Dose-dependent Hemodynamic Effect of Digoxin Therapy in Severe Verapamil Toxicity

Abstract

Calcium chloride (CaCl 2 ) alone is an ineffective antidote in severe calcium channel antagonist overdoses. Digoxin has been evaluated as a therapy to increase the effectiveness of calcium in severe calcium channel antagonist overdoses. Objective: To determine if there is a dose-dependent hemodynamic effect of digoxin in the setting of severe verapamil toxicity treated with high-dose CaCl 2 . Methods: Eight dogs were instrumented to measure systolic and diastolic blood pressure, cardiac output, pulmonary artery pressures, and left ventricular pressures. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil rate. Following verapamil toxicity, each dog received one dose of digoxin equivalent to 0, 1, 1.5, 2, 3, 4, 6, or 8 times the loading dose of digoxin (0.009 mg/ kg). The verapamil rate was changed to 4 mg/kg/hr and continued for the next five hours. CaCl 2 boluses were given (0.5 g immediately following verapamil toxicity and 1 g at one, two, and three hours). Measurements were compared with the loading dose of digoxin using linear regression analysis.

Calcium Channel Blocker Toxicology

“…The survival time showed a trend toward improved survival with increasing dose of digoxin, but a dose-dependent survival curve was not established. 31 Both of these studies are somewhat limited by the number of experimental subjects and the ability to generalize animal data to humans. Interestingly, in neither of these studies did the digoxin group develop a significant difference in bradycardia, as would be expected with a drug that both slows the cardiac conduction system and increases vagal tone.…”