Cv ii patho pharm fall 11

Disorders of Cardiac FunctionDisorders of Cardiac FunctionNURS 315/501NURS 315/501

Kathryn T. Von Rueden RN, MS, FCCMKathryn T. Von Rueden RN, MS, FCCM

University of MarylandUniversity of Maryland

School of NursingSchool of Nursing

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Global Tissue OxygenationGlobal Tissue OxygenationMade Ridiculously SimpleMade Ridiculously Simple

SvO2 = 75%

25%

Venous Oxygen Delivery

ArterialOxygenDelivery

Oxygen Consumption

100%

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Coronary Coronary CirculationCirculation

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Cardiac Conduction SystemCardiac Conduction System

Conduction system stimulates the Conduction system stimulates the myocardium to contract & pump bloodmyocardium to contract & pump blood

Conduction system usually controls the Conduction system usually controls the rhythm of the heart.rhythm of the heart.

Heart has two conduction systemsHeart has two conduction systems One controls atrial activity One controls atrial activity One that controls ventricular activityOne that controls ventricular activity

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Anatomy of the Conduction Anatomy of the Conduction SystemSystem

SA NodeSA Node

AV NodeAV Node

Bundle of HisBundle of His

Bundle branchesBundle branches

Purkinje fibersPurkinje fibers

Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 331.6

SA NodeSA Node

Pacemaker of the Pacemaker of the heartheart

Impulses originate Impulses originate herehere

Located in Located in posterior wall RAposterior wall RA

Fires at 60 -100 Fires at 60 -100 bpmbpm

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AV NodeAV Node Connects the atria & Connects the atria &

ventricles, provides ventricles, provides one way conductionone way conduction Would beat Would beat

independentlyindependently Fires at 40 -60 bpmFires at 40 -60 bpm Can assume Can assume

pacemaker function pacemaker function if SA fails to if SA fails to dischargedischarge

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Purkinjie FibersPurkinjie Fibers Supplies the ventriclesSupplies the ventricles Large fibers, rapid Large fibers, rapid

conduction for swift & conduction for swift & efficient ejection of efficient ejection of blood from heartblood from heart

Fire 15-40 bpmFire 15-40 bpm Assume pacemaker of Assume pacemaker of

ventricles if AV failsventricles if AV fails HR reflects intrinsic HR reflects intrinsic

firing of these structuresfiring of these structures

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Action Potentials (AP)Action Potentials (AP)Stimulus Stimulus

excitable tissues (muscle & conduction system) excitable tissues (muscle & conduction system)

evokes an AP characterized by a sudden change evokes an AP characterized by a sudden change in voltage resulting from transient depolarization in voltage resulting from transient depolarization & then repolarization.& then repolarization.

AP’s are electrical currents involving the AP’s are electrical currents involving the movement/flow of electrically charged ions at movement/flow of electrically charged ions at level of cell membrane.level of cell membrane.

AP’s are conducted thru-out the heart, responsible AP’s are conducted thru-out the heart, responsible for initiating each cardiac contraction.for initiating each cardiac contraction.

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SLOW SA & AV Nodes

FAST

Purkinje Fiber & Muscle

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Cardiac Action PotentialsCardiac Action Potentials 3 types of membrane ion channels that contribute to 3 types of membrane ion channels that contribute to

voltage changes during the phases of the APvoltage changes during the phases of the AP

1.1. Fast NaFast Na++ channels channels Rapid depolarization of musclesRapid depolarization of muscles

2.2. Slow NaSlow Na++ channels channels Pacemaker activity (SA, AV)Pacemaker activity (SA, AV)

3.3. Potassium channelsPotassium channels Speedy repolarizationSpeedy repolarization

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Three Phases of APThree Phases of AP RestingResting

Membrane is relatively Membrane is relatively permeable to Kpermeable to K++, but much , but much less so to Naless so to Na++

DepolarizationDepolarizationCell membrane becomes Cell membrane becomes

permeable to Napermeable to Na++ NaNa++ enters cell, enters cell, IC more +IC more +

RepolarizationRepolarizationOutward flow of positive Outward flow of positive

charges, mainly Kcharges, mainly K++ IC is more negativeIC is more negative Assisted by NaAssisted by Na++-K-K++ pump pump

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Cardiac Muscle Cell FiringCardiac Muscle Cell Firing

Cells begin with a Cells begin with a negative charge: negative charge: resting membrane resting membrane potentialpotential

Calcium leakCalcium leak lets lets CaCa2+2+ diffuse in, diffuse in, making the cell more making the cell more positivepositive

Threshold potential

Resting membrane potential Calcium

leak

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Cardiac Muscle Cell Firing (cont.)Cardiac Muscle Cell Firing (cont.) At threshold At threshold

potential, more Napotential, more Na++ channels openchannels open

NaNa++ rushes in, rushes in, making the cell making the cell very positive: very positive: depolarizationdepolarization

Action potential: Action potential: the cell responds the cell responds (e.g. by (e.g. by contracting)contracting)

Threshold potential

Resting membrane potential

Action potential

Calcium leak

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Cardiac Muscle Cell Firing (cont.)Cardiac Muscle Cell Firing (cont.)

KK++ channels open channels open KK++ diffuses out, diffuses out,

making the cell making the cell negative again, negative again, but Cabut Ca2+2+ channels channels are still allowing are still allowing CaCa2+2+ to enter to enter

The cell remains The cell remains positive: positive: plateauplateau

Threshold potential

PLATEAU

Action potential

Calcium leak

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Cardiac Muscle Cell Firing (cont.)Cardiac Muscle Cell Firing (cont.) During During

plateauplateau, the , the musclemuscle contracts contracts stronglystrongly

Then the CaThen the Ca2+2+ channels shut channels shut and it and it repolarizesrepolarizes

Threshold potential

PLATEAUAction potential

Calcium leak

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Cardiac Action PotentialsCardiac Action Potentials Unlike nerve cells, cardiac cells have five phases in Unlike nerve cells, cardiac cells have five phases in

their action potentialtheir action potential Phase 4 – the resting membrane potential.Phase 4 – the resting membrane potential. Phase 0 – there is rapid depolarizationPhase 0 – there is rapid depolarization Phase 1 – there is a short repolarization (only Phase 1 – there is a short repolarization (only

observed in ventricular muscle)observed in ventricular muscle) Phase 2 – the membrane potential remains Phase 2 – the membrane potential remains

depolarized in a plateaudepolarized in a plateau Phase 3 – the membrane potential becomes Phase 3 – the membrane potential becomes

repolarized.repolarized. The characteristics of the phases are different in nodal The characteristics of the phases are different in nodal

tissues of the heart when compared with heart muscle tissues of the heart when compared with heart muscle cells or Purkinje fibers.cells or Purkinje fibers.

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Cardiac Muscle Action PotentialCardiac Muscle Action Potential 5 Phases5 Phases

Phase 0Phase 0: : Upstroke, rapid depolarizationUpstroke, rapid depolarization

Phase 1:Phase 1: Early, short repolarizationEarly, short repolarization

Seen only in ventricular musSeen only in ventricular musclecle

Phase 2:Phase 2: Plateau phase; membrane potential Plateau phase; membrane potential

remains depolarizedremains depolarized

Phase 3:Phase 3: Final rapid repolarizationFinal rapid repolarization

Phase 4:Phase 4: Resting, Resting, diastolic repolarizationdiastolic repolarization

** Unlike nerve cells, cardiac cells ** Unlike nerve cells, cardiac cells have 5 phases in their action have 5 phases in their action

potential.potential.

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Cardiac Muscle Cell ContractionCardiac Muscle Cell Contraction During Phase 2, the plateau, calcium ion enters the During Phase 2, the plateau, calcium ion enters the

muscle cell, causing it to contract strongly.muscle cell, causing it to contract strongly.

The strength of contraction is directly proportional to The strength of contraction is directly proportional to the number of calcium ions that enter the cell.the number of calcium ions that enter the cell.

Calcium channel opening is controlled by voltage and Calcium channel opening is controlled by voltage and by betaby beta11 receptors in the ventricular myocardium. receptors in the ventricular myocardium.

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Lehne 5th ed Figure 47-2

Myocardium& His-Purkinje

System

SA Node &AV Node

Why are action Why are action potentials potentials important?important?

• Source of Source of dysrhythmiasdysrhythmias

• Targets of Targets of drug actiondrug action

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Cardiac Conduction Cardiac Conduction & &

Rhythm DisordersRhythm Disorders

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ECG: Relationship ECG: Relationship to Action Potentialto Action Potential

Electrical events recorded Electrical events recorded on ECGon ECG

Electrical events precede Electrical events precede mechanical events; mechanical events; know know what they represent!what they represent! PP QRSQRS TT

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Electrical event precedes mechanical event !!!

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Porth 2007, Figure 16-12

P waveP wave

PR IntervalPR Interval

QRS complexQRS complex

T wave: T wave: RepolarizationRepolarization

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Disorders of Cardiac Rhythm Disorders of Cardiac Rhythm and Conduction : 2 Typesand Conduction : 2 Types

1.1. Dysrhythmias (or arrhythmias)Dysrhythmias (or arrhythmias)

Term used to describe disorders of cardiac Term used to describe disorders of cardiac rhythmrhythm

Occur in healthy and non-healthyOccur in healthy and non-healthy Interfere with heart’s pumping abilityInterfere with heart’s pumping ability

2.2. Disorders of impulse conductionDisorders of impulse conduction

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Disorders of Cardiac Rhythm Disorders of Cardiac Rhythm and Conductionand Conduction

2 types of disorders of the cardiac conduction system2 types of disorders of the cardiac conduction system1. Disorders of rhythm1. Disorders of rhythm2. Disorders of impulse conduction2. Disorders of impulse conduction

Dysrhythmias (or arrhythmias)Dysrhythmias (or arrhythmias) Term used to describe disorders of cardiac rhythmTerm used to describe disorders of cardiac rhythm Occur in healthy and non-healthyOccur in healthy and non-healthy Interfere with heart’s pumping abilityInterfere with heart’s pumping ability

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CausesCauses

Congenital defects in conduction systemCongenital defects in conduction system Degenerative changesDegenerative changes Ischemia and MIIschemia and MI Fluid/electrolyte imbalancesFluid/electrolyte imbalances DrugsDrugs

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Sinus Node RhythmsSinus Node RhythmsNormal Sinus RhythmNormal Sinus Rhythm

P wave precedes each QRS, RR intervals P wave precedes each QRS, RR intervals reg, rate 60-100reg, rate 60-100

Sinus BradycardiaSinus BradycardiaP before QRS, RR regular, rate P before QRS, RR regular, rate < 60, slowing of conduction thru AV < 60, slowing of conduction thru AV node (Vagal, PNS)node (Vagal, PNS)

Sinus TachycardiaSinus TachycardiaP before QRS, RR regular, P before QRS, RR regular, rate > 100. Enhancedrate > 100. Enhancedautomaticity r/t SNS activation (fever, automaticity r/t SNS activation (fever, exercise, stress)exercise, stress)

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System

SA Node &AV Node

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Class II Antidysrhythmic

Class II Antidysrhythmic Class II Antidysrhythmic Beta BlockersBeta BlockersDepress Phase 4 in depolarizationDepress Phase 4 in depolarizationNonselective: Nonselective: Carvedilol, Propranolol: Carvedilol, Propranolol:

Block beta 1 & 2 receptorsBlock beta 1 & 2 receptorsCardioselective: Cardioselective: Metropolol, Esmolol:Metropolol, Esmolol:

Block beta 1 onlyBlock beta 1 only

Mechanism of Action:Mechanism of Action:(-) Inotrope(-) Inotrope(-) Chronotrope – SLOW the heart rate!(-) Chronotrope – SLOW the heart rate!(-) Dromotrope(-) Dromotrope

