Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-...

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Pharmacologic therapy in survivors of sudden cardiac

arrest
Author: Philip J Podrid, MD, FACC
Section Editors: Scott Manaker, MD, PhD, Samuel Lévy, MD
Deputy Editor: Brian C Downey, MD, FACC

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature rev iew current through: Mar 2020. | This topic last updated: May 08, 2019.

INTRODUCTION

Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of
cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia
(VT) or ventricular fibrillation (VF). The event is referred to as SCA (or aborted SCD) if an
intervention (eg, defibrillation, cardioversion, or drug therapy) or spontaneous reversion restores
circulation, while the SCD terminology is employed if the patient dies. However, the use of SCD
to describe both fatal and nonfatal cardiac arrest often persists by convention. (See "Overview of
sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.)

The treatment of SCA consists of acute resuscitation using standardized advanced cardiac life-
support protocols, followed by therapy to prevent recurrent arrhythmias and SCD. Patients who
survive SCA caused by VT/VF not due to a reversible cause generally receive an implantable
cardioverter-defibrillator (ICD). Antiarrhythmic drugs are used in select patients as adjunctive
therapy, or as primary therapy when an ICD is not indicated or refused by the patient. This
approach, endorsed by numerous professional societies, is based on the significant survival
benefit of patients receiving an ICD compared with antiarrhythmic drugs alone or no therapy.

This topic will review the role of pharmacologic therapy in survivors of SCA, with an emphasis on
the role of antiarrhythmic drugs. Issues related to the acute management of SCA, the evaluation
of survivors, and the utility of an ICD, arrhythmic surgery, or radiofrequency ablation are

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discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Cardiac
evaluation of the survivor of sudden cardiac arrest" and "Secondary prevention of sudden cardiac
death in heart failure and cardiomyopathy".)

INDICATIONS FOR PHARMACOLOGIC THERAPY

Nearly all survivors of sudden cardiac arrest (SCA) without a reversible cause should be
evaluated for placement of an implantable cardioverter-defibrillator (ICD). Because an ICD
treats, but does not prevent, arrhythmias, patients who have arrhythmias with symptoms or
device discharges may require adjunctive antiarrhythmic therapy.

In addition to ICD therapy for survivors of SCA, there are three main indications for concomitant
antiarrhythmic drug therapy [1-3]:

● To reduce the frequency of ventricular arrhythmias in patients with frequent ICD shocks. In
one analysis, the occurrence of frequent ICD shocks was the primary reason for adding an
antiarrhythmic drug (64 percent) [3].

● To suppress supraventricular arrhythmias that may cause symptoms or interfere with ICD
function, potentially resulting in "inappropriate" shocks. "Inappropriate" shocks result from
non-life-threatening arrhythmias which meet the programmed parameters for ICD therapy,
primarily based upon rate (eg, atrial fibrillation with a rapid ventricular response exceeding
the programmed threshold for delivering a shock). "Inappropriate" shocks have been
reported in up to 29 percent of ICD patients and can have a substantial impact on the
patient’s quality of life [4]. These shocks are caused by a variety of arrhythmias including
sinus tachycardia, atrial fibrillation, and nonsustained ventricular tachycardia (NSVT) [4,5].
(See "Cardiac implantable electronic devices: Long-term complications", section on
'Inappropriate shocks'.)

More sophisticated programming features of current-generation ICDs may allow the device
to ignore clinically unimportant and non-life-threatening arrhythmias rather than delivering
an unnecessary shock. (See "Implantable cardioverter-defibrillators: Optimal
programming".)

● To reduce the ventricular rate of VT so that it is better tolerated hemodynamically and/or

more amenable to termination by anti-tachycardia pacing or low energy cardioversion.

