EMERGENT MANAGEMENT OF ARRHYTHMIAS

Transcription

1 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

2 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: Rate Control Agents Considerations Suspicion of an accessory pathway (ECG) Hemodynamic status Comorbidities Severity of symptoms Home medications Am J Health Syst Pharm.2016;73:

3 IV RATE CONTROL AGENTS IN PATIENTS WITHOUT PRE EXCITATION Beta Blockers Esmolol Metoprolol tartrate Propranolol Nondihydropyridine Calcium Channel Blockers Verapamil Diltiazem Cardiac Glycoside Digoxin Other Amiodarone Circulation.2014;130: Rate Control: Beta blocker versus Diltiazem/Verapamil Lack of high quality randomized studies J Emerg Med.2015;49: Double blind study of 52 patients with AF (HR ) 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 mg/kg AF = atrial fibrillation, HR = heart rate J EMERG MED.2015;49: Study Limitations Convenience study Low max dose of metoprolol Many institutions use up to 3 doses of metoprolol 3

4 IV Rate Control Agents Drug IV Administration Onset Potential Adverse Effects Beta Blockers COR I, LOE B Esmolol Metoprolol tartrate Propranolol 500 mcg/kg IV bolus over 1 min then mcg/kg/min IV mg IV bolus over 2 min; up to 3 doses 1 mg IV over 1 min, up to 3 doses at 2 min intervals < 5 min Bradycardia, hypotension, heart failure, 5 min 5 min atrioventricular block, dyspnea, bronchospasm Considerations Useful: cardiovascular disease, HFrEF (use with caution), thyrotoxicosis Caution: reactive airway disease (asthma) COR = class of recommendation; HFrEF = heart failure reduced ejection fraction; LOE = level of evidence Circulation.2014;130: European Heart Journal.2016;37: IV Rate Control Agents Drug IV Administration Onset Potential Adverse Effects Nondihydropyridine Calcium Channel Blockers COR I, LOE B Verapamil mg/kg IV bolus over 2 min If no response, may give an additional 10.0 mg after 30 min Then begin mg/kg/min infusion Diltiazem 0.25 mg/kg IV bolus over 2 min If no response, may repeat dose of 0.35 mg/kg after 15 min Then begin 5 15 mg/hr infusion x 24 hours Circulation.2014;130: Pharmacotherapy.1997; 17(6): Diltiazem HCl Powder for Solution package insert. Lake Forest, IL: Hospira, Inc.; min Bradycardia, hypotension, heart failure 2 7 min COR = class of recommendation; HFrEF = heart failure reduced ejection fraction; LOE = level of evidence Considerations Avoid: HFrEF Useful: Reactive airway disease, hypertension Caution with hepatic and renal dysfunction Verapamil may increase digoxin concentration if used in combination 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: Pharmacotherapy.1997;17(6): Diltiazem HCl Powder for Solution package insert. Lake Forest, IL: Hospira, Inc.;

5 IV Calcium Prior to CCB Administration Citation Design N Drug Calcium Dose Results Kolkebeck T, et al. J Emerg Med.2004;26(4): Miyagawa K, et al. J Cardiovasc Pharmacol.1993;22:273 9 Kuhn M, et al. Am Heart J.1992;124:231 2 Barnett JC, et al. Chest.1990;97: Haft JL, et al. Arch Intern Med.1986;146: Prospective, randomized, double blind, placebo controlled Sequential study of 2 treatment protocols 34 Diltiazem Calcium chloride g SBP decreased 8 mmhg (Placebo SBP decreased 14 mmhg) 7 Verapamil Calcium gluconate 3.75 mg/kg Retrospective chart review 18 Verapamil Calcium gluconate 3 g or Calcium chloride 1 g Prospective report of protocol 19 Verapamil Calcium gluconate 1 g or Calcium chloride 1 g Sequential study of 2 treatment protocols No change in SBP No hypotension SBP increased 4 mmhg 50 Verapamil Calcium chloride 1 g SBP increased 2 mmhg 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 Effects Cardiac Glycoside COR IIb LOE C (ACS), COR I LOE B (acute HF) Digoxin* 0.25 mg IV with repeat dosing to a maximum of 1.5 mg over 24 hrs Other COR IIb LOE C (ACS), COR I LOE B (acute HF) Amiodarone* 300 mg IV over 1 hr, then mg/hr over 24 hrs min GI complaints, heart block, ventricular arrhythmias Considerations Useful: in combination with a BB for patient with HFrEF Dose adjustment with renal dysfunction, elderly, drug interactions < 20 min Hypotension, Useful: in patients with prolonged QT, hemodynamic instability or bradyarrhythmias severely reduced 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: IV Rate Control Agents Drug IV Administration Onset Potential Adverse Effects Considerations Adjunctive Therapy? Not in guidelines Magnesium 2 g over 15 min < 5 min Hypotension, respiratory muscle fatigue, cardiac pauses at high doses Can accumulate rapidly in patients with renal failure Ann Emerg Med.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

