Chapter 172. Calcium

Pharmacology

1. Calcium is a cation that is necessary for the normal functioning of a variety of enzymes and organ systems, including muscle and nerve tissue. Hypocalcemia, or a blockade of the effects of calcium, may cause muscle cramps, tetany, and ventricular fibrillation. Antagonism of calcium-dependent channels results in hypotension, bradycardia, and atrioventricular (AV) block.

2. Calcium ions rapidly bind to fluoride ions, abolishing their toxic effects.

3. Calcium can reverse the negative inotropic effects of calcium antagonists; however, depressed automaticity and AV nodal conduction velocity and vasodilation may not respond to calcium administration.

4. Calcium stabilizes cardiac cell membranes in hyperkalemic states.

Indications

1. Symptomatic hypocalcemia resulting from intoxication by fluoride, oxalate, or the intravenous anticoagulant citrate.

2. Hydrofluoric acid exposure (See Hydrogen Fluoride and Hydrofluoric Acid).

3. Hypotension in the setting of calcium channel antagonist (eg, verapamil) overdose (See Calcium Channel Antagonists).

4. Severe hyperkalemia with cardiac manifestations (relatively contraindicated in the setting of digitalis toxicity; see Item III.B below).

5. Symptomatic hypermagnesemia.

Contraindications

1. Hypercalcemia except in the setting of calcium channel antagonist poisoning, in which hypercalcemia may be desirable.

2. Although controversial, calcium is relatively contraindicated in the setting of intoxication with cardiac glycosides (may aggravate digitalis-induced ventricular tachydysrhythmias) and should be reserved for life-threatening situations.

3. Note: Calcium chloride salt should not be used for intradermal, subcutaneous, or intra-arterial injection because it is highly concentrated and may result in further tissue damage.

Adverse effects

1. Tissue irritation, particularly with calcium chloride salt; extravasation may cause local irritation or necrosis.

2. Hypercalcemia, especially in patients with diminished renal function.

3. Hypotension, bradycardia, syncope, and cardiac dysrhythmias caused by rapid intravenous administration.

4. Neuromuscular weakness.

5. Constipation caused by orally administered calcium salts.

6. Use in pregnancy. FDA Category C (indeterminate). This does not preclude its acute, short-term use for a seriously symptomatic patient (See Introduction in Section III).

Drug or laboratory interactions

1. Inotropic and dysrhythmogenic effects of digitalis may be potentiated by calcium. The use of intravenous calcium in the setting of cardiac glycoside toxicity is not absolutely contraindicated, but indications remain controversial.

2. A precipitate will form with solutions containing soluble salts of carbonates, phosphates, or sulfates and with various antibiotics.

Dosage and method of administration. Note: A 10% solution of calcium chloride contains three times the amount of calcium ions per milliliter that a 10% solution of calcium gluconate contains. (A 10% solution of calcium chloride contains 27.2 mg/mL of elemental calcium; a 10% solution of calcium gluconate contains 9 mg/mL of elemental calcium.)

1. Oral fluoride ingestion. Administer calcium-containing antacid (calcium carbonate) orally to complex fluoride ions.

2. Symptomatic hypocalcemia, hyperkalemia. Give 10% calcium gluconate, 20–30 mL (children: 0.3–0.4 mL/kg), or 10% calcium chloride, 5–10 mL (children: 0.1–0.2 mL/kg), slowly IV. Repeat as needed every 5–10 minutes.

3. Calcium antagonist poisoning. Start with doses as described above. High-dose calcium therapy has been reported to be effective in some cases of severe calcium channel blocker overdose. Corrected calcium concentrations of approximately 1.5–2 times normal have correlated with improved cardiac function. In the setting of calcium channel antagonist overdose, as much as 30 g of calcium gluconate has been given over 10 hours, resulting in a serum calcium concentration of 23.8 mg/dL, which was tolerated without adverse effect. However, not all patients will tolerate extreme elevations in serum calcium concentrations. Administer calcium as multiple boluses (eg, 1 g every 10–20 minutes) or as a continuous infusion (eg, 20–50 mg/kg/h). Serum calcium concentrations should be measured every 1–2 hours during therapy with high-dose calcium.

