
- Acute pancreatitis
- Extensive osteoblastic skeletal metastases
- Hyperphosphataemia (occurs after massive tissue breakdown in rhabdomyolysis, after accidental ingestion of phosphate-containing drugs, or in critically ill patients. Phosphate binds to calcium, leading to acute hypocalcaemia)
- Drug-induced hypocalcaemia
- Hypocalcaemia can be induced by certain drugs: these include bisphosphonates, particularly when given intravenously; chemotherapies; glucocorticoids; anticonvulsants; and chelating agents such as EDTA, citrate, foscarnet, and lactate. Cinacalcet, which is usually given to patients with renal failure to inhibit PTH release, can also cause hypocalcaemia. Proton-pump inhibitors may cause hypomagnesaemia, which in turn causes hypocalcaemia.
- Other causes
- Critically ill patients may have transient hypocalcaemia, as seen in conditions such as sepsis or extensive burns or after multiple blood transfusions. The low serum calcium levels seen in these patients can be caused by the citrate content of transfused blood, receiving large quantities of fluids, and/or hypoalbuminaemia. Any condition that lowers plasma protein levels can also cause hypocalcaemia.
Clinical features
Symptoms and signs of hypocalcaemia include:
- Perioral and digital paraesthesia
- Positive Trousseau’s and Chvostek’s signs
- Trousseau's sign is carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes.
- Chvostek's sign is the twitching of the facial muscles in response to tapping over the area of the facial nerve.
- Tetany and carpopedal spasm
- Laryngospasm
- ECG changes (prolonged QT interval) and arrhythmia
- Seizure
Investigations
- Historical and examination findings often narrow the differential diagnosis considerably. The initial tests to order in a patient presenting with hypocalcaemia are serum total calcium concentration, albumin, magnesium, phosphate, vitamin D, renal function, and serum intact parathyroid hormone level. Other investigations commonly include serum levels of ionised calcium, bicarbonate, alkaline phosphatase, and 24-hour urine calcium and creatinine.
- PTH levels will be low in overt hypoparathyroidism (e.g. iatrogenic or infiltrative damage, congenital absence) and are raised in vitamin D deficiency, renal disease, and in malignancies with skeletal metastases.
- 25-hydroxyvitamin D levels should be measured in patients suspected of having vitamin D deficiency. Serum alkaline phosphatase may also be useful in these patients (where levels may be elevated). Alkaline phosphatase is also raised in patients with skeletal metastases.
- High levels of phosphate in the absence of renal failure and tissue breakdown indicate hypoparathyroidism or pseudohypoparathyroidism.
- Hypomagnesaemia or severe hypermagnesaemia can cause hypocalcaemia and may indicate the underlying aetiology. It is important to identify hypomagnesaemia, because calcium cannot be adequately adjusted unless magnesium has first been replaced.
- Elevated urea and creatinine can indicate renal dysfunction.
- Amylase and/or lipase levels should be checked in patients with abdominal pain. In acute pancreatitis the amylase and lipase levels are significantly increased.
- Serum creatinine, creatine kinase, magnesium, and phosphorus levels are particularly relevant tests in patients suspected of having rhabdomyolysis and cell lysis syndrome.
- ECG changes in hypocalcaemia:
- Prolonged QT interval
- Heart block
- Cardiac arrest
Management
- The main aim of acute management of hypocalcaemia is to improve the acute clinical features, including cardiac hyperexcitability, tetany, hypotension, seizures, mental confusion, and carpopedal spasms, and not necessarily to return the calcium level to normal.
- Mild hypocalcaemia (>1.9 mmol/L and asymptomatic) can be managed with oral calcium supplements.
- Severe hypocalcaemia (< 1.9 mmol/L or symptomatic) is treated with intravenous calcium replacement. e.g. IV calcium gluconate. Electrocardiographic monitoring is recommended because dysrhythmias can occur if correction is too rapid. Treatment can be repeated until the patient is asymptomatic.
- Magnesium levels (especially hypomagnesaemia) should be checked and adjusted, because calcium cannot be adequately adjusted unless magnesium has first been replaced e.g. IV magnesium sulfate 2-4 mL: 4-8 mmol
- If vitamin D deficiency is the cause, commence vitamin D supplementation. If other cause of hypocalcaemia, treat underlying condition.