Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning

Crit Care Med. 1997 Apr;25(4):669-74. doi: 10.1097/00003246-199704000-00019.


Objectives: Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to investigate whether treatment with epinephrine or norepinephrine increases survival as compared with standard treatment with sodium bicarbonate in experimental amitriptyline poisoning.

Design: Nonrandomized, controlled intervention trial.

Setting: University laboratory.

Subjects: Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 91).

Interventions: Rats subjected to a 60-min infusion of amitriptyline (2 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, sodium bicarbonate, epinephrine plus sodium bicarbonate, norepinephrine plus sodium bicarbonate, or placebo.

Measurements and main results: Inotropic drug treatment was associated with an increased survival rate as compared with treatment with sodium bicarbonate and treatment with placebo. Epinephrine treatment was superior to norepinephrine. Additional treatment with sodium bicarbonate increased survival rate for each inotropic drug. Sodium bicarbonate and inotropic drug treatment independently increased the survival rate (p < .001 for both effects). No interaction between these two treatment effects was observed.

Conclusions: Both epinephrine and norepinephrine increased the survival rate in tricyclic antidepressant poisoning in rats. Sodium bicarbonate increased the survival rate independent of inotropic drug treatment. Furthermore, epinephrine was superior to norepinephrine when used both with and without sodium bicarbonate, and the most effective treatment was epinephrine plus sodium bicarbonate.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amitriptyline / toxicity*
  • Animals
  • Antidepressive Agents, Tricyclic / toxicity*
  • Arrhythmias, Cardiac / chemically induced
  • Disease Models, Animal*
  • Drug Combinations
  • Electrolytes / blood
  • Epinephrine / pharmacology
  • Epinephrine / therapeutic use*
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Norepinephrine / pharmacology
  • Norepinephrine / therapeutic use
  • Poisoning / blood
  • Poisoning / mortality
  • Poisoning / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Bicarbonate / pharmacology
  • Sodium Bicarbonate / therapeutic use*
  • Survival Rate
  • Sympathomimetics / pharmacology
  • Sympathomimetics / therapeutic use*


  • Antidepressive Agents, Tricyclic
  • Drug Combinations
  • Electrolytes
  • Sympathomimetics
  • Amitriptyline
  • Sodium Bicarbonate
  • Norepinephrine
  • Epinephrine