The rational use of intravenous amiodarone in the perioperative period.

Balser JR. Anesthesiology 1997; 86:974-87.

[ see abstract below ]

Amiodarone, a potent antiarrhythmic agent used for intractable ventricular arrhythmias, has been available in oral form for many years. It gained considerable notoriety among anesthesiologists because of its extraordinarily long half-life (29 days), and disconcerting hemodynamic and pulmonary side-effects. These include intractable bradyarrhythmias and heart block, polymorphic ventricular arrhythmias, markedly impaired response to beta-adrenergic inotropic agents, and postoperative ARDS (possibly related to oxygen toxicity).

In August 1995 intravenous amiodarone was approved by the FDA for the management of intractable ventricular arrhythmias, and is increasingly being used by cardiologists for supraventricular arrythmias as well. It is therefore timely for anesthesiologists to read Dr Balser's very thorough and complete Medical Intelligence Article in the April 1997 issue of Anesthesiology.

Amiodarone appears to achieve its antiarrhythmic effects by a combination of noncompetitive alpha- and beta-adrenergic blockade. This causes arterial vasodilation and AV nodal blockade, augmented by calcium channel blockers. It also acts as a Class I agent, blocking the sodium channels (slower upstroke of the action potential, slowed ventricular conduction) and Class III agent, reducing potassium egress (prolonged QT interval).

Amiodarone is extremely lipophilic. This accounts for its poor bioavailability and very delayed (10 day) onset of therapeutic effect by the oral route. In contrast, after an IV dose initial therapeutic effects are observed within 1-30 minutes. However, there is an extremely wide range in its pharmacokinetic and pharmacodynamic behavior, and serum levels are not very helpful in predicting effect; close ECG monitoring for arrhythmias is required.

The IV dosing regimen is very complex: 150 mg over the first 10 min, then 360 mg over the next 6 h, then 540 mg over the next 18 h (i.e. about 1000 mg in 24 h). Subsequently, the daily IV dose is about 720 mg; bolus doses of 150 mg are used to treat "breakthrough". The drug must be administered by central line to avoid venous sclerosis.

The duration of action is heavily dependent on duration of administration: the redistribution half life is about 1-2 d, whereas the elimination half life is up to 40 d. Elimination is largely dependent on hepatic function, and there is an active metabolite (N-desethylamiodarone) which may accumulate with prolonged IV therapy.

In the review, Dr. Balser presents a large amount of data on the efficacy of IV amiodarone in both ventricular and supraventricular arrhythmias. With severe, hemodynamically destabilizing ventricular arrhythmias, IV amiodarone appears to improve survival rate, and is as effective as bretylium with less hypotensive effect.

There are few data on its perioperative use, although amiodarone prophylaxis has been shown to decrease the incidence of nonsustained VT after coronary artery bypass, and there are several anecdotal reports of successful therapy of intractable ventricular arrhythmias after cardiac surgery. It should be considered when other standard agents (lidocaine, procainamide, bretylium) fail, and when there is severe hemodynamic compromise from the arrhythmia.

Amiodarone has not been FDA approved for supraventricular arrhythmias, but it has been used to attempt to convert atrial tachyarrhythmias to sinus rhythm. Although it was well tolerated hemodynamically, its conversion rate was no higher than that of procainamide, and less than that of high-dose magnesium. It may be useful for intractable supraventricular arrhythmias.

Given its increasing use in the perioperative period, amiodarone's toxic effects are of considerable importance to anesthesiologists. Acute postoperative (1-5 d) pulmonary toxicity (potentially lethal ARDS) is reported in up to 25% of patients on oral amiodarone undergoing surgery. The risk factors are unknown, although high FiO2, cardiopulmonary bypass, previous toxicity and cardiac failure have all been implicated. A similar incidence of ARDS has been reported in patients on preoperative IV amiodarone undergoing pneumonectomy. However, there have not yet been reports of ARDS occurring when IV amiodarone was given after cardiac surgery.

In patients on chronic oral amiodarone therapy undergoing cardiac surgery, there have been a number of anecdotal reports of AV blockade requiring prolonged pacing, impaired ventricular function and response to inotropic agents requiring balloon counterpulsation, and extreme systemic vasodilation. Acute, severe hypotension occurs in up to 25% of patients loaded with IV amiodarone, requiring volume challenge, cessation of infusion, or pressor agents.

Cardiac decompensation is likely when IV amiodarone is rapidly infused in patients with poor cardiac function immediately after cardiac surgery. Adverse effects are much less likely when ventricular function is normal, or when IV amiodarone is given prophylactically before surgery. Bradyarrhythmias and complete heart block may also occur, but the ability to provide atrial or atrioventricular pacing after cardiopulmonary bypass means that these seldom present real problems.

Although low, there is a risk that oral or IV amiodarone may cause polymorphic ventricular arrhythmias (torsade de pointes). Risk factors include hypokalemia, hypomagnesemia, bradycardia, diuretic therapy and female gender. The most important premonitory sign (although not a sensitive predictor) is a prolonged QT interval. Therapy consists of DC cadioversion, drug cessation, magnesium and measures to increase heart rate (atropine, isoproterenol or pacing).

In conclusion, amiodarone is a complex and effective third-line antiarrhythmic agent with an impressive potential for toxicity. With the approval of its IV form and increasing research on its safety and efficacy in the perioperative period, anesthesiologists can expect to encounter or administer the drug with greater frequency in the future. Dr Balser's review considerably bolsters our understanding of this challenging drug.

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