DESCRIPTION

Calcium is used to treat calcium channel blocker poisoning, local or systemic hydrogen fluoride poisoning, black widow spider envenomation, and potassium or magnesium toxicity, as well as other toxic causes of hypocalcemia (sodium fluoride, ammonium bifluoride, ethylene glycol, sodium or potassium phosphate).

FORMS AND USES

• Calcium chloride 10% (100 mg/ml). One ampule contains 10 ml (1 g calcium chloride; 13.6 mEq calcium ion).
• Calcium gluconate 10% (100 mg/ml). One ampule contains 10 ml (1 g calcium gluconate; 4.5 mEq calcium ion).

MECHANISM OF ACTION

• Hyperkalemia. Calcium directly antagonizes the membrane effects of excess potassium.
• Hydrogen fluoride poisoning
  • Fluoride ions bind calcium and magnesium, thereby inducing cellular and plasma electrolyte abnormalities that lead to cell death.
  • Administration of exogenous calcium binds the fluoride before this damage can occur and replenishes calcium that has already been bound by fluoride.
• Hypermagnesium. Calcium directly antagonizes the effect of magnesium on the level of the skeletal membrane.
• Calcium channel blocker toxicity. Calcium administration is used to simply overwhelm the blockade induced by the calcium channel blocker.
• Latrodectus mactans (black widow) spider bites. Increasing extracellular calcium levels may transiently counteract the calcium permeability derangements caused by black widow venom.

DRUG AND DISEASE INTERACTIONS

• Calcium use in the presence of digitalis has been reported to cause cardiac tetany.
• Calcium binds to some drugs (e.g., fluoro-quinolones), but this effect is not considered clinically important during acute therapy.

PREGNANCY AND LACTATION

Calcium is generally accepted as safe in pregnancy.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Calcium channel blocker overdose. Calcium administration is recommended at the first sign of bradycardia, hypotension, heart block, or any other serious signs of toxicity.
• Hydrogen fluoride poisoning
  • Local injury. Topical calcium administration is recommended for any symptomatic skin exposure to hydrogen fluoride. Dermal burns caused by hydrogen fluoride at a concentration of less than 20% can often be treated simply with calcium gluconate gel. Burns caused by higher concentrations of hydrogen fluoride may require tissue infiltration or other measures.
  • Systemic effects. Intravenous calcium administration is recommended at the first sign of hypocalcemia, usually evidenced by prolongation of the QTc interval.
• Calcium is used to treat hypocalcemia caused by other poisonings, for example, sodium fluoride or ammonium bifluoride, ethylene glycol, or phosphates such as sodium or potassium phosphate. The presence of hypocalcemia alone indicates the need for calcium treatment. Muscular twitching, QTc interval prolongation on the ECG, dysrhythmia, or seizure indicates the need for urgent infusion.
• Hyperkalemia. Intravenous calcium administration is recommended if ECG changes such as wide QRS or peaked T waves occur.
• Magnesium poisoning. Intravenous calcium administration is recommended if bradycardia, QTc interval prolongation, or muscular weakness develops (unless these effects need to be tolerated in order to administer high-dose magnesium antidotal therapy).
• Black widow envenomation. Calcium may be indicated as first-line therapy along with musculoskeletal agents and opioids.

Digitalis toxicity is a contraindication.

ADVERSE REACTIONS

• Transient hypercalcemia may cause cardiac dysrhythmia, hypertension, muscle weakness, and lethargy.
• Calcium chloride can cause venous thrombosis after intravenous infusion.
• Skin necrosis can result if calcium chloride is used intradermally, subcutaneously, or topically.

Intravenous or intraarterial calcium should always be administered to a patient on a cardiac monitor in an intensive care setting.

