ECG in Toxicology

OVERVIEW

The ECG is important in the assessment and management of poisoned patients for:

• screening
• diagnosis
• prognosis
• monitoring progression to guide management and disposition

USE AS A SCREENING TEST

A 12-lead ECG should be performed in all deliberate self-poisoning patients

•  non-invasive
• inexpensive
• readily available
• identifies occult but potentially lethal cardiac conduction abnormalities

MECHANISMS OF CARDIOTOXICTY AND THEIR MANIFESTATIONS

Fast sodium channel blockade leads to slowed phase 0 of the cardiac action potential

• Widened QRS
• Right axis deviation of the terminal QRS
• Bradycardia (although tachycardia secondary to other factors is more commonly observed)
• Ventricular tachycardia and ventricular fibrillation

Blockade of potassium efflux during cardiac repolarisation (phase 3)

• Prolongation of the QT interval
• Torsade de pointes

Na+-K+-ATPase pump blockade by cardiac glycosides

• Increased automaticity
• Decreased AV node conduction (1st to 3rd degree heart block)

Calcium channel blockade

• Sinus bradycardia
• Decreased AV node conduction (1st to 3rd degree heart block)
• Intraventricular conduction defects

Beta-adrenergic receptor blockade

• Sinus bradycardia
• Decreased AV node conduction (1st to 3rd degree heart block)

Myocardial ischaemia

• ST segment depression or elevation
• Conduction abnormalities

Hyperkalaemia

• Peaked T waves
• Conduction abnormalities

Hypocalcaemia (e.g. HF)

• QT prolongation

Tricyclic antidepressants

A QRS duration >100 ms suggests blockade of cardiac fast sodium channels. In combination with right axis deviation of the terminal QRS, it is virtually pathognomonic (see Figure 2.20.3). Most studies examine ECG changes in TCA intoxication and are small or retrospective. However, the following appear to be associated with major toxicity:

• QRS >100 ms (2.5 small squares) is associated with seizures
• QRS >160 ms (4 small squares) is associated with ventricular dysrhythmias
• Right axis deviation of the terminal QRS as defined by
  • a) Terminal R wave >3 mm in AVR
  • b) R/S ratio >0.7 in AVR.

APPROACH TO THE ECG IN TOXICOLOGY

• Rate and Rhythm
• PR interval – is there any degree of heart block?
• Determine QRS duration in lead II
  • The studies examining QRS duration in tricyclic antidepressant intoxication use manual measurements to measure QRS in limb lead II.
• Check for Right Axis Deviation of the QRS
  • A large terminal R wave in AVR or increased R/S ratio indicates slow rightward conduction and is characteristic of fast sodium channel blockade.
  • If not pathological, it remains static in appearance and severity throughout the course of the poisoning. Comparison with pre-poisoning ECGs is useful.
• Determine QT interval
  • Prolonged QT interval predisposes to the development of torsade de pointe, a polymorphic ventricular tachycardia.
  • Torsade des pointes is more likely to occur where there is co-existing bradycardia.
  • The arrhythmogenic risk for drug-induced QT prolongation is accurately predicted by the “QT nomogram” which plots QT versus heart rate
• Evidence of increased cardiac ectopy or automaticity
• Evidence of myocardial ischaemia.

SODIUM CHANNEL BLOCKERS

• Tricyclic antidepressants
  • Amitriptyline, Desipramine, Dothiepin, Imipramine, Nortriptyline
• Class 1A antidysrhythmic agents
  • Disopyramide, Procainamide, Quinidine
• Class 1C antidysrhythmic agents
  • Encainide, Flecainide
• Local anaesthetics
  • Bupivacaine, Cocaine, Ropivacaine
• Phenothiazines
  • Thioridazine
• Antimalarials
  • Chloroquine, Hydroxychloroquine,
  • Quinine
• Amantadine
• Diltiazem
• Diphenhydramine
• Carbamazepine
• Propoxyphene/dextropropoxyphene
• Propranolol

