Background

In 2016 the annual incidence of out-of-hospital cardiac arrest (OHCA) in the United States was roughly 360,000 and 209,000 for in-hospital cardiac arrest (IHCA) (Mozaffarian 2016). Though survival rates are relatively dismal, arrests in the setting of shock amenable rhythms – ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT) – have an overall better rate of return of spontaneous circulation (ROSC). While cardiac defibrillation may be effective in terminating VF/VT, defibrillation does not prevent recurrence of VF/VT.  According to the advanced cardiovascular life support (ACLS) algorithm, amiodarone is still the recommended first-line medication for shock refractory VF/VT.  These recommendations stem from two hallmark studies which demonstrated improved ROSC and survival rates to admission after amiodarone was administered (Dorian 2002, Kudenchuk 1999).  However, ROSC does not represent a clinically meaningful endpoint. Subsequent studies have questioned the utility of amiodarone in cardiac arrest from the perspective of improving survival to hospital discharge or survival with a good neurological outcome.

Clinical Question

How does amiodarone affect return of spontaneous circulation, survival, and neurological outcome following cardiac arrest?

Design

Systematic review and meta-analysis

Literature Search

Studies selected via literature review of MEDLINE via PUBMED and the Cochrane Library. Used the search terms “cardiopulmonary resuscitation”, “cardio-pulmonary resuscitation”, “CPR”, “ventricular fibrillation”, “pulseless ventricular tachycardia”, “pulseless electrical activity”, “death, sudden”, “heart arrest, induced”, “amiodarone”, “cordarone”, “pacerone”, “nexterone” and “angoron” to find eligible studies

Outcomes

Evaluated effects of amiodarone compared with alternative treatments (lidocaine, nifekalant, or placebo) on the following outcomes: (1) ROSC (2) survival to hospital admission (3) survival to 24 hrs (4) survival to hospital discharge (5) neurological outcome.

Inclusion

Included studies that were randomized or observational in nature of either adults or pediatric patients with either OHCA or IHCA.
Studies had to include one of the following outcomes: ROSC, short-term survival (i.e. survival to hospital admission for OHCA and 24 hour survival for IHCA), survival to hospital discharge, and neurologic outcome, comparing amiodarone to placebo or other antidysrrhythmic drug (lidocaine or nifekalant)

Excluded

All studies that did not meet inclusion listed above were excluded

Primary Results

Study Characteristics

  • Initially identified 1663 studies, of those studies 10 met inclusion criteria
    • 4 randomized studies (3 double-blinded, 1 controlled)
    • 6 retrospective studies
    • 7 studies evaluated OHCA, 3 studies evaluated IHCA
  • Total 5,326 patients (2,162 received amiodarone, 1422 received placebo, 1666 received lidocaine, and 76 received nifekalant)
  • Individual study sample size ranged from 25 to 3,026 subjects

Critical Results

Looked at effects of amiodarone versus alternative treatments (placebo or other antidysrhythmics) on the following 5 outcomes:

OUTCOME

OR

95% CI

P VALUE
ROSC (7/10 studies)

     IHCA

     OHCA

0.780

0.434*

0.949

0.574–1.059

0.278–0.676*

0.823–1.094

0.112

0.001*

0.469
Survival to hospital admission

(6/10 studies)

1.402*

1.068–1.840*

0.015*
Survival at 24 hours

(3/10 studies)

0.797

0.402–1.582

0.517
Survival to hospital discharge

(9/10 studies)

     IHCA

     OHCA

0.850

0.612*

1.021

0.631–1.144

0.411–0.91*

0.756–1.379

0.284

0.016*

0.891
Neurological outcome

(4/10 studies)

1.114

0.923–1.345

0.475

*Statistically Significant

Strengths

  • Large overall sample size
  • Includes 4 randomized control trials and 6 observational studies
  • Looked at multiple outcomes including the patient relevant outcomes of survival to hospital discharge and neurologic outcome.
  • One of the only studies of its kind (i.e. systematic review/meta-analyses) that evaluate the effects of amiodarone on overall survival and favorable neurologic outcome.

Limitations

  • Majority of studies (6 of 10) were retrospective. Given design of such studies, blinding was not possible leading to high risk of bias
  • Only 3 included studies were adequately blinded and determined to have low risk of bias
  • Limited studies looking at effects of amiodarone on both neurological outcome (4/10 studies) and survival at 24 hrs (3/10 studies)
  • Unable to perform subgroup analysis on these two outcomes secondary to limited number of studies

Author's Conclusions

“Amiodarone significantly improves survival to hospital admission. However, amiodarone does not improve survival to discharge or neurological outcomes compared to placebo or other antidysrhythmics.”

Our Conclusions

This systematic review and meta-analysis demonstrates that while amiodarone significantly increased survival to hospital to admission compared with placebo or other antidysrhythmics for OHCA, it does not significantly improve favorable neurological outcome or survival to hospital discharge. Ultimately, these outcomes are more meaningful from both a cost and quality of life perspective.

Potential Impact To Current Practice

Given this review and analysis, providers should consider removing amiodarone from their routine cardiac arrest algorithm and focus on interventions that have the ability to improve survival such as high quality chest compressions and defibrillation.

Bottom Line

Based on the available evidence, amiodarone does not appear to be associated with any meaningful clinical outcome in cardiac arrest including neurological outcome or survival to hospital discharge.

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