Amiodarone IV: Amiodarone IV: Indications, Dosing, Indications, Dosing,

Clinical Studies, Clinical Studies, Efficacy, and Efficacy, and BibliographyBibliography

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INDICATIONS INDICATIONS AMIODARONE IVAMIODARONE IV

Amiodarone I.V.(Cordarone® I.V.)

Indication: Indication: Amiodarone I.V. is Amiodarone I.V. is indicated for initiation of indicated for initiation of treatment and prophylaxis of treatment and prophylaxis of frequently recurring ventricular frequently recurring ventricular fibrillation and hemodynamically fibrillation and hemodynamically unstable ventricular tachycardia unstable ventricular tachycardia in patients refractory to other in patients refractory to other therapy.therapy.

Amiodarone I.V.Amiodarone I.V.((CordaroneCordarone®® I.V.)I.V.)

• Cordarone I.V. is contraindicated in patients Cordarone I.V. is contraindicated in patients with cardiogenic shock, marked sinus with cardiogenic shock, marked sinus bradycardia, and second- or third-degree AV bradycardia, and second- or third-degree AV block in the absence of a functioning block in the absence of a functioning pacemaker.pacemaker.

• Cordarone I.V. should be administered only Cordarone I.V. should be administered only by physicians who are experienced in the by physicians who are experienced in the treatment of life-threatening arrhythmias, who treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and are thoroughly familiar with the risks and benefits of Cordarone therapy, and who have benefits of Cordarone therapy, and who have access to facilities adequate for monitoring access to facilities adequate for monitoring the effectiveness and side effects of the effectiveness and side effects of treatment.treatment.

Amiodarone I.V.Amiodarone I.V.((CordaroneCordarone®® I.V.)I.V.)

• Hypotension is the most common adverse Hypotension is the most common adverse effect seen with Cordarone I.V. and may be effect seen with Cordarone I.V. and may be related to the rate of infusion. Hypotension related to the rate of infusion. Hypotension should be treated by slowing the infusion or should be treated by slowing the infusion or with standard therapy: vasopressor drugs, with standard therapy: vasopressor drugs, positive inotropic agents, and volume positive inotropic agents, and volume expansion.expansion.

• The most important treatment-emergent The most important treatment-emergent adverse effects are hypotension (16%), adverse effects are hypotension (16%), bradycardia (4.9%), liver function test bradycardia (4.9%), liver function test abnormalities (3.4%), cardiac arrest (2.9%), VT abnormalities (3.4%), cardiac arrest (2.9%), VT (2.4%), CHF (2.1%), cardiogenic shock (1.3%), (2.4%), CHF (2.1%), cardiogenic shock (1.3%), and AV block (0.5%).and AV block (0.5%).

AMIODARONE IV AMIODARONE IV DOSINGDOSING

Rapid Onset of ActionRapid Onset of Action1-1-44

Antiarrhythmic effects are seen in Antiarrhythmic effects are seen in minutesminutes3,43,4

Hypotension is the most common Hypotension is the most common adverse effect seen with Cordaroneadverse effect seen with Cordarone®® I.V. (amiodarone HCI) and may be I.V. (amiodarone HCI) and may be related to the rate of infusion.related to the rate of infusion.

1.1. Kadish A, Morady F. The use of intravenous amiodarone in the acute therapy of life-threatening Kadish A, Morady F. The use of intravenous amiodarone in the acute therapy of life-threatening tachyarrhythmias. tachyarrhythmias. Prog Cardiovasc DiscProg Cardiovasc Disc. 1989;31:281-294. . 1989;31:281-294.

2.2. Helmy I, Herre JM, Gee G, et al. Use of intravenous amiodarone for emergency treatment of life-Helmy I, Herre JM, Gee G, et al. Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias. threatening ventricular arrhythmias. J Am Coll CardiolJ Am Coll Cardiol. 1988;12:1015-1022.. 1988;12:1015-1022.

