In the United States, intravenous amiodarone has been approved by the U.S. Food and Drug Administration for the treatment and prophylaxis of recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia in patients in whom other therapy is unsuccessful [3]. Much interest has been generated about the use of intravenous amiodarone for the treatment of life-threatening arrhythmias because of amiodarone's rapid onset of action and beneficial electropharmacologic and hemodynamic profile [4]. In this article, we review the electropharmacology, pharmacokinetics, and side effects of intravenous amiodarone and define the role of amiodarone in the treatment of various types of arrhythmias.

Methods

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We searched the MEDLINE database for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. We also examined bibliographies of textbooks and articles. Studies that reported on the efficacy, toxicity, and hemodynamic dynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. We assessed study design and quality and relevant data on the efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and the hemodynamic changes seen with therapy.

Data Synthesis

Electropharmacology

Amiodarone is now used as an extremely potent antiarrhythmic drug. Although traditionally classified as a class III antiarrhythmic agent, oral amiodarone is now known to exert the entire spectrum of antiarrhythmic effects (Table 1) [2, 5]. It also has an antithyroid effect that may contribute to its antiarrhythmic potency [6]. Intravenous amiodarone shares many electrophysiologic properties with the oral form, but there are several important differences.

In animal and human studies, intravenous amiodarone caused electrophysiologic changes in atrioventricular nodal tissue similar to those caused by oral therapy; with both forms of the drug, atrioventricular nodal refractoriness and the intranodal conduction interval are increased [5, 7-11]. These changes are thought to be mediated by the drug's calcium-channel-blocking action [8] and by its noncompetitive antiadrenergic effect, whereby the total number of ß-adrenoreceptors is decreased rather than truly blocked [6, 12-15].

On the other hand, intravenous amiodarone seems to be less thorough than oral amiodarone in its electrophysiologic action against other myocardial tissues. Its effects on the effective refractory periods of atrial, ventricular, and His-Purkinje tissue and the accessory pathways are minimal, and it does not prolong the H-V interval (His bundle-to-ventricular conduction interval), the QRS interval, or the QTc duration [5, 7, 9, 10, 16]. One hypothesis for this difference is that the exertion of amiodarone's notable electrophysiologic effects requires long-term administration, which allows greater penetration of the drug and its active metabolite into these tissues.

Oral amiodarone depresses sinoatrial node automaticity by decreasing phase 4 depolarization in the sinoatrial node and reducing the pacemaker potential amplitude [17], thereby slowing the heart rate. This bradycardiac effect of intravenous amiodarone is counteracted by the drug's vasodilatory action, which triggers a sympathetic response and minimizes the net decrease in heart rate [2, 5, 9-11, 18].

Intravenous amiodarone lacks two important antiarrhythmic mechanisms that are seen with the oral form of the drug. First, it has minimal antithryoid action [19]. Second, its active metabolite, N-desethylamiodarone, which has significant antiarrhythmic potency, is not accumulated in serum or tissue sufficiently to generate any remarkable antiarrhythmic action [7].

The antiarrhythmic property of intravenous amiodarone is potentiated by this form's ability to exert three electrophysiologic actions faster than the oral form. First, intravenous amiodarone substantially inhibits inactivated sodium channels, especially those with shorter cycle lengths (use-dependency phenomenon) [11, 17, 20, 21]. This suggests that the intravenous form's short-term antiarrhythmic action should be greater during rapid tachyarrhythmias. In a canine model, this action on the sodium channel was shown to be more pronounced in ischemic myocardial tissues than in normal tissues [20].

Second, a study using isolated rat hearts showed that intravenous amiodarone significantly decreased the frequency of ventricular fibrillation. This decrease was associated with a substantial reduction in intracellular calcium concentration, suggesting that intravenous amiodarone's effect on cellular calcium homeostasis plays an important role in its antiarrhythmic action [22]. Third, indirect evidence in a rat heart model showed that intravenous amiodarone has a more potent and faster antiadrenergic action than does oral amiodarone [23].

Pharmacokinetics

Many of the unique pharmacokinetic properties of amiodarone are related to the drug's high lipophilicity. As a result of this quality, the drug tends to accumulate in most tissues, especially fatty tissue and liver [14]. Unlike the low bioavailability (35% to 65%) achieved with oral amiodarone, intravenous amiodarone is 100% bioavailable; thus, use of the intravenous form results in substantially higher plasma concentrations than does use of the oral form. These peak concentrations occur more rapidly with the intravenous form because absorption is not required [14]. Peak serum concentrations after single 15-minute intravenous infusions of 5 mg/kg of body weight range from 5 to 41 mg/L [4].

