Elsevier

Annals of Emergency Medicine

Volume 15, Issue 9, September 1986, Pages 1052-1059
Annals of Emergency Medicine

Special contribution
Experimental amitriptyline intoxication: Treatment of cardiac toxicity with sodium bicarbonate

https://doi.org/10.1016/S0196-0644(86)80128-7Get rights and content

Overdose with amitriptyline and other tricyclic antidepressants can result in ventricular conduction abnormalities as well as severe ventricular arrhythmias. The arrhythmogenic effects of these compounds may be attributed to their direct local anesthetic actions in blocking sodium channels in cardiac membranes. Thus tricyclic-induced ventricular arrhythmias usually do not respond well to therapy with standard Class I antiarrhythmic drugs that also have the same direct local anesthetic action and may potentiate the adverse effects of tricyclic antidepressants. Cardiac toxicity was produced in dogs by the administration of amitriptyline, both orally and IV. At serum concentrations less than 2,000 ng/mL, sinus tachycardia occurred with widened QRS complexes. At higher concentrations, QRS duration became more markedly prolonged and was followed by ventricular tachyarrhythmias. Occurrence of ventricular tachyarrhythmias was associated with QRS durations of more than 0.11 second. Sodium bicarbonate (18 to 36 mEq) administered IV over either 30 seconds or two minutes rapidly converted ventricular tachycardia to normal sinus rhythm. Conversion was associated with abbreviation of the QRS complex and was accompanied by a rise in both systolic and diastolic pressures. The duration of sodium bicarbonate effect paralleled the duration of the changes in arterial pH and plasma bicarbonate concentrations. In vitro studies in cardiac Purkinje fibers suggested that reversal of amitriptyline-induced cardiac membrane effects by sodium bicarbonate may be attributed not only to alkalinization but also to increases in extracellular sodium concentration, diminishing the local anesthetic action of amitriptyline and resulting in less sodium channel block. The direct depressant effect of amitriptyline on conduction is frequency dependent, and thus would be expected to be potentiated by the anticholinergic-mediated sinus tachycardia that accompanies toxicity. Counteracting the sinus tachycardia with either propranolol or physostigmine may reduce the direct cardiotoxic effect of the drug, but may exacerbate the hypotensive effects. Our results suggest that alkalinization with sodium bicarbonate provides an effective therapeutic modality for the treatment of tricyclic-induced cardiac toxicity.

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    Supported by grants from the Medical Research Council of Canada and the Quebec Heart Foundation.

    Presented at the UAEM/IRIEM Research Symposium on Toxicology in San Francisco, California, February 1986.

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