Acute Amiodarone-Induced Pulmonary Toxicity (AIPT)

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Amiodarone-induced ARDS [3, 4].

Although classic AIPT typically develops insidiously,

some patients present acutely in the form of diffuse sym-

metrical or asymmetrical pulmonary in ltrates and

respiratory failure requiring titrated oxygen therapy or

mechanical ventilation. The interval between the earliest

signs and symptoms of AIPT and development ARDS is

unknown, and it is possible that ARDS represents an

acute exacerbation of previously undiagnosed or sub-

clinical AIPT. In one study in 514 ARDS cases, 49

(9.5%) were thought to be related to exposure to drugs.

Fourteen of these 49 (28.5%), representing 2.7% of the

whole ARDS population, were associated with exposure

to amiodarone [35]. In another study, amiodarone was

shown to increase the risk of developing ARDS approxi-

mately 3.8-fold [125].

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Postoperative Amiodarone-associated/induced ARDS [3, 4]

This presentation can develop within days following car-

diac, coronary bypass graft or surgical pulmonary resec-

tion. Features include onset within a few hours or days of

surgery in patients who have been either chronically

treated with amiodarone or in those who received the drug

postoperatively. The complication can occur after a total

amount of as little as 1100 mg of amiodarone. In one

study, prophylactic amiodarone was given to combat

supraventricular brillation post-resectional lung surgery

[126]. This led to a sixfold increase in the incidence of

ARDS compared to controls, with a 66% mortality.

However, not all studies con rmed that nding since then.

Pathological examination of lung tissue from amiodarone-­

associated ARDS patients reveals DAD on a background

of pulmonary phospholipidosis [61]. It may take as little

as 2 days on the drug to develop foam cells and endoge-

nous lipoid pneumonia that are suggestive of AIPT. Foam

cells can also be retrieved in the BAL of such patients.

Intraoperative factors, such as high oxygen tensions, are

thought to trigger postoperative occurrence of amiodarone-­

associated ARDS. Intraoperative single lung ventilation

with 100% oxygen led to selective damage of the venti-

lated lung, while the “resting” lung was spared [127]. An

intriguing feature of those who survive an episode of

amiodarone-associated ARDS is that they can sometimes

be restarted on amiodarone after surgery without recur-

rence. This is consistent with the view that amiodarone-­

associated ARDS may arise due to a two-hit interaction

that includes exposure to amiodarone and perior intraop-

erative factors such as elevated high oxygen tension in the

inhaled air, barotrauma, cytokine release, impaired tho-

racic lymphatic damage from surgery, or any combination

thereof. The practical conclusion in terms of prevention is

that liberal or prophylactic use of amiodarone and above-­

needed inspired oxygen tensions preand post-operatively