4. Dermal hydrofluoric acid exposure. For any exposure involving the hand or fingers, obtain immediate consultation from an experienced hand surgeon or medical toxicologist. Regardless of the specific therapy chosen, systemic narcotic analgesics should be strongly considered as adjunctive therapy.

   1. Topical. Calcium concentrations for topical therapy have ranged from 2.5 to 33%; the optimal concentration has not been determined. In many industrial settings, a commercially available 2.5% calcium gluconate gel is kept at the work site for rapid treatment of occupational exposures (Calgonate). A 2.5% gel can be prepared in the emergency department by combining 1 g of calcium gluconate per 40 g (approximately 40 mL) of water-soluble base material (Surgilube, K-Y Jelly). A 32.5% gel can be made by compounding a slurry of ten 650-mg calcium carbonate tablets in 20 mL of water-soluble lubricant. For exposures involving the hand or fingers, place the gel in a large surgical latex glove to serve as an occlusive dressing to maximize skin contact. Topical calcium gluconate treatment is much more effective if applied within 3 hours of the injury.

   2. For subcutaneous injection (when topical treatment fails to relieve pain), inject 5–10% calcium gluconate (not chloride) SC intralesionally and perifocally (0.5–1 mL/cm2 of affected skin), using a 27-gauge or smaller needle. This can be repeated two to three times at 1- to 2-hour intervals if pain is not relieved. No more than 0.5 mL should be injected into each digit.

   3. Bier block technique

      1. Establish distal IV access in the affected extremity (eg, dorsum of the hand).

      2. Exsanguinate the extremity by elevation for 5 minutes. Alternatively, an Esmarch bandage may be used by wrapping from the distal to the proximal extremity.

      3. Inflate a blood pressure cuff to just above systolic blood pressure. The arm can then be lowered or the bandage removed.

      4. With the cuff kept inflated, infuse 25–50 mL of a 2% calcium gluconate solution (10 mL of 10% calcium gluconate diluted with 40 mL of D5W) into the empty veins.

      5. After 20–25 minutes, slowly release the cuff over 3–5 minutes.

      6. Repeat if pain persists or use the intra-arterial infusion.

   4. For intra-arterial administration, dilute 10 mL of 10% calcium gluconate with 50 mL of D5W and infuse over 4 hours through either the brachial or the radial artery catheter. The patient should be monitored closely over the next 4–6 hours, and if pain recurs, a second infusion should be given. Some authors have reported 48–72 hours of continuous infusion.

5. Other sites of hydrofluoric acid exposure

   1. Nebulized 2.5% calcium gluconate has been reported for cases of inhalational hydrofluoric acid exposure. Inhalational exposure should be considered with dermal exposures of more than 5% of the total body surface area. Add 1.5 mL of 10% calcium gluconate to 4.5 mL of sterile water to make a 2.5% solution.

   2. Ocular administration of 1% calcium gluconate solutions every 4–6 hours has been used for 24–48 hours but is of unproven efficacy compared with irrigation with saline or water. Higher concentrations of calcium gluconate may worsen corrosive injury to ocular structures. Ophthalmology consultation should be obtained.

Formulations

1. Oral. Calcium carbonate, suspension, tablets, or chewable tablets, 300–800 mg.

2. Parenteral. Calcium gluconate (10%), 10 mL (1 g contains 4.5 mEq of calcium); calcium chloride (10%), 10 mL (1 g contains 13.6 mEq).

3. Topical. Calcium gluconate gel (2.5%) in 25- and 30-g tubes, but none of these commercially available formulations has been approved by the FDA.

4. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours:

   1. Calcium chloride, first 8 hours: 10 g or 10 vials (1 g each) of 10% calcium chloride; first 24 hours: 10 g or 10 vials (1 g each) of 10% calcium chloride.

   2. Calcium gluconate, first 8 hours: 30 g or 30 vials (1 g each) of 10% calcium gluconate; first 24 hours: 30 g or 30 vials (1 g each) of 10% calcium gluconate.