9/7/2017 EMERGENT MANAGEMENT OF ARRHYTHMIAS ACCP Cardiology & Emergency Medicine PRN Joint Webinar Dr. Nicole Gasbarro, PharmD, BCPS Dr. Darrel Hughes, PharmD, BCPS Dr. James Tisdale, PharmD, FCCP, FAPhA, FAHA September 7, 2017 Disclosure Concerning possible financial or personal relationships with commercial entities (or their competitors) mentioned in this presentation, the speakers declare the following disclosures: Dr. Nicole Gasbarro, PharmD, BCPS None Dr. Darrel Hughes, PharmD, BCPS None Dr. James Tisdale, PharmD, FCCP, FAPhA, FAHA None RATE CONTROL STRATEGIES FOR ATRIAL FIBRILLATION WITH RAPID VENTRICULAR RESPONSE Nicole Gasbarro, PharmD, BCPS Clinical Pharmacy Specialist, Cardiology Boston Medical Center, Boston, Massachusetts 1 9/7/2017 Objective Assess the choice of rate control therapies for patients with atrial fibrillation (AF) with rapid ventricular response (RVR) with consideration of patient comorbidities and hemodynamic status. Atrial Fibrillation Treatment Approaches 1. Rate control Strict: HR < 80 bpm for symptomatic AF (COR IIa, LOE B) Lenient: HR < 110 bpm for asymptomatic AF (COR IIb, LOE B) 2. Rhythm control AF = atrial fibrillation, bpm = beats per minute, HR = heart rate, COR = class of recommendation, LOE = level of evidence Circulation.2014;130:2017‐104 Rate Control Agents Considerations Suspicion of an accessory pathway (ECG) Hemodynamic status Comorbidities Severity of symptoms Home medications Am J Health‐SystPharm.2016;73:2068‐76 2 9/7/2017 IV RATE CONTROL AGENTS IN PATIENTS WITHOUT PRE‐EXCITATION Beta Blockers Esmolol Metoprololtartrate Propranolol NondihydropyridineCalcium Channel Blockers Verapamil Diltiazem CardiacGlycoside Digoxin Other Amiodarone Circulation.2014;130:2017‐104 Rate Control: Beta blocker versus Diltiazem/Verapamil Lack of high‐quality randomized studies J EmergMed.2015;49:175‐82 Double blind study of 52 patients with AF (HR 137‐142) Primary efficacy outcome: HR < 100 within 30 min of drug admin Dosing 0.25 mg/kg diltiazem(max 30 mg) versus 0.15 mg/kg metoprolol (max 10 mg) Escalated at 15 min to 0.35 mg/kg vs. 0.25 mg/kg AF = atrial fibrillation, HR = heart rate J EMERGMED.2015;49:175‐82 Study Limitations • Convenience study • Low max dose of metoprolol • Many institutions use up to 3 doses of metoprolol 3 9/7/2017 IV Rate Control Agents Drug IV Administration Onset Potential Considerations Adverse Effects Beta Blockers –COR I, LOE B Esmolol 500 mcg/kg IV bolus over < 5 min Bradycardia, • Useful:cardiovascular 1 min then hypotension, disease, HFrEF(use 50‐300 mcg/kg/min IV heart failure, with caution), Metoprolol 2.5‐10mg IV bolus over 2 5 min atrioventricular thyrotoxicosis tartrate min; up to 3 doses block, dyspnea, • Caution:reactive bronchospasm airway disease Propranolol 1 mg IV over1 min, up to 5 min (asthma) 3 doses at 2 min intervals COR = class of recommendation; HFrEF= heart failure reduced ejection fraction; LOE = level of evidence Circulation.2014;130:2017‐104 European Heart Journal.2016;37:2893‐2962 IV Rate Control Agents Drug IV Administration Onset Potential Considerations Adverse Effects NondihydropyridineCalciumChannel Blockers –COR I, LOE B Verapamil • 0.075‐0.15mg/kg IV bolus over 3‐5 min Bradycardia, • Avoid:HFrEF 2 min hypotension, • Useful: Reactive airway • If no response, may give an heart failure disease, hypertension additional 10.0 mg after 30 min • Caution with hepatic and • Then begin 0.005 mg/kg/min renal dysfunction infusion • Verapamil may increase Diltiazem • 0.25 mg/kg IV bolus over 2 min 2‐7 min digoxin concentration if • If no response, may repeat dose used in combination of 0.35 mg/kg after 15 min • Thenbegin 5‐15 mg/hrinfusion x 24 hours COR = class of recommendation; HFrEF= heart failure reduced ejection fraction; LOE = level of evidence Circulation.2014;130:2017‐104 Pharmacotherapy.1997; 