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Class II Antidysrhythmic Class II Antidysrhythmic Beta BlockersBeta Blockers

ECGECG Prolong PR & bradycardiaProlong PR & bradycardia

Pharmacotherapeutics:Pharmacotherapeutics:PSVTPSVTAnginaAnginaAMIAMIHypertension (HTN) (Hypertension (HTN) (not esmolol)not esmolol)Heart Failure (HF) Heart Failure (HF) (carvedilol, metoprolol)(carvedilol, metoprolol)

See Lehne Table 18-2 & 18-332

Beta Blocker: Adverse effectsBeta Blocker: Adverse effects

HypotensionHypotension SyncopeSyncope Precipitate HFPrecipitate HF BradycardiaBradycardia AV blockAV block Sinus arrestSinus arrest Bronchospasm Bronchospasm (non-selective beta blockers)(non-selective beta blockers) Rebound cardiac excitation Rebound cardiac excitation (if abruptly stopped)(if abruptly stopped)

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Beta Blocker Administration Beta Blocker Administration (remember from last week)(remember from last week)

DrugDrug RouteRoute ½ Life (hrs)½ Life (hrs) IndicationIndication

EsmololEsmolol IV ONLY!IV ONLY! 0.150.15 Dysrh, anginaDysrh, angina

MetoprololMetoprolol IV, POIV, PO 3-73-7 Dysrh, angina, Dysrh, angina, AMI, HF, HTNAMI, HF, HTN

AtenololAtenolol IV, POIV, PO 6-96-9 Dysrh, angina, Dysrh, angina, AMIAMI

CarvedilolCarvedilol POPO 5-115-11 Angina, AMI, Angina, AMI, HF, HTNHF, HTN

PropanololPropanolol IV, POIV, PO 3-53-5 Dysrh, angina, Dysrh, angina, AMI, HTNAMI, HTN

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Atrial Dysrhythmias

Atrial FibrillationAtrial Fibrillation: : Chaotic & disorganized current.Chaotic & disorganized current.Atria are depolarizing without contracting (just quivering).Atria are depolarizing without contracting (just quivering).Ventricular rhythm irregular. Ventricular rhythm irregular.

Only irregularly irregular rhythm.Only irregularly irregular rhythm.No discernable P waves.No discernable P waves.

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A-Fib treatment: DigoxinA-Fib treatment: Digoxin

A cardiac glycoside that is used for atrial A cardiac glycoside that is used for atrial fibrillation or atrial flutter.fibrillation or atrial flutter.

Slows conduction in the AV node and Slows conduction in the AV node and thereby slows ventricular rate.thereby slows ventricular rate.

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DigoxinDigoxinMechanism of Action:Mechanism of Action: Inhibits NaInhibits Na++-K-K++ ATPase; more intracellular calcium ATPase; more intracellular calcium

availableavailable + inotrope+ inotrope

Enhance vagal influence Enhance vagal influence (SA & AV node effect)(SA & AV node effect)

- chronotrope, - dromotrope - chronotrope, - dromotrope

Pharmacotherapeutics:Pharmacotherapeutics: Heart failureHeart failure Atrial flutterAtrial flutter

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Digoxin: Digoxin: PharmacokineticsPharmacokinetics

AbsorptionAbsorption 60 – 80% (tabs)60 – 80% (tabs)

70 – 85% (elixir)70 – 85% (elixir)

90 – 100% (caps)90 – 100% (caps)

MetabolismMetabolism LiverLiver

Half LifeHalf Life 5-7 DAYS to eliminate 5-7 DAYS to eliminate

& T½ 1.5 days & T½ 1.5 days

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DigoxinDigoxinAdministration ConsiderationsAdministration Considerations PO or IV (mcg NOT mg)PO or IV (mcg NOT mg)

““Digitalization”Digitalization” IV loading doseIV loading dose

Digoxin levels (0.5 - 1.1 ng/ml)Digoxin levels (0.5 - 1.1 ng/ml) VERY narrow therapeutic rangeVERY narrow therapeutic range Digoxin immune FAB (antidote) for Digoxin immune FAB (antidote) for

toxic levels ( > 2.0 ng/ml)toxic levels ( > 2.0 ng/ml) D/C drug until toxicity resolvesD/C drug until toxicity resolves

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Adverse effect & S/S digoxin toxicityAdverse effect & S/S digoxin toxicity

Digoxin induced dysrhythmiasDigoxin induced dysrhythmiasAll types! All types! BradycardiaBradycardiaAV block most commonAV block most commonVentricular flutter/fib most dangerousVentricular flutter/fib most dangerous

GI : Anorexia, N/V GI : Anorexia, N/V CNS: Drowsiness/weakness,CNS: Drowsiness/weakness,

Blurred vision/colored (yellow) halosBlurred vision/colored (yellow) halos

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DigoxinDigoxinContraindications & PrecautionsContraindications & Precautions

ContraindicationsContraindications PrecautionsPrecautions

22ndnd/3/3rdrd degreedegree heart block heart block

V. Fib/V. TachV. Fib/V. Tach

Sick Sinus SyndromeSick Sinus Syndrome

Acute MIAcute MI

Renal insufficiencyRenal insufficiency

HypokalemiaHypokalemia

Severe pulmonary Severe pulmonary diseasedisease

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DigoxinDigoxinAdditional ConsiderationsAdditional Considerations

Potassium levels Potassium levels

Keep in 3.5 – 5.0 mEq/L rangeKeep in 3.5 – 5.0 mEq/L range Digoxin competes with KDigoxin competes with K++ @ binding sites @ binding sites Hyperkalemia Hyperkalemia decreases digoxin effect decreases digoxin effect Diuretics may cause hypokalemia Diuretics may cause hypokalemia

digoxin toxicitydigoxin toxicity

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DrugDrugDrug InteractionsDrug InteractionsReduce digoxin therapeutic effectReduce digoxin therapeutic effect ACE-I & ARBsACE-I & ARBs

Increase potassiumIncrease potassium

Additive digoxin effectAdditive digoxin effect SympathomimeticsSympathomimetics

Increase contractility & HRIncrease contractility & HR Increase risk of tachydysrhythmiasIncrease risk of tachydysrhythmias

Numerous interactions (Lehne Table 47-2)Numerous interactions (Lehne Table 47-2)

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DrugDrugDrug InteractionsDrug InteractionsIncrease risk of digoxin toxicityIncrease risk of digoxin toxicity

Calcium channel blockers (verapamil)Calcium channel blockers (verapamil) Increase serum dig levelIncrease serum dig level Decrease HRDecrease HR Bradydysrhythmias or complete heart blockBradydysrhythmias or complete heart block

Diuretics may reduce potassium levelsDiuretics may reduce potassium levels Increase risk of dig-induced dysrhythmiasIncrease risk of dig-induced dysrhythmias

Herbal interactions increase metabolismHerbal interactions increase metabolism

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Digoxin: Digoxin: Nursing ImplicationsNursing Implications

Apical pulse for 1 min. & document

Monitor ECG

Monitor potassium & dig levels

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A-Fib, PSVT TreatmentA-Fib, PSVT TreatmentClass IV Antidysrhythmic Class IV Antidysrhythmic Calcium Channel BlockersCalcium Channel Blockers

Verapamil, diltazemVerapamil, diltazem Mechanism of Action:Mechanism of Action:

Inhibits calcium influx during Inhibits calcium influx during depolarizationdepolarization

Depresses phase 4 of depolarizationDepresses phase 4 of depolarization Prolongs phases 1 & 2 of Prolongs phases 1 & 2 of

depolarizationdepolarization

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System

SA Node &AV Node

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Class IV Antidysrhythmic Class IV Antidysrhythmic Calcium Channel Blockers (verapamil, diltiazem)Calcium Channel Blockers (verapamil, diltiazem)

3 effects on heart3 effects on heart

1.1. Slow SA node automaticity Slow SA node automaticity slow HR slow HR

2.2. Delay AV node conduction Delay AV node conduction prolong PR prolong PR

3.3. myocardial contractility myocardial contractility CO CO

Note: same effects as Beta Blockers!!!!!Note: same effects as Beta Blockers!!!!!

PharmacotherapeuticsPharmacotherapeutics::

PSVTPSVT Atrial Fib/FlutterAtrial Fib/Flutter (slow ventricular (slow ventricular rate)rate)

Angina Angina HypertensionHypertension

Note: not effective for ventricular dysrhythmias !!Note: not effective for ventricular dysrhythmias !!50

Verapamil & DiltiazemVerapamil & DiltiazemAdverse Effects (Adverse Effects (Remember from last week)Remember from last week)

Cardiac:Cardiac:• BradycardiaBradycardia• AV blockAV block• Decreased Decreased myocardial myocardial contractility contractility decreased decreased cardiac outputcardiac output

General:General:• DizzinessDizziness• Facial FlushingFacial Flushing• HeadacheHeadache• Peripheral edemaPeripheral edema• Decreased Decreased GI motilityGI motility

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Disorders of Atrioventricular Conduction

1st degree AV block:1st degree AV block: Slightly Slightly prolonged PR interval; prolonged PR interval; ALLALL atrial impulses atrial impulses

are conducted to ventricles; asymptomatic. are conducted to ventricles; asymptomatic.

2nd degree AV block:2nd degree AV block: Not all atrial Not all atrial impulses are conducted to ventricles, see impulses are conducted to ventricles, see some P waves, not followed by QRS. some P waves, not followed by QRS.

Can be very symptomatic. Can be very symptomatic.

3rd degree AV block =3rd degree AV block =complete AV block:complete AV block:Conduction link between atria & ventricles Conduction link between atria & ventricles lost, each controlled by independent lost, each controlled by independent pacemakers. Atria continue at their rate, pacemakers. Atria continue at their rate, ventricles contract at their rate (30-40 bpm). ventricles contract at their rate (30-40 bpm).

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Case study: Digoxin toxicityCase study: Digoxin toxicitySerum dig level = 1.7 ng.ml Serum dig level = 1.7 ng.ml (0.5-1.1 desired)(0.5-1.1 desired)

33rdrd degree AV degree AV BlockBlock

Temporary pacemaker inserted, SR Temporary pacemaker inserted, SR 100% 100% pacedpaced

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Complete A-V block with 100% Complete A-V block with 100% atrio-ventricular pacingatrio-ventricular pacing

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Atrial Pacingspike

Ventricular Pacingspike

P QRS

Ventricular Dysrhythmias: More Serious!PVC:PVC: Ventricles contract prematurely. Ventricles contract prematurely. W/ a PVC, diastolic volume is insufficient for ejection of W/ a PVC, diastolic volume is insufficient for ejection of blood into arterial system. blood into arterial system. Therefore, no or weak pulse palpated. Therefore, no or weak pulse palpated. Few/day = OK, More/minute, the worse (>6). Few/day = OK, More/minute, the worse (>6). Common post MI, SNS activity, Common post MI, SNS activity, K+, hypoxia. K+, hypoxia.

V-Tachycardia: V-Tachycardia: rhythm originates below Bundle rhythm originates below Bundle of His, in ventricular muscle. Wide, tall QRS complexes. of His, in ventricular muscle. Wide, tall QRS complexes. Stops spontaneously or continue. Stops spontaneously or continue. Dangerous rhythm,Dangerous rhythm, diastolic diastolicfilling time filling time CO. Can cause CO. Can cause Cardiac ArrestCardiac Arrest

V-Fib: V-Fib: ventricle quivers but does ventricle quivers but does NOT contract! NOT contract! NO cardiac outputNO cardiac output,,and no pulses; and no pulses; Cardiac Arrest!!Cardiac Arrest!!grossly disorganized pattern.grossly disorganized pattern.

