Click here to load reader

Intravenous Amiodarone for Supraventricular Tachycardias

  • View
    55

  • Download
    1

Embed Size (px)

DESCRIPTION

Intravenous Amiodarone for Supraventricular Tachycardias. Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia. Supraventricular Tachycardias: Therapeutic Objectives. Determine the mechanism of the arrhythmia - PowerPoint PPT Presentation

Text of Intravenous Amiodarone for Supraventricular Tachycardias

  • Intravenous Amiodarone for Supraventricular TachycardiasJerrold H Levy, MDEmory University School of MedicineAtlanta, Georgia

  • Supraventricular Tachycardias: Therapeutic ObjectivesDetermine the mechanism of the arrhythmia Restore sinus rhythm with the simplest technique and approach as possibleEliminate or significantly reduce arrhythmia recurrences and underlying causeSingh 2002.

  • Types of Supraventricular TachyarrhythmiasRALALVRVSinus Node ReentryAtrial FlutterAutomatic Atrial TachycardiaReentrant Atrial TachycardiaAtrioventricular Nodal Reentry (AVNRT)AV Reentry via an Accessory AV Connection (AVRT)Atrial Fibrillation (Not Shown)Singh 2002.

  • Types of Paroxysmal Supraventricular TachycardiaAV Nodal ReentryAV Reciprocating TachycardiaSinus Nodal ReentryIntra-atrial ReentryAutomatic Atrial Tachycardia

  • Mechanisms of Paroxysmal Supraventricular TachycardiasEnhanced Automaticity:Paroxysmal and AcuteChronicRe-entry without Bypass Tracts:AV Nodal Re-entry: Slow Fast/Fast SlowSinoatrial Nodal Re-entryIntra-atrial Re-entryRe-entry in Association with Bypass Tracts:Re-entry with Anterograde AV Conduction (Orthodromic)With Evidence of Pre-excitation of 12-Lead ECGConcealed WPW (Bypass Tract Conducting Only Retrogradely)Re-entry with Anterograde Conduction Over Bypass Tract (Antidromic) During Tachycardia

  • Accessory Pathways: Concealed Bypass Tract AV Reentrant TachycardiaAV NodeBundle of HisLeft Bundle BranchPRight Bundle BranchConcealed Bypass TractSingh 2002.

  • Electrical Conduction in Atrial FlutterAV NodeVentricular Rate 150-160 (Most Often 2:1 AV Block)ECG of Flutter

  • Atrial FibrillationBaseline Coarsely or Finely Irregular; P Waves Absent.Ventricular Response (QRS) Irregular, Slow or RapidCoarse FibrillationFine FibrillationScheidt S, Erlebacher JA, Netter FH. Basic Electrocardiography ECG. Ciba-Geigy: First Printing, 1986, p23.Electrocardiogram

  • AF is Associated WithCV DiseasesCT surgeryValvular or congential diseaseHypertensionCardiomyopathyHeart failureMyocardial ischemia/MIPeri/myocarditisInfiltrative heart diseaseCardiac traumaSystemic DiseasesAgeDTs, sympathetic stormElectrolyte disordersThyrotoxicosisFever/hypothermiaHypovolemiaDiabetesAnemiaPulmonary diseaseCerebrovascular disease

  • Antiarrhythmic Drugs vs. Therapeutic GoalAtriumHis PurkinjeVentricleAPAV NodeIbutilideQuinidine Procainamide DisopyramideFlecainide Propafenone Sotalol AmiodaroneVagal Stimulation Digoxin b-Blocking Drugs Verapamil Diltiazem AdenosineSingh 2002.

  • Simulated Drug Level Curves= Full loading doseTime (Half-life)0123456TherapeuticConcentrationRangePlasma Drug Level= Half loading dose and infusionLevy 2002.

  • Agents Used in the Treatment of SVT Tachycardias by Vaughan Williams Class1A:Quinidine, procainamide, disopyramide1C:Flecainide, propafenone2: Esmolol, propranolol, metoprolol, atenolol, (et al)3: Amiodarone, sotalol4:Diltiazem, verapamilGlycosides: digoxin Purinergic: adenosineSingh 2002.

  • Amiodarone Historical Landmarks (1) 1962:Synthesized as an anti-anginal compound (Charlier) 1968:Novel action with new biological profile (Charlier) 1970:Unusual electrophysiology profile (Singh & Vaughan Williams)74/76:Unusual clinical potency as an antiarrhythmic drug (Rosenbaum M)

  • Amiodarone Historical Landmarks (2)1983:First US Symposium on Amiodarone (Singh & Zipes)1984:FDA Approval1993:Efficacy Unparalleled; Mode of Action Unknown1995:Amiodarone IV approved1999:Symposium, the last 15 years (Singh, AJC (Suppl))Singh 2002.

  • Unique Features of Amiodarone as an Anti-arrhythmic DrugLong elimination half-lifeCan be administered to anephric patients on dialysisWell tolerated in advanced CHFManageable drug-drug interactions (ie, digoxin, coumadin)Very low incidence of torsades de pointes even with diuretic therapySingh 2002.