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CHOICE OF PHARMACOLOGIC THERAPY

For patients with an implantable cardioverter-defibrillator (ICD) who require adjunctive

antiarrhythmic therapy due to ongoing ventricular arrhythmias, we recommend treatment with the
combination of amiodarone plus a beta blocker rather than treatment with amiodarone alone or
other antiarrhythmic agents. On occasion, therapy with mexiletine or sotalol may be useful. In
general, the class I antiarrhythmic drugs are not used as the majority of patients with sudden
cardiac arrest (SCA) have structural heart disease, and these drugs are not recommended in
patients with structural heart disease.

Pharmacologic therapy, in the form of beta blockers and antiarrhythmic medications, can be
helpful in controlling ventricular arrhythmias in survivors of SCA. Virtually all patients who have
survived SCA should be considered for beta blocker therapy. However, due to the efficacy of the
ICD in treating sustained ventricular tachyarrhythmias and improving mortality, antiarrhythmic
drugs are generally reserved for use in select patients as adjunctive therapy, or as primary
therapy when an ICD is not indicated or refused by the patient. (See "Secondary prevention of
sudden cardiac death in heart failure and cardiomyopathy".)

Empiric versus guided pharmacologic therapy — Empiric pharmacologic therapy for SCA
survivors, primarily with beta blockers and/or an antiarrhythmic drug, is an effective approach for
survivors of SCA who have refused ICD placement or are not candidates for an ICD. Beta
blockers have some efficacy with relatively few side effects, while for most patients amiodarone
is the most efficacious antiarrhythmic drug for preventing recurrent ventricular arrhythmias.

In the past, the choice of antiarrhythmic drug was guided by objective criteria based upon either
noninvasive (ambulatory electrocardiogram [ECG] monitoring) or invasive testing
(electrophysiologic studies). An effective drug, identified by either technique, was noted to
prevent recurrent arrhythmia and potentially improve survival compared with no therapy or an
ineffective drug [6-13]. In current practice, however, when pharmacologic therapy is administered
to a patient with or without (because of refusal or noncandidacy for) an ICD, empiric treatment
with beta blockers and/or amiodarone is the preferred approach. Other antiarrhythmic drugs (for
example mexiletine or sotalol) are considered if there is recurrent arrhythmia despite therapy
with amiodarone and/or a beta blocker.

Beta blockers — Nearly all patients who have survived SCA should receive a beta blocker as
part of their therapy. Beta blockers are not generally considered to be adequate monotherapy
and should be used in conjunction with an antiarrhythmic drug for most patients resuscitated
from SCA due to ventricular tachycardia (VT) or ventricular fibrillation (VF). However, the

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associated anti-adrenergic effects of beta blockers may be effective at reducing both arrhythmias
and SCA when no specific antiarrhythmic treatment is given. In an analysis from the AVID trial,
patients who were discharged from the hospital on a beta blocker had a mortality reduction
compared with those patients not receiving a beta blocker [14].

Most SCA survivors will have multiple indications for a beta blocker (eg, post-myocardial
infarction, heart failure, etc) from which they derive clinical benefit. Beta blockers reduce the
incidence of sudden death and total mortality in patients with a recent myocardial infarction and
in those with symptomatic heart failure or congenital long QT syndrome. However, even in the
absence of any additional indications, beta blockers should be used as part of the medical
regimen following SCA due to VT/VF. (See "Acute myocardial infarction: Role of beta blocker
therapy" and "Congenital long QT syndrome: Treatment" and "Initial pharmacologic therapy of
heart failure with reduced ejection fraction in adults", section on 'Beta blocker'.)

Beta blockers can potentiate the effects of class I antiarrhythmic drugs by preventing the effect of
sympathetic stimulation on reversing the depressant effect on slowing conduction. They can
also potentiate the action of class III antiarrhythmic drugs by preventing the sympathetic effect on
shortening repolarization.

Antiarrhythmic drugs — Among antiarrhythmic medications, amiodarone is the most effective

for preventing recurrent ventricular tachyarrhythmias, although mexiletine or sotalol are also
efficacious for reducing recurrent ventricular arrhythmias. We prefer empiric therapy with
amiodarone for treatment immediately following SCA in patients with recurrent ventricular
tachyarrhythmias as well as for those who have refused (or are not candidates for) ICD
placement [15]. Following stabilization of the patient, if there are concerns about potential toxicity
related to amiodarone, particularly for anticipated long-term use, mexiletine or sotalol may be
considered. (See "Amiodarone: Adverse effects, potential toxicities, and approach to
monitoring".)

