slide1 l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia PowerPoint Presentation
Download Presentation
Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia

Loading in 2 Seconds...

play fullscreen
1 / 72

Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia - PowerPoint PPT Presentation


  • 291 Views
  • Uploaded on

SLIDE ANTHOLOGY: Clinical Studies and Perspectives in Cardiac Arrest Management The 2000 A dvanced C ardiovascular L ife S upport Guidelines Amiodarone IV . Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia. ACLS Background: Historical Perspectives. 2000

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Jerrold H Levy, MD Emory University School of Medicine Atlanta, Georgia' - jacob


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

SLIDE ANTHOLOGY:Clinical Studies and Perspectives in Cardiac Arrest Management The 2000 Advanced Cardiovascular Life Support GuidelinesAmiodarone IV

Jerrold H Levy, MD

Emory University School of Medicine

Atlanta, Georgia

acls background historical perspectives
ACLS Background: Historical Perspectives

2000

1st International Guidelines

Conference on CPR and ECC

5th CPR and ECC

Conference

1992

4th CPR and ECC

Conference

1st Conference on Pediatric Resuscitation

1985

1983

1st, 2nd, & 3rd

Conference on CPR

1966-1979

Data from: Circulation. 2000;102:1–2.

1992 guidelines for treatment of vf pulseless vt
1992 Guidelines for Treatment of VF/Pulseless VT
  • Reflected scientific knowledge and experience in early 1990s
  • Defibrillation as key intervention
  • Three antiarrhythmics as treatment options
    • Lidocaine
    • Procainamide
    • Bretylium
  • No controlled trials existed to help evaluate efficacy of antiarrhythmics

Data from: Circulation. 2000;102:1-3. JAMA. 1992;268:2199–2241.

2000 acls guidelines primary goal of the aha ecc
2000 ACLS GuidelinesPrimary Goal of the AHA/ECC
  • Establish guidelines
    • Based on scientific evidence
    • Prompted by rapid changes and advances in knowledge
    • Developed as recommendations

Data from: Circulation. 2000;102:1–3.

2000 acls guidelines overall goals
2000 ACLS Guidelines: Overall Goals

Create valid, internationally accepted, resuscitation guidelines using scientific evidence

Develop a document to explainthe guidelines

Review and revise

recommendations

from past conferences

Collaborate with international resuscitation authorities on CPR and ECC

Data from: Circulation. 2000;102:I-2–I-3.

international guidelines 2000 conference on cpr and ecc objectives
International Guidelines 2000 Conference on CPR and ECC: Objectives
  • Establish ILCOR as the authority for coordination and communication
  • Ensure equal representation for AHA and non-U.S. committees
  • Review and revise recommendations from past conferences on the basis of accumulated evidence
  • Recommend changes in the methods for teaching life-support skills

Data from: Circulation. 2000;102:I-2–I-3.

chain of survival
Chain of Survival
  • Early access
  • Early CPR
  • Early defibrillation
  • Early advanced care

Data from: Circulation. 2000;102:I-22–I-23.

philosophy evidence based review
Philosophy: Evidence-Based Review
  • Systematically identify, evaluate,andappraise evidence to support proposed changes
  • Reviewall proposed changes for:
    • Scientific accuracy
    • Safety
    • Cost
    • Effectiveness
    • Teachability

Data from: Circulation. 2000;102:1–3.

reasons for modifying guidelines
Reasons for Modifying Guidelines

Lack of evidence to confirm effectiveness

Additional evidence to suggest harm or ineffectiveness

Evidence that superior therapies have become available

Data from: Circulation. 2000;102:I-1.

tools and principles of evidence based review
Tools and Principles of Evidence-Based Review

Step 1

Search for and gather evidence

Steps 2 & 3

Assess the quality and level of the evidence

Step 4

Determine class of recommendationby evidence

Data from: Circulation. 2000;102:I-3.

sorting studies by level of evidence
Sorting Studies by Level of Evidence

Positive RCTs (P < 0.05)

Level 1

Level 2

Neutral RCTs (NS)

Prospective, nonrandomized, observational study with control group

Level 3

Retrospective, nonrandomized, observational study with control group

Level 4

Level 5

Case series compilation, no control group

Animal/mechanical model; 6A – higher quality studies, 6B – less powerful design

Level 6

Level 7

Reasonable extrapolations from data gathered for other purposes

Level 8

Common sense; common practices before evidence-based guidelines

Data from: Circulation. 2000;102:I-4.

