Beta blockers should be reinstituted as soon as possible after CABG in all patients without contra- indications to reduce the incidence or clinical se- quelae of AF.604 608,608a 608c (Level of Evidence: B) 3. Beta blockers should be prescribed to all CABG patients without contraindications at the time of hospital discharge. (Level of Evidence: C) Class IIa 1. Preoperative use of beta blockers in patients without contraindications, particularly in those with an LVEF greater than 30%, can be effective in reduc- ing the risk of in-hospital mortality.609 611 (Level of Evidence: B) 2. Beta blockers can be effective in reducing the inci- dence of perioperative myocardial ischemia.612 615 (Level of Evidence: B) 3. Intravenous administration of beta blockers in clin- ically stable patients unable to take oral medications is reasonable in the early postoperative period.616 (Level of Evidence: B) Class IIb 1. The effectiveness of preoperative beta blockers in reducing inhospital mortality rate in patients with LVEF less than 30% is uncertain.609,617 (Level of Evidence: B) See Online Data Supplement 25 for additional data on beta blockers. Because beta blockers have been shown to reduce the inci- dence of postoperative AF in CABG patients who are receiving them preoperatively604,605,608 (Section 5.2.5), the STS and AHA recommend that they be administered preoperatively to all patients without contraindications and then be continued post- operatively.618,619 Despite this recommendation, uncertainty ex- ists about their efficacy in subjects not receiving them preoper- atively; in this patient population, their use appears to lengthen hospital stay and not to reduce the incidence of postoperative AF.604,607 Their efficacy in preventing or treating perioperative myocardial ischemia is supported by the results of observational studies and small RCTs.612 614 Although a meta-analysis of available data did not show an improvement in outcomes with perioperative beta blockers,615 observational analyses suggest that preoperative beta-blocker use is associated with a reduction in perioperative deaths.609 611 Another analysis of data from 629 877 patients reported a mortality rate of 2.8% in those receiving beta blockers versus 3.4% in those not receiving Few data are available on the pharmacokinetic disposition of beta blockers in the early postoperative period, when an alteration in gastrointestinal perfusion may adversely affect their absorption after oral administration. An RCT demon- strated a significant reduction in the incidence of postopera- tive AF when a continuous intravenous infusion of meto- prolol was used rather than oral administration.616 The efficacy of beta-blocker use in CABG patients after hospital discharge is uncertain, as data from 2 RCTs and 1 large detailed observational analysis suggest that they exert no benefit over 2 years postoperatively.621 623 In contrast, some observa- tional analyses have reported that they are, in fact, efficacious in high-risk subgroups (eg, those with perioperative myocardial ischemia or elderly subjects with heart failure).624 A contempo- rary analysis of prescription data from 3,102 Canadian patients, 83% of whom were prescribed a beta blocker at the time of discharge, reported that those receiving beta blockers had a reduced mortality rate during a mean follow-up of 75 months.625 Of note, improved survival was noted in all patient subgroups receiving beta blockers, even including those without perioper- ative myocardial ischemia or heart failure. 4.6. ACE Inhibitors/ARBs: Recommendations Class I 1. ACE inhibitors and ARBs given before CABG should be reinstituted postoperatively once the pa- tient is stable, unless contraindicated.622,626,627 (Level of Evidence: B) 2. ACE inhibitors or ARBs should be initiated postop- eratively and continued indefinitely in CABG pa- tients who were not receiving them preoperatively, who are stable, and who have an LVEF less than or equal to 40%, hypertension, diabetes mellitus, or CKD, unless contraindicated.622,627,627a,627b (Level of Evidence: A) Class IIa 1. It is reasonable to initiate ACE inhibitors or ARBs postoperatively and to continue them indefinitely in all CABG patients who were not receiving them preoperatively and are considered to be at low risk (ie, those with a normal LVEF in whom cardiovas- cular risk factors are well controlled), unless contra- indicated.622,627 630 (Level of Evidence: B) Class IIb 1. The safety of the preoperative administration of ACE inhibitors or ARBs in patients on chronic therapy is uncertain.631 636 (Level of Evidence: B) 2. The safety of initiating ACE inhibitors or ARBs before hospital discharge is not well estab- lished.622,628,630,640 (Level of Evidence: B) See Online Data Supplements 26 and 27 for additional data on ACE inhibitors. ACE inhibitors and ARBs are known to exert cardiovasculo- protective actions, particularly in subjects with LV systolic dysfunction, hypertension, diabetes mellitus, or chronic renal insufficiency.626 Nonetheless, the safety and effectiveness of preoperative ACE inhibitors and ARBs in patients undergoing cardiac or noncardiac surgery is uncertain638 because their administration has been associated with intraoperative hypoten- sion as well as a blunted response to pressors and inotropic agents after induction of anesthesia. Of particular concern during cardiac surgery is their reported association with severe hypo- tension after CPB (so-called vasoplegia syndrome) and postop- erative renal dysfunction.631,639 Although it has been postulated that these agents may protect against the development of postoperative AF, published studies have reached conflicting conclusions in this regard.634,636 The safety and efficacy of ACE inhibitors and ARBs after CABG in previously na ve low- to moderate-risk patients (ie, subjects without diabetes mellitus or renal insufficiency and with or Hillis et al 2011 ACCF/AHA CABG Guideline e681 without asymptomatic moderate LV systolic dysfunction) are uncertain; furthermore, ACE inhibitors and ARBs must be used with caution in these subjects. They should not be instituted in the immediate postoperative period if the systolic arterial pres- sure is 100 mm Hg or if the patient develops hypotension in the hospital after receiving them. The IMAGINE (Ischemia Management With Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme) study failed to show a bene- ficial effect of postoperative ACE inhibitor therapy 3 years after CABG, instead noting an increase in adverse events, particularly recurrent angina in the first 3 months of therapy.630 A subanal- ysis of the data from patients enrolled in EUROPA (European Trial on the Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) with previous revascularization (CABG or PCI no sooner than 6 months before enrollment) suggested a primary and secondary prevention benefit over a 4.2-year follow-up period; however, an analysis of the data from almost 3000 patients in the PREVENT IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection) trial, all of whom were taking either ACE inhibitors or ARBs at the time of hospital discharge, failed to demonstrate a significant reduction in death or MI after 2 years of follow-up in ideal candidates (based on P NS), whereas significance was achieved in non-ideal candi- 4.7. Smoking Cessation: Recommendations Class I 1. All smokers should receive in-hospital educational counseling and be offered smoking cessation therapy during CABG hospitalization.642 644 (Level of Evi- dence: A) Class IIb 1. The effectiveness of pharmacological therapy for smoking cessation offered to patients before hospital discharge is uncertain. (Level of Evidence: C) See Online Data Supplement 28 for additional data on smoking cessation. Smoking cessation after CABG is associated with a sub- stantial reduction in subsequent MACE, including MI and death. Data from the randomized portion of the CASS study showed 10-year survival rates of 82% among the 468 patients who quit smoking after CABG and only 77% in the 312 who continued to smoke (P 0.025).645 Those who continued to smoke were more likely to have recurrent angina and to require repeat hospitalization. Data from the CASS registry demonstrated 5-year mortality rates of 22% for those who continued to smoke and only 15% for those who successfully quit smoking after CABG (RR: 1.55; 95% CI: 1.29 to 1.85).646 Similar favorable outcomes with smoking cessation were reported from the MRFIT (Multiple Risk