Antiarrhythmic Therapy UTHSCSA Pediatric Resident Curriculum for the PICU

Antiarrhythmic TherapyAntiarrhythmic Therapy

UTHSCSA Pediatric Resident Curriculum for the PICUUTHSCSA Pediatric Resident Curriculum for the PICU


EmpiricArrhythmia Diagnosis

Interventions

Clinical OutcomesInterventions

Clinical Outcomes

PathophysiologicArrhythmia Diagnosis

Known or suspected mechanisms

Critical components

Vulnerable parameters

Targeted subcellular units

BLACK BOX


PathophysiologicArrhythmia Diagnosis

Interventions

Clinical Outcomes

Known or suspected mechanisms

Critical components

Vulnerable parameters

Targeted subcellular units

AV node reentrant tachycardia

AV node reentry

Anatomical fast/slow pathwayAV node (slow conduction)AV nodal action potential

L-type Ca++ channel

Ca++ channel blocker-blocker

Sinus rhythm

Vaughn-Williams Vaughn-Williams ClassificationClassification

• 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


EmpiricArrhythmia Diagnosis

Interventions

Clinical Outcomes

BLACK BOX

Goals•Identify the type of dysrhythmia•Be familiar with more common antiarrhythmics and their Vaughn-Williams Classification

Arrhythmia TypesArrhythmia Types

• Slow

• Fast Fast wide Fast narrow Too fast

Arrhythmia-focused Arrhythmia-focused TherapyTherapy

• Fast Narrow

• Supraventricular tachycardias– Re-entry type• Orthodromic SVT

– Automatic• A.E.T. , Atrial Flutter• J.E.T.


• Fast Wide– (rare) Antidromic SVT or SVT with

abberancy– Ventricular tachycardia • Inappropriate automaticity of

ventricular or His-Purkinje tissue


• Select one antiarrhythmic or a limited group of antiarrhythmics to treat the disorder.

Antiarrhythmic AgentsAntiarrhythmic AgentsVaughn-Williams ClassificationVaughn-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 PotentialThe Action Potential

Phase 0

Phase 4

Phase 3

Phase 2

Phase 1

- 90 mV

0 mV

30 mV

Class I Class I Na+ Channel BlockersNa+ Channel Blockers

• IA - Quinidine/Procainamide/Disopyramide• IB - Lidocaine/Mexiletine/Phenytoin• IC - Flecainide/Propafenone/Ethmozine

1

0

2

3

4

ERP RRP

AffectsPhase 0

Class IA - Class IA - Na+ Channel BlockersNa+ Channel BlockersProcainamide/Quinidine/DisopyramideProcainamide/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 BlockersClass IA - Na+ Channel Blockers ProcainamideProcainamide

• 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 %


• 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 IBClass IBLidocaine/Mexiletine/PhenytoinLidocaine/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 IBClass IBLidocaineLidocaine

• 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

• 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 IBClass IBLidocaineLidocaine

• Dose– 1 mg/kg, then 20-50 g/kg/min (level: 2-5

g/ml)

• Side effects– CNS toxicity w/ levels > 5 g/ml

• 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 IBClass IBMexiletineMexiletine

• 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 IBClass IBPhenytoinPhenytoin

• 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


• 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 ICClass ICFlecainide/Propafenone/EthmozineFlecainide/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 ICClass ICFlecainideFlecainide

• 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 ICClass ICFlecainideFlecainide

• 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 Arrhythmia –focused TherapyTherapy

• IC’s have a lot of side effects that make them appropriate for use only by experienced providers.

Class II AgentsClass II AgentsBeta-blockersBeta-blockers

• Propranolol• Atenolol• Metoprolol• Nadolol• Esmolol• d,l-Sotalol

Class IIClass IIPropranololPropranolol

• 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 IIClass IIPropranololPropranolol

• 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


• Beta-blockers are good for re-entry circuits and automatic dysrhythmias.

• Their effect of decreasing contractility may be limiting.

Class III Class III KK++ - channel blockers - channel blockers

• Properties– Prolong repolarization– Prolong action potential duration– Contractility is unchanged or increased

• Agents– Amiodarone– Sotalol– Bretylium– N-acetyl Procainamide (NAPA)

Arrhythmia-focused Arrhythmia-focused TherapyTherapy 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 AgonistsPurinergic AgonistsAdenosineAdenosine

• Mode of action– Vagotonic– Anti-adrenergic– Depresses slow inward Ca++ current– Increases K+ conductance

(hyperpolarizes)

• ECG/EP changes– Slows AV node conduction


• 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


• Drug interactions– Methylxanthines (caffeine/theophylline)

• Side effects– AFib/ sinus arrest/ sinus bradycardia– Bronchospasm– Flushing/headache– Nausea

• Great medicine: quick onset, quick degradation.

DigoxinDigoxin

• Mode of action– Na-K ATPase inhibition– Positive inotrope– Vagotonic

• ECG changes– Increases PR interval– Depresses ST segment– Decreases QT interval

DigoxinDigoxin

• 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 ToxicityDigoxin 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 ToxicityDigoxin ToxicityTreatmentTreatment

• 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!!

ProarrhythmiaProarrhythmiaTorsades de PointesTorsades 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%

SummarySummary

• SVT: Initial – Adenosine– ?Propranolol– Procainamide

• SVT: Long Term– Nothing– Propranolol– Digoxin

SummarySummary

• VT : Initial– Lidocaine– Procainamide

• VT: Long Term– Lidocaine/Procainamide– Beta-blockers– Cardiologist

60 Cycle Interference60 Cycle Interference

Atrial FlutterAtrial Flutter

SVTSVT

Ventricular TachycardiaVentricular Tachycardia

Ventricular FibrillationVentricular Fibrillation

Documents

Antiarrhythmic Therapy UTHSCSA Pediatric Resident Curriculum for the PICU