Abbreviation: RCT, randomized, controlled trial.

evaluating quality of evidence
Evaluating Quality of Evidence

Sort studies by level

Assess qualityof research design

and methods (Excellent, Good, Fair, Poor)

Determine direction of results and statistics

(Support proposal, Neutral, Oppose proposal)

Cross-tabulate by level, quality, and direction

Class of Recommendation

Data from: Circulation. 2000;102:I–4.

classes of recommendation
Class I

Excellent. Proven efficacy, safety, and usefulness

Acceptable. Good evidence, safe, clinically useful; standard of care

Acceptable. Fair evidence, safe, clinically useful; within standardof care

Not recommended. Minimal evidence; preliminary research

Not acceptable. May be harmful; not clinically useful

Classes of Recommendation

Class IIa

Class IIb

ClassIndeterminate

Class III

Data from: Circulation. 2000;102:I-5.

evidence based guidelines
Evidence-Based Guidelines

Step 1

State a

proposal

Steps 2 & 3

Assess quality and level of evidence

Step 4

Determine class

of recommendation(I, IIa, IIb, Indeterminate, III)

Summarizerationale

for proposal

Data from: Circulation. 2000;102:I-3–I-5.

placebo controlled methodology
Placebo-Controlled Methodology
  • Without placebo controls, the value of antiarrhythmic agents in cardiac arrest due to VF/pulseless VT cannot be determined
  • Prospective, randomized, placebo-controlled trials provide objective evaluation of antiarrhythmic agents
evidence evaluation template
Evidence Evaluation Template

Level

1 2 3 4 5 6 7 8

Excellent

Good

Fair

Fair

Good

Excellent

Supporting

+/- orOpposing

Level

1 2 3 4 5 6 7 8

Courtesy of Peter Kudenchuck.

lidocaine in cardiac life support review of quality of evidence
Lidocaine in Cardiac Life Support: Review of Quality of Evidence
  • Lidocaine did not fare well under evidence-based approach
  • Review of evidence showed poor or weak support for lidocaine as beneficial in cardiac arrest
  • Supporting evidence primarily consisted of levels 6, 7, and 8
  • Class indeterminate for shock-refractory VF/pulseless VT
  • Lack of evidence was key factor in revised lidocaine classification despite time-honored status and 1992 ACLS recommendation

Data from: Circulation. 2000;102:I-86–I-87.

quality and level of evidence analysis lidocaine in cardiac arrest due to vf vt

Excellent

Good

Fair

Fair

Good

Excellent

Quality and Level of Evidence Analysis Lidocaine in Cardiac ArrestDue to VF/VT

Author Year (n)

1. Alexander ’99 (43704)

2. Anastasiou ’94 (16)

3. Babbs ’79

4. Borer ’76

5. Carden ’56 (23)

6. Chow ’86

7. Dorian ’86

8. Echt ’89

9. Harrison ’63 (12)

10. Harrison ’81 (116)

11. Haynes ’81 (146)

12. Herlitz ’97 (1360)

13. Kentsch ’88 (20)

14. Kerber ’86

15. Lazzara ’73

16. Lazzara ’78

17. Lie ’74

18. Olson ’84 (108)

19. Redding ’68 (105)

20. Sadowski ’99 (903)

21. Spear ’72

22. Vachiery ’90 (18)

23. VanWalraven ’98 (773)

24. Weaver ’90 (199)

25. Other MI trials

26. MI Meta-analyses

Supporting

4, 9, 15,16, 17,21, 25

12

5

Current Practice

1 2 3 4 5 6 7 8

10

2, 3, 6,7, 8, 14,19, 22

Neutral/Opposing

13

18

23, 24

1, 20,

26

11

1 2 3 4 5 6 7 8

lidocaine in cardiac arrest due to vf vt
Lidocaine in Cardiac Arrest Due to VF/VT

Supporting (10)

  • Level 4 (1)
  • Level 6 (1)
  • Level 7 (7)
  • Level 8 (1)

Neutral/Opposing (17)

  • Neutral (5)
    • Level 2 (2)
    • Level 3 (1)
    • Level 6 (1)
    • Level 7 (1)
  • Opposing (12)
    • Level 1 (1)
    • Level 4 (2)
    • Level 6 (7)
    • Level 7 (2)
quality and level of evidence analysis amiodarone in cardiac arrest due to vf vt

1 2 3 4 5 6 7 8

Quality and Level of Evidence Analysis Amiodarone in Cardiac Arrest Due to VF/VT

Author Year (n)