Efficacy — Several clinical trials and systematic reviews have evaluated the efficacy of
antiarrhythmic drugs as adjuvant therapy in ICD patients [5,16-21]. There were significant
differences in trial methodologies, which limit direct comparisons. Amiodarone has generally
been the most effective antiarrhythmic drug for preventing ventricular arrhythmias (and
associated ICD shocks).

● In one systematic review which included eight randomized trials involving 1889 patients,
there was significant heterogeneity among the trials, including variation on the active
therapy, control therapy, and outcomes assessed, and the results were divided into those
trials that compared class III antiarrhythmic drugs (usually sotalol and amiodarone) with

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beta blockers, and those trials that compared class III drugs (sotalol, dofetilide, and
azimilide) with placebo or no antiarrhythmic therapy [20]. Key findings included:

• Amiodarone in combination with a beta blocker significantly reduced the incidence of

shocks compared with beta blocker alone (hazard ratio [HR] 0.27, 95% CI 0.14-0.52).
These results were largely driven by the OPTIC trial.

• Sotalol reduced the incidence of ICD shocks when compared with placebo (HR 0.55,
95% CI 0.4-0.78). There was also a trend toward fewer shocks in patients treated with
sotalol versus another beta blocker.

• Treatment with either azimilide or dofetilide resulted in nonsignificant trends towards

reduction in total ICD shocks (generally due to a decrease in supraventricular
arrhythmias) compared with placebo. However, the incidence of appropriate ICD
therapies (shocks plus antitachycardia pacing) was significantly reduced by azimilide
(HR 0.31, 95% CI 0.29-0.34).

● In a second systematic review of 17 randomized trials involving 5875 patients, patients

taking an antiarrhythmic drug had significantly fewer ICD shocks compared with those not
on an antiarrhythmic (odds ratio [OR] 0.59, 95% CI 0.36-0.96) [22]. However, the reduction in
shocks seen in patients receiving an antiarrhythmic drug was not associated with improved
survival (OR 1.07, 95% CI 0.72-1.59).

● In the OPTIC trial, a multicenter trial that randomized 412 patients with an ICD to treatment
with a beta blocker alone, a beta blocker plus amiodarone, or sotalol alone, the rate of any
ICD shock at one year was significantly lower with amiodarone plus a beta blocker than with
sotalol or a beta blocker alone (10.3 versus 24.3 and 38.5 percent, respectively) [16]. There
was a trend toward fewer total ICD shocks in the sotalol group compared with beta blockers
alone; however, sotalol had no significant effect compared with a beta blocker alone in
reducing the incidence of appropriate shocks or antitachycardia pacing.

Another major advantage of amiodarone is a very low frequency of proarrhythmia. Although

amiodarone can markedly prolong the QT/QTc interval, torsades de pointes is rare. However,
caution is necessary when amiodarone is given with other drugs that can prolong the QT interval
or therapy is complicated by hypokalemia or hypomagnesemia. Caution is necessary when
combining amiodarone with a beta blocker, as amiodarone also has beta blocking effects and
significant bradycardia or AV block may occur. This is not a concern in patients who have an ICD,
as there is backup pacing. However, for patients without an ICD or pacemaker this should be
considered and patients should be monitored carefully. (See "Amiodarone: Adverse effects,

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potential toxicities, and approach to monitoring" and "Acquired long QT syndrome: Definitions,
causes, and pathophysiology".)

Administration — When patients are started on an antiarrhythmic drug, they should have a
baseline ECG prior to drug initiation and then serial ECGs for the first two to three days,
particularly to monitor heart rate and assess for any significant QT/QTc interval prolongation.

