Dose-dependent hemodynamic effect of digoxin therapy in severe verapamil toxicity.
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.


RESULTS
Digoxin resulted in a dose-dependent increase in systolic blood pressure at 4 hours (10.23 mm Hg/loading dose of digoxin, 95% CI = 2.74 to 17.73), 4 hours, 15 minutes (13.9 mm Hg/loading dose of digoxin, 95% CI = 8.75 to 19.01), and 5 hours (17.04 mm Hg/loading dose of digoxin, 95% CI = 1.76 to 32.32). Digoxin resulted in a dose-dependent increase in maximal ventricular pressure at the end of hour 3 (8.55 mm Hg/loading dose of digoxin, 95% CI = 3.41 to 13.69), 3 hours, 15 minutes (11.81 mm Hg/loading dose of digoxin, 95% CI = 4.89 to 18.73), hour 4 (8.26 mm Hg/loading dose of digoxin, 95% CI = 1.03 to 15.48), and 4 hours, 15 minutes (9.74 mm Hg/loading dose of digoxin, 95% CI = 4.47 to 15.00). The authors were unable to detect a dose-dependent increase in other parameters, including diastolic relaxation (diastolic change in pressure over time) and time to onset of death. No ventricular arrhythmias developed in any dogs.


CONCLUSIONS
There is a dose-dependent effect of digoxin on systolic blood pressure and maximal ventricular pressure in the setting of severe verapamil toxicity treated with high-dose CaCl(2).
St. Luke's-Roosevelt Hospital Center, Department of Emergency Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10019, USA. toxtod@aol.com
Theodore C
TC
Bania
Jason
J
Chu
Gregory
G
Almond
Eric
E
Perez
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000633:toxicity*; D002122:Calcium Chloride / Q000008:administration & dosage; D004077:Digoxin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D012016:Reference Values; D016896:Treatment Outcome; D014700:Verapamil / Q000633:toxicity*
D000931:Antidotes; D002121:Calcium Channel Blockers; D004077:Digoxin; D014700:Verapamil; D002122:Calcium Chloride