Anesthesia for Myocardial Revascularization

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Chapter 13 Anesthesia for Myocardial Revascularization

Providing anesthesia care for patients undergoing coronary artery bypass grafting (CABG) continues to be a challenging yet rewarding endeavor. Surgical, anesthetic, and technologic advances continue to drive changes in clinical routines at a rapid pace, even at a time when the numbers of cases have declined because of the growth of percutaneous coronary interventions (PCIs).

Cardiac anesthesiologists who have been in practice for the past several decades have seen a variety of anesthetic and surgical practices come into vogue and fall out of favor based on new research and economic pressures. Perhaps the most striking example is the rise and fall of high-dose opioid anesthesia, which was initially driven by concern about excessive cardiovascular depression by volatile anesthetics in the 1970s and further accelerated in the mid-1980s by concerns about potential coronary steal with isoflurane. The prolonged postoperative mechanical ventilation resulting from the shift to high-dose opioids was also thought important to reduce stress on the recently revascularized myocardium. However, during the following decade, this approach was completely reversed by new basic and clinical research, such as lack of evidence for adverse effects of volatile agents, particularly as related to potential effects of coronary vasodilation on coronary steal, and by strong evidence of their benefits via rapid preconditioning; by social and economic factors (i.e., safety and efficacy of fast-tracking for most patients and recognition that time on the ventilator for many patients is an uncomfortable experience); and by the rapid rise in off-pump coronary artery bypass grafting (OPCAB), which by avoiding adverse physiologic effects of cardiopulmonary bypass (CPB) facilitates more rapid emergence and recovery in many patients.1,2 Given the increasing emphasis on pain control in all surgical patients and its reported association with enhanced postoperative outcome in a variety of surgical subgroups, there has been a resurgence in the use of neuraxial techniques in cardiac surgery, particularly in European and Asian countries.3 Although not commonly used in the United States because of logistical issues and liability concerns, the rapidly growing literature base mandates that clinicians familiarize themselves with their potential benefits and risks.

EPIDEMIOLOGY AND RISK ASSESSMENT

In 2001, coronary artery disease (CAD) was estimated to occur in 13.2 million individuals in the United States (6.4%), resulting in approximately 500,000 deaths, 2 million hospital discharges, and a societal cost of $133 billion. CABG surgery is clearly the established cornerstone of treatment of advanced degrees of CAD. Although its absolute frequency has recently declined, there is no doubt that it will remain a common procedure and that its complexity will continue to increase for many decades to come. An understanding of the basic epidemiology of CABG surgery and of risk assessment for patients undergoing it is important for the anesthesiologist for a variety of reasons, including interactions with surgeons and cardiologists; enhancing clinical management of patients by recognizing high-risk characteristics and situations where preoperative management may not be adequate (such that delay of a planned elective procedure or additional perioperative interventions are required); developing a better sense of long-term trends in surgical practice that may impact on future practice volume (e.g., growth or decline of CABG techniques); and changes in complexity of such procedures that may influence reimbursement or additional training requirements.

Preoperative risk assessment for patients undergoing CABG has evolved dramatically over the past 2 decades. The Department of Veterans Affairs in the 1970s established the first large-scale, multicenter surgical outcomes database applying rigorous statistical methodology for comparing outcomes between centers. This group and others have pioneered methodology for adjusting for different severity of illness between patients (i.e., risk adjustment) using multiple preoperative and perioperative variables thought to be of intrinsic value (usually by expert consensus) that could be easily captured and have high consistency of definition.

The Society of Thoracic Surgeons (STS) instituted a voluntary clinical database system with this approach in the early 1990s that has continued to grow rapidly as cardiac surgical groups are increasingly interested in benchmarking their practices against others.4 Many tertiary centers (e.g., Cleveland Clinic) and regional consortiums of hospitals (e.g., Northern New England Cardiovascular Disease Study Group) maintain databases, and some publish statistical models. Many states have established and maintain risk-adjusted mandatory reporting systems for hospital and individual surgeon performance (with New York State being an early and influential pioneer). A new scoring system (EuroSCORE) based on outcomes in 128 centers in eight European countries has received increasing attention. It appears to compare favorably with the STS model in North American patients.5 It is freely accessible by means of an interactive web-based calculator (www.euroscore.org) and is decidedly simpler and faster to use than the STS’s scoring system, which is now also freely accessible to the public at http://www.sts.org/sections/stsnationaldatabase/riskcalculator/index.html.

PATHOPHYSIOLOGY OF CORONARY ARTERY DISEASE

Anatomy

The anesthesiologist should be familiar with coronary anatomy if only to interpret the significance of angiographic findings. The coronary circulation and common sites for placement of distal anastomoses during CABG are shown in Figures 13-1 to 13-3.

image

Figure 13-1 Thirty-degree left anterior oblique angiographic view of the heart, which best shows the right coronary artery. Arrows indicate common sites of distal vein graft anastomoses.

(From Stiles QR, Tucker BL, Lindesmith GG, et al: Myocardial Revascularization: A Surgical Atlas. Boston, Little, Brown, 1976.)

image

Figure 13-3 Seventy-five-degree left anterior oblique angiographic view of the heart, which best shows branches of the left anterior descending and circumflex coronary arteries.

(Adapted from Stiles QR, Tucker BL, Lindesmith GG, et al: Myocardial Revascularization: A Surgical Atlas. Boston, Little, Brown, 1976.)

The right coronary artery (RCA) arises from the right sinus of Valsalva and is best seen in the left anterior oblique view on coronary cineangiography. It passes anteriorly for the first few millimeters; it then follows the right atrioventricular (AV) groove and curves posteriorly within the groove to reach the crux of the heart, the area where the interventricular septum (IVS) meets the AV groove. In 84% of cases, it terminates as the posterior descending artery (PDA), which is its most important branch, being the sole supply to the posterior-superior IVS. Other important branches are those to the sinus node in 60% of patients and the AV node in approximately 85% of patients. Anatomists consider the RCA to be dominant when it crosses the crux of the heart and continues in the AV groove regardless of the origin of the PDA. Angiographers, however, ascribe dominance to the artery, right coronary or left coronary (circumflex), that gives rise to the PDA.

