Alongside strengthening bone, calcium is used in the clotting cascade, in muscle contraction, and in nerve-signalling. As such, low levels can lead to coagulopathy, smooth and skeletal muscle-spasms, heart problems, altered sensation and even seizures.

Acute hypocalcaemia that is severe (<1.9 mmol/L) or symptomatic can be life-threatening and necessitates urgent treatment. It is often initially picked up when a patient has low ionised calcium on the blood gas as bone profiles are not routinely measured for every admission.

Total, Ionised and Adjusted Calcium

Of all the calcium in the body, about 99% is stored in the skeleton. The rest is held within fluid — and only a small proportion of that can be found in the extracellular, intravascular fluid of blood plasma. Of the calcium in the blood plasma, about half is bound to proteins like albumin or to other ions. Importantly, it is these ionised, free-floating plasma ions that do the physiological work.

Total plasma calcium does not always accurately represent the amount of active, useful calcium ions. If someone has very low serum albumin, then their protein-bound calcium levels will also be low. This will result in a low total serum calcium level, despite the fact that the free ionised calcium levels are unchanged.

Because of this, adjusted or corrected plasma calcium is often used, which estimates what the level would be if the albumin concentration were normal. This gives a better indication of the amount of useful, physiologically-active calcium in the body. However, this measure is not always reliable, and has been demonstrated to give falsely reassuring results in the critically ill. Serum pH also changes the balance between ionised and bound calcium, so in acidaemic and alkalaemic patients reported calcium levels may not represent the true, active concentration.

Calcium Regulation

As with all electrolytes, Calcium levels are maintained through a balance of intake and absorption (through the GI Tract), loss (through the kidneys), and distribution (between bones and fluid). When serum calcium is low, the Parathyroid Gland raised levels by releasing parathyroid hormone (PTH) which increases resorption in the kidneys and break-down of bone. PTH production is facilitated by Magnesium, calcium regulation requires sufficient magnesium levels.

Another hormone to be aware of is Calcitriol. Calcitriol increases absorption of calcium by the GI tract. Calcitriol is derived from Vitamin D through enzymatic processes in the kidney, which are stimulated by PTH. This is why low vitamin D intake can lead to calcium dysregulation.

Symptoms & Signs of Hypocalcaemia

• Perioral & digital paraesthesia
• Positive Trousseau’s and Chvostek’s signs
• Tetany & carpopedal spasm
• Laryngospasm
• ECG changes: prolonged QT, bradycardia & other arrhythmias
• Seizure

Causes

• Total thyroidectomy (or parathyroidectomy) / hypoparathyroidism
• Severe Vitamin D deficiency
• Hypomagnesaemia (often secondary to PPIs)
• Pancreatitis — as the inflammation increases calcium deposition within the abdomen
• Rhabdomyolysis and Tumour Lysis Syndrome — as dying cells spill phosphate into the blood, which binds with free calcium ions
• Drugs – loop diuretics, glucocorticoids, gentamicin, phosphates, theophylline, some cytotoxics
• Large volume blood transfusions
• Renal Failure

Investigations

• Bone Profile, U&Es, Magnesium, Vitamin D, PTH
• Consider amylase/lipase (pancreatitis) & creatine kinase (rhabdomyolysis) as clinically indicated

Treatment

You should use either your local guidelines or the guidelines produced by the Society for Endocrinology.

Mild (>1.9 mmol/L)

• Commence oral replacement using Sandocal (2 tablets BD) or Adcal (3 tablets BD) or any other available
• Treat the underlying cause e.g.:
  • Stop causative drugs
  • Vitamin D – load with around 300,000 units as per local guidelines
  • Hypomagnesaemia – IV Magnesium (usually requires 24 mmol or 6g in 24h) & stop any precipitating drugs e.g. PPIs
  • Thyroidectomy/Parathyroidectomy – may need 1-alpha hydroxylated Vitamin D. This should be started with specialist advice

Severe (<1.9 mmol/L or symptomatic)

• This is a medical emergency & should be treated whilst on a cardiac monitor
• Treatment in most trusts consists of first a rapid correction to address symptoms or to protect the heart, and then a slower restoration to normal levels.
• Example regime could be:
  1. 10-20ml 10% calcium gluconate. This can be administered diluted in 50-100ml of 5% dextrose over 10 minutes
  2. Calcium gluconate infusion – 100ml 10% calcium gluconate in 1L 0.9% saline/5% dextrose at 50-100ml/h
• Treat the underlying cause as above
• Ensure referral to the endocrinology team

References & Further Reading

• Society for Endocrinology Guidelines
• UK Medicines Information
• Hamilton, R.J., 2018. Tarascon adult emergency pocketbook. Jones & Bartlett Learning.
• Lewis III, J. L., 2018. Hypocalcemia. MSD Manual Professional Version.
• Turner, J., Gittoes, N., Selby, P. and Society for Endocrinology Clinical Committee, 2016. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypocalcaemia in adult patients. Endocrine connections, 5(5), p.G7.

Written By Dr Akash Doshi (ST4), additional material by Dr Glen Davies (F1)
Previous version by Dr Shoaib Hussain