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System

SA Node &AV Node

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Class I Antidysrhythmic

Class 1B: LidocaineClass 1B: Lidocaine Ventricular Dysrhthmias Ventricular Dysrhthmias

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Class 1B: LidocaineClass 1B: Lidocaine

Effect on Heart & ECGEffect on Heart & ECG1.1. Blocks Na+ channelsBlocks Na+ channels slow conduction slow conduction

thru atria, ventricles, HIS-Purkinjethru atria, ventricles, HIS-Purkinje

2.2. Reduces automaticityReduces automaticity

3.3. Accelerates repolarization (shortens Accelerates repolarization (shortens action potential)action potential)

No anticholinergic effectNo anticholinergic effect No change in ECGNo change in ECG

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Lidocaine: Precautions & Lidocaine: Precautions & Adverse EffectsAdverse Effects

Metabolized by LiverMetabolized by Liver Therapeutic range 1.5 – 5.0 microgm/mlTherapeutic range 1.5 – 5.0 microgm/ml Adverse CNS Effects: Adverse CNS Effects:

Drowsiness, confusion, paresthesiaDrowsiness, confusion, paresthesia Toxicity:Toxicity:

Convulsions & respiratory arrestConvulsions & respiratory arrest

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Lidocaine: AdministrationLidocaine: Administration IV PushIV Push

50-100mg (1mg/kg)50-100mg (1mg/kg) InfusionInfusion

1-4mg/min1-4mg/minDiluted in D5WDiluted in D5W

Special Considerations: Special Considerations: Use for as short a time as possibleUse for as short a time as possibleReduce dosage in pts with liver disordersReduce dosage in pts with liver disorders

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Class III AntidysrhythmicClass III Antidysrhythmic Potassium Channel Blockers:Potassium Channel Blockers: AmiodaroneAmiodarone ApprovedApproved for VT & VF for VT & VF Delay repolarizationDelay repolarization

Prolongs action potential & refractory periodProlongs action potential & refractory period

Increases PR & QT intervalsIncreases PR & QT intervals

Initial Initial catecholamine release catecholamine release brief exacerbation brief exacerbation of dysrhythmias of dysrhythmias

block catecholamine release block catecholamine release vasodilation / vasodilation / hypotensionhypotension

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System

SA Node &AV Node

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Class III Antidysrhythmic

Non-Pharmacologic Non-Pharmacologic Treatment of DysrhythmiasTreatment of Dysrhythmias

CardioversionCardioversion Atrial fibAtrial fib V-tachV-tach

DefibrillationDefibrillation V-fibV-fib

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http://www.zoll.com/product.aspx?id=395

Automated External DefibrillatorAutomated External Defibrillator Cardiac Arrest, AED “interrogates” rhythm.Cardiac Arrest, AED “interrogates” rhythm. Tells user what to do, eg “Shock Now”Tells user what to do, eg “Shock Now” Delivers shock for V-tach or V-fib.Delivers shock for V-tach or V-fib.

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Non-Pharmacologic Non-Pharmacologic Treatment of DysrhythmiasTreatment of Dysrhythmias

Implantable Cardioverter/DefibrillatorImplantable Cardioverter/Defibrillator Like a pacemakerLike a pacemaker Monitors & analyzes rhythmMonitors & analyzes rhythm Delivers shock to terminate V-tach, V-fibDelivers shock to terminate V-tach, V-fib

Radiofrequency Catheter AblationRadiofrequency Catheter Ablation Cardiac cath & electrophysiologic testCardiac cath & electrophysiologic test Identify cardiac tissue site which causes Identify cardiac tissue site which causes

dysrhythmiadysrhythmia RF energy delivered to destroy the tissue RF energy delivered to destroy the tissue

(remember, you can’t pace meatloaf)(remember, you can’t pace meatloaf)

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Antidysrhythmic Drugs: SummaryAntidysrhythmic Drugs: Summary

Class IClass I Depress phase 0 in depolarizationDepress phase 0 in depolarizationBlock sodium channelsBlock sodium channels

Class IIClass IIDepress phase 4 in depolarizationDepress phase 4 in depolarizationBlock beta 1 & 2 adrenergic receptorsBlock beta 1 & 2 adrenergic receptors

HRHR Contractility Contractility

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Class IIIClass IIIProlong phase 3 (repolarization)Prolong phase 3 (repolarization)

Class IVClass IVDepresses phase 4 depolarizationDepresses phase 4 depolarizationProlongs phases 1 & 2 repolarizationProlongs phases 1 & 2 repolarization

Antidysrhythmic Drugs: SummaryAntidysrhythmic Drugs: Summary

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Management of Management of Cardiac DysrhythmiasCardiac Dysrhythmias

REMEMBER:REMEMBER:Many drugs used to treat dysrhythmias Many drugs used to treat dysrhythmias

also may worsen them also may worsen them or cause new ones!or cause new ones!

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Coronary Heart Disease Coronary Heart Disease & &

Acute Myocardial InfarctionAcute Myocardial Infarction(MI or AMI)(MI or AMI)

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Coronary CirculationCoronary Circulation Two main coronary Two main coronary

arteries arise from arteries arise from coronary sinus (above coronary sinus (above aortic valve)aortic valve)

Primary factor Primary factor responsible for perfusion responsible for perfusion coronary arteries is BP coronary arteries is BP in aortain aorta

s aortic pressure -> s aortic pressure -> s coronary blood flow s coronary blood flow

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LVLV

Coronary CirculationCoronary Circulation

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Ischemic Heart DiseaseIschemic Heart Disease

a.k.a Coronary Heart Disease a.k.a Coronary Heart Disease a.k.a Coronary Artery Diseasea.k.a Coronary Artery Disease

AnginaAnginaMyocardial InfarctionMyocardial Infarction

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Coronary Heart DiseaseCoronary Heart Disease

Heart disease caused by impaired coronary blood Heart disease caused by impaired coronary blood flow (atherosclerosis)flow (atherosclerosis)

Cause angina, dysrhythmias, conduction defects, Cause angina, dysrhythmias, conduction defects, heart failure, sudden death, myocardial infarction heart failure, sudden death, myocardial infarction (“heart attack”)(“heart attack”)

If blood flow is temporarily inadequate (due to If blood flow is temporarily inadequate (due to increased oxygen demand), ischemia produces increased oxygen demand), ischemia produces pain (angina).pain (angina).

Myocardial Infarction is myocardial cell/tissue Myocardial Infarction is myocardial cell/tissue death due to oxygen starvationdeath due to oxygen starvation

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Assessment of Coronary Assessment of Coronary Blood FlowBlood Flow ECGECG Exercise Stress TestingExercise Stress Testing Pharmacologic Stress TestingPharmacologic Stress Testing Nuclear ImagingNuclear Imaging Cardiac Catheterization /Coronary Cardiac Catheterization /Coronary

angiographyangiography

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Collateral CirculationCollateral Circulation

With gradual occlusion of large coronary With gradual occlusion of large coronary vessels, the smaller collateral vessels vessels, the smaller collateral vessels in size in size and provide alternative channels for blood and provide alternative channels for blood flowflow

One of the reasons CHD does not produce One of the reasons CHD does not produce symptoms until it is far advanced is that the symptoms until it is far advanced is that the collateral channels develop at the same time collateral channels develop at the same time the atherosclerotic changes are occurring.the atherosclerotic changes are occurring.

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Collateral Circulation

77

Pathogenesis of CAD: Pathogenesis of CAD: AtherosclerosisAtherosclerosis Most common cause of CADMost common cause of CAD Plaque disruption is most frequent Plaque disruption is most frequent

cause of MI, sudden deathcause of MI, sudden death Can affect one or all 3 major coronary Can affect one or all 3 major coronary

arteries/branchesarteries/branches

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PlaquePlaque Plaques typically do not occlude the whole Plaques typically do not occlude the whole

coronary artery but produce a narrowing that coronary artery but produce a narrowing that restricts blood flow.restricts blood flow. In times of increased oxygen demand, such as with In times of increased oxygen demand, such as with

exercise, the restricted blood flow may produce exercise, the restricted blood flow may produce ischemia in cells supplied by that artery.ischemia in cells supplied by that artery.

This produces the pain of angina.This produces the pain of angina. A plaque may become unstable and rupture, A plaque may become unstable and rupture,

causing a clot to form which may completely causing a clot to form which may completely occlude the artery.occlude the artery. Occlusion of the artery causes death of the cardiac Occlusion of the artery causes death of the cardiac

cells downstream that are supplied by that artery.cells downstream that are supplied by that artery. When the cells die, that is an infarction – hence the When the cells die, that is an infarction – hence the

name name myocardial infarction.myocardial infarction.79

Atherosclerosis in Coronary ArteryAtherosclerosis in Coronary ArteryPlaque rupture & disruption of atheromaPlaque rupture & disruption of atheroma lipid core/contents exposed to bloodlipid core/contents exposed to blood

platelet aggregationplatelet aggregationcoagulation cascade coagulation cascade

fibrin clotfibrin clot

thrombosis, vasospasm thrombosis, vasospasm

myocardial ischemiamyocardial ischemia Coronary arteries unable to supply blood to Coronary arteries unable to supply blood to

meet metabolic demands of the heartmeet metabolic demands of the heart

80

Review of Terms Related to CHDReview of Terms Related to CHD Angina:Angina: symptomatic paroxysmal chest pain or symptomatic paroxysmal chest pain or

pressure sensation associated with transient pressure sensation associated with transient myocardial ischemiamyocardial ischemia

Stable angina:Stable angina: Occurs with exertion or stress Occurs with exertion or stress Variant or vasospastic angina:Variant or vasospastic angina: Occurs during rest or Occurs during rest or

with minimal activity (nocturnal, Prinzmetal’s)with minimal activity (nocturnal, Prinzmetal’s) Silent myocardial ischemiaSilent myocardial ischemia: Occurs in the absence of : Occurs in the absence of

anginal painanginal pain Unstable anginaUnstable angina: Symptoms at rest lasting >20 mins., : Symptoms at rest lasting >20 mins.,

marked limitations of ordinary activity (walking 1–2 marked limitations of ordinary activity (walking 1–2 blocks, climbing a flight of stairs), recent acceleration in blocks, climbing a flight of stairs), recent acceleration in anginal signsanginal signs

AMI:AMI: Acute myocardial infarction (STEMI or NSTEMI) Acute myocardial infarction (STEMI or NSTEMI) 81

Plaque RupturePlaque Rupture SpontaneousSpontaneous

SNS activation SNS activation BP, BP, HR, HR, contraction contraction Triggering event (stress: emotional, physical)Triggering event (stress: emotional, physical)

DiurnalDiurnal First hour of arisingFirst hour of arising SNS “surge” on arisingSNS “surge” on arising

SNS major playerSNS major player Beta-adrenergic blockersBeta-adrenergic blockers

86

““Severe” coronary stenosis and vulnerable Severe” coronary stenosis and vulnerable plaques co-existplaques co-exist

Califf, Atlas of Heart Diseases 200187

Ischemia, Injury, & Infarction Ischemia, Injury, & Infarction

3 Zones of Damage3 Zones of Damage

Infarction = NecrosisInfarction = Necrosis-MI, dead cells-MI, dead cells

InjuryInjury-some recovery possible-some recovery possible

IschemiaIschemia- full recovery possible- full recovery possible

88

Zones of Tissue DamageZones of Tissue Damage

Goal is to limit the area of Goal is to limit the area of necrosis (infarction) !necrosis (infarction) !