Amiodarone — The initial dosing of amiodarone will vary depending on the route
(intravenous [IV] or oral) as well as the clinical situation (table 1):

● For patients with electrical storm or incessant VT, we recommend IV amiodarone (150 mg IV
push, followed by 1 mg/minute IV infusion for six hours, followed by 0.5 mg/min IV infusion
for 18 additional hours) as the initial antiarrhythmic agent. (See "Electrical storm and
incessant ventricular tachycardia", section on 'Initial antiarrhythmic medical therapy'.)

● For patients who have been on IV therapy for more than two weeks, we start maintenance
oral amiodarone at a dose of 200 to 400 mg/day. (See "Amiodarone: Clinical uses", section
on 'Amiodarone for ventricular arrhythmias'.)

● For patients who have been on IV therapy for one to two weeks, we start an intermediate
maintenance oral amiodarone dose of 400 to 800 mg/day until an adequate loading dose
has been achieved, then the dose should be reduced to the usual maintenance dose of 200
mg/day. The recommended IV loading dose is 10 grams or the oral equivalent. As oral
amiodarone is approximately 50 percent bioavailable, a total of 20 to 30 grams of oral
amiodarone is equivalent to the IV loading dose.

● For patients who have been on IV therapy for one week or less, we usually start with a full
oral amiodarone loading dose of 400 to 1200 mg/day (typically in two or three divided
doses). This should be continued until a total loading dose of 10 grams has been received,
then the dose should be reduced to the usual maintenance dose of 200 mg/day.

Sotalol — In contrast to amiodarone, sotalol is not universally available in IV form.

Bradycardic and proarrhythmic events (especially due to QT/QTc prolongation) can occur after
the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol
should be initiated and doses increased in a hospital with facilities for cardiac rhythm
monitoring and assessment.

● We start sotalol at a dose of 80 mg twice daily, with dose adjustments at three-day intervals
once steady-state plasma concentrations have been achieved and the QT interval has been
reviewed on a surface ECG. Patients with renal insufficiency require a modification of the

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dosing interval. (See "Therapeutic use and major side effects of sotalol", section on
'Dosing'.)

Mexiletine — Mexiletine, which is a lidocaine-like antiarrhythmic drug, is only available for

oral use. It is often used with or without amiodarone for treating patients with an ICD who have
ventricular arrhythmias that are of concern. The usual dose is 200 to 400 mg three times daily.

Treatment of breakthrough arrhythmias — Patients who have recurrent, or breakthrough,

arrhythmias resulting in repeat ICD shocks or sudden cardiac arrest in spite of therapy with a
beta blocker and/or antiarrhythmic drug represent a significant clinical challenge. As with the
occurrence of any ventricular arrhythmia, any identifiable reversible causes (eg, myocardial
ischemia, electrolyte disturbances) should be corrected. In the absence of any reversible
causes, we approach treatment in the following way:

● For patients who are taking only a beta blocker, we add an antiarrhythmic drug, ideally
amiodarone.

● For patients who are taking only an antiarrhythmic drug, we add a beta blocker.

● For patients who are taking both a beta blocker and an antiarrhythmic drug, treatment
options include upward titration of either or both existing drugs or the discontinuation of the
current antiarrhythmic drug in favor of an alternative antiarrhythmic drug. We prefer to first
increase the dose of the beta blocker and the current antiarrhythmic drug to the maximum
recommended dose (or maximum tolerated dose if side effects arise). If this approach is
ineffective and the patient continues to have recurrent ventricular arrhythmias and shocks,
we would consider stopping the current antiarrhythmic drug and initiating treatment with
another agent.

Another important option for patients with recurrent arrhythmia despite amiodarone and beta
blocker is the addition of a class I antiarrhythmic agent (table 2) that does not alter the
QT/QTc interval (ie, mexiletine or propafenone).

