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 tricyclic 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

Nonrandomized, controlled intervention trial.

SETTING

University laboratory.

SUBJECTS

Eighty-six male Wistar rats anesthetized with pentobarbital and mechanically ventilated.

INTERVENTIONS

Rats subjected to a 60-min continuous infusion of amitriptyline (1.25 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, milrinone, magnesium, epinephrine + magnesium, or norepinephrine + magnesium.

MEASUREMENTS AND MAIN RESULTS

Without treatment, all animals exhibited arrhythmias on the electrocardiogram within 20 mins. All treatment drugs delayed the onset of arrhythmias, but significant differences were only observed after administration of epinephrine, epinephrine + magnesium sulfate, and norepinephrine + magnesium sulfate. All the inotropic drugs markedly increased survival. Sodium concentrations were unaffected by all treatments. In control animals, potassium concentrations increased during amitriptyline infusion. Norepinephrine treatment had no effect on potassium concentrations, whereas all other treatments resulted in decreased potassium concentrations.

CONCLUSIONS

All inotropic drugs used in the study increased survival in tricyclic antidepressant poisoning in rats without increasing the risk of arrhythmias. Furthermore, epinephrine and norepinephrine + magnesium sulfate were effective in preventing arrhythmias, possibly due to improved hemodynamic performance or potassium homeostasis.