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Ventricular Tachyarrhythmias
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Intravenous amiodarone is approved for rapid control of recurrent VT or VF. Three randomized, controlled trials of patients with recurrent in-hospital, hemodynamically unstable VT or VF with two or more episodes within the past 24 hours who failed to respond to or were intolerant of lidocaine, procainamide, and (in two of the trials) bretylium have been reported.42,44,46 Patients were critically ill with ischemic cardiovascular disease, 25% were on a mechanical ventilator or intra-aortic balloon pump before enrollment, and 10% were undergoing cardiopulmonary resuscitation at the time of enrollment. One study compared three doses of IV amiodarone: 525, 1050, and 2100 mg/d.44 Because of the use of investigator-initiated intermittent open-label amiodarone boluses for recurrent VT, the actual mean amiodarone doses received by the three groups were 742, 1175, and 1921 mg/d. There was no statistically significant difference in the number of patients without VT/VF recurrence during the 1-day study period: 32 of 86 (41%), 36 of 92 (45%), and 42 of 92 (53%) for the low-, medium-, and high-dose groups, respectively. The number of supplemental 150-mg bolus infusions of amiodarone given by blinded investigators was statistically significantly less in those randomized to higher doses of amiodarone.
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A wider range of amiodarone doses (125, 500, and 1000 mg/d) was evaluated by Sheinman and colleagues, including a low dose that was expected to be subtherapeutic.46 This stronger study design, however, also was confounded by open-label bolus amiodarone injections given by study investigators. There was, however, a trend toward a relationship between intended amiodarone dose and VT/VF recurrence rate (p =.067). After adjustment for baseline imbalances, the median 24-hour recurrence rates of VT/VF, from lowest to highest doses, were 1.68, 0.96, and 0.48 events per 24 hours.
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The third study compared two intravenous amiodarone doses (125 and 1000 mg/d) with bretylium (2500 mg/d).42 Once again, the target amiodarone dose ratio of 8:1 was compressed to 1.8:1 because of open-label boluses. There was no significant difference in the primary outcome, which was median VT/VF recurrence rate over 24 hours. For low-dose amiodarone, high-dose amiodarone, and bretylium, these rates were 1.68, 0.48, and 0.96 events per 24 hours, respectively (p =.237). There was no difference between high-dose amiodarone and bretylium; however, more than 50% of patients had crossed over from bretylium to amiodarone by 16 hours.
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The failure of these studies to provide clear evidence of amiodarone efficacy may be related to the "active-control study design" used, a lack of adequate statistical power, high rates of supplemental amiodarone boluses, and high crossover rates. Nonetheless, these studies provide some evidence that IV amiodarone (1 g/d) is moderately effective during a 24-hour period against VT and VF.
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Sustained Monomorphic Ventricular Tachycardia and Wide QRS Tachycardia
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Although the most effective and rapid treatment of any hemodynamically unstable sustained ventricular tachyarrhythmia is electrical cardioversion or defibrillation, intravenous antiarrhythmic drugs can be used for arrhythmia termination if the VT is hemodynamically stable. The Guidelines for Emergency Cardiovascular Care19 has removed former recommendation of lidocaine and adenosine use in stable wide QRS tachycardia, now labeled as "acceptable" but not primarily recommended (lidocaine) or not recommended (adenosine). Intravenous procainamide and sotalol are effective, based on randomized but small studies;10 amiodarone is also considered acceptable.19
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Shock-Resistant Ventricular Fibrillation
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The Guidelines for Emergency Cardiovascular Care recommends at least three shocks and epinephrine or vasopressin before any antiarrhythmic drug is administered.10,19 No large-scale controlled, randomized studies have demonstrated efficacy for lidocaine, bretylium, or procainamide in shock-resistant VF,10,19 and lidocaine and bretylium are no longer recommended in this setting.19 Two pivotal studies have been reported recently studying the efficacy of agents in acute shock-resistant cardiac arrest.
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The Amiodarone in the Out-of-Hospital Resuscitation of Refractory Sustained Ventricular Tachycardia (ARREST) study was randomized, double-blind, and placebo-controlled. The ARREST study in 504 patients showed that amiodarone 300 mg administered in a single intravenous bolus significantly improves survival to hospital admission in cardiac arrest still in VT or VF after three direct-current shocks (44% versus 34%; p <.03).43 Although the highest survival rate to hospital admission (79%) was achieved when the amiodarone was given within 4 to 16 minutes of dispatch, there was no significant difference in the proportional improvement in the amiodarone group compared with the placebo group when drug administration was delayed (up to 55 minutes). Amiodarone also had the highest efficacy in patients (21% of all study patients) who had a return of spontaneous circulation before drug administration (survival to hospital admission increased to 64% from 41% in the placebo group). Among patients with no return of spontaneous circulation, amiodarone only slightly improved outcome (38% versus 33%).
