ECG criteria
- A QRS duration in lead II ≥ 100 ms with a corresponding clinical presentation of suspected intoxication, especially with TCAs and other Na-channel blockers (carbamazepine, cocaine, quinidine-like antiarrhythmics), increases the risk of seizures and ventricular arrhythmias; with QRS >100 ms combined with hypotension, seizures, or ventricular arrhythmia, immediately consider a sodium bicarbonate bolus according to the toxicology protocol, monitoring QRS, pH, Na+, and K+; differential diagnosis of other causes of QRS widening (hyperkalemia, bundle branch block, ischemia) is performed in parallel
- An R wave in aVR ≥ 3 mm and/or an R/S ratio in aVR ≥ 0.7 are suggestive signs of TCA poisoning with limited sensitivity and specificity; interpret alongside QRS duration, clinical presentation, and history; their absence does not rule out intoxication
- A terminal R wave in aVR lasting > 40 ms reflects delayed terminal ventricular depolarization; assess the increase in the terminal positive QRS component in aVR, its amplitude, the R/S ratio, and duration; this is an auxiliary and non-specific criterion
- A Bazett's QTc interval greater than 450 ms in men and 460 ms in women is considered prolonged; a QTc ≥ 500 ms or an increase of more than 60 ms from baseline is associated with a substantially higher risk of torsades de pointes, particularly with potassium channel blockade (quetiapine, methadone, class IA/III antiarrhythmics); in the presence of a wide QRS, QTc should be interpreted with caution—evaluate JT/JTc or use QRS-corrected formulas; the risk of torsades is determined primarily by prolonged repolarization rather than QRS widening; Bazett's formula is unreliable in tachy- and bradycardia
- Verapamil and diltiazem can cause sinus bradycardia and AV block up to high degree; dihydropyridine calcium channel blockers more frequently cause vasoplegia and hypotension without marked bradycardia; beta-blockers cause bradycardia and AV conduction disturbances, and some agents additionally widen the QRS or prolong the QT
- Hyperkalemia can mimic or potentiate toxic QRS widening; tall peaked T waves, a flattened or absent P wave, progressive QRS widening, and a sine-wave pattern may occur—confirm the diagnosis with urgent potassium testing
- A Brugada type 1-like pattern—coved J-point/ST elevation of at least 2 mm in V1 or V2, including high leads in the 2nd–4th intercostal spaces, followed by a negative T wave; the criterion is met in one or both right precordial leads, not necessarily simultaneously in V1 and V2—described in TCA and other Na-channel blocker poisonings
- Torsades de pointes polymorphic VT against the background of a prolonged QTc—the endpoint of severe intoxication with cardiotoxic drugs
What it looks like on ECG
Toxicological ECG has no single uniform pattern—the presentation depends on the mechanism of action of the substance on ion channels and other cardiomyocyte structures.
| Mechanism | Typical Drugs | ECG Findings |
|---|---|---|
| Na-Channel Blockade | TCAs, carbamazepine, cocaine, quinidine, flecainide | Wide QRS (≥ 100 ms), increased terminal positive component in aVR (R ≥ 3 mm or R/S ≥ 0.7), terminal R in aVR > 40 ms, occasionally Brugada pattern in V1–V2 |
| K-Channel Blockade | quetiapine, sotalol, methadone, class IA/III antiarrhythmics | QTc prolongation, biphasic/flattened T wave, prominent U wave, risk of torsades de pointes |
| Ca-Channel Blockade (Sinus and AV Node) | verapamil, diltiazem | Sinus bradycardia, slowed AV conduction up to high-degree AV block, usually with negative inotropy and hypotension |
| β-Adrenergic Receptor Blockade | propranolol, atenolol, sotalol (dual effect) | Bradycardia, AV block, with sotalol — additional QT prolongation |
| Na/K-ATPase Inhibition | cardiac glycosides (digoxin) | Scoop-shaped ST depression, increased automaticity/triggered activity (ventricular premature beats, bigeminy, VT) alongside vagal slowing of sinus and AV conduction, various tachy- and bradyarrhythmias |
In lead II with a wide QRS, it is important to evaluate morphology and rule out hyperkalemia as a contributing factor—it exacerbates toxic complex widening.