3.3. Holt P, Curry P, Way B, et al. Intravenous amiodarone; an effective anti-arrhythmic agent. Holt P, Curry P, Way B, et al. Intravenous amiodarone; an effective anti-arrhythmic agent. Am J Cardiol. Am J Cardiol. 1982;49:1001. Abstract.1982;49:1001. Abstract.

4.4. Benjamin R, Denizeau J-P, Melon J, et al. Les effets antiarythmiques de l’amiodarone injectable: à propos Benjamin R, Denizeau J-P, Melon J, et al. Les effets antiarythmiques de l’amiodarone injectable: à propos de 100 cas. de 100 cas. Arch Mal Coeur. Arch Mal Coeur. 1976;69:513-522.1976;69:513-522.

Dose RecommendationsDose Recommendations -- First 24 Hours -- -- First 24 Hours --

Loading InfusionsLoading Infusions

FirstFirst Rapid: 150 mg over the FIRST 10 Rapid: 150 mg over the FIRST 10 minutes (15 mg/min). Add 3 mL of minutes (15 mg/min). Add 3 mL of Amiodarone I.V. (150 mg) to 100 mL Amiodarone I.V. (150 mg) to 100 mL DD55W (1.5 mg/mL) and infuse over 10 W (1.5 mg/mL) and infuse over 10 minutes.minutes.

Followed by Followed by Slow 360 mg over the Slow 360 mg over the NEXT 6 hours (1 mg/min). Add 18 mL NEXT 6 hours (1 mg/min). Add 18 mL of Amiodarone I.V. (900 mg) to 500 mL of Amiodarone I.V. (900 mg) to 500 mL DD55W concentration = 1.8 mg/mL).W concentration = 1.8 mg/mL).

Dose RecommendationsDose Recommendations -- First 24 Hours -- -- First 24 Hours --

Maintenance InfusionMaintenance Infusion

540 mg over the REMAINING 18 540 mg over the REMAINING 18 hours (0.5 mg/min). Decrease the hours (0.5 mg/min). Decrease the rate of the slow loading infusion to rate of the slow loading infusion to 0.5 mg/min.0.5 mg/min.

Supplemental Infusion*Supplemental Infusion*Add 150 mg to 100 mL DAdd 150 mg to 100 mL D55W; administer over W; administer over

10 minutes (15 mg/min) 10 minutes (15 mg/min) PVCPVC†† or glass container or glass container

•Hypotension is the most common adverse effect Hypotension is the most common adverse effect seen with Amiodarone I.V. and may be related to seen with Amiodarone I.V. and may be related to the rate of infusionthe rate of infusion

•Must use volumetric pump when administering Must use volumetric pump when administering Amiodarone I.V.; an in-line filter is recommendedAmiodarone I.V.; an in-line filter is recommended

•Store ampuls in cartons until ready for use to Store ampuls in cartons until ready for use to protect from lightprotect from light

•Prepared solutions should not be kept for more Prepared solutions should not be kept for more than 24 hoursthan 24 hours

** For the management of breakthrough episodes of life-threatening VT or VF.For the management of breakthrough episodes of life-threatening VT or VF.Alternatively, the rate of the maintenance infusion may be increased.Alternatively, the rate of the maintenance infusion may be increased.

†† 10% loss after two hours 10% loss after two hours

Supplemental Infusion*Supplemental Infusion*Add 150 mg to 100 mL DAdd 150 mg to 100 mL D55W; administer over W; administer over

10 minutes (15 mg/min) 10 minutes (15 mg/min) PVCPVC†† or glass container or glass container

•Concentrations greater than 3 mg/mL in DConcentrations greater than 3 mg/mL in D55W W have been associated with a high incidence have been associated with a high incidence of peripheral vein phlebitisof peripheral vein phlebitis

•For infusions longer than 1 hour, Cordarone For infusions longer than 1 hour, Cordarone I.V. concentrations I.V. concentrations should not exceed 2 mg/mL unless a central should not exceed 2 mg/mL unless a central venous catheter is usedvenous catheter is used

•Evacuated glass containers for admixing Evacuated glass containers for admixing Cordarone I.V. are not recommendedCordarone I.V. are not recommended

