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ECG manifestations of drug overdose
- 1. ECG manifestations of drug overdose Vera Ruchti 1st of May 2014 Sir Charles Gairdner Hospital Emergency Department
- 2. 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.
- 3. 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
- 4. Rate • Sinustachycardia – Anticholinergic: blockade of M2 muscarinic receptors – Sympathicomimetica – Serotonin syndrome • Sinusbradycardia – Calciumchannel blockade – Beta-adrenergic blockade – Sodium channel blockers – Cholinergic syndrome
- 5. 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
- 9. 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
- 10. 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
- 13. Prolonged QT interval • Incidence: unknown • UK survey: 3 % of total noncardiac prescription drugs have an official warning of QT-prolongation
- 14. 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
- 15. 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 Ikrto the cell membrane
- 19. 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
- 20. • 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
- 21. 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.
- 22. 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
- 24. Medications that can cause TdP • Antiarrhythmics • Calcium channel blockers • Antimicrobials, including antimalarials, antifungals • Antidepressants • Antispsychotics • Antiemetics • Antihistamines • immunosuppressants
- 25. • 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
- 26. QT prolongation
- 27. 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
- 29. 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
- 32. Digoxin toxicity
- 33. Cardiac ischemia • Tachycardia/ hypotension in pre excisting coronary artery disease • Cocaine. • (remember that cocaine can do all: ischemia, Na channel blockade and QT prolongation)
- 34. • Questions?
- 35. My question • How does Magnesium treat Torsade?
- 36. 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
Editor's Notes
- — The arrhythmogenic risk for drug-induced QT prolongation is accurately predicted by the “QT nomogram” which plots QT versus heart rate
- Sinustachycardia by increasing depolarisation speed Increased conduction velocity of AV node
- — The studies examining QRS duration in tricyclic antidepressant intoxication use manual measurements to measure QRS in limb lead II. -—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.
- Carbamazepine overdose
- Historically measured in lead II as the vectors of repolarisation usually result in a long singel wave instead of a discreet t and u wave Fridericia more accurate in extreme phsyciological heart rates. Bazet’s underestimates QT interval at low HR and overestimates at high rates, but Bazett is more frequently used in the literature, so values used from Bazetts formula
- Abnormal protein trafficking seen with fluoxetine and digoxin: takes a long time so requires a long exposure to the drugs.
- http://quoteko.com/the-action-potential.html
- http://www.medscape.com/viewarticle/722090_2
- Early after depolarisation by activation of L type Ca channel currents or Na-Ca exchanger (3 na in 1 Ca out) Prolonged repolarisation may result in subsequent activation of inward depolarisation current (early after depolarisation), which may promote triggered activity.
- However, Manual measurement of QT interval dispersion is just as inaccurate as manual measurement of QT interval
- If point is above the line than the QT-HR is regarded at risk for development of torsade de pointes
- Increased automaticity duet o increased intracellular calcium