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Dorian performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest.48 Patients were enrolled if they had out-of-hospital ventricular fibrillation resistant to three shocks, intravenous epinephrine, and a further shock or if they had recurrent ventricular fibrillation after initially successful defibrillation. They were randomly assigned in a double-blind manner to receive intravenous amiodarone plus lidocaine placebo or intravenous lidocaine plus amiodarone placebo. The primary end point was the proportion of patients who survived to be admitted to the hospital. In total, 347 patients (mean age 67 ± 14 years) were enrolled. The mean interval between the time at which paramedics were dispatched to the scene of the cardiac arrest and the time of their arrival was 7 ± 3 minutes, and the mean interval from dispatch to drug administration was 25 ± 8 minutes. After treatment with amiodarone, 22.8% of 180 patients survived to hospital admission compared with 12.0% percent of 167 patients treated with lidocaine (p = .009). Among patients for whom the time from dispatch to the administration of the drug was equal to or less than the median time (24 minutes), 27.7% of those given amiodarone and 15.3% of those given lidocaine survived to hospital admission (p = .05). The authors concluded that compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation.
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Supraventricular Arrhythmias
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A supraventricular arrhythmia is any tachyarrhythmia that requires atrial or atrioventricular junctional tissue for initiation and maintenance. It may arise from reentry caused by unidirectional conduction block in one region of the heart and slow conduction in another, from enhanced automaticity akin to that seen in normal pacemaker cells of the sinus node and in latent pacemaker cells elsewhere in the heart, or from triggered activity, a novel type of abnormally enhanced impulse initiation caused by membrane currents that can be activated and inactivated by premature stimulation or rapid pacing.56–58 Pharmacologic approaches to treating supraventricular arrhythmias, including atrial fibrillation, atrial flutter, atrial tachycardia, AV re-entrant tachycardia, and AV nodal re-entrant tachycardia, continue to evolve.56–60 Because atrial fibrillation is perhaps the most common arrhythmia after cardiac surgery, this condition is emphasized in detail.
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Atrial fibrillation (AF) is a common complication of cardiac surgery that increases the length of stay in the hospital with resulting increases in health-care resource utilization.56–61 Advanced age, previous AF, and valvular heart operations are the most consistently identified risk factors for this arrhythmia. Because efforts to terminate AF after its initiation are problematic, current interests are directed at therapies to prevent postoperative AF. Most studies suggest that prophylaxis with antiarrhythmic compounds can decrease the incidence of AF, length of hospital stay, and cost significantly. Class III antiarrhythmic drugs (eg, sotalol and ibutilide) also may be effective but potentially pose the risk of drug-induced polymorphic ventricular tachycardia (torsades de pointes). Newer promising intravenous agents including vernakalant are also being investigated. Defining which subpopulations benefit most from such therapy is important as older and more critically ill patients undergo surgery. Intravenous sotalol is currently available in the United States.
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Amiodarone is also an effective approach for prophylactic therapy of AF. Intravenous amiodarone is an important consideration because loading with oral therapy is often not feasible in part owing to time required. There also may be added benefits of prophylactic therapies in high-risk patients, especially those prone to ventricular arrhythmias (ie, patients with pre-existing heart failure).
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Two studies deserve mention regarding prophylaxis with amiodarone. To determine if IV amiodarone would prevent atrial fibrillation and decrease hospital stay after cardiac surgery, Daoud and colleagues assessed preoperative prophylaxis in 124 patients who were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of 7 days before elective cardiac surgery.62 Therapy consisted of 600-mg amiodarone per day for 7 days and then 200 mg/d until the day of discharge from the hospital. The preoperative total dose of amiodarone was 4.8 ± 0.96 g over 13 ± 7 days. Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25%) and 32 of the 60 patients in the placebo group (53%). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5 ± 2.6 versus 7.9 ± 4.3 days; p = .04). Total hospitalization costs were significantly less for the amiodarone group than for the placebo group ($18,375 ± $13,863 versus $26,491 ± $23,837; p = .03). Guarnieri and colleagues evaluated 300 patients randomized in a double-blind fashion to IV amiodarone (1 g/d for 2 days) versus placebo immediately after open-heart surgery.54 The primary end points of the trial were incidence of atrial fibrillation and length of hospital stay. Atrial fibrillation occurred in 67 of 142 (47%) patients on placebo versus 56 of 158 (35%) on amiodarone (p = .01). Length of hospital stay for the placebo group was 8.2 ± 6.2 days, and 7.6 ± 5.9 days for the amiodarone group. Low-dose IV amiodarone was safe and effective in reducing the incidence of atrial fibrillation after heart surgery but did not significantly alter length of hospital stay.
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In summary, AF is a frequent complication of cardiac surgery. Many cases can be prevented with appropriate prophylactic therapy. Beta-adrenergic blockers should be administered to most patients without contraindication. Prophylactic amiodarone should be considered in patients at high risk for postoperative AF. The lack of data on cost benefits and cost efficiency in some studies may reflect the lack of higher-risk patients in the study. Patients who are poor candidates for beta blockade may not tolerate sotalol, whereas amiodarone does not have this limitation. Additional studies also need to be performed to better assess the role of prophylactic therapy in off-pump cardiac surgery.