A Treatment Algorithm for Cardiac Arrest* A Treatment Algorithm for Cardiac Arrest* Utilizing CordaroneUtilizing Cordarone®®

I.V. (amiodarone HCI)I.V. (amiodarone HCI)

Pulseless VT/VFPulseless VT/VF

Shock x 3Shock x 3

Persistent or recurrentPersistent or recurrentVT/VFVT/VF

Continue CPRContinue CPRIntubateIntubate

Obtain IV accessObtain IV access

Epinephrine 1 mg I.V.Epinephrine 1 mg I.V.q 3 to 5 minutesq 3 to 5 minutes

Cordarone I.V. 300 mgCordarone I.V. 300 mgrapid peripheral infusionrapid peripheral infusion

DF 360 J withinDF 360 J within30 to 60 sec after each drug30 to 60 sec after each drug

“Drug-Shock”, “Drug-Shock”“Drug-Shock”, “Drug-Shock”

IIIIbb Medications, e.gMedications, e.g.,.,LidocaineLidocaineProcainamideProcainamideetc.etc.

*Due to persistent VF/pulseless VT*Due to persistent VF/pulseless VT

Adapted from Gonzalez ER, Kannewurf BS, Ornato JP. Adapted from Gonzalez ER, Kannewurf BS, Ornato JP. ResuscitationResuscitation. 1998;39:33-42.. 1998;39:33-42.

AMIODARONE IV AMIODARONE IV EFFICACYEFFICACY

Suppresses Highly Malignant Suppresses Highly Malignant Ventricular Arrhythmias in Patients Ventricular Arrhythmias in Patients

With Severe Underlying Heart DiseaseWith Severe Underlying Heart Disease11

In clinical studiesIn clinical studies• Decreased median number of life-threatening Decreased median number of life-threatening

events by 71%events by 71%22

• Increased median time to first event to 13.7 hoursIncreased median time to first event to 13.7 hours22

• 85% of patients in controlled studies survived the 85% of patients in controlled studies survived the critical first 24 hours.critical first 24 hours.33 Without a placebo comparison, Without a placebo comparison, a mortality benefit could not be established.a mortality benefit could not be established.

1.1. Kowey PR, Levine JH, Herre JM, et al. Randomized, double-blind comparison of intravenous Kowey PR, Levine JH, Herre JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent hemodynamically destabilizing amiodarone and bretylium in the treatment of patients with recurrent hemodynamically destabilizing ventricular tachycardia or fibrillation. ventricular tachycardia or fibrillation. CirculationCirculation. 1995;92:3255-3263.. 1995;92:3255-3263.

2.2. Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. in patients with life-threatening ventricular tachyarrhythmias. CirculationCirculation. 1995;92:3264-3272.. 1995;92:3264-3272.

3.3. Data on file, Wyeth-Ayerst Laboratories.Data on file, Wyeth-Ayerst Laboratories.

Reduction of VT/VF Events Reduction of VT/VF Events During Double-Blind TherapyDuring Double-Blind Therapy11

0.00

0.05

0.10

125 mg 500 mg 1000 mg

• The 125 mg dose group was used as a control group.The 125 mg dose group was used as a control group.• Due to administration of supplemental infusions, the 1000 mg dose group actually Due to administration of supplemental infusions, the 1000 mg dose group actually

received 1185 mg/24 hours compared to the 125 mg dose group, which received received 1185 mg/24 hours compared to the 125 mg dose group, which received 428 mg/24 hours428 mg/24 hours

0.070.07

0.020.02

PP=0.067=0.06771%71%

ReductionReduction

Ev

en

ts/h

r (m

ed

ian

)E

ve

nts

/hr

(me

dia

n)

Reproduced with permission. Reproduced with permission. Circulation. Circulation. Copyright 1995 American Heart Association.Copyright 1995 American Heart Association.

1.1. Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. threatening ventricular tachyarrhythmias. CirculationCirculation. 1995;92:3264-3272.. 1995;92:3264-3272.

