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Intravenous Amiodarone for Supraventricular Tachycardias Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia

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  • Intravenous Amiodarone for Supraventricular Tachycardias Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia
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  • Supraventricular Tachycardias: Therapeutic Objectives Determine the mechanism of the arrhythmiaDetermine the mechanism of the arrhythmia Restore sinus rhythm with the simplest technique and approach as possibleRestore sinus rhythm with the simplest technique and approach as possible Eliminate or significantly reduce arrhythmia recurrences and underlying causeEliminate or significantly reduce arrhythmia recurrences and underlying cause Singh 2002.
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  • RALA LV RV Types of Supraventricular Tachyarrhythmias Sinus Node Reentry Atrial Flutter Automatic Atrial Tachycardia Reentrant Atrial Tachycardia Atrioventricular Nodal Reentry (AVNRT) AV Reentry via an Accessory AV Connection (AVRT) Atrial Fibrillation (Not Shown) Singh 2002.
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  • Types of Paroxysmal Supraventricular Tachycardia AV Nodal Reentry AV Reciprocating Tachycardia Sinus Nodal Reentry Intra-atrial Reentry Automatic Atrial Tachycardia
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  • Mechanisms of Paroxysmal Supraventricular Tachycardias Enhanced Automaticity: Paroxysmal and AcuteParoxysmal and Acute ChronicChronic Re-entry without Bypass Tracts: AV Nodal Re-entry: Slow Fast/Fast SlowAV Nodal Re-entry: Slow Fast/Fast Slow Sinoatrial Nodal Re-entrySinoatrial Nodal Re-entry Intra-atrial Re-entryIntra-atrial Re-entry Re-entry in Association with Bypass Tracts: Re-entry with Anterograde AV Conduction (Orthodromic)Re-entry with Anterograde AV Conduction (Orthodromic) With Evidence of Pre-excitation of 12-Lead ECG Concealed WPW (Bypass Tract Conducting Only Retrogradely) Re-entry with Anterograde Conduction Over Bypass Tract (Antidromic) During TachycardiaRe-entry with Anterograde Conduction Over Bypass Tract (Antidromic) During Tachycardia
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  • Accessory Pathways: Concealed Bypass Tract AV Reentrant Tachycardia AV Node Bundle of His Left Bundle Branch P Right Bundle Branch Concealed Bypass Tract Singh 2002.
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  • AV Node Electrical Conduction in Atrial Flutter Ventricular Rate 150-160 (Most Often 2:1 AV Block) ECG of Flutter
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  • Baseline Coarsely or Finely Irregular; P Waves Absent. Ventricular Response (QRS) Irregular, Slow or Rapid Coarse FibrillationFine Fibrillation Atrial Fibrillation Scheidt S, Erlebacher JA, Netter FH. Basic Electrocardiography ECG. Ciba-Geigy: First Printing, 1986, p23. Electrocardiogram
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  • AF is Associated With CV Diseases CT surgeryCT surgery Valvular or congential diseaseValvular or congential disease HypertensionHypertension CardiomyopathyCardiomyopathy Heart failureHeart failure Myocardial ischemia/MIMyocardial ischemia/MI Peri/myocarditisPeri/myocarditis Infiltrative heart diseaseInfiltrative heart disease Cardiac traumaCardiac trauma Systemic Diseases AgeAge DTs, sympathetic stormDTs, sympathetic storm Electrolyte disordersElectrolyte disorders ThyrotoxicosisThyrotoxicosis Fever/hypothermiaFever/hypothermia HypovolemiaHypovolemia DiabetesDiabetes AnemiaAnemia Pulmonary diseasePulmonary disease Cerebrovascular diseaseCerebrovascular disease
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  • Antiarrhythmic Drugs vs. Therapeutic Goal Atrium His Purkinje Ventricle AP AV Node Ibutilide Quinidine Procainamide Disopyramide Flecainide Propafenone Sotalol Amiodarone Vagal Stimulation Digoxin -Blocking Drugs Verapamil Diltiazem Adenosine Singh 2002.
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  • Simulated Drug Level Curves = Full loading dose Time (Half-life) 0123456 Therapeutic Concentration Range Plasma Drug Level = Half loading dose and infusion = Infusion without loading dose Levy 2002.
