Medicines Q&As
Q&A 373.1
How is acute hypocalcaemia treated in adults?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Date prepared: 13th September 2011
Background
There are no national guidelines for the treatment of acute hypocalcaemia, and practice varies
widely across hospital Trusts. Following a thorough search of the literature, this guidance has
been prepared and adopted in Leeds Teaching Hospitals NHS Trust. The use of calcium for other
indications has not been considered.
Reference ranges for serum calcium concentrations vary between laboratories. For the purpose of
this document, the reference range used for adjusted calcium is 2.2 - 2.6 mmol/L.
Intestinal calcium absorption is enhanced by 1,25-dihydroxyvitamin D3 (1,2) and the concentration
of serum calcium is maintained within a narrow normal range under the influence of parathyroid
hormone and 1,25-dihydroxyvitamin D3 (2-5).
Mild hypocalcaemia is usually asymptomatic (4). Symptoms of hypocalcaemia generally correlate
with the rate and magnitude of calcium depletion (2,3). It has been suggested that patients are
less likely to be symptomatic if the serum calcium concentration has declined slowly (3).
Features of hypocalcaemia may include: (2-7)
 Paraesthesia
 Tremors
 Muscle weakness
 Chvostek and Trousseau signs
 Muscle cramps
 Tetany
 Laryngospasm
 Bronchospasm
 Prolonged QT interval
 Hypotension
 Cardiac arrhythmias
 Seizures
 Coagulation irregularities
 Nausea, vomiting, diarrhoea
 Changes in mental state, e.g. confusion, irritability, anxiety
Hypocalcaemia has been associated with the following conditions: (1-5,7,8)
 Septic shock
 Severe acute pancreatitis
 Rhabdomyolysis
 Chronic renal insufficiency
 Hypomagnesaemia
 Hypoparathyroidism
 Pseudohypoparathyroidism
 Post parathyroidectomy
 Malignant disease
 Inadequate dietary calcium intake
 Calcium malabsorption
 Vitamin D deficiency
 Massive blood transfusion
 Drug-induced: including some anticonvulsants, bisphosphonates, calcitonin,
phosphate, colchicine overdose, foscarnet, citrated blood transfusions, radio contrast
dye, ketoconazole and some antineoplastic agents
From the National Electronic Library for Medicines. www.nelm.nhs.uk
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Medicines Q&As
Answer
The cause of the hypocalcaemia should be established and if possible steps taken to correct it
before calcium is administered, as in many cases the hypocalcaemia will reoccur if the underlying
cause is not treated (9). Although this document offers guidance, the dose of calcium to correct
hypocalcaemia should be determined on an individual patient basis.
Oral calcium replacement
Asymptomatic, mild hypocalcaemia is usually treated with oral calcium supplements (1,2) at a
dose of 10 to 50 mmol daily for simple deficiency states and adjusted to the patient’s individual
requirements (10). Calcium carbonate is the most frequently supplied calcium salt (11) and is well
tolerated by most patients (3). In mild, asymptomatic hypocalcaemia, intravenous calcium
replacement is not thought to be of any greater benefit than oral replacement and carries the risk
of administration site reactions (12).
Intravenous calcium replacement
In severe acute hypocalcaemia or hypocalcaemic tetany, 2.2 to 4.5 mmol calcium (as gluconate) is
administered as a slow intravenous injection over 5 to 10 minutes with ECG monitoring throughout
the injection and afterwards (13-15). Note there is a risk of cardiac arrhythmias if the calcium is
administered too quickly (3,13,14). The injection is usually followed with a calcium infusion to
prevent recurrence (2,10,13). Practice varies, but a suggested regimen is 22.5 mmol calcium (as
gluconate) in 1 litre sodium chloride 0.9% and administered at 50ml/hour (10,13,16). 10ml/kg of
the above described preparation is estimated to increase serum calcium concentrations by 0.3 0.5 mmol/L (16).
Calcium gluconate and calcium chloride are the most commonly used intravenous calcium
preparations. Some prefer calcium chloride to calcium gluconate for parenteral administration,
because retention of calcium from the chloride salt is thought to be greater than from the gluconate
salt, and results in a more predictable increase in extracellular ionised calcium concentration.
However, calcium chloride is considered to be the most irritant of the calcium salts (10). In
September 2010, the MHRA published an alert regarding the use of calcium gluconate in small
volume containers and the risk of aluminium exposure (17).