POTASSIUM EFFLUX BLOCKERS

• Antipsychotic agents
  • Amisulpride, Chlorpromazine, Droperidol, Haloperidol, Quetiapine, Olanzapine, Thioridazine
• Class 1A antidysrhythmic agents
• Quinidine
• Disopyramide
• Procainamide
• Class 1C antidysrhythmic agents
  • Encainide, Flecainide
• Class III antidysrhythmic agents
  • Sotalol, Amiodarone
• Tricyclic antidepressants
  • Amitriptyline, Desipramine, Dothiepin, Imipramine, Nortriptyline
• Other antidepressants
  • Citalopram, Escitalopram, Bupropion, Moclobemide
• Antihistamines
  • Diphenhydramine, Astemizole, Loratadine, Terfenadine
• Antimalarials
  • Chloroquine, Hydroxychloroquine, Quinine
• Amantadine
• Macrolides
  • Erythromycin

References and Links

LITFL

• ECG Library — ECG A to Z by diagnosis
• ECG Library – Drugs causing prolonged QT

Journal articles

• Boehnert MT, Lovejoy FH. Value of the QRS duration verus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. New England Journal of Medicine 1985; 313:474-479.
• Chan A, Isbister GK, Kirkpatrick CMJ et al. Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram. Quarterly Journal of Medicine 2007:100:609-615
• Holstege CP, Eldridge DL, Rowden AK. ECG manifestations: the poisoned patient. Emergency Medicine Clinics of North America 2006; 159-177.
• Liebelt EL, Francis D, Woolf AD. ECG lead AVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Annals of Emergency Medicine 1995; 26:195-201
• Niemann JT, Bessen HA, Rothstein RJ et al. Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. American Journal of Cardiology 1986; 57:1154-1159.
• Wolfe TR, Caravati EM, Rollins DE. Terminal 40-ms frontal plane QRS axis as a marker for tricyclic antidepressant overdose. Annals of Emergency Medicine 1989; 18:348-351
• Yates C, Manini AF. Utility of the electrocardiogram in drug overdose and poisoning: theoretical considerations and clinical implications. Curr Cardiol Rev. 2012 May;8(2):137-51

Advanced Reading

Online

• Wiesbauer F, Kühn P. ECG Mastery: Yellow Belt online course. Understand ECG basics. Medmastery
• Wiesbauer F, Kühn P. ECG Mastery: Blue Belt online course: Become an ECG expert. Medmastery
• Kühn P, Houghton A. ECG Mastery: Black Belt Workshop. Advanced ECG interpretation. Medmastery
• Rawshani A. Clinical ECG Interpretation ECG Waves
• Smith SW. Dr Smith’s ECG blog.
• Wiesbauer F. Little Black Book of ECG Secrets. Medmastery PDF

Textbooks

• Zimmerman FH. ECG Core Curriculum. 2023
• Mattu A, Berberian J, Brady WJ. Emergency ECGs: Case-Based Review and Interpretations, 2022
• Straus DG, Schocken DD. Marriott’s Practical Electrocardiography 13e, 2021
• Brady WJ, Lipinski MJ et al. Electrocardiogram in Clinical Medicine. 1e, 2020
• Mattu A, Tabas JA, Brady WJ. Electrocardiography in Emergency, Acute, and Critical Care. 2e, 2019
• Hampton J, Adlam D. The ECG Made Practical 7e, 2019
• Kühn P, Lang C, Wiesbauer F. ECG Mastery: The Simplest Way to Learn the ECG. 2015
• Grauer K. ECG Pocket Brain (Expanded) 6e, 2014
• Surawicz B, Knilans T. Chou’s Electrocardiography in Clinical Practice: Adult and Pediatric 6e, 2008
• Chan TC. ECG in Emergency Medicine and Acute Care 1e, 2004

LITFL Further Reading

• ECG Library Basics – Waves, Intervals, Segments and Clinical Interpretation
• ECG A to Z by diagnosis – ECG interpretation in clinical context
• ECG Exigency and Cardiovascular Curveball – ECG Clinical Cases
• 100 ECG Quiz – Self-assessment tool for examination practice
• ECG Reference SITES and BOOKS – the best of the rest