Treatment of ventricular tachyarrhythmias resulting from amitriptyline toxicity in dogs

S Nattel and M Mittleman

This study was designed to analyze the effects of lidocaine and sodium bicarbonate on ventricular arrhythmias resulting from amitriptyline infusion in dogs. Amitriptyline was infused i.v. at 0.5 mg/kg/min for 30 min, followed by 1 mg/kg/min to dogs anesthetized with morphine and alpha-chloralose. When arrhythmia occurred, the infusion rate was reduced by one-third and the effect of various interventions studied. In the initial 18 dogs, lidocaine, sodium bicarbonate or isotonic saline was administered i.v. to six dogs each in a randomized, blinded fashion. The prevalence of ventricular ectopic complexes was not changed after isotonic saline, but was reduced by lidocaine at concentrations greater than or equal to 5 mg/l and by sodium bicarbonate. The effects of lidocaine were transient and associated with significant blood pressure reduction. Sodium bicarbonate produced more dramatic and sustained arrhythmia reversal along with a reduction in amitriptyline-induced conduction slowing. Administration of hypertonic sodium chloride in equimolar quantities to sodium bicarbonate failed to affect amitriptyline-induced ventricular arrhythmias significantly, but hyperventilation to a pH similar to that produced by sodium bicarbonate (7.48) significantly reduced the frequency of amitriptyline-induced ventricular ectopy. When amitriptyline was infused into dogs ventilated with various respiratory rates, ventricular arrhythmia resulted in 18 of 18 (100%) dogs with pH less than 7.42, 2 of 4 (50%) dogs with pH between 7.48 and 7.51 and 0 of 8 (0%) dogs with a pH between 7.59 and 7.65 (P less than or equal to .001). These results suggest that sodium bicarbonate is effective treatment for amitriptyline-induced cardiac arrhythmias with beneficial effects largely due to alkalinization.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 231, Issue 2, pp. 430-435, 11/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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