|
| ARTICLES |
|
| Year : 2007 | Volume
: 51
| Issue : 4 | Page : 287 |
 |
|
Perioperative myocardial ischaemia and infarction - a review
Satinder Gombar1, Ashish Kumar Khanna2, Kanti Kumar Gombar3
1 MD, Professor, Department Of Anaesthesia & Intensive Care, Government Medical College and Hospital, Sector 32, Chandigarh, India
2 P.G.Student, Department Of Anaesthesia & Intensive Care, Government Medical College and Hospital, Sector 32, Chandigarh, India
3 MD, Professor & Head, Department Of Anaesthesia & Intensive Care, Government Medical College and Hospital, Sector 32, Chandigarh, India
| Date of Web Publication | 20-Mar-2010 |
Correspondence Address:
Satinder Gombar
#1111,Sector 32 B, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | Check |
Keywords: Cardiac; Ischaemia; Infarction; Preoperative; Anaesthesia; Complications
How to cite this article:
Gombar S, Khanna AK, Gombar KK. Perioperative myocardial ischaemia and infarction - a review. Indian J Anaesth 2007;51:287 |
 Introduction | |  |
Preoperative myocardial ischaemia and infarction (PMI) is a major cause of short and long term morbidity and mortality in the surgical population. It is estimated that more than one half of postoperative deaths are caused by cardiac events, most of which are ischaemic in origin. Over 50,000 patients each year sustain a perioperative MI at an average additional cost to the health infrastructure of $12,000 per patient. [1] Thus prevention of a PMI is important to improve overall postoperative outcome. However, the exact nature of perioperative myocardial injury remains elusive and an area of continued debate and controversy. [2] The following review will address these issues and the nature of perioperative ischaemia in both the cardiac and non-cardiac surgery scenarios along with its management, including both preventive and therapeutic aspects of the problem.
| Preoperative myocardial ischaemia and infarction (PMI): Defining the problem | | |
Myocardial ischaemia is a dual state composed of in adequate myocardial oxygenation and accumulation of anaerobic metabolites and occurs when myocardial oxygen demand exceeds the supply. Myocardial infarction is defined as the death of myocardial myocytes due to prolonged ischaemia. [3] Though perioperative MI was thought to be related to the presence of a perioperative ischaemia, it was not until the landmark article by Slogoff and Keats in 1985 that the association between the two was clearly established. [4]
| Incidence of PMI | | |
In patients with, or at risk of coronary artery disease (CAD), the reported incidence of perioperative myocardial ischaemia is 20 - 63%.Various studies have shown that postoperative myocardial ischaemia was consistently found to occur considerably more often than preoperative and intraoperative ischaemia (ratio approximately 3:1 and 5:1 respectively). Reported incidence of postoperative cardiac events (the combined incidence of non-fatal myocardial infarction, unstable angina, congestive heart failure, cardiac death) is 5.5-53% and that of postoperative myocardial infarction between 1.4 and 38%. Postoperative myocardial infarction increased the odds for long term cardiac events 20-fold. [5],[6],[7] Unfortunately, there is no reliable data available on the incidence of perioperative ischaemia & infarction in our country.
| Pathophysiology | | |
A. Myocardial ischaemia
Myocardial ischaemia is characterized by an imbalance between myocardial oxygen supply and demand. The two most common conditions that predispose to myocardial ischaemia are CAD and left ventricular hypertrophy(LVH). Reduced oxygen supply or low-flow ischaemia (coronary vasoconstriction, intracoronary platelet aggregation orthrombus formation) is largely responsible for myocardial infarction and unstable angina. Increased myocardial oxygen demand or high-flow ischaemia is mostly responsible for ischaemic episodes in chronic stable angina (tachycardia, exercise or emotional stress) in the presence of fixed coronary artery stenosis. Often, myocardial ischaemia is a culmination of multiple factors and results from both a reduction in supply and an increase in oxygen demand. [8]
Endothelial function is also impaired in CAD, and is an important cause of myocardial ischaemia. Increases in coronary blood flow secondary to an increase in myocardial oxygen demand and sympathetic nervous system activation (e.g. during exercise, mental stress or increase in heart rate) induce vasodilatation in normal coronary arteries but lead on to paradoxical vasoconstriction in the atherosclerotic vessels [9],[10] .Such limitation of coronary flow and the inability of vessels to dilate near the site of an atherosclerotic plaque may result in regional myocardial supply- or low-flow ischaemia. In the face of an unfavorable oxygen supply demand ratio, the manifestations of myocardial dysfunction progressively set in and subsequently compromise tissue perfusion and cellular aerobic metabolism.
The clinical manifestations of myocardial ischaemia range from asymptomatic or "silent" episodes to angina, arrhythmia, conduction blocks, wall motion abnormalities, pulmonary congestion, infarction, and sudden cardiac death. Systolic (contractile) and diastolic (ventricular filling) dysfunction occur first; followed by electrocardiographic changes, and finally by chest pain. All these events often occur in a short time course of less than 1 minute [Figure 1]. [11] An 80% reduction in coronary blood flow causes akinesis, whereas a 95% decrease causes dyskinesis. If the ischaemia becomes severe, the increase in left ventricular end-diastolic pressure may lead to pulmonary oedema. After a brief period of severe ischaemia, contractile function can return gradually (stunning).Alternatively, severe chronic ischaemia can result in diminished contractile performance, such as chronic regional wall motion abnormalities (hibernation). In stunning normal blood flow and energy metabolism are accompanied by reduced contractility, designated as 'flow-contractility mismatch'. Hibernation is characterized by reduced contractility accompanied by reduced oxygen consumption as a consequence of reduced blood flow. Partially damaged cardiomyocytes can be rescued to full function after stunning as well as hibernation, provided normal blood flow is restored after the latter within the critical time period before irreversible cell damage has occurred. Despite their distinct definition, stunning and hibernation may merely represent intermediary states in a continuum extending from unimpaired functional myocytes to necrosis. [12]
It is worth mentioning here that perioperatively, the single most common abnormality that is often associated with ischaemia is tachycardia, which by causing both an increase in demand and reduction in supply can in susceptible patients jeopardize the myocardium and bring about ischaemic changes. [4] Preoperative tachycardia can result from many causes, including light plane of anesthesia, endotracheal intubation and extubation, hypovolemia, fever, anaemia, congestive heart failure(CHF), and postoperative pain. Similarly hypertension can cause increased demand and hypotension can lead to decreased supply in the perioperative period.
B. Myocardial infarction
Majority of perioperative infarctions occur in patients with significant preexisting CAD, however hypertensive patients with LVH are also susceptible. The transition from stable coronary artery disease to an acute coronary syndrome and infarction is characterized by coronary plaque disruption and subsequent thrombosis, which constitute the major pathogenic components of unstable or vulnerable plaques. [12]
A vulnerable plaque is an inflamed fibroatheroma with a lipid-rich core containing cholesterol crystals and necrotic debris, a thin fibrous cap with an infiltration of macrophages and lymphocytes, and low smooth muscle content. Inflammatory mediators closely regulate the balance between the synthetic and degradative processes controlling the strength of the cap, specifically the synthesis of collagen. [8],[13]
When intraluminal thrombi attach to a ruptured atheromatous plaque, total occlusion of an epicardial coronary artery may occur, resulting in interruption of nutrient blood flow to the myocardium and death of myocardial myocytes. The situation may be worsened by distal embolization of microthrombi and by coronary vasoconstriction induced by local, mediator release-induced or systemic sympathetic activation. If coronary blood flow is interrupted for longer than 30 min, myocardial infarction may result. Loss of functional myocardium results in impaired left ventricular function, which may impair quality of life and usually leads to premature death. [14] The presence of myocardial ischaemia, nonfatal MI, or both within the first 7 postoperative days increases the risk of adverse cardiovascular events by 2- to 20-fold in the first 2 years after a noncardiac operation.