Factor Inter- vention Trial), in which the impact of smoking cessation on MACE was assessed after 10.5 years of follow-up in 12 866 men; the risk of death was greater among smokers than non- smokers (RR: 1.57).647 Notably, the risk of dying from cardiac causes was lower for those who successfully quit than for nonquitters after only 1 year of smoking cessation (RR: 0.63), and it remained so in those who quit for at least the first 3 years of the study (RR: 0.38).647 The beneficial effects of smoking cessation after CABG seem to be durable during long-term follow-up (ie, even 30 years postoperatively).648 650 In fact, smoking cessation was associated with a reduction in mor- tality rate of greater magnitude than that resulting from any other treatment or intervention after CABG.649 In these long-term follow-up studies, patients who continued to smoke had significantly higher rates of MI, reoperation, and death. Smoking is a powerful independent predictor of sudden cardiac death in patients with CAD (HR: 2.47; 95% CI: 1.46 to 4.19). It has been associated with accelerated disease and occlusion of SVGs as well as endothelial dysfunction of arterial grafts.651 653 Compared with nonsmokers, subjects who are smoking at the time of CABG more often have pulmonary complications that require prolonged postopera- tive intubation and a longer ICU stay as well as postoperative infections.654 656 Even smokers who quit just before CABG have fewer postoperative complications than those who continued to smoke.654 As a result, all smokers referred for CABG should be counseled to quit smoking before surgery. Smoking cessation seems to be especially beneficial for patients hospitalized with ACS who then require CABG.644,657 Independent predictors of continued nonsmok- ing 1 year after CABG included 3 previous attempts to quit nonsmoking (OR: 10.0; 95% CI: 2.0 to 50), a definite intention to quit smoking (OR: 12.0; 95% CI: 2.6 to 55.1), and no difficulty with smoking cessation while in the hospital cessation intervention directed at patients early after post- CABG discharge appears to be more effective than a conser- vative approach.642 In a systematic review of 33 trials of smoking cessation, counseling that began during hospitaliza- tion and included supportive contacts for 1 month after hospital discharge increased the rates of smoking cessation (OR: 1.65; 95% CI: 1.44 to 1.90), whereas the use of pharmacotherapy did not improve abstinence rates.643 These findings are supported by a 2009 RCT comparing intensive or minimal smoking cessation intervention in patients hospital- ized for CABG or acute MI.644 In this trial, the 12-month self-reported rate of abstinence was 62% among patients randomly assigned to the intensive program and 46% among those randomly allocated to the minimal intervention (OR: 2.0; 95% CI: 1.2 to 3.1). Overall, a higher rate of continuous abstinence was observed in patients undergoing CABG than in those who had sustained an MI. Interestingly, the rates of abstinence were lower in subjects who used pharmacotherapy regardless of the intervention group (OR: 0.3; 95% CI: 0.2 to Seven first-line pharmacological treatments are available for smoking cessation therapy, including 5 nicotine- replacement therapies; the antidepressant bupropion; and varenicline, a partial agonist of the 4 2 subtype of the nicotinic acetylcholine receptor.659 661 The data supporting the use and timing of nicotine-replacement therapy after CABG are unclear. One study from a large general practice database reported no increased risk of MI, stroke, or death with nicotine-replacement therapy,662 whereas a retrospective case control study of critically ill patients reported a higher in-hospital mortality rate in those receiving nicotine replace- ment (20% versus 7%; P 0.0085). Despite adjusting for the severity of illness, nicotine-replacement therapy was an independent predictor of inhospital mortality (OR: 24.6; 95% CI: 3.6 to 167.6; P 0.0011).663 Similarly, in a cohort study of post-CABG patients, nicotine-replacement therapy was shown to be an independent predictor of in-hospital mortality after adjusting for baseline characteristics (OR: 6.06; 95% CI: 1.65 to 22.21).663,664 Additional studies are needed to deter- mine the safety of nicotine-replacement therapy in smokers undergoing CABG as well as the optimal time at which to begin such therapy postoperatively. 4.8. Emotional Dysfunction and Psychosocial Considerations: Recommendation Class IIa 1. Cognitive behavior therapy or collaborative care for patients with clinical depression after CABG can be beneficial to reduce objective measures of depres- sion.665 669 (Level of Evidence: B) The negative impact of emotional dysfunction on risk of morbidity and mortality after CABG is well recognized. In a multivariate analysis of elderly patients after CABG, the 2 most important predictors of death were a lack of social participation and a lack of religious strength.670 Social isola- tion is associated with increased risk of death in patients with CAD,671 and treatment may improve outcomes.672 The most carefully studied mood disorder, depression, occurs com- monly after CABG. Several studies have shown that the primary predictor of depression after CABG is its presence before CABG and that only rarely does CABG cause depres- sion in patients who were not depressed beforehand. In 1 report, half the patients who were depressed before CABG were not depressed afterward, and only 9% of subjects who were not depressed before CABG developed depression postoperatively.673 The prevalence of depression at 1 year after CABG was 33%, which is similar to the prevalence in those undergoing other major operations. Patients with stron- ger perceptions of control of their illness were less likely to be depressed or anxious after CABG.674 No difference in the incidence of mood disturbances was noted when off-pump and on-pump CABG were compared.675 4.8.1. Effects of Mood Disturbance and Anxiety on CABG Outcomes Depression is an important risk factor for the development and progression of CAD. In fact, it is a more important predictor of the success of cardiac rehabilitation than many other functional cardiac variables.676 Both the presence of depressive symptoms before CABG and the postoperative worsening of these symptoms correlate with poorer physical and psychosocial functioning and poorer quality of life after CABG.677 In a study of 440 patients who underwent CABG, the effects of both preoperative anxiety and depression (as defined by the Depression Anxiety and Stress Scale) on mortality rate were assessed for a median of 5 years postop- eratively.678 Interestingly, preoperative anxiety was associ- ated with a significantly increased risk of death (HR: 1.88; sion was not.678 In a multivariate analysis of 817 patients at Duke University Medical Center, severe depression (assessed using the Center for Epidemiological Studies Depression scale before surgery and 6 months postoperatively665 was associated with increased risk of death (HR: 2.4; 95% CI: 1.4 to 4.0), as was mild or moderate depression that persisted at 6 months (HR: 2.2; 95% CI: 1.2 to 4.2). In another study of 309 subjects followed up for 1 year after CABG, those with diagnostic criteria for a major depressive disorder before discharge were nearly 3 times as likely to have a cardiac event, such as heart failure requiring hospitalization, MI, cardiac arrest, PCI, repeat CABG, or cardiac death.666 Fi- nally, depression after CABG is an important predictor of the recurrence of angina during the first 5 postoperative 4.8.2. Interventions to Treat Depression in CABG Patients The Bypassing the Blues investigators identified 302 patients who were depressed before CABG and 2 weeks after dis- charge.668 They were randomly assigned to 8 months of telephone-delivered collaborative care (150 patients) or usual care (152 patients). The 2 groups were compared with each other and also to another group of 151 randomly selected nondepressed post-CABG patients. At 8 month follow-up, the collaborative care group showed an improve- ment in quality of life and physical functioning and were more likely to report a 50% decline in the Hamilton Rating Score for Depression than the usual care group (50.0% versus 29.6%; P 0.001). Men were more likely to benefit from the intervention.668,669 In another study, 123 patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for major or minor depression within 1 year of CABG were randomly assigned to 12 weeks of cognitive behavior therapy, 12 weeks of supportive stress management, or usual care.667 Both interventions were efficacious for treating depression after CABG, and cognitive behavior therapy had the most durable effects on depression and several secondary psychological outcome variables.667 Thus, both collaborative intervention and cognitive behavior ther- apy are effective for treating depression in patients after CABG. Given that depression is associated with adverse outcomes after CABG, it is likely that these interventions also may lead to reduced rates of morbidity and mortality. 