The patient with coronary artery disease scheduled for noncardiac surgery

The Patient With Coronary Artery Disease Scheduled for Noncardiac Surgery Erin A. Sullivan

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~ERIOPERATIVE CARDIAC events represent a significant cause of morbidity in patients undergoing noncardiac surgery. Perioperative myocardial ischemia predicts unfavorable outcomes and occurs in as many as 41% of patients with coronary artery disease or cardiac risk factors. Obtaining a comprehensive patient history is a critical part of the diagnostic risk and stratification process. Many factors associated with perioperative morbidity are amenable to treatment and early, aggressive management seems to have beneficial effects. Newer alternatives to conventional anesthetic management are undergoing evaluation and may turn out to be the key to preventing or at least reducing the incidence of morbid postoperative cardiac events. This article discusses preoperative assessment, intra-operative monitoring and anesthetic management, postoperative management, and newer anesthetic techniques for the cardiac patient scheduled for noncardiac surgery. PREOPERATIVE ASSESSMENT

Approximately 7 million Americans anesthetized annually for noncardiac surgery have either overt or asymptomatic cardiovascular disease.l'2 The assessment of high-risk surgical patients should include an evaluation of the patient's probability of having coronary artery disease along with the quality of their left ventricular function. Once this has been determined, further workup may be warranted, particularly if the morbidity and mortality for the planned surgical procedure is high. Depending on the results of the patient's workup, further interventions such as coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or preoperFrom the Department of Anesthesiology, UCLA School of Medicine, Los Angeles, CA. Address reprint requests to Erin A. Sullivan, MD, Department ofAnesthesiology, UCLA School of Medicine, 10833 Le Conte Avenue Los Angeles, CA 90024-1778. Copyright 9 1995 by W.B. Saunders Company 02 77~0326/95/1403-001055.00/0 236

ative insertion of an intra-aortic balloon pump may be necessary before proceeding with elective noncardiac surgery, Coronary Artery Disease and R i s k Factors

More than 6 million Americans have documented coronary artery disease manifested by a prior myocardial infarction or the occurrence of angina? Many studies show that there is an increased risk of perioperative morbidity and mortality in patients with a history of coronary artery disease. 4-6 When assessing a patient's probability for coronary artery disease, it is important to obtain a detailed medical history with particular attention to the following: (1) a history of angina (stable or unstable); (2) a history of previous myocardial infarction; (3) signs and symptoms of congestive heart failure; (4) a history of dysrhythmias or palpitations; (5) a history of shortness of breath, paroxysmal nocturnal dyspnea or orthopnea; (6) an assessment of exercise tolerance (ie, the patient's ability to climb stairs or walk distances; (7) a history of prior cardiac angioplasty or cardiac surgery; (8) family history; (9) a history of smoking; (10) a history of hypercholesterolemia; (1 1) a history of diabetes mellitus and associated autonomic dysfunction; and (12) a history of hypertension. It is also important to perform a thorough physical examination. Findings of jugular venous distention, heart murmurs, ectopic cardiac beats, displaced point of maximal impulse, pulmonary congestion, and peripheral edema may indicate cardiac disease. In general, patients with a history of unstable angina are at high risk for perioperative cardiac events and should undergo further medical and/ or surgical treatment for their coronary artery disease unless delay of the noncardiac surgical procedure is impossible. 6 Those patients with stable angina have a variable occurrence of perioperative myocardial infarction that seems to depend on the surgical procedure. Although extensive coronary artery disease may be present, patients with a history of previous myocardial