IMPACT ON ICD THERAPIES

The primary goal of using blockers and/or antiarrhythmic drugs in patients with an implantable
cardioverter-defibrillator (ICD) is to minimize the frequency of recurrent ventricular arrhythmias,
thereby decreasing the likelihood of the patient receiving additional ICD shocks. Beyond
reducing the likelihood of ICD shocks, however, antiarrhythmic drug therapy may impact the
efficacy of ICD therapies by potentially altering defibrillation thresholds and by slowing the

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ventricular rates of any recurrent sustained tachyarrhythmias.

Alterations in DFTs — Any antiarrhythmic drug can potentially alter the defibrillation threshold
(DFT), although the effect has been most pronounced with amiodarone and its major metabolite
desethylamiodarone, which increase the DFT in a dose-dependent fashion [23-25]. DFT testing
has historically been performed at the time of ICD implantation, although the routine necessity
for this evaluation with the current generation of ICDs has been questioned. However, repeat
DFT testing may be warranted after the initiation of amiodarone if there is concern about rising
DFT thresholds (as may occur in certain clinical situations, including atrial fibrillation,
hypertension, and left ventricular hypertrophy).

In the report on the efficacy of routine ICD testing discussed above, 71 patients had an ICD test
due to the initiation or dose-adjustment of an antiarrhythmic drug (primarily amiodarone or
sotalol), and the ICD failed to defibrillate only two patients [26]. The role of ICD testing after the
initiation of antiarrhythmic therapy was more directly assessed in a substudy of the OPTIC trial,
in which 94 patients underwent serial ICD testing to determine the impact of each of three drug
regimens (beta blockers, amiodarone plus a beta blocker, and sotalol) on DFTs [27]. At a mean
follow-up of 60 days after drug initiation, the mean DFT decreased from baseline in the patients
assigned to beta blockers or sotalol (8.8 to 7.1 and 8.1 to 7.2 joules, respectively), while among
patients taking amiodarone there was a nonsignificant increase in the mean DFT from 8.5 to 9.8
joules. Given the relatively small number of patients in each arm of this study, the small mean
increase in DFT does not preclude the possibility that there may be a larger increase in some
patients. Thus, the necessity for ICD testing after the initiation of antiarrhythmic drugs, primarily
amiodarone, remains uncertain.

VT rate slowing — In patients receiving chronic antiarrhythmic drug therapy, the rate of recurrent
ventricular tachycardia (VT) is often slower than the rate seen during the index arrhythmia. This
slower ventricular rate can have both positive and negative impacts on the delivery of ICD
therapy:

● Antitachycardia pacing is often more effective for the treatment of VT with a slower ventricular
rate. When antitachycardia pacing effectively terminates the VT, the ICD does not deliver a
shock and many patients will have no knowledge of the event.

● Slower ventricular rates during VT may result in the VT falling below the previously defined
rate thresholds for the ICD to detect and treat the arrhythmia. As a result, if no ICD
programming changes are made, and the VT is hemodynamically significant (ie, resulting in
syncope, palpitations, chest pain, dyspnea, or even SCA), the patient may not receive an
appropriately-indicated therapy.

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Thus, it is common practice to lower the VT detection cutoff when initiating antiarrhythmic drug
therapy, with the specific detection threshold individualized based on the specific data available
from prior events in the individual patient.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias"
and "Society guideline links: Basic and advanced cardiac life support in adults".)

SUMMARY AND RECOMMENDATIONS

● Because of the survival benefit associated with an implantable cardioverter-defibrillator

(ICD) compared with antiarrhythmic therapy alone, most survivors of sudden cardiac arrest
(SCA) due to ventricular tachycardia (VT) or ventricular fibrillation (VF) not associated with a
reversible cause should receive an ICD. Antiarrhythmic drugs can be considered as the
primary therapy when an ICD is not indicated or refused by the patient. (See 'Indications for
pharmacologic therapy' above and "Secondary prevention of sudden cardiac death in heart
failure and cardiomyopathy".)

● Nearly all patients who have survived SCA should receive a beta blocker as part of their
therapy, which may also provide additional antiarrhythmic benefits. (See 'Empiric versus
guided pharmacologic therapy' above.)

