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.

The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine

“…Starting with an initial exposure of 25 mg/kg, each subsequent dosage was raised or lowered based on the survival of the preceding animal. The maximum likelihood estimate for LD 50 with SE was established using the following equation: / N x (A + C), where average (Xi) is the average test level (in mg/ kg) for the last n trials, N is the nominal number of samples or total number of samples, minus 1 less than the number of identical samples at the beginning of the trial, A and C values are acquired from Dixon's tables after the series of experiments are performed, and d is the distance between data points [11][12][13][14].…”