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
Interventions
Clinical Outcomes
Clinical Outcomes
Antiarrhythmic Therapy

Pathophysiologic AV node reentrant tachycardia

Arrhythmia Diagnosis

Known or suspected AV node reentry

mechanisms
Anatomical fast/slow
Critical components pathway
AV node (slow conduction)
Vulnerable parameters AV nodal action potential

Targeted subcellular units L-type Ca++ channel

Ca++ channel blocker
Interventions -blocker

Clinical Outcomes 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 Goals
Arrhythmia Diagnosis •Identify the type of
dysrhythmia
•Be familiar with more
common
BLACK BOX antiarrhythmics and
their Vaughn-Williams
Classification

Interventions

Clinical Outcomes
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
Phase 1
30 mV
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 3
0
Phase 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, pro-
arrhythmic
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
1/2 : 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 re-
entry 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 2-8%
– Procainamide 2-3%
– Disopyramide 2-3%
• Class III
– d,l-Sotalol 1-5%
– d-Sotalol 1-2%
– NAPA 3-4%
– Amiodarone < 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