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Page 4 of 12 Waterford et al. Vessel Plus 2022;6:28 https://dx.doi.org/10.20517/2574-1209.2021.115

loading dose has been completed.

Amiodarone is an excellent choice for use in patients with structural heart disease or congestive heart
[33]
failure , but there are also contraindications and side effects that should be considered. Contraindications
to the use of amiodarone include severe sinus node dysfunction, including symptomatic sinus bradycardia,
and advanced conduction system disease. A prolonged QT interval on amiodarone also represents a
contraindication to its use, with different physicians choosing different intervals for discontinuation. Before
choosing amiodarone for the treatment of atrial fibrillation, clinicians can consider other options, such as a
trial of rate control agents. These agents have a lower risk profile than amiodarone, but their use depends on
the clinical setting . Amiodarone is associated with both cardiovascular and non-cardiovascular adverse
[33]
events. The most frequent cardiovascular side effect is bradycardia, which is often dose-related, occurs more
[34]
frequently in elderly patients than in younger patients, and can often be mitigated by dose reduction . The
conduction system should be monitored for QTc prolongation, but amiodarone is not generally associated
with torsades de pointes (< 0.5%) as compared with other drugs that prolong the QT interval (e.g., sotalol
and dofetilide) [23,35] . Clinical evidence of hypothyroidism occurs in up to 20% of patients taking amiodarone.
This is likely because of interference with the iodothyronine deiodinases, which metabolize thyroid
hormones . Hypothyroidism is easily managed with levothyroxine and generally is not cause for
[36]
discontinuing amiodarone. Thyrotropin levels should be checked in all patients at least every 6 months after
initiation [37,38] .

Pulmonary toxicity is one of the most serious complications of amiodarone use. It occurs in less than 3% of
[26]
patients and is thought to be related to the total cumulative dosage , and therefore applies to chronic use
rather than use in the postoperative period. Chronic amiodarone therapy should therefore be used
cautiously in patients with preexisting pulmonary disease (e.g., severe asthma, chronic obstructive
pulmonary disease) or those requiring oxygen therapy, as they are at higher risk of pulmonary toxicity .
[39]
The management of pulmonary toxicity involves discontinuation of therapy, supportive management, and
potential corticosteroid administration for extreme cases . Side effects resulting in discontinuation of
[40]
[38]
therapy occur in 13%-18% of patients after 1 year .
Amiodarone is frequently used for the prevention and treatment of atrial fibrillation associated with cardiac
[33]
surgery, including the maze procedure for the treatment of atrial fibrillation . However, there are no major
clinical trials that directly compare the use of amiodarone to beta-blocker alone. In addition, there have not
been thorough studies on combinations of drugs such as ARBs with amiodarone. Emerging data suggest
that combination therapy is more effective than either agent alone [26,41] . It is important to emphasize that the
goal of a short 2-3 day course of amiodarone before surgery is to reduce the incidence of new-onset POAF,
not to treat chronic atrial fibrillation. The increased efficacy of amiodarone in preventing new-onset POAF
compared to treating chronic atrial fibrillation may arise from its action as a class I through IV
antiarrhythmic, particularly its action as a beta-blocker (class II) and calcium channel blocker (class IV), as
[25]
discussed above .
Finally, three important drug-drug interactions deserve mention. First, QT prolongation due to lengthened
repolarization from potassium channel blockade is a known side effect of amiodarone. This effect can be
exacerbated by combining amiodarone with other drugs that prolong the QT interval . Quinolones are one
[42]
example, but digoxin is another medication that increases the risk of torsades de pointes in patients with
long QT interval. In addition, antipsychotic agents including haloperidol, antidepressants such as
fluoxetine, macrolide antibiotics, and methadone are common drugs that prolong QT interval . Therefore
[42]
obtaining a daily electrocardiogram to measure the QT interval is warranted in postoperative patients on