The vertical and superior orientation of the RCA ostium allows easy passage of air bubbles during aortic cannulation, CPB, or open valve surgery. In sufficient concentration (e.g., coronary air embolus), myocardial ischemia involving the inferior LV wall segments and the right ventricle may occur (Fig. 13-4). In contrast, the nearperpendicular orientation of the left main coronary ostium makes air embolization much less common.

The left coronary artery arises from the left sinus of Valsalva as the left main coronary artery. This is best seen in a shallow right anterior oblique projection. The left main coronary artery courses anteriorly and to the left, where it divides in a space between the aorta and pulmonary artery (PA). Its branches are the left anterior descending (LAD) and circumflex arteries. The LAD passes along the anterior intraventricular groove. It may reach only two thirds of the distance to the apex or extend around the apex to the diaphragmatic portion of the left ventricle. Major branches of the LAD are the diagonal branches, which supply the free wall of the left ventricle, and septal branches, which course posteriorly to supply the major portion of the IVS. Although there may be many diagonal and septal branches, the first diagonal and first septal branches serve as important landmarks in the descriptions of lesions of the LAD.

The circumflex arises at a sharp angle from the left main coronary artery and courses toward the crux of the heart in the AV groove. When the circumflex gives rise to the PDA, the circulation is said to be left dominant and the left coronary circulation supplies the entire IVS and the AV node. In approximately 40% of patients, the circumflex supplies the branch to the SA node. Up to four obtuse marginal (OM) arteries arise from the circumflex and supply the lateral wall of the left ventricle. All of the previously described epicardial branches give rise to small vessels that supply the outer third of the myocardium and penetrating vessels that anastomose with the subendocardial plexus. This capillary plexus is unique in that it functions as an end-arterial system. Each epicardial arteriole supplies a capillary plexus that forms an end loop rather than anastomosing with an adjacent capillary from another epicardial artery. Significant collateral circulation does not exist at the microcirculatory level. This capillary anatomy explains the very distinct areas of myocardial ischemia or infarction that can be related to disease in a discrete epicardial artery.

CAD most commonly affects the epicardial muscular arteries with rare intramyocardial lesions. However, severe disorders of the microcirculation and primary impairment of coronary vascular reserve in normal coronary arteries have been described, especially in diabetics, female patients, and those with variant angina. Atherosclerosis in all organs is most common at the outer edges of vessel bifurcations, because in these regions blood flow is slower and changes direction during the cardiac cycle resulting in less net shear stress than in other regions with more steady blood flow and higher shear stress. Low shear stress has been shown to stimulate an atherogenic phenotype in the endothelium. Epicardial lesions can be single but are more often multiple. A combined lesion of the RCA and both branches of the left coronary artery is referred to as triple-vessel disease. The left coronary artery supplies the thickest portions of the left ventricle, at least the exterior two thirds of the IVS, and the greater part of the atria. Most bypass grafts are done on the left coronary system.

Venous drainage of the myocardium is primarily to the coronary sinus, which drains 96% of the LV free wall and septum, and the remainder of the venous return goes directly into the right atrium.6 A small fraction may enter other cardiac chambers directly through the anterior-sinusoidal, anterior-luminal, and thebesian veins.

Myocardial Ischemia and Infarction

In patients with CAD, myocardial ischemia usually results from increases in myocardial oxygen demand (Fig. 13-5) that exceed the capacity of the stenosed coronary arteries to increase their oxygen supply. However, the determinants of myocardial oxygen balance are complex, and alterations may have several effects. For example, an increase in blood pressure (i.e., increased afterload) increases wall tension and oxygen demand while also increasing coronary blood flow (CBF). It is now appreciated that myocardial ischemia may occur without changes in systemic hemodynamics and in awake patients may occur in the absence of chest pain (i.e., silent ischemia), particularly in diabetic patients.

In atherosclerotic heart disease, the fundamental lesion is an intimal lipid plaque that causes chronic stenosis and episodic thrombosis, occurring most often in an epicardial coronary artery, thereby reducing myocardial blood supply. Characteristics of the vulnerable plaque include high lipid content, a thin fibrous cap, a reduced number of smooth muscle cells, and increased macrophage activity. The lipid core is the most thrombogenic component of the plaque. Fuster described five phases in the progression of CAD by plaque morphology. Phase 1 is a small plaque present in many people younger than 30 years and usually progresses very slowly depending on the presence of risk factors associated with CAD (i.e., elevated low-density lipoprotein cholesterol). Phase 2 is a plaque with a high lipid content that has the potential to rupture. If it ruptures, it will lead to thrombosis and increased stenosis (phase 5), possibly producing unstable angina or an acute coronary syndrome. The phase 2 plaque usually does not rupture; it instead progresses onto phases 3 and 4, with enlargement and fibrous tissue organization, which may ultimately produce an occlusive plaque at phase 5.7

ANESTHESIA FOR CORONARY ARTERY BYPASS GRAFTING

Conventional CABG with CPB is still the most commonly performed cardiac surgical procedure (Box 13-1). Fast-track management with early extubation (4 to 8 hours postoperatively) has become the standard of care in nearly all centers. OPCAB is increasing steadily, although its use tends to be very frequent in some centers or infrequent in others as various surgeons have become “early adopters” or are waiting for firm evidence-based recommendations from future randomized, controlled trials. However, anesthetic management of the sickest patients undergoing multivessel operations combined with valve repair or replacement, repeat operations, and other complex procedures (e.g., ventricular septal defect repairs along with CABG after acute myocardial infarction) has changed relatively little over the past decade as the long duration of surgery usually mandates greater cumulative doses of fixed anesthetic agents with overnight or even prolonged postoperative mechanical ventilation. However, many clinicians have adopted use of infusions of shorter-acting agents (e.g., sufentanil, propofol, remifentanil), avoided large cumulative dosing of fixed agents with potentially long half-lives (e.g., midazolam), and now rely on a volatile anesthesia “base,” taking a “wait and see” attitude toward early extubation if surgery is “smooth” and physiologic parameters remain within acceptable limits (e.g., good urine output, normothermic, adequate hematocrit).