4.9. Cardiac Rehabilitation: Recommendation Class I 1. Cardiac rehabilitation is recommended for all eligi- ble patients after CABG.679 681,681a 681d (Level of Evidence: A) See Online Data Supplement 29 for additional data on cardiac rehabilitation. Cardiac rehabilitation, including early ambulation during hospitalization, outpatient prescriptive exercise training, and education, reduces risk of death in survivors of MI.682 684 Beginning 4 to 8 weeks after CABG, 3-times-weekly educa- tion and exercise sessions for 3 months are associated with a Hillis et al 2011 ACCF/AHA CABG Guideline e683 35% increase in exercise tolerance (P 0.0001), a slight (2%) (P 0.05) increase in high-density lipoprotein cholesterol, and a 6% reduction in body fat (P 0.002).421 Exercise training is a valuable adjunct to dietary modification of fat and total caloric intake in maximizing the reduction of body fat while minimizing the reduction of lean body mass. Aerobic training improves volume of maximum oxygen consumption at 6 months compared with moderate continu- ous training (P 0.001).685 After hospital discharge, CABG patients were randomly assigned to standard care (n 109) or standard care plus rehabilitation (n 119). At 5 years, the groups were similar in symptoms, medication use, exercise capacity, and depression scores, but rehabilitated patients reported better physical mobility, better perceived health, and better perceived overall life situation. A larger proportion of the rehabilitated patients were working at 3 years, although this difference disappeared with longer follow-up.679 Subjects who sustained an MI followed by CABG had greater improvement in exercise tolerance after rehabilitation than did those who had an MI alone. Improvement was sustained for 2 years.686 Observa- tional studies have reported that cardiac events are reduced with rehabilitation after revascularization.680 In many CABG patients, initiation of rehabilitation is a substantial hurdle. Medically indigent patients seem to have rehabilitation compliance and benefit rates similar to those of insured or private-paying patients if rehabilitation is initiated promptly and is structured appropriately.687 In addition to contributing to a patient s sense of well-being, participation in cardiac rehabilitation offers an economic benefit. During a 3-year (mean: 21 months) follow-up after CABG or another coronary event, per capita hospitalization charges were $739 lower for rehabilitated patients compared with nonpartici- pants.688 Post-CABG patients are more likely to resume sexual activity than are survivors of MI. Anticipatory and proactive advice by the physician or surgeon on the safety of resumption of sexual activity as the patient reengages in other daily activities is beneficial.682 Recommendations for intensive risk-reduction therapies for patients with established coronary and other atheroscle- rotic vascular disease are detailed in the AHA/ACC Second- ary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Vascular Disease: 2011 Update. 689 This updated guideline includes recommendations on smoking, blood pressure control, lipid management, physical therapy, weight management, type 2 diabetes management, antiplate- let agents and anticoagulants, renin angiotensin aldosterone system blockers (ACE inhibitors and ARBs), beta blockers, influenza vaccination, depression, and cardiac rehabilitation. 4.10. Perioperative Monitoring Monitoring: Recommendations Class I 1. Continuous monitoring of the electrocardiogram for arrhythmias should be performed for at least 48 hours in all patients after CABG.606,690,691 (Level of Evidence: B) Class IIa 1. Continuous ST-segment monitoring for detection of ischemia is reasonable in the intraoperative period for patients undergoing CABG.53,692 694 (Level of Evidence: B) Class IIb 1. Continuous ST-segment monitoring for detection of is- chemia may be considered in the early postoperative period after CABG.613,690,695 698 (Level of Evidence: B) 4.10.2. Pulmonary Artery Catheterization: Recommendations Class I 1. Placement of a pulmonary artery catheter (PAC) is indicated, preferably before the induction of anes- thesia or surgical incision, in patients in cardiogenic shock undergoing CABG. (Level of Evidence: C) Class IIa 1. Placement of a PAC can be useful in the intraoperative or early postoperative period in patients with acute hemo- dynamic instability.699 704 (Level of Evidence: B) Class IIb 1. Placement of a PAC may be reasonable in clinically stable patients undergoing CABG after consider- ation of baseline patient risk, the planned surgical procedure, and the practice setting.699 704 (Level of Evidence: B) 4.10.3. Central Nervous System Monitoring: Recommendations Class IIb 1. The effectiveness of intraoperative monitoring of the processed electroencephalogram to reduce the pos- sibility of adverse recall of clinical events or for detection of cerebral hypoperfusion in CABG pa- tients is uncertain.705 707 (Level of Evidence: B) 2. The effectiveness of routine use of intraoperative or early postoperative monitoring of cerebral oxygen saturation via near-infrared spectroscopy to detect cerebral hypoperfusion in patients undergoing CABG is uncertain.708 710 (Level of Evidence: B) See Online Data Supplement 30 for additional data on central nervous system monitoring. Requirements for basic perioperative monitoring in pa- tients undergoing CABG, including heart rate, blood pres- sure, peripheral oxygen saturation, and body temperature, are well accepted. Additional intraoperative standards established by the American Society of Anesthesiologists, including the addition of end-tidal carbon dioxide measurement in the intubated patient, are uniformly applied.711 Specialized mon- itoring of cardiac and cerebral function varies among centers and includes the use of PACs, TEE, or other forms of echocardiography (Section 2.1.7); noninvasive monitors of cardiac output; processed electroencephalographic monitor- ing; and cerebral oximetry with near-infrared spectroscopy. Given the added expense and potential hazards of such monitors (eg, pulmonary artery rupture with PAC, false- positive changes with cerebral oximetry or processed electro- encephalogram), substantial controversy exists about indica- tions for their use. None of these monitoring methods is routinely recommended. Electrocardiographic monitoring includes an assessment of heart rate and rhythm as well as the morphology and deviation of the QRS complex and ST segments for evidence of ischemia, infarction, or abnormal conduction.690 Continu- ous telemetric monitoring of cardiac rate and rhythm is recommended for 48 to 72 hours after surgery in all patients because of the high incidence of post-CABG AF, which most often occurs 2 and 4 days after surgery.606,613,690,691,697,698 In addition, other arrhythmias and conduction abnormalities may occur in patients with ischemia because of incomplete revascularization or in those undergoing concurrent valve replacement. Uncertainty continues with regard to the utility of PAC in low-risk patients undergoing CABG.712 Several observational studies suggest that such patients can be managed only with monitoring of central venous pressure, with insertion of a PAC held in reserve should the need arise. In fact, it has even been suggested that patients in whom a PAC is placed incur greater resource utilization and more aggressive therapy, which may lead to worse outcomes and higher costs. The reported rates of PAC use range from 10% in a combined private academic setting to 90% in patients in the Depart- ment of Veterans Affairs health system.61,639,701,702,713 Aside from providing an indirect assessment of left atrial pressure and the presence and severity of pulmonary hyper- tension, PAC can be used to measure cardiac output (by thermodilution) and to monitor the mixed venous