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THE PATIENT WITH CORONARY ARTERY DISEASE

infarction may have already infarcted the myocardium at risk leaving no further areas predisposed to further ischemic damage. Asymptomatic patients with risk factors for coronary artery disease are perhaps the most difficult to assess for probability of significant risk. The timing of a myocardial infarction in relationship to the planned surgical procedure has generated much discussion. Traditionally, a myocardial infarction that occurs within 6 months of a surgical procedure is associated with an increased rate ofperioperative reinfarctionY ,8 It has recently been suggested that the rate of reinfarction in these patients can be attenuated through the use of medications (ie, beta-blockers), invasive monitoring, and prolonged intensive care unit stays. 7'9 Other interventions that improve coronary artery blood flow (ie, angioplasty, and thrombolytic therapy) may reduce the myocardium at risk. More recently, thoracic epidural anesthesia is being used in patients with coronary artery disease and unstable angina to improve coronary artery blood flow a n d blunt the sympathetic nervous system effect on the heart. 1~ Some authors suggest that the perioperative risk for reinfarction in a patient with a recent myocardial infarction is not only dependent on timing, but also dependent on the extent of the patient's myocardium at risk. 13 We have already mentioned several patient risk factors that indicate a higher probability of coronary artery disease. There are a few that deserve some further explanation. Diabetes is well known to be a risk factor for atherosclerotic disease and is frequently associated with autonomic dysfunction (believed to be the best predictor of silent myocardial ischemia in these patients).14 Autonomic dysfunction may also be responsible for producing exaggerated blood pressure responses to anesthetic agents. This may lead to hemodynamic instability, inadequate coronary artery perfusion pressure, and subsequent myocardial ischemia. Hypertension exists in a significant percentage of the population presenting for surgical procedures. Approximately 40% of these patients are either untreated or inadequately managed pharmacologically.15 Hypertension may also indicate congestive heart failure and ischemic myocardial disease. Recent criteria describing classification schema for hypertension now include both sys-

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tolic and diastolic levels that are used to assess c a r d i o v a s c u l a r risk. 16 It is well documented that in the perioperative period, uncontrolled or inadequately controlled hypertension is associated with an increased incidence of ischemia, dysrhythmias, myocardial infarction, and cerebral vascular insult. ~7 Therefore, strict attention should be applied to adequately controlling a patient's blood pressure in the preoperative period. Goldman et al implicated congestive heart failure as the factor that contributed to the highest risk for perioperative morbidity. 5 Congestive heart failure may result from ischemic myocardial disease with subsequent left ventricular dysfunction, diastolic dysfunction, or dilated cardiomyopathy. Careful fluid and hemodynamic management is essential for these patients.

Preoperative Testing In addition to evaluating a high-risk patient's electrocardiogram (looking for ischemic changes, dysrhythmias, or conduction defects) or chest radiograph (looking for abnormal cardiac silhouette, pulmonary vascular congestion, and atherosclerosis of the aorta), other more invasive studies may be required. A general rule to follow when deciding whether or not to order these more invasive studies follows: if patient care for an elective surgical procedure will be modified based on the test results, perform the test. If your an-. esthetic management will not change despite the test results, it probably is not worth the monetary cost to the patient or the potential risk of the test to the patient. Another consideration for the patient with high probability of or documented coronary artery disease is the type of surgical procedure that the patient will undergo. A low incidence of cardiac morbidity is associated with transurethral prostatectomy or minor ortfiopedic procedures. 18 Surgical procedures involving aortic cross clamping have an extremely high incidence of ischemia and cardiac morbidity. A recent study conducted by Shah et al included abdominal, thoracic, aortic, and peripheral vascular operation as an independent and additive predictor ofperioperative myocardial infarction and/or cardiac death. 6 Perhaps in this instance further cardiovascular testing or intervention would prove useful in patients with cardiac risk factors] 9

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Many testing modalities may be incorporated into the preoperative evaluation of patients at risk for coronary artery disease. Bayes' theorem dictates that the predictive value of a test in a given patient is a function of the sensitivity and specificity of the test, and the pretest probability of disease. 2~Patients with a high pretest probability of disease often do not benefit from noninvasive testing. In this population, an invasive test such as coronary angiography may be the best initial evaluation. Additionally, the appropriate sequencing of diagnostic tests has been shown to not only improve the sensitivity and specificity for coronary artery disease, but also improves risk stratification.21,22 Detailed algorithms for the use of cardiac diagnostic tests are well described 1,23 but beyond the scope of this article. PERIOPERATIVE INTERVENTIONS