To put it in simple words , it is a complex and unpredictable interaction between the structural (central lipid core, thin cap) and functional (plaque thrombogenicity, intraplaque inflammatory cell infiltrate) intrinsic plaque factors as well as the exogenous factors (e.g. mechanical stress, vasomotor tone, infection, blood viscosity and coagulability) which leads to the final outcome of myocardial ischaemic damage.
Most ischaemic episodes tend to start at the end of surgery and during emergence from anesthesia. This period is characterized by increases in heart rate (HR), arterial blood pressure (BP), sympathetic tone, and procoagulant activity. Increased sympathetic tone may lead to increases in coronary vasomotor tone and vascular stress which in turn may trigger coronary vasospasm, plaque disruption and coronary thrombosis. Increases in HR & BP may lead to subendocardial ischaemia by increasing myocardial oxygen demand in the presence of limited coronary vasodilator reserve. Simultaneously, surgery induced procoagulant and anti-fibrinolytic activity may trigger coronary artery thrombosis during low flow conditions even in the absence of acute plaque disruption.
| Mechanisms and triggers of perioperative myocardial injury | | |
Surgery, with its associated trauma, anesthesia and analgesia, intubation and extubation, pain, hypothermia, bleeding and anaemia, and fasting, is analogous to an extreme stress test. [Figure 2] illustrates how these factors initiate inflammatory, hypercoagulable, stress and hypoxic state, which is associated with perioperative elevations in troponin levels, arterial thrombosis and mortality. [14]
Increasing grades of surgical trauma and general anaesthesia can initiate inflammatory and hypercoagulable states. The inflammatory state involves increases in tumour necrosis factor-alpha, interleukin (IL)-1, IL-6 and C-reactive protein; these factors may have a direct role in initiating plaque fissuring and acute coronary thrombosis. The hypercoagulable state involves increases in plasminogen activator inhibitor-1, factor VIII and platelet reactivity, as well as decreases in antithrombin III; all of these factors can lead to acute coronary thrombosis. The stress state involves increased levels of catecholamines (epinephrine and norepinephrine) and cortisol. Preoperative catecholamine and cortisol levels increase with general anesthesia, anaesthetic reversal, extubation, increasing pain scores, increasing grades of surgical trauma, anaemia, fasting and hypothermia. Increased stress hormone levels result in increases in blood pressure, heart rate, coronary artery sheer stress, relative insulin deficiency and free fatty acid levels all increase oxygen demand. Coronary artery shear stress may trigger plaque fissuring and acute coronary thrombosis. Factors that can initiate a hypoxic state include anaemia, hypothermia (through shivering), and anesthesia and analgesia (through suppression of breathing). Preoperative hypoxia can result in myocardial ischaemia in the setting of a haemodynamically significant coronary artery stenosis. [14]
| Making a diagnosis | | |
A. Definition and diagnosis of perioperative myocardial ischaemia:
Though there is no accepted gold standard for the diagnosis of myocardial ischaemia, the diagnosis can usually be based on clinical, haemodynamic (pulmonary artery capillary wedge and/or left atrial pressure wave), electrocardiographic (ECG), functional (echocardiogram), metabolic (coronary lactate production), biochemical (release of creatine kinase-MB isoenzyme and/or troponin) or regional perfusion (scintigram) parameters. [8] All these techniques in the setting of ischaemia or infarction detection have considerable limitations, varying sensitivity and specificity and poor inter technique correlation [Table 1] [15] .
Chest pain: The onset of new cardiac pain can be extremely important when one is diagnosing myocardial ischaemia preoperatively, during surgery under local or regional anesthesia and in the recovery room. Typically cardiac pain is a sense of chest constriction and may be referred to arm, neck, jaw, teeth or even post scapular area. However diabetics may have silent ischaemia because pain pathways are impaired by diabetic neuropathy. In fact, it is reported that 70 % of myocardial ischaemic episodes in fully awake humans are asymptomatic.
Electrocardiography (ECG): Preoperative myocardial ischaemia has predominantly been detected and defined by ECG. The reported incidence of perioperative myocardial ischaemia greatly depends on choice and number of precordial leads, on the definition of ischaemic STsegment change (extent and duration of ST-segment change), and on the mode of data acquisition (continuous vs intermittent). [16]
The standard ECG consists of 12 leads, however, during anesthesia, monitoring is usually limited to five or seven leads. Blackburn et al demonstrated that 89% of significant ST depression was found in precordial lead V 5 . They also demonstrated that 100% of ST segment changes can be detected by recording leads V 3 -V 6 and leads II and a VF. [17] In routine practice, leads II and V 5 are continuously monitored, giving views of inferior and lateral myocardium. The ECG must be calibrated to give a pen deflection of 10mm for 1mV potential. This is important because excessive gain can give false ST depression and inadequate gain can mask such depression. Proper diagnosis of ischaemia from ECG depends on the diagnostic mode which brackets a frequency bandwidth of 0.05-100 Hz. It is equally important to have a working knowledge of critical ST segment analysis. Horizontal or down sloping ST segment depression of 1mm or more indicates significant subendocardial ischaemia while ST segment elevation greater than 1mm indicates severe transmural ischaemia. Patients with left ventricular hypertrophy, left bundle branch block (LBBB), digitalis effect, ventricular pacing and those not in sinus rhythm are not suitable for ECG-derived diagnosis of myocardial ischaemia. In addition, perioperative changes in acid-base balance and electrolytes can affect the ECG in a way that interferes with ischaemia detection. [16]
Pulmonary artery pressure: The quantitative increase in pulmonary capillary wedge pressure and characteristic changes in its waveform have been suggested as an ischaemia monitor, but it is believed that the pulmonary artery catheter is an insensitive monitor of myocardial ischaemia and should not be inserted with this as a primary indication. In addition, the use of pulmonary artery catheters in the perioperative period may actually contribute to increased morbidity. [11]
Transoesophageal echocardiography (TEE): TEE is a highly sensitive ischaemia monitor and demonstrates development of new regional wall motion abnormalities, decreased systolic wall thickening, and ventricular dilation as a result of ischaemic events. Usually, a transgastric cross-sectional view of the left ventricle is imaged because this view displays the myocardial perfusion territories of the three major coronary arteries. The use of TEE has become increasingly common in the operating room for cardiac surgery but is less frequently used in noncardiac surgery. In addition to cost, significant limitations exist to the routine use of TEE as an ischaemia monitor. Pre-intubation events are missed, and the image plane may miss events in other areas of the myocardium. It has been shown that if the anaesthesiologist has the training, experience and equipment to perform TEE, it can be valuable in the early detection of myocardial ischaemia. [16] However, the incremental value of adding TEE to electrocardiographic monitoring in noncardiac surgery is unclear at this time.