oxygen saturation information that may be helpful in the manage- ment of high-risk patients.712,714 The need for careful consid- eration of baseline patient risk, the planned procedure, and the patient setting before use of a PAC are outlined in several opinion pieces, consensus documents, the Practice Guide- lines for Pulmonary Artery Catheterization: An Updated Report by the American Society of Anesthesiologists, and the 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guide- lines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery. 699,712,714 716 Pulmonary artery per- foration or rupture is fatal in 50% of patients in whom it occurs. This complication usually can be avoided by 1) withdrawal of the catheter tip into the main pulmonary artery before initiation of CPB; 2) withdrawal of the catheter into the pulmonary artery before balloon inflation, especially if the pressure tracing suggests damping; and 3) avoiding routine measurement of the pulmonary artery wedge pressure, reserving this maneuver as a specific diagnostic event. Perioperative monitoring of cerebral function (primarily with an electroencephalogram) has been used in certain high-risk patients, such as those undergoing neurosurgery or carotid vascular surgery.717 In the setting of cardiac surgery, the potentially deleterious effects of CPB on cerebral hypop- fusion or embolic events (ie, air or aortic calcific debris) have been investigated via transcranial Doppler techniques, with a lesser emphasis on the electroencephalogram (in part because of excessive artifact in this setting).57,718 Although processed electroencephalographic monitors and bifrontal cerebral oxi- metry have been available for more than 2 decades, contro- versy remains about their clinical effectiveness.719,720 Pro- cessed electroencephalographic monitoring is aimed primarily at assessing the risk of conscious recall of intraop- erative events, but it also has been used to gauge the depth of anesthesia, theoretically allowing more precise titration of the anesthetic.721,722 Although a variety of electroencephalo- graphic variables are commonly accepted as markers of cerebral ischemia, the ability of current commercial devices to detect or quantify ischemia is limited.706,707,717,718 Given the intuitive link between reflectance oximetry (ie, for peripheral oxygen or mixed venous oxygen saturation) and clinical interventions (ie, manipulating hemodynamic variables, the fraction of inspired oxygen, etc.), there is considerable interest in the use of bifrontal cerebral oximetry as a measure of brain perfusion.723 Two RCTs in CABG patients suggest that bifrontal cerebral oximetry may be helpful in predicting early perioperative cognitive decline, stroke, noncerebral complications, and ICU and hospital length of stay.709,710 A 2011 observational cohort (1178 CABG patients) suggested that a patient s preoperative re- sponse to breathing oxygen for 2 minutes (ScO2 50%) is an independent predictor of death at 30 days and 1 year after 5. CABG-Associated Morbidity and Mortality: Occurrence and Prevention Several comprehensive data registries for CABG have been developed in the United States, the largest being the STS Adult Cardiac Database. For 20 years, these registries have collected data on all aspects of the procedure.306,725,727 A detailed analysis of these data and their correlation to out- comes has facilitated the creation of risk-assessment models that estimate the rates at which various adverse events occur. On the basis of these models, risk-adjusted outcomes for hospitals and surgeons have been calculated and, in some instances, publicly reported. 5.1. Public Reporting of Cardiac Surgery Outcomes: Recommendation Class I 1. Public reporting of cardiac surgery outcomes should use risk-adjusted results based on clinical data.728 735 (Level of Evidence: B) See Online Data Supplement 31 for additional data on public reporting of cardiac surgery outcomes. To address the need for valid and reliable risk-adjusted outcomes data, cardiac surgery registries were developed by the STS,306,725,727 Veterans Administration,306,736 738 North- ern New England Cardiovascular Disease Study Group,739,740 and the state of New York.741,742 These have been the basis for several performance assessment and improvement strate- gies, including public report cards,742 744 confidential feed- back to participants showing their performance relative to national benchmarks,306,737,745 748 and state or regional col- Hillis et al 2011 ACCF/AHA CABG Guideline e685 laboratives that identify and disseminate best-practices infor- mation.749 Public report cards are the most controversial of these 3 approaches. Although they provide transparency and public accountability, it is unclear if they are the only or best way to improve quality. Reductions in the CABG mortality rate after the publication of such report cards in New York were encour- aging,742,750 752 but subsequent studies revealed comparable reductions in other states, regions, and countries that used confidential feedback with or without performance improvement initiatives.752 754 These findings suggest that the common de- nominator among successful performance improvement strate- gies is the implementation of a formal quality assessment and feedback program benchmarked against regional or national results.755 The incremental value of public (as opposed to confidential) reporting is controversial. Although providers fear the potential negative impact of public reporting on referrals and market share, this concern seems to be unfounded.756 765 Even when such impact has been observed, it has generally been modest, transient, and limited to areas populated by more affluent and educated subjects.760 762,766 With implementation of healthcare reform legislation that increases access of consumers and payers to objective data and more easily understood data presentations, the influence of public report cards is likely to increase in the future.762,767 771 As this occurs, it will be important to monitor unintended negative consequences, such as gaming of the reporting system772 and avoidance of high-risk patients (risk aversion), the precise group of patients who are most likely to benefit from aggressive intervention.773 776 Methodological considerations are important for provider profiling and public reporting. Numerous studies have shown the superiority of clinical over administrative data for these purposes.728 731,733,734 The latter data lack critical clinical variables that are necessary for adequate risk adjust- ment,732,735 they may confuse comorbidities and complica- tions, and they may contain inaccurate case numbers and mortality rates. Outcomes measures, such as mortality, should always be adjusted for patient severity on admission (ie, risk-adjusted or risk-standardized )777 780; otherwise, pro- viders will be hesitant to care for severely ill patients, who are more likely to die from their disease. In addition, if a hospital or surgeon is found to be a low-performing outlier on the basis of unadjusted results, the hospital or surgeon may claim that their patients were sicker. Statistical methodologies should account for small sample sizes and clustered patient observations within institutions, and hierarchical or random- effects models have been advocated by some investiga- tors.743,781 787 Point estimates of outcomes should always be accompanied by measures of statistical uncertainty, such as CIs. The units of analysis and reporting for provider profiling also have implications. Surgeon-level reports are published together with hospital reports in several states, but their smaller sample sizes typically require data aggregation over several years. Surgeon-level reporting may also increase the potential for risk aversion, as the anticipated worse results of the highest-risk patients are not diluted by the larger volume of a hospital or group. Finally, because the distribution of patient severity may vary substantially among providers, direct comparison of the results of one surgeon or hospital with those of another, even by using indirectly risk- standardized results, is often inappropriate.788 Rather, these results should be interpreted as comparisons of a provider s outcomes for his or her specific patient cohort versus what would have been expected had those patients been cared for by an average provider in the benchmark population. Although risk-adjusted mortality rate has been the domi- nant