6 Approach to Selecting Drug Therapy for Ventricular Rate Control No other CV Disease Beta Blocker Non DHP CCB Atrial Fibrillation HTN or HFpEF Non DHP CCB Beta Blocker Amiodarone LV Dysfunction or HFrEF Beta Blocker* Digoxin Reactive airway disease Non DHP CCB Beta Blocker* * With caution Final Considerations Lack of high quality evidence for choosing one rate control class over another Patient specific characteristics key More than 1 rate control may be needed Don t forget about PO! 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: Case AB is a 58 yo male 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 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: hctz 25 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

7 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:

8 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: 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 Aged >65 years No history of congestive heart failure Failure or contraindications to antiarrhythmic drugs Hypertension Coronary artery disease Unsuitable for cardioversion Rhythm control Symptomatic patients Newly detected lone atrial fibrillation No hypertension HFrEF triggered by atrial fibrillation No previous failure of antiarrhythmic drugs Atrial fibrillation secondary to a treated/corrected precipitant 8

9 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? Weigner et al, patients with AF < 48 hours who were converted to NSR 3 thromboembolic events >80 years old after spontaneous conversion von Besser et 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:

10 What is Hemodynamic Instability Chest Pain Altered Mental Status/light headedness Shortness of breath/pulmonary edema Symptomatic hypotension Methods of Cardioversion Pharmacologic Advantages No need for conscious sedation or anesthesia Might enhance subsequent electrical cardioversion Disadvantages Need for continuous ECG monitoring Proarrhythmic effects Thromboembolic risk Low success rate for longstanding AF Electrical Advantages Higher success rate For longstanding atrial fibrillation Disadvantages Need for conscious sedation or anesthesia Skin burn Thromboembolic risk Potential interference with medical device Lancet 2012; 379: Synchronized Cardioversion Direct current cardioversion (DCC) Synchronization to an R or S wave prevents the delivery of a shock during the vulnerable period of cardiac repolarization when VF can be induced. 10

11 Procedural Sedation Meds for DCC Fentanyl Opioid analgesic Quick onset Dose 1 mcg/kg iv push Etomidate OR Sedative hypnotic that lacks analgesia Quick on and off Dose 0.15 ( ) mg/kg iv push Plus Midazolam Benzodiazepine sedative/hypnotic Quick on Dose 0.05 mg/kg iv push up to 5 mg Consider Avoiding Ketamine tachycardia Propofol hypotension RHYTHM CONTROL AGENTS FOR CHEMICAL CARDIOVERSION Drug Administration Efficacy & Onset Adverse Events Amiodarone 150 mg IV over 10 min Infusion at 1 mg/min (360 mg) over next 6 h; then 0.5 mg/min (540 mg) over remaining 18 h 34 95% Usually >24 h Hypotension, bradycardia, phlebitis, QT prolongation, torsades de pointes (rare), increased INR, drug interactions Ibutilide* 1 mg over 10 min (if 60 kg) If <60 kg, then 0.01 mg/kg 50 71% at 90 min (usually 30 min) QT prolongation, torsades de pointes, AV block Procainamide mg/kg over 1 hour 1000 mg over 1 hour 50 60% at 1 hour Hypotension, QRS widening *Contraindicated QTc > 440 msec; pretreatment with magnesium sulfate may reduce post ibutilide ventricular arrhythmias Can J Cardiol. 2011;27(1): J Am Coll Cardiol. 2014;64(21):e1 e76. CJEM. 2010;12(3): Amiodarone Pearls Controls heart rate in minutes Rhythm control typically takes at least 6 hours Ensure anticoagulation is onboard for AF > 48 h duration Doses should be prepared in non PVC bags 11

12 Ibutilide Pearls Ensure adequate magnesium supplementation regardless of current serum magnesium level prior to administration Works fast, but must be given slow IV push Cardiologist at bedside Continuous ECG monitoring Stop the dose as soon as rhythm is restored Procainamide Pearls Preferred agent for pre excitation AF Loading doses may be run up to 50 mg/min Terminate load for hypotension, QRS widening by greater than 50%, or total of 17 mg/kg given Ottawa Protocol calls for 1,000 mg over 1 hour (~17 mg/min) Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy Case AB is a 58 yo male 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 bpm. While his blood pressure is holding steady at 106/58 mmhg, the nurse reports that he is know altered. What is your plan for AB? PMH: hypertension, dyslipidemia Home meds: hctz 25 mg and atorvastatin 20 mg daily ECG: narrow QRS complex tachycardia with an irregularly irregular rhythm 12