BOX 13-1 Management Strategies for Anesthesia for Myocardial Revascularization

Preoperative Evaluation and Management

Assessment of Cardiac Characteristics

Preoperative Medication Management

Intraoperative Management

5. Anesthetic induction

Management before Revascularization

7. Cannulation

Revascularization Management

2. Off-pump CABG

Management after Revascularization

Premedication

The concept of “premedication” has been evolving with new knowledge and the increasing role of the cardiac anesthesiologist as a “perioperative physician.” The cardiac anesthesiologist must be familiar with the potential benefits of administering (or hazards of not administering) a variety of cardiovascular medications, particularly anti-anginal medications, and ensure that appropriate medications are ordered for morning administration with sips of water.

Anxiolysis, Amnesia, and Analgesia

The purposes of premedication are to pharmacologically reduce apprehension and fear, to provide analgesia for potentially painful events before induction (e.g., vascular cannulation), and to produce some degree of amnesia. In patients with CAD, premedication may help prevent preoperative anginal episodes that are relatively commonly observed on continuous ambulatory ECG monitoring but are often silent clinically. Regardless of the drugs used, the clinician should be prepared to give intravenous drugs (e.g., benzodiazepines, opiates) when the patient arrives in the preoperative area to supplement inadequate sedation. All patients receive supplemental oxygen after premedication and are monitored with at least pulse oximetry during vascular cannulation (if performed before entry into the operating room suite).

A variety of drugs and regimens are used for sedation depending on the practice setting (e.g., same-day admission), the patient’s condition, and the clinician’s preferences. Use of oral, intramuscular, or intravenous benzodiazepines is very common and provides effective anxiolysis and some degree of amnesia. Diazepam remains popular as an oral premedicant (0.1 to 0.15 mg/kg), and midazolam is most popular intravenously (1 to 2 mg). Opioids, most commonly morphine (0.1 to 0.15 mg/kg) given by the intramuscular route, and fentanyl (50 to 75 μg), administered intravenously, are recommended to provide analgesia, particularly during radial artery cannulation. Scopolamine, usually given intramuscularly (0.2 to 0.4 mg) but occasionally intravenously, has been commonly used for its potent amnestic effects. Given its potential to induce delirium and disorientation, particularly in the elderly, it is less frequently used today. Acute toxicity associated with overdosage can be effectively reversed with physostigmine.

Management of Antianginal and Antihypertensive Medications

β-adrenergic receptor antagonists

For the newly trained anesthesiologist who is told to provide “perioperative β-blockade” to all patients with known CAD, or those with multiple risk factors undergoing major noncardiac (particularly vascular) surgery, it may come as a surprise that in 1972, a case series from the prestigious Cleveland Clinic admonished clinicians to withdraw such medication at least 2 weeks before CABG surgery reporting that 5 such patients died within 24 hours of surgery. Several years later, Kaplan and coworkers found that it was safe to continue β-blockade and that operative mortality was similar in patients in whom propranolol had been continued within 24 to 48 hours of surgery. Randomized trials evaluating the safety of administration of propranolol within 12 hours of surgery showed a significantly greater increase in the incidence of pre-CPB ischemia in patients withdrawn from propranolol (within 24 to 72 hours); they also recommended continuation of therapy up until the time of surgery. Further work in the 1980s documented the efficacy of continuation of β-blockers through surgery with regard to reducing pre-CPB ischemia. These studies were instrumental in laying the groundwork for the subsequent noncardiac surgery studies in the late 1980s. These led to the contemporary randomized perioperative β-blocker trials, which despite ongoing controversy regarding the exact efficacy of this therapy resulted in its becoming a clinical routine.8 Several contemporary observational studies have documented associations of β-blocker therapy with reduction in perioperative mortality in CABG patients. The largest of these by Ferguson and colleagues9 considered 629,877 patients in the STS database (1996 to 1999) in which a modest but statistically significant reduction in 30-day risk-adjusted mortality was reported (OR = 0.94, 95% CI = 0.91 to 0.97). This treatment effect was observed in many high-risk subgroups, although a trend toward increased mortality was seen in patients with an ejection fraction (EF) less than 30% (OR = 1.13; 95% CI, 0.96 to 1.33). Considerable efforts are being expended by major organizations (STS, ACC) in increasing compliance with existing guidelines for use of β-blockers at the time of hospital discharge (along with use of aspirin, statins, and angiotensin-converting enzyme [ACE] inhibitors).

other medications

Aspirin (and other platelet inhibitors such as dipyridamole) have long been recognized to have strong efficacy in the prevention of early graft thrombosis after CABG, and are a well-recognized component of primary and secondary prevention strategies for all patients with ischemic heart disease. A large observational analysis reported substantial reduction in overall mortality (1.3% vs. 4.0%) and ischemic complications of the heart, brain, kidneys, and gastrointestinal tract when aspirin was administered within 48 hours after surgery. However, patients receiving aspirin immediately before surgery have more mediastinal bleeding and may receive more blood products. A consensus conference of the American College of Chest Physicians on antithrombotic and thrombolytic therapies recommended institution of aspirin within 6 hours after CABG surgery over continuation of preoperative therapy (level of evidence Ia).10

