Tricyclic antidepressant overdose is generally neglected by the college examiners. Question 3 from the first paper of 2022 and Question 28.2 from the second paper of 2009 was the one and only time TCA overdose has ever made it into the SAQs in any major way. Even in these cases, the college asked not about the management of TCA overdose but rather about the specific role of bicarbonate in the management thereof. Similarly, Question 7 from the second paper of 2017 asked about the specific antidote to TCA overdose, and the mechanism of its action. Consequently, this chapter dedicates an undue attention to this specific issue. Otherwise, TCA overdose is well covered in such resources as the LITFL toxicology conundrum. Generally speaking, one may safely limit their exam reading to the LITFL page. If one has unlimited time resources, one may also wish to explore this 2001 BMJ article by Kerr et al.
- TCA toxicity has four main toxicological features:
- Sodium channel blockade and QRS prolongation
- Alpha-1 receptor blockade and hypotension
- Anticholinergic toxidrome (tachycardia, delirium etc)
- Antihistamine-related sedation
- Management consists of:
- Alkalinising the body fluids to increase drug-protein binding
- Giving sodium to antagonise sodium channel blockade
- Enhancing elimination with activated charcoal
- Basic ICU supportive care (intubation, vasopressors, etc)
Central nervous system features
The indication for the use of bicarbonate in tricyclic overdose is the widening of the QRS interval, rather than the metabolic acidosis (which may or may not accompany TCA poisoning). Exactly how this works is a topic of some debate. The following list mentions some of the theoretical mechanisms. Jerome Hofmann seems to be the guru of this topic; practically half the articles on it are co-authored by him. Notably, his 1993 paper is particularly good for answering Question 28.2 from the second paper of 2009.
Beyond the use of bicarbonate itself, the desired alkaline pH can be achieved by hyperventilation. This is very old-school (eg. Kingston, 1979). The aim is a pH of 7.50-7.55, and in order to achieve this one would generally need a PaCO2 of 25-30. Apart from the undesirable cerebral vasoconstriction and the whole ionised calcium circus, one would want to be mindful of the potential synergistic effects between hyperventilation and IV bicarbonate. Wrenn et al (1992) reported on two patients with TCA overdose rendered severely alkalaemic by their combine bicarbonate-hyperventilation strategy. One of them died, which was probably nothing to do with their pH of 7.61 - but it can't have helped. These days it is not widely recommended; for instance, the UpToDate page doesn't mention it at all. Intermittently, when ringing the local Poisons Information Centre hotline, one still ends up speaking with somebody who believes in this therapy, in which case one is probably safe to follow their advice provided frequent ABG analysis takes place.
Hoffman, J. R., and C. R. McElroy. "Bicarbonate therapy for dysrhythmia and hypotension in tricyclic antidepressant overdose." Western Journal of Medicine134.1 (1981): 60.
Kerr, G. W., A. C. McGuffie, and S. Wilkie. "Tricyclic antidepressant overdose: a review." Emergency Medicine Journal 18.4 (2001): 236-241.
Brown, T. C., et al. "The use of sodium bicarbonate in the treatment of tricyclic antidepressant-induced arrhythmias." Anaesthesia and intensive care 1.3 (1973): 203-210.
McCabe, James L., et al. "Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation." Annals of emergency medicine 32.3 (1998): 329-333.
Bou-Abboud, Elias, and Stanley Nattel. "Molecular mechanisms of the reversal of imipramine-induced sodium channel blockade by alkalinization in human cardiac myocytes." Cardiovascular research 38.2 (1998): 395-404.
Hoffman, Jerome R., et al. "Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose." The American journal of emergency medicine 11.4 (1993): 336-341.
Dargan, Paul I., Mark G. Colbridge, and Alison L. Jones. "The management of tricyclic antidepressant poisoning." Toxicological reviews 24.3 (2005): 187-194.
Kingston, Michael E. "Hyperventilation in tricyclic antidepressant poisoning." Critical care medicine 7.12 (1979): 550-551.
Wrenn, Keith, Brian A. Smith, and Corey M. Slovis. "Profound alkalemia during treatment of tricyclic antidepressant overdose: a potential hazard of combined hyperventilation and intravenous bicarbonate." The American journal of emergency medicine 10.6 (1992): 553-555.