UTHSCSA Pediatric Resident Curriculum for the PICU
Antiarrhythmic
Therapy
Antiarrhythmic Therapy
Empiric
Pathophysiologic
Arrhythmia Diagnosis
Arrhythmia Diagnosis
Known or suspected
mechanisms
BLACK BOX
Critical components
Vulnerable parameters
Targeted subcellular units
Interventions
Clinical Outcomes
Interventions
Clinical Outcomes
Antiarrhythmic Therapy
Pathophysiologic
Arrhythmia Diagnosis
Known or suspected
mechanisms
Critical components
Vulnerable parameters
Targeted subcellular units
Interventions
Clinical Outcomes
AV node reentrant tachycardia
AV node reentry
Anatomical fast/slow
pathway
AV node (slow conduction)
AV nodal action potential
L-type Ca++ channel
Ca++ channel blocker
-blocker
Sinus rhythm
Vaughn-Williams
Classification
• Based on cellular properties of normal
His-Purkinje cells
• Classified on drug’s ability to block
specific ionic currents (i.e. Na+, K+, Ca++)
and beta-adrenergic receptors
• Advantages:
– Physiologically based
– Highlights beneficial/deleterious effects
of specific drugs
Antiarrhythmic Therapy
Empiric
Arrhythmia Diagnosis
BLACK BOX
Interventions
Clinical Outcomes
Goals
•Identify the type of
dysrhythmia
•Be familiar with more
common
antiarrhythmics and
their Vaughn-Williams
Classification
Arrhythmia Types
• Slow
• Fast
Fast
wide
Fast narrow
Too fast
Arrhythmia-focused
Therapy
• Fast Narrow
• Supraventricular tachycardias
– Re-entry type
• Orthodromic SVT
– Automatic
• A.E.T. , Atrial Flutter
• J.E.T.
Arrhythmia-focused
Therapy
• Fast Wide
– (rare) Antidromic SVT or SVT with
abberancy
– Ventricular tachycardia
• Inappropriate automaticity of
ventricular or His-Purkinje tissue
Arrhythmia-focused
Therapy
• Select one antiarrhythmic or
a limited group of
antiarrhythmics to treat the
disorder.
Antiarrhythmic Agents
Vaughn-Williams Classification
• Class I - Na+ - channel blockers (direct
membrane action)
• Class II - Sympatholytic agents
• Class III - Prolong repolarization
• Class IV- Ca++ - channel blockers
• Purinergic agonists
• Digitalis glycosides
The Action Potential
30 mV
Phase 1
Phase 2
0 mV
Phase 3
Phase 0
Phase 4
- 90 mV
Class I
Na+ Channel Blockers
• IA - Quinidine/Procainamide/Disopyramide
• IB - Lidocaine/Mexiletine/Phenytoin
• IC - Flecainide/Propafenone/Ethmozine
1
2
Affects
Phase 0
3
0
4
ERP
RRP
Class IA -
Na+ Channel Blockers
Procainamide/Quinidine/Disopyramide
• Mode of action
–
Depress conduction and prolong
refractoriness
•
–
–
–
Atrial, His-Purkinje, ventricular tissue
Peripheral alpha block
Vagolytic
Negative inotrope
• ECG changes
–
–
–
Increase PR, QRS (Diso: PR  > QRS  )
Toxicity: QTc increases by 30% or QT > 0.5 sec
Ca++ channel blockade / potent anticholinergic
(Diso)
Class IA - Na+ Channel
Blockers Procainamide
• Uses
SVT (reentry) or VT
– Afib/flutter (on digoxin)
• Drug interactions-Decrease metabolism of
Amiodarone
–
• Dose
–
–
–
IV: load 15 mg/kg over 1 hour, then 30-80
g/kg/min
(level 5-10 ng/ml)
PO: 30-70 mg/kg/day
• Side effects: Lupus- in slow acetylators
–
ANA + : 50-90% Symptoms: 20-30 %
Arrhythmia-focused
Therapy
• Procainamide has been a long-used intravenous
•
infusion for a wide range of dysrhythmias:
– Narrow complex tachycardia:
• Atrial tachycardia, resistant re-entrant
tachycardia
– Wide-complex tachycardia:
