How do I prevent or treat atrial fibrillation in postoperative critically ill patients?

55 How Do I Prevent or Treat Atrial Fibrillation in Postoperative Critically Ill Patients? Jonathan K. Frogel and Stuart J. Weiss

Supraventricular arrhythmias are the most common rhythm disturbance encountered in postsurgical patients.1 The incidence of postoperative atrial fibrillation (POAF) may be as high as 50% after cardiac surgery,2 40% after pneumonectomy,3 and 20% after lung resection.4 In contrast, other postsurgical patients have a lower incidence of new-onset supraventricular arrhythmias approaching 10%.5 Patients who develop supraventricular arrhythmias after major noncardiac surgery are at increased risk for stroke and have significantly higher early and late mortality.5 After cardiac surgery, atrial fibrillation may herald a prolonged intensive care unit (ICU) course,2 increased risk of stroke, and increased risk of early and late mortality.6 Cost of care in a patient who has postoperative atrial fibrillation is increased by an average of $10,000.7 The human and economic toll of this disease entity is substantial.

WHAT ARE THE PATIENT RISK FACTORS AND PERIOPERATIVE CONDITIONS THAT INCREASE THE RISK OF POAF? Multiple risk factors that predispose patients to atrial fibrillation have been identified (Box 55.1).8–10 Every 10-year increase in age beyond 30 years is associated with a 75% increase in risk after cardiac surgery.8 Thus the risk of POAF after cardiac surgery in octogenarians may be greater than 50%.9 A history of cardiac disease (atrial fibrillation, hypertension, valvular disease, and cardiomyopathy) and chronic pulmonary disease are significant factors that predispose to POAF. In addition, obesity and increased body mass index (BMI) have also been shown to be predictors of POAF.10 Multiple studies have demonstrated that lifestyle modification aimed at improving cardiorespiratory fitness and goaldirected weight loss reduce the burden of atrial fibrillation in outpatients with atrial fibrillation.11,12 It is possible that similar interventions prior to surgery may reduce new-onset POAF, although specific data demonstrating such an effect are lacking.

WHAT IS THE PATHOGENESIS OF POAF? The pathogenesis of atrial fibrillation in the postoperative period is complex and multifactorial. Several preoperative

disease processes and conditions predispose to atrial enlargement and fibrosis, which in turn provides the substrate for the development of conduction abnormalities.13 The inflammatory response induced by surgery is associated with increased release of endogenous catecholamines or administration of exogenous inotropes or vasopressors. These and other factors (Box 55.2) trigger supraventricular arrhythmias by altering atrial refractoriness and conductivity, thereby predisposing to increased automaticity and reentrant rhythms.14 The type of surgery performed has a marked impact on the incidence of POAF. In patients undergoing intrathoracic or cardiac procedures, direct surgical manipulation or compression of the atria and/or pulmonary veins contributes to the pathogenesis.15 During cardiac surgery, myocardial ischemia and ventricular dysfunction can lead to atrial dilation and elevation of atrial pressure that further contribute to atrial irritability. Although the data for general surgery patients are not as robust as cardiac surgical patients, minimally invasive laparoscopic techniques may decrease the risk of POAF when compared with open approaches.15,16 This finding has been taken to imply that attenuation of the perioperative inflammatory and stress responses to surgery may decrease the risk of developing POAF.

WHAT STRATEGIES ARE EFFECTIVE FOR THE PREVENTION OF POAF? Although atrial fibrillation in postsurgical patients has long been recognized, the search for and implementation of prophylactic strategies to prevent new or recurrent arrhythmias has only gained traction relatively recently. As knowledge of the causative factors and resulting pathophysiology continues to evolve, the pool of potentially beneficial interventions has broadened. Conceptually, prophylactic strategies fall into one of five categories: administration of antiarrhythmic agents, electrolyte repletion or maintenance, atrial pacing (in cardiac surgical patients), modulation of the perioperative inflammatory response, and alterations of surgical technique. In general, the utility of prophylactic strategies has been most thoroughly evaluated in cardiac surgical patients. Therefore, considerations pertaining to specific risk and pathophysiology must be considered before extrapolation to the general surgical population. 379