CALCIUM CHANNEL BLOCKER OVERDOSE

• Calcium chloride 10% is preferred over calcium gluconate.
• Calcium should be administered intravenously over 5 minutes to avoid cardiac effects of transient hypercalcemia.
  • Initial dose for adults is one ampule (10 ml of 10% solution) infused over 5 minutes.
  • The pediatric dose is 10 to 25 mg/kg up to one ampule per dose.
  • The dose may be repeated every 10 minutes as needed; however, if more than two additional treatments are needed, consultation with a poison center or medical toxicologist is strongly recommended.
• Calcium gluconate 10% may alternatively be used.
  • The adult dose is 10 to 30 ml (i.e., 1-3 g) intravenously over 5 minutes.
  • The pediatric dose is 30 to 75 mg/kg over 5 minutes, with a maximum of 1 g/dose.
  • The dose may be repeated every 10 minutes as needed; however, if more than two additional treatments are needed, consultation with a poison center or medical toxicologist is strongly recommended.
• ECG should be monitored continuously during therapy.
• Serum calcium, preferably ionized calcium, should be monitored frequently during therapy.
• In severe calcium channel blocker overdose, large doses of calcium (producing significant hypercalcemia) may be required.

HYDROGEN FLUORIDE POISONING: LOCAL EFFECTS

• Poisoning from hydrogen fluoride at a concentration of less than 20% can often be treated with topical application of 2.5% calcium gluconate gel.
  • The gel can be extemporaneously prepared in the pharmacy using 3.5 g calcium gluconate powder in 150 ml of water-soluble lubricant such as K-Y Jelly.
  • The gel may be kept in contact with the burned area using a latex glove or other occlusive dressing.
• Poisoning from hydrogen fluoride at a concentration of more than 20% or any burn unresponsive to topical gel application is often treated with calcium gluconate infiltration.
  • The use of calcium chloride must be avoided intradermally.
  • The initial therapy is intradermal injection of 10% calcium gluconate solution.
    • Standard calcium gluconate 10% solution is injected intradermally in the affected area with a 30-gauge needle to administer 0.5 ml/cm².
    • This use of this method is limited because most dermal exposures involve areas such as the fingers where significant volume cannot be injected.
• Persistent pain in fingers or toes despite calcium gluconate gel or infiltration may be treated with regional perfusion or intraarterial calcium gluconate. These methods should be chosen in consultation with a medical toxicologist.
  • Regional perfusion method
    • Using a technique similar to Bier block, an intravenous line is placed in the dorsum of the affected hand. The veins are emptied by elevating the arm.
    • A double-cuffed pneumatic tourniquet is applied above the elbow, inflated to 100 mm Hg above the systolic blood pressure, and 10 cc of 10% calcium gluconate infused. The cuff is maintained for 25 minutes and then deflated over 5 minutes.
  • Intraarterial method
    • This method should be chosen in consultation with a medical toxicologist.
    • A proximal artery (e.g., brachial or radial) is cannulated with a 20-gauge needle, and 20 ml of 10% calcium gluconate (2 g) in 40 ml of normal saline is infused intraarterially over 4 hours with an infusion pump.
    • If pain persists, the dose may be repeated.

HYDROGEN FLUORIDE POISONING: SYSTEMIC EFFECTS

• Calcium chloride 10% is preferred over calcium gluconate.
• Calcium should be administered intravenously over 5 minutes to avoid cardiac effects of transient hypercalcemia.
  • Initial dose for adults is one ampule (10 ml of 10% solution) infused over 5 minutes.
  • For children the infused dose is 10 to 25 mg/kg up to one ampule per dose
  • The dose may be repeated every 10 minutes as needed; however, if more than two additional treatments are needed, consultation with a poison center or medical toxicologist is strongly recommended.
• Calcium gluconate 10% may be used.
  • Adult dose is 10 to 30 ml (i.e., 1-3 g), administered intravenously over 5 minutes; the pediatric dose is 30 to 75 mg/kg, administered intravenously over 5 minutes, with a maximum pediatric amount of 1 g/dose.
  • The dose may be repeated every 10 minutes as needed.
• ECG should be monitored continuously during therapy.
• Serum calcium, preferably ionized calcium, should be monitored frequently during therapy.