• Ventricular tachycardia
• Downside:
•
Side effects, negative inotrope, proarrhythmic
Class IB
Lidocaine/Mexiletine/Phenytoin
• Mode of action
–
–
–
–
–
Little effect on normal tissues
Decreases Purkinje ERP/ automaticity
Increases Ventricular fibrillation
threshold
Depresses conduction, esp. at high rates
(Mexiletine)
Suppresses dig-induced delayed
afterdepolarizations (Phenytoin)
• ECG changes
– Slight  QTc (Lidocaine/Phenytoin)
Class IB
Lidocaine
• Use: VT (acute)
–
Acts rapidly; no depression of contractility/AV
conduction
• Kinetics
–
t1/2 : 5-10 min (1st phase); 80-110 min (2nd
phase)
• Drug interactions
–
–
Decreased metabolism w/ CHF/hepatic failure,
propranolol, cimetidine
Increased metabolism w/ isuprel, phenobarbital,
phenytoin
Class IB
Lidocaine
• Dose
–
1 mg/kg, then 20-50 g/kg/min (level: 2-5
g/ml)
• Side effects
–
CNS toxicity w/ levels > 5 g/ml
Class IB
Mexiletine
•
•
•
•
Use: VT (post-op CHD)
Kinetics: t1/2 = 8 - 12 hrs
Drug interactions- rare
Dose
–
3-5 mg/kg/dose (adult 200-300mg/dose) po q
8 hrs
• Side effects
–
–
Nausea (40%)
CNS - dizziness/tremor (25%)
Class IB
Phenytoin
• Uses
– VT (post-op CHD), digoxin-induced
arrhythmias
• Drug interactions
– Coumadin-  PT; Verapamil-  effect
(displaces from protein)
• Dose
– PO: 4 mg/kg q 6 hrs x 1 day, then 5-6
mg/kg/day ÷ q 12hr
– IV: bolus 15 mg/kg over 1 hr; level 15-20
g/ml
• Side effects
– Hypotension, gingival hyperplasia, rash
Arrhythmia-focused
Therapy
• Class IB antiarrhythmics are very effective
and very safe.
• Little or no effect on “normal” tissues
• First line for ischemic, automatic
arrhythmia's (Ventricular tachycardia)
• Not a lot of effect on normal conduction
tissue – not a good medicine for reentry
and atrial tachycardias.
Class IC
Flecainide/Propafenone/Ethmozine
• Mode of action
–
–
–
–
–
Depresses abnormal automaticity
(Flec/Ethmozine)
Slows conduction in AV node, AP, ventricle
(Flec/Prop)
Shortens repolarization (Ethmozine)
Negative inotrope (Propafenone)
Prolongs atrial/ventricular refractoriness
(Propafenone)
• ECG changes

PR, QRS
  QTc (Propafenone)
Class IC
Flecainide
• Uses: PJRT, AET, CAT, SVT, VT, Afib
• Kinetics
–
t1/2 = 13 hrs (shorter if between 1-15 mos old)
• Drug interactions
–
–
Increases digoxin levels (slight)
Amiodarone: increases flecainide levels
Class IC
Flecainide
• Dose
–
70-225 mg/m2/day ÷ q 8-12 hr
–
Level: 0.2-1.0 g/ml
• Side effects
–
–
Negative inotrope- use in normal hearts only
• (NO POST-OPs)
PROARRHYTHMIA - 5-12% (CAST)
Arrhythmia –focused
Therapy
• IC’s have a lot of side effects
that make them appropriate for
use only by experienced
providers.
Class II Agents
Beta-blockers
•
•
•
•
•
•
Propranolol
Atenolol
Metoprolol
Nadolol
Esmolol
d,l-Sotalol
Class II
Propranolol
• Uses
– SVT (reentry, ectopic)
– Sinus tachycardia (thyrotoxicosis)
– VT (exercise-induced)
• Kinetics
–
t1/2 = 3 hrs (increased if cyanotic)
• Drug interactions
– Verapamil
•
•
Hypotension
Decreased LV function
Class II
Propranolol
• Dose
– PO: 2-4 mg/kg/day  q 6 hrs
– IV: 0.05-0.15 mg/kg
• Side effects
– Avoid in asthma/diabetes
– CNS effects
•
–
Nonpolar - crosses BBB
 BP
•
Suppresses renin-aldo-angiotensin axis
Arrhythmia-focused
Therapy
• Beta-blockers are good for reentry circuits and automatic
dysrhythmias.