Myocardial lactate: Although used mainly as a research tool, the coronary sinus catheter represents the accepted standard for myocardial ischaemia monitors. However, the coronary sinus catheter requires the use of fluoroscopy, echocardiography, or both for proper placement. In addition, small areas of ischaemia may not be recognized because the lactate produced from these areas will be diluted by the blood from nonischaemic regions. [18]
The use of numerical indices of myocardial oxygen consumption (MVO 2 ) has been popular in general cardiologic practice. Unfortunately, their theoretical advantages have failed validation in anaesthetized patients. The rate-pressure product (RPP = systolic blood pressure × heart rate) has been shown to be a useful measure of MVO 2 in awake patients, but direct correlation of this index to MVO 2 measurement in anaesthetized patients has been unreliable. Other indices developed to overcome the deficiencies of the rate-pressure product have also failed validation in anaesthetized patients, probably because it has been shown that most intraoperative ischaemia is related to decrease supply rather than increased demand. Most intraoperative ischaemic events occur with relatively normal haemodynamic parameters. Thus, the indices that are based on increased demand have little sensitivity for intraoperative ischaemia. Although heart rates above 110 beats/minute double the incidence of myocardial ischaemia, ischaemia frequently occurs even with heart rates between 60 and 80 beats/minute. [11]
In summary, there is no single best indicator of intraoperative myocardial ischaemia. Use of an array of monitoring modalities may facilitate the highest yield of ischaemic episodes.
B. Definition and diagnosis of perioperative myocardial infarction
According to the definition of the World Health Organization (WHO), at least two of three criteria must be fulfilled to diagnose myocardial infarction: typical ischaemic chest pain; increased serum concentration of creatine kinase-MB isoenzyme; and typical electrocardiographic findings, including development of pathological Q-waves. [19] This definition provides adequate specificity but lacks high sensitivity.
Clinical presentation: Patients receiving GA obviously will not complain of chest pain but may have hypotension, arrhythmias, and signs of congestive heart failure. Most postoperative myocardial infarctions occur early after surgery and are asymptomatic.
ECG: ECG may show changes of subendocardial or transmural ischaemia (ST elevation >1mm).The vast majority of perioperative myocardial infarctions are of the non-Q-wave type and preceded by episodes of ST-segment depression and T wave inversion. [2] Long-duration (single duration >20-30 min or cumulative duration >1-2 h) ST-segment change, rather than merely the presence of postoperative ST-segment depression, seems to be associated with adverse cardiac outcome. [4],[18]
The development of assays for the cardiac troponins T and I, which are highly specific and sensitive for myocardial injury, formed the basis of a revised definition of myocardial infarction proposed by the European Society of Cardiology and the American College of Cardiology. [19] The following two criteria satisfy the diagnosis of an acute, evolving or recent myocardial infarction: (i) a typical increase and gradual decrease in troponin concentrations or more rapid increase and decrease in creatine kinase-MB concentration in combination with at least one of the following: (a) typical ischaemic symptoms, (b) development of pathological Q-waves in the ECG, (c) ECG changes indicative of myocardial ischaemia(ST-segment elevation or depression), and (d) coronary artery intervention; and (ii) pathological findings of an acute myocardial infarction.
Biochemical markers: Increased concentration of CPK-MB is not useful intraoperatively because the leakage of these enzymes into the circulation can occur 8-24 hours after an MI. Because of the inherent limitations of CPK-MB concentration and lack of specificity, MI may be best detected with cardiac TnT concentrations. TnT binds to tropomyosin, troponin C binds to Ca ++ ,and troponin I (TnI) binds to actin and inhibits actin-myosin interactions. While CPK-MB concentrations may rise only 10-20 times of normal during infarction and return to normal within 72 hrs, TnT and TnI levels may rise more than 20 times above the reference range within 3 hrs after onset of chest pain and may persist for up to 10-14 days [Figure 3].This may assist in late diagnosis of infarction. [16]
Evidence is accumulating that other biochemical markers may further enhance sensitivity or improve risk stratification in patients with ACS including myoglobin (earliest rise after MI), C-reactive protein( a marker of inflammation that is increasingly appreciated as the primary acute physiological process leading to plaque rupture and thrombosis) and B-type natriuretic peptide ( sensitive but non-specific response to left ventricular pressure or volume overload caused by severe ischaemia or heart failure) [20],[21]
TEE : The sudden appearance of severe wall motion abnormalities in patients being monitored by TEE may also indicate MI, though it may be difficult to distinguish evolving infarction, stunned myocardium and hibernating myocardium using TEE. [16]
The question remains whether a reported incidence of perioperative myocardial injury based on the traditional definition underestimates the true incidence of clinically relevant myocardial injury or whether a reported incidence based on serum concentrations of troponins overestimates it. When using exclusively biochemical markers, specificity may be sacrificed for sensitivity. Given accumulating evidence that even low levels of troponin elevation in otherwise asymptomatic patients are associated with higher long term (6months -1 year) morbidity and mortality, it appears that they are accurate in detecting perioperative myocardial injury. At present there is a paucity of formal guidelines on this topic which clearly specify the ideal diagnostic criteria for perioperative infarction. [18]
Despite widespread use of the TEE and the PA catheter, the ECG is still the best validated tool for detection of ischaemic episodes postoperatively.
The ACC/AHA Guidelines [Table 2] on perioperative evaluation provide specific recommendations for perioperative surveillance and evaluation of such patients that is applicable in most settings. [22] We need more intensive investigations to determine whether this warrants a change in the current patterns of perioperative care.
| Preoperative risk assessment | | |
Non cardiac surgery
The fundamental purpose of ascertaining the presence of coronary artery disease, myocardial ischaemia, or both preoperatively is (1) to determine which patients are at risk and whether any further preoperative treatment is necessary, (2) to design an intraoperative management plan to reduce the incidence and consequences of ischaemia in patients at risk, and (3) in these at risk patients attempt to reduce the risk of adverse outcome by implementing aggressive preventive and treatment modalities. Interventions based on this assessment may include preoperative medical optimization, coronary revascularization or both. History and physical examination can identify variables associated with postoperative ischaemia: LVH, hypertension, diabetes mellitus, definite coronary artery disease, smoking and use of digoxin or any other medications. The incidence of postoperative ischaemia increases from 22% in patients with none of these variables to 77% in patients with four variables present. [11]
The Goldman Cardiac Risk Index (1977) [23] first identified the importance of surgery-specific risks, which was validated in large prospective series of general surgery patients. Subsequently, Detsky et al in large prospective studies in the 1980s confirmed and refined the original Goldman index by adding categories of angina and prior history of congestive heart failure. [24] An alternate clinical risk prediction tool, the Revised Cardiac Risk Index (RCRI) [25] may equally predict risk. It involves the presence or absence of six clinical risk factors. Zero, one, two, or three (or more) risk factors are categorized into Class I, II, III, or IV respectively. The corresponding postoperative cardiac complication rates range from less than 1% to over 10%.