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ANTIARRHYTHMIC AGENTS

perioperative beta blockers.19 On the basis of this evidence, the American College of Cardiology Foundation (ACCF)/ American Heart Association (AHA) guidelines for patients undergoing coronary artery bypass graft (CABG) surgery recommend that all such patients receive perioperative beta blockers from 24 hours prior to surgery onward.20 Following general thoracic (noncardiac) surgery, a metaanalysis of two studies totaling 129 subjects demonstrated that perioperative beta blockade significantly reduced the incidence of POAF but also increased the risk of hypotension and pulmonary edema.21 Of greater concern, the PeriOperative Ischemia Evaluation (POISE) trial, a large (8351 subjects), randomized controlled trial (RCT) in noncardiac surgical patients found that perioperative beta blockers decreased the incidence of cardiac arrest (3.6 vs. 5.1%) and myocardial infarction (4.2 vs. 5.7%) but increased the risk of perioperative hypotension, bradycardia, stroke (1.0 vs. 0.5%) and all-cause mortality.22 A post hoc analysis suggested that the increased incidence of clinically significant hypotension, bradycardia, and stroke may contribute to the observed increased mortality in the treatment groups. A meta-analysis of 33 RCTs totaling 12,306 subjects confirmed an increased risk of hypotension, bradycardia, and nonfatal stroke observed in the group receiving beta blockers.23 The guidelines from the American Association for Thoracic Surgery (AATS) on the prevention of POAF in patients undergoing noncardiac thoracic surgery recommend continuation of beta blockers in patients already receiving them. They do not, however, recommend initiation in betablocker naïve patients.24 The 2016 European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation assign a class 1 recommendation for beta-blocker administration for POAF prophylaxis in all adult patients undergoing cardiac surgery, not limited to CABG.25 In summary, all patients undergoing CABG surgery should receive beta blockers. As for patients undergoing noncardiac surgery, those who currently take beta blockers should continue receiving them throughout the perioperative period. However, the risk of initiating new beta-blocker therapy appears to outweigh the prophylactic benefit of administration.

Beta Blockers

Amiodarone

Considering the inciting role of increased sympathetic tone in the pathogenesis of atrial fibrillation, it is not surprising that beta-blocker administration for postoperative prevention has been extensively examined. Many studies have confirmed the utility of prophylactic beta blockers to limit the occurrence of POAF. A meta-analysis of 27 trials published in 2002 found that beta blockers reduce the risk of new-onset POAF after cardiac surgery by more than 60%.17 These findings were reaffirmed by the same author in a larger 2004 meta-analysis of 58 studies.18 The antiarrhythmic benefit was observed when adrenergic beta-antagonists were started before or immediately after surgery and was independent of the agent or dose used. A meta-analysis comprising 33 studies and 4698 subjects demonstrated a significant atrial fibrillation risk reduction in cardiac surgical patients receiving

Amiodarone, one of the most commonly used antiarrhythmic agents in the ICU setting, is frequently the antiarrhythmic of choice in patients with obstructive lung disease or cardiomyopathy. The prophylactic use of amiodarone to prevent POAF has been extensively studied. A meta-analysis comprising 33 studies and 5402 subjects demonstrated a significant reduction in the risk of POAF in amiodarone-treated patients undergoing cardiac surgery.19 However, the use of amiodarone is not benign; long-term use has been associated with hepatic, pulmonary, and endocrine toxicity. In addition, amiodarone administration can cause hypotension, bradycardia, and heart block. A meta-analysis of 18 trials (3408 patients) performed to assess the safety of amiodarone to prevent POAF after cardiac surgery noted an increased risk of bradycardia and hypotension in the amiodarone-treated

BOX 55.1  Risk Factors for Postoperative

Atrial Fibrillation.

Epidemiologic Genetics Advanced age Male gender Medical conditions History of atrial fibrillation Coronary artery disease Valvular heart disease Congestive heart failure Diabetes mellitus Potentially modifiable risk factors Hypertension Obstructive sleep apnea Obesity Perioperative stresses Type of surgery Pain Respiratory insufficiency Volume overload Use of catecholamine inotropes and pressors Electrolyte disturbances

BOX 55.2  Stressors of the Perioperative

and Intensive Care Periods.