Excellent

Good

Fair

9

8

1. AnastasiNana ’94 (16)

2. Drexler (14)

3. Fain ’87 (12)

4. Helmy ’88 (46)

5. Horowitz (5)

6. Kentsch ’88 (20)

7. Klein (13)

8. Kowey ’95 (228)

9. Kudenchuk ‘99 (504)

10. Levine ’96 (273)

11. Mooss (35)

12. Morady (15)

13. Nalos ’91 (22)

14. Ochi (22)

15. Rosalion ’91 (23)

16. Saksena (9)

17. Scheinman ’95 (342)

18. Schutzenberger ’89 (26)

19.Zhou ’98 (24)

1, 3

15

Supporting

2, 4, 5, 7,

11, 12, 13,

14, 16, 18

6

Fair

Good

Excellent

10

17

19

Neutral/Opposing

1 2 3 4 5 6 7 8

amiodarone in cardiac arrest due to vf vt
Amiodarone in Cardiac Arrest Due to VF/VT

Supporting (16)

  • Level 1 (2)
  • Level 2 (1)
  • Level 5 (10)
  • Level 6 (2)
  • Level 7 (1)

Neutral/Opposing (3)

  • Neutral (2)
    • Level 2 (2)
  • Opposing (1)
    • Level 7 (1)
2000 acls guidelines recommended antiarrhythmic agents
2000 ACLS Guidelines: Recommended Antiarrhythmic Agents
  • Amiodarone HCl received a Class-IIb rating in cardiac arrest; no other antiarrhythmic agent received a more favorable rating in this setting
  • The 2000 ACLS Guidelines recommend using only one antiarrhythmic agent in resuscitation efforts

Data from: Circulation. 2000;102:I-115, I-149–I-159.

slide24

Guidelines for Dosing and Administration for VF and Hemodynamically Unstable VT

First 24 Hours

First Rapid

Add 150 mg (1 ampul) to 100 mL D5W; administer over FIRST 10 minutes (15 mg/min)

PVC,* glass,† or polyolefin container

Followed by Slow

Add 900 mg (6 ampuls) to 500 mL D5W; administer 33.3 mL/hr over NEXT 6 hours (1 mg/min)

Glass† or polyolefin container

Reduce to 0.5 mg/min; administer 16.6 mL/hr for REMAINING 18 hours

*<10% loss at 2 hours.

†Use of evacuated glass containers for admixing Cordarone I.V. is not recommended, as incompatibility with a buffer in the container may cause precipitation.

‡After the first 24 hours, the maintenance infusion rate of 0.5 mg/min (720 mg/24 hours) should be continued utilizing a concentration of 1–6 mg/mL; concentrations greater than 2 mg/mL should be administered via a central venous catheter. Infusions for longer than 3 weeks have not been studied. Transition to oral therapy is recommended at the earliest possible time.

Loading Infusions

NOTE: In cardiac arrest due to shock-refractory VF/pulseless VT, the initial dose should be 300 mg, I.V. push, as recommended in the VF/pulseless VT algorithm in the 2000 ACLS guidelines.

Maintenance Infusion‡

the 2000 acls guidelines overview and conclusion
The 2000 ACLS Guidelines: Overview and Conclusion

“Amiodarone is recommended after defibrillation and epinephrinein cardiac arrest with persistent VT or VF (Class IIb).”

“In summary, evidence supports the use of IV amiodarone,following epinephrine, to treat shock-refractory cardiac arrestdue to VF or pulseless VT (Class IIb).”

“The evidence supporting amiodarone is much stronger [than that for lidocaine]. . .and justifies the use of amiodarone before lidocaine. . .”

“The expert panel members would have no problem with clinicians routinely using amiodarone as the first-choice antiarrhythmic for shock-refractory VF/VT”

From: Circulation. 2000;102(suppl):I-86, I-87, I-117, I-120.

preparation of iv amiodarone for cardiac arrest due to vf vt
Preparation of IV Amiodarone for Cardiac Arrest Due to VF/VT

“In cardiac arrest due to pulseless VT or VF, IV amiodarone is initially administered as a 300-mg rapid infusion diluted in a volume of 20 to 30 mL of saline or dextrose in water.”

  • Use 2 ampuls of amiodarone, appropriate size syringe and needle, gauze, sponges or alcohol pad
  • Check route, dose, date
  • Avoid excessive shaking of ampuls
  • Tap top of ampul before opening to promote transfer of medication

From: Circulation. 2000;102(suppl):I-121.

acute myocardial infarction
Acute Myocardial Infarction
  • 900,000 people in the U.S. experience an MI annually
  • ~225,000 die

~125,000 die “in the field”

Most deaths are arrhythmic in etiology

Data from: Ryan TJ et al. J Am Coll Cardiol. 1996;28:1333.

slide28
Amiodarone in out-of-hospital Resuscitation of REfractory Sustained ventricular Tachyarrhythmias (ARREST)