Amiodarone's calculated volume of distribution exceeds 5000 L. This large volume occurs because amiodarone and its major metabolite, N-desethylamiodarone, are taken up from plasma and concentrated (as much as 1000-fold) in erythrocyte membranes and peripheral tissue, especially tissues with a high fat content. In fact, it has been hypothesized that amiodarone exerts at least some of its pharmacologic effects by concentrating in lipid-rich cell membranes and pertubing the milieu around ion channels rather than by modulating ion flow through channels [14].

Intravenous amiodarone is rapidly distributed. Tissue distribution accounts for most of the decline in plasma concentration. Concentrations can decline to 10% of peak values within 30 to 45 minutes after completion of infusion [4, 24]. These distribution characteristics explain why plasma concentrations of the drug do not correlate well with observable clinical effect.

Finally, amiodarone is highly protein bound (approximately 98% of the compound). As a result, neither amiodarone nor N-desethylamiodarone appear in dialysis fluid, a fact that has important implications for the treatment of amiodarone toxicity [14]. Amiodarone is biotransformed in the liver to N-desethylamiodarone. This metabolite has been reported to be equipotent as a sodium-channel blocker and less potent as a calcium-channel blocker compared with the parent compound. N-desethylamiodarone can be detected in plasma shortly after large oral doses of amiodarone but not after intravenous doses [14].

Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion. Urinary excretion of amiodarone or N-desethylamiodarone is negligible [14]. No dosage adjustments seem to be needed in patients with renal or hepatic insufficiency or left ventricular dysfunction [3].

Clinical Applications

Supraventricular Arrhythmias

Atrial fibrillation and atrial flutter. The oral form of amiodarone has been used to convert atrial fibrillation and atrial flutter to normal sinus rhythm and to maintain normal sinus rhythm after conversion. Success rates for conversion and maintenance of normal sinus rhythm range from 53% to 87% (Table 2).

The efficacy of intravenous amiodarone in converting atrial fibrillation to sinus rhythm in an acute setting seems to be controversial, although most studies suggest that efficacy is modest at best. Kerin and Zehender and their colleagues [35, 42] independently compared intravenous amiodarone and quinidine for the conversion of chronic atrial fibrillation to sinus rhythm. Kerin and coworkers [35] found that both treatments were equally effective: Rates of conversion to sinus rhythm were 44% for intravenous amiodarone and 47% for quinidine and digoxin. Zehender and colleagues [42] found similar results; Conversion rates were 55% with quinidine and verapamil and 60% with intravenous amiodarone. In comparing intravenous procainamide with intravenous amiodarone, Chapman and associates [41] examined 21 patients with atrial tachyarrhythmias (atrial fibrillation, atrial flutter, and regular supraventricular tachycardia) and found that by 12 hours, 71% of patients treated with procainamide and 70% of patients treated with amiodarone converted to normal sinus rhythm [41].

The data on flecainide and intravenous amiodarone for atrial fibrillation again suggest no significant difference in response rates. Specifically, Donovan and coworkers [36] randomly assigned 98 patients with recent-onset atrial fibrillation to receive intravenous flecainide or intravenous amiodarone. At 8 hours, the rate of conversion to normal sinus rhythm did not significantly differ between groups: 68% of the flecainide group and 59% of the amiodarone group had conversion. Capucci and colleagues [37] compared the effectiveness of oral flecainide with that of intravenous amiodarone in 62 patients who had recent-onset atrial fibrillation; at 24 hours, rates of conversion to sinus rhythm were not significantly different between the treatment groups (95% for the flecainide group and 89% for the amiodarone group).

Intravenous amiodarone was recently compared with placebo, intravenous propafenone, oral propafenone, and oral flecainide for the conversion of recent-onset atrial fibrillation to sinus rhythm [34]. At 8 hours, no significant differences in the percentage of patients who converted were seen between the intravenous amiodarone and placebo groups (43% and 37%, respectively). Negrini and coworkers [43] compared the effectiveness of intravenous amiodarone with that of propafenone for conversion of recent-onset atrial fibrillation to sinus rhythm. At 24 hours, 78% (14 of 18) of amiodarone recipients and 89% (16 of 18) of propafenone recipients responded. Finally, Horner [38] compared amiodarone with direct-current cardioversion for atrial fibrillation in 52 patients; conversion to sinus rhythm occurred in 29% of patients randomly assigned to receive oral amiodarone, 64% of those assigned to receive intravenous amiodarone, and 42% of those assigned to receive direct-current cardioversion. Sagrista-Sauleda and associates [44] showed that direct-current cardioversion could be done safely in patients receiving oral or intravenous amiodarone, and they observed a trend toward lower energy requirements for cardioversion in patients receiving amiodarone (this trend was more prominent with the intravenous form than with the oral form).