HYPOCALCEMIA CAUSED BY OTHER POISONINGS (SODIUM FLUORIDE, AMMONIUM BIFLUORIDE, ETHYLENE GLYCOL, PHOSPHATES)

• Calcium chloride 10% is preferred over calcium gluconate.
• Calcium should be administered intravenously over 5 minutes to avoid the cardiac depressant effects of transient hypercalcemia.
  • The initial adult dose is one ampule of calcium chloride (10 ml of 10% solution) infused over at least 5 minutes.
  • The initial pediatric dose is 10 to 25 mg/kg of calcium chloride (10 ml of 10% solution) up to one ampule per dose.
  • The dose may be repeated every 10 minutes as needed; however, if more than two additional treatments are needed, consultation with a poison center or medical toxicologist is strongly recommended.
• Calcium gluconate 10% also may be used; adult, 10 to 30 ml (i.e., 1-3 g) intravenously over 5 minutes; pediatric, 30 to 75 mg/kg intravenously over 5 minutes; the maximum pediatric amount is 1 g/dose. The dose may be repeated every 10 minutes as needed.
• ECG should be monitored continuously during therapy.
• Serum calcium, preferably ionized calcium, should be monitored frequently during therapy.

HYPERKALEMIA

• The adult dose is 10 ml (i.e., 1 g) of calcium chloride administered intravenously over 5 minutes.
• The pediatric dose is 0.5 to 1 mg/kg of calcium chloride administered intravenously over 5 minutes, with a maximum pediatric amount of 1 g/dose.
• The dose may be repeated in 5 minutes or as needed, guided by the ECG.

MAGNESIUM TOXICITY

• The adult dose is 10 ml (i.e., 1 g) of calcium gluconate 10%, administered intravenously over 5 minutes.
• The pediatric dose is 20 mg/kg of calcium gluconate 10%, administered intravenously over 5 minutes, with a maximum pediatric amount of 1 g/dose.
• The dose may be repeated in 5 minutes.

BLACK WIDOW ENVENOMATION

• Initial dose in adults is 10 ml (1 g) of 10% calcium chloride intravenously over 5 minutes.
• Initial dose in children is 10 mg/kg of 10% calcium chloride intravenously over 5 minutes.
• The dose may be repeated in 15 minutes if no effects are seen. If no improvement is seen with calcium chloride, muscle relaxants, and narcotics, then consideration should be given to the use of Latrodectus antivenom.

Section Outline:

• CALCIUM CHANNEL BLOCKER OVERDOSE
• HYDROGEN FLUORIDE POISONING: LOCAL EFFECTS
• HYDROGEN FLUORIDE POISONING: SYSTEMIC EFFECTS
• HYPOCALCEMIA CAUSED BY OTHER POISONINGS (SODIUM FLUORIDE, AMMONIUM BIFLUORIDE, ETHYLENE GLYCOL, PHOSPHATES)
• HYPERKALEMIA
• MAGNESIUM TOXICITY
• BLACK WIDOW ENVENOMATION

• The onset of life-threatening toxicity from hypocalcemia may be abrupt; for example, cardiac arrest due to dysrhythmia may occur precipitously following hydrofluoric acid ingestion or severe hyperkalemia.
• Patients with a significant overdose of calcium channel blocker overdose should be monitored at least 24 hours because signs and symptoms may be delayed following poisoning with sustained-release preparations.
• Large amounts of calcium may be needed to treat hypocalcemia from severe fluoride or calcium channel blocker poisoning.
• Myocardial depression from transient hypercalcemia may occur if intravenous calcium is administered too rapidly.
• In patients with renal failure, systemic calcium administration must be individually tailored.

None.

See Also: SECTION IV, Calcium Channel Blocking Drugs, Hydrofluoric Acid and Ammonium Bifluoride, Black Widow Spider chapters.

RECOMMENDED READING

Graudins A, Burns MJ, Aaron CK. Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of the upper extremity. Ann Emerg Med 1997;30:604-607.

Vance MV, Curry SC. Digital hydrofluoric acid burns: treatment with intra-arterial calcium infusion. Ann Emerg Med 1986;15:890-896.

Author: Lada Kokan

Reviewer: Katherine M. Hurlbut