• Necrotic myocardial cells Necrotic myocardial cells are gradually replaced with are gradually replaced with scar tissue scar tissue • Scar tissue cannot contract Scar tissue cannot contract or conduct action potentialsor conduct action potentials

89

An Acute MI (AMI) Leaves Behind an An Acute MI (AMI) Leaves Behind an Area of Yellow NecrosisArea of Yellow Necrosis

90

Pathologic ChangesPathologic Changes

Ischemic areas cease to function within Ischemic areas cease to function within minutesminutes

Irreversible damage/death to myocardial cells Irreversible damage/death to myocardial cells occurs within 20-40 minutesoccurs within 20-40 minutes

Early reperfusion (20min) after onset of Early reperfusion (20min) after onset of ischemia can prevent necrosis, prevent further ischemia can prevent necrosis, prevent further ischemia and necrosisischemia and necrosis

91

Pathologic Changes Pathologic Changes

Extent of infarct depends on :Extent of infarct depends on : locationlocation extent of occlusion extent of occlusion amount of heart tissue supplied by amount of heart tissue supplied by

vessel, duration of occlusionvessel, duration of occlusion metabolic needs of the affected tissuemetabolic needs of the affected tissue extent of collateral circulationextent of collateral circulation

92

Pathologic Pathologic ChangesChanges

Transmural infarctTransmural infarctFull thickness of ventricular Full thickness of ventricular

wall, wall, Occurs with obstruction of a Occurs with obstruction of a

single artery; single artery; May involve RV, LV and/or IV May involve RV, LV and/or IV

septumseptum Subendocardial infarctSubendocardial infarct

Involve inner 1/3 to 1/2 Involve inner 1/3 to 1/2 ventricular wall, ventricular wall,

May occur with severely May occur with severely narrowed arteries or with narrowed arteries or with occlusion of a very small occlusion of a very small arteryartery

Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 328.

93

Chest Pain AssessmentChest Pain Assessment

P - ProvocationP - Provocation Q - QualityQ - Quality R – Region/RadiationR – Region/Radiation S - SeverityS - Severity T – TimingT – Timing

95

Categories (PQRST)Categories (PQRST) Angina that occurs with stress Angina that occurs with stress

(physical/emotional)(physical/emotional)Relieved within minutes by Relieved within minutes by

rest or NTG?rest or NTG? Angina that occurs with restAngina that occurs with rest Is of new onsetIs of new onset Increasing intensityIncreasing intensity

risk risk forforMIMI

96

Stable AnginaStable Angina Fixed coronary obstructionFixed coronary obstruction 0022 Demand Demand 0 022 supply supply pain pain

Physical/emotional stress, coldPhysical/emotional stress, cold Provoked by stressorProvoked by stressor

Relieved with rest/NTGRelieved with rest/NTG Not everyone with CHD has anginaNot everyone with CHD has angina

Sedentary lifestyle (couch potatoes), Sedentary lifestyle (couch potatoes), development of collateral circulation, development of collateral circulation, altered perception painaltered perception pain

98

Usual distribution of pain Less common sites of pain distribution

Typically precordial, substernalAnginaAngina

99

Variant or Vasospastic AnginaVariant or Vasospastic Angina ““Prinzmetal’s angina”Prinzmetal’s angina” Due to coronary artery spasms Due to coronary artery spasms Occurs during rest or with minimal exertion, frequently Occurs during rest or with minimal exertion, frequently

nocturnalnocturnal Mechanism uncertainMechanism uncertain

?SNS activation, VSM Ca?SNS activation, VSM Ca++++ channel dysfunction, channel dysfunction, imbalance of endothelial cell vasodilating/constricting imbalance of endothelial cell vasodilating/constricting substancessubstances

Dysrhythmias can occurDysrhythmias can occur Person usually aware; High risk sudden deathPerson usually aware; High risk sudden death

100

Hamon M and Hamon M. N Engl J Med 2006;355:2236

A 38-year-old man was scheduled to undergo invasive coronary angiography after cardiac scintigraphy revealed silent ischemia of the anterior myocardial wall

Variant or Vasospastic AnginaVariant or Vasospastic Angina

101

Acute Coronary Syndrome (ACS)Acute Coronary Syndrome (ACS)

NSTEMI STEMI

Unstable or ruptured plaque

102


103

Unstable AnginaUnstable Angina

Clinical syndrome of myocardial ischemia Clinical syndrome of myocardial ischemia ranging between stable angina and MIranging between stable angina and MI

Usually d/t atherosclerotic plaque disruption, Usually d/t atherosclerotic plaque disruption, plt aggregationplt aggregation

Three presentationsThree presentations

1.1. Symptoms at rest (> 20 minutes)Symptoms at rest (> 20 minutes)

2.2. Severe, frank pain, new onset (< 1month)Severe, frank pain, new onset (< 1month)

3.3. More severe, prolonged, or frequentMore severe, prolonged, or frequent

104

Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 392. 105


106

ST Segment ElevationST Segment Elevation ST segment elevations ST segment elevations

are indicative of are indicative of myocardial damage or myocardial damage or ischemia.ischemia.

It may take some time It may take some time (minutes to hours) for (minutes to hours) for the changes to show the changes to show up, and they may not up, and they may not be present in all EKG be present in all EKG leads.leads.

Porth, 2007, Essentials of Pathophysiology, 2nd ed.,

Lippincott, p. 394.

107

ECG : STEMI vs NSTEMIECG : STEMI vs NSTEMI

108

Non ST Segment Elevation Myocardial InfarctionNon ST Segment Elevation Myocardial Infarction (NSTEMI)(NSTEMI)

How is this different from unstable angina or STEMI?How is this different from unstable angina or STEMI?

Unstable anginaUnstable angina, plaque disruption but no thrombus , plaque disruption but no thrombus or occlusion of the coronary artery, therefore no or occlusion of the coronary artery, therefore no myocardial cell death (no MI).myocardial cell death (no MI).

NSTEMINSTEMI, a thrombus partially occludes a coronary , a thrombus partially occludes a coronary artery. Depending on the degree of occlusion and artery. Depending on the degree of occlusion and oxygen demand of downstream heart cells, there may oxygen demand of downstream heart cells, there may be myocardial cell death (an MI) but insufficient to be myocardial cell death (an MI) but insufficient to produce ST segment elevations.produce ST segment elevations.

109

ST Segment Elevation MIST Segment Elevation MI

Characterized by ischemia of cardiac tissueCharacterized by ischemia of cardiac tissue Area of infarction is determined by the Area of infarction is determined by the

coronary artery that is affected and by its coronary artery that is affected and by its distribution of blood flowdistribution of blood flow40-50% of time - LAD40-50% of time - LAD30-40% of time - RCA30-40% of time - RCA15-20% of time - LCA15-20% of time - LCA

111

Diagnosis CHD and MIDiagnosis CHD and MI

Good history & identification of risk Good history & identification of risk factorsfactors

R/O Other causes of CP, eg GERDR/O Other causes of CP, eg GERD ECGECG Serum myocardial markersSerum myocardial markers Stress testing Stress testing Cardiac catheterizationCardiac catheterization

113

““Classic” Manifestations of MIClassic” Manifestations of MI Abrupt onset or progression of unstable, Abrupt onset or progression of unstable,

non-ST elevationnon-ST elevation Pain is severe, crushing, “someone sitting Pain is severe, crushing, “someone sitting

on my chest”on my chest” Radiates to left arm, jaw, neckRadiates to left arm, jaw, neck MI pain is prolonged, not relieved by rest MI pain is prolonged, not relieved by rest

and/or NTG (unlike angina)and/or NTG (unlike angina) N/V, SNS activation N/V, SNS activation HR, HR, RR, RR,

diaphoresis, cool/clammy skindiaphoresis, cool/clammy skin114

ECG ChangesECG Changes T wave inversionT wave inversion ST segment elevationST segment elevation Abnormal Q waveAbnormal Q wave

(may not appear immediately)(may not appear immediately)

Changes can occur over Changes can occur over time, depending on time, depending on duration of ischemia duration of ischemia (extent & location)(extent & location)

Changes may not be Changes may not be present in all leads – take present in all leads – take 12-lead EKG12-lead EKG

115

ST SegmentsST Segments 11stst to change during to change during

ischemia or MI ischemia or MI because myocardial because myocardial repolarization is repolarization is altered.altered.

Ischemia reduces Ischemia reduces membrane potential membrane potential and shorten duration and shorten duration of AP in ischemic of AP in ischemic area.area.

116

Abnormal Q WavesAbnormal Q Waves

Develop because there is no Develop because there is no depolarizing current conduction depolarizing current conduction from necrotic tissuefrom necrotic tissue

May not appear immediatelyMay not appear immediately Diagnostic of MIDiagnostic of MI Q waves are permanent after MIQ waves are permanent after MI

117

Serum Markers for Ischemia & MISerum Markers for Ischemia & MI Necrotic cells release intracellular enzymes Necrotic cells release intracellular enzymes

into blood streaminto blood stream Measure these in blood, larger the number, Measure these in blood, larger the number,

the larger the amount of necrotic tissuethe larger the amount of necrotic tissueCK-MB CK-MB (Creatine-kinase-myocardial bands)(Creatine-kinase-myocardial bands)TroponinTroponinC-reactive ProteinC-reactive Protein

118

CK-MBCK-MB

CK normal in all muscle cells, has 3 CK normal in all muscle cells, has 3 isoenzymes BB, MM, MBisoenzymes BB, MM, MB

CK-MB Creatine kinase -myocardial CK-MB Creatine kinase -myocardial bands is cardiac specificbands is cardiac specific

Elevated within 8 hours after MIElevated within 8 hours after MI Returns to normal in 2-3 daysReturns to normal in 2-3 days Nl ~ 24-195 IU/LNl ~ 24-195 IU/L

119

Troponin Troponin (TnC, TnI, TnT)(TnC, TnI, TnT) Part of the actin-myosin filamentPart of the actin-myosin filament Rises within 3 hours after MIRises within 3 hours after MI Remains elevated 3-4 days, & up to 10 daysRemains elevated 3-4 days, & up to 10 days Diagnostic of MI; No change with ischemiaDiagnostic of MI; No change with ischemia Nl ~ 0.4 ng/mlNl ~ 0.4 ng/ml

120

C-Reactive Protein (CRP)C-Reactive Protein (CRP)

Marker of chronic inflammationMarker of chronic inflammation Maybe a marker of riskMaybe a marker of risk Identifies people before they are Identifies people before they are

symptomaticsymptomatic May guide preventative therapy in future May guide preventative therapy in future

121

Cardiac MarkersCardiac Markers

Hr 1 2 3 4 5 6 7 8 9 10 11 12 Day 2 3 4 5

Troponin

CK-MB

122

NSTEMINSTEMIUnstable anginaUnstable angina

No ECG No ECG ssElevation of serum Elevation of serum

markersmarkers

Unstable AnginaUnstable AnginaPain is severePain is severe

No ECG No ECG ssNo change in markersNo change in markers

ACSACS

No ST ElevationNo ST Elevation STEMISTEMI

123

ACS Case Presentation 1 68 yr male; 3 mos. h/o progressive chest pain; day of adm, with minimal exertion

Risk factors: Smoking; HTN; cholesterol; diabetes

Physical exam: normal

ECG: sinus rhythm; no ST or T-wave abnormalities

Biochemical markers at 10 hours: CK = 58; CKMB = <1 ng/ml; Tn= 0.31 ng/ml

Not an MI !! 125

Management of Management of Angina & CHD/AMIAngina & CHD/AMI

Goals: Goals: • Prevent or minimize infarctionPrevent or minimize infarction• Increase oxygen supply to myocardiumIncrease oxygen supply to myocardium• Decrease metabolic (oxygen) demandsDecrease metabolic (oxygen) demands• Symptom reliefSymptom relief