0.040.04

Cordarone I.V. Dosing (mg/24 Hours)Cordarone I.V. Dosing (mg/24 Hours)

Reduction from BaselineReduction from Baselinein VT/VF Eventsin VT/VF Events11

No significant difference observed between the 1000 mg dose No significant difference observed between the 1000 mg dose and the 500 mg dose or the 125 mg dose and the 500 mg doseand the 500 mg dose or the 125 mg dose and the 500 mg dose

1000 mg1000 mg 125 mg125 mg DifferenceDifferencefrom baselinefrom baseline

4.04.0

0.480.48

3.03.0

1.681.68

3.523.52(88%(88%reduction)reduction)

1.321.32(44%(44%reduction)reduction)

PP=0.0425=0.0425

BaselineBaseline

Cordarone I.V. 125 mgCordarone I.V. 125 mg

Cordarone I.V. 1000 mgCordarone I.V. 1000 mg

Med

ian

VT

/VF

Eve

nts

Med

ian

VT

/VF

Eve

nts

per

24

Ho

urs

per

24

Ho

urs

Reproduced with permission. Reproduced with permission. Circulation. Circulation. Copyright 1995 American Heart Association.Copyright 1995 American Heart Association.

1.1. Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. threatening ventricular tachyarrhythmias. CirculationCirculation. 1995;92:3264-3272.. 1995;92:3264-3272.

AMIODARONE IV AMIODARONE IV CLINICAL CLINICAL STUDIESSTUDIES

Amiodarone in out-of-hospital Amiodarone in out-of-hospital Resuscitation of REfractory Sustained Resuscitation of REfractory Sustained

ventricular Tachyarrhythmias (ARREST)ventricular Tachyarrhythmias (ARREST)

A prospective, randomized, double-blind, placebo-A prospective, randomized, double-blind, placebo-controlled comparison of ACLS guidelines with and controlled comparison of ACLS guidelines with and without intravenous amiodarone in out-of-hospital cardiac without intravenous amiodarone in out-of-hospital cardiac arrest due to shock-refractory VF/VTarrest due to shock-refractory VF/VT

Kudenchuk PJ, Cobb LA, Copass LA, et al. Kudenchuk PJ, Cobb LA, Copass LA, et al. New Engl J Med. New Engl J Med. 1999. 341:871-878. 1999. 341:871-878.

ARREST Eligibility CriteriaARREST Eligibility Criteria

•Age >18 yearsAge >18 years

•Nontraumatic out-of-hospital Nontraumatic out-of-hospital cardiac arrestcardiac arrest

•Ongoing VF/VT after 3+ shocksOngoing VF/VT after 3+ shocks

•Medics and study drug on sceneMedics and study drug on scene

• I.V. accessI.V. access

•PrimaryPrimary- Admission to hospital with a Admission to hospital with a

spontaneously perfusing spontaneously perfusing rhythm (assigned to a hospital rhythm (assigned to a hospital bed)bed)

ARREST ARREST Study End PointsStudy End Points

•Secondary Secondary -Adverse effectsAdverse effects-Total duration of resuscitative effortsTotal duration of resuscitative efforts-Number of shocks after study drugNumber of shocks after study drug-Need for additional antiarrhythmic drugsNeed for additional antiarrhythmic drugs

•Also EvaluatedAlso Evaluated -Survival to hospital discharge*Survival to hospital discharge*-Neurologic status at hospital discharge*Neurologic status at hospital discharge*

ARREST Study End ARREST Study End PointsPoints

** Due to sample size, trial was not powered to detect significant differences Due to sample size, trial was not powered to detect significant differences between treatment groups.between treatment groups.

Study AlgorithmStudy Algorithm

Cardiac ArrestCardiac Arrest

VF or Pulseless VTVF or Pulseless VT

Study DrugStudy Drug

Standard ACLS CareStandard ACLS Care

PlaceboPlaceboI.V. amiodaroneI.V. amiodarone

ETTETTI.V.I.V.EPIEPI

Persistent or Persistent or Recurrent VF/VTRecurrent VF/VT

StableStableRhythmRhythm

AsystoleAsystoleor PEAor PEA

Excluded From StudyExcluded From Study

ETT:ETT: endotracheal intubationendotracheal intubationI.V.:I.V.: intravenous access establishedintravenous access establishedEPI:EPI: epinephrineepinephrinePEA:PEA: pulseless electrical activitypulseless electrical activity

