ISDB WHO Single Medicines Review

Calcium gluconate

Introduction

Hypocalcaemia presents with symptoms ranging from paraesthesia and

muscle cramps, to tetany with the classical features of carpo-pedal spasm,
laryngeal stridor and convulsions. Calcium gluconate is a calcium supplement
listed in the 2004 WHO Model Formulary as a complementary drug for the
treatment of hypocalcaemic tetany. No other calcium supplements are listed
for this (or any other) indication.
Product and Dosage

Calcium gluconate is listed as a solution for intravenous injection. The solution

contains calcium gluconate (monohydrate) 100 mg (Ca2+ 220 micromol)/ml,
10-ml ampoule.
Adult dosage for the treatment of hypocalcaemic tetany is 1 g (2.2 mmol) by
slow intravenous injection, followed about 4 g (8.8 mmol) daily by continuous
intravenous infusion.1 Supplementation should be continued till serum
calcium is within the normal range. No dosage is given for children.
Evidence of value

There are no clinical trials or systematic reviews covering the treatment of

hypocalcaemic tetany, and this assessment is based on 'standard' practice as
reflected mainly by textbooks. Acute, symptomatic hypocalcaemia requires
emergency treatment to bring the calcium concentration back to the normal
range. This can be achieved by giving intravenous calcium, and calcium
gluconate is the recommended calcium salt.2-13 The advantage of calcium
gluconate (90 mg elemental calcium per 10-mL ampule) is that it irritates the
veins less than does calcium chloride (272 mg of elemental calcium per 10mL ampule).4, 10 Symptoms refractory to appropriate doses of calcium may be
caused by coexisting hypomagnesemia. In patients with normal renal function,
administration of 2 - 4 g of 10% magnesium sulfate should be considered.3
Adverse effects

The most common adverse effects of intravenous calcium are hypertension,

nausea, vomiting, and flushing. Bradycardia and heart block occur in rare
cases. Patients receiving IV calcium should be placed on a cardiac monitor,
and administration should be discontinued if bradycardia ensues.3 Patients
may complain of tingling sensations, a sense of oppression or heat waves and
a calcium or chalky taste following the intravenous administration of calcium
gluconate. Rapid intravenous injection of calcium salts may cause
vasodilatation, decreased blood pressure, bradycardia, cardiac arrhythmias,
syncope and cardiac arrest. 14
Calcium should be administered with particular caution in patients taking
digoxin because it may precipitate (or exacerbate) digoxin-induced
cardiotoxicity. Because extravasated calcium may cause severe tissue
irritation and necrosis, it should be given through a well-functioning catheter.3
Recommendation

Calcium gluconate injection is important for the acute treatment of

hypocalcaemic tetany and should be retained in the WHO Model List of

Essential Medicines. Consideration should be given to the inclusion in the
Model List of other forms of calcium supplementation both for the less acute
treatment of hypocalcaemic tetany, and as part of the management of bone
diseases such as osteoporosis.15-22
Fariba Jaffary, Therapeutics Initiative, Vancouver,
Canada
(October 2004)
References

1. Mehta DK, Ryan RSM, Hogerzeil HV, editors. WHO model formulary
2004 Geneva: World Health Organization; 2004;P 423
2. Goldman: Cecil Textbook of Medicine, 21st ed., Copyright 2000 W.
B. Saunders Company;P1404-06
3. Marx: Rosen's Emergency Medicine: Concepts and Clinical Practice,
5th ed., Copyright 2002 Mosby, Inc. 1733
4. Noble: Textbook of Primary Care Medicine, 3rd ed., Copyright 2001
Mosby, Inc. P 896-7
5. Ford: Clinical Toxicology, 1st ed., Copyright 2001 W. B. Saunders
Company Hypocalcaemia P 85-86
6. Kapoor M , Chan GZ. Fluid and electrolyte abnormalities. Crit Care Clin
- 01-JUL-2001; 17(3): 503-29
7. Ariyan CE, Sosa JA. Assessment and management of patients with
abnormal calcium
Crit Care Med - 01-APR-2004; 32(4 Suppl): S146-54
8. Bansal A, Miskoff J, Lis RJ. Otolaryngologic critical care
Crit Care Clin - 01-JAN-2003; 19(1): 55-72
9. Edwards BF. Postoperative medical complications: postoperative renal
insufficiency Med Clin North Am - 01-SEP-2001; 85(5): 1241-54
10. Vasa F Prolonged critical illness management of long term acute care
Endocrine Problems in the Chronically Critically Ill Patient. Clin Chest
Med - 01-MAR-2001; 22(1): 193-2
11 Nader S ,Thyroid disease and other endocrine disorders in pregnancy.
Obstet Gynecol Clin North Am ,2004; 31(2): 257-85, v-vi
12 Boger MS , Advantages and disadvantages of surgical therapy and
optimal extent of thyroidectomy for the treatment of hyperthyroidism.
Surg Clin North Am - 01-JUN-2004; 84(3): 849-74