Induction and emergence of general anesthesia Hemodynamic shifts Surgical trauma Manipulation of the heart and pulmonary veins Pain Electrolyte abnormalities (hypokalemia, hypomagnesemia) Hypervolemia (distension of the atria) Subtherapeutic levels of antiarrhythmics (i.e., beta blockers) Administration of catecholamine inotropes Pulmonary insufficiency (dyspnea, weaning from ventilator)

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group, but no statistically significant differences in heart block, myocardial infarction, stroke, or death.26 These findings were most apparent in patients treated with high doses (.1 g/day), with intravenous formulations, and in those in whom the drug was initiated in the postoperative period. Both the ACCF/AHA guidelines20 and ESC guidelines25 ascribe a class IIa recommendation for amiodarone POAF prophylaxis in cardiac surgical patients. The American College of College of Cardiology (ACC) guidelines recommend consideration of amiodarone prophylaxis for cardiac surgical patients in whom beta blockers are contraindicated.27 There are insufficient data available to recommend amiodarone prophylaxis for patients undergoing noncardiac surgery.

Sotalol Sotalol is a class II antiarrhythmic agent that has both betaantagonist and potassium channel-blocking activity. A review of 11 studies (1609 subjects) found significant reductions in the incidence of POAF in patients undergoing cardiac surgery who received perioperative sotalol.19 Despite these findings, potentially dangerous side effects (QT prolongation, torsades de pointes, hypotension, and bradycardia) have limited the use of this agent in both cardiac and noncardiac surgical populations.

Calcium Channel Blockers and Digoxin Few data support the use of other antiarrhythmic drugs for POAF prophylaxis. Early data regarding the use of nondihydropyridine calcium channel antagonists were inconclusive and an early meta-analysis failed to demonstrate benefit.28 A more promising review of four studies in noncardiac thoracic surgical patients found that calcium channel blockers were effective in POAF prevention.21 However, a more 2013 RCT failed to demonstrate benefit in this population.29 Currently, the ACCP, ACC/AHA, and ESC do not recommend calcium channel blockers for POAF prophylaxis. Digoxin was at one time advocated for POAF prophylaxis. However, the literature does not support its use.28 In fact one study noted an increased risk of POAF after thoracic surgery in digoxin-treated patients.21 Although it can be effectively used for rate control of atrial fibrillation, no current guidelines recommend digoxin for POAF prophylaxis.

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controls (23 vs. 31%).30 A review of 19 studies and 2988 subjects demonstrated similar reductions in patients treated with supplemental magnesium during or after cardiac surgery.19 It remains unclear whether avoidance of hypomagnesemia or achievement of supernormal magnesium levels is responsible for the observed benefit. Nonetheless, current guidelines of the ACCP recommend maintenance of serum magnesium levels in the normal range after cardiac surgery and suggest that empirical supplementation be considered in this high-risk population.31

ATRIAL PACING Atrial pacing has been proposed as a strategy to decrease the incidence of atrial fibrillation after cardiac surgery. It is theorized that overdrive suppression of supraventricular foci may retard the development of atrial fibrillation in the immediate postsurgical period. Heterogeneity within the literature examining pacing for atrial fibrillation prophylaxis makes interpretation of the data challenging. Nonetheless, several meta-analyses have been published. In a review of 13 prospective RCTs in which right atrial pacing, left atrial pacing, or biatrial pacing was used, Archbold and Schilling found that the most significant reduction in POAF occurred in patients receiving biatrial pacing (relative risk [RR] 0.46; 95% confidence interval [CI] 0.30–0.71).32 Pacing protocols varied, but usually were set 10–20 beats above the intrinsic rate for a period ranging from 1 to 5 days. Atrial pacing after cardiac surgery appears to be efficacious in preserving sinus rhythm, but identification of the optimal site and pacing algorithm is limited by the lack of large, well-controlled studies. Although potentially advantageous, this strategy has not been explored in the noncardiac surgery population. Pacing is limited to patients with implanted pacemakers and those with transvenous or temporary epicardial pacing wires placed after cardiac surgery.

REDUCTION OF PERIOPERATIVE STRESSORS AND MODULATION OF THE INFLAMMATORY RESPONSE TO SURGERY

ELECTROLYTE REPLETION AND MAINTENANCE

Given the role that the inflammatory response seems to play in the pathogenesis of POAF, various interventions targeting this response have been used in efforts to reduce risk.