Because intravenous amiodarone seems to be equivalent, but not superior, to other antiarrhythmic agents, consideration of cost is prudent. A 1500-mg supply of intravenous amiodarone costs $550.00 ($55.00 per 150-mg vial) [3]. In contrast, the cost of 1 g of intravenous procainamide ranges from $6.00 to $24.00 (mean, $12.00). In addition, intravenous amiodarone often requires a central venous line for infusion. Use of other antiarrhythmic agents may therefore prove more cost-effective in the setting of atrial fibrillation.

Other supraventricular arrhythmias. The efficacy of intravenous amiodarone in the treatment of other supraventricular arrhythmias (such as paroxysmal supraventricular tachycardia and atrial tachycardia) is difficult to determine because of the lack of large randomized studies. In a retrospective study of 142 patients, Cybulski and colleagues [45] found that intravenous amiodarone therapy resulted in conversion to sinus rhythm in 65% of patients with atrial fibrillation and 61% of patients with paroxysmal supraventricular tachycardia. In 42 patients with atrial tachyarrhythmias (including atrial fibrillation, atrial tachycardia, multifocal atrial tachycardia, and atrial flutter), Moran and colleagues [46] compared intravenous amiodarone with intravenous magnesium sulfate in the conversion of these arrhythmias to sinus rhythm. Fifty percent of the amiodarone recipients and 78% of the magnesium sulfate recipients responded, although subgroup analysis according to type of arrhythmia was not done. An equally important finding was that conventional therapy (including that with intravenous adenosine and verapamil) for supraventricular tachycardias seems more efficacious [46] than intravenous amiodarone therapy and does not carry the attendant costs of central venous access and lengthy hospitalizations for intravenous loading.

The efficacy of intravenous amiodarone has not been determined in the setting of other supraventricular arrhythmias. Conventional therapy with adenosine or verapamil may be preferred because of the well-established efficacy of these two drugs and their low attendant costs.

Ventricular Arrhythmias

Although oral amiodarone has been used primarily in patients with ventricular tachyarrhythmia that is refractory to other pharmacologic agents, it is now being used more often as a first-line therapy. Many studies have examined intravenous amiodarone in the setting of ventricular tachycardia and ventricular fibrillation and have shown that the efficacy of this form ranges from 51% to 100% (Table 3). Scheinman and colleagues [55] conducted a double-blind, dose-ranging study comparing three different doses of intravenous amiodarone: 125 mg, 500 mg, and 1000 mg, each infused over 24 hours. A total of 342 patients were enrolled into the study and randomly assigned to receive one of the three treatments. Efficacy end points included the arrhythmia event rate, the time to the first arrhythmic event, and the number of supplemental infusions administered (150-mg infusions). The authors found that the event rate decreased with increasing doses: 0.07 events per hour with the 125-mg dose, 0.04 events per hour with the 500-mg dose, and 0.02 events per hour with the 1000-mg dose. A significant dose-related decrease occurred in the number of supplemental boluses required per hour. Hypotension was the most common treatment-related adverse effect (it occurred in 26% of patients), but no dose-response relation was seen [55].

Kowey and coworkers [56] compared intravenous bretylium (2500 mg/24 hours) with two doses of intravenous amiodarone (125 mg and 1000 mg). The primary end point measured at 48 hours was the arrhythmia event rate. Among 302 patients, intravenous amiodarone was found to be as efficacious as bretylium in the acute setting of unstable ventricular tachyarrhythmias, and the 1000-mg dose was more effective than the 125-mg dose. Bretylium therapy, however, was associated with a higher rate of hypotension and dropout (32% of patients receiving bretylium compared with 20% of patients receiving 1000 mg of amiodarone) [56].

Levine and colleagues [57] studied 273 patients with recurrent hypotensive ventricular tachyarrhythmias that were refractory to lidocaine, procainamide, and bretylium. These patients were randomly assigned to receive one of three doses of intravenous amiodarone: 525 mg, 1050 mg, and 2100 mg, each infused over 24 hours. The response rate (the primary end point) was 40.3%, but no clear dose-response relation was observed. However, the rate of response tended to improve with increasing doses of amiodarone. Adverse events occurred in 385 patients, with a similar frequency at each dose.