American Heart Association/American College of Cardiology (AHA/ACC) published a guideline for perioperative cardiovascular evaluation for noncardiac surgery in 1996.This guideline has been recently updated in 2002 and offers the most comprehensive approach to preoperative cardiac evaluation for noncardiac surgeries. [22] It focuses clinicians' attention on three major areas:
- clinical risk predictors,
- surgery-specific risks, and
- functional capacity
The guideline stratifies clinical risk predictors into minor, intermediate, or major based on estimated risk of postoperative cardiac events. Minor risk factors are not known to be associated with postoperative cardiac events, while the presence of major risk predictors warrants prompt and aggressive investigation and treatment. [Table 3]. [22]
The duration of the procedure, site of operation, and amount of tissue handling combine to confer different risks associated with various types of surgeries. The AHA/ ACC guideline included a more detailed estimate of surgery-specific risks based on postoperative cardiac events for each type of surgery based on the Coronary Artery Surgery Study (CASS) registry. [26] Surgeries were then categorized into low, intermediate, and high-risk surgical groups.[Table 4] A patient with minor clinical predictors has an overall low risk except for high risk or urgent/ emergent surgeries. Conversely, a patient with major clinical predictors who is in stable condition has an acceptable overall risk if the proposed procedure is a low risk procedure. The final major component of this evaluation is an assessment of current functional capacity. This assessment is based on metabolic equivalents (METs)
(1 MET= O2 consumption at rest- 3.5ml.kg -1 .min -1 )
Functional capacity of less than 4 METs of activity confers a 4% risk of postoperative cardiac events, whereas the risk is as low as 0.7% in patients with greater than 4 METS of capacity. Examples of exercise equal to 4 METs being, climbing a flight of stairs/walking up a hill/ walking on level ground at 4mph/running a short distance
Careful consideration of all three aspects, including clinical characteristics, functional capacity, and surgery specific risk in accordance with the published AHA/ACC guideline, form the basis for informed decision making regarding further diagnostic testing and/or risk reduction interventions. [26]
| Cardiac surgery | | |
In patients undergoing CABG, myocardial ischaemia that occurs during the intraoperative period has the strongest correlation with perioperative MI. Looking at the cardiac patient in the cardiac surgical setting, it is important to realize that the lesion causing ischaemic changes in the pre operative period is usually remedied in the postoperative period thus outcomes are favourable as compared to the non cardiac surgery patient who has to go through the post operative vulnerable period with an ischaemic myocardium.
Various studies in the cardiac surgery population have identified certain factors namely, NYHA functional class, urgency of surgery, valvular lesions secondary to ischaemia, mean PAP>30mmHg, ejection fraction <40% and a low cardiac index as being predictors of poor out comes after cardiac surgery. [27],[28]
| Preoperative evaluation | | |
While clinical assessment of risk is necessary for every patient, in populations deemed to be at high risk we need a more definitive assessment in the form of preoperative non-invasive testing. Although a battery of such tests are now available, recent guidelines by the AHA/ ACC clearly state the class I indications for pre operative evaluation in the cardiac patient and limit testing only to the population groups deemed to be at the highest risk (e.g, patients undergoing vascular operations). A number of non invasive tests have been used and studied.
The standard 12-lead electrocardiogram is an insensitive test of the risk for myocardial ischaemia. It is normal in up to 50% of patients with CAD, and some patients have conduction defects that render the electrocardiogram uninterpretable for ischaemia. When further workup is required cardiac stress testing is used. The purpose of a stress test is to determine
- The status of ventricular function,
- The amount of myocardium at risk for ischaemia, and
- The need for further interventions, e.g., medication, angioplasty, or coronary artery bypass grafting, before the proposed surgical procedure.
Stress testing can be subdivided into exercise and pharmacologic testing. Each test method stresses the components of myocardial oxygen consumption (contractility, heart rate, and afterload) to varying degrees. [29]
Exercise stress testing assesses a patient's functional capacity. The ability to achieve a target heart rate of >100/min or 85% of the maximum predicted HR predicts a low complication rate. ST segment depression greater than 0.1 mV on a preoperative exercise stress test is an independent predictor of perioperative cardiac complications.
When exercise testing is contraindicated (LBBB, significant arrhythmias, CHF) or if patient is unable to exercise because of claudication , pharmacologic and other testing is substituted which include ischaemia monitoring by ambulatory ECG (AECG),ejection fraction estimation by radionuclide ventriculography (RNV), dipyridamole thallium scintigraphy (DTS),and dobutamine stress echocardiography. The dipyridamole-thallium stress test reduces after load and thereby alters supply; whereas dobutamine stress echocardiography test increases demand. Mantha et al believe that DSE may show the greatest promise in predicting cardiac events. [29]
AHA/ACC guidelines also try and answer a question that so often comes up in the mind of every perioperative physician "Should patients with significant coronary artery disease undergo 'prophylactic' coronary artery bypass grafting or percutaneous coronary intervention before non-cardiac surgery?" Patients with a severe pattern of coronary disease, such as a critical left main stem stenosis or severe proximal three vessel coronary disease have a poor prognosis and, irrespective of planned surgery, should be urgently considered for coronary revascularization. This intervention significantly improves prognosis especially where an exercise test is strongly positive or left ventricular function is impaired. Preoperative percutaneous coronary intervention with angioplasty and stenting, on the other hand, exposes destabilized plaque and coronary stent to the prothrombotic post-operative milieu with potentially catastrophic consequences and thus its role as a prophylactic intervention to tide over a high risk non cardiac surgery is questionable if not worth condemning. [22]
The underlying theme of these guidelines is that any intervention in the form of prophylactic revascularization procedures should be reserved for those who warrant such therapy independent of their surgical procedure. [22] Otherwise medical optimization is needed.
| Preoperative interventions for prevention of perioperative MI | | |
Two principal strategies used in an attempt to reduce the incidence of PMIs and other cardiac events are
- Preoperative coronary revascularization- PCI or CABG
- Pharmacological interventions
The decision for or against preoperative coronary revascularization- PCI or CABG, should be based entirely on universally accepted medical indications for coronary revascularization. The philosophy of performing preoperative coronary revascularization merely 'to get the patient through surgery' is contrary to all available evidence. If the decision for preoperative coronary revascularization is made, then timing with respect to the subsequent surgery appears crucial. [18]
| Coronary artery stenting - challenges and controversies | | |
The advent of coronary artery stenting adds further complexity to perioperative management. Since placement of coronary stents denudes the arterial endothelial surface, the risk of intrastent thrombosis is high for the first several weeks after the procedure. The use of aspirin and clopidogrel decreases this risk, but if surgery must occur in the first several weeks after stent placement, the risk of intrastent thrombosis is high, and may occur even when aspirin and clopidogrel are continued. This is likely due both to the activation of the sympathetic nervous system and to the hypercoagulable state which occurs perioperatively. Current guidelines advocate continuing combination anti platelet therapy for a minimum of 2-3 weeks and ideally for 3 months post stent placement to allow for complete re-endothelialization of the stent. [26] The advent of drug-eluting stents may further complicate perioperative care. These stents prolong the re-endothelialization of coronary arteries, thus increasing the period of thrombotic risk for surgical patients with new stents. Initial guidelines recommended 3 months of combination antiplatelet therapy for patients with the sirolimuseluting stent and 6 months for those with the paclitaxeleluting stent which have now been extended for upto one year uniformly and continuation of aspirin upto the day of the planned surgical procedure has also been made mandatory, unless the risks of bleeding are significantly more than those of perioperative stent thrombosis [30] . If angioplasty must occur before the surgical procedure, some authors recommend either plain angioplasty without a stent, or use of a bare metal stent followed by 2 weeks of aspirin and clopidogrel before proceeding to noncardiac surgery, since the highest risk of stent thrombosis appears to occur in the first two weeks. [18] Close preoperative consultation between the interventionalist and anaesthetist is required to minimize the risk of perioperative cardiac morbidity and mortality.
| Pharmacological interventions | | |
Several classes of drugs have been proposed in order to reduce the risk of ischaemic complications of anaesthesia and surgery. However, based on current clinical data, only aspirin, beta-blockers, alpha 2 -adrenoceptor agonists, and statins may have the potential to affect perioperative cardiovascular outcome.