Magnesium

Corticosteroids

Electrolyte derangements and membrane instability are postulated to play important roles in the pathogenesis of atrial fibrillation, particularly in the postoperative setting. The importance of the magnesium depletion that typically occurs during cardiopulmonary bypass and after diuretic administration has been studied in patients after cardiac surgery. In a meta-analysis, 16 trials totaling 2029 patients evaluating the use of prophylactic magnesium administration were identified. Supraventricular arrhythmias occurred significantly less often in patients treated with magnesium compared with

A meta-analysis of 50 RCTs of prophylactic steroid administration for patients undergoing cardiac surgery supported a role in reducing postoperative atrial fibrillation in patients receiving steroids (25.1 vs. 35.1% incidence).33 Conversely, the Dexamethasone in Cardiac Surgery (DECS) study and Steroids In caRdiac Surgery (SIRS) trials failed to demonstrate a beneficial response.34,35 Given the potential risks of routine administration of corticosteroids (hyperglycemia, increased risk of infection), they are not currently recommended for postoperative atrial fibrillation prophylaxis.

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Cardiovascular Critical Care

Statins

Colchicine

In addition to their effects on lipid profiles, statins have known anti-inflammatory effects that are thought to contribute to the observed reduction in new-onset atrial fibrillation. A meta-analysis of three RCTs and 16 observational studies comprising 31,725 patients found that the incidence of postoperative atrial fibrillation after cardiac surgery was significantly reduced by statins (odds ratio [OR] 0.67; 95% CI 0.51–0.88).36 Interestingly, a meta-analysis examining data on patients undergoing either isolated CABG or isolated aortic valve replacement (AVR) demonstrated a reduction in atrial fibrillation in the CABG group but not in the AVR group.37 Current ACCF/AHA recommendations call for perioperative statins in all patients with CABG, regardless of baseline lipid profile.20 A large prospective RCT of 1922 patients undergoing elective cardiac surgery failed to demonstrate reduction of POAF in patients receiving statins.38 On the basis of this and other studies, current ESC guidelines do not recommend statin administration for POAF prophylaxis in cardiac surgical patients.25

Colchicine is a powerful anti-inflammatory drug that inhibits neutrophil activity. The initial COPPS (COlchicine for Prevention of Postcardiotomy Syndrome) trial demonstrated a reduction in POAF in patients receiving the drug 3 days after undergoing cardiac surgery.41 But the COPPS-2 trial failed to show a statistically significant reduction in early POAF (postoperative days 1–2) and incurred an increased risk of gastrointestinal side effects of the drug.42 Although current AHA/ ACC/Heart Rhythm Society (HRS) guidelines ascribe a class IIb recommendation for the use of colchicine for atrial fibrillation prophylaxis in cardiac surgical patients,27 the COPPS-2 data suggest that colchicine should not be used for this indication.

Perioperative Anesthetic Management One of the more sweeping initiatives to decrease perioperative stressors and improve outcomes has been implementation of Enhanced Recovery After Surgery (ERAS©) type protocols. The multifaceted “bundled” approach to support less invasive procedures, improved pain management, earlier liberation from mechanical ventilation, goaldirected volume resuscitation, and earlier mobilization has become an international focus of many surgical subspecialties. There is some evidence that such protocols have a positive effect on decreasing the incidence of POAF, in addition to improved patient satisfaction, earlier hospital discharge, and lower health-care costs.39 The rationale for such a decrease in POAF is most likely multifactorial, including use of anti-inflammatory agents, goal-directed volume resuscitation, aggressive pain management, and reduction in catecholamines to restore vascular tone and hemodynamics. While it is unlikely that any one single component of ERAS protocols will have a positive effect on decreasing POAF, institution of concerted bundled, programmatic changes in perioperative care may prove to decrease the risk of developing POAF.