Monitoring requirements
Monitor electrolytes and urea (2,8). Parathyroid hormone and vitamin D levels should ideally be
checked before initiating treatment for hypocalcaemia (8,16).
If the patient has sepsis or renal failure, metabolic acidosis may accompany the hypocalcaemia.
Calcium must be replaced to achieve serum levels close to normal range before the acidosis can
be corrected. Failure to do this may result in convulsions or cardiac arrest (2,9).
Serum magnesium concentrations should be monitored (2,4,8,16). If hypocalcaemia is secondary
to hypomagnesaemia, correction of the magnesium may lead to spontaneous normalisation of
calcium concentrations after a lag period of about 2 days (7). Without replenishing the magnesium,
any increase in calcium concentrations may be transient (7,16).
Cautions and contraindications of calcium use
Calcium salts are contraindicated in patients with ventricular fibrillation or hypercalcaemia and
should be used with great caution in patients who are taking cardiac glycosides as calcium
enhances the effects of digoxin on the heart and may precipitate digitalis intoxication
(4,8,10,15,16,18,19).
If administered too quickly, parenteral calcium solutions can cause cardiac arrhythmias and
hypotension (3,13,14). ECG monitoring should be performed during intravenous administration of
calcium, especially in patients with a history of cardiac disease or those at risk of arrhythmias
(4,13,14,).
Calcium salts should be used with caution in patients with calcium renal calculi or in patients with
diseases associated with hypercalcaemia such as sarcoidosis and some malignancies (10,18).
From the National Electronic Library for Medicines. www.nelm.nhs.uk
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Closer monitoring of serum calcium concentrations should be performed in patients with renal
impairment (20). If parenteral calcium is used to treat hypocalcaemia when hyperphosphataemia is
present (for example some acute cases of rhabdomyolysis), damaging precipitation of calciumphosphate in soft tissues can result (3).
Adverse effects of calcium therapy
Hypercalcaemia, gastrointestinal irritation and constipation have all been reported following
calcium administration (10,18). A high dietary intake of calcium has long been suspected as
contributing to the risk of renal calculi and calcium should be used with caution in patients at risk of
renal calculi (18).
Rapid intravenous injection of calcium salts may cause venous irritation (10,13,15,18), symptoms
of hypercalcaemia, as well as a chalky taste (10,18), hot flushes, and peripheral vasodilatation
(10,15). Hypotension, bradycardia, cardiac arrhythmias, syncope, and cardiac arrest have
occurred following rapid intravenous administration of calcium salts (18). Soft-tissue calcification
has followed the use of calcium salts parenterally (10,15). Care should be taken to avoid
extravasation.
Summary
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There is no national guidance on the treatment of hypocalcaemia, and practice varies
widely between hospital Trusts. The guidance in this document reflects practice at
Leeds Teaching Hospitals NHS Trust.
The cause of the hypocalcaemia should be established and if possible, steps taken to
correct it before calcium is administered
Mild, asymptomatic hypocalcaemia is usually treated with oral calcium replacement at
a dose of 10 to 50 mmol calcium daily for simple deficiency states and adjusted to the
patient’s individual requirements.
In severe acute hypocalcaemia or hypocalcaemic tetany, 2.2 to 4.5 mmol calcium is
administered as a slow intravenous injection over 5 to 10 minutes and is usually
followed by a calcium infusion to prevent recurrence. Intravenous calcium
administration has been associated with adverse effects including serious venous
irritation, hypotension, bradycardia, cardiac arrhythmias and cardiac arrest especially if
calcium is administered too quickly. Care should be taken to avoid extravasation.
Monitor urea and electrolytes including magnesium as only transient rises in serum
calcium concentrations will be seen if concurrent hypomagnesaemia is not adequately
treated. Check parathyroid hormone and vitamin D levels before initiating treatment for
hypocalcaemia.
Limitations
This Q&A is designed for adult patients only. This guidance is not suitable for chronic
hypocalcaemia, patients with complex medical problems, or those with renal impairment. The dose
and route of calcium to correct hypocalcaemia should be determined on an individual patient
basis. There are no national guidelines for the treatment of acute hypocalcaemia, and practice
varies widely across Hospital Trusts.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
 Q&As are believed to accurately reflect the medical literature at the time of writing.
