Effects of epinephrine, norepinephrine, magnesium sulfate, and milrinone on survival and the occurrence of arrhythmias in amitriptyline poisoning in the rat.
OBJECTIVE
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.


METHODS
Nonrandomized, controlled intervention trial.


METHODS
University laboratory.


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


METHODS
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.


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.
Department of Anesthesia and Intensive Care, University of Göteborg, Sweden.
K
K
Knudsen
J
J
Abrahamsson
D000639:Amitriptyline / Q000506:poisoning*; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000627:therapeutic use*; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008297:Male; D020105:Milrinone; D009638:Norepinephrine / Q000627:therapeutic use*; D011041:Poisoning / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D013997:Time Factors
D002316:Cardiotonic Agents; D011728:Pyridones; D000639:Amitriptyline; D008278:Magnesium Sulfate; D020105:Milrinone; D009638:Norepinephrine; D004837:Epinephrine