Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation

Abstract

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.