126

Management of Management of Angina & CHD/AMIAngina & CHD/AMI

TreatmentTreatment Non-pharmacologic: Percutaneous Non-pharmacologic: Percutaneous Coronary Intervention (PCI), life style Coronary Intervention (PCI), life style modificationsmodifications Pharmacologic: anti-platelet drugs, Pharmacologic: anti-platelet drugs, beta blockers, nitratesbeta blockers, nitrates

127

Acute Management: ReperfusionAcute Management: Reperfusion PTCA/PCIPTCA/PCI

ASAPASAPWith or without With or without

thrombolyticsthrombolyticsOften includes Often includes

placement of a placement of a stentstent

CABGCABG

•ThrombolyticsThrombolytics- Tissue plasminogen - Tissue plasminogen activator (t-PA)activator (t-PA)

- Streptokinase- Streptokinase

- Urokinase- Urokinase

- Reteplase Reteplase (modification of t-PA)(modification of t-PA)

128

ReperfusionReperfusion

McCance 5th Ed, 2006 Figure 30-2129

Reperfusion – Balloon Angioplasty, Reperfusion – Balloon Angioplasty, Possibly with StentingPossibly with Stenting

Copyright © 2005 Nucleus Communications, Inc. All rights reserved. www.nucleusinc.com

http://www.orbusneich.com/patients/genous/treatment/stenting/?PHPSESSID=d3bf5eb0eed5f6a353d73c

130

http://www.nucleusinc.com/

Complication of PCIComplication of PCI

N Engl J Med 2011;364:453-64.131

Administration of Thrombolytic Administration of Thrombolytic Therapy Must be Done PromptlyTherapy Must be Done Promptly

Giugliano & Braunwald, Circulation 2003;108;2828-2830

IRA = infarct-related artery

132

PCI (angioplasty ± stenting) must be PCI (angioplasty ± stenting) must be done promptlydone promptly

Nallamothu B et al. N Engl J Med 2007;357:1631-1638 133

Emergency Pain ReliefEmergency Pain Relief

Morphine SulfateMorphine Sulfate VenodilationVenodilation

Reduces preload & cardiac workReduces preload & cardiac work ““Modest” arterial vasodilationModest” arterial vasodilation

Reduces afterload & cardiac workReduces afterload & cardiac work

134

NitroglycerinNitroglycerinAnginaAnginaAcute myocardial infarctionAcute myocardial infarction

Mechanism of Action:Mechanism of Action:Prevents vasospasm of coronary arteriesPrevents vasospasm of coronary arteriesVenodilator Venodilator Decreases preload Decreases preload

Decreases LVEDV Decreases LVEDV

Decreases cardiac Decreases cardiac workwork

135

NitroglycerinNitroglycerin

Purpose/OnsetPurpose/Onset AdministrationAdministration DurationDuration

SLSL Acute anginaAcute angina

1 – 3 min1 – 3 min

0.3 – 0.6 mg 0.3 – 0.6 mg prnprn

30 - 60 30 - 60 minmin

IVIV Acute, unstable Acute, unstable

1-3 min1-3 min

5 microgm/min 5 microgm/min then increasethen increase

Special tubingSpecial tubing Glass bottlesGlass bottles Increased Increased

tolerancetolerance

3 - 5 min3 - 5 min

Lehne, 2006 Tables 50-3 and 50-4136

NitroglycerinNitroglycerinPharmacokineticsPharmacokinetics

• Metabolized in the liver• Excreted by liver & kidneys• Use with caution in patients with liver

or kidney disease• Onset & duration of action administration route dependent

137

NitroglycerinNitroglycerin

ContraindicationsContraindications Severe hypotensionSevere hypotension Increased ICPIncreased ICP Cerebral hemorrhageCerebral hemorrhage Severe anemiaSevere anemia

138

Nitroglycerin Nitroglycerin DrugDrugDrug InteractionsDrug Interactions AlcoholAlcohol

SEVERE hypotension; CV collapseSEVERE hypotension; CV collapse HeparinHeparin

Decreased anticoagulationDecreased anticoagulation LithiumLithium

Possible lithium toxicityPossible lithium toxicity FentanylFentanyl

SEVERE hypotension; Increased fluid SEVERE hypotension; Increased fluid requirementsrequirements

139

Chronic HD & Angina ManagementChronic HD & Angina Management NitratesNitrates Beta BlockersBeta Blockers Calcium channel Calcium channel

blockersblockers

140

Nitrates: Chronic AnginaNitrates: Chronic AnginaPurpose/OnsetPurpose/Onset AdministrationAdministration DurationDuration

OralOral

Isosorbide Isosorbide dinitratedinitrate

Sustained txSustained txPrevent stable Prevent stable

anginaangina

20 - 45 min20 - 45 min

2.5 - 6.5 mg 2.5 - 6.5 mg

1 – 4 x daily1 – 4 x daily

3 - 8 hrs3 - 8 hrs

TransdermalTransdermal

NitroglycerineNitroglycerine

Sustained txSustained txPrevent stable Prevent stable

anginaangina

20 – 60 min20 – 60 min

Patch 1 / dayPatch 1 / day

Ointment Ointment

1-2 in., 4-6 hrs1-2 in., 4-6 hrs Avoid Avoid tolerance tolerance

(PM respite)(PM respite)

2 – 24 hrs2 – 24 hrs

Lehne, 2006 Tables 50-3 and 50-4141

Nitroglycerin Nitroglycerin Patient/Family EducationPatient/Family Education

SLSL Tabs between cheek/lip & gumTabs between cheek/lip & gum Don’t swallowDon’t swallow 1 tab q 5 min x 3, Call 911 if chest pain continues1 tab q 5 min x 3, Call 911 if chest pain continues

NO ALCOHOL!NO ALCOHOL! Slow position changes; orthostatic hypotensionSlow position changes; orthostatic hypotension Headaches are not uncommonHeadaches are not uncommon Check expiration date on tabletsCheck expiration date on tablets

142

Angina ProphylaxisAngina Prophylaxis

““Medical management” of symptomatic coronary Medical management” of symptomatic coronary artery disease (stable angina) has been shown to have artery disease (stable angina) has been shown to have similar outcomes when compared with interventions similar outcomes when compared with interventions such as balloon angioplasty with stenting.such as balloon angioplasty with stenting.

Most stents are actually not FDA approved for stable Most stents are actually not FDA approved for stable angina.angina. They are indicated for acute coronary syndromes They are indicated for acute coronary syndromes

(to be covered in a few minutes).(to be covered in a few minutes).

143

Beta-adrenergic Blocking AgentsBeta-adrenergic Blocking Agents Manage stable angina (not vasospastic)Manage stable angina (not vasospastic) Block beta-1 receptorsBlock beta-1 receptors

Negative inotropeNegative inotrope Negative chronotropeNegative chronotrope Negative dromotropeNegative dromotrope

reduce myocardial oxygen demandreduce myocardial oxygen demand Prevent Sudden Death!Prevent Sudden Death!

More on these later……More on these later……

144

Calcium Channel BlockersCalcium Channel Blockers

Verapamil, diltiazem, nifedipineVerapamil, diltiazem, nifedipine Manage stable & vasospastic anginaManage stable & vasospastic angina Block calcium entry into cellBlock calcium entry into cell

Arterial vasodilationArterial vasodilation Decreases heart rate (SA node firing, AV Decreases heart rate (SA node firing, AV

node conduction)node conduction) Negative intotropeNegative intotrope

reduce myocardial oxygen demandreduce myocardial oxygen demand

145

Anti-platelet drugsAnti-platelet drugsAspirin, Aspirin,

clopidorel (Plavix), clopidorel (Plavix), IIb,IIIa inhibitors (Repro)IIb,IIIa inhibitors (Repro)

Decrease platelet Decrease platelet aggregation aggregation

Prevent thrombus Prevent thrombus formationformation

AnticoagulantsAnticoagulants

Heparin, warfarinHeparin, warfarin

Reduce fibrin Reduce fibrin production production

Suppress clottingSuppress clotting

OPEN!OPEN!Keep arteriesKeep arteries

146

Kumar (2003)

IIb-IIIa Inhibitors Abciximab (RePro@)Alter Platelet Aggregation

- Onset 2 hours

- Duration 48 hours

- Infuse with filter147

Anti-platelet & Anticoagulant DrugsAnti-platelet & Anticoagulant Drugs

Contraindications Contraindications Active bleedingActive bleedingCVA w/i 2 yrsCVA w/i 2 yrsGI/GU bleedingGI/GU bleeding

w/i 6 weeksw/i 6 weeks

ThrombocytopeniaThrombocytopeniaAneurysmAneurysmIntracranial neoplasmIntracranial neoplasm

Major side effectMajor side effect BLEEDINGBLEEDING Intracranial, Intracranial,

retroperitoneal, retroperitoneal, hematemesishematemesis

LabsLabs PT/INR, PTT, PT/INR, PTT,

Activated clotting Activated clotting Time (ACT), Time (ACT), platelet countplatelet count

148

You having an MI ??You having an MI ??

149

Which of the following is present in Which of the following is present in stable angina?stable angina?

An uns

table

pla

que

A ruptu

red p

laque

A sta

ble p

laqu

e

A pla

que with

a th

ro...

25%25%25%25%

1.1. An unstable plaque.An unstable plaque.

2.2. A ruptured plaqueA ruptured plaque

3.3. A stable plaqueA stable plaque

4.4. A plaque with a A plaque with a thrombus.thrombus.

150

Which of the following is Which of the following is diagnosticdiagnostic of an acute myocardial infarction?of an acute myocardial infarction?

ST s

egm

ent e

le...

Incr

ease

d ser

u...

Chest

pai

n at r

est

Incr

ease

d C-re

activ

e p.

..

25% 25%25%25%

1.1. ST segment elevationST segment elevation

2.2. Increased serum CK-MB Increased serum CK-MB

3.3. Increased serum troponinsIncreased serum troponins

4.4. Increased C-reactive Increased C-reactive proteinprotein

151

Management of unstable angina or acute Management of unstable angina or acute myocardial infarction must include myocardial infarction must include interventions/medications that:interventions/medications that:

Incr

ease

oxy

ge...

Dec

reas

e th

e o...

Rel

ieve

the

sy...

All

of the

abo...

25% 25%25%25%1.1. Increase oxygen supply Increase oxygen supply to the myocardium to the myocardium

2.2. Decrease the oxygen Decrease the oxygen demands of the demands of the myocardium myocardium

3.3. Relieve the symptomsRelieve the symptoms

4.4. All of the above All of the above

152

Need a break?Need a break?

153

Heart FailureHeart Failure

154

Heart FailureHeart Failure Failure of the heart to function as a pumpFailure of the heart to function as a pump Normally pumping ability adjusts to body Normally pumping ability adjusts to body

needs for Oneeds for O22

Cardiac ReserveCardiac Reserve Ability to Ability to CO during CO during need need Athletes have large cardiac reserveAthletes have large cardiac reserve HF pts (and elderly) have poor cardiac HF pts (and elderly) have poor cardiac

reserve reserve

155

Heart FailureHeart Failure

HF involves interplay between 2 factors:HF involves interplay between 2 factors:1.1. Inability of failing heart to maintain Inability of failing heart to maintain

sufficient CO to support body functionssufficient CO to support body functions

2.2. Recruitment ( and subsequent failure) of Recruitment ( and subsequent failure) of compensatory mechanisms designed to compensatory mechanisms designed to maintain cardiac reservemaintain cardiac reserve

156

Cardiac OutputCardiac Output

Stroke Stroke VolumeVolume

Heart Heart RateRate

PreloadPreload

LVEDVLVEDV

AfterloadAfterload

SVRSVR

ContractilityContractility

LVSWI LVSWI

Determinant of Cardiac OutputDeterminant of Cardiac Output

157

SV

Contractility

CO

O2 to Organs

Trigger Compensatory

Mechanisms

Blood volumeVascular resistance

Cardiac work

HF

158

Vicious Cycle of Heart FailureVicious Cycle of Heart Failure

Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 518 159

Compensatory Mechanisms Compensatory Mechanisms Maintain Vital Organ PerfusionMaintain Vital Organ Perfusion

Compensated heart failureCompensated heart failureShort term useShort term use

Decompensated heart failureDecompensated heart failureCompensatory mechanisms no longer Compensatory mechanisms no longer

effectiveeffectiveCompensatory mechanisms become Compensatory mechanisms become

detrimentaldetrimental

160

Compensatory MechanismsCompensatory Mechanisms Frank Starling mechanismFrank Starling mechanism Increased SNS activityIncreased SNS activity

HR, HR, preload d/t alpha receptor stimulation preload d/t alpha receptor stimulation Renin-angiotensin-aldosterone systemRenin-angiotensin-aldosterone system Atrial natriuretic peptideAtrial natriuretic peptide

Hormone release from atrial cells in response to Hormone release from atrial cells in response to stretch. stretch. Promotes diuresis.Promotes diuresis.