13 PHARMACOLOGIC AND NON PHARMACOLOGIC THERAPIES FOR VENTRICULAR ARRHYTHMIAS James E. Tisdale, PharmD, FCCP, FAPhA, FAHA Professor Department of Pharmacy Practice College of Pharmacy Purdue University & Adjunct Professor School of Medicine Indiana University Indianapolis, IN Objective Compare and contrast pharmacologic and nonpharmacologic therapies for patients with ventricular arrhythmias Emergent Ventricular Arrhythmias Monomorphic ventricular tachycardia Torsades de pointes (TdP) Pulseless ventricular tachycardia/ventricular fibrillation 39 13

14 Emergent Ventricular Arrhythmias Monomorphic ventricular tachycardia Torsades de pointes (TdP) Pulseless ventricular tachycardia/ventricular fibrillation 40 Monomorphic Ventricular Tachycardia Tisdale JE. Acute management of arrhythmias. In: Erstad B, ed. Critical Care Pharmacotherapy, ACCP, 2016 Circulation 2010;122(Suppl 3):S729 S Monomorphic Ventricular Tachycardia 90 Comparative Studies of Drug Efficacy for Termination of Ventricular Tachycardia Termination of VT (%) p=0.03 p<0.01 p< Lancet 1994;344:18 23 (n=33) Am J Cardiol 1996;78:43 6 (n=29) Am J Cardiol 2002;90:853 9 (n=29) Sotalol Lidocaine Procainamide Amiodarone 14

15 Emergent Ventricular Arrhythmias Monomorphic ventricular tachycardia Torsades de pointes (TdP) Pulseless ventricular tachycardia/ventricular fibrillation 43 Drug Induced TdP Drugs withdrawn due to TdP deaths: Cisapride, terfenadine, astemizole, grepafloxacin > 150 drugs with risk of TdP remain available: Cardiovascular: Dofetilide, sotalol, ibutilide, quinidine, procainamide, amiodarone, dronedarone Noncardiovascular: Quinolones, macrolides, antifungals Methadone Antipsychotics, antidepressants, Many others QT drugs lists on 44 Risk Factors for Drug Induced TdP QT c > 500 ms Female sex Age > 65 years Hypokalemia Hypomagnesemia Heart failure Bradycardia Genetic predisposition Sepsis Elevated plasma concentrations of QT prolonging drugs Multiple QTc interval prolonging drugs Curr Med Res Opin 2013;29: Circ CV Qual 2013;6:

16 Torsades de Pointes Management Tisdale JE. Acute management 46 of arrhythmias. In: Erstad B, ed. Critical Care Pharmacotherapy, ACCP, 2016 Evidence for Magnesium for Management of TdP Study Design Population Magnesium dose Results Circulation 1988;77: Observational Herz 1997;22 Observational Suppl 1: n=12 consecutive patients who developed TdP n=10 women Age year n=4 patients with TdP 2g IV bolus over 1 2 minutes, followed (in n=9 patients) by continuous infusion of 3 20mg/minute TdP terminated after IV bolus of 2g (n=9) TdP terminated after 2 nd bolus of 2g and during continuous infusion (n=3) 2 x 1g IV boluses TdP terminated in all 4 patients TdP = Torsades de pointes 47 Emergent Ventricular Arrhythmias Monomorphic ventricular tachycardia Torsades de pointes (TdP) Pulseless ventricular tachycardia/ventricular fibrillation 48 16

17 Pulseless VT/Ventricular Fibrillation Circulation 2015;132(Suppl 2):S444 S Pulseless VT/Ventricular Fibrillation Survival to hospital admission (%) Survival to hospital admission (%) Comparative Studies of Drug Therapy for Patients with Out of Hospital Cardiac Arrest due to Pulseless VT or VF p=0.03 p=0.03 A vs P, p=0.08 L vs P, p=0.16 A A vs vs L, P, p=0.70 p=0.08 p=0.009 L vs P, p=0.16 A vs L, p=0.70 p=0.009 Survival to hospital discharge (%) Survival to hospital discharge (%) 0 NEJM 1999;341:871 8 (n=504) NEJM 2002;346: (n=347) NEJM 2016;374: (n=3026) Amiodarone Placebo Lidocaine 50 17

18 Questions? library/atrial fibrillation/ 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,