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  • Agents Used in the Treatment of SVT Tachycardias by Vaughan Williams Class 1A:Quinidine, procainamide, disopyramide 1C:Flecainide, propafenone 2: Esmolol, propranolol, metoprolol, atenolol, (et al) 3: Amiodarone, sotalol 4:Diltiazem, verapamil Glycosides: digoxin Purinergic: adenosine Singh 2002.
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  • Amiodarone Historical Landmarks (1) 1962:Synthesized as an anti-anginal compound (Charlier) 1962:Synthesized as an anti-anginal compound (Charlier) 1968:Novel action with new biological profile (Charlier) 1968:Novel action with new biological profile (Charlier) 1970:Unusual electrophysiology profile (Singh & Vaughan Williams) 1970:Unusual electrophysiology profile (Singh & Vaughan Williams) 74/76:Unusual clinical potency as an antiarrhythmic drug (Rosenbaum M)
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  • Amiodarone Historical Landmarks (2) 1983:First US Symposium on Amiodarone (Singh & Zipes) 1984:FDA Approval 1993:Efficacy Unparalleled; Mode of Action Unknown 1995:Amiodarone IV approved 1999:Symposium, the last 15 years (Singh, AJC (Suppl)) Singh 2002.
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  • Unique Features of Amiodarone as an Anti-arrhythmic Drug Long elimination half-lifeLong elimination half-life Can be administered to anephric patients on dialysisCan be administered to anephric patients on dialysis Well tolerated in advanced CHFWell tolerated in advanced CHF Manageable drug-drug interactions (ie, digoxin, coumadin)Manageable drug-drug interactions (ie, digoxin, coumadin) Very low incidence of torsades de pointes even with diuretic therapyVery low incidence of torsades de pointes even with diuretic therapy Singh 2002.
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  • Unique Features of Amiodarone as an Anti-arrhythmic Drug (Contd.) Has Class 1 properties without the associated proarrhythmic actions or negative impact on mortalityHas Class 1 properties without the associated proarrhythmic actions or negative impact on mortality Has antisympathetic actions without beta-blocker side effectsHas antisympathetic actions without beta-blocker side effects Increases LVEF and improves CHFIncreases LVEF and improves CHF Antifibrillatory actions in the ventricles may be augmented by addition of beta-blockadeAntifibrillatory actions in the ventricles may be augmented by addition of beta-blockade Singh 2002.
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  • Intravenous Amiodarone Pharmacokinetics Peak levels after single 5 mg/kg 15 min infusions: 5-41 mg/LPeak levels after single 5 mg/kg 15 min infusions: 5-41 mg/L After 10 min 150 mg load for VF/VT: 7-26 mg/LAfter 10 min 150 mg load for VF/VT: 7-26 mg/L Levels decline to 10% of peak within 30-45 min at the end of the infusionLevels decline to 10% of peak within 30-45 min at the end of the infusion After 48 hrs of continued infusions, levels 0.7 to 1.4 mg/LAfter 48 hrs of continued infusions, levels 0.7 to 1.4 mg/L Singh 2002.
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  • Pharmacokinetics of Oral Amiodarone Absorption: T max :2-12 h (lab 0.4-3 h)Absorption: T max :2-12 h (lab 0.4-3 h) Extent of absorption: Poor and slowExtent of absorption: Poor and slow Bioavailability: Variable (22-86%)Bioavailability: Variable (22-86%) Protein binding: 96.3 0.6%Protein binding: 96.3 0.6% Volume of distribution: 1.3-65.8 l/kgVolume of distribution: 1.3-65.8 l/kg Negligible renal excretionNegligible renal excretion Biotransformation: Hepatic and intestinalBiotransformation: Hepatic and intestinal Elimination half-life: 3.2-20.7 h (acute), 13.7-52.6 day (chronic)Elimination half-life: 3.2-20.7 h (acute), 13.7-52.6 day (chronic) Singh 2002.
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  • Pharmacokinetics of Oral Amiodarone Total body clearance: 0.10-0.77 l/minTotal body clearance: 0.10-0.77 l/min Pattern of elimination: First orderPattern of elimination: First order Metabolites: Major: mono N- desethylamiodarone, Minor: bis-N- desethylamiodarone, deiodinated metabolitesMetabolites: Major: mono N- desethylamiodarone, Minor: bis-N- desethylamiodarone, deiodinated metabolites Therapeutic levels: 1.0-2.5 g/mL rangeTherapeutic levels: 1.0-2.5 g/mL range Special factors: Slow onset and offset of actionSpecial factors: Slow onset and offset of action Singh 2002.