• Their effect of decreasing
contractility may be limiting.
Class III
K+ - channel blockers
• Properties
–
–
–
Prolong repolarization
Prolong action potential duration
Contractility is unchanged or increased
• Agents
–
–
–
–
Amiodarone
Sotalol
Bretylium
N-acetyl Procainamide (NAPA)
Arrhythmia-focused
Therapy
 Can be very powerful antiarrhythmics
but limited indications for first-line use –
beyond the spectrum of primary care
providers
 Amiodarone: may become a first-line
medicine for a broad spectrum of
arrhythmias, currently still high-risk
Purinergic Agonists
Adenosine
• Mode of action
–
–
–
–
Vagotonic
Anti-adrenergic
Depresses slow inward Ca++ current
Increases K+ conductance
(hyperpolarizes)
• ECG/EP changes
–
Slows AV node conduction
Purinergic Agonists
Adenosine
• Uses
–
–
SVT- termination of reentry
Aflutter- AV block for diagnosis
• Kinetics
–
–
t1/2 = < 10 secs
Metabolized by RBCs and vascular
endothelial cells
• Dose
– IV: 100-300 g/kg IV bolus
Purinergic Agonists
Adenosine
• Drug interactions
–
Methylxanthines (caffeine/theophylline)
• Side effects
–
–
–
–
AFib/ sinus arrest/ sinus bradycardia
Bronchospasm
Flushing/headache
Nausea
• Great medicine: quick onset,
quick degradation.
Digoxin
• Mode of action
–
–
–
Na-K ATPase
inhibition
Positive inotrope
Vagotonic
• ECG changes
–
–
–
Increases PR interval
Depresses ST
segment
Decreases QT interval
Digoxin
• Use: SVT (not WPW)
• Kinetics
–
t1/2 = preemie (61hrs), neonate (35hrs), infant
(18hrs), child (37hrs), adult (35-48hrs )
• Interactions


Coumadin-  PT
 Digoxin level
 Quinidine, amiodarone, verapamil
  renal function/renal tubular excretion
(Spironolactone)
 Worse with  K+,  Ca++
Digoxin Toxicity
• Nausea/vomiting, lethargy, visual changes
• Metabolic
–
–
–
–
Hyper K+, Ca++
Hypo K+, Mg++
Hypoxemia
Hypothyroidism
• Proarrhythmia
–
–
–
AV block- decreased conduction
SVT- increased automaticity
VT- delayed afterdepolarizations
Digoxin Toxicity
Treatment
• GI decontamination
–
Ipecac/lavage/charcoal w/ cathartic
• Arrhythmias
–
–
–
SA node /AV node depression- Atropine; if
dig > 6, may need pacing
SVT- Phenytoin or  -blocker
VT- Lidocaine (1 mg/kg) or Phenytoin
• DC Cardioversion may cause
refractory VT/VF!!
Proarrhythmia
Torsades de Pointes
• Class IA
–
–
–
Quinidine
Procainamide
Disopyramide
2-8%
2-3%
2-3%
• Class III
–
–
–
–
d,l-Sotalol
d-Sotalol
NAPA
Amiodarone
1-5%
1-2%
3-4%
< 1%
Summary
• SVT: Initial
–
–
–
Adenosine
?Propranolol
Procainamide
• SVT: Long Term
–
–
–
Nothing
Propranolol
Digoxin
Summary
• VT : Initial
– Lidocaine
– Procainamide
• VT: Long Term
– Lidocaine/Procainamide
– Beta-blockers
– Cardiologist
60 Cycle Interference
Atrial Flutter
SVT
Ventricular Tachycardia
Ventricular Fibrillation