performance metric in cardiac surgery for 2 decades, other more comprehensive approaches have been advo- cated.789 The STS CABG composite illustrates one such multidimensional approach, consisting of 11 National Quality Forum endorsed measures of cardiothoracic surgery perfor- mance grouped within 4 domains of care.619,790 5.1.1. Use of Outcomes or Volume as CABG Quality Measures: Recommendations Class I 1. All cardiac surgery programs should participate in a state, regional, or national clinical data registry and should receive periodic reports of their risk-adjusted outcomes. (Level of Evidence: C) Class IIa 1. When credible risk-adjusted outcomes data are not available, volume can be useful as a structural metric of CABG quality.309,751,791 798,800 804,807,818 (Level of Evidence: B) Class IIb 1. Affiliation with a high-volume tertiary center might be considered by cardiac surgery programs that perform fewer than 125 CABG procedures annually. (Level of Evidence: C) See Online Data Supplement 32 for additional data on outcomes or volume as CABG quality measures. Numerous studies have demonstrated an association be- tween hospital or individual practitioner volume and outcome for a variety of surgical procedures and some medical conditions.805 831 CABG was one of the original procedures for which this volume outcome association was investi- gated.309,751,791 798,800 804,807,818 The CABG volume outcome association is generally weaker than that of other procedures, such as esophagectomy or pancreatectomy, which are per- formed less often. In addition, the results of volume outcome studies vary substantially according to methodology. The apparent strength of the volume outcome association often diminishes with proper risk adjustment based on clinical (as opposed to administrative) data.802,808 It is also weaker in more contemporary studies, presumably because of improved techniques and increasing experience.795,802 Finally, volume outcome associations appear weaker when hierarchical mod- els are used that properly account for small sample sizes and clustering of observations.832 The impact of CABG volume was studied in an observational cohort of 144 526 patients from 733 hospitals that participated in the STS Adult Cardiac Surgery Database in 2007.309 In this analysis, a weak associ- ation between volume and unadjusted mortality rate was noted (2.6% unadjusted mortality rate for hospitals perform- ing 100 procedures versus 1.7% for hospitals performing 450 procedures).309 Using multivariate hierarchical regres- sion, the largest OR (1.49) was found for the lowest-volume ( 100 cases) group versus the highest-volume group. Desir- able processes of care (except for use of the IMA) and morbidity rates were not associated with volume. The average STS-CABG composite score for the lowest-volume group ( 100 cases per year) was significantly lower than that of the 2 highest-volume groups, but volume explained only 1% of variation in the composite score.619,790 In general, the best results are achieved most consistently by high-volume surgeons in high-volume hospitals and the worst results by low-volume surgeons in low-volume hospi- tals.793,794 However, many low-volume programs achieve excellent results, perhaps related to appropriate case selec- tion; effective teamwork among surgeons, nurses, anesthesi- ologists, perfusionists, and physician assistants; and adoption of best practices derived from larger programs.833,834 As a quality assessment strategy, participation in a state, regional, or national clinical data registry that provides regular performance feedback reports is highly recommended for all cardiac programs. Random sampling variation is greater at low volumes,309,797,798,803,827,834,835 which compli- cates performance assessment of smaller programs. Several strategies may be considered to mitigate this measurement issue, including analysis over longer periods of time; appro- priate statistical methodologies, such as hierarchical (random- effects) models; composite measures, which effectively in- crease the number of endpoints; and statistical quality control approaches, such as funnel plots835 and cumulative sum plots.836 838 Small programs may benefit from direct super- vision by a large tertiary center.834 Ultimately, state or national regulatory authorities must decide whether the lower average performance of very small programs and the added difficulty in accurately measuring their performance are outweighed by other considerations, such as the need to maintain cardiac surgery capabilities in rural areas with limited access to referral centers.834 Volume, a structural quality metric, is an imperfect proxy for direct measurement of outcomes.822,839 Risk- adjusted outcomes based on clinical data are the preferred method of assessing CABG quality except in very low- volume programs, in which performance is generally weakest and small sample size makes accurate assessment of performance difficult. 5.2. Adverse Events 5.2.1. Adverse Cerebral Outcomes The incidence of stroke after CABG ranges from 1.4% to 3.8%,840 depending on the patient population and the criteria for diagnosis of stroke. Risk factors for stroke include advanced age, history of stroke, diabetes mellitus, hyperten- sion,841 and female sex,842 with newer research emphasizing the importance of preoperative atherosclerotic disease (in- cluding radiographic evidence of previous stroke or aortic atheromatous disease).843 Although macroembolization and microembolization are major sources of stroke, hypoperfu- sion,844 perhaps in conjunction with embolization,845 is a risk factor for postoperative stroke. The mortality rate is 10-fold higher among post-CABG patients with stroke than among those without it, and lengths of stay are longer in stroke Although off-pump CABG was introduced in large part to reduce stroke and other adverse neurological outcomes asso- ciated with CPB, several RCTs comparing on-pump and off-pump CABG have shown no difference in stroke See Online Data Supplement 33 for additional data on stroke rates. 5.2.1.1.1. Use of Epiaortic Ultrasound Imaging to Reduce Stroke Rates: Recommendation Class IIa 1. Routine epiaortic ultrasound scanning is reasonable to evaluate the presence, location, and severity of plaque in the ascending aorta to reduce the incidence of atheroembolic complications.847 849 (Level of Evi- dence: B) Identification of an atherosclerotic aorta is believed to be an important step in reducing the risk of stroke after CABG.850 Intraoperative assessment of the ascending aorta for detection of plaque by epiaortic ultrasound imaging is superior to direct palpation and TEE.851,852 Predictors of ascending aortic atherosclerosis include increasing age, hypertension, extracardiac atherosclerosis (peripheral ar- tery and cerebrovascular disease), and elevated serum creatinine concentrations.853 855 Prospective RCTs to eval- uate the role of epiaortic scanning in assessing stroke risk have not been reported, but several observational studies reported stroke rates of 0 to 1.4%847 849,853,856,857 when surgical decision making was guided by the results of epiaortic scanning. Separate guidelines for the use of intraoperative epiaortic ultrasound imaging in cardiac surgery were endorsed and published in 2008 by the American Society for Echocardiography, Society of Car- diovascular Anesthesiologists, and STS.147 5.2.1.1.2. The Role of Preoperative Carotid Artery Noninva- sive Screening in CABG Patients: Recommendations Class I 1. A multidisciplinary team approach (consisting of a cardiologist, cardiac surgeon, vascular surgeon, and neurologist) is recommended for patients with clin- ically significant carotid artery disease for whom CABG is planned. (Level of Evidence: C) Class IIa 1. Carotid artery duplex scanning is reasonable in selected patients who are considered to have high- risk features (ie, age >65 years, left main coronary stenosis, PAD, history of cerebrovascular disease [transient ischemic attack [TIA], stroke, etc.], hyper- tension, smoking, and diabetes mellitus).858,859 (Level of Evidence: C) Hillis et al 2011 ACCF/AHA CABG Guideline e687 2. In the CABG patient with a previous TIA or stroke and a significant (50% to 99%) carotid artery stenosis, it is reasonable to consider carotid revascu- larization in conjunction with CABG. In such an individual, the sequence and timing (simultaneous or staged) of carotid intervention and CABG should be determined by the patient s