Myocardial HypertrophyMyocardial Hypertrophy in number of contractile elements in myocardial cells to in number of contractile elements in myocardial cells to

contractile performance contractile performance

161

Causes of CHFCauses of CHFImpaired Cardiac FunctionImpaired Cardiac Function Excess Work DemandsExcess Work Demands

Myocardial DiseaseMyocardial Disease Increased PressureIncreased Pressure

CardiomyopathyCardiomyopathy Systemic hypertensionSystemic hypertension

Myocardial infarctionMyocardial infarction Pulmonary hypertensionPulmonary hypertension

Coronary artery diseaseCoronary artery disease Coarctation of aortaCoarctation of aorta

MyocardititsMyocarditits Increased Volume WorkIncreased Volume Work

Cardiac Valve DiseaseCardiac Valve Disease A-V shuntA-V shunt

Congenital Heart DefectsCongenital Heart Defects Excessive administration Excessive administration of IV fluidsof IV fluids

164

Heart FailureHeart Failure Pulmonary and/or systemic venous congestionPulmonary and/or systemic venous congestion Described asDescribed as

Systolic vs diastolic failureSystolic vs diastolic failure Right vs left sided failureRight vs left sided failure

165

Systolic DysfunctionSystolic Dysfunction

Impaired ejectionImpaired ejection

cardiac contractilitycardiac contractility CO CO

Conditions that Conditions that contractility: contractility:ischemic heart disease,ischemic heart disease, preload, preload, afterload afterload

Symptoms mainly result of Symptoms mainly result of COCO “ “forward” flowforward” flow

Porth 2005 28-4

EF

167

Diastolic DysfunctionDiastolic Dysfunction

Porth 2005 28-4

Impaired fillingImpaired filling

LV Filling LV Filling CO CO

Conditions that cause diastolic Conditions that cause diastolic dysfunction: conditions that restrict dysfunction: conditions that restrict diastolic fillingdiastolic filling

- MV stenosis- MV stenosis- - ventricular hypertrophy ventricular hypertrophy- Delay diastolic relaxation (aging)- Delay diastolic relaxation (aging)

EF

168

“Backward”

“Forward”

170

Right Heart Failure (RHF) fluid fluid accumulation in accumulation in systemic venous systemsystemic venous system venous congestion venous congestion peripheral edemaperipheral edema

CausesCauses::Pulmonic valve stenosis Pulmonic valve stenosis or regurgitationor regurgitationRV infarctionRV infarctionCardiomyopathyCardiomyopathyPEPE (or anything else (or anything else PVR)PVR)

Cor Pulmonale:Cor Pulmonale: RHF RHF caused by lung diseasecaused by lung disease

Signs &Symptoms:

171

Left Heart Failure (LHF)

PathophysiologyPathophysiology::

COCO LA & LV EDV & LA & LV EDV & pulmonary pressure pulmonary pressure eventually pulmonary eventually pulmonary edema.edema.

CausesCauses::

Acute MIAcute MIHypertensionHypertensionCardiomyopathyCardiomyopathyMV stenosis/regurgitationMV stenosis/regurgitation

Signs & Symptoms

• Renal dysfunction

172

BNP: B-Type natriuretic peptideBNP: B-Type natriuretic peptide Synthesized in myocardium Synthesized in myocardium

of ventriclesof ventricles Released in response to Released in response to

ventricular dilation & ventricular dilation & overloadoverload

Normal ~ 1-30 picogms/mlNormal ~ 1-30 picogms/ml Normally increases with Normally increases with

age, renal failure, age, renal failure, B-Blockers, diureticsB-Blockers, diuretics

173

BNP in BNP in Heart FailureHeart Failure

• DiagnosisDiagnosis BNP < 100, used to rule out new HF BNP < 100, used to rule out new HF Higher levels associated with more myocardial Higher levels associated with more myocardial

damagedamage

• Prognosis and guiding therapyPrognosis and guiding therapy Increased risk of death or readmission, Increased risk of death or readmission,

independent of clinical findingsindependent of clinical findings Relevant changes in level and role for Relevant changes in level and role for

determining treatmentdetermining treatment

174

HF ClassificationsHF ClassificationsACC/AHAACC/AHA NYHA Functional ClassNYHA Functional Class

AA High Risk; no structural High Risk; no structural disease or symptomsdisease or symptoms

BB Structural disease; no Structural disease; no symptomssymptoms

II Asymptomatic Asymptomatic

CC Structural disease with Structural disease with symptomssymptoms

IIII Symptomatic w/ moderate Symptomatic w/ moderate exertionexertion

IIIIII Symptomatic w/ minimal Symptomatic w/ minimal exertionexertion

DD Advanced structural Advanced structural disease; severe symptoms; disease; severe symptoms; invasive tx neededinvasive tx needed

IVIV Symptomatic at rest Symptomatic at rest

175

Heart Failure ManagementHeart Failure ManagementGOALSGOALS

1. Reduce myocardial restructuring / remodeling1. Reduce myocardial restructuring / remodeling ACE-I, ARB, beta blockers ACE-I, ARB, beta blockers

2. Reduce/minimize symptoms 2. Reduce/minimize symptoms improve quality of life!!!improve quality of life!!! diuretics, digoxindiuretics, digoxin

3. Improve contractility 3. Improve contractility increase CO, vital organ perfusionincrease CO, vital organ perfusion dobutamine, digoxindobutamine, digoxin

176

Diuretics Preload

Vasodilators Afterload

177

Diuretic TherapyDiuretic Therapy

Furosemide (Lasix)Furosemide (Lasix) Ascending loop of Ascending loop of

HenleHenle Block Na+ & Cl- Block Na+ & Cl-

reabsorption reabsorption prevent water prevent water reabsorptionreabsorption

Rapid onsetRapid onset PO 60 minPO 60 min IV 5 minIV 5 min

Lehne 2007, Fig 40-2178

Loop Diuretics Adverse EffectsLoop Diuretics Adverse Effects HypotensionHypotension

Volume lossVolume lossVenodilationVenodilation

HypokalemiaHypokalemiaVentricular dysrythmiasVentricular dysrythmiasIncrease risk of dig toxicityIncrease risk of dig toxicity

HyponatremiaHyponatremia HypochloremiaHypochloremia

179

Afterload Reduction in HFAfterload Reduction in HFVasodilationVasodilation - - Decrease resistance to ventricular Decrease resistance to ventricular ejection of blood ejection of blood- Improves forward blood flow- Improves forward blood flow- Reduce cardiac workload- Reduce cardiac workload- Reduce compensatory myocardial - Reduce compensatory myocardial remodeling remodeling

180

Angiotensin Converting Enzyme Angiotensin Converting Enzyme Inhibitors (ACE-I)Inhibitors (ACE-I)

(captopril, lisinopril, enalipril)(captopril, lisinopril, enalipril)

Mechanism of ActionMechanism of ActionInhibit angiotensin I conversion to angiotensin IIInhibit angiotensin I conversion to angiotensin II

Prevents vasoconstrictionPrevents vasoconstriction Dilate arterioles (Dilate arterioles ( afterload) afterload)

Decreases aldosterone release (Decreases aldosterone release ( preload) preload)

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Angiotensin II Receptor Blockers Angiotensin II Receptor Blockers (ARBs)(ARBs)

(valsartan)(valsartan)

Mechanism of ActionMechanism of ActionBlocks actions of angiotensin II at its receptorBlocks actions of angiotensin II at its receptor

Aldosterone release Aldosterone release Dilate arterioles Dilate arterioles

Na & HNa & H22O excretionO excretion AfterloadAfterload

PreloadPreload

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ALLALL Heart Failure Patients Heart Failure Patients SHOULD BE ONSHOULD BE ON

an ACE-I or ARB !!!!!!!!an ACE-I or ARB !!!!!!!!

American College of Cardiologists, American College of Cardiologists,

TJC, NQF, AHRQTJC, NQF, AHRQ

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Beta blockers and HFBeta blockers and HF

Selective use due to negative inotropic effectSelective use due to negative inotropic effect Decrease contractility and afterload Decrease contractility and afterload reduce reduce

cardiac re-modelingcardiac re-modeling Cardioselective beta blockers have been Cardioselective beta blockers have been

shown to improve morbidity & mortalityshown to improve morbidity & mortality Ex. metoprolol (Ex. metoprolol (beta)beta), bisoprolol (, bisoprolol (beta)beta), ,

carvedilol carvedilol (alpha & beta blocker) (alpha & beta blocker)

184

Digoxin: Considerations in HFDigoxin: Considerations in HF Increases intracellular calcium concentration Increases intracellular calcium concentration

improves contractility improves contractility PLUSPLUS slows heart rate slows heart rate

Provides symptom reliefProvides symptom relief Treatment should begin with low doses (≤ 0.125 Treatment should begin with low doses (≤ 0.125

mg/d), esp. in elderly, women or kidney diseasemg/d), esp. in elderly, women or kidney disease Serum concentrations 0.5–0.9 ng/mL Serum concentrations 0.5–0.9 ng/mL Risk factors for digoxin toxicity (≥ 1 ng/mL): old Risk factors for digoxin toxicity (≥ 1 ng/mL): old

age, female sex, high serum creatinine, use of age, female sex, high serum creatinine, use of non– potassium-sparing diuretics non– potassium-sparing diuretics

ACE-I & ARBs ACE-I & ARBs Reduce digoxin therapeutic effect Reduce digoxin therapeutic effect

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Aldosterone receptor blockerAldosterone receptor blocker (spironolactone [Aldactone])(spironolactone [Aldactone])Advanced HF, symptomatic despite ACE-I, dig, Advanced HF, symptomatic despite ACE-I, dig,

etc.etc.Blocks aldosterone receptors & actionsBlocks aldosterone receptors & actionsBenefits in HFBenefits in HF reduces cardiac remodelingreduces cardiac remodeling decreased sympathetic NS activation decreased sympathetic NS activation

Positive inotropic agents: Positive inotropic agents: more on these latermore on these later

186

The renin-angiotensin-aldosterone system contributes to The renin-angiotensin-aldosterone system contributes to worsening of heart failure and myocardial remodeling. worsening of heart failure and myocardial remodeling. Appropriate management includes administration of Appropriate management includes administration of ______ which targets this system.______ which targets this system.

25% 25%25%25%

1.1. Calcium channel Calcium channel blocker blocker

2.2. Angiotensin Angiotensin converting enzyme converting enzyme inhibitor inhibitor

3.3. Diuretic Diuretic

4.4. DigoxinDigoxin187

A patient has severe mitral stenosis which greatly limits blood A patient has severe mitral stenosis which greatly limits blood flow between the left atrium and the left ventricle. This flow between the left atrium and the left ventricle. This condition may produce heart failure due to which of the condition may produce heart failure due to which of the following?following?