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  • Actions of IV Amiodarone vs Chronic Amiodarone Actions IV Amio Chronic Amio Repolarization (QT interval) prolongation (atria & ventricles) ++++ Conduction velocity (atria & vent) reduced ++ ++ (function of rate) Sinus rates reduced ++++ AV nodal conduction slowed +++
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  • Actions of IV Amiodarone vs Chronic Amiodarone Actions IV Amio Chronic Amio AV nodal refactoriness increased ++++++ Atrial refactoriness increased +++ Ventricular refactoriness increased +++ Noncompetitive alpha and beta blocking activity ++ Singh 2002.
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  • Pharmacokinetics of IV Amiodarone Summary: More rapid onset and offset of action with IV versus oral
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  • Comparison of Oral vs. IV Amiodarone: Conversion of Atrial Fibrillation N=52 patients with atrial fibrillationN=52 patients with atrial fibrillation 86 episodes of attempted cardioversion with oral, intravenous, or DC cardioversion Conversion to sinus rhythm achievedConversion to sinus rhythm achieved 29% of pts treated with oral amiodarone 42% of pts treated with DC cardioversion 64% of pts treated with intravenous amiodarone Overall statistical significance: P = 0.032 Horner SM. Acta Cardiol. 1992;47:473.
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  • Efficacy of IV Amiodarone for the Conversion of Atrial arrhythmia Vietti-Ramus et al. 1992 44 pts 86% w/ SVT reverted to SR
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  • Management of Atrial Tachyarrhythmias in the Critically Ill: a Comparison of Intravenous Procainamide and Amiodarone 24 pts atrial fibrillation more than 1 h evaluated 10 Amiodarone, 14 Procainamide Methods: Amiodarone IV 3 mg/kg then 10 mg/kg/24 h with repeat dose of 3 mg/kg at 1 h if no response or Procainamide IV 10 mg/kg at 1 mg/kg/min then 2-4 mg/min for 24 h with repeat dose of 5mg/kg at 1 h if no responseAmiodarone IV 3 mg/kg then 10 mg/kg/24 h with repeat dose of 3 mg/kg at 1 h if no response or Procainamide IV 10 mg/kg at 1 mg/kg/min then 2-4 mg/min for 24 h with repeat dose of 5mg/kg at 1 h if no responseResults: 7/10 Amiodarone-treated patients, 10/14 Procainamide-treated patients converted to sinus rhythm by 12 hours 7/10 Amiodarone-treated patients, 10/14 Procainamide-treated patients converted to sinus rhythm by 12 hours No significant change in SBP from baselineNo significant change in SBP from baseline Chapman MJ et al Intensive Care Med 1993;19:48-52.
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  • Amiodarone Versus Propafenone for Conversion of Chronic Atrial Fibrillation: Results of a Randomized, Controlled Study 118 pts with atrial fibrillation lasting more than 3 weeks, 34 amiodarone, 32 propafenone, 35 control Methods: IV amiodarone 300 mg over 1 h, then 20 mg/kg over 24 hours plus 600 mg orally, in 3 doses for 1 week, then 400 mg/day orally for 3 weeks. IV propafenone 2 mg/kg over 15 minutes, then 10 mg/kg over 24 h and then 450 mg/day orally for 1 month. All patients received digoxin and anticoagulation (INR 2-3)IV amiodarone 300 mg over 1 h, then 20 mg/kg over 24 hours plus 600 mg orally, in 3 doses for 1 week, then 400 mg/day orally for 3 weeks. IV propafenone 2 mg/kg over 15 minutes, then 10 mg/kg over 24 h and then 450 mg/day orally for 1 month. All patients received digoxin and anticoagulation (INR 2-3)Results: 16/34 (47.05%) amiodarone-treated patients vs. 13/32 (40.62%) propafenone-treated16/34 (47.05%) amiodarone-treated patients vs. 13/32 (40.62%) propafenone-treated Patients converted to sinus rhythm, P