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Intravenous Amiodarone for Supraventricular Tachycardias

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

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Intravenous Amiodarone for Supraventricular Tachycardias

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

  2. Supraventricular Tachycardias: Therapeutic Objectives • Determine the mechanism of the arrhythmia • Restore sinus rhythm with the simplest technique and approach as possible • Eliminate or significantly reduce arrhythmia recurrences and underlying cause Singh 2002.

  3. Types of Supraventricular Tachyarrhythmias Sinus Node Reentry Atrial Flutter Automatic Atrial Tachycardia Reentrant Atrial Tachycardia Atrioventricular NodalReentry (AVNRT) AV Reentry via an AccessoryAV Connection (AVRT) Atrial Fibrillation (Not Shown) RA LA LV RV Singh 2002.

  4. Types of Paroxysmal Supraventricular Tachycardia AV ReciprocatingTachycardia Sinus Nodal Reentry Intra-atrial Reentry Automatic AtrialTachycardia AV NodalReentry

  5. Mechanisms of Paroxysmal Supraventricular Tachycardias Enhanced Automaticity: • Paroxysmal and Acute • Chronic Re-entry without Bypass Tracts: • AV Nodal Re-entry: Slow – Fast/Fast – Slow • Sinoatrial Nodal Re-entry • Intra-atrial Re-entry Re-entry in Association with Bypass Tracts: • Re-entry with Anterograde AV Conduction (Orthodromic) • With Evidence of Pre-excitation of 12-Lead ECG • Concealed WPW (Bypass Tract ConductingOnly Retrogradely) • Re-entry with Anterograde Conduction Over BypassTract (Antidromic) During Tachycardia

  6. Accessory Pathways: Concealed Bypass Tract AV Reentrant Tachycardia Concealed BypassTract AV Node Bundle of His Right Bundle Branch Left Bundle Branch P Singh 2002.

  7. Electrical Conduction in Atrial Flutter AV Node ECG of Flutter Ventricular Rate 150-160 (Most Often 2:1 AV Block)

  8. Atrial Fibrillation Electrocardiogram Coarse Fibrillation Fine Fibrillation Baseline Coarsely or Finely Irregular; P Waves Absent. Ventricular Response (QRS) Irregular, Slow or Rapid Scheidt S, Erlebacher JA, Netter FH. BasicElectrocardiography ECG. Ciba-Geigy: First Printing, 1986, p23.

  9. CV Diseases CT surgery Valvular orcongential disease Hypertension Cardiomyopathy Heart failure Myocardial ischemia/MI Peri/myocarditis Infiltrative heart disease Cardiac trauma Systemic Diseases Age DTs, sympathetic storm Electrolyte disorders Thyrotoxicosis Fever/hypothermia Hypovolemia Diabetes Anemia Pulmonary disease Cerebrovascular disease AF is Associated With

  10. Antiarrhythmic Drugs vs. Therapeutic Goal Vagal StimulationDigoxinb-Blocking DrugsVerapamilDiltiazemAdenosine Ibutilide Atrium AV Node QuinidineProcainamideDisopyramide FlecainidePropafenoneSotalolAmiodarone His Purkinje AP Ventricle Singh 2002.

  11. = Infusion without loading dose Simulated Drug Level Curves = “Full” loading dose = Half loading dose and infusion Therapeutic Concentration Range Plasma Drug Level 0 1 2 3 4 5 6 Time (Half-life) Levy 2002.

  12. 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.

  13. 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)

  14. 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.

  15. Unique Features of Amiodarone as an Anti-arrhythmic Drug • Long elimination half-life • Can be administered to anephric patientson dialysis • Well tolerated in advanced CHF • Manageable drug-drug interactions(ie, digoxin, coumadin) • Very low incidence of torsades de pointes even with diuretic therapy Singh 2002.

  16. Unique Features of Amiodarone as an Anti-arrhythmic Drug (Cont’d.) • Has Class 1 properties without the associated proarrhythmic actions or negative impact on mortality • Has antisympathetic actions withoutbeta-blocker side effects • Increases LVEF and improves CHF • Antifibrillatory actions in the ventricles may be augmented by addition of beta-blockade Singh 2002.

  17. Intravenous Amiodarone Pharmacokinetics • Peak levels after single 5 mg/kg15 min infusions: 5-41 mg/L • After 10 min 150 mg load for VF/VT:7-26 mg/L • Levels decline to 10% of peak within30-45 min at the end of the infusion • After 48 hrs of continued infusions,levels 0.7 to 1.4 mg/L Singh 2002.