Systo

lic d

ysfu

nctio

n

Diast

olic d

ysfu

nctio

n

50%50%

1.1. Systolic dysfunctionSystolic dysfunction

2.2. Diastolic dysfunctionDiastolic dysfunction

188

A patient is newly diagnosed with heart failure. A patient is newly diagnosed with heart failure. Which of the following drugs should Which of the following drugs should alwaysalways be be prescribed?prescribed?

A bet

a blo

cker

A cal

cium

chan

nel b

l...

A diu

retic

An ACE in

hibito

r or A

RB

25%25%25%25%1.1. A beta blockerA beta blocker

2.2. A calcium channel A calcium channel blockerblocker

3.3. A diureticA diuretic

4.4. An ACE inhibitor An ACE inhibitor or ARBor ARB

189

Disorders of Heart ValvesDisorders of Heart Valves

191

Valvular Heart DiseaseValvular Heart Disease Function of the valves is to ensure Function of the valves is to ensure

unidirectionalunidirectional flow of blood in the heart flow of blood in the heart

Dysfunction of valves Dysfunction of valves Narrowing of valve openingNarrowing of valve opening does notdoes not openopen properly = properly = StenosisStenosis Distortion of the valve Distortion of the valve does not does not closeclose properly =properly =RegurgitationRegurgitation

192

StenosisStenosis Valve does not open Valve does not open

properlyproperly resistance to blood flow resistance to blood flow

thru valvethru valve volume & work of the volume & work of the

chamber that empties thru chamber that empties thru narrowed valvenarrowed valve Ex. LA for mitral Ex. LA for mitral

stenosisstenosis Produces distention in one Produces distention in one

chamber & impaired chamber & impaired filling in anotherfilling in another

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RegurgitationRegurgitation Valve does not close Valve does not close

properlyproperly Permits backflow to occur Permits backflow to occur

when valve should be when valve should be closedclosed Ex. Blood flows back Ex. Blood flows back

into LV during diastole into LV during diastole when aortic valve should when aortic valve should be closedbe closed

Produces distention & Produces distention & work demands on ejecting work demands on ejecting chamber chamber

194

195

Mitral Valve ProlapseMitral Valve Prolapse 2-7% of the population2-7% of the population Most asymptomaticMost asymptomatic Usually unknown cause, Usually unknown cause,

although can be associated although can be associated with a variety of conditionswith a variety of conditions

Palpations (awareness of the Palpations (awareness of the heartbeat) and dysrhythmias heartbeat) and dysrhythmias are common.are common. Dysrhythmias may Dysrhythmias may

produce light-headedness produce light-headedness or fainting.or fainting.

Mitral regurgitation may Mitral regurgitation may necessitate valve repair or necessitate valve repair or replacement.replacement.

Sudden death is rare.Sudden death is rare.

Porth, 2007, Essentials of Pathophysiology, 2nd ed., Lippincott, p. 407.

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Valvular Heart DiseaseValvular Heart Disease Valve defects are Valve defects are

characterized by heart characterized by heart murmurs resulting from murmurs resulting from turbulent flow thru valveturbulent flow thru valve

Dysfunction d/tDysfunction d/t Congenital, trauma, Congenital, trauma,

ischemia, age, inflammationischemia, age, inflammation Any valve can be involvedAny valve can be involved Aortic & mitral most Aortic & mitral most

commoncommon

196

Diagram in Handout- Use it to figure out murmurs &Problems with blood flow d/t valvular defects!

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Mitral StenosisMitral Stenosis Incomplete opening of MV Incomplete opening of MV

during diastole during diastole LA distention LA distention

& impaired LV filling& impaired LV filling Resistance thru MV Resistance thru MV LA dilates LA dilates LA pressures LA pressures pulmonary vasculaturepulmonary vasculature pulmonary congestion & pulmonary congestion & HTNHTN Symptoms of Symptoms of CO occur with CO occur with

exertion, or exertion, or HR ( HR (diastolic diastolic filling time)filling time)

198

Mitral Stenosis: Signs & SymptomsMitral Stenosis: Signs & SymptomsWhen would you hear a murmur?

DIASTOLE

199

Mitral Valve RegurgitationMitral Valve Regurgitation Incomplete closure of MVIncomplete closure of MV During systole, part of LV SV During systole, part of LV SV

goes forward into aorta & goes forward into aorta & regurgitant blood flows back regurgitant blood flows back into LA into LA

Result Result CO &/or pulmonary CO &/or pulmonary congestioncongestion

LV enlarges d/t LV enlarges d/t LVEDV LVEDV LA dilates d/t extra volumeLA dilates d/t extra volume Murmur heard during ????Murmur heard during ????

200

Mitral Valve RegurgitationMitral Valve Regurgitation AcuteAcute

forward SV, forward SV, regurgitant SV regurgitant SV LAP LAP pulmonary edema pulmonary edema

Occur with MI, infective endocarditisOccur with MI, infective endocarditis ChronicChronic

Well tolerated, asymptomatic, until LV Well tolerated, asymptomatic, until LV function becomes impaired function becomes impaired

forward SV, forward SV, regurgitant SV regurgitant SV LAP LAP pulmonary edema pulmonary edema

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Mitral Valve RegurgitationMitral Valve RegurgitationManagementManagement Acute Acute

Improve forward flow with vasodilator, Improve forward flow with vasodilator, eg nitroprussideeg nitroprusside

MV repair, reconstruction, replacementMV repair, reconstruction, replacement ChronicChronic

MV repair, reconstruction, replacementMV repair, reconstruction, replacement

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Aortic Valve StenosisAortic Valve Stenosis resistance to ejection of resistance to ejection of

blood from LV into aortablood from LV into aorta resistance resistance work of LV work of LV

& & volume of blood ejected volume of blood ejected into systemic circulationinto systemic circulation

ManifestationsManifestations R/T R/T SV SV Hypotension, syncope, Hypotension, syncope,

angina, fatigue, angina, fatigue, HR HR (takes longer to eject (takes longer to eject volume)volume)

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Aortic Valve RegurgitationAortic Valve Regurgitation Incompetent AoV Incompetent AoV backflow of blood to LV backflow of blood to LV

during diastole during diastole LV volume d/t LA & LV volume d/t LA &

blood leaking back thru blood leaking back thru incompetent valveincompetent valve

Turbulent flow across Turbulent flow across AV during diastole AV during diastole high pitched blowing high pitched blowing sound sound

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Aortic Valve RegurgitationAortic Valve Regurgitation

AcuteAcuteSudden uncompensated Sudden uncompensated LVEDP LVEDP

pulmonary edema & pulmonary edema & CO CO sympathetic stimulation sympathetic stimulation peripheral vasoconstriction peripheral vasoconstriction afterload afterload CO CO

ChronicChronic Compensated for a whileCompensated for a while

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Valve Disease Summary

206

Which of the following might Which of the following might produce pulmonary edema?produce pulmonary edema?

Mitr

al s

tenosi

s

Pumon

ic s

tenosi

s

Tricusp

id s

tenosi

s

Tricusp

id re

gurgita

tion

25%25%25%25%

1.1. Mitral stenosisMitral stenosis

2.2. Pulmonic stenosisPulmonic stenosis

3.3. Tricuspid stenosisTricuspid stenosis

4.4. Tricuspid Tricuspid regurgitationregurgitation

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Kathryn !!!

Pleeeaaase!Release the students!

Mmmm…excellent!

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Shock:Shock:The rude unhinging of the The rude unhinging of the

machinery of life!machinery of life!

209

ShockShock Adequate perfusion of body tissues depends on:Adequate perfusion of body tissues depends on:

Functioning heart to pump 0Functioning heart to pump 022 into systemic circulation into systemic circulation A vascular system to transport OA vascular system to transport O22 to tissues to tissues Sufficient amount of blood/OSufficient amount of blood/O22

Tissues able to extract OTissues able to extract O22, nutrients from blood, nutrients from blood ShockShock is a condition in which is a condition in which

OO22 & energy supply to tissues is not adequate to meet & energy supply to tissues is not adequate to meet demandsdemands

210

Shock Shock Impairment of cellular metabolismImpairment of cellular metabolism

Impairment of Impairment of oxygen useoxygen use Aerobic to Aerobic to

anaerobic anaerobic metabolismmetabolism

Impairment of Impairment of glucose useglucose use Impaired Impaired

glucose delivery glucose delivery or impaired or impaired glucose uptakeglucose uptake

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SvO2 = 75%

25%



Oxygen Consumption

100%

212

Aerobic Metabolism Anaerobic Metabolism

36 molecules ATP36 molecules ATP 2 molecules ATP2 molecules ATP

Supports normal Supports normal cell functioncell function

Eventual Eventual cell dysfunctioncell dysfunction

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4 Types of Circulatory Shock4 Types of Circulatory Shock1.1. HypovolemicHypovolemic

Diminished blood volume Diminished blood volume inadequate inadequate filling of vascular compartmentfilling of vascular compartment

Loss of whole blood/plasma, extracellular fluidLoss of whole blood/plasma, extracellular fluid

2.2. CardiogenicCardiogenic Failure of the heart to function as a pumpFailure of the heart to function as a pump

3.3. ObstructiveObstructive Mechanical barrier to blood flow in circulationMechanical barrier to blood flow in circulation

PE, cardiac tamponadePE, cardiac tamponade

4.4. DistributiveDistributive Enlargement of vascular compartmentEnlargement of vascular compartment

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Compensatory MechanismsCompensatory MechanismsSympathetic Nervous SystemSympathetic Nervous System Heart rateHeart rate Respiratory rateRespiratory rate GlycolysisGlycolysis Urine outputUrine output Blood flow to internal organsBlood flow to internal organs PeristalsisPeristalsis Cool skinCool skin DiaphoresisDiaphoresis

215

CardiogenicCardiogenicShockShock

218

PreloadPreload

SVSV

Restore Cardiac Pump Restore Cardiac Pump Ventricular ContractilityVentricular Contractility

Positive Inotropic AgentsPositive Inotropic Agents

DepressedDepressed

NormalNormal

EnhancedEnhanced

219

Enhance ContractilityEnhance ContractilityBeta –1 Effect, increase contractilityBeta –1 Effect, increase contractility EpinephrineEpinephrine DobutamineDobutamine DopamineDopamine

AdministrationAdministration Correct hypovolemia 1Correct hypovolemia 1stst !! !! Use infusion pumpUse infusion pump Central venous catheter (CVC) preferred routeCentral venous catheter (CVC) preferred route

220

DobutamineDobutamineBeta-1 selective adrenergic agonistBeta-1 selective adrenergic agonist First line to increase cardiac outputFirst line to increase cardiac output

Increase contractility & HR via beta-1Increase contractility & HR via beta-1 Typical dose 2.5 – 10 microgm/kg/minTypical dose 2.5 – 10 microgm/kg/min

Adverse EffectsAdverse Effects DysrhythmiasDysrhythmias

When possible give via central venous catheter (CVC) When possible give via central venous catheter (CVC) !!!!

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EpinephrineEpinephrineNon-selective adrenergic agonistNon-selective adrenergic agonist First line in cardiac arrest & anaphylaxisFirst line in cardiac arrest & anaphylaxis

Increase contractility & HR via beta-1Increase contractility & HR via beta-1 Vasoconstriction via alpha-1Vasoconstriction via alpha-1 Bronchodilation via beta-2Bronchodilation via beta-2

Adverse EffectsAdverse Effects DysrhythmiasDysrhythmias AnginaAngina Hyperglycemia in diabeticsHyperglycemia in diabetics Necrosis w/ extravasation Necrosis w/ extravasation Give via CVC!!Give via CVC!!