1.β-blockers
These drugs, at present, occupy centre stage both for cardiac prophylaxis and treatment following an ACS. Several studies have shown a reduction in the incidence of cardiac complications of anaesthesia and surgery in patients deliberately given beta-blockers prophylactically. Cardio protective effects of β-blockers are attributed to numerous cardiovascular and other effects (anti-arrhythmic, anti-inflammatory, altered gene expression, protection against apoptosis etc). [31] Randomized trials in at risk patients having non-cardiac surgery [32] and high-risk patients having vascular surgery [33] have supported the use of perioperative beta-blockade. According to the recent up-date by the AHA/ACC unless there is a clear contraindication, perioperative beta-blocker therapy should be given to all patients who are to have vascular surgery and to most patients with cardiovascular disease who are to undergo major non-cardiac surgery and also those group of patients who test positive for inducible ischaemia in a myocardial stress test. Withdrawal of chronic beta-blocker therapy may have serious adverse effects. [34],[35] It is important that beta-blocker therapy is maintained perioperatively in at risk patients and a rebound 'withdrawal syndrome' must be avoided. Beta-blockers may be given intravenously during or after surgery in patients unable to take oral drugs.
2.Antiplatelet therapy (APA)-aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors
Aspirin forms an integral part of the acute therapy not only after an ACS but also in patients not known to have a pre existing CAD. It eliminates the diurnal variation in plaque rupture. Apart from reducing platelet aggregation, its anti-inflammatory effect may be additive to its antithrombotic effect in patients with plaque instability. [18] Perioperative antiplatelet therapy presents both benefits and risks. For elective surgery the practice of withdrawing all forms of APA has been challenged because of fear of an unopposed and even increased risk of ischaemic events. Most experts recommend surgery while continuing APA for most vascular procedures and in settings where bleeding risk is likely to be low. [36] French Society of anaesthesiology and intensive care (SFAR) recommends that "aspirin can be discontinued in the perioperative period only when, compared with benefits, the specific haemorrhagic risks inherent to the intervention is definitely greater than the cardiovascular risk associated with discontinuation". [37] For those patients who are on combination of two APA, the anaesthesiologist needs to discuss the risk benefit ratio with the surgical team and preferably put the patient on monotherapy at least 5 days preoperatively.
3.Alpha 2 -adrenoceptor agonists
Alpha-2 adrenoceptor agonists improve cardiovascular morbidity and mortality following cardiac and noncardiac surgery. [38] These drugs attenuate perioperative haemodynamic instability, inhibit central sympathetic discharge, reduce peripheral norepinephrine release, and dilate post-stenotic coronary vessels. [39]
4. Statins
Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors or statin therapy is associated with major benefits in patients with vascular disease. 'Pleiotropic' effects of statins independent of their lipid lowering action have been proposed as the mechanism of their beneficial effects. [18] These benefits are now recognized to occur not only in patients with coronary artery disease, but also in patients with peripheral vascular disease, cerebrovascular disease, and those with multiple risk factors. [40],[41] These benefits may, in part, relate to the stabilization of the atherosclerotic plaque surface and cap, making plaque rupture less likely and enhancing plaque remodelling. All patients with vascular disease should be established on a statin, given the powerful evidence provided by the Heart Protection Study, statin therapy may be even more critical in the perioperative period. [40] In a recent meta analysis Biccard et al concluded that statin therapy is not only preventive but also is of proven benefit in the early stabilization of patients following the occurrence of an ACS in the perioperative period. [42]
5. Nitroglycerine
While nitroglycerine is used successfully in the treatment of myocardial ischaemia, there is no evidence that its prophylactic administration before anaesthesia and surgery decreases the risk of perioperative cardiac complications. [39]
6. Miscellaneous
Though effective in the management of ischaemic heart disease, Ca 2+ channel blockers have never been shown to offer any protection against perioperative cardiac complications of anaesthesia and surgery. [39],[43]
ACE inhibitors have a proven benefit in patients with a recent ACS and also in patients with vascular disease and normal left ventricular function. [44] These benefits extend to patients with diabetes mellitus where there is the added advantage of a reduction in progression to microalbuminuria. Patients with vascular disease or diabetes mellitus should be maintained on angiotensin converting enzyme inhibitor therapy perioperatively.ACE inhibitors have anti-ischaemic actions with a 20% relative reduction for myocardial infarction. [44],[45]
The balance of benefits and risks of ACE inhibition in the perioperative period is uncertain. Inhibition of both the sympathetic nervous system with a beta-blocker and the renin-angiotensin system with an ACE inhibitor removes the major protective reflexes for intravascular volume regulation and homeostasis. Such combination therapy may result in a greater risk of hypotension and may necessitate more detailed and invasive haemodynamic monitoring and more frequent intervention. In the presence of ACE inhibition, acute renal failure can be precipitated by hypotension, hypovolaemia, radiocontrast, or NSAID administration. [46]
Antithrombin therapy (Heparin) has been used effectively in the management of unstable angina or acute PMI, both as a single agent or as a part of combination therapy with aspirin and thrombolytics. These patients are high risk candidates for perioperative embolic events and are often on subcutaneous low molecular weight heparin (LMWH) to reduce the risk of deep vein thrombosis and pulmonary embolism. Low dose heparin has been shown to reduce hypercoagul ability after elective abdominal aortic surgery. [47]
Adenosine modulators facilitate the release of the coronary vasodilator adenosine by the ischaemic myocardium, thereby improving collateral blood flow toward the compromised area. Promising results have been obtained, [48] with the only agent tested in clinical trials, acadesine.
Nicorandil is both a nitrate and a K ATP channel opener. It is effective in the management of ischaemic heart disease and its associated dysrhythmias. It may prove useful in the perioperative prevention of cardiac complications. In clinical practice, nicorandil, a K ATP channel opener and nitrate, is widely used in the treatment of angina. It appears to protect by opening K ATP channels and to interact with ischaemic preconditioning and appears to offer additional protection when administered with isoflurane, in terms of functional recovery of the stunned myocardium. [49]
Preoperative medication: High risk patients benefit from optimal preoperative anti-ischaemia and antihypertensive therapy which should be continued in perioperative period. Pharmacological and psychological attempts should be made to allay anxiety, the goals being to produce maximum sedation without undesirable circulatory and ventilatory depression.
| Intraoperative management | | |
The basic challenge during the perioperative period is to prevent myocardial ischaemia, this goal is logically achieved by maintaining the balance between myocardial oxygen delivery and demand. [Table 5] summarizes the various intraoperative events that can adversely influence this balance, and hence should be avoided.
| Choice of anaesthetic technique | | |
Induction of anaesthesia in patient with IHD should be smooth and attempts should be made to minimize pressor response to laryngoscopy and intubation. Various drugs like lidocaine, nitroprusside, esmolol, fentanyl, nitroglycerine etc. have been used for this purpose.
