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 micrograms/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/m2. Following verapamil-induced toxicity, mean CI was 2.2 L/min/m2. After administration of amrinone, a significant (p < 0.05) increase in CI was observed at 30 minutes (CI = 3.6 L/min/m2), 45 minutes (CI = 4.2 L/ min/m2), and 60 minutes (CI = 4.2 L/min/m2). There was no statistically significant difference noted for MAP or HR compared with "point of toxicity" values.


CONCLUSIONS
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.
Koury
S I
SI
East Carolina University School of Medicine, Greenville, NC, USA.
Stone
C K
CK
Thomas
S H
SH
D000676:Amrinone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D004285:Dogs; D062787:Drug Overdose / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000506:poisoning*
D000931:Antidotes; D014700:Verapamil; D000676:Amrinone