Elsevier

Annals of Emergency Medicine

Volume 32, Issue 3, September 1998, Pages 329-333
Annals of Emergency Medicine

Experimental Tricyclic Antidepressant Toxicity: A Randomized, Controlled Comparison of Hypertonic Saline Solution, Sodium Bicarbonate, and Hyperventilation,☆☆,

https://doi.org/10.1016/S0196-0644(98)70009-5Get rights and content

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 NaHCO 3 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 NaHCO 3 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 NaHCO 3 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.]

Section snippets

INTRODUCTION

Tricyclic antidepressants (TCAs) continue to be a leading cause of death and major morbidity by drug ingestion. Despite the proliferation of newer antidepressant agents with benign toxicity profiles, the incidence of TCA ingestions is still high. 1 The most recent report from the Medical Letter recommends TCAs as first-line therapy for severe depression. 2 Cardiovascular toxicity, manifested by hypotension, ventricular dysrhythmias, and high-grade heart block, is the predominant cause of death.

MATERIALS AND METHODS

This experiment was approved by the University of Pittsburgh Animal Care and Use Committee. Twenty-four mixed-breed domestic swine of either sex weighing 20 to 25 kg were used. All animals were prepared and instrumented in the same fashion and randomly assigned to 4 groups according to a computerized randomization schedule (Epistat, version 3.5, 1989, Richardson, TX). Animals were sedated with 10 mg/kg of ketamine and 1 mg/kg of xylazine intramuscularly. After cannulation of an ear vein,

RESULTS

There were no statistically significant differences between groups in measured variables at baseline ( P >.1) (Table 1) . There were no statistically significant differences between groups in mean NT levels at toxicity (Table 2) .

The mean pH in the NaHCO 3 group at 10 and 15 minutes after treatment was 7.54±0.03 and 7.56±.02, respectively. The mean pH in the HV group at 10 and 15 minutes after treatment was 7.56±.04 and 7.59±.03, respectively. The control and HTS groups remained physiologic

DISCUSSION

The results of this experiment show that HTS is highly efficacious in reversing severe TCA cardiotoxicity, even more so than sodium bicarbonate. Hyperventilation alone appears to have little effect. This is, to our knowledge, the first large-animal model of severe TCA toxicity that has directly compared these modes of therapy. Arterial pH was strictly controlled and supportive therapy (including antiarrhythmics and vasopressors) was not used in an effort to isolate the effects of each therapy.

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Cited by (0)

From the Department of Emergency Medicine, University of Pittsburgh School of Medicine, * and the Center for Emergency Medicine of Western Pennsylvania, Pittsburgh, PA, the Division of Emergency Medicine, Thomas Jefferson University, § Philadelphia, PA, and the Department of Emergency Medicine, II University of Rochester, Rochester, NY. II

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Reprint no. 47/1/91992

Address for reprints: James L McCabe, MD Department of Emergency Medicine Kennedy Health System 435 Hurffville-Cross Keys Road Turnersville, NJ 08012 609-582-2816 Fax 609-727-4965

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