Choice of drugs for maintenance depends on left ventricular function as determined by preoperative evaluation. In patients with normal LV function, a combination of N 2 O-opioid with addition of volatile agent (isoflurane, desflurane, sevoflurane) is acceptable. In patients with severely impaired LV function, a high dose opioid (fentanyl 50-100 µg.kg -1 IV )may be utilized as sole anaesthetic. [50] Opioid-based anaesthetics have become popular because of the cardiovascular stability associated with their use. The use of high doses, however, is associated with the need for postoperative ventilation. Because weaning from the ventilator in an intensive care setting has been associated with myocardial ischaemia, this feature is important in the overall risk-benefit equation.
Neuraxial anaesthetic techniques can result in sympathetic blockade, resulting in decreases in both preload and after load. The decision to use neuraxial anaesthesia for the high-risk cardiac patient may be influenced by the dermatomal level of the surgical procedure. Infrainguinal procedures can be performed under spinal or epidural anaesthesia with minimal haemodynamic changes if neuraxial blockade is limited to those dermatomes. Abdominal procedures can also be performed using neuraxial techniques; however, high dermatomal levels of anaesthesia may be required and may be associated with significant haemodynamic effects. High dermatomal levels can potentially result in hypotension and reflex tachycardia if preload becomes compromised or blockade of the cardioaccelerators occurs. Studies that have evaluated regional vs. general anaesthesia for high risk patients undergoing noncardiac surgery found no difference in outcome in terms of cardiac morbidity. [22]
Monitored anaesthesia care by an anaesthesia caregiver includes the use of local anaesthesia supplemented with intravenous sedation/analgesia and is believed by some to be associated with the greatest safety margin. Although this technique can eliminate some of the undesirable effects of general or neuraxial anaesthesia, it provides poor blockade of the stress response unless the local anaesthetic provides profound anaesthesia of the affected area. If the local anaesthetic block is less than satisfactory or cannot be used at all, monitored anaesthesia care could result in an increased incidence of myocardial ischaemia and cardiac dysfunction compared with general or regional anaesthesia. To achieve the desired effect, excess sedation can occur. Therefore, there may be no significant difference in overall safety with monitored anaesthesia care, and general or regional anaesthesia may be preferable.
| Perioperative pain management | | |
From the cardiac perspective, pain management may be a crucial aspect of perioperative care. Because the majority of cardiac events in noncardiac surgical patients occur postoperatively, the postoperative period may be the time during which ablation of stress, adverse haemodynamics, and hypercoagulable responses is most critical. Although no randomized, controlled study specifically addressing analgesic regimens has demonstrated improvement in outcome, patient-controlled analgesia techniques are associated with greater patient satisfaction and lower pain scores. Epidural or spinal opiates are becoming more popular and have several theoretical advantages. The patients having epidural anaesthesia/analgesia have demonstrated lower opiate dosages, better ablation of the catecholamine response, and a less hypercoagulable state. Most importantly , an effective analgesic (i.e., one that blunts the stress response) regimen must be included in the perioperative plan. [51],[52]
| Maintenance of body temperature | | |
Hypothermia is common during the perioperative period in the absence of active warming of patients. Several methods of maintaining normothermia are available in clinical practice, the most widely studied being forced air warming. Perioperative morbid cardiac events have been found to occur less frequently in the normothermic population than in the hypothermic group.
| Treatment of perioperative myocardial ischaemia | | |
1. Prevention of myocardial ischaemia: Careful attention to prevention of tachycardia during anaesthesia is extremely important. Maintenance of adequate depth of anaesthesia along with judicious use of ultra short acting â blockers can be very useful in preventing tachycardia. Apart from this, one should take adequate measures to attenuate pressor responses to laryngoscopy and endotracheal intubation. If haemodynamic aberrations are associated with myocardial ischaemia, they may precede and be the cause of ischaemia ;or ischaemia may precede and may cause haemodynamic aberrations. For example if an anaesthetized patient has normal ST segment and then develops tachycardia followed by ST depression, one should assume tachycardia as the cause of ischaemia, so efforts should be made to reduce the rate. However, if hypovolemic hypotension precedes the onset of ST depression, perhaps the hypotension and consequent decrease in myocardial oxygen supply is the cause, which should be managed accordingly. [16]
2. Treatment of myocardial ischaemia without accompanying haemodynamic alterations: In susceptible patients, myocardial ischaemia often occurs without attendant haemodynamic alterations. In these patients nitroglycerine (sublingual or intranasal) can be useful. Nitroglycerine decreases preload and wall tension, dilates epicardial coronary arteries, and increases subendocardial blood flow.
3. Treatment of myocardial ischaemia accompanied by tachycardia and hypertension: A combination of tachycardia and hypertension can precipitate myocardial ischaemia by disturbing the myocardial oxygen demand and supply balance. After ensuring adequate ventilation, oxygenation and anaesthetic depth, â blockers (esmolol or metoprolol) may be administered in a titrated manner provided there is no evidence of CHF or bronchospasm.
4. Treatment of myocardial ischaemia accompanied by tachycardia and hypotension: A combination of tachycardia and hypotension (mostly due to hypovolemia) can precipitate myocardial ischaemia because both can drastically reduce myocardial oxygen supply. Apart from volume replacement, it is important to restore coronary perfusion pressure and slow the rate.
5. Severe resistant myocardial ischaemia: Occasionally one may come across severe myocardial ischaemia, which is resistant to all antianginal drugs. Here intraaortic balloon pump (IABP) can be useful; it acutely decreases myocardial oxygen requirements and may increase myocardial oxygen supply.
| Treatment of perioperative myocardial infarction | | |
Cardiologists usually do treatment of an acute pre or postoperative MI; however, in the intraoperative setting the anaesthesiologist has a major role to play. Once the diagnosis of acute MI is made, it is important to monitor the patient carefully: pulse oximetry, automated noninvasive blood pressure and in selected cases a radial arterial line should be inserted to have a continuous monitoring. 100% oxygen should be administered and volatile agent discontinued. As soon as PMI is diagnosed, aspirin 325 mg is administered orally (through ryle's tube if unable to take orally) and is continued thereafter. Prompt and aggressive treatment of changes in HR and/or BP is indicated. Tachycardia is treated with IV β blockers like esmolol while nitroglycerine is the drug of choice in the presence of normal to modestly elevated systemic BP. Class I recommendations for intraoperative nitroglycerine include high-risk patients previously taking nitroglycerine, who have active signs of myocardial ischaemia with out hypotension. [22]
Morphine is a venodilator that reduces ventricular preload and oxygen requirements. It is the analgesic of choice for continuing pain unresponsive to nitrates, and it is also effective in patients with pulmonary vascular congestion complicating ACS.