A prospective, randomized, double-blind, placebo-controlled study of IV amiodarone in patients with out-of-hospital cardiac arrest due to shock-refractory VF/VT

Data from:Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

arrest eligibility criteria
ARREST Eligibility Criteria
  • Older than 18 years
  • Nontraumatic out-of-hospital cardiac arrest
  • Ongoing or recurrent VF/VT after 3+ shocks
  • Paramedics and study drug on scene
  • IV access

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

arrest study end points
ARREST Study End Points
  • Primary
    • Admission to hospital with a spontaneously perfusing rhythm (assigned to a hospital bed)
  • Secondary
    • Adverse effects
    • Total duration of resuscitative efforts
    • Number of shocks after administration of study drug
    • Need for additional antiarrhythmic drugs
  • Also evaluated
    • Survival to hospital discharge*
    • Neurological status at hospital discharge*

* By design, the trial did not have sufficient statistical power to demonstrate differences in these outcomes.

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

arrest study algorithm
ARREST Study Algorithm

VF or Pulseless VT

Cardiac Arrest

Shock x 3

Persistent or Recurrent VF/VT

Stable

Rhythm

Asystole

or PEA

ETT

IV

EPI

Excluded From Study

Placebo

IV amiodarone

Study Drug

ETT: endotracheal intubation

IV: intravenous access established

EPI: epinephrine

PEA: pulseless electrical activity

Standard ACLS Care

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871-878.

november 1994 february 1997 out of hospital cardiac arrest
November 1994-February 1997Out-of-Hospital Cardiac Arrest

(n=3,954)

Ineligible/NotTreated(n=3,260)

Ineligible/Treated(n=27)

Met Study Criteria

(n=667)

Eligible/NotTreated(n=160)

Eligible/Treated

(n=507)

Drug AssignmentUnknown

(n=3)

Study Group

(n=504)

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

arrest patient characteristics
ARREST Patient Characteristics

IV Amiodarone(n=246)

Placebo(n=258)

P Value

Male 187 (76%) 203 (79%) NS

Age (yr) 66 ± 14* 65 ± 14* NS

Cardiac History 137 (64%) 135 (59%) NS

Other Medical History 101 (47%) 119 (52%) NS

Witnessed Arrest 155 (70%) 182 (77%) 0.07

Bystander CPR 155 (68%) 138 (59%) 0.06

VF Amplitude (mV) 0.42 ± 0.2* 0.45 ± 0.2* NS

* Values shown are means ± SD.

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871-878.

slide34

Initial Cardiac Arrest Rhythm

83

83

% of Patients

12

11

5

4

Abbreviation: PEA, pulseless electrical activity.

Data from:Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

slide35

Response/Treatment Times in Minutes

IVAmiodarone

Placebo

P Value

First unit 4.3  2.0 (4.0) 4.4  2.3 (4.0) NS

Paramedic/ALS 8.4 4.1 (7.8) 8.8  4.9 (7.9) NS

Shock 8.9  5.4 (7.6) 9.5  7.5 (7.4) NS

IV access 13.1  4.1 (12.7) 13.7  4.1 (13.2) NS

Intubation 14.3  5.8 (12.7) 13.8  4.6 (13.1) NS

Study drug 21.4  8.3 (19.2) 20.5  7.0 (19.3) NS

Values shown are the means ± SD with medians shown in parentheses.

Abbreviations: ALS, advanced life support; IV, intravenous; NS, not statistically significant; SD, standard deviation.

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

slide36

Resuscitation CharacteristicsBefore Study Drug

IVAmiodarone(n=246)

Placebo(n=258)

P Value

Number of shocks 5  2 (4)* 5  2 (4)* 0.73

Transient ROSC 55 (22%) 52 (20%) 0.61

Antiarrhythmic drug 65 (26%) 91 (35%) 0.04

Bradycardia treatment 32 (13%) 51 (20%) 0.04

Pressor treatment 19 (8%) 22 (9%) 0.74

Abbreviations: ROSC, return of spontaneous circulation; SD, standard deviation.

*The values shown are the means ± SD, with the median in parentheses.

Data from: Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

slide37

197

211

91

69

63

36

246

258

153

145

153

145

Treatment After Study Drug

P = 0.70

82

80

P = 0.04

59

P = 0.004

48

% of Patients

41

25

No. Receiving Drug

Total No.

* In patients with return of spontaneous circulation.

Data from:Kudenchuk PJ et al. N Engl J Med. 1999;341:871-878.

admission to hospital by arrhythmia characteristics
Admission to Hospital by Arrhythmia Characteristics

Patients Surviving

to Admission (%)

No. Surviving 108 89 101 84 7 5 35 22 73 67

Total No. 246 258 205 216 41 42 55 53 191 205

Abbreviations: PEA, pulseless electrical activity; ROSC, return of spontaneous circulation.

