Amrinone as an antidote in experimental verapamil overdose

Objective: To evaluate the effect of amrinone as a treatment for the hemodynamic effects of verapamil overdose in a canine model. Methods: This nonblind interventional study was performed in an established canine model of verapamil toxicity, without concurrent control animals, Pentobarbital-anesthetized and instrumented dogs (n = 8) were maintained and observed for 60 minutes or until death, The animals were overdosed with verapamil, 15 mg/kg IV, over 30 minutes. Hemodynamic parameters, including cardiac index (CI), heart rate (HR), and mean arterial pressure (MAP), were monitored. Completion of the verapamil infusion represented the defined point of toxicity; at that point, all the animals received an amrinone bolus of 2 mg/kg IV over 2 minutes followed by an amrinone drip at 10 mu g/kg/min. The hemodynamic values at the defined point of toxicity were compared with those obtained postinitiation of the amrinone infusion. Results: Two animals died before the 60-minute observation period elapsed, Baseline CI was 5.6 L/min/m(2). Following verapamil-induced toxicity, mean CI was 2.2 L/min/m(2). After administration of amrinone, a significant (p < 0.05) increase in CI was observed at 30 minutes (CI = 3.6 L/min/m(3)), 45 minutes (CI = 4.2 L/min/m(2)), and 60 minutes (CI = 4.2 L/min/m(2)). There was no statistically significant difference noted for MAP or HR compared with ''point of toxicity'' values. Conclusion: Amrinone appears to reverse the depressed cardiac index associated with verapamil overdose in a canine model while having no significant effect on the hypotension or bradycardia.