Studies that used higher doses of intravenous amiodarone have shown important therapeutic effects, but at the cost of substantially higher rates of adverse effects. Specifically, Mooss and colleagues [53] reported that serious side effects, including hypotension, symptomatic bradycardia, and sinus arrest, occurred in 37% of patients who received the 20 to 30 mg/kg per day treatment regimen. On the basis of the trials discussed in this section, 1000 mg of intravenous amiodarone administered over 24 hours is suggested as a starting dosage for the treatment of ventricular tachycardia or ventricular fibrillation. This dose is efficacious and is not associated with an increase in the rate of adverse effects or death.

Arrhythmias Related to Acute Myocardial Infarction

Although several clinical trials indicate that oral amiodarone therapy may prolong long-term survival in patients who have had myocardial infarction [2, 58-60], this therapy does not have a role in ventricular arrhythmias related to acute myocardial infarction because of the long-delayed onset of anti-arrhythmic action.

The incidence of ventricular tachycardia in patients who have had acute myocardial infarction ranges from 10% to 40%, and the incidence of ventricular fibrillation is 4% to 18% [61]. Because these ventricular arrhythmias carry a high mortality rate and can be refractory to conventional therapy (that is, cardioversion, lidocaine, and bretylium), intravenous amiodarone may play an important role in this setting.

Intravenous amiodarone has several favorable electropharmacologic properties that can theoretically help terminate ventricular arrhythmias related to myocardial infarction and improve the overall survival rate. If a ventricular arrhythmia is induced by acute myocardial ischemia, intravenous amiodarone may help relieve ischemia and thereby control the arrhythmia.

Several clinical trials have shown that short-term treatment with a ß-adrenoreceptor-blocking agent improves the survival rate and reduces infarction size and reinfarction rate in acute myocardial infarction [62-64]. Intravenous amiodarone exerts the same antiadrenergic effect and probably provides a benefit similar to that of ß-adrenoreceptor-blocking agents [34].

Intravenous amiodarone may be particularly useful in patients who have had myocardial infarction and have a compromised hemodynamic status. Although it generates a negative inotropic effect, this action is counterbalanced by an afterload reduction and improvement in coronary blood flow, thereby increasing overall cardiac output with minimal or no decrease in blood pressure [34, 65, 66]. Therefore, intravenous amiodarone can often be used safely in patients with left ventricular systolic dysfunction and patients with hypotension.

Some experimental studies support the beneficial effect of intravenous amiodarone in acute myocardial infarction. Investigators for a canine study [67] induced acute myocardial infarction with ventricular fibrillation that was refractory to epinephrine, lidocaine, and direct-current cardioversion by ligating the proximal left anterior descending artery. Intravenous amiodarone infused into these hearts significantly improved the defibrillation rate. Another experiment in dogs showed that intravenous amiodarone had a preferential antiarrhythmic action against ischemic myocardial tissues when compared with normal cardiac tissues [20].

Only 6% to 8% of all patients in previous studies had acute myocardial infarction-related arrhythmias [55, 56, 68]. Because of the small sample sizes, no firm conclusions can be drawn about the effect of intravenous amiodarone on this subset of patients. Thus, although experiments have shown that intravenous amiodarone has beneficial attributes for the treatment of patients with myocardial infarction-related ventricular arrhythmias, the true clinical effect of the intravenous form of the drug has yet to be seen and evaluated.

Advanced Cardiac Life Support

With the advent of intravenous amiodarone and its aforementioned fast onset of clinical effect, the rationale for its incorporation into protocols of advanced cardiac life support for treatment of ventricular fibrillation or hemodynamically unstable ventricular tachycardia is appealing. Intravenous bretylium is currently the only approved class III agent in this setting. As noted earlier, however, Kowey and colleagues [56] showed that 1 g of intravenous amiodarone infused over 24 hours is as effective as intravenous bretylium in preventing recurrences of highly malignant ventricular arrhythmias. In fact, within the first 6 hours of monitoring, intravenous amiodarone was more effective than intravenous bretylium in preventing arrhythmia recurrence, and intravenous bretylium was associated with a higher incidence of hypotension [56].