Shock x 3Shock x 3

November 1994 – February 1997November 1994 – February 1997Out-of-Hospital Cardiac ArrestOut-of-Hospital Cardiac Arrest

Ineligible/NotIneligible/NotTreatedTreated(n=3260)(n=3260)

• BLS Only/DOABLS Only/DOA• Age/TraumaAge/Trauma• PEA/AsystolePEA/Asystole• <3 Shocks<3 Shocks

• Insufficient Insufficient number of shocksnumber of shocks

• ROSC at time of RxROSC at time of Rx• TraumaTrauma

• VF/VT terminated VF/VT terminated before Rxbefore Rx

• Protocol violationProtocol violation

Ineligible/TreatedIneligible/Treated(n=27)(n=27)

Eligible/NotEligible/NotTreatedTreated(n=160)(n=160)

Drug AssignmentDrug AssignmentUnknownUnknown

(n=3)(n=3)

(n=3954)(n=3954)

Met Study CriteriaMet Study Criteria(n=667)(n=667)

Eligible/TreatedEligible/Treated(n=507)(n=507)

Study GroupStudy Group(n=504)(n=504)

BLS:BLS: basic life supportbasic life support

PEA:PEA: pulseless electrical activitypulseless electrical activity

ROSC:ROSC: return of spontaneous circulationreturn of spontaneous circulation

ARREST Patient CharacteristicsARREST Patient Characteristics

MaleMale 187187 (76%) (76%) 203 203 (79%)(79%) NSNS

Age (yrs)Age (yrs) 66 66 1414 65 65 1414 NSNS

Cardiac HistoryCardiac History 137137 (64%) (64%) 135135 (59%) (59%) NSNS

Other Medical HistoryOther Medical History 101101 (47%) (47%) 119 119 (52%)(52%) NSNS

Witnessed ArrestWitnessed Arrest 155155 (70%) (70%) 182182 (77%) (77%) 0.070.07

Bystander CPRBystander CPR 155 155 (68%)(68%) 138 138 (59%)(59%) 0.060.06

VF Amplitude (mV)VF Amplitude (mV) 0.42 0.42 0.2 0.2 0.45 0.45 0.20.2 NS NS

I.V. AmiodaroneI.V. Amiodarone(n=246)(n=246)

PlaceboPlacebo(n=258)(n=258) PP-value-value

0

20

40

60

80

100

VF Asystole VF PEA VF

I.V. Amiodarone

Placebo

Initial Cardiac Arrest RhythmInitial Cardiac Arrest Rhythm

PEA: pulseless electrical activityPEA: pulseless electrical activity

% o

f P

atie

nts

8383 8383

44 551212 1111

Response/Treatment TimesResponse/Treatment TimesFrom DispatchFrom Dispatch

Mean Mean 1 SD (Median) Minutes 1 SD (Median) Minutes

1st unit (EMT-D)1st unit (EMT-D) 4.3 4.3 2.0 (4) 2.0 (4) 4.4 4.4 2.3 (4) 2.3 (4) NSNS

Paramedic/ALSParamedic/ALS 8.4 8.4 4.1 (7.8)4.1 (7.8) 8.8 8.8 4.9 (7.9) 4.9 (7.9) NSNS

EMT-DEMT-D ALS ALS 4.1 4.1 4.0 (3) 4.0 (3) 4.5 4.5 4.3 (3.3) 4.3 (3.3) NSNS

1st shock1st shock 8.9 8.9 5.4 (7.6) 5.4 (7.6) 9.5 9.5 7.5 (7.4) 7.5 (7.4) NSNS

I.V.I.V. 13.1 13.1 4.1 (12.7) 4.1 (12.7) 13.7 13.7 4.1 (13.2) 4.1 (13.2) NSNS

IntubationIntubation 14.3 14.3 5.8 (12.7) 5.8 (12.7) 13.8 13.8 4.6 (13.1) 4.6 (13.1) NSNS