  18. Pharmacokinetics of Oral Amiodarone • Absorption: Tmax:2-12 h (lab 0.4-3 h) • Extent of absorption: Poor and slow • Bioavailability: Variable (22-86%) • Protein binding: 96.3 ± 0.6% • Volume of distribution: 1.3-65.8 l/kg • Negligible renal excretion • Biotransformation: Hepatic and intestinal • Elimination half-life: 3.2-20.7 h (acute),13.7-52.6 day (chronic) Singh 2002.

  19. Pharmacokinetics of Oral Amiodarone • Total body clearance: 0.10-0.77 l/min • Pattern of elimination: First order • Metabolites: Major: mono N-desethylamiodarone, Minor: bis-N-desethylamiodarone, deiodinated metabolites • Therapeutic levels: 1.0-2.5 µg/mL range • Special factors: Slow onset and offsetof action Singh 2002.

  20. Actions of IV Amiodarone vs Chronic Amiodarone

  21. Actions of IV Amiodarone vs Chronic Amiodarone Singh 2002.

  22. Pharmacokinetics of IV Amiodarone Summary: More rapid onset and offsetof action with IV versus oral

  23. Comparison of Oral vs. IV Amiodarone:Conversion of Atrial Fibrillation • N=52 patients with atrial fibrillation • 86 episodes of attempted cardioversion with oral, intravenous, or DC cardioversion • Conversion 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.

  24. Efficacy of IV Amiodarone for the Conversion of Atrial arrhythmia

  25. 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 response Results: • 7/10 Amiodarone-treated patients, 10/14 Procainamide-treated patients converted to sinus rhythm by 12 hours • No significant change in SBP from baseline Chapman MJ et al Intensive Care Med 1993;19:48-52.

  26. 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) Results: • 16/34 (47.05%) amiodarone-treated patients vs. 13/32 (40.62%) propafenone-treated • Patients converted to sinus rhythm, P<0.001 • 1 propafenone-treated patient discontinued treatment because of QRS widening Kochiadakis GE et al J Am Coll Cardiol 1993;33:966-71.

  27. PIAF Trial Rhythm or Rate Control in Atrial Fibrillation Pharmacological Intervention in Atrial Fibrillation (PIAF): a Randomized Trial • 252 pts enrolled, 125 diltiazem, 127 amiodarone Methods: Pts randomized to diltiazem or amiodarone Results: • 76 pts on diltiazem, 70 on amiodarone reportedimproved symptoms, P=0.317 • 23% of amiodarone pts returned to sinus rhythm • amiodarone-treated pts did better on 6 min walk test than diltiazem Conclusion: 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.

  28. IV Amiodarone Treatment for Acute Heart Rate Control in Critically Ill Patients Methods • Retrospective study of 38 ICU patients • Pts received IV amiodarone for resistant atrial tachyarrhythmias • Onset of rapid heart rate (mean 149 ± 13 beats/min was associated with decrease in systolic blood pressure of 20 ± 5 mm Hg (P<0.05) Clemo HF, Wood MA, Gilligan DM, Ellenbogen KA. Am J Cardiol. 1998;81:594-8.

  29. IV Amiodarone Treatment for Acute Heart Rate Control in Critically Ill Patients • Intravenous diltiazem (n=34), esmolol(n=4), and digoxin (n=24) had no effect,while reducing systolic blood pressureof 6 ± 4 mm Hg (P<0.05) • Infusion of amiodarone (242 ± 137 mgover 1 hr decreased heart rate by 37 ± 8 beats/min and increased systolic blood pressure by 24 ± 6 mm Hg (P<0.05) • Beneficial outcomes noted inpulmonary artery occlusive pressureand cardiac output Clemo HF, Wood MA, Gilligan DM, Ellenbogen KA. Am J Cardiol. 1998;81:594-8.

  30. Caveats RegardingAmiodarone Dosing • Complex PK/PD with extremely longhalf life • Different efficacy rates with studies dueto dosing issues, and different patient populations

  31. Amiodarone IV for Atrial Arrhythymias: Summary • Effective in SVT, but best studied in AF • Acute IV therapy is different than chronic oral administration: dosing and PK needsto be considered • In critically ill patients, IV therapyis required

  32. Questions and Answers

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