Data from:Kudenchuk PJ et al. N Engl J Med. 1999;341:871-878.

arrest trial conclusions
ARREST Trial Conclusions
  • IV amiodarone is effective therapy for shock-refractory VF
  • Adverse effects expected but manageable
  • Improving survival from cardiac arrest remains an important challenge

Data from:Kudenchuk PJ et al. N Engl J Med. 1999;341:871–878.

a miodarone versus l idocaine i n pre hospital refractory v entricular fibrillation e valuation
Amiodarone Versus Lidocaine In Pre-hospital Refractory Ventricular Fibrillation Evaluation A L I V E

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

.

alive rationale
ALIVE: Rationale
  • Patients in cardiac arrest due to VF unresponsive to initial defibrillation have a poor prognosis
  • Lidocaine has been the traditional treatment for shock-resistant VF
  • No large-scale, controlled clinical trials show lidocaine superior to placebo or other antiarrhythmic agents in cardiac arrest due to shock-refractory VF
  • Results of the ARREST trial (Kudenchuk et al, N Engl J Med. 1999) showed an increase in survival to hospital admission with IV amiodarone in patients with shock-refractory VF
  • The ALIVE study was designed to compare IV amiodarone with IV lidocaine in out-of-hospital shock-refractory VF

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive hypothesis
ALIVE: Hypothesis
  • Amiodarone can produce better outcomes than lidocaine in patients with out-of-hospital cardiac arrest due to shock-refractory VF

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive study design
ALIVE: Study Design
  • Blinded, randomized, controlled trial of IV amiodarone (5 mg/kg) vs. IV lidocaine (1.5 mg/kg)
  • Men and women were eligible if they were at least 18 years of age and in documented VF refractory to standard protocol in the Toronto EMS system (defibrillations and epinephrine infusion)
  • Eligibility was determined by paramedics in the City of Toronto EMS system, under the direction of a physician

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive outcome measures
ALIVE: Outcome Measures
  • Primary end point
    • Survival to hospital admission
  • Subgroup analyses
    • Survival to hospital admission by initial rhythm (VF, PEA, asystole)
    • Survival to hospital admission by time from EMS crew dispatch to administration of study drug
  • Secondary end point
    • Survival to hospital discharge

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive study protocol
ALIVE: Study Protocol

VF

3 Failed shocks

IV epinephrine

Defibrillation shock

Persistent/recurrent VF

ALIVE Study

1.5 mg/kg Lidocaine/placebo IV OR

5 mg/kg Amiodarone/placebo IV

Defibrillation shock

Persistent VF

1.5 mg/kg Lidocaine/placebo IV OR

2.5 mg/kg Amiodarone/placebo IV

Defibrillation shock

ACLS treatment as guided by protocols

= VF persists or recurs

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive demographics
ALIVE: Demographics

Amiodarone* Lidocaine*

Characteristic (n=180) (n=167)

Age (yrs) 68 ± 14 66 ± 13

Male (%) 76 81

Weight (kg) 80 ± 16 82 ± 13

Hx heart disease (%) 61.1 59.3

Witnessed arrest (%) 76 79.3

Bystander CPR (%) 26.3 28.7

* There were no significant differences between the two study groups for any characteristic.

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive baseline characteristics
ALIVE: Baseline Characteristics

Amiodarone* Lidocaine*Characteristic (n=180) (n=167)

Initial rhythm (%):

VF 77.8 79.0

Asystole 11.1 9.6

PEA 7.8 6.6

Last recorded rhythm before study drug administration (%):

VF 88.9 91.0

VT 1.7 2.4

Asystole 1.1 1.2

PEA 5.0 3.0

SV 1.7 0.6Total no. shocks 5 ± 1.9† 5 ± 2.2†

Abbreviations: VF, ventricular fibrillation; PEA, pulseless electrical activity; VT, ventricular tachycardia; SV, supraventricular; SD, standard deviation. * There were no significant differences between the two study groups for any characteristic.

† The values shown are the means ± SD.

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

time intervals from ems crew dispatch
Time Intervals From EMS Crew Dispatch

Amiodarone* Lidocaine* Intervals* (n=180) (n=167)

Time from dispatch toarrival at patient (min) 7.3 ± 2.7 7.5 ± 2.6

Time to first defibrillationshock (min) 8.4 ± 2.8 8.7 ± 3.6

Time to IV initiation (min) 13.4 ± 4.4 13.6 ± 3.7

Time to study drug (min) 25.2 ± 8.0 24.3 ± 6.8

* There were no significant differences between the two study groups for any of these measurements.