Aggressive Pain Management Epidural analgesia modulates the sympathetic nervous system and the inflammatory response to surgery. There is some evidence that use of epidural analgesia in patients undergoing noncardiac surgery under general anesthesia reduces the risk of POAF. A meta-analysis of 9 studies and 2016 subjects demonstrated a statistically significant reduction in the incidence of atrial fibrillation in patients receiving epidural analgesia for noncardiac surgery when compared with controls (20.1 vs. 25.4%).40

Evacuation of Pericardial Blood In addition to systemic inflammation in response to surgery, a growing body of evidence suggests that retained blood in the pericardium may induce a local, surface inflammatory response and predispose to the development of POAF.43 Strategies to reduce retained blood, including aggressive postoperative drainage of the space and posterior pericardiectomy may prove effective in reducing POAF.44

WHAT IS APPROPRIATE THERAPY FOR POAF IN A HEMODYNAMICALLY STABLE PATIENT: RATE CONTROL OR RHYTHM CONTROL? The initial approach to the development of POAF in the patient who is not hemodynamically compromised is to initially control the ventricular response rate. After this has been accomplished, electrical or pharmacologic cardioversion may be attempted. Early restoration of sinus rhythm theoretically avoids the need for anticoagulation, improves quality of life, decreases the risk for thromboembolic events, improves hemodynamics, and decreases the incidence of future episodes of atrial fibrillation. However, regardless of how intuitively attractive the concept, the data supporting the advantages of chronic rhythm control over rate control in the outpatient population have failed to demonstrate clear superiority of rhythm control. No studies have definitively shown that rhythm control is superior to rate control or vice versa for the primary outcome measure of mortality in outpatients. These conclusions are based on several large RCTs. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was the largest of these studies, enrolling 4060 patients. The mean follow-up in the study was 3.5 years, and no significant mortality difference between the rate control and rhythm control groups was found.45 However, there was a slightly higher incidence of noncardiovascular death, stroke (7.3 vs. 5.7%), and hospitalization (80 vs. 73%) in the rhythm control group. The author’s initial conclusion was that the strategy of rhythm control offered no overall mortality benefit and may have contributed to an increased incidence of noncardiac death. However,

CHAPTER 55

reevaluation of the data suggests that remaining in sinus rhythm may confer several advantages, including improved hemodynamics, reduction of thromboembolic events, lower mortality, improved quality of life, and improved exercise tolerance.46,47 A good discussion supporting the early restoration and maintenance of sinus rhythm was presented by van Gelder and Hemels.48 A post hoc analysis of the AFFIRM trial, Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STA) trial, and Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) trial concluded that restoration of sinus rhythm is a marker for improved survival.45,49,50 The largest multicenter randomized study of 4060 patients found sinus rhythm to be a predictor of survival, with a 47% reduction in mortality. The premise that maintenance of sinus rhythm improves outcome remains controversial and awaits further clari­ fication. In addition, a multimodal approach with wider application of angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and statins may potentially affect success in restoring and maintaining sinus rhythm. Postoperative atrial fibrillation should be considered an entity distinct from chronic atrial fibrillation. More than 90% of patients who develop post-CABG atrial fibrillation revert to sinus rhythm within 6–8 weeks.51 Although not demonstrated in the noncardiac surgical patient population, cardioversion to sinus rhythm after the stressors of the

383

postoperative period have abated seems to be a reasonable but as yet unproven strategy.

Rate Control Beta blockers, with their ability to modulate the hyperadrenergic tone encountered in the postoperative patient, are considered first-line agents for rate control in the ACC/AHA guidelines section on postoperative atrial fibrillation27 and the ACCP guidelines on the management of postoperative atrial fibrillation after cardiac surgery (Table 55.1).31

Rhythm Control Despite the self-limited nature of most cases of postoperative atrial fibrillation, the current ACC/AHA guidelines ascribe a class IIa recommendation for pharmacologic or electrical cardioversion in this patient population. The ACCP guidelines recommend the use of amiodarone, particularly for patients with depressed left ventricular function. Antiarrhythmic use for postoperative atrial fibrillation should be continued for 4–6 weeks after surgery.52 A randomized trial of rate vs. rhythm control in POAF failed to find a difference in hospital admissions during a 60-day follow-up.53 Given the absence of superiority of either approach, the ESC currently recommends rhythm control for the improvement of symptoms in the patient with POAF. In the asymptomatic patient, rate control or deferred cardioversion after anticoagulation are recommended.25

TABLE 55.1  Common Medication Dosage for Rate Control of Atrial Fibrillation. Intravenous Administration

Usual Oral Maintenance Dose

Beta Blockers Metoprolol tartrate

2.5–5.0 mg IV bolus over 2 min; up to 3 doses

25–100 mg BID

Metoprolol XL (succinate)