Mechanism
Cardiotoxicity is driven by various pathways, and ion channel blockade is only one of the primary mechanisms. Blockade of fast sodium channels (local anesthetic effect of TCAs, carbamazepine, class IA/IC antiarrhythmics) slows phase 0 depolarization of the action potential, resulting in QRS widening. Slowed conduction alters the terminal depolarization vector, shifting it superiorly and to the right, which increases the terminal positive QRS component in aVR. Potassium channel (hERG) blockade delays phase 3 repolarization, prolonging the QT interval and creating conditions for triggered activity and torsades de pointes. Calcium channel blockers and beta-blockers suppress sinus node automaticity and AV nodal conduction, where calcium current predominates, leading to bradyarrhythmias up to complete AV block. A distinct mechanism is the inhibition of Na/K-ATPase by digoxin: intracellular Ca2+ increases, promoting enhanced automaticity/triggered activity, while vagal effects slow sinus and especially AV conduction, potentially causing various tachy- and bradyarrhythmias. Other poisons also exert adrenergic and metabolic effects.
Causes
- Tricyclic and tetracyclic antidepressants
- Carbamazepine and other anticonvulsants with membrane-stabilizing effects
- Antipsychotics, particularly quetiapine, thioridazine
- Class IA, IC, III antiarrhythmics (quinidine, flecainide, sotalol)
- Beta-blockers
- Calcium channel blockers, especially verapamil and diltiazem
- Cocaine and local anesthetics in toxic doses
- Chloroquine and hydroxychloroquine
- Diphenhydramine and other antihistamines in high doses
- Methadone and certain opioids
- Cardiac glycosides (a separate category of digoxin toxicity)
Differential diagnosis
- True Brugada syndrome — toxic QRS widening from Na-channel blockade can mimic a Brugada type 1 phenocopy; they cannot be reliably differentiated by ECG alone. A history of drug ingestion, ECG dynamics following substance elimination, and repeat recordings after resolution of toxicity are required
- Hyperkalemia — may coexist and exacerbate toxic QRS widening; check the T wave (peaked), P wave (flattened/absent), patient history of renal function, and confirm potassium levels with laboratory testing
- Organic bundle branch block — toxic QRS widening may present with non-specific or pseudoblock morphology; typical LBBB/RBBB patterns are not mandatory. Differentiation requires comparison with a baseline ECG, clinical assessment, electrolyte panels, and serial changes during treatment
- Congenital long QT syndrome — consider family and syncopal history, repeat ECGs after electrolyte normalization and drug discontinuation, QT dynamics, and specialized/genetic evaluation if needed. Reversibility of QT prolongation supports an acquired etiology but does not prove it; a combination of congenital predisposition and drug-induced QT prolongation is possible
- Polymorphic VT in acute ischemia or structural heart disease — can occur with a normal QT interval and is typically not torsades; torsades is defined by the presence of a prolonged QT and is characteristically pause-dependent
Clinical significance and management
In suspected TCA toxicity with QRS >100 ms, hypotension, seizures, or ventricular arrhythmia, a sodium bicarbonate bolus should be considered immediately according to toxicological protocols, with monitoring of QRS, pH, Na+, and K+; differential diagnosis is carried out in parallel. For other sodium channel blockers, evidence levels and regimens should be specified separately. The R wave in aVR remains an auxiliary sign and should not be the sole basis for therapy. In case of QTc prolongation and the risk of torsades de pointes, discontinue the QT-prolonging drug, administer intravenous magnesium sulfate regardless of baseline Mg levels, correct K+ to the upper limit of normal and Mg2+, and perform defibrillation for hemodynamic instability/pulselessness; for recurrent pause-dependent torsades, temporary pacing or another rate-acceleration strategy under the supervision of an intensivist. In bradyarrhythmia secondary to beta-blockers or calcium channel blockers, management is determined by hemodynamics and the type of poison—ranging from atropine to specific antidote strategies, with the decision made by a toxicologist or intensivist. ECG in toxicology is a dynamic tool: a single tracing does not rule out poisoning, and serial recordings are required during monitoring.