Study drugStudy drug 21.4 21.4 8.3 (19.2) 8.3 (19.2) 20.5 20.5 7.0 (19.3) 7.0 (19.3) NSNS

I.V.I.V.AmiodaroneAmiodarone PlaceboPlacebo PP-value-value

Resuscitation CharacteristicsResuscitation CharacteristicsBefore Study DrugBefore Study Drug

Number of shocksNumber of shocks 5 5 2 (4)* 2 (4)* 5 5 2 (4)* 2 (4)* 0.730.73

Transient ROSCTransient ROSC 55 (22%)55 (22%) 52 (20%)52 (20%) 0.610.61

Antiarrhythmic drugAntiarrhythmic drug 65 (26%)65 (26%) 91 (35%)91 (35%) 0.040.04

Bradycardia treatment Bradycardia treatment 32 (13%)32 (13%) 51 (20%)51 (20%) 0.040.04

Pressor treatmentPressor treatment 19 (8%)19 (8%) 22 (9%)22 (9%) 0.740.74

I.V.I.V.AmiodaroneAmiodarone

(n=246)(n=246)PlaceboPlacebo(n=258)(n=258) PP-value-value

ROSC: return of ROSC: return of spontaneous spontaneous circulationcirculation

*Median in parentheses.*Median in parentheses.

0

20

40

60

80

100

Antiarrhythmic Pressor* Bradycardiatreatment*

I.V. Amiodarone

Placebo

Treatment After Study DrugTreatment After Study Drug

* In patients with return of spontaneous circulation.* In patients with return of spontaneous circulation.

% o

f P

atie

nts

8080 8282

5959

48484141

2525

197/246197/246 211/258211/258 91/15391/153 69/14569/145 63/15363/153 36/14536/145

PP=0.70=0.70

PP=0.04=0.04

PP=0.004=0.004

No. Receiving Drug/No. Receiving Drug/Total No.Total No.

0

10

20

30

40

50

60

70

All patients VF Asystole or PEAconverting to VF

ROSC No ROSC

Amiodarone Placebo

Admission to Hospital byAdmission to Hospital byArrest CharacteristicsArrest Characteristics

PEA: pulseless electrical activityPEA: pulseless electrical activityROSC: return of spontaneous circulationROSC: return of spontaneous circulation

Pat

ien

ts S

urv

ivin

gto

Ad

mis

sio

n (

%)

4444

108/246108/246

3434

4949

3939

17171212

6464

41413838

3333

89/25889/258 101/205101/205 84/21684/216 7/417/41 5/425/42 35/5535/55 22/5322/53 73/19173/191 67/20567/205No. Surviving/No. Surviving/Total No.Total No.

0

10

20

30

40

50

60

70I.V. AmiodaronePlacebo

Patient Status at Patient Status at Hospital DischargeHospital Discharge

This trial was not designed or powered to detect significance in survival to hospital discharge.This trial was not designed or powered to detect significance in survival to hospital discharge.

% o

f P

atie

nts

13.4 13.2 16 15

5550

Alive,all patients

Alive,VF only

Resumed independent living

Outcome

ARREST Trial ARREST Trial ConclusionsConclusions

•I.V. amiodarone is effective I.V. amiodarone is effective therapy for shock-refractory VFtherapy for shock-refractory VF

•Adverse effects expected, butAdverse effects expected, butmanageablemanageable

•Improving survival from cardiac Improving survival from cardiac arrest remains an important arrest remains an important challengechallenge

ACC/AHA Treatment ACC/AHA Treatment

Recommendations Recommendations for VT/VFfor VT/VF

•900,000 people in U.S. 900,000 people in U.S. experience an MI annuallyexperience an MI annually

•225,000 die225,000 die- 125,000 die “in the field”125,000 die “in the field”- Most deaths are arrhythmic in Most deaths are arrhythmic in

etiologyetiology

Acute Acute Myocardial InfarctionMyocardial Infarction

Source: Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of Source: Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. patients with acute myocardial infarction. J Am Coll CardiolJ Am Coll Cardiol. 1996;28:1333.. 1996;28:1333.