ACE inhibitors and statins are receiving attention as agents given a variety of important “pleiotropic” effects (e.g., effects independent of their primary actions of antihypertensive effects or lipid-lowering effects, respectively).11 Potent anti-inflammatory effects and beneficial effects on endothelial function have been reported for both agents, as well as less clear effects on angiogenesis. Both agents are commonly administered acutely during PCI for their purported benefits. ACE inhibitors are widely considered to be vasculoprotective, particularly with regard to ventricular remodeling after acute myocardial infarction, and they appear to reduce damage after ischemic reperfusion (likely related to reduction in ischemic-induced vasoconstriction and reduction in leukocyte adhesion). Statins have been reported to reduce circulating levels of adhesion molecules, which have been implicated in endothelial dysfunction after CPB. Both agents appear to have direct effects on platelet aggregation and plasminogen activator inhibitors. Of the two classes of drugs, the greatest interest appears to be on the statins because of the greater number of publications and intense concurrent interest with regard to cardioprotection for noncardiac (particularly vascular) surgery. Several investigators have published similar reports of efficacy in observational cohorts of CABG patients.

Monitoring

Pulmonary Artery Catheterization

The efficacy of PA catheterization in medical and surgical settings has evolved over the past 20 years from steadily increasing use in the 1980s and 1990s to distinctly lower use now. Increasing literature evidence from a variety of experimental designs has strongly suggested that despite the substantial amount of physiologic information obtained, major clinical outcomes are little influenced. Earlier studies suggested that clinicians were unable to accurately judge filling pressures based on clinical signs and that therapy could be influenced by these data in the surgical and medical settings. Intraoperatively, PA catheterization was also shown to detect decreased left ventricular (LV) compliance associated with myocardial ischemia. It also appeared better suited for monitoring high-risk patients.

Based on the existing literature it is not possible to give precise criteria for use of a PA catheter in CABG.12 The higher the patient risk (based primarily on established preoperative clinical predictors), the more favorable is the risk-benefit ratio. Risk factors include the following:

Although most of the recent clinical reports of patients undergoing OPCAB have used, and many recommend use of PA catheterization, it is not possible to give firm recommendations on this because of the lack of evidence-based data.

Transesophageal Echocardiography

It is appreciated that the earliest signs of myocardial ischemia include diastolic dysfunction followed by systolic segmental wall motion abnormalities that occur within seconds of acute coronary occlusion. Comparison of TEE with continuous (Holter) ECGs have shown a greater incidence of segmental wall motion abnormalities than ECG changes in patients with CAD. However, it is thought that new segmental wall motion abnormalities detected in the intraoperative period may frequently occur due to nonischemic causes, particularly changes in loading conditions, and alteration in electrical conduction in the heart. The use of inotropic agents or elevations of catecholamine levels can aggravate (by increased oxygen demand) or improve wall motion. Changes in preload and afterload are likely the most important factors in the CABG setting; transient reversible segmental wall motion abnormalities are commonly related to acute myocardial stunning due to ischemia before or during weaning from CPB. TEE is highly sensitive but not specific for myocardial ischemia. The short-axis midpapillary muscle view, commonly used because of its inclusion of myocardium supplied by the three major coronary arteries, may entirely miss segmental wall motion abnormalities occurring in the basal or apical portions of the heart. These changes necessitate interrogation of additional components of the comprehensive TEE examination recommended by the ASE/SCA Task Force before and after CPB or after completion of revascularization in OPCAB. The ASA Practice Guidelines for TEE (which have not been revised since their initial publication in 1996) list the perioperative uses in patients with increased risk of myocardial ischemia or infarction as a category II indication (supported by weaker evidence and expert consensus). The indication is strengthened when ECG monitoring cannot be used to diagnose ischemia (e.g., in patients with left bundle-branch block, extensive Q waves, or ST-T abnormalities on the baseline ECG), and it is weakened when baseline segmental wall motion abnormalities are present (particularly akinesis or dyskinesis due to fibrotic, calcified, or aneurysmal myocardium). Use of perioperative TEE to evaluate myocardial perfusion, coronary anatomy, or graft patency is listed as a category III indication, but newer technology will upgrade this indication. Evaluation of ischemic mitral regurgitation by TEE may even influence the surgical management during CABG.13

Induction and Maintenance

Induction of anesthesia should take place in a calm and relaxed manner, preferably in a quiet operating room. Attention should be paid to the ambient room temperature because entry into an excessively cold operating room can elicit a sympathetic response increasing blood pressure and sometimes heart rate, particularly in the elderly and thin patients. Allaying the patient’s anxiety with premedication and calm, reassuring verbal interaction is also critical. Preoxygenation should be used and monitoring should be in place, including PA catheterization in patients at very high risk, whose condition may be unstable during or after induction.

There are two main considerations in choosing an induction technique for patients undergoing CABG. The first is LV function. Patients with good LV function often have a strong sympathetic response to surgical stimulation and may require supranormal doses of anesthetics, plus the addition of β-blockers with or without vasodilators, to control these responses. Patients with poor LV function often do not tolerate normal doses of anesthetics and are unable to produce a significant hemodynamic response to sympathetic stimulation or the response may precipitate major reductions in cardiac output.

The second consideration is the desirability of early extubation. Time spent in the intensive care unit (ICU) is one of the most expensive aspects of hospital care for CABG and is heavily influenced by postoperative ventilator management. The patient with normal preoperative LV function, assuming an uneventful intraoperative course, will have recovered 90% of baseline LV function by 4 hours postoperatively and can usually be extubated within 4 to 6 hours postoperatively if attention is paid to adequate rewarming and postoperative analgesia and if high doses of respiratory depressant anesthetics (particularly opioids and benzodiazepines) have been avoided. With the routine application of fast-track techniques, some centers have adopted immediate extubation in the operating room. However, this remains relatively uncommon and requires the close cooperation of a highly coordinated team. Because this is not always the case (particularly in teaching institutions in which residents and fellows rotate for short intervals or in some private institutions in which staffing at night is relatively low), many centers take a more measured, less aggressive approach.