Common interpretation errors
- Evaluating only the QT interval without QRS duration — in severe sodium channel blocker poisoning, QRS is more important for predicting seizures and arrhythmias
- Failing to recognize an increase in the terminal positive QRS component in aVR while focusing solely on standard QRS duration
- Mistaking a toxic Brugada phenocopy for primary syndrome without considering medical history, clinical presentation, and dynamics after eliminating the provoking factor
- Forgetting that bradycardia can be of mixed etiology (calcium channel blocker and beta-blocker in combined poisoning)
- Failing to repeat ECG dynamically — toxic effects may progress as drug absorption continues
1. Which ECG sign is most characteristic of tricyclic antidepressant poisoning?
Fast sodium channel blockade slows terminal ventricular depolarization, resulting in QRS widening and a characteristic increase in the terminal positive QRS component in aVR.
2. Which rhythm disturbance most frequently develops against the background of marked QTc prolongation in drug intoxication?
QTc prolongation due to potassium channel blockade creates conditions for triggered activity and the development of torsades de pointes.
3. What mechanism of toxic action is typical for verapamil poisoning?
Verapamil blocks calcium channels of the sinus and AV nodes, leading to bradycardia and impaired AV conduction.
Frequently asked questions
Why does the terminal positive QRS component increase specifically in aVR during TCA poisoning?
Sodium channel blockade slows terminal ventricular depolarization. The slowed conduction alters the resulting terminal vector, directing it more to the right and superiorly, i.e., toward aVR. Therefore, the terminal positive QRS component in aVR increases; its amplitude, R/S ratio, and terminal R duration are evaluated, but this sign is auxiliary and not pathognomonic.
What QRS duration is considered dangerous in poisoning?
A QRS duration greater than 100 ms in TCA toxicity increases the risk of seizures and ventricular arrhythmias; a QRS greater than 160 ms is specifically associated with a high risk of ventricular arrhythmias. These thresholds are probabilistic rather than absolute and do not replace clinical assessment.
Can a single ECG determine what substance a patient has ingested?
No, the ECG reflects the mechanism of action (blockade of Na+, K+, or Ca2+ channels, effect on Na/K-ATPase, and other pathways) rather than a specific substance. Medical history, clinical presentation, and toxicological analysis are required for accurate identification.
Is QT prolongation dangerous in quetiapine poisoning?
Yes, marked QTc prolongation increases the risk of polymorphic ventricular tachycardia of the torsades de pointes type, especially at a QTc of 500 ms or more or with concomitant hypokalemia and hypomagnesemia, which is why serial ECG monitoring is necessary.
How does the ECG in beta-blocker poisoning differ from that in calcium channel blocker poisoning?
ECG signs overlap significantly. Bradycardia, AV block, negative inotropy, and hypotension are typical for verapamil and diltiazem. Beta-blockers cause bradycardia and AV block with potential hypotension, hypoglycemia, seizures, or QRS widening depending on the drug. These intoxications cannot be reliably distinguished based on a single ECG; diagnosis relies on medical history and clinical syndrome.
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Related terms
More in "Pharmacology and Toxicology"
Sources
- Goldberger A. Clinical Electrocardiography
- Surawicz B., Knilans T. Chou's Electrocardiography in Clinical Practice
- Hampton J. The ECG in Practice
Educational material for medical students and physicians. Does not replace clinical guidelines and physical examination; the ECG must always be interpreted in conjunction with the clinical picture.