relative magnitudes of cerebral and myocardial dysfunction. (Level of Evi- dence: C) Class IIb 1. In the patient scheduled to undergo CABG who has no history of TIA or stroke, carotid revasculariza- tion may be considered in the presence of bilateral severe (70% to 99%) carotid stenoses or a unilateral severe carotid stenosis with a contralateral occlu- sion. (Level of Evidence: C) Because the presence of extracranial disease of the internal carotid artery is a risk factor for adverse neurological events after CABG,860 one might argue for use of carotid noninva- sive scanning (duplex ultrasonography or noninvasive carotid screening) in all patients scheduled for CABG. At issue is the effectiveness of noninvasive carotid screening in identifying carotid artery stenoses of hemodynamic significance. Alter- natively, the identification of preoperative risk factors known to be associated with the presence of carotid artery disease could be used to stratify patients into high- and low-risk categories, thereby allowing for a more selective use of noninvasive carotid screening. A retrospective analysis of 1421 consecutive CABG patients identified the following as risk factors for significant carotid artery disease: age 65 years, presence of a carotid bruit, and a history of cerebro- vascular disease.858 In so doing, they reduced preoperative testing by 40%, with only a negligible impact on surgical management or neurological outcomes. Similarly, the follow- ing risk factors have been identified as predicting the pres- ence of 50% reduction in internal diameter of the internal carotid artery: smoking, diabetes mellitus, hypertension, a previous cerebrovascular event, PAD, left main CAD, and a history of cervical carotid disease.859 All subjects found to have significant carotid disease were noted to have 1 of these criteria. In addition, the probability of detecting signif- icant carotid disease increased almost 3 times for each additional criterion that was present. The authors noted that the presence of a single preoperative risk factor increased the sensitivity of the screening test to 100% and increased the specificity to 30%. As a result, they strongly recommend a selective approach to the use of preoperative noninvasive carotid screening, allowing for a decrease in the number of unnecessary tests but exerting little effect on the detection of significant carotid disease. In patients undergoing carotid endarterectomy, the rates of periprocedural stroke have been reported to be as high as 2.5% in those with asymptomatic carotid stenoses861 and 5% in those with previous cerebrovascular symptoms.862 In CABG patients with 50% unilateral carotid stenoses in whom carotid endarterectomy is not performed concomi- tantly with CABG, the peri-CABG stroke rate is reportedly 3%, rising to 5% in those with bilateral carotid artery stenoses and 11% in those with an occluded carotid artery.860 In light of these data, the issue of combined carotid and coronary revascularization (performed simultaneously or in a staged, sequential fashion) as a strategy to reduce the postoperative stroke risk in CABG patients with known carotid artery disease has received substantial attention. The lack of clarity about the optimal approach to the management of such patients is the result of several factors: To date, no published randomized, prospective study has addressed this important clinical scenario.863 The etiology of postoperative stroke often is multifac torial (eg, ascending aortic calcifications with resultant atherothrombotic embolization, preexisting carotid ar- tery disease, air or debris cerebral embolization associ- ated with CPB, episodes of transient intraoperative hypotension). Many risk factors for stroke coexist in CABG patients. The rates for postoperative stroke and death for carotid endarterectomy and for CABG, independent of or in conjunction with one another, vary considerably in different patient populations (eg, young versus old, male versus female, etc.). More than half of all post-CABG strokes occur after uneventful recovery from CABG and are believed to be caused by supraventricular arrhythmias, low cardiac output, or postoperative hypercoagulability.863 A substantial proportion of post-CABG strokes occur in patients without significant carotid artery disease or in an anatomic distribution not consistent with a known significant carotid arterial stenosis. Advances in technologies for carotid and coronary revas- cularization make the decision-making process for the proce- dures even more complex. In addition to conventional CABG with CPB, the surgeon may choose an off-pump technique in certain patients (eg, those with a heavily calcified ascending aorta). Likewise, carotid artery stenting provides an alterna- tive to endarterectomy, which may reduce the risk of postop- erative stroke. Still, the ultimate impact of such stenting on postoperative stroke rates in CABG patients awaits the results of properly designed trials. At present, carotid artery stenting is reserved for CABG patients in whom a contraindication to open endarterectomy exists. When combined carotid and coronary revascularization is indicated, an awareness of the stroke and mortality rates for different patient subgroups will help to guide decision mak- ing. Several factors favor combined revascularization, includ- ing (but not limited to) 1) severe carotid artery disease, 2) unfavorable morphological characteristics of the carotid le- sion(s) (eg, ulcerated lesions), 3) the presence of related symptoms, and 4) a history of TIA or stroke. In those with a history of TIA or stroke who have a significant carotid artery stenosis (50% to 99% in men or 70% to 99% in women), the likelihood of a post-CABG stroke is high; as a result, they are likely to benefit from carotid revascularization.863 Con- versely, CABG alone can be performed safely in patients with asymptomatic unilateral carotid stenoses, because a carotid revascularization procedure offers no discernible reduction in the incidence of stroke or death in these individuals. Men with asymptomatic bilateral severe carotid stenoses (50% to 99%) or a unilateral severe stenosis in conjunction with a contralateral carotid artery occlusion may be considered for carotid revascularization in conjunction with CABG. Little evidence exists to suggest that women with asymptomatic carotid artery disease benefit from carotid revascularization in conjunction with CABG.864 Whether the carotid and coronary revascularization procedures are performed simul- taneously or in a staged, sequential fashion is usually dictated by the presence or absence of certain clinical variables. In general, synchronous combined procedures are performed only in those with both cerebrovascular symptoms and ACS. The optimal management of patients with coexisting ca- rotid artery disease and CAD is poorly defined. Several therapeutic approaches can be used, including staged carotid endarterectomy and CABG, simultaneous carotid endarterec- tomy and CABG, or similar variations that use endovascular stenting as the primary carotid intervention. At present, no prospective RCTs comparing neurological outcomes after these different treatment strategies in patients with coexisting carotid artery disease and CAD have been reported.865 The incidence of postoperative delirium after CABG is 10%, similar to that reported after noncardiac surgery.866 868 The risk factors for postoperative delirium are similar for cardiac and noncardiac surgery and include advanced age, preexisting cognitive impairment, and vascular disease.866,868,869 The burden of intraoperative cerebral microemboli does not pre- dict the presence or severity of postoperative delirium.870 The development of postoperative delirium has been linked to functional decline at 1 month, short-term cognitive decline,871 and risk of late mortality.867,872 5.2.1.3. Postoperative Cognitive Impairment Short-term cognitive changes occur in some patients after on-pump CABG.873 875 The precise incidence depends on the timing of the postoperative assessment and the choice of criteria for cognitive decline.876,877 Similar short-term cogni- tive changes also are noted in elderly patients receiving general anesthesia for noncardiac surgery.878 880 Risk factors for short-term postoperative cognitive decline include preex- isting risk factors for cerebrovascular disease,881 preexisting central nervous system disease,882 and preexisting cognitive impairment.75 Up to 