Hypocalcaemic Crisis

Hypocalcaemic crisis is severe or acute hypocalcaemia, with albumin corrected calcium under 1.9 mmol/L (7.6 mg/dL) or ionised calcium under 0.8 mmol/L (3.2 mg/dL), causing tetany, seizures, laryngospasm or cardiac effects.

Epidemiology. It is common after thyroid and parathyroid surgery, in vitamin D deficiency and in chronic kidney disease. It is also frequent in critical illness, massive transfusion, pancreatitis, rhabdomyolysis and tumour lysis syndrome.

Causes and associations.

• Hypoparathyroidism: post-surgical, autoimmune and genetic (including 22q11.2 deletion).
• Vitamin D deficiency or resistance, chronic kidney disease and malabsorption.
• Hypomagnesaemia and hyperphosphataemia, and hungry bone syndrome after parathyroidectomy.
• Acute pancreatitis, rhabdomyolysis, sepsis and tumour lysis.
• Massive transfusion with citrate, and alkalosis.
• Drugs: denosumab, bisphosphonates, foscarnet, cisplatin, loop diuretics, phenytoin and phenobarbital.

Pathophysiology. Low ionised calcium lowers the threshold for neuromuscular excitation, causing tetany and seizures, and prolongs cardiac repolarisation, causing QT prolongation and arrhythmia. Alkalosis reduces ionised calcium by increasing protein binding.

Presentation is perioral and fingertip paraesthesia, muscle cramps, carpopedal spasm, tetany, stridor from laryngospasm, wheeze, seizures and confusion. Chvostek and Trousseau signs may be present. ECG shows QT prolongation, and severe cases cause hypotension, heart failure and torsades de pointes.

Red flags.

• Seizure, stridor or laryngospasm.
• QT prolongation, arrhythmia or hypotension.
• Ionised calcium under 0.8 mmol/L.
• Recent neck surgery or massive transfusion, concurrent hypomagnesaemia or digoxin use.

Measure corrected and ionised calcium, magnesium, phosphate, albumin, potassium, creatinine, parathyroid hormone (before treatment where possible), 25-hydroxyvitamin D, alkaline phosphatase, creatine kinase and lipase. Do a blood gas for pH and an ECG for the QT interval.

Differential diagnosis.

• Hyperventilation with respiratory alkalosis and tetany.
• Hypomagnesaemia and hypokalaemia.
• Epilepsy and tetanus.
• Pseudohypocalcaemia from low albumin, and panic disorder.

Symptomatic or severe (tetany, seizure, laryngospasm, arrhythmia, QT over 500 ms).

• Calcium gluconate 10% 10 to 20 mL (1 to 2 g) IV over 10 minutes with continuous ECG, repeated if symptoms persist.
• Then an infusion of calcium gluconate 10% 100 mL (10 g) in 1 L of 5% dextrose or 0.9% sodium chloride at 50 to 100 mL/h, which delivers elemental calcium of about 0.5 to 1.5 mg/kg/h. Adjust to keep calcium at the lower end of the normal range.
• Calcium chloride 10% 10 mL IV (through a central line only) when a rapid effect is needed, such as arrest or transfusion related hypocalcaemia.
• Do not mix with bicarbonate or phosphate. Extravasation causes tissue necrosis. In patients taking digoxin, give slowly with monitoring.

Magnesium. Magnesium sulphate 2 g (8 mmol) IV over 15 to 20 minutes when magnesium is under 0.7 mmol/L, repeated as needed and reduced in renal impairment.

Oral therapy and long term care.

• Calcium carbonate 1 to 2 g elemental calcium daily in divided doses with meals.
• Alfacalcidol 0.25 to 1 microgram daily (up to 2 microgram) or calcitriol 0.25 to 0.5 microgram twice daily for hypoparathyroidism, with calcium and renal monitoring.
• Colecalciferol 50,000 units weekly for 6 to 8 weeks, or 1,000 to 2,000 units daily, for vitamin D deficiency.
• Correct hyperphosphataemia and the cause.

Hungry bone syndrome. Large doses of calcium (6 to 12 g elemental calcium daily) and calcitriol up to 4 microgram daily may be needed for weeks.

Monitoring. Ionised calcium every 4 to 6 hours during infusion, magnesium, phosphate, potassium, QT interval and clinical signs. After surgery, check calcium daily until stable.

Referral and escalation. Endocrinology for hypoparathyroidism. Intensive care or high dependency for arrhythmia, stridor, seizures or a large calcium requirement.

Special groups. In children, calcium gluconate 10% is 0.5 to 1 mL/kg (50 to 100 mg/kg) IV over 5 to 10 minutes, maximum 20 mL, followed by an infusion with ECG monitoring. In renal impairment, use active vitamin D and manage phosphate.