The benefits of coronary artery revascularization before noncardiac surgery in patients with significant coronary artery disease remains controversial. Although there are studies supporting the benefit of coronary artery bypass grafting before vascular surgery in young, nondiabetic patients with documented coronary artery disease, they were not randomized, thus, producing a strong source of bias. 24'25 The group with the greatest potential benefit from revascularization, vascular surgery patients, have a high morbidity and mortality rate after coronary artery bypass grafting. Retrospective studies using percutaneous transluminal coronary angioplasty before vascular surgery 26,27 show low perioperative cardiac morbidity rates. The lower morbidity and mortality rates for percutaneous transluminal coronary angioplasty may benefit patients with coronary artery disease and prove to be a much lower risk than coronary artery bypass grafting. Many have advocated preoperative optomization of a patient's cardiac status using invasive hemodynamic monitoring as a means of reducing perioperative cardiac morbidity and mortality in high-risk patients. Unfortunately, the rate of complication remains high] There is evidence to report that the use of intra-aortic balloon counterpulsation may provide an adjunct in the stabilization of patients with unstable angina and severe coronary artery disease who require urgent noncardiac surgery. 28-3~ A study by Siu et al 3~

describes the perioperative use of the intra-aortic balloon pump in patients with unstable angina and coronary artery disease undergoing urgent noncardiac surgery. They had no perioperative cardiac events while the intra-aortic balloon p u m p was in place. There were two postoperative cardiac events (myocardial infarction and congestive heart failure) in the first postoperative week after the intra-aortic balloon pump was removed. The intra-aortic balloon augments diastolic aortic pressure which increases coronary artery perfusion pressure, reduces afterload, and decreases myocardial oxygen demand. 32 Potential serious complications of intra-aortic balloon pumps include arterial thrombosis, gas embolism, infection, and vascular dissection. These complications may occur in as many as 20% of patients, and are most prevalent in women, patients with peripheral vascular disease, and patients undergoing intra-aortic balloon pump insertion percutaneously. 33 It may be argued that the cardiac risks outweigh the risks for a complication from intra-aortic balloon pump insertion. Early removal of the intra-aortic balloon pump in the postoperative period may diminish its overall effectiveness as the risk of myocardial infarction may persist until the fifth or sixth postoperative day with mobilization of fluids and ambulation. 34 INTRA-OPERATIVE MANAGEMENT

After a thorough evaluation of risk factors and once the decision is made to proceed with the noncardiac surgery, anesthetic planning is straightforward. The patient should receive their prescribed medications on the morning ~ of surgery. Premedication is dependent on the degree of the patient's anxiety as well as their underlying pathophysiology. Another important factor is the anesthesiologist's plan for anesthesia. Thus, some patients a n d / o r practitioners will require a heavy premedication whereas others require very little. As long as the risk to benefit ratio is maintained in favor o f patient benefit, either m e t h o d is feasible. There is no single correct anesthetic for the patient with coronary artery disease undergoing noncardiac surgery. Some anesthesiologists prefer to use narcotic based anesthetics while others will prefer inhalation anesthetics. Still others, the author included, prefer to combine general and re-

