Hypocalcaemia

Hypocalcaemia (serum calcium <2.2 mmol/L) is a common and occasionally severe electrolyte disorder.

Extracellular calcium is split (approximately evenly) into:

Ionised calcium (1.1-1.3mmol/L)
Only biologically important version as bound calcium is not active.
- Ionised calcium is affected by pH, as an ↑ in H⁺ concentration displaces calcium from albumin and therefore ↑ iCa²⁺
  For every 0.1 ↓ in pH, iCa²⁺ ↑ by ~0.05mmol/L.
Bound calcium
- Majority (90%) of non-ionised calcium is bound to albumin, and so total calcium is affected by albumin levels
- Remainder bound to beta-globulins, phosphate, citrate, sulphate, ketones
  Generally of little clinical importance.

Epidemiology and Risk Factors

Common electrolyte abnormality:

18% of hospital inpatients
85% of ICU patients

Pathophysiology

Calcium is an important cation with multiple critical functions:

Muscular contraction
Coagulation
Neurotransmission
Hormone release
Cellular apoptosis

Calcium homeostasis is regulated by:

PTH
- Release stimulated by ↓ serum calcium and magnesium
- ↑ Renal and bone reabsorption
- ↑ Calcitriol production
  ↑ Gut calcium absorption.
Vitamin D
Calcitriol precursor.
Calcitonin
Functionally a PTH antagonist.
- Release stimulated by hypercalcaemia, catecholamines, and gastrin
- ↓ Bone reabsorption and ↑ renal elimination

Aetiology

↓ PTH
- Primary
  - Parathyroid/thyroid surgery
  - Autoimmune disease
- Secondary
  - Sepsis
  - Hypomagnesaemia
    <0.4mmol/L.
↑ PTH
- ↓ Vitamin D
  - Dietary
    - Malabsorption
  - ↓ Sunlight exposure
  - Renal failure
  - Pregnancy
- PTH resistance
  - Hypomagnesaemia
- Calcium loss/consumption
  - Hyperphosphataemia
    - TLS
  - Acute pancreatitis
  - Clotting
  - Bone metastases
  - Alkalosis
- Drugs
  - Citrate
    Total calcium remains normal, because the citrate-calcium complex is measured and accounted for.
  - Bisphosphonates
  - Phenytoin

A primary alkalosis (e.g. from hyperventilation) causes an ionised hypocalcaemia by ↑ calcium binding to albumin. However, many other causes of hypocalcaemia also cause metabolic acidosis (e.g. TLS, renal failure).

Clinical Manifestations

C
- Long QT
  TDP if severe.
D
- Paraesthesias
- Confusion/delirium
E
- Twitching
- Spasm/Tetany
  - Carpopedal spasm

Chvostek’s sign - tapping the parotid gland over the facial nerve to induce facial spasm - is a poor discriminator of ↓ calcium. 10% of normal patients are positive, and ~30% of hypocalcaemic patients are negative.

Investigations

Bedside:

Laboratory:

Three equations exist to correct measured calcium:

Correction of ionised calcium for pH:
\(iCa^{2+}_{7.4}c = iCa^{2+} \times (1 - 0.53 \times (7.40 - pH))\)
Correcting total calcium for:
- Albumin:
  Measured total calcium will ↓ (or ↑) by 0.02 mmol/L for every 1g/L ↓ (or ↑) the albumin is above 40g/L.
- Globulins:
  Measured total calcium will ↓ (or ↑) by 0.04mmol/L for every 10g/L ↓ (or ↑) in serum globulin.

Bloods
- PTH
  Should be ↑ in the setting of hypocalcaemia.
- 25-hydroxyvitamin D
- Renal function
- Albumin
- Lipase
  Pancreatitis.
- Magnesium
- Phosphate
  - ↑ Phosphate associated with primary hypoparathyroidism
    Phosphate also chelates calcium, which may contribute to ↓ calcium.
  - ↓ Phosphate associated with secondary hypoparathyroidism

Other:

ECG
Long QT, TDP.

Management

Mild hypocalcaemia (iCa²⁺ 0.8-1.1) in the critically ill is common and does not require replacement.

IV replacement should be used for anyone with:

Neuromuscular irritability
Serum calcium <1.9mmol/L

Acute:

Correct any hypomagnesaemia
IV Calcium Gluconate
- 10mL 10% (diluted to 50-100mL) over 10 minutes
  Cardiac monitor due to risk of dysrhythmia.
- Infusion
  100mL 10% (diluted to 1L), run at 50mL/hr. Expect ~0.3-0.5mmol/L ↑ in calcium over 6 hours. IV Calcium Gluconate infusion if required, titrating rate to serum calcium.

Calcium chloride can also be used, but requires a large reliable drip or CVC due to the risk of devastating tissue necrosis on extravasation.

Calcium Dose Equivalents
Formulation	Dose	Elemental Ca²⁺/g
Calcium Gluconate	10mL	2.3mmol
Calcium Chloride	10mL	8.6mmol

Sub-acute:

↓ PTH
- Calcitriol 0.25-1ug/day
- Oral calcium supplementation
Normal/↑ PTH
- 50,000 IU Cholecalciferol

Cholecalciferol requires PTH for conversion, which is why calcitriol is used in the ↓ PTH group.

Persistent:

If calcium continues to fall despite treatment, consider:
- Thiazide
  ↑ Renal calcium reabsorption.
- Recombinant PTH

References

Cooper, Mark S, and Neil J L Gittoes. Diagnosis and Management of Hypocalcaemia. BMJ: British Medical Journal 336, no. 7656 (June 7, 2008): 1298–1302.
Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.