17(6):1238‐1245 DiltiazemHClPowder for Solution package insert. Lake Forest, IL: Hospira, Inc.; 2008 Hypotension Concerns with CCB Symptomatic hypotension IV diltiazem ~ 3%, IV verapamil ~ up to 10% Alternative diltiazem dosing strategies in practice?? Reduction of IV bolus dose Elimination of IV bolus prior to continuous infusion Pre‐treatment with IV calcium Am J Cardiol.1989;63:1046‐1051 Pharmacotherapy.1997;17(6):1238‐1245 Diltiazem HClPowder for Solution package insert. Lake Forest, IL: Hospira, Inc.; 2008 4 9/7/2017 IV Calcium Prior to CCB Administration Citation Design N Drug Calcium Dose Results KolkebeckT, et al. J Emerg Prospective, randomized, 34 Diltiazem Calciumchloride 0.333 g SBP decreased 8 Med.2004;26(4):395‐400 double‐blind, placebo‐controlled mmHg (PlaceboSBP decreased 14 mmHg) MiyagawaK, et al. J Sequential study of 2 treatment 7 Verapamil Calcium gluconate3.75 Nochange in SBP Cardiovasc protocols mg/kg Pharmacol.1993;22:273‐9 Kuhn M, et al. Am Heart Retrospective chart review 18 Verapamil Calcium gluconate 3 g or No hypotension J.1992;124:231‐2 Calciumchloride 1 g Barnett JC, et al. Prospective report of protocol 19 Verapamil Calcium gluconate 1 g or SBP increased 4 mmHg Chest.1990;97:1106‐9 Calcium chloride1 g Haft JL, et al. ArchIntern Sequential study of 2 treatment 50 Verapamil Calcium chloride 1 g SBP increased 2 mmHg Med.1986;146:1085‐9 protocols Bottom Line: Lack of high quality literature CCB = calcium channel blocker; SBP = systolic blood pressure Ann Pharmacother.2000:34:622‐9 IV Rate Control Agents Drug IV Administration Onset Potential Adverse Considerations Effects Cardiac Glycoside –COR IIbLOEC (ACS),COR I LOE B (acute HF) Digoxin* 0.25 mg IV with repeat dosing 30‐180 GI complaints, • Useful: in combination with to a maximum of 1.5 mg over min heart block, aBB for patient with HFrEF 24 hrs ventricular • Dose adjustment with renal arrhythmias dysfunction, elderly, drug interactions Other –COR IIbLOEC (ACS),COR I LOE B (acute HF) Amiodarone* 300 mg IV over 1 hr, then 10 – < 20 min Hypotension, • Useful:in patients with 50 mg/hrover 24 hrs prolongedQT, hemodynamic instability or bradyarrhythmias severelyreduced left ventricular EF • Consideration of length of time of AF onset *Multiple dosing schemes exist ACS = acute coronary syndrome; COR = class of recommendation; HFrEF= heart failure reduced ejection fraction; LOE = level of evidence Circulation.2014;130:2017‐104 IV Rate Control Agents Drug IV Administration Onset Potential Adverse Effects Considerations AdjunctiveTherapy? –Not in guidelines Magnesium 2 g over 15 min < 5 min Hypotension, respiratory • Can accumulate rapidly in muscle fatigue, cardiac patients with renal failure pauses at high doses Ann EmergMed.2005;45(4):347 • Prospective, randomized, double‐blind, placebo‐controlled study of 199 patients • Safety and efficacy of magnesium sulfate infusion in addition to usual care for acute rate reduction • Magnesium sulfate 2.5 g over 20 min, then 2.5 g over 2 hours or placebo • Results: • Magnesium increased likelihood of achieving a ventricular rate < 100 beats/min (65% vs. 34%, RR 1.89; CI 1.38 to 2.59; p < 0.001) • Limitations Bottom Line: Lack of high quality literature 5 9/7/2017 Approach to Selecting Drug Therapy for Ventricular Rate Control Atrial Fibrillation Final Considerations • Lack of high quality evidence for choosing one NoD oistehaesre CV HHTFNp EoFr Dyosrf uHLnVFcr EtiFon Rdaeiisarewcataisvyee raantoet choenrtrol class over • Patient specific characteristics key NBoenta‐D BHloPc CkeCrB NBoenta‐D BHloPc CkeCrB BetDa iBgoloxcinker* NBeotna‐ DBHloPc kCeCrB* • More than 1 rate control may be needed • Don’t forget about PO! * With caution Amiodarone CCB = calcium channel blocker, HF = heart failure, HFpEF= heart failure with preserved ejection fraction, HTN = hypertension, LV = left ventricular, Non‐DHP = non‐dihydropyridine Circulation.2014;130:2017‐104 Case AB is a 58 yomale who presents from clinic for new onset AF. His symptoms of shortness of breath and dizziness started abruptly earlier that day and have steadily become worse. His pulse ranges between 130 –175 bpm, while his blood pressure is holding steady at 106/58 mmHg. The decision is made to administer an IV medication for rate control. Which agent do you recommend? PMH: hypertension, dyslipidemia Home meds: hctz25 mg and atorvastatin 20 mg daily ECG: narrow QRS complex tachycardia with an irregularly irregular rhythm RHYTHM CONTROL STRATEGIES FOR ATRIAL FIBRILLATION WITH RAPID VENTRICULAR RESPONSE Darrel W. Hughes, PharmD, BCPS Clinical Specialist, Emergency Medicine University Health System & UT Health San Antonio, Texas 6 9/7/2017 Objective Describe rhythm control strategies for recent onset atrial fibrillation (AF) with rapid ventricular response. Perspective Atrial Fibrillation Classifications •Recent Onset ‐ < 48 hours •Paroxysmal ‐ Terminates spontaneously or with intervention within 7 days of onset •Recurrent –Two or more episodes of AF •Persistent ‐Continuous AF lasting >7 days •Longstanding ‐Continuous AF >12 months of duration •Permanent ‐No more active attempts to restore/ maintain sinus rhythm J Am Coll Cardiol. 2014;64:e1‐e76. Lancet 2012; 379: 648–61. 7 9/7/2017 Goals •In patients presenting with newly diagnosed atrial fibrillation, the short‐term treatment goal should be control of their symptoms with rate or rhythm control therapies J Am Coll Cardiol. 2014;64:e1‐e76. Lancet 2012; 379: 648–61. Rate vs. Rhythm Control •Limitations of literature •Chronic AF patients •Many had heart failure •Did not include •Paroxysmal AF at low risk of recurrence •Recent‐onset AF •Low risk of thromboembolism How To Choose Rate control Rhythm control • Aged >65 years • Symptomatic patients • No history of congestive heart • Newly detected lone atrial fibrillation failure • No hypertension • Failure or contraindications to antiarrhythmic drugs • HFrEFtriggered by atrial fibrillation • Hypertension • No previous failure of antiarrhythmic • Coronary artery disease drugs • Unsuitable for cardioversion • Atrial fibrillation secondary to a treated/corrected precipitant 8 9/7/2017 Emergency Management of AF •Assess for hemodynamic instability •Identify and treat underlying/precipitating causes of AF •Assess patient history for risk of thromboembolism •Consider emergent cardioversion Is 48 hours Safe for Cardioversion? •Weigneret al, 1997 •357 patients with AF < 48 hours who were converted to NSR •3 thromboembolic events •>80 years old after spontaneous conversion •von Besseret al, 2011 •Review of 5 articles addressing safety of ED cardioversion •No thromboembolic events reported in total any of the studies (n≈ 1700 visits) 26 Lancet 2012; 379: 648–61 9 9/7/2017 What is Hemodynamic Instability •Chest Pain •Altered Mental Status/light headedness •Shortness of breath/pulmonary edema •Symptomatic hypotension Methods of Cardioversion Pharmacologic Electrical Advantages Advantages •No need for conscious sedation or anesthesia •Higher success rate •Might enhance subsequent electrical •For longstanding atrial fibrillation cardioversion Disadvantages Disadvantages •Need for conscious sedation or anesthesia •Need for continuous ECG monitoring •Skin burn •Proarrhythmiceffects •Thromboembolic risk •Thromboembolic risk •Potential interference with medical device •Low success rate for longstanding AF Lancet 2012; 379: 648–61 Synchronized Cardioversion •Direct current cardioversion (DCC) •Synchronization to an R or S wave prevents the delivery of a shock duringthe vulnerable period of cardiac repolarization when VF can be induced. 10
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