Calcium is essential to maintaining the normal function of the heart, vascular smooth muscle, skeletal system, and nervous system. It is vital in enzymatic reactions, in neurohormonal transmission, and in the maintenance of cellular integrity.25 The endocrine system maintains calcium homeostasis. Approximately half of the total serum calcium is ionized and active, and the remainder is primarily bound to albumin. Hypercalcemia raises the threshold for nerve and muscle excitation, resulting in muscle weakness, lethargy, cardiac conduction disturbances and coma.25 Hypocalcemia can result in hyperreflexia, muscle spasms, tetany, and seizures (Chap. 16).25
Although calcium enters cells in numerous ways, only one of these, the voltage-dependent L-type channels in cardiac and smooth muscles, is inhibited by the calcium channel blockers (CCBs) available in the United States.5,71 Calcium channel blocker overdoses (Chap. 60) may result in nausea, vomiting, hypotension, bradycardia, myocardial depression, sinus arrest, atrioventricular (AV) block, and metabolic acidosis with hyperglycemia, shock, pulmonary edema, altered mental status, and seizures.58 Because CCBs do not alter either receptor-operated channels or the release of calcium from intracellular stores,76 the serum calcium concentration remains normal in CCB overdose.
Intravenous (IV) administration of calcium to dogs poisoned with verapamil or diltiazem improves cardiac output secondary to increased inotropy.29 The heart rate and cardiac conduction are affected minimally, if at all.26,29,65 Case reports and reviews of the literature suggest similar findings in humans.2,3,13,20,24,30,33,38,47,61,62,73
Calcium should be administered to symptomatic patients with CCB overdoses.34,43,46 Unfortunately, the most seriously ill patients respond inadequately, and other measures are often required. The dose of calcium needed to treat patients with CCB overdose is unknown. In animal experiments, there appears to be a dose-related improvement.13,29 Since calcium chloride is extremely irritating to small vessels, subcutaneous tissue and muscle and may cause necrosis following extravasation, it is usually only administered through a central venous line. The customary approach is to administer an initial IV dose of 3 g of calcium gluconate (30 mL of 10% calcium gluconate) or 1 g of calcium chloride (10 mL of 10% calcium chloride) to adults.58 Based on case reports, this dose may need to be repeated as clinically indicated. The hypothesis is that sufficient calcium must be present to compete with the CCB for binding to the L-type calcium channel. One author used a total of 10 g of calcium gluconate as 1 g boluses over 12 minutes after diltiazem-induced asystole and another 2.5 g of calcium gluconate minutes later for a second asystolic event, with a resultant serum calcium concentration of 3.36 mmol/L (normal: 2.2–2.6 mmol/L) about 1 hour after administration of the calcium gluconate.36 Several authors have successfully treated patients with a total of 18 to 30 g of calcium gluconate or 13 g of calcium chloride over 2 to ...