● Because an ICD does not prevent arrhythmias, patients who have arrhythmias (ventricular
or supraventricular) with symptoms or device discharges may require adjunctive
antiarrhythmic therapy or consideration of catheter ablation. The three main indications for
concomitant antiarrhythmic drug therapy are (see 'Indications for pharmacologic therapy'
above):

• To reduce the frequency of ventricular arrhythmias in patients with frequent ICD shocks.

• To suppress other arrhythmias that cause symptoms or interfere with ICD function (eg,
causing "inappropriate" shocks).

• To reduce the ventricular rate of VT so that it is better tolerated hemodynamically and

more amenable to termination by anti-tachycardia pacing or low-energy cardioversion.

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● For patients with an ICD who require adjunctive antiarrhythmic therapy due to ongoing
arrhythmias, we recommend treatment with the combination of amiodarone plus a beta
blocker rather than treatment with amiodarone alone or other antiarrhythmic agents (Grade
1B). This approach is especially preferred in patients with significant left ventricular
dysfunction who require adjunctive antiarrhythmic therapy, since amiodarone does not
exacerbate heart failure and is less proarrhythmic than other agents. (See 'Choice of
pharmacologic therapy' above.)

● Adverse effects related to antiarrhythmic medications include increased defibrillation

thresholds (DFTs) and slowing of the tachycardia rate, which may preclude its recognition by
the ICD. (See 'Impact on ICD therapies' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Jie Cheng, MD, who contributed to an
earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Knilans TK, Prystowsky EN. Antiarrhythmic drug therapy in the management of cardiac
arrest survivors. Circulation 1992; 85:I118.

2. Manz M, Jung W, Lüderitz B. Interactions between drugs and devices: experimental and
clinical studies. Am Heart J 1994; 127:978.

3. Steinberg JS, Martins J, Sadanandan S, et al. Antiarrhythmic drug use in the implantable
defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study. Am
Heart J 2001; 142:520.

4. Nanthakumar K, Paquette M, Newman D, et al. Inappropriate therapy from atrial fibrillation

and sinus tachycardia in automated implantable cardioverter defibrillators. Am Heart J
2000; 139:797.

5. Pacifico A, Hohnloser SH, Williams JH, et al. Prevention of implantable-defibrillator shocks

10 of 18 4/24/2020, 11:05 PM
Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-...

by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N

Engl J Med 1999; 340:1855.

6. Kim SG. The management of patients with life-threatening ventricular tachyarrhythmias:

programmed stimulation or Holter monitoring (either or both)? Circulation 1987; 76:1.

7. Wilber DJ, Garan H, Finkelstein D, et al. Out-of-hospital cardiac arrest. Use of

electrophysiologic testing in the prediction of long-term outcome. N Engl J Med 1988;
318:19.

8. Graboys TB, Lown B, Podrid PJ, DeSilva R. Long-term survival of patients with malignant
ventricular arrhythmia treated with antiarrhythmic drugs. Am J Cardiol 1982; 50:437.

9. Lampert S, Lown B, Graboys TB, et al. Determinants of survival in patients with malignant
ventricular arrhythmia associated with coronary artery disease. Am J Cardiol 1988; 61:791.

10. Vlay SC, Kallman CH, Reid PR. Prognostic assessment of survivors of ventricular
tachycardia and ventricular fibrillation with ambulatory monitoring. Am J Cardiol 1984;
54:87.

11. Mason JW. A comparison of electrophysiologic testing with Holter monitoring to predict
antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. Electrophysiologic Study
versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:445.

12. Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular
tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring
Investigators. N Engl J Med 1993; 329:452.

13. Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in patients with ventricular
tachyarrhythmias. N Engl J Med 1983; 308:1436.

14. Exner DV, Reiffel JA, Epstein AE, et al. Beta-blocker use and survival in patients with
ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus
Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 1999; 34:325.

