ecg manifestations of drug overdose
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ECG manifestations of drug overdose
Vera Ruchti1st of May 2014
Sir Charles Gairdner Hospital Emergency Department
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Approach to ECG in Toxicology• rate and rhythm
• PR interval, heart block
• Determine QRS duration in lead II
•Check for right axis deviation of the terminal QRS
•Determine QT interval
•evidence of increased cardiac ectopy or automaticity
•evidence of myocardial ischaemia.
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Normal ECG Parameters
• Rate 60-100/minute• PR: < 200 ms, > 120 ms (3-5 small squares)• QRS duration: < 100 ms (2.5 small squares)• QTc interval: < 450 ms• QTc = QT/ RR1/2
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Rate
• Sinustachycardia– Anticholinergic:
blockade of M2 muscarinic receptors
– Sympathicomimetica– Serotonin syndrome
• Sinusbradycardia– Calciumchannel
blockade– Beta-adrenergic
blockade– Sodium channel blockers– Cholinergic syndrome
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PR interval heart block
• From beginning of p-wave till beginning of QRS complex
• PR prolongation is an early sign of Beta- or Ca-channel blockade
• Significes AV nodal conduction delay
• Drugs: – Beta blockers, Digoxin, Calcium Channel blockers
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Beta blocker overdose
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Sodium channel blockade
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ECG manifestations of Na channel blockade
• Bradycardia (ominous sign in TCA toxicity)
• QRS duration > 100 ms measured in lead II– > 100 ms: seizure– > 160 ms: ventricular dysrhythmia
• Right axis deviation of the terminal QRS
– Terminal R wave > 3 mm in aVR
– R/S ratio > 0.7 in aVR
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Drugs that cause fast sodium channel blockade
• Trycyclic antidepressants– Amitriptyline– Desipramine– Dothiepine– Imipramine– nortriptyline
• Class 1A antidysrhythmic agents– Procainamide– Quinidine– disopyramide
• Class 1c antidysrhythmic – Flecainide– encainide
• Local anaesthetics– Bupivacaine– Cocaine– ropivacaine
• Pheothiazines• Amantadine• Carbamazepine• Chloroquine• Diltiazem• Dephenhydramine• Hydroxychloroquine• Propoxyphene• Propranolol• quinine
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Sodium channel blockade
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Prolonged QT interval• Incidence: unknown• UK survey: 3 % of total noncardiac
prescription drugs have an official warning of QT-prolongation
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How to measure QT-interval• Men: > 440 ms• Women: > 460 ms
• From start of QRS-complex to end of t-wave• Lead II• Correction for heart rate:– Bazett’s square root formula:– QTc = QT/ RR1/2
– Fridericia’s cube root formula:– QTc = QT/RR1/3
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Pathophysiology of drugs induced QT prolongation
• Prolongation of action potential: prolongation of repolarisation.
• Two proposed mechanisms:
– Blockade of Ikr (rapid delayed rectifier channels)
– Abnormal protein trafficking required for the Ikr to the cell membrane
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Why does QT prolongation cause TdP?
• Prolonged repolarisation may result in early after depolarisation
• M-cells (midventricular myocardcells) show a more pronounced AP prolongation in response to Ikr blockade.
• This causes a dispersion of repolisation (heterogenous recovery of excitability)
• Re-entry, may provoke TdP
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• No linear relationship between drug dose and QT-prolongation
• No relationship between the degree of QT-prolongation and the likelihood of development of TdP
• So maybe it is better to measure QT interval dispersion: maximum-minimum QT-interval, as it is an indirect measure of spatial heterogeneity of repolarisation
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All drugs are equal, but some drugs are more equal than others
• Example of amiodarone and sotalol– Same potent effect on QT prolongation
– Amiodarone: • No higher risk with higher dose• incidence of QT prolongation is 0-0.7%, all in patients with
other co-existing risk factors
– Sotalol• 0.3 % incidence 80 mg• 3.8 % incidence > 680 mg• >3.8 mg in patients with risk factors.
