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
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
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
16.
17.
18.
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
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
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)
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
Notas del editor
— 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