15. Weinberg BA, Miles WM, Klein LS, et al. Five-year follow-up of 589 patients treated with
amiodarone. Am Heart J 1993; 125:109.

16. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus
beta-blockers, or sotalol for prevention of shocks from implantable cardioverter

11 of 18 4/24/2020, 11:05 PM
Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-...

defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165.

17. Dorian P, Borggrefe M, Al-Khalidi HR, et al. Placebo-controlled, randomized clinical trial of
azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable
cardioverter defibrillator. Circulation 2004; 110:3646.

18. Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular

tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol
2004; 43:39.

19. Kühlkamp V, Mewis C, Mermi J, et al. Suppression of sustained ventricular

tachyarrhythmias: a comparison of d,l-sotalol with no antiarrhythmic drug treatment. J Am
Coll Cardiol 1999; 33:46.

20. Ferreira-González I, Dos-Subirá L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in

patients with implantable cardioverter defibrillators: a systematic review. Eur Heart J 2007;
28:469.

21. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE
Study). The CASCADE Investigators. Am J Cardiol 1993; 72:280.

22. Ha AH, Ham I, Nair GM, et al. Implantable cardioverter-defibrillator shock prevention does
not reduce mortality: a systemic review. Heart Rhythm 2012; 9:2068.

23. Zhou L, Chen BP, Kluger J, et al. Effects of amiodarone and its active metabolite
desethylamiodarone on the ventricular defibrillation threshold. J Am Coll Cardiol 1998;
31:1672.

24. Pelosi F Jr, Oral H, Kim MH, et al. Effect of chronic amiodarone therapy on defibrillation
energy requirements in humans. J Cardiovasc Electrophysiol 2000; 11:736.

25. Nielsen TD, Hamdan MH, Kowal RC, et al. Effect of acute amiodarone loading on energy
requirements for biphasic ventricular defibrillation. Am J Cardiol 2001; 88:446.

26. Brunn J, Böcker D, Weber M, et al. Is there a need for routine testing of ICD defibrillation
capacity? Results from more than 1000 studies. Eur Heart J 2000; 21:162.

27. Hohnloser SH, Dorian P, Roberts R, et al. Effect of amiodarone and sotalol on ventricular
defibrillation threshold: the optimal pharmacological therapy in cardioverter defibrillator
patients (OPTIC) trial. Circulation 2006; 114:104.

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Topic 972 Version 19.0

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GRAPHICS
Amiodarone dosing in adults by indication
Indications
Atrial arrhythmias
Prevention of recurrent PAF
Pharmacologic cardioversion of
PAF
Pretreatment before elective
cardioversion or catheter
ablation of AF
Restoration and maintenance
of NSR in critically ill patients
with AF
Ventricular rate control in
critically ill patients with AF and
rapid ventricular response
Ventricular arrhythmias
Primary and secondary
prevention of SCD in patients
with LV dysfunction who are
not candidates for or refuse
ICD implantation
Prevention of ventricular
arrhythmias in patients with
ICDs to decrease risk of shocks
Cardiac arrest associated with
VF or pulseless VT
Electrical (VT) storm and
incessant VT in
hemodynamically stable
patients
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Loading dose Maintenance dose
Total loading dose: 6 to 10 grams Lowest effective dose, usually 100
Given as 400 to 1200 mg orally to 200 mg orally once per day
per day in divided doses Maximum 400 mg orally per day
Total loading dose: 6 to 10 grams Lowest effective dose, usually 100
orally over 2 to 6 weeks to 200 mg orally once per day
Given as 400 to 1200 mg orally Maximum 400 mg orally per day
per day in divided doses
Total IV loading dose: 1050 mg
Given as 150 mg IV bolus over 10
to 30 minutes, followed by
continuous IV infusion at 1 mg per
minute for 6 hours, then 0.5 mg
per minute for 18 hours*
IV infusion (0.5 mg per minute)
may need to be extended past 24
hours if unable to transition to oral
therapy
Following IV infusion 400 to 1200
mg orally per day in divided doses
to complete a total (IV plus oral)
loading dose of 10 grams
Total oral loading dose: 6 to 10 Lowest effective dose, usually 200
grams to 400 mg orally once per day or
400 to 1200 mg orally per day in in divided doses
divided doses Maximum 400 mg orally per day
Total loading dose: 6 to 10 grams Lowest effective dose, usually 200
400 to 1200 mg orally per day in to 400 mg orally per day
divided doses Maximum 400 mg orally per day
300 mg IV or IO rapid bolus with a
repeat dose of 150 mg as
indicated
Upon return of spontaneous
circulation follow with an infusion
of 1 mg per minute for 6 hours
and then 0.5 mg per minute for
18 hours*
Total IV loading dose: 1050 mg
150 mg IV bolus over 10 minutes,
followed by continuous IV infusion
at 1 mg per minute for 6 hours,
then 0.5 mg per minute for 18
hours
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IV infusion (0.5 mg per minute)

