Calcium and digoxin vs. calcium alone for severe verapamil toxicity.
Calcium chloride (CaCl(2)) is ineffective in severe calcium channel antagonist overdoses. Digoxin increases intracellular calcium by inhibiting the sodium-potassium adenosine triphosphatase enzymes.


OBJECTIVE
To examine the effect of calcium and digoxin on the treatment of verapamil toxicity.


METHODS
Sixteen dogs were instrumented to monitor hemodynamics. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil (VER) at 6 mg/kg/hr and maintained for 30 minutes by titrating the VER rate. Following toxicity, the dogs received either digoxin (0.018 mg/kg) (DIG) (n = 8) or saline (No-DIG) (n = 8). Both groups received VER at three sequential rates (1 mg/kg/hr from 0 to 90 min, 6 mg/kg/hr from 90 to 130 min, and 18 mg/kg/hr from 130 to 170 min). Calcium boluses were given (500 mg at 0 and 15 min; 1 g at 140, 150, and 160 min). Data were analyzed using a repeated-measures analysis of covariance comparing DIG vs No-DIG across the infusion rates and time. Animal weight, does of VER administered during the toxicity phase, and baseline values were included as covariates. Mortality rates were compared at 230 minutes following a total dose of 500 mg of VER.


RESULTS
The DIG group had a higher systolic blood pressure (SBP) than the No-DIG group during the 1-mg/kg/hr (early p = 0.028, late p = 0.01), 6-mg/kg/hr (p = 0.051), and 18-mg/kg/hr (p = 0.038) VER infusion rates. There were no deaths in the DIG group and four deaths in the No-DIG group (Fisher = 0.08). Neither ventricular tachycardia nor ventricular fibrillation developed in either group. Other hemodynamic parameters did not show significant changes.


CONCLUSIONS
In a model of severe verapamil toxicity, digoxin plus calcium raised SBP and did not result in ventricular arrhythmias when compared with calcium alone.
Bania
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TC
Department of Emergency Medicine, the College of Physicians and Surgeons at Columbia University, St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA. toxtod@aol.com
Blaufeux
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Hughes
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Almond
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Homel
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D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000633:toxicity*; D016009:Chi-Square Distribution; D004077:Digoxin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D062787:Drug Overdose / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D008297:Male; D012016:Reference Values; D015996:Survival Rate; D016896:Treatment Outcome; D014700:Verapamil / Q000633:toxicity*
D002121:Calcium Channel Blockers; D004077:Digoxin; D014700:Verapamil; D002118:Calcium