30% of candidates for CABG have been shown to have cognitive impairment before surgery.75 A few studies have reported a lower incidence of short-term cogni- tive decline after off-pump CABG than on-pump CABG,883 but most studies have shown no difference in cognitive outcomes between them.884 Studies with appropriate compar- ison groups have demonstrated that most patients do not suffer cognitive decline after CABG.885,886 For those who do, the postoperative cognitive changes are generally mild, and for most patients, they resolve within 3 months of surgery.887 Long-term cognitive decline after CABG has been re- ported,888,889 but other studies have shown that a similar degree of late cognitive decline occurs in comparison groups of demographically similar patients with CAD but without surgery, suggesting that the late decline is not related to the use of CPB.890 An RCT comparing late cognitive outcomes after on-pump and off-pump CABG has reported no differ- ence between them.891 See Online Data Supplement 34 for additional data on the role of perioperative cognitive impairment. Infection: Recommendations Class I 1. Preoperative antibiotics should be administered to all patients to reduce the risk of postoperative infection.892 897 (Level of Evidence: A) 2. A first- or second-generation cephalosporin is rec- ommended for prophylaxis in patients without methicillin-resistant Staphylococcus aureus coloniza- tion.897 905 (Level of Evidence: A) 3. Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recom- mended for prophylaxis in patients with proven or suspected methicillin-resistant S. aureus coloniza- tion.900,906 908 (Level of Evidence: B) 4. A deep sternal wound infection should be treated with aggressive surgical debridement in the absence of complicating circumstances. Primary or second- ary closure with muscle or omental flap is recom- mended.909 911 Vacuum therapy in conjunction with early and aggressive debridement is an effective adjunctive therapy.912 921 (Level of Evidence: B) 5. Use of a continuous intravenous insulin protocol to achieve and maintain an early postoperative blood glucose concentration less than or equal to 180 mg/dL while avoiding hypoglycemia is indicated to reduce the risk of deep sternal wound infec- tion.583,586,590,591,922,923 (Level of Evidence: B) Class IIa 1. When blood transfusions are needed, leukocyte- filtered blood can be useful to reduce the rate of overall perioperative infection and in-hospital death.924 927 (Level of Evidence: B) 2. The use of intranasal mupirocin is reasonable in nasal carriers of S. aureus.928,929 (Level of Evidence: A) 3. The routine use of intranasal mupirocin is reason- able in patients who are not carriers of S. aureus, unless an allergy exists. (Level of Evidence: C) Class IIb 1. The use of bilateral IMAs in patients with diabetes mellitus is associated with an increased risk of deep sternal wound infection, but it may be reasonable when the overall benefit to the patient outweighs this increased risk. (Level of Evidence: C) See Online Data Supplements 35 and 36 for additional data on mediastinitis and perioperative infection. Nosocomial infections occur in 10% to 20% of cardiac surgery patients. To prevent surgical site infections in CABG patients, a multimodality approach involving several periop- Hillis et al 2011 ACCF/AHA CABG Guideline e689 erative interventions must be considered. Preoperative inter- ventions include screening and decolonization of patients with methicillin-resistant and methicillin-sensitive S. aureus colonization and adequate preoperative preparation of the patient. Nasal carriage of S. aureus is a well-defined risk factor for subsequent infection. In proven nasal carriers of S. aureus, intranasal mupirocin reduces the rate of nosocomial S. aureus infection, but it does not reduce the rate of surgical site infection with S. aureus.928,929 Preoperative patient bath- ing, the use of topical antiseptic skin cleansers (chlorhexidine gluconate),930 932 and proper hair removal techniques (using electric clippers or depilatories rather than razors)933 937 are important measures with which to prepare the patient for surgery. Intraoperative techniques to decrease infection include strict adherence to sterile technique, minimization of operat- ing room traffic, less use of flash sterilization of surgical instruments, minimization of electrocautery933,936 and bone wax,938 use of double-gloving,938 943 and shorter operative times. identification of patients at high risk for preoperative infection allows the clinician to maximize prevention strate- gies. Superficial wound infection occurs in 2% to 6% of patients after cardiac surgery,656,944 946 and deep sternal wound infection occurs in 0.45% to 5%, with a mortality rate The etiology of deep sternal wound infection is multifac- torial. Risk factors for deep sternal wound infection are diabetes mellitus,25,27,28 obesity (body mass index 30 kg/ ),947,949,950,953,954 chronic obstructive pulmonary disease,950 prolonged CPB time, reoperation, prolonged intubation time, and surgical reexploration.945,947,955 Potentially modifiable risk factors are smoking cessation, optimized nutritional status, adequate preoperative glycemic status (with hemoglo- bin A1c 6.9%), and weight loss. The use of bilateral IMAs has been a subject of investigation as a risk factor for deep sternal wound infection. Each IMA provides sternal branches, which provide 90% of the blood supply to each hemi- sternum. As a result, IMA harvesting can compromise sternal wound healing. Although no RCTs assessing the risk of deep sternal wound infection after bilateral IMA grafting have been reported, the use of bilateral IMAs in patients with diabetes and those with other risk factors for surgical site infection increases the incidence of deep sternal wound infection.956,957 Skeletonization of the IMA may be associated with a beneficial reduction in the incidence of sternal wound complications, more evident in patients with diabetes Transfusion of homologous blood is a risk factor for adverse outcomes after cardiac surgery. Blood transfusions after CABG are correlated in a dose-related fashion to an increased risk of transfusion-related infection, postoperative infection, postoperative morbidity, and early and late death.959 962 In addition, they have been associated with a higher incidence of sternal wound infections.949,963,964 In a retrospective analysis of 15 592 cardiovascular patients, the risk of septicemia/bacteremia and Superficial and deep sternal wound infections increased incrementally with each unit of blood transfused.961 The leukocytes that are present in packed red blood cells induce the immunomodu- latory effects associated with blood transfusions. Allo- genic transfusions of blood containing leukocytes induce higher concentrations of proinflammatory mediators (such as interleukins 6 and 10) than does the transfusion of leukocyte-depleted blood.924 927,965 In patients undergoing cardiac surgery, RCTs have shown that those receiving leukocyte-filtered blood have lower rates of perioperative infection and in-hospital death than those receiving non leukocyte-filtered blood.924 927 An RCT showed that those receiving leukocyte-depleted blood had a reduced rate of ity (transfused/nonfiltered patient mortality rate, 7.8%; trans- fused/filtered at the time of donation, 3.6%; and transfused/ filtered at the time of transfusion, 3.3% [P 0.019]).927 Leukodepletion can be accomplished by the blood bank at the time of donation or at the bedside at the time of transfusion (with the use of an inexpensive in-line transfusion filter). Preoperative antibiotics reduce the risk of postoperative infection 5-fold.892 Interest has grown in administering anti- biotic prophylaxis as a single dose rather than as a multiple- dosing regimen for 24 to 48 hours, because single-dose antibiotic prophylaxis reduces the duration of prophylaxis, its cost, and the likelihood of antimicrobial resistance. Staphylococcus coagulase negative epidermidis or S. au- reus (including methicillin-resistant S. aureus) account for 50% of surgical site infections. Other organisms that are often involved are Corynebacterium and enteric gram-negative bacilli.966 968 Antibiotic prophylaxis against these organisms should be initiated 30 to 60 minutes before surgery, usually at the time of anesthetic induction, except for vancomycin, which should be started 2 hours before surgery and infused slowly to avoid the