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Angela Mund CRNA DNPAANA Region 2 DirectorAssociate Professor and Division DirectorMedical University of South Carolina

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¡ Discuss the cardiac action potential and the relevance to pharmacologic interventions

¡ Describe the Vaughn-Williams Classification¡ Discuss clinical application and decision

making for nurse anesthesia

¡ Incidence of chronic AF¡ Incidence of new onset POAF

§ Non-cardiac, non-thoracic minor surgery 1%§ Vascular or colorectal surgery 5-10%§ Lung resections or esophagogastrectomy 10-30%§ CABG 30%§ Valve 40%§ CABG +valve 50%

Philip, et al 2014 Normal electrophysiology impulses

Ion changes in the cardiac cell

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w.pathophys.org

Sodium Channels: resting–activated-inactivated

Most sodium channels are inactivated/unavailable

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¡ Spontaneous depolarization occurs during phase 4

¡ Gradual increase of depolarizing current through special hyperpolarization-activated ion channels

¡ Ectopic pacemaker cells more effected by changes in potassium levels (as compared with SA node)

ArrhythmiaDefinition

¡ Disturbances of conduction§ Reentry▪ “circus arrhythmias”

▪ One pathway or multiple pathways▪ Round trips determine the duration of the arr.

▪ Needs: Obstacle, unidirectional block, conduction time§ If conduction is too slow – bidirectional block▪ Depression of sodium or calcium currents

§ If conduction is too rapid –bidirectional conduction▪ Reaches refractory tissue and may die out

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¡ Disturbances of impulse formation§ Interval between depolarizations = sum of the duration of

the AP and duration of the diastolic interval▪ Shortening of either results in an increase in pacer rate

§ Diastolic interval (slope of phase 4)▪ Duration determines chronotropy▪ Decreased slope = slower HR▪ Increased slope = higher HR

§ Afterdepolarizations▪ Early: related to long QT syndrome▪ Delayed: related to catecholamines, myocardial

ischemiahttp://www.cvphysiology.com/Arrhythmias/A003.htm

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Primary effects are on ectopic pacemakers cells rather than the SA nodeReduce excitability and increase refractory periods in depolarized tissue (rather than normal polarized tissue)Use-dependent blockadeDrug induced arrhythmias

¡ Class I§ Sodium channel blockers: § Divided up into subclasses based on the effect on the

action potential duration¡ Class II

§ Sympatholytic ¡ Class III

§ Potassium channel blockers with prolongation of APD

¡ Class IV§ Calcium channel blockers: slows conduction in SA

and AV node

Sodium channel blockers

Local anesthetic properties

Divided into 1A, 1B, and 1C

http://www.cvpharmacology.com/antiarrhy/sodium-blockers.htm

¡ Direct depressant effects on SA and AV conduction

¡ Most effective on inactivated Na channels¡ Reduces PVR and may cause hypotension

§ Relationship with fast IV push and underlying LV dysfunction

¡ Toxicity§ Excessive AP prolongation§ Prolonged QT with induction of torsades§ Long-term use

¡ Usage

§ Ventricular arr. (off label

atrial arr.)

§ Typically a third line

drug

¡ 3-4 hour half-life

§ Need for SR dosing

¡ Dosing

§ IV, IM, and oral dosing

§ IV dose: 12 mg/kg slow

bolus then 1-4 mg/min

¡ Active metabolite

§ Hepatic metabolism

▪ NAPA: issues with

renal pts – implicated

with torsades- long

half-life

§ Renal excretion

▪ Reduce dose in RF

patients

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¡ Slows upstroke and conduction; prolongs QRS¡ Prolong APD: influence on K channels (blockade)¡ Metabolized in the liver (inhibits P450s) and 20% renally

excreted§ Can increase levels of BB, lidocaine, and opioids

¡ Issues with GI tolerance¡ Rarely used except in patients who have been on long term,

effective therapy

¡ Usage§ Ventricular arr.

¡ Anti-muscarinic effects§ Similar effects as atropine (opposite of SLUDGE)§ Need to add drug that slows conduction

¡ Toxicity§ Negative inotrope: caution in HF patients

¡ Dosage§ Oral administration

¡ Least cardiotoxic of all Class I drugs§ Very few pro-arrhythmic effects§ In large doses: myocardial depressant with hypotension

¡ Greater effects on ventricular and Purkinje cells (as compared with atrial)§ Rapid recovery

¡ Most effective on open Na++ channels¡ Patients with acute MI or acute illness will tolerate higher

concentrations

¡ Extensive first pass effect§ IV administration only

¡ Half-life of 1-2 hours¡ Dosing

§ Bolus (1mg/kg – 1.5 mg/kg)