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Risk factors for QT prolongation/ TdP
• female gender
• Advanced age (> 60 yrs)
• Genetic predisposition– Congenital long QT syndrome– Family history of sudden death– Previous history of drug induced QT-prolongation
• Structural heart disease/ LV dysfunction
• Hypokalemia/severe hypomagnesaemia– Hyper/hypothyroidism, diabetes
• Absolute or relative bradycardia ( recent conversion from AF)
• Starvation/obesity/ metabolic disorders
• Use of sympathicomimetics
• High drug concentrations:– Rapid iv-administration– High dosages– overdose
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QT interval nomogram
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Medications that can cause TdP• Antiarrhythmics• Calcium channel blockers• Antimicrobials, including antimalarials,
antifungals• Antidepressants• Antispsychotics• Antiemetics• Antihistamines• immunosuppressants
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• Antiarrhythmic drugs • Type 1A (TdP reported in all) • Quinidine (TdP reported) • Procainamide (TdP reported) • Disopyramide (TdP reported) • Ajmaline (TdP reported) • Type 1C (increase QT by prolonging QRS interval) • Encainide • Flecainide • Type 3 (TdP reported in all) • Amiodarone • Sotalol • d-Sotalol • Bretylium • Ibutilide • Dofetilide • Amakalant • Semantilide
• Calcium channel blockers
• Psychiatric drugs Thioridazine (TdP reported) • Chlorpromazine (TdP reported) • Haloperidol (TdP reported) • Droperidol (TdP reported) • Amitriptyline • Nortriptyline • Imipramine (TdP reported) • Desipramine (TdP reported) • Clomipramine • Maprotiline (TdP reported) • Doxepin (TdP reported) • Lithium (TdP reported) • Chloral hydrate • Sertindole (TdP reported, withdrawn in the UK) • Pimozide (TdP reported) • Ziprasidone
• Antihistamines Terfenadine (TdP reported, withdrawn in the USA)
• Astemizole (TdP reported) • Diphenhydramine (TdP reported) • Hydroxyzine • Ebastine • Loratadine • Mizolastine
• Antimicrobial and antimalarial drugs • Erythromycin (TdP reported) • Clarithromycin (TdP reported) • Ketoconazole • Pentamidine (TdP reported) • Quinine • Chloroquine (TdP reported) • Halofantrine (TdP reported) • Amantadine (TdP reported) • Sparfloxacin • Grepafloxacin (TdP reported, withdrawn in the UK and USA) • Pentavalent antimonial meglumine
• Serotonin agonists/antagonists • Ketanserin (TdP reported) • Cisapride (TdP reported, withdrawn in the UK and USA)
• Immunosuppressant Tacrolimus (TdP reported)
• Antidiuretic hormone Vasopressin (TdP reported)
• Other agents Adenosine • Organophosphates • Probucol (TdP reported) • Papaverine (TdP reported) • Cocaine
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QT prolongation
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Increased cardiac ectopics, increased automaticity
• Ectopics: – Digoxin, alcohol, cocaine, caffeine, TCA’s– Autonomic stimulation
• Increased automaticity– Accelerated juncional rhythm• Rate 60-120/min• Retrograde p-waves: inverted in inferior leads, upright
in aVR and V1• QRS less than 120 ms
– Digoxin toxicity
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Accelerated Junctional rhythm
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Na/K ATPase pump blockade• Increased automaticity • Decreased AV conduction
• Dysrhythmia: supraventricular tachycardia with slow ventricular response
• Frequent PVCs (the most common abnormality), including ventricular bigeminy and trigeminy
• Sinus bradycardia or slow AF
• Any type of AV block (1st degree, 2nd degree & 3rd degree)
• Regularised AF = AF with complete heart block and a junctional or ventricular escape rhythm
• Ventricular tachycardia, including polymorphic and bidirectional VT
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Digoxin toxicity
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Cardiac ischemia
• Tachycardia/ hypotension in pre excisting coronary artery disease
• Cocaine.• (remember that cocaine can do all: ischemia,
Na channel blockade and QT prolongation)
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• Questions?
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My question
• How does Magnesium treat Torsade?
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literature• Medscape: Keeping the Rhythm: hERG and
Beyond in Cardiovascular Safety Pharmacology• Life in the fast lane• Toxicology handbook• Yee Guan Yap & A. John Camm. “Drug induced
QT prolongation and Torsade de pointes. Heart; Nov:2003:89 (11) 1363-1372
• C. Holstege, D Eldridge, A Rowede. “ECG manifestations: the poisoned patient”. Emerg. Med. Clin. N. Ame 24(2006) 159-177