Study objective: We sought to compare the effects of hypertonic sodium chloride solution (HTS), sodium bicarbonate solution, and hyperventilation (HV) on severe tricyclic antidepressant (TCA) toxicity in a swine model. Methods: Twenty-four mixed-breed, domestic swine of either sex were given an intravenous infusion of nortriptyline (NT) until development of both a QRS duration longer than 120 ms and a systolic blood pressure (SBP) less than or equal to 50 mm Hg. Animals were randomly assigned to 1 of 4 groups. On reaching toxicity, the control group received 10 mL/kg of 5% dextrose in water (D5W); the HTS group received 10 mL/kg of 7.5% NaCl solution (15 mEq Na ⁺ /kg); the NaHCO₃ group received 3 mEq/kg of 8.4% sodium bicarbonate solution followed by enough D5W solution to equal 10 mL/kg of total volume; and the HV group was mechanically hyperventilated to maintain arterial pH between 7.50 and 7.60 and given 10 mL/kg of D5W. Results: The mean SBP 10 minutes after treatment was 54±18 mm Hg in the control group, 134±21 mm Hg in the HTS group, 85±19 mm Hg in the NaHCO₃ group, and 60±12 mm Hg in the HV group ( P <.05). Mean QRS duration 10 minutes after treatment was 144±38 ms in the control group, 80±14 ms in the HTS group, 105±38 ms in the NaHCO₃ group, and 125±46 ms in the HV group ( P <.05). Conclusion: In this model of TCA, toxicity HTS was more effective than sodium bicarbonate. Hyperventilation had little effect. Sodium loading may be the most important factor in reversing TCA toxicity. [McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J: Experimental tricyclic antidepressant toxicity: A randomzed, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med September 1998;32:329-333.]