Definition of hypocalcaemia

Hypocalcaemia can be defined as a corrected calcium level or an ionised calcium level below normal values for age.

It can be regarded as:

• Mild symptomatic (parasthesia, perioral numbness, muscle cramps, carpopedal spasm), OR
• Mild biochemical (see below), OR
• Severely symptomatic (e.g. tetany, seizures, arrhythmia/QTc >0.44, stridor), OR
• Severe biochemical (see below)

Corrected Calcium

Serum calcium exists in an ionised form (50%) or is bound to albumin and other ions. Many medical conditions can cause a decrease in albumin. The serum calcium must be interpreted in relation to serum albumin and can be corrected using the following formula:

The normal range for Corrected Calcium is 2.2 to 2.7 mmol/L (all ages).

Ionised Calcium

Ionised Calcium is the most accurate assessment of serum calcium concentration and should be measured if available (gas machine).

The normal range for ionised calcium is 1.15 to 1.33 mmol/L (all ages).

Definition of mild and severe biochemical hypocalcaemia

Hypocalcaemia is defined as:

Risk factors for Vitamin D deficiency:

• Ethnicity (darker skin)
• Reduced sun exposure, due to clothing or factors such as chronic disease requiring prolonged hospital admission
• Prolonged breast feeding
• Dietary history: decreased intake of dairy products, oily fish, eggs

Other history:

• History of head and neck surgery
• Family history of hypocalcaemia (suggesting genetic cause)
• Other autoimmune disease (autoimmune hypoparathyroidism/polyglandular autoimmune disease type1)
• Developmental delay (possible genetic factor such as 22q deletion)

Symptoms of hypocalcaemia in infants and children

Children and neonates may be asymptomatic.
Symptoms may include:

Signs suggestive of rickets:

• swollen wrists
• craniotabes (prominent forehead)
• rachitic rosary (prominent costochondral junction)
• bow legs or knock knees (if weight bearing/walking).

Signs suggestive of chronic hypocalcaemia:

• Dry skin, course hair, brittle nails
• Enamel hypoplasia /dental caries
• Cataract/papilloedema
• Extra pyramidal signs secondary to basal ganglia calcification.

Latent tetany

• Trousseau’s sign: induction of carpopedal spasm by inflation of a sphygmomanometer above systolic blood pressure for three minutes.
• Chvostek’s sign: contraction of ipsilateral facial muscle elicited by tapping the facial nerve just anterior to the ear.

Dysmorphic features

• Pseudohypoparathyroidism
• 22q11 deletion syndrome (Di-George syndrome).

The blood tests listed below are time-critical and should be obtained at time of hypocalcaemia.

¹Hypophosphataemia can induce hypocalcaemia due to metastatic calcification of calcium phosphate in soft tissue and lungs (usually associated with renal disease).

²Hypomagnesaemia can induce hypocalcaemia due to end organ resistance to parathyroid hormone and impaired PTH secretion. Serum magnesium is automatically added to ICE requests if corrected calcium is <1.80 mmol/L (and sufficient sample available).

³Alkalaemia can induce hypocalcaemia due to increased protein binding of calcium.

Neonatal cases

In neonatal cases, the following maternal bloods should be obtained: Calcium, phoshate, ALP, PTH, 25 hydroxyvitamin D, HbA1c.

Clinical significance

Hypocalcaemia in children is potentially life threatening due to cardiac arrhythmias and stridor/laryngospasm (usually at values of corrected calcium <1.6 mmol/l in children). The severity of the presentation depends on the rate of development and the chronicity of the hypocalcaemia in addition to the corrected calcium value.

Serum calcium is maintained at the expense of sequestration of bone (potentially leading to rickets ) and retention of calcium by the kidneys leading to phosphate loss. Hypocalceamia in this context is a late presentation of a chronic process and indicates that the child has significant total body calcium depletion. Large doses of calcium are usually needed for replacement with cautious weaning to prevent rebound hypoglycaemia due to “bone hunger”.

Common causes of hypocalcaemia in children and associated biochemistry

^aTransient PTH resistance seen in neonates/toddlers may result in high phosphate, low Ca, low vit D
^bAdolescents : alk phos may be only marginally raised

Rarer causes of hypocalcaemia

• Vitamin D dependent rickets (Type 1 and 2)
• Chronic Renal Failure
• Acute severe illness (eg. sepsis, toxic shock syndrome)
• Pancreatitis
• Tumour metastasis
• Di George Syndrome (causes hypoparathyroidism).

All children/neonates with symptomatic or severe biochemical hypocalcaemia need to be monitored in HDU with continuous ECG monitoring.