release of histamine.903,969,970 In patients without methicillin-resistant S. aureus colonization, a cepha- losporin (cefazolin, 1 g given intravenously every 6 hours, or cefuroxime, 1.5 g given intravenously every 12 hours) is the agent of choice for standard CABG.897 905 Antibiotic redosing is performed if the operation lasts 3 hours.970 Vancomycin is reserved for the patient who is allergic to cephalosporins or has known or presumed methicillin-resistant S. aureus The incidence of deep sternal wound infection has de- creased over the past 15 years despite an increased risk profile of patients undergoing cardiac surgery (ie, increased comor- bidities, obesity, diabetes mellitus, and advanced age).971 Several options are available for the treatment of deep sternal wound infection. The main treatment is surgical debridement with primary or delayed reconstruction with vascularized soft tissue (pectoral muscle or omentum).909 912,972 Conventional treatment with pectoralis flap muscle or omentum is associ- ated with procedure-related morbidities, such as destabiliza- tion of the thoracic cage, surgical trauma, and potential failure of the flap. In current practice, the vacuum-assisted closure system is often used in the treatment of mediastini- tis.913 With it, local negative pressure is applied to the open wound, accelerating granulation tissue formation and increas- ing blood supply. Such vacuum-assisted closure therapy, which is less invasive than conventional surgical treatment, has been used as standalone therapy, as a bridge to flap advancement, or as sternal preconditioning and preservation followed by titanium plate sternal osteosynthesis.913,914,973 Although several studies have suggested that vacuum- assisted closure therapy can be a successful alternative to conventional standard therapy,913 921,973 the data are from single-center retrospective studies of patients with heteroge- neous disease processes. As a result, it seems reasonable to suggest that both conventional and vacuum-assisted closure therapy can be used in the treatment of mediastinitis. 5.2.3. Renal Dysfunction: Recommendations Class IIb 1. In patients with preoperative renal dysfunction (cre- atinine clearance <60 mL/min), off-pump CABG may be reasonable to reduce the risk of acute kidney injury (AKI).974 978 (Level of Evidence: B) 2. In patients with preexisting renal dysfunction under- going on-pump CABG, maintenance of a perioper- ative hematocrit greater than 19% and mean arte- rial pressure greater than 60 mm Hg may be reasonable. (Level of Evidence: C) 3. In patients with preexisting renal dysfunction, a delay of surgery after coronary angiography may be reasonable until the effect of radiographic contrast material on renal function is assessed.979 981 (Level of Evidence: B) 4. The effectiveness of pharmacological agents to pro- vide renal protection during cardiac surgery is un- certain.982 1004 (Level of Evidence: B) See Online Data Supplements 37 to 39 for additional data on CABG and renal dysfunction. Depending on the definition used, the incidence of AKI (defined in various studies as an increase in serum creatinine concentration and/or decrease in calculated glomerular filtration rate of a certain magnitude) after isolated CABG is 2% to 3%, and the incidence of AKI requiring dialysis is 1%.1005 Risks factors for developing AKI after CABG are preoperative renal dysfunction, LV systolic dysfunction, PAD, advanced age, race, female sex, type of surgery, diabetes mellitus requiring insulin, emergency surgery, preoperative intraaortic balloon support, and congestive heart failure or shock.1005 1013 The pathogenesis of postoperative AKI is usually multi- factorial. The identification and effective management of mod- ifiable variables can minimize its occurrence. CPB can lead to renal dysfunction if renal perfusion is not adequately maintained. In addition, CPB leads to a systemic inflammatory response, with the release of 1) inflammatory cytokines (eg, kallikrein, bradykinin), 2) catecholamines, and 3) other hormones (eg, renin, aldosterone, angiotensin II, vasopressin), all of which influence renal function. The effects of hypothermia during CPB on renal function are uncertain. Two RCTs1014,1015 showed no effect of CPB temperature on renal function in patients under- going CABG, whereas a 2010 observational study1016 of 1072 subjects identified a relationship between a CPB temperature 27 C and the development of AKI (OR: 1.66; 95% CI: 1.16 to 2.39; P 0.005). Although off-pump CABG may theoretically avoid CPB-related renal injury, the cardiac manipulation that is often required to obtain adequate exposure may cause transient decreases in cardiac output, increased peripheral vasoconstric- tion, and decreased renal perfusion.1017 A meta-analysis of 6 RCTs and 16 observational studies (encompassing data from 27 806 patients) suggested a modest beneficial effect of off- pump CABG in reducing the incidence of AKI but no advantage in reducing the incidence of AKI dialysis.977 These findings were confirmed by another published RCT of 2203 patients, in which the incidence of AKI dialysis was similar among those undergoing off-pump and on-pump CABG (0.8% for off pump; 0.9% for on pump; P 0.82).61 Considering the low (approxi- mately 1%) incidence of AKI dialysis in subjects undergoing CABG, available RCTs are underpowered to detect a difference in outcome. In patients with renal dysfunction preoperatively, it might be reasonable to perform off-pump CABG to reduce the risk of AKI.974 976,978,996 During CPB, hemodilution is induced to reduce blood viscosity and plasma oncotic pressure to improve regional blood flow in the setting of hypothermia and hypoperfusion. However, an excessively low hematocrit on CPB is associated with increased adverse events and in-hospital deaths.1018 In patients undergoing isolated CABG, it has been reported that the mortality rate of patients with a single hemat- ocrit value 19% was twice that of those with a hematocrit of 25%.1019 On the basis of these data, a hematocrit 19% on CPB should be avoided. No drugs have been identified that prevent or alleviate CABG-associated AKI. N-acetylcysteine reduces proinflam- matory cytokine release, oxygen free radical generation, and reperfusion injury, but a review of 10 RCTs containing data from 1163 patients982 showed that it did not reduce the incidence of AKI and AKI dialysis.987 In several RCTs, atrial natriuretic peptide was shown to reduce peak postop- erative serum creatinine concentrations, increase urine out- put, and reduce the need for dialysis in individuals with normal renal function preoperatively, but it did not prevent AKI dialysis in patients with preexisting renal Fenoldopam, a selective dopamine D1 receptor agonist that causes vasodilatation and increases renal cortical and outer medullary blood flow, seems to exert protective renal effects in critically ill patients.994,995 A meta-analysis of the data from 1059 patients reported in 13 randomized and case-matched studies showed that fenoldopam exerts a beneficial effect on renal function. Compared with standard therapy, fenoldopam reduced the need for renal replacement therapy (5.7% versus lowered the peak value for serum creatinine concentration. Nevertheless, this beneficial effect was counterbalanced by an increased rate of hypotension and vasopressor require- P 0.008). Dopamine at low doses increases renal blood flow and blocks the tubular reabsorption of sodium. A meta-anal- ysis on the use of low-dose dopamine reported that it increased urine output and improved serum creatinine con- centrations without influencing the need for renal replace- ment therapy or the rates of adverse events or death.990 Diltiazem and mannitol have been used to prevent AKI after cardiac surgery.988 Diltiazem may inhibit the inflamma- tory response that occurs with CPB,992 whereas mannitol produces an osmotic diuresis.1000 The role of mannitol in preventing AKI is unclear.983,1004 Diltiazem does not prevent Hillis et al 2011 ACCF/AHA CABG Guideline e691 renal dysfunction.983 Contrast-induced nephropathy is a com- mon cause of AKI. It is usually self-limited and manifests its peak effect 3 to 5 days after the administration of contrast material. In patients with preoperative renal dysfunction, it is reasonable to delay surgery for several days after coronary angiography to reduce the incidence of AKI.979 981 5.2.4. Perioperative Myocardial Dysfunction: Recommendations Class IIa 1. 