A patient is in refractory ventricular fibrillation and has received multiple appropriate

The Effects of Amiodarone:

Amiodarone can prolong AV conduction, the AV refractory period, and QRS and QT intervals—ultimately slowing the heart rate. Amiodarone is a well known multi channel blocker, because it blocks sodium, potassium, and calcium channels and is an alpha and beta blocker.

Amiodarone Indications for Use:

Amiodarone is an antiarrhythmic drug. It is specifically used for its broad range of electrophysiologic effects.

Amiodarone is primarily chosen for ACLS as the first-line antiarrhythmic agent for cardiac arrest. This is because it is effective in improving the rate of return of spontaneous circulation (ROSC) and improved ROSC to hospital admission in adults with refractory v-fib or pulseless v-tach.

Amiodarone may be considered when v-fib and v-tach is unresponsive to CPR, defibrillation, and epinephrine.

Amiodarone Precautions & Contraindications:

With amiodarone, there are multiple complex drug interactions, so caution must be used when administering this drug.

Rapid infusion may lead to hypotension. But since there is no blood pressure during cardiac arrest, the American Heart Association still recommends rapid IV push for antiarrhythmic treatment.

Significant hypotension has been noted in clinical trials when multiple doses of Amiodarone are used. Multiple doses could be a cumulative dose of greater than 2.2 g over 24 hours.

Amiodarone should not be administered with other drugs that prolong QT interval, such as procainamide.

Terminal elimination of amiodarone is extremely long. As a result, amiodarone can be complicated to work around when treating a patient who has experienced return of spontaneous circulation, as one may not be able to use certain other medications until amiodarone has been effectively eliminated from the patient’s body.

Adult Dosage for Amiodarone:

When using amiodarone to treat ventricular fibrillation or pulseless ventricular tachycardia, the first dose should be 300 mg IV/IO push. The second dose is delivered at 150mg IV/IO push.

Rapid Infusion:

  • For life threatening arrhythmias, the maximum cumulative dose is 2.2g IV over 24 hours
  • For patients with a pulse but who are suffering life threatening arrhythmias, amiodarone should be given by rapid infusion delivered 150 mg IV over the first 10 minutes, equally 15 mg per minute
  • Rapid infusion may be repeated every 10 minutes as needed up to a total of 2.2 g in 24 hours

Slow Infusion:

  • To give amiodarone by slow infusion, 360 mg IV should be delivered over 6 hours, or 1 mg per minute
  • The maintenance infusion is 540 mg IV over 18 hours, which is .5 mg per minute

These infusions must not exceed 2.2 g in a 24 hour period. When delivered in this amount, its effects can last upwards of 40 days.

Commentary

In 2015, the American Heart Association and European Resuscitation Council updated the guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care according to the International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (1-3). The guidelines recommend administration of amiodarone for sustained ventricular fibrillation (Vf) and ventricular tachycardia (VT) refractory to CPR, defibrillation, and vasopressor in out-of-hospital cardiac arrest. Lidocaine is recommended as an alternative to amiodarone. However, these recommendations remain weak and are based on the two previous randomized controlled trials (RCTs) performed more than 10 years ago. In these trials, compared with both placebo and lidocaine, amiodarone improved the rate of return of spontaneous circulation (ROSC) but not the survival to hospital discharge and neurological outcome (4). However, these studies were not statistically powered to investigate survival and neurological outcome, so the actual efficacy of amiodarone therapy remains undetermined.

To address this issue, the Resuscitation Outcomes Consortium performed the RCT called “ALPS”, the results of which were published recently (5). In the trial, amiodarone, lidocaine, or placebo was administered by paramedics for sustained Vf/VT after at least one shock in patients with non-traumatic out-of-hospital cardiac arrest. As per-protocol population, 3,026 patients were evaluated, of whom 974 were assigned to the amiodarone group, 993 to the lidocaine group, and 1,059 to the placebo group. The proportion of survival to hospital discharge, which was the primary outcome of this study, did not significantly differ between the three groups (24.4%, 23.7%, and 21.0% in the amiodarone, lidocaine, and placebo groups, respectively). The neurological function at discharge, which was the secondary outcome, also did not significantly differ. Regarding the ROSC at emergency department arrival, only lidocaine was significantly superior to placebo.

What do these results mean? Should we refrain from the use of amiodarone for shock-refractory Vf/VT in cardiac arrest?

This study gives us a different message when we focus on the time from collapse to the use of antiarrhythmic drugs. As the authors mentioned in the Discussion section, both amiodarone and lidocaine therapies resulted in significantly better rate of survival to hospital discharge than placebo in bystander-witnessed arrest (27.7%, 27.8%, and 22.7% with amiodarone, lidocaine, and placebo, respectively). Especially in emergency medical services-witnessed cardiac arrest, the rate of survival to discharge was twice higher with amiodarone than with placebo (38.6% vs. 16.7%). This study is the first RCT that showed the efficacy of amiodarone and lidocaine therapies in terms of survival to hospital discharge, although the result was obtained from the subanalysis. The immediate response to cardiac arrest and bystander CPR could be considered as the prerequisite to attaining the efficacy of antiarrhythmic drugs. It may be said that we should use amiodarone or lidocaine at least in witnessed arrest, instead of giving up the use of both drugs.