§ Infusion (2-4 mg/min)¡ Ventricular arr. And

prevention of VF after cardioversion

¡ No prophylaxis

¡ Toxicity§ CNS

¡ Heart failure§ Decrease loading and

maintenance dose¡ Liver failure

§ Decrease maintenance dose

§ No change to load¡ Renal disease

§ No change

¡ Orally active lidocaine ¡ Elimination half-life 8-20 hours¡ Dose related adverse effects:

§ Predominately neurologic (tremor, blurred vision, lethargy)

¡ May be useful in chronic pain management and radicular pain§ Dose 450-750mg/d (smaller than arr doses)

¡ Potent sodium and potassium channel blocker

§ Does not prolong APD or the QT duration¡ Used with patients with normal cardiac function and SVT¡ May have pro-arrhythmic properties in patients with prior MI

and ventricular ectopy¡ Long half-life – 20 hours¡ CAST trial: large RCT. Use of class I meds to block

asymptomatic arr after MI. Successfully blocked PVCs but increased mortality rate

§ Contraindicated in patients with prior MI or heart disease with reduced LV function

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¡ Na++ channel blocker but does not prolong APD¡ Has some beta-antagonist activities and inward K+ current

inhibition¡ Metabolized in the liver¡ Half-life 4-7 hours¡ Used for SVTs¡ Can exacerbate arrhythmias or cause ventricular arrhythmias¡ Contraindicated in patients with prior MI or heart disease

with reduced LV function

Beta adrenoreceptor blocking agentsLimited antiarrhythmic effects except rate controlCan be used for both VT and SVT

¡ Competitively binds to B1 receptors and prevent catecholamines from producing positive chronotropic and inotropic responses

¡ Augments coronary perfusion¡ Decreased automaticity in the SA and AV node; His-Purkinje

system; atria and ventricles§ Slows ventricular response§ Prolongs PRI

¡ Reduces ectopic pacemaker depolarization

¡ Selective B1

¡ Extensive liver metabolism (CYP2D6)

¡ Renal excretion 10% unchanged

¡ Mild lipid solubility

¡ Half-life 3-4 hours

¡ Okay in “mild” HF

¡ Dose

§ 1-5 mg IVP up to 15 mg

¡ Side effects

§ B2 effects can occur with high doses

¡ B1 selective¡ Half-life 8-9 minutes¡ Ester hydrolysis¡ Low lipid solubility¡ Dosing

§ For infusion: load 0.5mg/kg then infusion 50mcg/kg/min up to 300mcg/kg/min

§ Anesthesia dosing: 10-100mg IVP

¡ High dose glucagon§ 5-10mg IV then infusion

¡ Isuprel¡ Epinephrine

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Prolong effective refractory period by prolonging APD“Reverse use dependence”QT prolongation

http://www.cvpharmacology.com/antiarrhy/potassium-blockers.htm

¡ Marked prolongation of QT interval§ Does not have reverse use dependence

¡ Broad spectrum of actions§ High efficacy and low incidence of torsades§ Slowing of heart rate and AV nodal conduction

¡ Oral and IV use¡ Management of serious ventricular arrhythmias¡ Management of atrial fibrillation

¡ Peripheral vasodilation¡ Toxicity

§ Symptomatic bradycardia and heart block▪ Underlying sinus or AV nodal disease

§ Pulmonary toxicity▪ Can occur (but rarely) with low doses

§ Abnormal LFTs§ Skin deposits and asymptomatic corneal deposits§ Hypo- or hyperthyroidism▪ Blocks conversion of T4-T3 or exogenous source of

iodine

¡ Variable bioavailability¡ Hepatic metabolism with active metabolite

§ CYP450 inhibitor¡ No - minimal renal elimination¡ Prolonged duration of action (up to months oral dosing; 8-

14 hours IV)

§ High lipid solubility and binding to tissues¡ Perioperative dosing

§ Load: 150-300mg

§ Infusion: 1mg/min x6 hrs; 0.5 mg/min x 18 hrs¡ Monitor for AV block with bradycardia **; QT prolongation

¡ Similar to amiodarone§ Developed to remove issues with thyroid and pulmonary

complications§ Approved in 2009 (most recently approved

antiarrhythmic)¡ Multichannel actions

§ K, Ca, and Na¡ Used to restore SR¡ Not used for persistent AF = increased risk of death¡ Not used in patients with class IV HF (FDA black box

warning)

¡ Has both Class II and Class III actions¡ Well absorbed orally¡ Not metabolized in the liver or protein bound¡ Eliminated in the kidneys¡ Dose related risk of torsades de pointes¡ Use

§ Treatment of life-threatening vent arr and maintenance of SR in patients with AF

