EFFECTS OF EPINEPHRINE, NOREPINEPHRINE, MAGNESIUM-SULFATE, AND MILRINONE ON SURVIVAL AND THE OCCURRENCE OF ARRHYTHMIAS IN AMITRIPTYLINE POISONING IN THE RAT

Objectives: Cardiac depression is the main adverse effect of severe tr icyclic antidepressant poisoning. The aim of this study was to compare the effects of several inotropic drugs on survival and the occurrence of arrhythmias in the treatment of amitriptyline poisoning. Design: N onrandomized, controlled intervention trial. Setting: University labor atory. Subjects: Eighty-six male Wistar rats anesthetized with pentoba rbital and mechanically ventilated. Interventions: Rats subjected to a 60-min continuous infusion of amitriptyline (1.25 mg/kg/min) were tre ated with a continuous infusion of either epinephrine, norepinephrine, milrinone, magnesium, epinephrine + magnesium, or norepinephrine + ma gnesium. Measurements and Main Results: Without treatment, all animals exhibited arrhythmias on the electrocardiogram within 20 mins. All tr eatment drugs delayed the onset of arrhythmias, but significant differ ences were only observed after administration of epinephrine, epinephr ine + magnesium sulfate, and norepinephrine + magnesium sulfate. All t he inotropic drugs markedly increased survival. Sodium concentrations were unaffected by all treatments. In control animals, potassium conce ntrations increased during amitriptyline infusion. Norepinephrine trea tment had no effect on potassium concentrations, whereas all other tre atments resulted in decreased potassium concentrations. Conclusions: A ll inotropic drugs used in the study increased survival in tricyclic a ntidepressant poisoning in rats without increasing the risk of arrhyth mias. Furthermore, epinephrine and norepinephrine + magnesium sulfate were effective in preventing arrhythmias, possibly due to improved hem odynamic performance or potassium homeostasis.