After the induction of anesthesia, the pre-bypass period (for conventional CABG) may last less than an hour (e.g., only one or two saphenous vein grafts harvested) or several hours (e.g., for dissection of the left internal mammary artery, right internal mammary artery, or radial or gastroepiploic arteries after a repeat sternotomy). Surgical stimulus may be severe, such as during sternotomy or dissection around the ascending aorta. Between 50% and 70% of patients in most series presenting for CABG have normal LV function (when not ischemic) and are capable of mounting significant blood pressure and heart rate responses to noxious stimuli, whereas others with poor LV function may require pharmacologic support of the blood pressure for such stimuli. It is evident that no single approach to anesthesia for CABG procedures is suitable for all patients. Most hypnotics, opioids, and volatile agents have been used in different combinations for the induction and maintenance of anesthesia with good results in the hands of experienced clinicians.

Primary Induction Agents

Considerations for choice of induction agent in the patient undergoing CABG are based on theoretical and practical clinical considerations. Desirable goals include avoidance of hypertension and tachycardia, which is most likely to occur in the patient with normal ventricular function, hypertension, and LV hypertrophy; avoidance of hypotension and excessive myocardial depression in a patient with depressed ventricular function or with severe flow-dependent stenoses; and provision of smooth intubating conditions with a lack of effect on airway resistance.

Thiopental has been used for decades for induction in this setting. Its predominant hemodynamic effects include reduction in mean arterial pressure and cardiac output accompanied by a modest increase in heart rate. These are believed to result from a combination of direct myocardial depression, venodilation, and a decrease in central sympathetic outflow. The use of thiopental in most centers has declined substantially in favor of propofol. Adverse effects on airway resistance, a greater propensity to elicit bronchospasm, and a greater association with postoperative nausea and vomiting are other potential factors.

The clinical effects of propofol are in general similar to those of thiopental. However, it has numerous advantages over thiopental based on its predictable pharmacokinetics and dynamics. Based on these, it has been widely adopted in the operating room for anesthesia delivery by computer-controlled devices and for postoperative ICU sedation. It is often used for sedation after CABG surgery.14

Inhalation Anesthetics and Myocardial Protection

There is steadily increasing evidence that inhalation anesthetic agents have favorable properties in patients undergoing CABG surgery, particularly in comparison to total intravenous anesthesia approaches. Along with the now routine use of fast-track anesthesia techniques, there has been a major resurgence in their use as the primary anesthetic for cardioprotection, with opioids and benzodiazepines increasingly relegated to a “supplemental” status.

myocardial protection and preconditioning

Inhalation anesthetics are thought to protect the myocardium against ischemia by their ability to mimic ischemic preconditioning. They have been shown to reduce myocardial infarction size after periods of ischemia, protect the heart against postischemic LV dysfunction, and reduce the incidence of arrhythmias after cardiac surgery. Intravenous anesthetics such as propofol do not appear to have the same cardioprotective properties. There is increasing evidence from prospective randomized clinical studies in patients undergoing CABG surgery that volatile anesthetic agents should be part of the anesthetic regimen, particularly in patients at high risk for ischemic events.15

The exact mechanisms of preconditioning are still actively under investigation. After the administration of a preconditioning signal such as ischemia, inhalation anesthetics, opioids, bradykinin, or nitroglycerin, membrane-bound receptors (adenosine A1, adrenergic, bradykinin, muscarinic, delta-1 opioid) coupled to inhibitory G-proteins are activated. Consequently, products of intracellular transduction pathways (e.g., protein kinase C, tyrosine kinases, mitogen-activated protein kinases) mediate the opening and stabilization of adenosine triphosphate (ATP)-sensitive mitochondrial KATP channels, the effectors thought to be mainly responsible for the preconditioning phenomenon. Increased formation of nitric oxide, free oxygen radicals, and enzymes such as cyclooxygenase-2 are also involved in the preconditioning process.

There is increasing evidence that the choice of anesthetic in patients at risk for cardiac events may have a significant effect on myocardial protection. Inhalation anesthetics have multiple cardioprotective effects, including triggering the preconditioning cascade and blunting of reperfusion injury. The mode of administration, dose, timing, differences between various inhalation agents, patient selection, and the impact on cardiac morbidity and mortality remain to be more precisely elucidated by larger randomized clinical trials.

sevoflurane

Sevoflurane has been increasingly used during cardiac surgery owing to its favorable hemodynamic effects and cardioprotective properties. It is a potent trigger of the preconditioning cascade.16 It has beneficial effects on intraoperative myocardial function after CPB, and it may also favorably influence long-term morbidity and mortality after CABG.

Choice of Technique

A wide variety of techniques have been used for anesthetic induction and maintenance for CABG. Hemodynamic alterations such as hypotension after induction, or hypertension and tachycardia at intubation, are not infrequent. They can be readily treated with small doses of vasopressors, such as phenylephrine or ephedrine for hypotension, or deepening anesthesia or adding β-blockade to treat hyperdynamic responses. No single technique was demonstrated to be superior in terms of reduced intraoperative ischemia, postoperative myocardial infarction, or death.

Interest in the use of thoracic epidural anesthesia (TEA) for cardiac surgery has steadily increased over the past 15 years. It has been long appreciated that thoracic sympathectomy has favorable effects on the heart and coronary circulation. Its coronary vasodilating effects have been well documented and it has been used to treat unstable angina for many years. There has been a resurgence in interest, and it is frequently used as a supplement to general anesthesia for cardiac surgery, particularly in Europe and Asia (Fig. 13-7). However, in the United States, medicolegal concerns about the rare but present danger of a devastating neurologic injury and the substantial logistical issues regarding placement the night before surgery, increased time to place relative to inducing general anesthesia, and the potential for cancellation of a case in event of bloody return are major limiting factors. The advent of fast-tracking could be considered a potential driving force (e.g., ability to extubate faster and have a more comfortable patient with TEA), although most evidence suggests that a wide variety of techniques can be effectively used to facilitate early extubation and that the cardioprotective effects of volatile agents may be as effective as the beneficial effects of thoracic sympathectomy.