This study is a meaningful study also for lidocaine. Lidocaine has been widely used, but no RCT has shown its efficacy for ROSC in shock-refractory Vf/VT. Although the rate of ROSC at ED arrival was the mechanistic outcome in this study, the rate of ROSC in the per-protocol population was significantly higher with lidocaine than with placebo. On the other hand, amiodarone failed to show this efficacy in the per-protocol population (35.9%, 39.9%, and 34.6% for amiodarone, lidocaine, and placebo, respectively).

Is lidocaine just an alternative to amiodarone? Piccini et al. reported that administration of amiodarone, but not lidocaine, was associated with increased mortality in patients with sustained Vf/VT (6). However, this was a retrospective study of GUST IIB and III, which enrolled patients with acute myocardial infarction, and not those who had an out-of-hospital cardiac arrest. From the ALPS trial, we cannot determine which between amiodarone and lidocaine is a more potent drug for shock refractory Vf/VT in cardiac arrest. As mentioned earlier, the rate of survival to discharge did not significantly differ between the two drugs both in the per-protocol population and in the witnessed-arrest patients. Considering the adverse events, the proportion of patients who needed temporary cardiac pacing was higher in the amiodarone group. Moreover, this study used the amiodarone formulation containing a solvent that does not cause hypotension. In countries where this formulation is unavailable, more attention might be paid to the adverse events, especially to hypotension. These results seem to be more advantageous for lidocaine rather than to amiodarone. However, about half of the patients assigned to lidocaine were given amiodarone within 24 h after hospital arrival. This shows that the physicians felt the necessity to use amiodarone, and we cannot simply prefer lidocaine to amiodarone.

The time from collapse is a key factor in the resuscitation of cardiac arrest patients. Joshua et al. reported that the probability of survival with good neurological outcome declined rapidly after about 16 min of CPR (7). The mean time from initial call to first drug administration in non-witnessed cardiac arrest patients was about 19 min in this trial. Within this time frame, the patients would have already fallen into the “metabolic phase” in the 3-phase model of cardiac arrest (8). Even CPR and defibrillation would become ineffective in this phase, so the antiarrhythmic drugs might play an insignificant role. For patients in the metabolic phase, we should seek the novel approach such as extracorporeal resuscitation, rather than expecting vasopressors or antiarrhythmic drugs to take effect.

In summary, ALPS showed that both amiodarone and lidocaine therapies would be effective for shock-refractory Vf and pulseless VT in bystander-witnessed arrest but might be useless in the later phase of CPR. Immediate response to cardiac arrest and good-quality CPR are key to attaining the efficacy of antiarrhythmic drugs.


Acknowledgements

None.


Provenance: This is an invited Commentary commissioned by the Section Editor Zhongheng Zhang (Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua, China).

Conflicts of Interest: The authors have no conflicts of interest to declare.

Comment on: Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med 2016;374:1711-22.


References

  1. Kudenchuk PJ, Brown SP, Daya M, et al. Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial. Am Heart J 2014;167:653-9.e4. [Crossref] [PubMed]
  2. Soar J, Nolan JP, Böttiger BW, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation 2015;95:100-47. [Crossref] [PubMed]
  3. Soar J, Callaway CW, Aibiki M, et al. Part 4: Advanced life support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015;95:e71-120. [Crossref] [PubMed]
  4. Dorian P, Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med 2002;346:884-90. [Crossref] [PubMed]
  5. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;374:1711-22. [Crossref] [PubMed]
  6. Piccini JP, Schulte PJ, Pieper KS, et al. Antiarrhythmic drug therapy for sustained ventricular arrhythmias complicating acute myocardial infarction. Crit Care Med 2011;39:78-83. [Crossref] [PubMed]
  7. Reynolds JC, Frisch A, Rittenberger JC, et al. Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: when should we change to novel therapies? Circulation 2013;128:2488-94. [Crossref] [PubMed]
  8. Weisfeldt ML, Becker LB. Resuscitation after cardiac arrest: a 3-phase time-sensitive model. JAMA 2002;288:3035-8. [Crossref] [PubMed]

Cite this article as: Sugiyama K, Kashiura M, Hamabe Y. Amiodarone and lidocaine for shock refractory ventricular fibrillation or ventricular tachycardia in out-of-hospital cardiac arrest: are they really effective? J Thorac Dis 2016;8(8):E791-E793. doi: 10.21037/jtd.2016.06.59

What drug is indicated for patients with refractory ventricular fibrillation?

The guidelines recommend administration of amiodarone for sustained ventricular fibrillation (Vf) and ventricular tachycardia (VT) refractory to CPR, defibrillation, and vasopressor in out-of-hospital cardiac arrest. Lidocaine is recommended as an alternative to amiodarone.

What is the most appropriate action when you view a patient with ventricular fibrillation?

Call 911 or your local emergency number. If the person is unconscious, check for a pulse. If no pulse, begin CPR to help keep blood flowing through the body until an automated external defibrillator (AED) is available.

What does refractory mean in ventricular fibrillation?

Refractory ventricular fibrillation (RVF) is thought to be defined as failure to obtain return of spontaneous circulation (ROSC) within 10 min despite 3 defibrillation attempts, 3 mg of epinephrine, and 300 mg of amiodarone [2].

What is refractory ventricular fibrillation ACLS?

However, refractory VF, which is defined as VF that persists despite three defibrillation attempts, is challenging for all ACLS providers; the best resuscitation strategy for patients that persist in refractory VF remains unclear.