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive results before study drug
ALIVE: ResultsBefore Study Drug

Amiodarone Lidocaine P Value Characteristic (n=180) (n=167)

Number of shocks 5 ± 1.9* (4%) 5 ± 2.2* (4%) NS

Transient spontaneouscirculation 24 (13.3%) 11 (6.6%) < 0.04

Treatment for bradycardia(atropine) 98 (54%) 96 (57%) NS

Pressor treatment(dopamine) 2 (1%) 0 NS

Antiarrhythmic drugtreatment (open label lidocaine) 4 (2%) 1 (1%) NS

*Values shown are the means ± SD.

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive results after study drug
ALIVE: ResultsAfter Study Drug

Amiodarone Lidocaine P ValueCharacteristic (n=180) (n=167)

Treatment for bradycardia(atropine) 43 (24%) 38 (23%) NS

Pressor treatment(dopamine) 13 (7%) 6 (4%) NS

Antiarrhythmic drugtreatment (open label lidocaine) 11 (6%) 10 (6%) NS

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive survival to hospital admission
ALIVE: Survival to Hospital Admission

Amiodarone Lidocaine

(n=180) (n=167) P Value

Number of patients

surviving to hospital 41 (22.8%) 20 (12.0%) 0.0083

admission

Odds ratio 2.17 (1.21, 3.83)

(95% CI)

Relative risk

reduction 53%

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive survival to hospital discharge
ALIVE: Survival to Hospital Discharge

Amiodarone Lidocaine

(n=180) (n=167) P Value

Number of patients

surviving to hospital 9 (5%) 5 (3%) 0.3427

discharge

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive survival by time from ems crew dispatch to study drug administration

(P=0.05)

(P=0.046)

ALIVE: Survival by Time from EMS Crew Dispatch to Study Drug Administration

A: 19 +/- 3 min

L: 19 +/- 4 min

A: 32 +/- 7 min

L: 31 +/- 5 min

28%

Percent Survival to Hospital Admission

18%

15%

6%

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive survival of all patients and selected subgroups
ALIVE: Survival of All Patients and Selected Subgroups

50

Amiodarone

41.2

Lidocaine

40

27.3

30

24.8

Percent Surviving to Admission

22.8

19.9

20

14.2

12.9

12.0

10.9

10

3.7

0

All Patients

VF

Asystole or PEA Converting to VF

ROSC

No ROSC

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive multivariate predictors of survival to hospital admission
ALIVE: Multivariate Predictors of Survival to Hospital Admission

OR (95% CI) P Value

Treatment

(amiodarone 2.5 (1.3, 4.9) 0.0071

vs. lidocaine)

Time to drug

administration (min) 0.9 (0.8, 0.9) <0.0001

Transient return of spontaneous circulationbefore study drug 5.9 (2.5, 14.3) <0.0001

Corrected for all factors which may influence outcome: initial rhythm (VF vs. other), witnessed arrest, bystander CPR, BLS shock, age, sex, weight, and number of shocks.

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

alive conclusions and clinical significance
ALIVE: Conclusions and Clinical Significance
  • First large-scale direct comparison of amiodarone with lidocaine in patients with out-of-hospital VF
  • Significantly (P = 0.0083) more patients treated with amiodarone than with lidocaine (22.8% vs. 12.0%) survived to hospital admission
  • The difference between amiodarone and lidocaine was similar in various subgroup analyses (time of dispatch to administration of study drug, by initial rhythm, and by presence or absence of ROSC) of survival to hospital admission
  • Amiodarone is substantially more effective than lidocaine as an adjunct to ACLS procedures in patients with cardiac arrest due to shock-refractory VF, with regard to survival to hospital admission

Data from:Dorian P et al. N Engl J Med. 2002;346:884-890.

amiodarone i v cordarone i v
Amiodarone I.V. (Cordarone® I.V.)

Indication

Cordarone I.V. is indicated for initiation of treatmentand prophylaxis of frequently recurring ventricularfibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy

Please see accompanying Prescribing Information.