THE PATIENT WITH CORONARY ARTERY DISEASE gional anesthetic techniques. The benefits of general versus regional anesthesia have been discussed at length. 35'36 Regardless of the choice of anesthetic technique, the goal is the same: maintain stable hemodynamics, adequate tissue perfusion and oxygen delivery, and balance myocardial oxygen supply and demand. Yet another controversial issue is the type of intra-operative monitoring that is best for patients with coronary artery disease presenting for noncardiac surgery. Although there exists some limited evidence that the use of pulmonary artery catheters and transesophageal echocardiography are not only helpful but necessary tools for some anesthesiologists, their proper and optimal use does require special training. For the trained anesthesiologist, these tools may facilitate the manipulation of a variety of end-points in the high-risk patient. Unfortunately, the data to document a true difference in patient outcome is scant. In addition to the standard monitoring described in the American Society of Anesthesiologists guidelines for routine anesthetics, consider therapeutic goals. The monitor should not only warn or remind us of duty, but should also provide relevant clinical information that assists our therapeutic interventional care of the patient for his benefit. With this argument in mind, the author recommends the following monitors in addition to the standard ones: an arterial catheter and central venous pressure line are useful for monitoring beat-to-beat blood pressure and heart rhythm and cardiac filling pressures; a central venous line also provides an avenue for the delivery of vasoactive drugs if necessary. Arterial lines may also serve as an access for obtaining arterial blood gases and other laboratory values. Central venous gases and central venous oxygen saturation may provide us with an approximation of cardiac output and tissue oxygen delivery via the Fick equation. This author does not mean to imply that pulmonary artery catheters are not helpful. The point of emphasis for the use of pulmonary artery catheters has already been stated: in order to benefit the patient, the clinician must possess the skill, knowledge, and training to interpret the data generated and be able to render beneficial therapy.

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One of the major monitoring goals in caring for the patient with coronary artery disease is the detection and prevention of myocardial ischemia. Ischemia is a potentially reversible condition that may be a marker of the increased perioperative risk for a morbid cardiac event. Studies using single- or multiple-lead electrocardiography (ECG) show that 18% to 78% of patients with coronary artery disease undergoing noncardiac or cardiac surgery experience ST segment depression. ST segment elevation occurs in less than 5% of these patients. 37 Most ECG ischemia is detected in the lateral leads. Patients monitored with a continuous 12-lead ECG during surgery show that 90% of the ischemic S T s e g m e n t changes could be identified by examining leads V4 and Vs; 75% could be identified by looking at V5 alone. 38 Previous studies of the mechanisms for intraoperative ischemia indicate that most episodes ofintra-operative ischemia were related to an increase in myocardial oxygen demand: hypertension, tachycardia, and increases in pulmonary capillary wedge pressure. Studies conducted recently found that most intra-operative ischemic episodes occur spontaneously, without evidence o f increases in oxygen demand. 39'4~ Proposed mechanisms for supply-related ischemia are changes in coronary artery tone and coagulation. Pulmonary capillary wedge pressure has been described as a method for detecting ischemia. Increases in left ventricular end-diastolic pressure is a sensitive measure of myocardial ischemia, however, recent studies show that changes in pulmonary capillary wedge pressure or pulmonary artery diastolic pressure are specific but not sensitive. 40,41 Transesophageal echocardiography (TEE) is the most sensitive clinical measure for detection of cardiac ischemia. Animal and human studies show that wall-motion and wall-thickening abnormalities occur early during myocardial ischemia and preceed ECG changes. Smith et a142 identified ischemic episodes (wall-motion abnormalities) using transesophageal echocardiography in 24 of 50 patients, whereas 7-lead ECG detected changes in only 6 of these patients. All four patients who developed perioperative myocardial infarction had preceeding intra-operative wallmotion abnormalities but only one patient had ST segment changes shown on ECG. This study

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supports the findings of Slogoffand Keats43: intraoperative ischemia may be predictive of adverse patient outcome. POSTOPERATIVE MANAGEMENT

Humoral changes, alterations in hemodynamics and the incidence ofischemia seems to be highest during the postoperative period. Patterns of postoperative ischemia observed in patients undergoing noncardiac surgery suggest that extension of anesthesia to the postoperative period may be beneficial in decreasing the incidence of myocardial ischemia. 44 The implication is that prevention of the stress response through attenuation of the sympathetic nervous system in the postoperative period reduces the imbalance of myocardial oxygen supply and demand. This should reduce the incidence of myocardial ischemia. Studies of perioperative myocardial ischemia in patients undergoing noncardiac surgery found a higher incidence of myocardial ischemia in the postoperative period (38%) versus the preoperative (24%), or intra-operative (21%) periods. 45 Postoperative ischemia was silent in 97% of cases: it tended to occur at elevated heart rate (90 v 74 beats per minute) and had a longer duration (51 v 30 minutes) than in the preoperative period. Similar studies examined the pattern of myocardial ischemia for 1 week after noncardiac surgery using continuous real-time ECG monitoring.46 Ischemia occurred throughout the week with the highest incidence on postoperative days two and three. Eighty-two percent of these episodes were silent and 64% were associated with tachycardia. Both early and late ischemia in the postoperative period were believed to be associated with adverse outcomes. Elevated levels of plasma epinephrine, norepinephrine, corticotropin, and cortisol occur soon after surgery. 47 The stress response is precipitated by hypothermia, hypotension, hypoxia, and hypercarbia. Therapeutic supression of the stress response has been suggested in studies that show that the perioperative stress response affects patient outcome.48 Pain sensation and its ineffective management leads to propagation of the stress response and release of stress hormones. Studies of normal volunteers infused with glucagon, cortisol, and epinephrine show an adverse synergistic effect of these three hormones on