222

EpinephrineEpinephrineCardiac ArrestCardiac Arrest IV Push IV Push

Pre-filled syringePre-filled syringe Intracardiac Intracardiac

Pre-filled syringePre-filled syringe

w/ really long needle!w/ really long needle!

IV infusionIV infusion Increase contractilityIncrease contractility

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Cardiogenic Shock

Vasodilators Afterload

224

Afterload Manipulation: Restore Afterload Manipulation: Restore perfusion or Decrease Work of Heartperfusion or Decrease Work of Heart

Systemic Vascular Resistance (SVR)

Vasopressors SV & CO BP & perfusion pressure

SVRSVR

VasodilatorsVasodilators SV& CO SV& CO

BP & work of heartBP & work of heart

SVSV

SVRSVR

225

Sodium Nitroprusside (Nipride)Sodium Nitroprusside (Nipride)

Arterial vasodilatorArterial vasodilator reduces resistance to LV ejectionreduces resistance to LV ejection Improves forward flow & increases SV Improves forward flow & increases SV reduces “backward” pressure in the reduces “backward” pressure in the pulmonary pulmonary

vasculature vasculature decrease pulmonary congestiondecrease pulmonary congestion

Also used in acute mitral regurgitation & Also used in acute mitral regurgitation & hypertensive emergencieshypertensive emergencies

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Hypovolemic ShockHypovolemic Shock

Acute loss of 15-20% of blood volumeAcute loss of 15-20% of blood volume Characterized by Characterized by blood volume blood volume inadequate inadequate

filling of the vascular compartment filling of the vascular compartment

venous return to right heartvenous return to right heart

preloadpreload

SV SV CO CO

02 delivery to tissues02 delivery to tissues

227

HypovolemicHypovolemicShockShock

228

Clinical ManifestationsClinical Manifestations Mild Mild

HR, HR, BP, cool extremitiesBP, cool extremities Moderate Moderate

HR >100, sBP~90, Restless, diaphoretic, HR >100, sBP~90, Restless, diaphoretic, oliguriaoliguria

Severe Severe HR >120, BP<60, cold extremities, HR >120, BP<60, cold extremities, LOC LOC

229

Frank-Starling Curve:Frank-Starling Curve:PreloadPreload

SVSV

LVEDVLVEDV

LV dysfunctionLV dysfunction

HypovolemiaHypovolemia

NormalNormal

230

Restore Intravascular VolumeRestore Intravascular Volume

Crystalloid InfusionCrystalloid Infusion Isotonic Fluids Isotonic Fluids

0.9% NaCl 0.9% NaCl

(“Normal Saline”)(“Normal Saline”) Plasmalyte (pH 7.40)Plasmalyte (pH 7.40) Ringers LactateRingers Lactate

Colloid Infusion “Volume Expander”

• Albumin• Hetastarch (Hespan)

231

Stop Intravascular Volume Loss Stop Intravascular Volume Loss &/or DIC&/or DIC

Blood productsBlood productsPlatelets Platelets plug the holes plug the holesFresh frozen plasma (Fresh frozen plasma (FFP)FFP)

correct coagscorrect coags

Restore Oxygen Carrying CapacityRestore Oxygen Carrying Capacity– PRBC replace lost boxcars

– Erythropoietin

232

Distributive SDistributive ShockhockLoss of vessel tone, enlargement of vascular Loss of vessel tone, enlargement of vascular

compartment, displacement of vascular compartment, displacement of vascular volume away from heart & central circulationvolume away from heart & central circulation

Loss of sympathetic tone (Loss of sympathetic tone (neurogenic SCIneurogenic SCI)) Presence of vasodilating substances in blood Presence of vasodilating substances in blood

((anaphylactic shockanaphylactic shock)) Presence of inflammatory mediators in blood Presence of inflammatory mediators in blood

((septic shockseptic shock))

233

Septic ShockSeptic Shock Associated with severe infection and the systemic Associated with severe infection and the systemic

response to the infection.response to the infection. Gram negative organisms most common Gram negative organisms most common Mechanisms related to mediators of inflammatory Mechanisms related to mediators of inflammatory

response response VasodilationVasodilation capillary permeabilitycapillary permeability

Endotoxins induce tissue damage by activating Endotoxins induce tissue damage by activating coagulation cascadecoagulation cascade

Manifests as fever, vasodilationManifests as fever, vasodilation

234

Septic shockSeptic shockEndotoxin & inflammatory mediator release Endotoxin & inflammatory mediator release

Vasodilation Vasodilation Decrease preload Decrease preload Increase cardiac outputIncrease cardiac output

Capillary “leakage” Capillary “leakage” Edema Edema

Coagulopathies Coagulopathies Disseminated Disseminated Intravascular Coagulation Intravascular Coagulation (DIC)(DIC)

236

What is SIRS?What is SIRS?Systemic Inflammatory Response SyndromeSystemic Inflammatory Response SyndromeOften a precursor to sepsis!Often a precursor to sepsis!

Clinical response arising from a nonspecific insult.Clinical response arising from a nonspecific insult.

SIRS criteria includes 2 or more of the following:SIRS criteria includes 2 or more of the following: Temperature Temperature >> 38 38C or C or << 36 36CC Heart Rate Heart Rate >> 90 beats/min 90 beats/min Respiration Respiration >> 20 breaths/min 20 breaths/min WBC WBC >> 12,000/mm 12,000/mm33, < 4,000/mm, < 4,000/mm33 or >10% or >10%

immature cells (bands)immature cells (bands) PaCOPaCO22 < 32mm Hg < 32mm Hg

237

Continuum of SContinuum of Sepsisepsis

SIRS with a suspected or confirmed infx

SepsisSepsisSIRSSIRS Septic Septic ShockShock

≥2 of the following:Temp: >38°C or <36°CH R: >90 beats/minResps: >20/minWBC : >12,000/mm3, or < 4,000/mm3

1992 Consensus Conf Bone et al. Chest. 1992;101:1644-1654.; 2001 SCCM/ESICM/ACCP/TS/SIS International Sepsis Definition Conference. Crit Care Med 2003 31(4):1250-1256.

Sepsis

+ Hypotension despite fluid

+ perfusion abnormalities+ MODS (>1 organ failure, inability to maintain homeostasis w/o tx)

Severe Severe SepsisSepsis

Sepsis +

> 1 organ dysfunction

238

Sepsis Resuscitation BundleSepsis Resuscitation Bundlewithin 1within 1stst hour of recognition hour of recognition

Obtain serum lactateObtain serum lactate Blood cultures (percutaneous) prior to antibioticsBlood cultures (percutaneous) prior to antibiotics AntibioticsAntibiotics Initiate BP, CVP & ScvO2 monitoringInitiate BP, CVP & ScvO2 monitoring If CVP If CVP << 8 mmHg, Hypotension &/or Lactate >4 8 mmHg, Hypotension &/or Lactate >4

Start:Start:

1000ml crystalloid over 30 min.1000ml crystalloid over 30 min.

Vasopressor if no response to fluidVasopressor if no response to fluid

(Clinically important but not on exam)(Clinically important but not on exam)Dellinger P, et al: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis Dellinger P, et al: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis

and Septic Shock 2008. and Septic Shock 2008. Crit Care MedCrit Care Med. 2008;36(1):296-327. 2008;36(1):296-327239

Sepsis Resuscitation BundleSepsis Resuscitation Bundlewithin 1within 1stst 6 hours of recognition 6 hours of recognition

PRBC for Hgb < 7 g/dl, target 7-9 g/dlPRBC for Hgb < 7 g/dl, target 7-9 g/dl Fluid to keep CVP Fluid to keep CVP >> 8 mmHg 8 mmHg MAP MAP >> 65 mmHg 65 mmHg

Crystalloid; Vasopressor if no response to fluidCrystalloid; Vasopressor if no response to fluid ScvO2 ScvO2 >> 70 % 70 %

Dobutamine; RBC if Hct < 30%Dobutamine; RBC if Hct < 30% Transfer to ICUTransfer to ICU

(Clinically important but not on exam)(Clinically important but not on exam)

Dellinger P, et al: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis Dellinger P, et al: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2008. and Septic Shock 2008. Crit Care MedCrit Care Med. 2008;36(1):296-327. 2008;36(1):296-327

240

Catecholamines: Adrenergic AgonistsCatecholamines: Adrenergic Agonists

Alpha 1Alpha 1 Beta 1Beta 1 Beta 2Beta 2 DopamineDopamine

VasoconstrictVasoconstrict CardiacCardiac

stimulationstimulation

BronchodilateBronchodilate Renal artery Renal artery dilationdilation

Phenylephrine

Epinephrine

Norepinephrine (Levophed)

Dobutamine

Dopamine Dopamine Dopamine

241

Complications of ShockComplications of Shock““Shock not only stops the machinery, but it wrecks the Shock not only stops the machinery, but it wrecks the

machinery” (Wiggers)machinery” (Wiggers) Many body systems are “wrecked” by shockMany body systems are “wrecked” by shock ComplicationsComplications

Acute respiratory failure/respiratory distress syndromeAcute respiratory failure/respiratory distress syndrome Acute renal failureAcute renal failure GI bleedingGI bleeding Disseminated intravascular coagulationDisseminated intravascular coagulation Multiple organ dysfunction syndromeMultiple organ dysfunction syndrome

242

Cardiac OutputCardiac Output

Stroke Stroke VolumeVolume

Heart Heart RateRate

PreloadPreload AfterloadAfterload

ContractilityContractility

Management of Shock: Oxygen DeliveryManagement of Shock: Oxygen Delivery

SaO2 & HgbSaO2 & Hgb XX

Reverse the causative factor(s)Reverse the causative factor(s)Restore perfusion to cells, tissues, organsRestore perfusion to cells, tissues, organs

243


SvO2 = 75%

25%



Oxygen Consumption

100%

244

Appropriate treatment of Appropriate treatment of hypotension related to cardiogenic hypotension related to cardiogenic shock includes:shock includes:

Volu

me

infu

sio...

Vas

opres

sor (

e...

Posi

tive

inotr.

..

Incr

easi

ng hea

...

25% 25%25%25%1.1. Volume infusionVolume infusion

2.2. Vasopressor (eg Vasopressor (eg levophed)levophed)

3.3. Positive inotrope (eg Positive inotrope (eg dobutamine)dobutamine)

4.4. Increasing heart rate Increasing heart rate (eg atropine)(eg atropine)

245

Appropriate treatment of Appropriate treatment of hypotension related to hypovolemic hypotension related to hypovolemic shock includes:shock includes:

Volu

me

infu

sio...

Vas

opres

sor (

e...

Posi

tive

inotr.

..

Incr

easi

ng hea

...

25% 25%25%25%

1.1. Volume infusionVolume infusion

2.2. Vasopressor (eg Vasopressor (eg levophed)levophed)

3.3. Positive inotrope Positive inotrope (eg dobutamine)(eg dobutamine)

4.4. Increasing heart Increasing heart rate (eg atropine)rate (eg atropine)

246

Which of the following will produce Which of the following will produce cold extremities?cold extremities?

Cardi

ogenic

sho

ck

Anaphyl

actic

sho

ck

Septic

shock

Obstru

ctiv

e sh

ock

25%25%25%25%

1.1. Cardiogenic shockCardiogenic shock

2.2. Anaphylactic Anaphylactic shockshock

3.3. Septic shockSeptic shock

4.4. Spinal shockSpinal shock

247

SaO2/HbSaO2/Hb

COCO

O2 Utilization

Extraction & VO2

O2 Utilization

Extraction & VO2

VenousReturnSvOSvO22

O2 Delivery

248

Questions?Questions?

249

Cv ii patho pharm fall 11

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Transcript of Cv ii patho pharm fall 11