may need to be extended past 24
hours if unable to transition to oral
therapy ¶
Additional 150 mg boluses may be
given if VT storm recurs

PAF: paroxysmal atrial fibrillation; AF: atrial fibrillation; NSR: normal sinus rhythm; IV: intravenous; SCD: sudden cardiac
death; LV: left ventricular; ICD: implantable cardioverter-defibrillator; VF: ventricular fibrillation; VT: ventricular
tachycardia; IO: intraosseous.
* When administered to critically ill patients with atrial fibrillation and rapid ventricular response, repeated 150 mg boluses
can be given over 10 to 30 minutes if needed, but no more than six to eight additional boluses should be administered in
any 24-hour period.
¶ Typically, patients are given 1 or 2 doses of oral amiodarone prior to discontinuation of the IV infusion.

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Revised (2018) Vaughan Williams classification of antiarrhythmic drugs

abridged table

Class 0 (HCN channel blockers)

Ivabradine

Class I (voltage-gated Na+ channel blockers)

Class Ia (intermediate dissociation):

Quinidine, ajmaline, disopyramide, procainamide

Class Ib (rapid dissociation):

Lidocaine, mexilitine

Class Ic (slow dissociation):

Propafenone, flecainide

Class Id (late current):

Ranolazine

Class II (autonomic inhibitors and activators)

Class IIa (beta blockers):

Nonselective: carvedilol, propranolol, nadolol

Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol

Class IIb (nonselective beta agonists):

Isoproterenol

Class IIc (muscarinic M2 receptor inhibitors):

Atropine, anisodamine, hyoscine, scopolamine

Class IId (muscarinic M2 receptor activators):

Carbachol, pilocarpine, methacholine, digoxin

Class IIe (adenosine A1 receptor activators):

Adenosine

Class III (K+ channel blockers and openers)

Class IIIa (voltage dependent K+ channel blockers):

Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant

Class IIIb (metabolically dependent K+ channel openers):

Nicorandil, pinacidil

Class IV (Ca++ handling modulators)

Class IVa (surface membrane Ca++ channel blockers):

Bepridil, diltiazem, verapamil

Class IVb (intracellular Ca++ channel blockers):

Flecainide, propafenone

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Class V (mechanosensitive channel blockers):

No approved medications

Class VI (gap junction channel blockers)

No approved medications

Class VII (upstream target modulators)

Angiotensin converting enzyme inhibitors

Angiotensin receptor blockers

Omege-3 fatty acids

Statins

HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium.

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Contributor Disclosures
Philip J Podrid, MD, FACC Nothing to disclose Scott Manaker, MD, PhD Consultant/Advisory Boards:
Expert w itness in w orkers' compensation and in medical negligence matters [General pulmonary and critical
care medicine]. Equity Ow nership/Stock Options (Spouse): Johnson & Johnson; Pfizer. Other Financial
Interest: National Board for Respiratory Care [Director]. Sam uel Lévy, MD Nothing to disclose Brian C
Dow ney, MD, FACC Nothing to disclose

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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