Intravenous amiodarone and off-pump coronary artery bypass graft procedures: A new role for intraoperative antiarrhythmic therapy?

Abstract

INTRAVENOUS (IV) amiodarone is an antiarrhythmic agent with a broad pharmacologic spectrum that includes β-receptor; α-receptor; and sodium, calcium, and potassium channel antagonism. Amiodarone has been used worldwide for the treatment of life-threatening ventricular arrhythmias since the early 1980s and was approved by the U.S. Food and Drug Administration (FDA) on August 3, 1995 for treatment of ventricular arrhythmias “resistant to other therapy.” Since its FDA approval, IV amiodarone has increasingly seen off-label use for treating a myriad of nonventricular arrhythmias, including perioperative atrial fibrillation (AF). Inclusion of IV amiodarone in the American Heart Association emergency care guidelines for many atrial arrhythmias1American Heart Association in collaboration with the International Liaison Committee on Resuscitation (ILCOR)Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6. Advanced cardiovascular life support: Section 5. Pharmacology I: Agents for arrhythmias.Circulation. 2000; 102: I112-I128Crossref PubMed Google Scholar promises to expand its overall use in hospital settings and requires in-depth consideration of how this agent should be used in the period surrounding cardiac surgery. AF occurs within the first 4 postoperative days in 20% to 50% of patients who undergo cardiac surgical procedures and significantly prolongs intensive care unit and ward length of stay.2Mathew JP Parks R Savino JS et al.Atrial fibrillation following coronary artery bypass graft surgery.JAMA. 1996; 276: 300-306Crossref PubMed Google Scholar, 3Daoud EG Strickberger SA Man KC et al.Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.N Engl J Med. 1997; 337: 1785-1791Crossref PubMed Scopus (447) Google Scholar As overall hospital stay after cardiac surgery has sharply declined, the morbidity of this complication has become more apparent, and substantial hospital costs associated with AF have been quantified (approximately $10,000 per patient).3Daoud EG Strickberger SA Man KC et al.Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.N Engl J Med. 1997; 337: 1785-1791Crossref PubMed Scopus (447) Google Scholar, 4Aranki SF Shaw DP Adams DH et al.Predictors of atrial fibrillation after coronary artery surgery: Current trends and impact on hospital resources.Circulation. 1996; 94: 390-397Crossref PubMed Scopus (967) Google Scholar Patients who experience postoperative AF are at increased risk for perioperative stroke (3.3% v 1.4%), ventricular tachycardia or fibrillation (9.2% v 4.0%), and the need for a permanent pacemaker (3.7% v 1.6%).5Cresswell LL Scheussler RB Rosenbloom M et al.Hazards of postoperative atrial arrhythmias.Ann Thorac Surg. 1993; 56: 539-549Abstract Full Text PDF PubMed Scopus (824) Google Scholar In the case of perioperative stroke, it is unclear whether this risk relates directly to postoperative AF or to an underlying pathophysiologic substrate conducive to AF and stroke. Whether interventions aimed at preventing or treating postoperative AF would lower the incidence of postoperative stroke remains an open question. Prophylactic administration of drug therapies aimed at preventing postoperative AF has met with mixed success. After cardiac surgery, oral β-blocker therapy is usually well tolerated but has only a modest benefit for prevention of AF.6Parikka H Toivonen L Heikkila L et al.Comparison of sotalol and metoprolol in the prevention of atrial fibrillation after coronary artery bypass surgery.J Cardiovasc Pharmacol. 1998; 31: 67-73Crossref PubMed Scopus (83) Google Scholar At a minimum, patients receiving β-blockade therapy preoperatively should resume this therapy postoperatively to avoid AF resulting from β-blocker withdrawal.7Leitch JW Thomson D Baird DK et al.The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 1990; 100: 338-342PubMed Google Scholar Although most studies suggest digoxin and verapamil are ineffective for AF prophylaxis,8Kowey PR Taylor JE Rials SJ et al.Meta-analysis of the effectiveness of prophylactic drug therapy in preventing supraventricular arrhythmia early after coronary artery bypass grafting.Am J Cardiol. 1992; 69: 963-965Abstract Full Text PDF PubMed Scopus (201) Google Scholar, 9Andrews TC Reimold SC Berlin JA et al.Prevention of supraventricular arrhythmia after coronary artery bypass surgery: A meta-analysis of randomized control trials.Circulation. 1990; 84: 236-244Google Scholar beneficial effects of prophylactic IV diltiazem have been shown after pneumonectomy.10Amar D Roistacher N Burt ME et al.Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.Ann Thorac Surg. 1997; 63: 1374-1381Abstract Full Text PDF PubMed Google Scholar Promising results with high-dose IV magnesium (approximately 10 g/d)11Balser JR Pro: All patients should receive pharmacologic prophylaxis for atrial fibrillation after cardiac surgery.J Cardiothorac Vasc Anesth. 1999; 13: 98-100Abstract Full Text PDF PubMed Google Scholar have been described in small controlled trials, but close monitoring of serum magnesium levels is crucial and cumbersome. Many antiarrhythmic drugs are effective for preventing postoperative AF after cardiac surgery, but concerns about cost and side effects have limited their use. Q-Tc prolongation (with the risk of torsades de pointes) is a concern with either oral or IV procainamide or oral sotalol.12Pfisterer ME Kloter-Weber UC Huber M et al.Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: A prospective, double-blind, randomized, placebo-controlled study.Ann Thorac Surg. 1997; 64: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar For IV amiodarone, proarrhythmia is rare, and pulmonary toxicity (approximately 2% incidence during long-term oral therapy) proves to be of little concern with short-duration IV therapy.3Daoud EG Strickberger SA Man KC et al.Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.N Engl J Med. 1997; 337: 1785-1791Crossref PubMed Scopus (447) Google Scholar The largest amiodarone prophylaxis trial to date, involving 300 patients in Baltimore (the Amiodarone Reduction in Coronary Heart [ARCH] trial), found, however, that 2 days of IV amiodarone started immediately after surgery produced a disappointing 35% to 47% reduction in the incidence of postoperative AF, with no significant change in the duration of hospital stay.13Guarnieri T Nolan S Gottlieb SO et al.Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: The Amiodarone Reduction in Coronary Heart (ARCH) trial.J Am Coll Cardiol. 1999; 34: 343-347Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar Longer duration postoperative IV therapy (4 days, 1 g/d) seems to produce greater benefit,14Hohnloser SH Meinertz T Dammbacher T et al.Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: Results of a prospective, placebo-controlled study.Am Heart J. 1991; 121: 89-95Abstract Full Text PDF PubMed Scopus (171) Google Scholar but the significant cost of the medication and the need to use a central venous catheter (to avoid thrombophlebitis with sustained use) limit enthusiasm for this practice at many centers. Many studies suggest a nonpharmacologic therapy, right atrial or bipolar atrial pacing in the early postoperative period, may be the safest and most effective means of preventing postoperative AF.15Fan K Lee KL Chiu CS et al.Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.Circulation. 2000; 102: 755-760Crossref PubMed Scopus (136) Google Scholar, 16Daoud EG Dabir R Archambeau M et al.Randomized, double-blind trial of simultaneous right and left atrial epicardial pacing for prevention of post-open heart surgery atrial fibrillation.Circulation. 2000; 102: 761-765Crossref PubMed Scopus (90) Google Scholar In the article by Gallagher et al in this issue, the investigators describe 3 cases in which IV amiodarone was used to manage intraoperative AF in patients undergoing off-pump coronary artery bypass (OP-CAB) surgery. Generally, new-onset AF is relatively well tolerated during surgery and may evoke mild hypotension manageable with fluid, phenylephrine, or both. The principal feature of management is rapid ventricular rate control to prevent myocardial ischemia, requiring either an IV calcium channel blocker or β-blocker. Digoxin has a limited role in the intraoperative setting because of its slow onset of action (approximately 6 hours).17Tisdale JE Padhi ID Goldberg AD et al.A randomized, double-blind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery.Am Heart J. 1998; 135: 739-747Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Intraoperative AF is usually self-limited, spontaneously converting to sinus rhythm by the end of the procedure. Nonetheless, the OP-CAB procedure may present a unique situation that calls for more aggressive measures. As Gallagher et al point out, positioning of the heart for the OP-CAB procedure effectively reduces preload, and the concurrent development of AF may evoke a degree of hemodynamic instability that compromises the off-pump procedure. Is IV amiodarone a rational agent to use in this circumstance? In the 3 cases discussed by Gallagher et al, important questions are raised that are central to the use of all antiarrhythmic agents during rapid AF. The data showing that IV amiodarone may prevent some cases of postoperative AF13Guarnieri T Nolan S Gottlieb SO et al.Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: The Amiodarone Reduction in Coronary Heart (ARCH) trial.J Am Coll Cardiol. 1999; 34: 343-347Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar are similar to those of other antiarrhythmic agents used in AF management (including sotalol).18Villemaire C Talajic M Nattel S Mechanisms by which sotalol prevents atrial fibrillation at doses that fail to terminate the arrhythmia.Circulation. 1997; 96: I-236Google Scholar Overall, these antiarrhythmic agents appear to be more effective at maintaining sinus rhythm (slow atrial rate, 60 to 100 beats/min) than at chemically converting AF (rapid atrial rate, approximately 300 beats/min). Although the clinical data in nonsurgical patients with AF are conflicting in this regard, it is clear that the 50% to 70% conversion rates cited for many agents in uncontrolled studies are misleading because placebo rates of conversion are routinely this high. In the case of IV amiodarone, a trial of 100 medical patients with recent-onset AF (approximately 350 mg IV amiodarone during 30 minutes, then 1200 mg during 24 hours) found 60% and 68% 24-hour conversion rates in the placebo and treatment arms (p = not significant) and no difference in the time to conversion to sinus rhythm.19Galve E Rius T Ballester R et al.Intravenous amiodarone in treatment of recent-onset atrial fibrillation: Results of a randomized, controlled study.J Am Coll Cardiol. 