13 ACOG Practice Bulletin, Clinical management guidelines for

Obstetrician- Gynecologists,Osteoporosis, NUMBER 50, JANUARY
2004
14 MD consult;drugs,.generic drugs, Calcium Gluconate(000600)
15 Royal College of Physicians (RCP),Osteoporosis - (2001),
Clinical guidelines for prevention and treatment,
Update on pharmacological interventions and an algorithm for
management,
http://www.rcplondon.ac.uk/pubs/wp_osteo_update.htm
16 CREST, Management of postmenopausal osteoporosis: position
statement of the North American Menopause Society. Menopause
2002 Mar-Apr; 9(2):84-101
17 CREST Guidance in the prevention and treatment of osteoporosis,
March 2001 www.n-i.nhs.uk/crest Based on the Royal College of
Physicians documents OSTEOPOROSIS clinical guidelines for
prevention and treatment
(1999), Update (2000), the Department of Healths Quick Reference
Primary Care Guide on the Prevention and Treatment of Osteoporosis
(1998) and the National Osteoporosis Society documents
18 Cumming R G, Nevitt M C. Calcium for prevention of osteoporotic
fractures in postmenopausal women. Journal of Bone and Mineral
Research. 1997. 12(9). 1321-1329
19 PRODIGY Guidance, Osteoporosis treatment and prevention of falls
http://www.prodigy.nhs.uk/ (PRODIGY)
Applies to: Patients over 192 months (16 years)
This guidance is based on the Scottish Intercollegiate Guidelines
Network (SIGN) Guideline Management of Osteoporosis (2003) and
the Royal College of Physicians guideline Glucocorticoid-induced
Osteoporosis (2003)
20 Primary Care Rheumatology Society (PCR), Osteoporosis: minimum
standard guidelines 1999,
http://www.pcrsociety.com/guidelines/minimum_standards.html
21 National Guideline Clearinghouse(NGC), WWW.guideline.gov,
Recommendations for the prevention and treatment of glucocorticoidinduced osteoporosis: 2001 update
22 Homik J. Suarez-Almazor ME. Shea B. Cranney A. Wells G. Tugwell
P.Calcium and vitamin D for corticosteroid-induced osteoporosis.
[Review] [5 refs]
Cochrane Database of Systematic Reviews. (2):CD000952, 2000

Search Strategy
The medical literature was searched to identify scientifically valid, systematic
reviews (with or without meta-analyses) related to parenteral calcium
gluconate use for the treatment of hypocalcemic tetany.
Practice guidelines where also reviewed, but were considered much less valid
source of scientifically rigorous findings:
Details of searches:
Search in MD Consult Practice guidelines,
Database: MD Consult, http://home.mdconsult.com/das/search/
The Cochrane Database of Systematic Reviews
Guidelines search websites:
National Guidelines Clearing house
National Library of Medicine HSTAT
NeLH Guidelines Finder
Database: Australian Centre for Evidence Based
Clinical Practice (ACEBCP).
www.acebcp.org.au/terms.htm
Databases were searched using the search term calcium gluconate,
hypocalcemia/ hypocalcaemia and tetany.
Databases were also searched for any guidelines about using calcium
gluconate as search term for the probable use of calcium in the treatment of
hypocalcemic tetany.
In addition, Medline (OVID) was search for any available randomized clinical
trial using search terms calcium gluconate ,calciumand
hypocalcemic/hypocalcaemic tetany, hypocalcemia and randomized
controlled trials(RCT) in publication type.
As it was predicted there was not any RCT for calcium and hypocalcemic
tetany in adult. The only available RCT was [Turner TL. Cockburn F. Forfar
JO. Magnesium therapy in neonatal tetany. Lancet. 1(8006):283-4, 1977 Feb
5] comparing calcium gluconate, phenobarbitone and magnesium sulphate for
the treatment of symptomatic hypocalcaemia in infants. They have
recommended Magnesium sulphate as the treatment of choice in
symptomatic neonatal tetany whether or not there is hypomagnesaemia
There was not any guideline or systematic review regarding the use of
calcium gluconate for hypocalcemic tetany.