TEA in conscious patients (with supplemental intravenous sedation) appears to be increasingly used for off-pump CABG (OPCAB or minimally invasive direct CABG [MIDCAB] approaches) with reports from diverse settings (e.g., Germany, Turkey, India) and has been designated conscious off-pump coronary artery bypass grafting (COPCAB). In most series, 2% to 3% of catheters are unable to be placed in potential candidates and 2% to 3% of patients are converted to general anesthesia because of a large pneumothorax or incomplete analgesia. Patients were fast-tracked, an ICU stay was not used, and some were discharged from the hospital the day of surgery. Patient acceptance appeared to be quite high. No complications related to TEA were observed. This is clearly an area of growing interest and one that has potential advantages, particularly for countries with different health care systems, resource constraints, and sociocultural differences.

Safety concerns are a major consideration in use of TEA in this setting given chronic use of antiplatelet agents, use of systemic anticoagulation and platelet inhibition for acute therapy of unstable angina, and systemic anticoagulation and potential coagulopathy induced by CPB. The true incidence of serious complications (particularly epidural hematoma) is unknown. A widely quoted estimate is 1 in 1528 for TEA with 95% confidence. Intrathecal risks are quoted as 1 in 3610. These estimates were based on consideration of more than 4000 reported cases (cardiac surgery) in which no complications were reported. Chakravarthy and coworkers presented an audit of 2113 cardiac surgery TEA cases over a 13-year period with no permanent neurologic deficits, a 0.9% dural puncture rate, and 0.2% transient neurologic deficits.19

FAST-TRACK MANAGEMENT FOR CORONARY ARTERY BYPASS GRAFTING

The fast-track clinical pathway encompasses a variety of perioperative (and after hospital discharge) management strategies, but early extubation is the one that has received the greatest attention (Box 13-2). Because it is a simple, continuous variable (e.g., hours to extubation), it is one that many observational reports and a smaller number of randomized, controlled trials have reported. It also appears to be the only one that has resulted in meta-analyses showing the practice is safe and effective.20 Early extubation is acknowledged as a key component of the fast-track clinical pathway and one that was considered perhaps the most radical change in practice during the peak of scrutiny of the fast-track pathway (Box 13-3).

CORONARY ARTERY BYPASS GRAFTING WITHOUT CARDIOPULMONARY BYPASS

Off-pump coronary artery bypass grafting is the single greatest change in CABG techniques in the past 2 decades.21,22 Although this term encompasses a range of surgical approaches (based on the degree of invasiveness encompassing full, limited, or no sternotomy), the technique that is most commonly performed is OPCAB with a full sternotomy. The precise number of such procedures performed remains largely speculative; however, it is likely in the 20–30% range at the present time. Surgeons appear to adopt it enthusiastically or not at all, an unsurprising finding given the unsettled state of the literature. Although the literature base is increasing rapidly, the final word is still years away (given several large ongoing randomized, controlled trials). However, it appears that OPCAB is as effective as routine CABG, is safer for certain patient subsets, and may be associated with improvement in several outcomes at slightly lower resource use. Its use is likely to increase, especially for high-risk patients with serious comorbidities associated with higher morbidity/mortality from CPB (e.g., severe cerebrovascular and renal disease). The clinician will immediately notice that the pace and tempo of anesthetic management differs substantially from that of conventional CABG. The focused involvement of the anesthesiologist is perhaps more important in OPCAB than during on-pump CABG (including use of TEE and PA catheterization).

Although OPCAB is perceived as a contemporary development, surgery on the beating heart was first performed in the 1950s and early 1960s, preceding the widespread use of CPB-based CABG because of the slower development and application of CPB techniques in the late 1960s. In the late 1980s and early 1990s, introduction of the short-acting β-blocker esmolol led some surgeons to “experiment” with OPCAB (on the LAD) by lowering of the heart rate. However, it was not until the mid- to late 1990s when surgical researchers developed efficient mechanical stabilizer devices that minimized motion around the anastomosis site (independent of heart rate) that this technique became widespread. The ability to expose the posterior surface of the heart to access the posterior descending and the circumflex vessels using suction devices usually placed on the apex of the heart, pericardial retraction sutures, slings, or other techniques, without producing major hemodynamic compromise, was critical for multivessel application of this technique. This is commonly referred to as verticalization, in contrast to displacement for the LAD and diagonal anastomoses.

OPCAB extends the range of surgeon-induced hemodynamic changes the anesthesiologist encounters relative to routine CABG. The skilled cardiac anesthesiologist must be able to anticipate and communicate with the surgeon to minimize the adverse impact of these changes on the heart and other important organs. The surgical manipulations involve a variety of geometric distortions of cardiac anatomy (most notably compression of the right ventricle and, to a lesser degree, some distortion of the mitral valve annulus). The magnitude of distortion varies with the patient’s individual anatomy (most notably the size and shape of the right and left ventricles), the skill of the surgeon in placement of stabilizer devices, use of “deep” pericardial stay sutures (which facilitate forward superior apical displacement for LAD anastomosis), and manipulation of the pleural space (e.g., right pleural incision to create space for the compressed right ventricle). With a skilled surgeon, the changes are usually modest or easily treated with the Trendelenburg position, use of vasoconstrictors or inotropes, and judicious volume expansion. However, severe changes due to acute ischemia, mitral regurgitation, or unrecognized right ventricular compression may occur, necessitating emergent conversion to CPB.