Hypotension should be rapidly treated in order to restore coronary perfusion pressure (CPP). Moderate hypotension often responds to volume expansion with 300-500ml of crystalloid. If severe hypotension (60-80mmHg systolic) persists despite volume expansion, vasoactive or inotropic drugs may be given to elevate CPP above critical value.
In the presence of significant left ventricular dysfunction, CVP monitoring may not be a good guide for fluid therapy so more invasive haemodynamic monitoring (pulmonary artery catheterization) is indicated in patients with refractory hypotension (unresponsive to volume expansion), hypotension in the presence of CHF or haemodynamic deterioration severe enough to require vasopressors, vasodilators or an IABP. If PCWP is 12mmHgor less, volume expansion with crystalloid should continue. If PCWP is high, use of an inotropic agent like dopamine 3-5μg.kg -1 .min -1 or dobutamine 2.5-20 μg.kg1 .min -1 is considered. If hypotension persists, consider epinephrine or milrinone. Milrinone is a class III cAMP phosphodiesterase inhibitor, 10 times more potent than amrinone, shorter half-life and less potential for thrombocytopenia. After a bolus of 25-50μg.kg -1 and infusion of 0.375 to 0.75μg.kg -1 .min -1 , cardiac output and blood pressure increase in a few minutes. In some patients who don't respond, use of percutaneous IABP is life saving. [16]
| Treatment of cardiac dysrrhythmias | | |
[50]
Apart from attempts to increase the cardiac output, one should look for and correct metabolic acidosis (due to low cardiac output), electrolyte imbalance (esp hypokalemia), ensure good oxygenation and treat arrhythmias. Sinus bradycardia is common following acute MI especially inferior wall infarctions reflecting acute ischaemia of SA/ AV node. Treatment with atropine and a temporary pacemaker is needed when there is haemodynamic compromise. Some patients with severe bradycardia may require emergency cardiac pacing (transcutaneous or transvenous as appropriate).
Atrial fibrillation (AF) occurs in > 10 % of patients following acute MI and may result from an acute increase in left atrial pressure caused by LV dysfunction. When AF is haemodynamically significant, cardioversion should be promptly done however if AF is well tolerated, â-blocker therapy is indicated.
Ventricular tachycardia (VT) is common following acute MI. Sustained or haemodynamically significant VT is treated with electrical defibrillation while asymptomatic VT is treated with lidocaine, procainamide, or amiodarone.
Ventricular fibrillation (VF) occurs in 3-5% of patients with acute MI. Prophylactic lidocaine is no longer recommended because of an increased incidence of bradydysrhythmias and associated asystole. When VF occurs, rapid defibrillation with 120-200 Joules biphasic or 360 Joules monophasic current should be administered. Mortality is high when VF occurs in patients with hypotension and/or CHF.
Thrombolytic or reperfusion therapy using thromboplastin activator (t-PA) or streptokinase is recommended to minimize the damage caused by intraoperative infarct. To be effective, they should be preferably given within 4 hrs (maximum up to 12 hrs).The major limitation is a predisposition for bleeding so it is contraindicated in patients with fresh surgical wounds however it may be useful in patients who have suffered PMI after procedures like cystoscopy or direct laryngoscopy.
In addition to thrombolytics, medical therapy with β blockers, antithrombotics and antiplatelet drugs can be started to ensure maximum myocardial salvage. Heparin should be started in patients in whom thrombolytic is not given. Heparin has been shown to reduce morbidity and mortality from thromboembolism and reinfarction. Early administration of (3 blockers may decrease the size of infarct, so all patients should receive intravenous β-blockers unless contraindications like CHF or large anterior wall MI with EF <40% exist. Such patients should receive ACE inhibitors.
| Intra-aortic balloon counterpulsation device | | |
Placement of an intra-aortic balloon counterpulsation device has been suggested as a means of reducing perioperative cardiac risk in noncardiac surgery. Although the rate of cardiac complications is low compared with other series of patients at similarly high risk, there are no randomized trials to assess its true effectiveness. There is currently insufficient evidence to determine the benefits vs. risks of prophylactic placement of an intra-aortic balloon counterpulsation device for high-risk noncardiac surgery.
| Conclusions | | |
Perioperative myocardial infarction is a significant issue in patients undergoing not only high risk surgery but also those with clinical predictors that put them at a higher risk even with minor surgical interventions. Though the understanding of the pathophysiology and management of ischaemia in the perioperative period has increased tremendously over the last decade but lot of questions still remain unanswered. In view of the poor positive predictive value of non-invasive cardiac stress tests, the emphasis is on a combination of selective non-invasive testing (to reliably identify those patients whotruly benefit from preoperative intervention such as preoperative coronary revascularization, initiation or optimization of cardio protective medication, aggressive perioperative pharmacological therapy or cancellation of surgery).The perioperative period induces large, unpredictable and unphysiological changes in sympathetic tone, cardiovascular performance, coagulation and inflammatory response which in turn lead to alterations in plaque morphology and function. The importance of sympathetic activation in ischaemic syndromes leading to plaque rupture and secondary insults have targeted therapy towards stabilization of the so called vulnerable plaque by pharmacological means (statins, aspirin, β-blockers)which may be as important in the prevention of PMI as an increase in myocardial oxygen supply (by coronary revascularization),or a reduction in myocardial oxygen demand (by β-blockers or α- 2 -agonists).
Having said that, there is still some way to go before we can have formal strategies and guidelines for preventing, identifying and managing perioperative sub clinical myocardial injury and further research in this area is the need of the hour.