 The authors of Medicines Q&As are not responsible for the content of external
websites and links are made available solely to indicate their potential usefulness to
users of NeLM.You must use your judgement to determine the accuracy and relevance
of the information they contain.
 See NeLM for full disclaimer.
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References
1. Ariyan CE and Sosa JA. Assessment and Management of Patients with Abnormal
Calcium. Critical Care Medicine. 2004;32(4)S146-S154
2. Bushinsky DA, Monk RD. Electrolyte Quintet: Calcium. The Lancet. 1998; 352: 305–11
3. Tohme JF and Bilezikian JP. Diagnosis and Treatment of Hypocalcaemic Emergencies.
The Endocrinologist. 1996;6:10-18
4. Compston, JE. Investigation of Hypocalcaemia. Clinical Endocrinology. 1995; 42: 195-198
5. Goldhill DR. Calcium and Magnesium. Care of the Critically Ill. 1997;13(1):112-115
6. Forsythe RM, Wessel CB, Billiar TR et al. Parenteral Calcium for Intensive Care Unit
Patients (Review). A Cochrane Review. The Cochrane Library. 2009. Issue 3
7. Dickerson RN, Morgan LM, Croce MA et al. Treatment of Moderate to Severe Acute
Hypocalcaemia in Critically Ill Trauma Patients. Journal of Parenteral and Enteral
Nutrition. 2007; 31(3):228-233
8. Dickerson RN. Guidelines for the Intravenous Management of Hypophosphatemia,
Hypomagnesemia, Hypokalemia, and Hypocalcemia. Hospital Pharmacy.
2001;36(11):1201-1208
9. Leeds Teaching Hospitals NHS Trust. Clinical Guideline for the Treatment of
Hypocalcaemia in Adults. In house document. Review date August 2013.
10. Sweetman S (ed.). Martindale. The Complete Drug Reference, online edition. The
Pharmaceutical Press, London. http://medicinescomplete.com. (Date accessed
09/09/2011)
11. Steichen O. Use of Oral Calcium to Treat Hypocalcaemia (letter). British Medical Journal.
2008;336:1392
12. Chen HC. Intravenous Calcium Replacement for Asymptomatic Hypocalcemia of Critical
Illness. The Endocrinologist. 2001;11:364-367
13. Martin J (Editor). British National Formulary. No. 61 March 2011. The British Medical
Association and the Royal Pharmaceutical Society of Great Britain. Available online at
www.bnf.org
14. Medusa Injectable Medicines Guide. Available at http://medusa.wales.nhs.uk (Date
accessed 17/06/2011)
15. Summary of Product Characteristics. Electronic Medicines Compendium. Datapharm
Communications Ltd. (Hameln Ltd Calcium Gluconate Injection BP).
http://emc.medicines.org.uk/ (date accessed 24/1/2010; date last updated: 09/08/2010)
16. Cooper, MS, Gittoes, NJL. Diagnosis and Management of Hypocalcaemia. British Medical
Journal. 2008;336:1298-1302
17. Medicines and Healthcare products Regulatory Authority. Public Assessment Report Calcium gluconate 10% injection in 10ml glass containers: risk of aluminium exposure.
September 2010. Available at
http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarnings
andmessagesformedicines/CON093935
18. McEvoy GK (ed.). AHFS Drug Information 2009, online edition. American Society of
Health-System Pharmacists, Bethesda, USA. http://medicinescomplete.com. (Date
accessed 17/06/2011)
19. Baxter K (ed). Stockley’s Drug Interactions, online edition. The Pharmaceutical Press,
London. http://medicinescomplete.com. (Date accessed 17/06/2011)
20. Ashley, C and Currie, A (Eds). The Renal Drug Handbook, 3rd Edition (2009). Radcliffe
Medical Press, Oxford.
Quality Assurance
Prepared by
Lucy Hennessy, Leeds Medicines Information Centre
Date Prepared
13th September 2011
Checked by
David Abbott, Leeds Medicines Information Centre
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Date of check
13th September 2011
External QA check by
Chris Proudlove
Date of check
14th September 2011
Search strategy
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Embase [terms used: calcium (exp), calcium deficiency (exp), limited to English,
Human and Adult.]
Medline [terms used: calcium (exp), calcium deficiency (exp), limited to English, Human
and Adult]
In-house Database/resources
eMC
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