Outcomes in Off-Pump Coronary Artery Bypass Grafting

Several investigators and working groups have comprehensively reviewed outcomes in patients undergoing OPCAB. Investigators have analyzed 37 randomized trials of 3369 patients with comparable treatment groups with the exception of a marginal difference in number of grafts performed (2.6 OPCAB versus 2.8 CABG).21 All but one of the studies specifically excluded “high-risk” patients. Although various definitions were used, most excluded patients with low ejection fractions, repeat procedures, and renal failure, and several studies excluded patients with diseased circumflex vessels. As expected, not all studies reported on all outcomes. The investigators found no significant differences in 30-day or 1- to 2-year mortality, myocardial infarction, stroke (30 day and 1 to 2 years), renal dysfunction, need for IABP, wound infection, or reoperation for bleeding or reintervention (for ischemia). OPCAB was associated with a significant reduction in atrial fibrillation (OR = 0.58), numbers of patients transfused (OR = 0.43), respiratory infections (OR = 0.41), need for inotropes (OR = 0.48), duration of ventilation (weighted mean difference [WMD] of 3.4 hours), ICU length of stay (WMD of 0.3 day), and hospital length of stay (WMD of 1.0 days). Changes in neurocognitive dysfunction were not different in the immediate postoperative period; they were significantly improved at 2 to 6 months (OR = 0.57), but there were no differences seen at 12 months. The critical issue of graft patency was addressed in only four studies, and these varied substantially with regard to when this was assessed (3 months in two and 12 months in two). Only one study reported a difference (reduction in circumflex patency with OPCAB). Because of the small numbers of patients, the overall data for this category were considered inadequate for meta-analysis. A large-scale, randomized, controlled trial is being conducted by the Department of Veterans Affairs with evaluation of graft patency at 1 year postoperatively. Four randomized, controlled trials have analyzed quality of life. Various methods precluded inclusion in the meta-analysis, but it generally appears there is little difference between operations. Of the 20 trials reporting conversion rates, 8% of OPCAB patients required conversion to CABG, whereas only 1.7% were converted from CABG to OPCAB. The conversion rate for OPCAB in these low- to medium-risk patients is substantial and would be expected to be even higher in higher-risk patients with greater disease burdens, more complex lesions, or impaired ventricular function in whom tolerance of stabilization and verticalization may be less. The anesthesiologist must be prepared for rapid institution of CPB at all times.

The ultimate adoption of OPCAB resides in demonstration of similar rates of long-term graft patency. Given the longevity of most grafts, particularly the internal mammary artery (>15 years), this will take some time to be conclusively established. With ongoing technologic advances, it is likely this approach will continue to expand in numbers of patients and surgical complexity.

MYOCARDIAL ISCHEMIA DURING REVASCULARIZATION

Hemodynamic Changes Related to Myocardial Ischemia

Besides ECG abnormalities, some hemodynamic changes should alert the anesthesiologist to the possibility of intraoperative myocardial ischemia. The association of tachycardia with hypotension or increased LV filling pressure (both of which reduce coronary perfusion pressure [CPP] is a particularly undesirable combination jeopardizing the oxygen supply-demand relationship. Figure 13-8 demonstrates how hypertension in the absence of tachycardia, in response to surgical stress (skin incision), can be associated with pulmonary hypertension, elevated pulmonary capillary wedge pressure, and prominent A and V waves on the PCWP waveform. Although ECG changes occurred later, the early hemodynamic abnormalities almost certainly were the result of ischemic LV dysfunction. Treatment included deepening anesthesia and administering a nitroglycerin infusion.

LV diastolic dysfunction detected with TEE is the earliest change identified after coronary artery occlusion, and it often precedes the development of abnormal systolic function. Regional wall motion abnormalities also have been described as early signs of ischemia. They occur within seconds of inadequate blood flow or oxygen supply. Regional wall motion abnormalities detected by TEE have been shown to be a more sensitive method of detecting myocardial ischemia in patients undergoing CABG compared with ST-segment changes. Myocardial ischemia on repositioning the heart during OPCAB can be the cause of a sudden onset of mitral regurgitation or worsening of preexisting mitral regurgitation, both of which can be detected with TEE monitoring.

Hypotension, tachycardia IV α-agonist Phenylephrine, 25-100 μg Alter anesthetic regimen (e.g., lighten) Norepinephrine, 2-4 μg IV nitroglycerin when normotensive Nitroglycerin, as above Hypotension, bradycardia

Hypotension, normal heart rate No abnormality

* Ensure adequacy of oxygenation, ventilation, and intravascular volume status and consider surgical factors, such as manipulation of heart of coronary grafts.

Tachyarrhythmias (e.g., paroxysmal atrial tachycardia, atrial fibrillation) should be treated directly with synchronized cardioversion or specific pharmacologic agents.

Bolus doses (25-50 μg) and high infusion rate may be required initially.

Intravenous Nitroglycerin

Since the introduction in 1976 by Kaplan and colleagues of the V5 lead to diagnose myocardial ischemia and intravenous nitroglycerin to treat it, nitroglycerin has been one of the mainstays in the treatment for perioperative myocardial ischemia. Intravenous nitroglycerin acts immediately to reduce LV preload and wall tension, primarily by decreasing venous tone in lower doses, whereas in larger doses it may also decrease arterial resistance and epicardial coronary arterial resistance. Nitroglycerin has been shown to consistently decrease LV filling pressure, systemic blood pressure, and myocardial oxygen consumption and to improve LV performance in patients with severe dysfunction. It is most effective in treating acute myocardial ischemia with induced ventricular dysfunction accompanied by sudden elevations in LVEDV, LVEDP, and PA pressure. These elevations in LV preload and wall tension further exacerbate perfusion deficits to the ischemic subendocardium and usually respond immediately to nitroglycerin.