minute ventilation and the rate pressure product. This increase in heart rate and minute ventilation may be harmful to patients with marginal cardiac and pulmonary function in terms of increased length of hospitalization, cost, morbidity, and mortality. In the postoperative period, adequate management of pain is essential, especially in the high-risk surgical patient. The primary goal of postoperative pain management is the early restoration of tissue, organ, and patient function. Surgical manipulation and tissue trauma interferes with nutrient delivery via vasoconstriction. Vasoconstriction is a consequence of pain or direct vascular injury and may result in cellular dysfunction. Sympathetic blockade can decrease pain-mediated increases in vascular resistance, thus allowing an increase in blood flow to the skin and coronary arteries. 49 Regional anesthesia for pain management permits improved mobilization of the injured part. 5~ Another goal of postoperative pain management is the prevention of the adverse sequelae of pain and tissue injury. When used in high-risk patients, epidural analgesia decreases postoperative morbid events. 35 Preliminary studies in a canine model using thoracic epidural anesthesia showed a decrease in the parameters associated with myocardial oxygen consumption, improved regional or ischemic zones of endocardial perfusion and a decrease in myocardial infarct size52 and a reduction in the incidence of malignant ventricular arrhythmias.53 Subsequent studies in humans depicted improved coronary artery blood flow via selective sympathetic blockade (T 1 to T5) and resultant dilation of stenotic epicardial coronary arteries without dilating coronary arterioles, l~ Improvement in the determinants of myocardial oxygen consumption in the absence of adversely affecting coronary perfusion pressure was shown using thoracic epidural anesthesia in patients with severe coronary artery disease and unstable angina. ~ Still another beneficial effect of thoracic epidural anesthesia is the improvement of global and regional ejection fractions, fewer regional wall motion abnormalities, decreased rate pressure product, and lessened ST segment changes during exercise as evaluated by radionuelide angiography.12 Liem et a154 noted improved recovery time, postoperative pain relief, less sedation, and superior cardiac and pulmonary outcome

THE PATIENT WITH CORONARY ARTERY DISEASE after combining local anesthetic and opioid for thoracic epidural anesthesia. This superior postoperative pain relief was also accompanied by an attenuation of the stress response (quantified by less epinephrine and cortisol release into the plasma). All of the above reasons coupled with a potential reduction in the length of stay in the intensive care unit and hospital and a decrease in overall medical cost makes neuraxial analgesia an attractive alternative to conventional pain management modalities. SUMMARY Cardiovascular morbidity continues to represent the single most important contributor to surgical mortality. The impact of postoperative interventions in potentially improving cardiovascular morbidity and mortality is extremely difficult to separate from the influence of the intra-operative technique. It is most likely that the combination of techniques used intra-operatively and postoperatively have a combined impact on cardiovascular outcome. A thorough preoperative assessment of the patient to determine the probability of risk for coronary artery disease and whether further workup will improve patient outcome is essential. Perioperative interventions such as coronary artery bypass grafting have not always shown a subsequent reduction in patient morbidity before noncardiac surgery. Other perioperative interventions such as percutaneous transluminal coronary angioplasty and the insertion of an intraaortic balloon p u m p m a y provide more patient benefit with less risk than coronary artery bypass graft. Intra-operative monitoring devices are only helpful if clinicians can interpret and extrapolate meaningful data that will assist them in achieving an end-point (detection and prevention of myocardial ischemia) for their patient's management. A familiarity of the sensitivity and specificity of a particular monitoring device is helpful to determine the best method for detecting myocardial ischemia. A smooth transition from the intraoperative to the postoperative period is desirable. Attenuation of the neurohumeral stress response through adequate pain management m a y reduce the incidence of postoperative morbid cardiac events. Regional techniques may hold the greatest promise for effecting significant improvements in cardiovascular outcome. Yeager's