1990 – ACC/AHA Introduces “Guidelines for the Early 1990 – ACC/AHA Introduces “Guidelines for the Early Management of Patients with Acute MI”Management of Patients with Acute MI”• Not a rigid prescriptionNot a rigid prescription• A “guide” – to be modified by clinical judgment, A “guide” – to be modified by clinical judgment,

patient needs, patient needs, and new findingsand new findings

1994 – ACC/AHA Task Force on Practice Guidelines 1994 – ACC/AHA Task Force on Practice Guidelines ConvenesConvenes• Purpose: to review knowledge accumulated since Purpose: to review knowledge accumulated since

1990 and recommend appropriate changes to the 1990 and recommend appropriate changes to the original guidelinesoriginal guidelines

• Estimated 5,000 publications reviewed over next 1 Estimated 5,000 publications reviewed over next 1 1/2 years1/2 years

1996 – ACC/AHA Publishes Revised Guidelines1996 – ACC/AHA Publishes Revised Guidelines

ACC/AHA Practice GuidelinesACC/AHA Practice Guidelines

Source: Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute Source: Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. myocardial infarction. J Am Coll CardiolJ Am Coll Cardiol. 1996;28:1336.. 1996;28:1336.

Class I:Class I:• Sustained monomorphic VT – Sustained monomorphic VT – Treat with one Treat with one

of the following:of the following:- Lidocaine: bolus 1.0 to 1.5 mg/kgLidocaine: bolus 1.0 to 1.5 mg/kg- Procainamide: 20 to 30 mg/min loading infusion, Procainamide: 20 to 30 mg/min loading infusion,

up to 12 to 17 mg/kg. This may be followed by an up to 12 to 17 mg/kg. This may be followed by an infusion of 1 to 4 mg/mininfusion of 1 to 4 mg/min

- Amiodarone IV: 150 mg infused over 10 min Amiodarone IV: 150 mg infused over 10 min followed by 1.0 mg/min for 6 hrs and then a followed by 1.0 mg/min for 6 hrs and then a maintenance infusion of 0.5 mg/minmaintenance infusion of 0.5 mg/min

- Synchronized electrical cardioversion starting at Synchronized electrical cardioversion starting at 50 J50 J

Amiodarone I.V. is indicated in life-threatening VT/VF refractory to other therapy.Amiodarone I.V. is indicated in life-threatening VT/VF refractory to other therapy.

ACC/AHA Treatment ACC/AHA Treatment Recommendations for VT/VFRecommendations for VT/VF

Class I (Cont’d.):Class I (Cont’d.):

• Sustained monomorphic VT with angina, Sustained monomorphic VT with angina, pulmonary edema, or hypotension (<90 mm pulmonary edema, or hypotension (<90 mm Hg)Hg) – synchronized cardioversion 100 J – synchronized cardioversion 100 J initial energy. Increasing energies may be initial energy. Increasing energies may be used if not initially successfulused if not initially successful

• VF or sustained (>30 sec) polymorphic VTVF or sustained (>30 sec) polymorphic VT – defibrillate up to 3 times if needed (200 J, – defibrillate up to 3 times if needed (200 J, 200 to 300 J, 360 J)200 to 300 J, 360 J)

ACC/AHA Treatment ACC/AHA Treatment Recommendations for VT/VFRecommendations for VT/VF

Class IIa:Class IIa:• Infusions of antiarrhythmic drugs Infusions of antiarrhythmic drugs (discontinue after 6 to 24 hours and (discontinue after 6 to 24 hours and reassess need)reassess need)

•Correction of electrolyte and acid-base Correction of electrolyte and acid-base disturbances (to prevent VF disturbances (to prevent VF recurrence following treatment of initial recurrence following treatment of initial episode)episode)

ACC/AHA Treatment ACC/AHA Treatment Recommendations for VT/VFRecommendations for VT/VF

Class IIb:Class IIb:• Drug-refractory polymorphic VTDrug-refractory polymorphic VT

- Manage aggressively with Manage aggressively with -blockers, intra-aortic -blockers, intra-aortic balloon pumping, PTCA/CABG surgeryballoon pumping, PTCA/CABG surgery

