A29: Antidotes in Depth

INTRODUCTION

Calcium is essential to maintain the normal function of the heart, vascular smooth muscle, skeletal system, and the nervous system. It is vital in enzymatic reactions, in neurohormonal transmission, and in the maintenance of cellular integrity.²¹ 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.²¹ Hypocalcemia can result in hyperreflexia, muscle spasms, tetany, seizures, and QT interval prolongation (Chaps. 16 and 19).²¹

PHARMACOLOGY

Early evidence suggested that in hypocalcemic children,¹⁰ intravenous (IV) infusions of calcium chloride produce slightly larger increases in ionic calcium than infusions of calcium gluconate, but this concept has been challenged.^43,70 Administration of equivalent molar doses of calcium found in calcium chloride (1 g CaCl₂10%) and calcium gluconate (3 g Ca gluconate 10%) produce similar serum ionized calcium concentrations, with both peaks occurring within 30 seconds in a model utilizing the anhepatic stage of liver transplant.⁴³ These results support the concept that simple dissociation of calcium from gluconate is responsible for releasing calcium, rather than hepatic metabolism.

ROLE IN CALCIUM CHANNEL BLOCKER TOXICITY

Calcium enters cells in numerous ways. In cardiac and smooth muscles the voltage-dependent L-type channels are inhibited by the calcium channel blockers (CCBs) available in the United States.^5,60 Patients with CCB overdose (Chap. 61) may develop nausea, vomiting, hypotension, bradycardia, myocardial depression, sinus arrest, atrioventricular (AV) block, and metabolic acidosis with hyperglycemia, shock, pulmonary edema, altered mental status, and seizures.⁵⁰ Because CCBs do not alter either receptor-operated channels or the release of calcium from intracellular stores,⁶⁵ the serum calcium concentration remains normal in overdose.

IV administration of calcium to dogs poisoned with verapamil or diltiazem improves cardiac output secondary to increased inotropy.²⁵ The heart rate and cardiac conduction are affected minimally, if at all.^22,25,56 Case reports and reviews of the literature suggest similar findings in humans.^{2,3,11,17,20,26,31,34,41,53,54,62}

Calcium should be administered to symptomatic patients with CCB overdoses.^30,37,40 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.^11,25 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 ...