N/A

50–400 mg QD

Atenolol

N/A

25–100 mg QD N/A

Esmolol

500 mg/kg IV bolus over 1 min, then 50–300 mg/kg/min IV

Propranolol

1 mg IV over 1 min, up to 3 doses at 2-min intervals

10–40 mg TID or QID

Nadolol

N/A

10–240 mg QD

Carvedilol

N/A

3.125–25 mg BID

Bisoprolol

N/A

2.5–10 mg QD

Nondihydropyridine Calcium Channel Antagonists Verapamil 0.075–0.15 mg/kg IV bolus over 2 min; may give an additional 10.0 mg after 30 min if no response, then 0.005 mg/kg/min infusion

180–480 mg QD (ER)

Diltiazem

0.25 mg/kg IV bolus over 2 min, then 5–15 mg/h

120–360 mg QD (ER)

Digitalis Glycosides Digoxin

0.25 mg IV with repeat dosing to a maximum of 1.5 mg over 24 h

0.125–0.25 mg QD

Others Amiodaronea

300 mg IV over 1 h, then 10–50 mg/h over 24 h

100–200 mg QD

Multiple dosing schemes exist for the use of amiodarone. BID, twice daily; ER, extended release; IV, intravenous; N/A, not applicable; QD, once daily; QID, 4 times a day; TID, 3 times a day. From January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Task Force on practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-e76. a

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ANTICOAGULATION STRATEGY BEFORE RESTORATION OF SINUS RHYTHM: ATRIAL FIBRILLATION FOR LESS THAN 48 HOURS

ESC recommends lifelong anticoagulation after cardioversion of new-onset atrial fibrillation for patients at high risk for stroke as assessed by the CHADS2 (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism [doubled]) and CHA2DS2VASc (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism [doubled], Vascular disease, Age 65 to 74 years, Sex thromboembolic) Risk Stratification Scoring Systems (Table 55.2).25 Although these recommendations were based on studies of nonsurgical patients, the guidelines have been applied to the postsurgical patients, as the inflammatory response to surgery induces a hypercoagulable state that may increase the risk for an early thromboembolic event. Therefore, it may be prudent to selectively anticoagulate before cardioversion of high-risk patients with atrial fibrillation of less than 48 hours’ duration. However, it is clear that in the postoperative setting, the risk of thrombotic events in the absence of anticoagulation

It is common practice for patients with new onset of atrial fibrillation of less than 48 hours’ duration to proceed to cardioversion without the need for transesophageal echocardiography or anticoagulation. There is evidence in the literature that new-onset atrial fibrillation (duration ,48 hours) may be associated with an incidence of left atrial thrombus formation of up to 4%.54 Prospective data after cardioversion of 3143 patients found a 0.7% incidence of thromboembolic complications during a 30-day follow-up period but a significantly higher incidence in patients with increased stroke risk factors.55 Since 2010, the ESC has recommended consideration of anticoagulation with unfractionated or lowmolecular-weight heparin for all patients with new-onset atrial fibrillation undergoing cardioversion.25 In addition, the

TABLE 55.2  Comparison of the CHADS2 And CHA2DS2-VASc Risk Stratification Scores for

Subjects with Nonvalvular Atrial Fibrillation. DEFINITION AND SCORES FOR CHADS2 AND CHA2DS2-VASC Score CHADS2 Acronym Congestive HF

STROKE RISK STRATIFICATION WITH THE CHADS2 AND CHA2DS2-VASC SCORES Adjusted Stroke Rate (%/year)

1

CHADS2 Acronyma 0

1.9

Hypertension

1

1

2.8

Age 75 years

1

2

4.0

Diabetes mellitus

1

3

5.9

Stroke/TIA/TE

2

4

8.5

Maximum score

6

5

12.5

6

18.2

CHA2 DS2-VASc Acronym Congestive HF Hypertension Age 75 years

1

CHA2 DS2-VASc Acronymb 0

0

1

1

1.3

2

2

2.2

Diabetes mellitus

1

3

3.2

Stroke/TIA/TE

2

4

4.0

Vascular disease (prior MI, PAD, or aortic plaque)

1

5

6.7

Age 65–74 years

1

6

9.8

Sex category (i.e., female sex)