  • Unique Features of Amiodarone as an Anti-arrhythmic Drug (Contd.)Has Class 1 properties without the associated proarrhythmic actions or negative impact on mortalityHas antisympathetic actions without beta-blocker side effectsIncreases LVEF and improves CHFAntifibrillatory actions in the ventricles may be augmented by addition of beta-blockadeSingh 2002.

  • Intravenous Amiodarone PharmacokineticsPeak 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/LLevels decline to 10% of peak within 30-45 min at the end of the infusionAfter 48 hrs of continued infusions, levels 0.7 to 1.4 mg/LSingh 2002.

  • Pharmacokinetics of Oral AmiodaroneAbsorption: Tmax:2-12 h (lab 0.4-3 h)Extent of absorption: Poor and slowBioavailability: Variable (22-86%)Protein binding: 96.3 0.6%Volume of distribution: 1.3-65.8 l/kgNegligible renal excretionBiotransformation: Hepatic and intestinalElimination half-life: 3.2-20.7 h (acute), 13.7-52.6 day (chronic)Singh 2002.

  • Pharmacokinetics of Oral AmiodaroneTotal body clearance: 0.10-0.77 l/minPattern of elimination: First orderMetabolites: Major: mono N-desethylamiodarone, Minor: bis-N-desethylamiodarone, deiodinated metabolitesTherapeutic levels: 1.0-2.5 g/mL rangeSpecial factors: Slow onset and offset of actionSingh 2002.

  • Actions of IV Amiodarone vs Chronic Amiodarone

    ActionsIV AmioChronic AmioRepolarization (QT interval) prolongation (atria & ventricles)++++Conduction velocity (atria & vent) reduced++++ (function of rate)Sinus rates reduced++++AV nodal conduction slowed+++

  • Actions of IV Amiodarone vs Chronic AmiodaroneSingh 2002.

    ActionsIV AmioChronic AmioAV nodal refactoriness increased++++++Atrial refactoriness increased+++Ventricular refactoriness increased+++Noncompetitive alpha and beta blocking activity++

  • Pharmacokinetics of IV AmiodaroneSummary: More rapid onset and offset of action with IV versus oral

  • Comparison of Oral vs. IV Amiodarone:Conversion of Atrial FibrillationN=52 patients with atrial fibrillation86 episodes of attempted cardioversion with oral, intravenous, or DC cardioversionConversion to sinus rhythm achieved29% of pts treated with oral amiodarone42% of pts treated with DC cardioversion64% of pts treated with intravenous amiodaroneOverall statistical significance: P = 0.032Horner SM. Acta Cardiol. 1992;47:473.

  • Efficacy of IV Amiodarone for the Conversion of Atrial arrhythmia

  • Management of Atrial Tachyarrhythmias in the Critically Ill: a Comparison of Intravenous Procainamide and Amiodarone24 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 response Results: 7/10 Amiodarone-treated patients, 10/14 Procainamide-treated patients converted to sinus rhythm by 12 hoursNo significant change in SBP from baselineChapman MJ et al Intensive Care Med 1993;19:48-52.

  • Amiodarone Versus Propafenone for Conversion of Chronic Atrial Fibrillation: Results of a Randomized, Controlled Study118 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) Results: 16/34 (47.05%) amiodarone-treated patients vs. 13/32 (40.62%) propafenone-treated Patients converted to sinus rhythm, P
  • PIAF TrialRhythm or Rate Control in Atrial Fibrillation PharmacologicalIntervention in Atrial Fibrillation (PIAF): a Randomized Trial252 pts enrolled, 125 diltiazem, 127 amiodaroneMethods: Pts randomized to diltiazem or amiodaroneResults:76 pts on diltiazem, 70 on amiodarone reported improved symptoms, P=0.31723% of amiodarone pts returned to sinus rhythmamiodarone-treated pts did better on 6 min walk test than diltiazemConclusion: In patients with atrial fibrillation, the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall

    Hohnloser et al. Lancet. 2000;356:1789-94.

  • IV Amiodarone Treatment for Acute Heart Rate Control in Critically Ill PatientsMethodsRetrospective study of 38 ICU patientsPts received IV amiodarone for resistant atrial tachyarrhythmiasOnset of rapid heart rate (mean 149 13 beats/min was associated with decrease in systolic blood pressure of 20 5 mm Hg (P
  • IV Amiodarone Treatment for Acute Heart Rate Control in Critically Ill PatientsIntravenous diltiazem (n=34), esmolol (n=4), and digoxin (n=24) had no effect, while reducing systolic blood pressure of 6 4 mm Hg (P
  • Caveats RegardingAmiodarone DosingComplex PK/PD with extremely long half lifeDifferent efficacy rates with studies due to dosing issues, and different patient populations

  • Amiodarone IV for Atrial Arrhythymias: SummaryEffective in SVT, but best studied in AFAcute IV therapy is different than chronic oral administration: dosing and PK needs to be considered In critically ill patients, IV therapy is required

  • Questions and Answers

    21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro21104 Cytocom Las Vegas: Barnes Intro