Preoperatively, it is often used to treat patients with unstable angina or ischemic mitral regurgitation and to limit the size of an evolving myocardial infarction, reduce associated complications, and reverse segmental wall motion abnormalities. In the pre-CPB period and during OPCAB, nitroglycerin is used to treat signs of ischemia such as ST-segment depression, hypertension uncontrolled by the anesthetic technique, ventricular dysfunction, or coronary artery spasm (Box 13-4). During CPB, nitroglycerin can be used to control the mean arterial pressure; however, nitroglycerin is not always effective in controlling mean arterial pressure during CPB (approximately 60% of patients respond) because of alterations of the pharmacokinetics and pharmacodynamics of the drug with CPB. Factors contributing to the reduction of its effectiveness include adsorption to the plastic in the CPB system, alterations in regional blood flow, hemodilution, and hypothermia. Different oxygenators and filters sequester up to 90% of circulating nitroglycerin during CPB. After revascularization, nitroglycerin is used to treat residual ischemia or coronary artery spasm and reduce preload and afterload, and it may be combined with vasopressors (e.g., phenylephrine) to increase the CPP when treating coronary air embolism (Box 13-5).

Intravenous nitroglycerin has been compared with other vasodilators such as nitroprusside and the calcium channel blockers during CABG and in other clinical situations. Kaplan demonstrated that nitroglycerin was preferable to nitroprusside during CABG. Both drugs were shown to control intraoperative hypertension and to decrease myocardial oxygen consumption; however, nitroglycerin improved ischemic changes on the ECG but nitroprusside did not. The lack of improvement in the ischemic ST segments with nitroprusside was thought to result from a decrease in CPP or the production of an intracoronary steal.

Calcium Channel Antagonists

Calcium antagonists have been found to be cardioprotective against reperfusion injury. This is due to their energy-saving actions of negative inotropy and chronotropy. These antagonists have also been shown to reduce reperfusion arrhythmias and attenuate myocardial stunning. In a review of methods to reduce ischemia during OPCAB, Kwak included the calcium antagonists along with newer drugs such as nitric oxide–releasing agents, free radical scavengers, and Na+/H+ exchange inhibitors in the management of ischemia-reperfusion injury.23

Nicardipine is a short-acting dihydropyridine calcium antagonist similar to nifedipine but possessing a tertiary amine structure in the ester side chain. Unlike other available dihydropyridines, nicardipine is stable as a parenteral solution and therefore can be administered intravenously. It has highly specific modes of action, which include coronary antispasmodic and vasodilatory effects and systemic vasodilation. Among the calcium antagonists, nicardipine is unique in its consistent augmentation of coronary blood flow and its ability to induce potent and more selective vasodilator responses in the coronary bed than in the systemic vascular bed. Other important hemodynamic effects include reductions in blood pressure and systemic vascular resistance and increases in myocardial contractility and cardiac output. Nicardipine also produces minimal myocardial depression and significant improvement in diastolic function in patients with ischemic heart disease. Intravenous doses of 5 to 10 mg of nicardipine administered to patients with CAD produce therapeutic plasma levels. Plasma concentrations decline in a biphasic manner, with an initial half-life of 14 minutes and a terminal half-life of 4.75 hours. Clearance of nicardipine results mainly from its metabolism by the liver, and excretion is primarily through bile and the feces. It undergoes rapid and extensive first-pass hepatic metabolism with the production of inactive metabolites. Nicardipine’s rapid onset and cessation of action make it an attractive drug for the perioperative management of hypertension or myocardial ischemia. It has been administered to control hemodynamics during and after noncardiac vascular surgery and CABG.

Esmolol

Hypertension, tachycardia, arrhythmias, and myocardial ischemia from sympathetic stimulation are common occurrences in the perioperative period. Despite the benefits of early use of β-blockers in the treatment of myocardial ischemia, the relatively long half-life and prolonged duration of action of previously available β-blockers have limited their usefulness during surgery and the immediate postoperative period. The introduction of esmolol, an ultra-short-acting cardioselective β1-blocker with a half-life of 9 minutes because of rapid esterase metabolism, provides a β-blocker that is extremely useful in the perioperative period. Esmolol has been shown to be effective in treating patients with acute unstable angina or during acute coronary occlusion. During percutaneous transluminal coronary angioplasty, esmolol was also found to reduce the amount of ST-segment elevation and the onset of segmental wall motion abnormalities. Esmolol has been used during CABG in a prophylactic manner to prevent hypertension, tachycardia, and myocardial ischemia. Before the introduction of newer stabilizing mechanical devices, it had been used frequently during OPCAB procedures to slow the heart rate during the surgical procedure. Esmolol has also been used to treat intraoperative hypertension, tachycardia, and myocardial ischemia. Bolus doses of 1.5 mg/kg have been found to be effective in treating ST-segment changes in patients with CAD. More commonly, a smaller bolus dose is used and is combined with an infusion of esmolol. Bolus doses ranging from 0.5 to 1.0 mg/kg have been used, followed by infusions of 50 to 300 μg/kg/min. These doses have been found to effectively treat increases in heart rate that occur during surgery and to block the β-adrenergic effects of catecholamines associated with surgical stress.

Coronary Artery and Arterial Conduit Spasm

Spasm has usually been associated with profound ST-segment elevation on the ECG, hypotension, severe dysfunction of the ventricles, and myocardial irritability. Many hypotheses have been put forward to explain the origin of coronary artery spasm; some of the mechanisms that may play a role are demonstrated in Figure 13-9. The mechanism of postoperative spasm may or may not be the same as that underlying Prinzmetal’s variant angina, but the same stimuli seem to be present and therapy is usually effective with a wide range of vasodilators such as nitroglycerin, calcium channel blockers, milrinone, or combinations of nitroglycerin and calcium channel blockers in both situations. Arterial grafts such as the internal mammary artery, and particularly radial artery grafts, are prone to spasm after revascularization and its prevention and recognition are crucial to prevent serious complications.

SUMMARY

REFERENCES

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