| References | | |
| 1. | Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990; 72: 153-84.  [PUBMED] [FULLTEXT] |
| 2. | Landesberg G. The pathophysiology of perioperative myocardial infarction: facts and perspectives. Cardiothorac VascAnesth 2003;17:90-100. |
| 3. | Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined: a consensus document of the Joint European Societyof Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J 2000; 21: 1502-13. |
| 4. | Slogoff S, Keats AS: Does perioperative myocardial ischemia lead to postoperative myocardial infarction?Anesthesiology1985; 62:107-14. |
| 5. | Mangano DT, Browner W, Hollenberg M, et al. For the Study of Perioperative Ischemia Research Group. Long-term cardiac prognosis following noncardiac surgery. JAMA 1992; 268: 233-9. |
| 6. | Ouyang P, Gerstenblith G, Furman WR, et al. Frequency and significance of early postoperative silent myocardial ischemia in patients having peripheral vascular surgery. Am J Cardiol 1989;64: 1113-6. [PUBMED] [FULLTEXT] |
| 7. | Raby KE, Barry J, Creager MA, et al. Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral vascular surgery. JAMA 1992;268:222-7. [PUBMED] |
| 8. | Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction.Br J Anaesth 2004;93:9-20. [PUBMED] [FULLTEXT] |
| 9. | Selwyn AP, Kinlay S, Creager M, et al. Cell dysfunction in atherosclerosis and the ischemic manifestations of coronary artery disease. Am J Cardiol 1997;79: 17-23. [PUBMED] |
| 10. | Yeung AC, Vekshtein VI, Krantz DS, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med 1991; 325: 1551-56. [PUBMED] |
| 11. | Marschall KE, Barash PG. Myocardial ischemia monitoring :A sequential approach. ASARefresher Courses in Anesthesiology 2004; 32:135-144. |
| 12. | Kloner RA, Bolli R, Marban E, et al. Medical and cellular implications of stunning hibernation and preconditioning: An NHLBI Workshop. Circulation 1998; 97:1848-67. [PUBMED] [FULLTEXT] |
| 13. | Maseri A, Fuster V. Is there a vulnerable plaque? Circulation 2003; 107: 2068-71. [PUBMED] [FULLTEXT] |
| 14. | Devereaux PJ,Goldman L,Cook DJ, et al. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology, of the events and methods to estimate and communicate risk.CMAJ 2005;173:627-634. [PUBMED] |
| 15. | London MJ. What is the best method of diagnosing perioperative myocardial infarction? In:Evidence based practice of anesthesiology. Ed: Fleisher LA.Saunders 2004;344-349. |
| 16. | Harris SH. Hypotension, Hypertension, Perioperative myocardial ischemia and Infarction. In: Benumof JL,Saidman LJ, Editors. Anesthesia and Perioperative Complications. Mosby St Louis 2nd ed.1999:293-307. |
| 17. | Blackburn H,Katigbak R. What electrocardiographic leads to take after exercise? Am Heart J 1964;67:184. [PUBMED] |
| 18. | Priebe HJ. Perioperative myocardial infarction-Aetiology and prevention(Review Article) Br J Anaesth 2005;95:3-19. |
| 19. | The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined-a consensus document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J 2000; 21: 1502-13. |
| 20. | McCord J, Nowak RM, McCullough PA, et al. Ninety minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I. Circulation 2001; 104:1483-1488. [PUBMED] [FULLTEXT] |
| 21. | Sabatine MS,Morrow DA, de Lemos JA, et al. Multimarker approach to risk stratification in non-ST elevation acute cotonary syndromes: Simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 2002; 105: 1760-1763. [PUBMED] [FULLTEXT] |
| 22. | Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery update: A report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery).American College of Cardiology Web site.Available at: http://www.acc.org/ q u a l i t y a n d s c i e n c e / c l i n i c a l / g u i d e l i n e s / p e r i o / perioupdate_index.htm, 2002 . |
| 23. | Goldman L, Caldera DL, Nussbaum SR, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 1977; 297: 845-850. [PUBMED] |
| 24. | DetskyAS, Abrams HB, Forbath N, Scott JG, Hilliard JR. Cardiac assessment for patients undergoing noncardiac surgery: a multifactorial clinical risk index. Arch Intern Med 1986; 146:2131-2134. |
| 25. | Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049. [PUBMED] [FULLTEXT] |
| 26. | Eagle KA, Rihal CS, Mickel MC, et al. Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations. CASS Investigators and University of Michigan Heart Care Program. Coronary Artery Surgery Study. Circulation 1997; 96:1882-1887. |
| 27. | Higgins TL, Estafanous FG, Loop FD, et al. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. A clinical severity score. JAMA 1992; 267: 2344-8. [PUBMED] |
| 28. | Magovern J, Sakert T, Magovern G, et al. A model that predicts morbidity and mortality after coronary artery bypass surgery. J Am Coll Cardiol 1996; 28: 1147-53. |
| 29. | Stolovitz G,Ramsay JG. Perioperative myocardial ischaemia. In : MurrayMJ, Coursin DB, Pearl RG, Prough DS, Eds.Critical Care Medicine: Perioperative management. 2nd ed. Lippincot Raven, Philadelphia; NewYork1997,pg 307-327. |
| 30. | AHA/ACC/SCAI/ACS/ADA Science Advisory. Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients with Coronary Artery Stents. Circulation 2007; 115:813-818. |
| 31. | London MJ, Zaugg M, Schaub MC, Spahn DR. Perioperative J 3 adrenergic receptor blockade. Physiologic foundations and clinical controversies. Anesthesiology 2004;100:170-5. [PUBMED] [FULLTEXT] |
| 32. | Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996; 335: 1713-20. [PUBMED] [FULLTEXT] |
| 33. | Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341: 1789-94. [PUBMED] [FULLTEXT] |
| 34. | Miller RR, Olson HG, Amsterdam EA, Mason DT. Propranolol withdrawal rebound phenomenon. Exacerbation of coronary events after abrupt cessation of antianginal therapy. N Engl J Med 1975; 293: 416-8. [PUBMED] |
| 35. | Psaty BM, Koepsell TD, Wagner EH, LoGerfo JP, Inui TS. The relative risk of incident coronary heart disease associated with recently stopping the use of beta-blockers. JAMA 1990; 263: 1653-57. [PUBMED] |
| 36. | Lecompte T,Hardy JF.Antiplatelet agents and perioperative bleeding. Can JAnaesth 2006,53:S 103-112. |
| 37. | Samama CM, BastienO, Forestier F,et al. Antiplatelet agents in the perioperative period, expert recommendations of the French society of Anaesthesiology and Intensive care(SFAR)2001-Summary statement. Can J Anaesth,2002,49:S 26-35. |
| 38. | Nishina K, Mikawa K, Uesugi T, et al. Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature. Anesthesiology 2002; 96: 323-9. [PUBMED] [FULLTEXT] |
| 39. | Stevens RD, Burri H, Tramer MR. Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review. Anesth Analg 2003; 97: 623-33. |
| 40. | Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7-22. |
| 41. | Sever PS, Dahlof B, Poulter NR and ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149-58. |
| 42. | Biccard, B. M., Sear, J. W., Foex, P. Statin therapy: a potentially useful peri-operative intervention in patients with cardiovascular disease. Anaesthesia 2005;60:1106-1114. |
| 43. | Slogoff S, Keats AS. Does chronic treatment with calcium entry blocking drugs reduce perioperative myocardial ischemia? Anesthesiology 1988; 68: 676-80. |
| 44. | Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Eng J Med 2000; 342: 145-53. |
| 45. | Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355: 1575-81. |
| 46. | Schoolwerth AC, Sica DA, Ballermann BJ, et al. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation 2001; 104: 1985-91. |
| 47. | Gibbs NM, Bell R. The effect of low-dose heparin on hypercoagulability following abdominal aortic surgery. Anaesth Intens Care 1998; 26: 503-8. |
| 48. | Mangano DT. Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of perioperative ischemia (McSPI) Research Group. JAMA 1997; 277: 325-32. |
| 49. | Kaneko T, SaitoY, Hikawa Y, Yasuda K, Makita K. Dose-dependent prophylactic effect of nicorandil, an ATP-sensitive potassium channel opener, on intra-operative myocardial ischaemia in patients undergoing major abdominal surgery. Br J Anaesth 2001;86: 332-7. |
| 50. | Stoelting RK, Dierdorf SF. Ischemic heart disease. In Anesthesia and co-existing disease 4thedition Stoelting, Dierdorf eds Churchill Livingstone,Philadelphia,2002,1-24. |
| 51. | Parker SD, Breslow MJ, Frank SM, et al, Perioperative Ischemia Randomized Anesthesia Trial Study Group. Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Crit care Med 1995;23:1954-61. |
| 52. | Rosenfeld BA, Beattie C, Christopherson R, et al. Perioperative Ischemia Randomized Anesthesia Trial Study Group. The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 1993; 79: 435-43. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|