As noted previously, experimental data support the use of intravenous amiodarone in protocols of advanced cardiac life support. In a canine study, Anastasiou-Nana and colleagues [67] reported that intravenous amiodarone was very efficacious in improving the rate of defibrillation in acute myocardial infarction-related ventricular fibrillation that is refractory to epinephrine, lidocaine, and multiple direct-current cardioversion. More important, a clinical study conducted by Williams and coworkers [69] showed that intravenous amiodarone had remarkable efficacy when it was administered to 14 patients who underwent conventional resuscitation for more than 30 minutes. Seventy-nine percent of patients survived the resuscitative effort, and 57% of these patients survived to hospital discharge even though resuscitation lasted a mean of 75 minutes before amiodarone was administered [69]. These data are in striking contrast to previously reported survival rates of close to 0% after cardiopulmonary resuscitation prolonged to more than 30 minutes [70].

In summary, the available experimental and clinical data suggest that the short-term infusion of intravenous amiodarone may improve patient outcomes in the setting of advanced cardiac life support, but additional large, randomized clinical trials are required.

Hemodynamics

Intravenous amiodarone has many different hemodynamic effects, largely because of its multiple pharmacologic actions. First, as a result of its direct effect on smooth muscle and its ability to block calcium channels and -adrenergic receptors, intravenous amiodarone dilates coronary arteries and increases coronary blood flow. It also causes peripheral arterial vasodilation and reduces afterload and systemic blood pressure [2]. The reduced blood pressure seen with the intravenous form of amiodarone has complicated the use of this form, particularly in the setting of a rapid infusion. In a dose-ranging study of intravenous amiodarone done by Scheinman and colleagues [55], hypotension occurred in 26% of patients, but no dose-response relation was found. Some authors have suggested that part of the drug-induced hypotension may be secondary to the effects of amiodarone's vehicle, polysorbate 80 [24].

A reduction in the rate of cardiac contractility has also been shown. Remme and colleagues [65] found a 17% to 19% decrease in contractility in patients who were treated with intravenous amiodarone. However, cardiac output actually improved in patients who had poor left ventricular function at baseline; it is hypothesized that the decrease in inotropy is balanced by a decrease in afterload and increase in coronary blood flow, which in turn improves cardiac performance [65]. This theory is supported by Twidale and coworkers [66], who showed that although both intravenous amiodarone and intravenous racemic sotalol had modest negative inotropic effects, amiodarone caused a 13% increase in cardiac output and intravenous sotalol produced no increase. Hohnloser and associates [34] also reported that a slow bolus of 300 mg infused over 2 hours was not associated with a reduction in cardiac output. This finding suggests that, like the incidence of hypotension, reduced cardiac output may be related to the rapidity of bolus or infusion.

Side Effects and Drug Interactions

Amiodarone, especially when used over the long term (as the oral form often is), has many side effects involving multiple organ systems. Because the incidence of side effects increases over time and may be related to the total amount of drug accumulated, most of these effects are thought to be minimal in the setting of short-term intravenous therapy. The most frequent adverse effect seen with intravenous amiodarone infusion is hypotension, as discussed earlier. Proarrhythmic effects are rarely noted in clinical trials. In the study by Scheinman and colleagues [55], only 3 of 342 patients had new arrhythmias, all of which were torsade de pointes. Levine and coworkers [57] reported that 6 of 273 patients (2%) had proarrhythmic effects; 2 of these 6 patients had new-onset ventricular fibrillation and 4 had torsade de pointes. Other adverse cardiovascular events, such as bradycardia, electromechanical dissociation, asystole, congestive heart failure, and shock, occurred in less than 5% of patients [55, 57]. Abnormal liver test results, fever, and nausea or vomiting were reported in less than 5% of patients [55, 57]. The adult respiratory distress syndrome occurred in 2% of the patients in Scheinman and colleagues' study [55]. An important side effect specific to amiodarone that is administered intravenously through peripheral lines is local phlebitis; this event is especially likely to occur if the drug concentration exceeds 2 mg/mL [24]. Thus, unlike the oral form of amiodarone, intravenous amiodarone has an appealing side effect profile.

Amiodarone can decrease cytochrome P-450 enzyme activity and increase the serum concentration of such medications as lidocaine, flecainide, digoxin, quinidine, procainamide, warfarin, dextromethorphan, and cyclosporine [71]. It is therefore important to adjust the dosages of these medications when they are given concurrently with amiodarone. In addition, medications that alter amiodarone levels include cholestyramine and cimetidine, which can increase serum amiodarone levels, and phenytoin, which can decrease serum amiodarone levels [71]. Because of amiodarone's prolonged half-life, these drug-drug interactions often persist for some time after amiodarone therapy is discontinued.

