Tox in The Land: Toxic Ticker - Cardiac Involvement of Common Toxidromes

Overview

  • Quick review of the cardiac action potential

  • Cardiac medication toxicity

  • Non-cardiac medication toxicity

  • ECG toxidromes: guessing an agent based on conduction changes

Important Ions

Any perturbation of ion flow, whether through a direct effect of the drug or through indirect mechanisms (e.g. acidosis, etc), can cause conduction abnormalities

 
 

Beta Blockers

Mechanism of Toxicity

  • Any BB: decrease conduction velocity through AV node

  • May exhibit Na+ and/or K+ blocking effects (see below)

  • Sotalol: more K+ channel blockade

  • Propranolol: more Na+ channel blockade (acts TCA-esque)

EKG Changes

  • Decreased conduction velocity à bradycardia, 1st/2nd/3rd degree AV block

  • Sotalol: Prolonged QT —> Torsades

  • Propranolol: Widened QRS à ventricular arrhythmias

Management

  • Hypotension d/t brady: atropine, pressor support

  • Glucagon increases Ca2+ influx —> increases chronotropy and inotropy

  • QT prolongation: Mg (if c/f TdP)

  • QRS widening: sodium bicarb (if VT)

 

Cardiac Meds: Calcium channel blockers (NDHPs)

Mechanism of Toxicity

  • Main effects on the SA and AV node

  • Because calcium is a major driver of the action potential at these sites, CCBs decrease chronotropy and increase refraction at the AV node

ECG Changes

  • Decreased conduction velocity —> bradycardia, 1st/2nd/3rd degree AV block

  • Can also have some QT prolongation

Management

  • Like management of severe BB toxicity, focus is on maintaining CO and SVR

  • Like BBs, can also use hyperinsulinemic euglycemia to combat many downstream effects of CCB toxicity



Cardiac Meds: Digoxin and other cardiac glycosides

 

Mechanism of Toxicity

  • Inhibition of Na/K exchanger (phase 4) —> increased Ca2+ influx —> increased automaticity

  • Increases vagal tone to suppress SA-to-AV conduction

ECG Changes

  • Frequent PVCs (including ventricular bigeminy and trigeminy)

  • SVT (2/2 increased automaticity) + slow ventricular response (2/2 decreased AV conduction)

Management

  • Digibind/Digifab for life-threatening arrhythmias

  • If Fab not available, can use antiarrhythmics like atropine/lidocaine

 
 

Non-Cardiac Meds: Tricyclic antidepressants

Mechanism of Toxicity

  • Inhibition of Na+ channels à prolongs absolute refractory period

  • Inhibition of K+ channels à QT prolongation

  • Anticholinergic effects: reflex tachycardia (M3 blockade, see later)

ECG Changes

  • Na+ blockade: increased QRS duration

  • Right side of conduction system more susceptible —> R axis deviation with deep, slurred S wave in lead I and aVL

  • K+ blockade: QTc prolongation

  • M3 blockade: tachycardia and tachyarrhythmia

Management

  • Sodium bicarbonate is the mainstay therapy for life-threatening arrhythmias

Non-Cardiac Meds: Antipsychotics (Haloperidol, quetiapine, chlorpromazine)

Mechanism of Toxicity

  • Inhibition of inward K+ rectifier channels —> prolonged cardiac repolarization

  • Some Na+ inhibition but less commonly causes issues

  • Note: 1st and 2nd gen can all cause increased QTc to varying degrees

ECG Changes

  • K+ blockade: QTc prolongation —> TdP

  • Na+ blockade: rare QRS widening

Management

  • Magnesium sulfate, especially if polymorphic VT begins

  • Can also use overdrive pacing or isoproterenol

  • Of highest import in preventing TdP: correct electrolytes! (especially K and Mg)





Non-Cardiac Meds: Sedating antihistamines and other anticholinergics

 

Mechanism of Toxicity

  • At large doses: Na+ and K+ channel blockade

  • Antimuscarinic effects: increased chronotropy

  • Remember that these agents are often mixed with others (e.g. alpha-adrenergic agonists) and, thus, care needs to be taken to consider mechanisms from polypharmacy as well

ECG Changes

  • K+ blockade: QTc prolongation—> TdP

  • Na+ blockade: QRS widening

Management

  • QRS widening and ventricular arrhythmia: sodium bicarbonate

  • TdP: correct hypoxia, hypokalemia, hypomagnesemia, hypocalcemia

  • Use isoproterenol or overdrive pacing if severe



Non-Cardiac Meds: Antidepressants (SSRIs, buproprion)

Mechanism of Toxicity

  • Bupropion: blockade of K+ current, Na+ blockade

    • Note: Na+ blockade theorized to be due to gap-junction blockade and not fast Na+ channels and, thus, does not respond to sodium bicarb for wide complex arrhythmias

  • Citalopram and escitalopram cause dose-dependent QT prolongation

ECG Changes

  • Bupropion: wide complex, ventricular arrhythmias, QT prolongation and risk for TdP

  • Citalopram/escitalopram: QT prolongation and risk for TdP

Management

  • See note for bupropion

  • Can use sodium bicarb for wide complex tachyarrhythmias for due to the other agents

 

ECG Toxidromes

 
 
 

*Note the extensive overlap between Na+ channel blocking and K+ channel blocking agents! While this presentation goes over just a few of the ECG effects in isolated channel blockade, there will often be a combination of effects and, thus, a difficult to determine ECG. Ultimately, the clinical toxidrome and history will be much more reliable than ECG alone, but ECGs can be used to bolster confidence in the underlying pathophysiology or the identity of an unknown agent!

POST BY: DAVID SWEET, MS4

FACULTY EDITING BY: DR. LAUREN PORTER

References

Nickson C (Feb 5, 2021). EKG in Toxicology. LITFL. Available from: https://litfl.com/ecg-in-toxicology/

Alberter AA, Chambers AJ, Wills BK. Bupropion Toxicity. [Updated 2022 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580478/

Barrueto FB. Beta blocker poisoning. In: UpToDate. Stolbach A, Grayzel J (Eds). Available from: https://www.uptodate.com/contents/beta-blocker-poisoning

Barrueto FB. Calcium channel blocker poisoning. In: UpToDate. Stolbach A, Grayzel J (Eds). Available from: https://www.uptodate.com/contents/calcium-channel-blocker-poisoning?search=calcium%20channel%20blocker%20overdose&source=search_result&selectedTitle=1~26&usage_type=default&display_rank=1

Chakraborty RK, Hamilton RJ. Calcium Channel Blocker Toxicity. [Updated 2023 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. https://www.ncbi.nlm.nih.gov/books/NBK537147/

Cummings ED, Swoboda HD. Digoxin Toxicity. [Updated 2022 Jul 4]. In: StatPearls Available from: https://www.ncbi.nlm.nih.gov/books/NBK470568/

Khalid MM, Galuska MA, Hamilton RJ. Beta-Blocker Toxicity. [Updated 2023 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448097/

Salhanick SD. Tricyclic antidepressant poisoning. In: UpToDate. Hendrickson RG, Ganetsky M (Eds.) Available from: https://www.uptodate.com/contents/tricyclic-antidepressant-poisoning?search=tca%20overdose&sectionRank=2&usage_type=default&anchor=H5&source=machineLearning&selectedTitle=1~62&display_rank=1#H15

Yates and Manini. (2012) Utility of the Electrocardiogram in Drug Overdose and Poisoning: Theoretical Considerations and Clinical Implications. Curr Cardiol Rev. 8(2):137-151

ToxLauren McCaffertytox, toxicology, cardiotoxicity