1

7

9.6

Maximum score

9

8

6.7

9

15.20

These adjusted-stroke rates are based on data for hospitalized patients with atrial fibrillation and were published by Shepard and colleagues in 2001. Because stroke rates are decreasing, actual stroke rates in contemporary, nonhospitalized cohorts might vary from these estimates. b Adjusted-stroke rate scores are based on data from Lip and colleagues. Actual rates of stroke in contemporary cohorts might vary from these estimates. CHADS2, Congestive heart failure, Hypertension, Age  75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism (doubled); CHA2DS2VASc, Congestive heart failure, Hypertension, Age  75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism (doubled), Vascular disease, Age 65–74 years, Sex thromboembolic; HF, heart failure; MI, myocardial infarction; PAD, peripheral artery disease; TE, thromboembolism; TIA, transient ischemic attack. From January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Task Force on practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-e76. a

CHAPTER 55

must be weighed against the risk of bleeding from fresh surgical sites after anticoagulation administration.

ANTICOAGULATION STRATEGY BEFORE RESTORATION OF SINUS RHYTHM: ATRIAL FIBRILLATION FOR MORE THAN 48 HOURS At times, patients enter the ICU with atrial fibrillation for more than 48 hours. In these individuals, anticoagulation before cardioversion is the accepted standard. ACC/AHA, ESC, and ACCP guidelines recommend 3 weeks of anticoagulation before cardioversion of patients with chronic atrial fibrillation.14,25,27 However, in cases of hemodynamic instability, cardioversion should not be delayed for initiation of anticoagulation. Timing for initiation of anticoagulation therapy (heparin as a bridge to an oral agent) in the postoperative patient must account for the potential for bleeding complications. Selection of an antithrombotic regimen should balance the risks of harm and potential benefit of avoiding ischemic stroke or other embolic complications. Platelet inhibitors, alone or in combination (aspirin and clopidogrel), are less effective than warfarin in preventing stroke.14 Administration of a direct thrombin inhibitor (dabigatran) or factor Xa inhibitors (rivaroxaban, apixaban) are gaining wider use for in-hospital and outpatient settings. Although these agents are more convenient, they are more costly and difficult to reverse in cases of bleeding or if the need to perform emergency invasive procedures arises. Data from a European observational study found that a greater international normalized ratio (INR) produced better outcomes. The incidence of thromboembolic events was 0.8% (4 of 530 patients) when the INR was 2.0–2.4 compared with no events when the INR was 2.5.56 In addition, reversal of warfarin anticoagulation has the benefit of being dependably achieved by the administration of vitamin K, plasma, or prothrombin complex concentrate. Timing and choice of anticoagulation strategy are made on an individual case basis with input from the primary stakeholders.

WHAT IS APPROPRIATE MANAGEMENT OF POAF IN A HEMODYNAMICALLY UNSTABLE PATIENT? In the hemodynamically unstable patient with POAF, immediate electrical cardioversion is the therapy of choice. Synchronized, direct current (DC) using a biphasic defibrillator is most effective for converting unstable POAF to a sinus rhythm.25 It goes without saying that considerations discussed above for the stable POAF patient do not apply for the patient who is hemodynamically unstable.

SHOULD ANTICOAGULATION BE INSTITUTED OR CONTINUED AFTER ELECTRICAL CARDIOVERSION TO SINUS RHYTHM? The period after conversion to sinus rhythm is associated with an increased risk of thrombus formation and subsequent