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study is conclusive in showing that epidural anesthesia and analgesia results in decreased morbidity and mortality for major vascular surgery patients. T u m a n 55 showed decreased hypercoagulability with epidural anesthesia that m a y be a critical physiological benefit in reducing the incidence of vascular graft occlusion, coronary artery occlusion, and deep venous thromboses. Blomberg's studies in patients with severe coronary artery disease provide insight into the mechanisms by which epidural anesthesia m a y be a therapeutic measure in preventing and treating myocardial ischemia. Perhaps we should consider using thoracic epidural anesthesia for patients with coronary artery disease scheduled for noncardiac surgery to reduce the incidence or even the occurrence of perioperative myocardial infarction. Perhaps thoracic epidural anesthesia will replace our conventional therapies for myocardial ischemia. Only further investigation of this hypothesis will elucidate the answer. REFERENCES 1. FleisherLA, Barash PG: Preoperativecardiac evaluation for noncardiac surgery: A functional approach. Anesth Analg 74:586-598, 1992 2. Mangano DT: Perioperativemorbidity. Anesthesiology 72:153, 1990 3. American Heart Association: Heart and Stroke Facts. American Heart Association, Dallas, 1991 4. Freeman WK, Gibbons RJ, Shub C: Preoperative assessment of cardiac patients undergoing noncardiac surgical procedures. Mayo Clin Proc 64:1105-1117, 1989 5. Goldman L, Caldera DL, Nussbaum SR, et al: Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 297:845-850, 1977 6. Shah KB, Kleinman BS, Rao T, et al: Angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations. Anesth Analg 70:240-247, 1990 7. Rao TK, Jacobs KH, EI-EtrAA: Reinfarction following anesthesia in patients with myocardial infarction. Anesthesiology 59:499-505, 1983 8. Tarhan S, Moffitt EA, Taylor WF, Giuliani ER: Myocardial infarction after general anesthesia. JAMA 220:14511454, 1972 9. Shah KB, Kleinman BS, Sami H, et al: Reevaluation of perioperative myocardial infarction in patients with prior myocardial infarction undergoing noncardiac operations. Anesth Analg 71:231-235, 1990 10. BlombergS, Emanuelsson H, Dvist H, et al: Effectsof thoracic epidural anesthesiaon coronaryarteriesand arterioles in patients with coronary artery disease. Anesthesiology 73: 840-847, 1990 11. BlombergS, Emanuelsson H, Ricksten S-E: Thoracic epidural anesthesiaand central hemodynamicsin patientswith unstable angina pectoris. Anesth Analg 69:558-562, 1989