Practical Guidelines

On the basis of the available data on treatment and prevention of arrhythmias, the following conclusions can be made for intravenous amiodarone therapy. First, intravenous amiodarone is moderately effective in converting atrial fibrillation to sinus rhythm and is equivalent but not superior to existing antiarrhythmic agents, such as procainamide, quinidine, flecainide, and propafenone. Given the higher cost and requirement of a central venous line for infusion, intravenous amiodarone should usually not be used as first-line therapy for the conversion of atrial fibrillation. Similar conclusions can be drawn for other supraventricular arrhythmias; conventional treatments using intravenous adenosine and verapamil are highly effective, relatively inexpensive, and safe to use. Again, however, intravenous amiodarone would not be a first choice in therapy.

Second, for hemodynamically stable and unstable ventricular tachycardia, intravenous amiodarone is highly effective and safe, even for patients in whom other antiarrhythmic agents have failed. Clinical trials also support its effectiveness in the treatment of ventricular fibrillation. Third, intravenous amiodarone will probably improve survival rates in patients who have had acute myocardial infarction and in patients receiving advanced cardiac life support. However, most of the supporting evidence for these claims derives from experimental and retrospective studies; randomized clinical trials are needed to fully evaluate the extent of intravenous amiodarone's beneficial effects.

Several important issues should be considered with the use of intravenous amiodarone. First, the underlying cause of arrhythmia (such as congestive heart failure, myocardial ischemia, left ventricular dysfunction, electrolyte or acid-base disturbance, hypoxia, or use of certain drugs) must be addressed and reversed or optimized whenever possible. Next, once the patient is stabilized, a physician must decide whether the patient requires long-term antiarrhythmic therapy. In choosing an antiarrhythmic agent for long-term use, one must remember that the oral form of amiodarone has significantly different antiarrhythmic effects and a significantly different side effect profile compared with the intravenous form. Therefore, the decision to use intravenous amiodarone over the long term must be made according to the needs of the individual patients, and all oral antiarrhythmic agents available should be considered.

No clinical trials have systematically evaluated methods for converting from intravenous amiodarone to oral amiodarone. However, two different approaches to this can be used. First, intravenous amiodarone therapy can be discontinued and oral amiodarone therapy can be started immediately in a full loading dosage (800 to 1600 mg/d). Second, oral amiodarone therapy can overlap with intravenous therapy for 2 to 3 days because the onset of antiarrhythmic action is delayed with oral amiodarone.

Special precautions must be followed when intravenous amiodarone is used. To avoid phlebitis, administration through a central venous line is recommended. If amiodarone is to be given by way of a peripheral line, the concentration of the drug should not exceed 2 mg/mL. Intravenous amiodarone does not need to be protected from light and is stable in a solution of 5% dextrose in water placed in polyolefin or glass containers. Because of the formation of precipitate, intravenous amiodarone should not be given concurrently with acetic acid, aminophylline, mezlocillin sodium, cefamandole nafate, cefazolin sodium, heparin sodium, sodium acetate, or quinidine gluconate [24]. As mentioned earlier, intravenous amiodarone can interact with various medications; thus, doses of each drug, including intravenous amiodarone, should be adjusted accordingly. No specific dose adjustment is indicated for patient age or presence of renal disease, hepatic disease, or left ventricular dysfunction, but elderly patients and patients with clinically significant left ventricular dysfunction should be closely monitored for any sign of toxicity. Finally, amiodarone and its active metabolite, desethylamiodarone, are not dialyzable.

Conclusions

Intravenous amiodarone distinguishes itself by its unique and multifaceted electropharmacology, its unusual pharmacokinetics, and its widespread applicability in the clinical setting with favorable hemodynamic and side effect profiles. It is highly effective against a wide range of arrhythmias; because of its rapid onset of antiarrhythmic action, it has a special use in the short-term management of life-threatening or hemodynamically unstable rhythm disturbances. It seems clear from the available data that intravenous amiodarone is an excellent choice in the setting of refractory ventricular tachyarrhythmias and that it has few adverse effects; controlled clinical trials are warranted to examine its use in acute myocardial infarction and advanced cardiac life support settings. The beneficial hemodynamic properties of intravenous amiodarone in patients with left ventricular dysfunction suggest that it is an excellent drug for this condition. A formal cost-effectiveness analysis of intravenous amiodarone in the various clinical settings is needed.