Data from: Cordarone I.V. Prescribing Information.

amiodarone i v cordarone i v58
Amiodarone I.V. (Cordarone® I.V.)
  • Cordarone I.V. is contraindicated in patients with cardiogenic shock, marked sinus bradycardia, and second- or third-degree AV block in the absence of a functioning pacemaker.
  • Cordarone I.V. should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of Cordarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.
  • Hypotension is the most common adverse effect seen with Cordarone I.V. and may be related to the rate of infusion. Hypotension should be treated by slowing the infusion or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion.
  • In clinical trials, the most important treatment-emergent adverse events were hypotension (15.6%), bradycardia (4.9%), liver function test abnormalities (3.4%), cardiac arrest (2.9%), VT (2.4%), congestive heart failure (2.1%), cardiogenic shock (1.3%), and AV block (0.5%).
  • Please see accompanying Prescribing Information.
  • Data from: Cordarone I.V. Prescribing Information; Data on file, Wyeth-Ayerst Laboratories.
amiodarone i v cordarone i v59
Amiodarone I.V. (Cordarone® I.V.)
  • Cordarone I.V. is contraindicated in patients with cardiogenic shock, marked sinus bradycardia, and second- or third-degree AV block in the absence of a functioning pacemaker.
  • Cordarone I.V. should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of Cordarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.
  • Hypotension is the most common adverse effect seen with Cordarone I.V. and may be related to the rate of infusion. Hypotension should be treated by slowing the infusion or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion.
  • In clinical trials, the most important treatment-emergent adverse effects were hypotension (15.6%), bradycardia (4.9%), liver function test abnormalities (3.4%), cardiac arrest (2.9%), VT (2.4%), congestive heart failure (2.1%), cardiogenic shock (1.3%),and AV block (0.5%).

Data from: Cordarone I.V.Prescribing Information; Data on file, Wyeth-Ayerst Laboratories.

slide60

Amiodarone I.V. (Cordarone® I.V.)

Indication

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

Data from: Cordarone I.V. Prescribing Information.

slide61

Suppresses Highly Malignant Ventricular Arrhythmias in Patients with Severe Underlying Heart Disease

In clinical studies, IV amiodarone:

  • Decreased median number of life-threatening events by 71%
  • Increased median time to first event to 13.7 hours
  • 85% of patients in controlled studies survived the critical first 24 hours; without a placebo comparison, a mortality benefit could not be established
  • Patients should be monitored carefully for QTc prolongation during infusion; <2% incidence of proarrhythmia

Data from: Kowey PR et al. Circulation. 1995;92:3255–3263; Scheinman MM et al. Circulation. 1995;92:3264–3272; Data on file, Wyeth-Ayerst Laboratories.

slide62

Reduction of VF/VT Events During Double-Blind Therapy

0.07

P = 0.067

71%Reduction

0.04

Events/hr (median)

0.02

IV Amiodarone Dosing (mg/24 Hours)

  • The 125-mg dose group was used as a control group.
  • Due to administration of supplemental infusions, the 1,000-mg dose group actually received 1,185 mg/24 hours compared with the 125-mg dose group, which actually received 428 mg/24 hours.

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

Data from: Scheinman MM et al. Circulation. 1995;92:3264–3272; Data on file, Wyeth-Ayerst Laboratories.

reduction from baseline in vf vt events

Baseline

IV amiodarone 125 mg

Reduction from Baselinein VF/VT Events

P = 0.0425

IV amiodarone 1,000 mg

4.0

3.52(88% reduction)

3.0

Median VF/VT Events per 24 Hours

1.68

1.32(44% reduction)

0.48

No significant difference was observed between the 1,000-mg dose and the 500-mg dose or the 125-mg dose and the 500-mg dose groups

Reprinted with permission. Circulation. Copyright 1995 American Heart Association.Data from: Scheinman MM et al. Circulation. 1995;92:3264–3272.

clinically manageable safety profile
Clinically Manageable Safety Profile

~9% Overall discontinuation rate due to adverse events

<2% Incidence of proarrhythmia

<1% Discontinuation due to CNS side effects

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

Data from: Cordarone I.V. Prescribing Information; Data on file, Wyeth-Ayerst Laboratories.

most important treatment emergent drug related adverse events n 1 836
Most Important Treatment-Emergent, Drug-RelatedAdverse Events (n=1,836)

% Requiring permanent Event % Incidence discontinuation

Hypotension 15.6% 1.6%

Bradycardia 4.9% <1%

Liver function test abnormalities 3.4% <1%

Cardiac arrest 2.9% 1.2%

Ventricular tachycardia 2.4% 1.1%

Congestive heart failure 2.1% <1%

Cardiogenic shock 1.3% 1.0%

AV block 0.5% <1%

Data from: Cordarone® I.V (amiodarone HCl) Prescribing Information; Data on file, Wyeth-Ayerst Laboratories.

fewer drug related adverse events than bretylium
Fewer Drug-Related Adverse Events than Bretylium

Treatment Group

IV amiodarone 1,000 mg

(n = 105)

IV amiodarone

125 mg

(n = 94)

Bretylium

(n = 103)

Event

Cardiovascular events

Hypotension 33 (32) 21 (20) 17 (18)

Heart block 4 (4) 0 (0) 2 (2)

CHF 5 (5) 0 (0) 0 (0)

Proarrhythmia 3 (3) 0 (0) 1 (1)

Nodal rhythm 0 (0) 3 (3) 0 (0)

Phlebitis 0 (0) 3 (3) 0 (0)

Other 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) 0 (0)

Values shown are n (%).