- Amiodarone I.V. Amiodarone I.V. Class III:Class III:• Treating isolated PVCs, couplets, runs of Treating isolated PVCs, couplets, runs of

accelerated idioventricular rhythm, nonsustained accelerated idioventricular rhythm, nonsustained VTVT

• Prophylactic antiarrhythmic therapy when using Prophylactic antiarrhythmic therapy when using thrombolytic agentsthrombolytic agents

• Amiodarone I.V. is indicated in life-threatening Amiodarone I.V. is indicated in life-threatening VT/VF refractory to other therapy.VT/VF refractory to other therapy.

ACC/AHA Treatment ACC/AHA Treatment Recommendations for VT/VFRecommendations for VT/VF

AMIODARONE IV AMIODARONE IV SAFETYSAFETY

Clinically Manageable Clinically Manageable Safety ProfileSafety Profile

~~9% overall discontinuation rate due 9% overall discontinuation rate due to adverse eventsto adverse events11

<1% incidence of proarrhythmia<1% incidence of proarrhythmia11

<1% discontinuation due to CNS side <1% discontinuation due to CNS side effectseffects11

Hypotension is the most common adverse effect seen with Hypotension is the most common adverse effect seen with Amiodarone I.V. and may be related to the rate of infusion. Amiodarone I.V. and may be related to the rate of infusion. Hypotension should be treated by slowing the infusion or with Hypotension should be treated by slowing the infusion or with standard therapy: vasopressor drugs, positive inotropic agents, and standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion.volume expansion.

1. Data on file, Wyeth-Ayerst Laboratories.1. Data on file, Wyeth-Ayerst Laboratories.

Most Important Treatment-Emergent Most Important Treatment-Emergent Drug-RelatedDrug-Related

Adverse Events (n=1836)Adverse Events (n=1836)

% Requiring% Requiring permanent permanent

EventEvent % Incidence % Incidence discontinuationdiscontinuation

HypotensionHypotension 16%16% 1.6%1.6%

BradycardiaBradycardia 4.9%4.9% <1%<1%

Liver function tests abnormalLiver function tests abnormal 3.4%3.4% <1%<1%

Heart arrestHeart arrest 2.9%2.9% 1.2%1.2%

Ventricular tachycardiaVentricular tachycardia 2.4%2.4% 1.1%1.1%

Congestive heart failureCongestive heart failure 2.1%2.1% <1%<1%

Cardiogenic shockCardiogenic shock 1.3%1.3% 1.0%1.0%

AV blockAV block 0.5%0.5% <1% <1%

Cordarone I.V.Cordarone I.V.1000 mg1000 mg

n=105n=105

Cardiovascular eventsCardiovascular eventsHypotension 33 (32%) 21 (20%) 17 (18%)Heart block 4 (4) 0 2 (2)CHF 5 (5) 0 0Proarrhythmia 3 (3) 0 1 (1)Nodal rhythm 0 3 (3) 0Phlebitis 0 3 (3) 0

Other eventsOther events Nausea 6 (6) 2 (2) 2 (2)Confusion 4 (4) 3 (3) 3 (3)Thrombocytopenia 3 (3) 1 (1) 1 (1)Fever 1 (1) 2 (2) 1 (1)Diarrhea 5 (5) 0 0

Fewer Drug-Related Adverse Fewer Drug-Related Adverse Events Than BretyliumEvents Than Bretylium11

EventEvent

Treatment GroupTreatment Group

BretyliumBretyliumn=103n=103

Cordarone I.V.Cordarone I.V.125 mg125 mg

n=94n=94

Reproduced with permission. Reproduced with permission. Circulation. Circulation. Copyright 1995 American Heart Association.Copyright 1995 American Heart Association.

1.1. Kowey PR, Levine JH, Herre JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium Kowey PR, Levine JH, Herre JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. CirculationCirculation. 1995;92:3255-3263.. 1995;92:3255-3263.

AMIODARONE IV AMIODARONE IV BIBLIOGRAPHYBIBLIOGRAPHY

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