1996; 27: 1079-1082Abstract Full Text PDF PubMed Scopus (226) Google Scholar In a more recent IV amiodarone trial, patients received 125 mg/h (total dose, 3 g/d) and did experience a higher 24-hour rate of conversion compared with placebo (92% v 64%; p = 0.0017), but the conversion rates in the treatment and placebo arms were identical during the first 8 hours of therapy.20Cotter G Blatt A Kaluski E et al.Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: The effect of no treatment and high-dose amiodarone: A randomized, placebo-controlled study.Eur Heart J. 1999; 20: 1833-1842Crossref PubMed Scopus (87) Google Scholar A third trial of patients with persistent AF evaluated the combination of IV amiodarone loading (24 hours) followed by long-term oral amiodarone and found no difference in the rate of conversion within the first 3 days but did note a difference in conversion rates during 1 month of therapy.21Kochiadakis GE Igoumenidis NE Solomou MC et al.Efficacy of amiodarone for the termination of persistent atrial fibrillation.Am J Cardiol. 1999; 83: 58-61Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar Only 1 trial has reported a small (statistically significant) effect of IV amiodarone over placebo for acute chemical cardioversion (38% v 25% within 1 hour, using 300 mg/h).22Vardas PE Kochiadakis GE Igoumenidis NE et al.Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: A randomized, controlled study.Chest. 2000; 117: 1538-1545Crossref PubMed Scopus (106) Google Scholar Overall, these data indicate that IV amiodarone is generally ineffective for rapid conversion of AF. Although the drug may effect chemical cardioversion during prolonged administration periods,20Cotter G Blatt A Kaluski E et al.Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: The effect of no treatment and high-dose amiodarone: A randomized, placebo-controlled study.Eur Heart J. 1999; 20: 1833-1842Crossref PubMed Scopus (87) Google Scholar, 21Kochiadakis GE Igoumenidis NE Solomou MC et al.Efficacy of amiodarone for the termination of persistent atrial fibrillation.Am J Cardiol. 1999; 83: 58-61Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar this clinical benefit has little relevance to the acute circumstances of an OP-CAB procedure. In contrast, there is growing evidence that IV amiodarone is helpful in maintaining sinus rhythm in patients who are susceptible to AF.3Daoud EG Strickberger SA Man KC et al.Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.N Engl J Med. 1997; 337: 1785-1791Crossref PubMed Scopus (447) Google Scholar, 13Guarnieri T Nolan S Gottlieb SO et al.Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: The Amiodarone Reduction in Coronary Heart (ARCH) trial.J Am Coll Cardiol. 1999; 34: 343-347Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar, 14Hohnloser SH Meinertz T Dammbacher T et al.Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: Results of a prospective, placebo-controlled study.Am Heart J. 1991; 121: 89-95Abstract Full Text PDF PubMed Scopus (171) Google Scholar It was essential that synchronous electrical cardioversion was applied in conjunction with IV amiodarone loading in all 3 OP-CAB surgery cases discussed by Gallagher et al. Although the authors speculate that the agent may have facilitated electrical cardioversion in 1 patient, the major effect of IV amiodarone in all 3 cases was prevention of arrhythmia recurrence after successful cardioversion. Are there other IV antiarrhythmic options during OP-CAB procedures? Ibutilide, a relatively new rapid-acting antiarrhythmic agent, produces an impressive 31% to 50% rate of conversion of AF or atrial flutter within 30 minutes,23VanderLugt JT Mattioni T Denker S et al.Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery.Circulation. 1999; 100: 369-375Crossref PubMed Scopus (123) Google Scholar but provokes a polymorphic ventricular arrhythmia (torsades de pointes) in 8% of patients24Stambler BS Wood MA Ellenbogen KA et al.Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation.Circulation. 1996; 94: 1613-1621Crossref PubMed Scopus (431) Google Scholar and may not provide sustained antiarrhythmic effects, so its role in the operating room would appear limited. Although procainamide may provide similar antiarrhythmic efficacy (in combination with electrical cardioversion) in the OP-CAB surgery setting, Gallagher et al point out the undesirable hemodynamic effects of rapid IV procainamide loading in such patients. Although other antiarrhythmic agents (ie, flecainide, propafenone, dofetilide) may be effective for AF management in medical patients, they are available in the United States only in oral form. In the context of the available literature, the cases presented by Gallagher et al illustrate that IV amiodarone may be a helpful option for managing hemodynamically destabilizing AF intraoperatively, when used in combination with synchronous electrical cardioversion. Anesthesiologists choosing this therapeutic option should be aware of the potential for acute hemodynamic compromise during IV amiodarone loading in patients with poor vascular tone or severely compromised ventricular function (owing to the α-blocking and β-blocking effects of the agent), and the means to provide immediate inotropic support should be available. Randomized trials evaluating the overall, longer term risks and benefits of intraoperative IV amiodarone use have not been performed. Without question, the use of IV amiodarone for arrhythmia management during intraoperative procedures, including OP-CAB procedures, deserves additional study. The author thanks Dr Katherine Murray, for helpful comments and discussion.