1. Assess ABC and basic resuscitation.
2. Treat seizures with anti-epileptics as per seizure protocol.
3. Admit to HDU for continuous cardiac monitoring - discuss arrhythmias with consultant on call.
4. Establish good venous access (calcium gluconate should be infused into a large vein as irritant) and take blood for investigations.

IV therapy is required for:

Severe symptomatic Hypocalcaemia (e.g. tetany, seizures, arrhythmia/QTc >0.44, stridor) - any value lower than normal range

OR

Severe biochemical hypocalcaemia - as defined by the following:

Oral therapy is required for:

Mild symptomatic Hypocalcaemia (e.g. parasthesia, perioral numbness, muscle cramps, carpopedal spasm)

OR

Mild biochemical Hypocalcaemia - as defined by the following:

Oral therapy (see below for doses)

Calcium – oral calcium supplements 6 hourly AND

Alfacalcidol (1a-Hydroxycholecalciferol) once daily.

Monitor

• IV access and investigations
• Routine ward observations
• ECG - calculate QTc.

Oral Calcium supplements

Can be given as:

• Calcium gluconate oral syrup (0.51 mmol/ml) NB this is a food supplement and is not classed as a medicine; also contains sugar, OR
• Sandocal ® 1000 effervescent tablets (25mmol calcium/tablet). Tablet dissolved in 25mls of water = solution strength of 1mmol/1mL OR
• Calcichew ® tablets (12.5mmol calcium/tablet).

Alfacalcidol (1a-hydroxycholecalciferol)

Alfacalcidol is the active form of vitamin D and increases Calcium gut absorption and retention from the kidneys. This is given in preference to vitamin D in the acute phase of treatment when vitamin D and Parathyroid hormone (PTH) levels are not yet known (PTH is responsible for converting inactive vitamin D into the active 25OH form - low levels of PTH will result in less active Vit D, and so less absorption from the gut).

External Links

BNFc - Calcium gluconate

BNFc - Alfacalcidol

IV therapy

Slow bolus 10% IV Calcium gluconate over 10 minutes, followed by IV Calcium gluconate infusion. If serum Mg <0.6 mmol/l consider IV Magnesium Sulphate.

Dosage/administration of calcium gluconate

See below for links to BNFc.

Acute hypocalcaemia, urgent correction (intravenous bolus):

• 0.11mmol/kg (0.5mL/kg of calcium gluconate 10%) as a single dose by intravenous injection over 5-10 minutes. Maximum dose 4.5 mmol (20ml calcium gluconate 10%).
• Concentrations greater than 0.045mmol/mL should be given via a central venous access device. Can be given undiluted in emergencies over 3-5 minutes.
• Onset within 3 minutes but effect lasts 30-60 minutes therefore may need to repeat dose.
• Can be repeated following discussion with consultant or followed by continuous infusion.

Acute hypocalcaemia, maintenance (continuous intravenous infusion):

• Adjusted according to response, dose to be given over 24 hours.
• Use oral route as soon as possible due to risk of extravasation.

Reconstitution of calcium gluconate:

• Draw up 10mL (2.2mmol) of calcium gluconate 10% and dilute to a final volume of 50mL with sodium chloride 0.9%.
• This produces a stock solution containing 0.044mmol/mL.
• Draw up required dose - 0.11mmol/kg urgent correction dose is equivalent to 2.5mL/kg.

Monitor

• ECG - ?arrhythmia
• BP - hourly
• IV site for local reaction/extravasation - regular direct observation
• Ionised Calcium - initialy 6 hourly and then 6-12 hourly as indicated, aiming for Ca2+ ≥1.0 mmol/l (corrected Ca ≥1.9 mmol/l).

Start oral therapy

Start oral therapy early as it takes 2-3 days to increase Ca absorption from the gut (see mild hypocalcaemia node for doses).

• Calcium – oral calcium 6 hourly, AND
• Alfacalcidol (1a-Hydroxycholecalciferol) once daily.

Alfacalcidol is the active form of vitamin D and increases Calcium gut absorption and retention from the kidneys. This is given in preference to vitamin D in the acute phase of treatment when vitamin D and Parathyroid hormone (PTH) levels are not yet known (PTH is responsible for converting inactive vitamin D into the active 25OH form - low levels of PTH will result in less active Vit D, and so less absorption from the gut).

Weaning IV therapy

Wean IV Calcium gluconate slowly over 24-48 hours guided by ionised Calcium.

Stopping the calcium infusion is likely to result in a rapid fall in serum Ca2+ due to uptake into bone (“bone hunger”). Reduce infusion in 10-20% increments 4-6 hourly as calcium normalises.

Liaise with endocrine team about follow up bloods via tay.paediatricendocrine@nhs.scot

External Links

BNFc - calcium gluconate

BNFc - magnesium sulphate

BNFc - alfacalcidol