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ERIN A. SULLIVAN 29. Foster ED, Olsson CA, Rutenberg AM, Berger RL: Mechanical circulatory assistance with intra-aortic balloon counterpulsation for major abdominal surgery. Ann Surg 183: 73-76, 1976 30. Grotz RL, Yeston NS: Intra-aortic balloon counterpulsation in high-risk cardiac patient undergoing noncardiac surgery. Surgery 106:1-5, 1989 31. Siu SC, Kowalchuk GJ, Welty FK, et al: Intra-aortic balloon counterpulsation support in the high-risk cardiac patient undergoing urgent noncardiac surgery. Chest 99:13421345, 1991 32. Amsterdam EA, Avian NA, Lee G, Low R, et al: Intraaortic balloon counterpulsation: Rationale, application and results. Cardiovasc Clin 11:79-96, 1981 33. Gottlieb SO, Brinker JA, Borkon AM, et al: Identification of patients at high risk for variate risk factor analysis. Am J Cardiol 53:1135-1139, 1984 34. Weitz HH, Goldman L: Noncardiac surgery in the patient with heart disease. Med Clin North Am 71:413-432, 1987 35. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729-736, 1987 36. Rawal N, Sjostrand U, Christofferson E, et al: Comparison of IM and epidural morphine for postoperative analgesia in the grossly obese: Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583-592, 1984 37. London MJ, Tubau JF, Wong MG, et al: The "natural" history of segmental wall motion abnormalities detected by intraoperative transesophageal echocardiography: A clinically blinded prospective approach. Anesthesiology 69:A7, 1988 (abstr) 38. London M J, Hollenberg M, Wong MG, et al: Intraoperative myocardial ischemia: Localization by 12-lead electrocardiography. Anesthesiology 67:232, 1988 39. Mangano DT, SPI Research Group: Detection ofperioperative myocardial ischemia. Eur Heart J 10:2-9, 1989 (suppl) 40. Leung JM, O'Kelly BF, Mangano DT, et al: Relationship of regional wall motion abnormality to hemodynamic indices of myocardial oxygen supply and demand in patients undergoing CABG surgery. Anesthesiology 73:802-814, 1990 41. Haggmark S, Hohner P, Ostman M, et al: Comparison of hemodynamic, electrocardiographic, mechanical and metabolic indications of intraoperative myocardial ischemia in vascular surgery patients with coronary artery disease. Anesthesiology 70:19-25, 1989 42. Smith JS, Calahan MK, Benefiel DJ, et al: Intraoperative detection of myocardial ischemia in high-risk patients: Electrocardiography versus 2D TEE. Circulation 72:10151021, 1985 43. Slogoff S, Keats AS: Does perioperative myocardial ischemia lead to postoperative myocardial infarction? Anesthesiology 62:107-114, 1985 44. Mangano DT, SPI Research Group: Myocardial ischemia following surgery: Preliminary findings. J Card Surg 5: 288-293, 1990 45. Fegert G, Hollenberg M, Browner W, et al: Perioperative myocardial ischemia in the noncardiac surgical patient. Anesthesiology 69, A49, 1988 (abstr)

THE PATIENT WITH CORONARY ARTERY DISEASE 46. Wong MG, Wellington YC, London M J, et al: Prolonged postoperative myocardial ischemia in high-risk patients undergoing noncardiac surgery. Anesthesiology 69(3A):A56, 1988 (abstr) 47. Udelsman R, Norton JA, Jelenich SE, et al: Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J Clin Endocrinol Metab 64:986-994, 1987 48. Roizen MF: Should we all have a sympathectomy at birth? Or at least preoperatively? Anesthesiology 68:482-484, 1988 49. Cousins M J, Wright CJ: Graft, muscle and skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 133:59-69, 1971 50. Pflug AE, Murphy TM, Butler SH, et al: The effects of postoperative peridural analgesia on pulmonary therapy and pulmonary complications. Anesthesiology 41:8-17, 1974

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51. Bridenbaugh PO: Anesthesia and influence on hospitalization time. Reg Anaesth 7:S 151-S 155, 1982 (suppl) 52. Davis RF, DeBoer LWV, Maroko PR: Thoracic epidural anesthesia reduces myocardial infarct size after coronary occlusion in dogs. Anesth Analg 65:711-717, 1986 53. Blomberg S, Ricksten S-E: Thoracic epidural anesthesia decreases the incidence of ventricular arrhythmias during acute myocardial ischemia in the anesthetized rat. Acta Anaesthesiol Scand 32:173-178, 1988 54. Liem TH, Hasenbos MAWM, Booij LHD, et al: Coronary artery bypass grafting using two different anesthetic techniques: Part 2: Postoperative outcome. J Cardiothor Vasc Anesth 6(2):156-161, 1992 55. Tuman KJ, McCarthy RJ, March RJ, et al: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696-704, 1991