385

embolization. The recurrence of asymptomatic atrial fibrillation ranges from 40 to 60%,46,57 and other predisposing factors such as atheromatous disease and poor ventricular function also may increase the risk for thromboembolism.58 Perhaps the most significant factor is the transient decrease in atrial mechanical function that occurs after cardioversion to sinus rhythm.59 Mechanical dysfunction after cardioversion appears to last 24 hours in patients having atrial fibrillation of less than 2 weeks’ duration, 1 week in patients with atrial fibrillation of 2–6 weeks’ duration, and 1 month for more prolonged precardioversion atrial fibrillation.59 To date, there is no pharmacologic intervention to hasten the return of atrial mechanical activity. Support for continued anticoagulation can be gleaned from the AFFIRM and RACE (RAte Control vs. Electrical cardioversion) trials.48,60 Anticoagulation during these studies was often discontinued after restoration of sinus rhythm. Ischemic events occurred at equal frequency in both arms of the trials (rate control and rhythm control). Review of the data showed that such complications occurred most often after anticoagulation was terminated early (rhythm group) or when the INR was subtherapeutic (rate control group). Although the patients in these studies had chronic (not acute postoperative) atrial fibrillation, restoration of sinus rhythm in subtherapeutic or nonanticoagulated patients was associated with the increased incidence of thromboembolic events. Furthermore, the literature that provides the basis for these recommendations in general does not distinguish between patients who required electric cardioversion and those who spontaneously or pharmacologically converted to sinus rhythm. It seems prudent that guidelines for electrical and pharmacologic cardioversion be followed in a similar manner. Current guidelines of the ACCP recommend 4 weeks of anticoagulation for patients who undergo cardioversion after an episode of atrial fibrillation lasting .48 hours. For episodes ,48 hours’ duration, the ACCP guidelines do not recommend post-cardioversion anticoagulation.61 Similarly, the ESC guidelines recommend that for atrial fibrillation of .48 hours’ duration, postcardioversion oral anticoagulation should be maintained for at least 4 weeks.25 In addition, the ESC guidelines assign a class IIa recommendation for postPOAF oral anticoagulation in cardiac surgical patients after consideration of bleeding risk, noting that these patients are at double the risk for stroke and mortality compared with postoperative patients who remain in sinus rhythm.25 The ACC/AHA guidelines add that the decision to initiate postcardioversion anticoagulation for patients with atrial fibrillation of ,48 hours’ duration should be based on the patients’ risk for development of thromboembolism.27 Although neither the ACCP nor ACC/AHA guidelines specifically address postcardioversion anticoagulation for POAF, it seems prudent to follow these recommendations, provided that the risk for bleeding does not outweigh the risk for a thromboembolic event.

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Cardiovascular Critical Care

AUTHORS’ RECOMMENDATIONS • The pathogenesis of atrial fibrillation in the postoperative period is complex and multifactorial. The inflammatory response and increased levels of circulating catecholamines induced by surgery trigger supraventricular arrhythmias by altering atrial refractoriness and conductivity, predisposing to automaticity and re-entrant rhythms. • The type of surgery performed has a significant impact on the incidence of perioperative atrial fibrillation. Direct surgical manipulation or compression of the atria or pulmonary veins is associated with postoperative atrial fibrillation. • Prophylactic strategies against atrial fibrillation include maintenance of electrolytes, atrial pacing, and administration of antiarrhythmic agents (beta blockers and amiodarone). Other strategies that include a role for anti-inflammatory agents and anesthetic choices have been proposed and are under active investigation. • b-Adrenergic antagonists and alternative agents (such as amiodarone) are recommended for prophylaxis against atrial fibrillation by the ACC/AHA guidelines. Patients taking beta blockers on an outpatient basis should continue receiving them during the perioperative period. However, the prophylactic use of such agents in patients with low cardiac risk is controversial. • Beta blockers are recommended for all patients undergoing CABG surgery and should be considered for all patients undergoing cardiac surgery. • Postoperative atrial fibrillation associated with hemodynamic instability should be treated with biphasic cardioversion at 200 J. • Postoperative atrial fibrillation is often an acute event with a high conversion rate to sinus rhythm. Rate and rhythm control are both acceptable approaches to managing chronic atrial fibrillation. The premise that maintenance of sinus rhythm improves outcome remains controversial. • Patients with new onset of atrial fibrillation of .48 hours’ duration are at increased risk for thromboembolic events and should receive anticoagulant therapy. Anticoagulation should be temporarily continued after restoration of sinus rhythm because of a transient decrease in atrial mechanical function that increases the risk for thromboembolic events. Potential benefits of anticoagulation must be weighed against the risks for postoperative bleeding. • After cardioversion, anticoagulation may be considered for patients at high risk for stroke. The decision to initiate anticoagulation in this setting should balance the risk of a thromboembolic event with that of bleeding complications in postsurgical patients.

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e1 Abstract: Postoperative atrial fibrillation is a commonly encountered issue that places patients at risk for morbidity and mortality and significantly increases the cost of care. In this chapter, we review the epidemiology and pathophysiology of postoperative atrial fibrillation, current strategies for primary

prevention, and up-to-date recommendations for its treatment and management. Keywords: postoperative atrial fibrillation, pharmacologic prevention, enhanced recovery after surgery, cardioversion, anticoagulation, rate control, rhythm control