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¡ Selectively blocks rapid component of the K current§ Increases refractory period§ Increases QTc

¡ High bioavailability¡ Metabolism 20% liver P450s¡ Excreted 80% unchanged in the kidneys¡ Used for maintenance of SR after conversion out of AF¡ Significant pro-arrhythmic effects

Calcium channel antagonists

¡ Blocks activated and inactivated L-type Ca++ channels§ Acts on tissue with frequent firing ▪ Consistently prolongs AV conduction▪ Slows SA node conduction ▪ Hypotensive effect may increase HR

§ Does not affect accessory pathways¡ Extensively metabolized in the liver (half-life 3-7 hours)¡ Renal excretion: 70%¡ Low bioavailability and highly protein bound

¡ May cause peripheral vasodilation¡ Caution with pts with low EF¡ Careful with administration in patients with VT

§ May cause hypotension and VF¡ AF: better for rate control than conversion¡ May potentiate paralytics¡ IV dosing for SVT

§ 2.5-10 mg then infusion 5mcg/kg/min§ Max dose of 20mg

¡ IV Ca++ prior to administration may counter vasodilation effects

¡ May have less hypotension than verapamil¡ Half-life

§ 4 hours¡ Dosing

§ 5-20 mg or 0.25 mg/kg

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¡ Naturally occurring nucleotide

¡ Very short half-life (10 seconds)

¡ Directly inhibits AV nodal conduction and increases

refractory period

§ Less effect on SA node

§ Works on accessory pathway arr with WPW

¡ Hyperpolarization and suppression of Ca++ dependent action

potentials

§ Interaction with A1 receptor – efflux of K+ from the cell

¡ Drug of choice for conversion of PSVT § Not for AF/F

¡ Dose§ Bolus 6mg then 12 mg

¡ Less effective: Adenosine receptor blockers ¡ More effective: Adenosine uptake inhibitors¡ Side effects

§ Flushing, headache, chest discomfort, nausea§ Transient AV block§ Bronchospasm (rare)

¡ Vernakalant¡ Ranolazine¡ Dantrolene (???)¡ Upstream Therapy

¡ Prevention of atrial fibrosis§ RAAS inhibitors▪ ACEI▪ ARB

¡ Prevention of atrial tissue inflammation§ Glucocorticoids§ Omega-3 FA§ HMGCoA inhibitors

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• Brady, tachy, or irregular• First: look at the patient ?stable vs. unstable • Evaluate and determine the clinical variables underlying the

arrhythmia• Consider rate reduction strategies• Correctly evaluate the arrhythmia• Underlying patient pathology• Underlying cardiac disease

Date of download: 8/24/2015 Copyright © 2015 American Society of Anesthesiologists. All rights reserved.

Fig. 1. AF = atrial fibrillation–flutter; DC = direct current; bpm = beats/min; LV = left ventricular; TIA = transient ischemic attack; CVA = cerebrovascular accident.

Figure Legend:

From: Perioperative Atrial TachyarrhythmiasAnesthesiology. 2002;97(6):1618-1623.

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¡ Amar, D. (2002) Perioperative Atrial Tachyarrhythmias. Anesthesiology, 97(2), 1618-1623.

¡ Amar, D (2004). Strategies for Perioperative Arrhythmias. Best Practice and Clinical Anesthesiology, 18(4), 565-577.

¡ Amar, D. (2008). Prevention and Management of Perioperative Arrhythmias in the Thoracic Surgical Population. Anesthesiology Clinics, 26, 325-335.

¡ ASA/AHA 2014 Joint Statement and Guidelines on Management of Atrial Fibrillation ¡ Dobrev, D & Nattel, S (2010). New antiarrhythmic drugs for treatment of atrial

fibrillation. The Lancet, 375, 1212-1223.¡ Gerstein, NS., Gerstein, WH, Carey, MC, Lam, NCK, Ram, H., Spassil, NR & Schulman,

PM. (2014) The thrombotic and arrhythmogenic effects of NSAIDs. Journal of Cardiothoracic and Vascular Anesthesia, 28(2), 369-378.

¡ Heijman, J., Voigt, N., & Dobrev, D. (2013) New Directions in Antiarrhythmic Drug Therapy for Atrial Fibrillation, Future Cardiology, 1, 71-88.

¡ Katsung, Masters, & Trevor (2012). Basic and Clinical Pharmacology, 12th ed. ¡ Philip, I., Berroeta, C., & Leblanc, I. (2014). Perioperative challenges of atrial

fibrillation. Current Opinion, 3(27), 344-352. ¡ Stoelting. Pharm and Phys in Anesthesia practice 4th ed