Reprinted with permission. Circulation. Copyright 1995 American Heart Association.Data from: Kowey PR et al. Circulation. 1995;92:3255-3263.

rapid onset of action
Rapid Onset of Action

Antiarrhythmic effects are seen in minutes

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

Data from: Kadish A, Morady F. Prog Cardiovasc Dis. 1989;31:281–294; Helmy I et al. J Am Coll Cardiol. 1988;12:1015–1022; Holt P et al. Am J Cardiol. 1982;49:1001. Abstract; Benamin R et al. Arch Mal Coeur. 1976;69:513–522.

slide68

The Only IV Antiarrhythmic with All Four Vaughan Williams’ Class Effects

Class I effect

Sodium channel blockade

Class II effect

Noncompetitive alpha- and beta-adrenergic inhibition

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Ca++

Ca++

Ca++

Ca++

Ca++

Ca++

Ca++

Ca++

Class III effect

Prolongation of repolarization and refractoriness by increased action potential duration

Class IV effect

Calcium channel blockade

Data from: Siddoway LA. Pharmacologic principles of antiarrhythmic drugs. In: Podrid PJ, Kowey PR, eds. Cardiac Arrhythmias: Mechanisms, Diagnosis, and Management. Baltimore, MD: Williams & Wilkins; 1995:355-368.

slide69

Guidelines for Dosing and Administration for VF and Hemodynamically Unstable VT

First 24 Hours

First Rapid

Add 150 mg (1 ampul) to 100 mL D5W; administer over FIRST 10 minutes (15 mg/min)

PVC,* glass,† or polyolefin container

Followed by Slow

Add 900 mg (6 ampuls) to 500 mL D5W; administer 33.3 mL/hr over NEXT 6 hours (1 mg/min)

Glass† or polyolefin container

Reduce to 0.5 mg/min; administer 16.6 mL/hr for REMAINING 18 hours

*<10% loss at 2 hours.

†Use of evacuated glass containers for admixing Cordarone I.V. is not recommended, as incompatibility with a buffer in the container may cause precipitation.

‡After the first 24 hours, the maintenance infusion rate of 0.5 mg/min (720 mg/24 hours) should be continued utilizing a concentration of 1–6 mg/mL; concentrations greater than 2 mg/mL should be administered via a central venous catheter. Infusions for longer than 3 weeks have not been studied. Transition to oral therapy is recommended at the earliest possible time.

Loading Infusions

NOTE: In cardiac arrest due to shock-refractory VF/pulseless VT, the initial dose should be 300 mg, I.V. push, as recommended in the VF/pulseless VT algorithm in the 2000 ACLS guidelines.

Maintenance Infusion‡

slide70

Supplemental Infusion*

  • Add 150 mg to 100 mL D5W; administer over 10 minutes (15 mg/min); PVC,† glass,‡ or polyolefin container

Hypotension is the most common adverse effect seen withCordarone® I.V. (amiodarone HCl) and may be related to the rate of infusion.

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

Concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis.

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

†<10% loss at 2 hours.

‡Use of evacuated glass containers for admixing Cordarone I.V. is not recommended, as incompatibility with a buffer in the container may cause precipitation.

Data from: Cordarone I.V. Prescribing Information.

slide71

Supplemental Infusion(Cont’d.)

Cordarone® I.V. (amiodarone HCl) has been found to leach out plasticizers, including DEHP, from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing Cordarone I.V. at higher concentrations and lower flow rates than provided in the Dosage and Administration section of the Prescribing Information.

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

Prepared solutions should not be kept for more than 24 hours.

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

Data from: CordaroneI.V. Prescribing Information.

slide72

Y-Site Injection Incompatibility

Amiodarone Drug Vehicle Concentration Comments

Aminophylline D5W 4 mg/mL Precipitate

Cefamandole nafate D5W 4 mg/mL Precipitate

Cefazolin sodium D5W 4 mg/mL Precipitate

Mezlocillin sodium D5W 4 mg/mL Precipitate

Heparin sodium D5W – Precipitate

Sodium bicarbonate D5W 3 mg/mL Precipitate

Data from: Cordarone® I.V. (amiodarone HCl)Prescribing Information.