Introduction to perioperative myocardial infarction

Introduction to perioperative myocardial infarction and prophylactic beta-blockade 王永彬 1 Perioperative myocardial infarction 2 Who ? • Patients who experience a PMI have angiographic evidence of extensive CAD. • At one end are those patients who develop an MI after episodes of unstable angina over a period of days to weeks, and who often develop post-infarction angina and/or reinfarction. • At the other end are those patients who suffer a sudden MI without any preceding episode of angina, and not followed by recurrent instability. 3 Why ? critical stenosis • Stenotic atherosclerotic lesions may develop acute MI if there is a marked decrease in myocardial oxygen supply, or a marked increase in myocardial oxygen demand. 4 Why ? Acute coronary syndrome • Rupture of the intimal surface of a plaque is the result of a combination of cellular processes that promote plaque instability, and of physical (hemodynamic) processes that influence the magnitude and distribution of stress on the plaque. • Plaque progression is frequently abrupt, mostly unpredictable, and often related to episodes of thrombosis (which, in turn, are triggered by plaque rupture, erosion, endothelial activation, or inflammation). 5 Why ? sympathetic activation • Plaque rupture is more common during various kinds of strenuous physical activity and emotional stress. Activation of the sympathetic nervous system in these situations leads to increased plasma concentrations of catecholamines, blood viscosity, which are accompanied by detectable increases in platelet aggregation and decreases in fibrinolytic activity that both tend to favor thrombosis. 6 Why ? Prolonged ischemia • Prolonged stress-induced myocardial ischemia (single duration >20–30 min) is the likely primary cause of PMI. • Repeated brief ischemic episodes (cumulative duration >1–2 h) may well have a cumulative effect and ultimately cause myocardial necrosis. 7 What ? • PMIs are more often the result of prolonged ischemia than of thrombotic occlusion, similar to the presumed pathophysiology of silent ischemia. • Non-Q wave MI accompanied by increased cardiac troponin concentrations and prolonged elevation of heart rate and STsegment depression is the predominant form of PMI. • The probability of a Q-wave infarction increases with MI size. Q-wave takes time to develop. • Although ST-segment depression usually reflects subendocardial ischemia and is often regarded as reversible injury, it is not inconsistent with an MI. During the early evolution of an MI, significant ST-segment elevation may be lacking. 8 When ? • Most ischemic episodes tend to start at the end of surgery and during emergence from anesthesia. This period is characterized by increases in sympathetic tone, coronary vasoconstriction and procoagulant activity. • Surgery-induced simultaneous procoagulant and anti-fibrinolytic activity may trigger coronary artery thrombosis during low-flow conditions in the presence of underlying stable CAD even in the absence of acute plaque disruption. 9 How ? coronary revascularization • Its effectiveness continues to be debated. • The indications for preoperative coronary revascularization are essentially identical to those in the non-operative setting • Postpone elective surgery for several months 10 How ? ß-blockade • Perioperative ß-blockade improves cardiac outcome in patients with or at risk CAD, and in patients with documented inducible myocardial ischemia undergoing non-cardiac surgery 11 How ? Other drugs • Alpha-2 agonists • Aspirin: anti-inflammatory, anti-thrombotic • Statins: lipid-lowering, pleiotropic Pleiotropic effects include reversal of endothelial dysfunction, modulation of macrophage activation, immunological effects, andanti-inflammatory, antithrombotic, and antiproliferative actions 12 How ? Miscellaneous measures • Normothermia (陽光) • Oxygenation, hemoglobin concentration (空氣) • Normovolemia (水) • Adequate pain control (舒適) 13 Perioperative ß-blockade 14 Why ? • reduce myocardial O2 consumption by decreasing sympathetic tone (HR, BP) and myocardial contractility. • reduce heart rate and prolong diastolic filling and coronary diastolic perfusion time . • reduce renin release and angiotensin II and aldosterone production by blocking of β1-adrenoceptors on renal juxtaglomerular cells. • decrease ß2-adrenoceptor-mediated release of intracardiac norepinephrine during ischemia (reducing cardiac toxicity) • increase the threshold for ventricular fibrillation during myocardial ischaemia (antiarrhythmic properties ). 15 Why ? • Activation of the hypothalamus–pituitary– adrenal axis persists for at least 1 week following surgery. • Blockade of the perioperative adrenergic stress response and prevention of the cardiotoxic effects of catecholamines play a central role. 16 Who ? 17 Who ? cardiac patient risk • • • • • • • • • • • • • • • • • Major Unstable coronary syndromes Acute or recent MI* with evidence of important ischemic risk by clinical symptoms or noninvasive study Unstable or severe† angina (Canadian Class III or IV)ffi Intermediate Mild angina pectoris (Canadian Class I or II) Previous MI by history or pathological Q waves Compensated or prior heart failure Diabetes mellitus (particularly insulin-dependent) Renal insufficiency Minor Advanced age Abnormal ECG (left ventricular hypertrophy, left bundle-branch block, ST-T abnormalities) Rhythm other than sinus (e.g., atrial fibrillation) Low functional capacity (e.g., inability to climb one flight of stairs with a bag of groceries) History of stroke Uncontrolled systemic hypertension 18 Who ? 19 Who ? Vascular diseases ? • ß-blockers decrease tissue blood flow due to blockade of vascular ß2-receptors and unopposed stimulation of vascular α-adrenoceptors. • They can produce cold extremities and Raynaud's phenomenon and worsen the symptoms in patients with severe peripheral vascular disease. • These side-effects are less pronounced with drugs exhibiting vasodilator effects and with ß1 selective agents. 20 Who ? Diabetes mellitus ? • In patients with insulin-dependent diabetes, nonselective ß-blockers mask some of the warning symptoms of hypoglycemia (tremor, tachycardia; but not sweating) and blunt compensatory glycogenolysis. A selective ß-blocker should therefore be preferred at least in insulin dependent patients. • Most non-insulin-dependent diabetic patients can tolerate these drugs. • CAD with DM have a poorer outcome. The clinical benefit of treatment with ß-blockers outweighs the risk, at least after myocardial infarction. 21 Who ? COPD ? • ß-blockers can lead to a life-threatening increase in airway resistance. • In some patients with COPD, the potential benefit of using ß-blockers may outweigh the risk of worsening pulmonary function. • COPD is not a contraindication unless there is a significant asthma, or reactive bronchospastic airway disease. 22 Who ? CHF ? • β-blockers have become first-line agents for the treatment of CHF of ischemic and non-ischemic origin. • The benefits of β-blockers have been attributed – to normalization and remodeling of the ventricle that begins after 1 month of β-blockade, – to decreased norepinephrine-related cardiomyocyte apoptosis in the presence of β1-blockade, – to decreased sudden cardiac death because of the β-blockers' antiarrhythmic activity. • To avoid worsening a patient's heart failure symptoms and to minimize negative inotropic effects, β-blockers are started at very low doses and titrated to the target dose. 23 Who not? • symptomatic bradycardia (usually a heart rate <50– 60 beats min–1) • symptomatic hypotension (usually a systolic arterial pressure <90–100 mm Hg) • severe heart failure requiring i.v. diuretics or inotropes • cardiogenic shock • asthma or reactive airway disease requiring bronchodilator and/or steroids • 2° or 3° AV block. 24 When ? • Perioperative cardioprotection was demonstrated when the medication had been initiated either weeks before the scheduled surgery, or as late as during premedication and induction of anesthesia. • In patients without clear indications for longterm ß-blocker therapy, ß-blockers should probably be continued for at least the time of hospitalization, and preferably for up to 1 month postoperatively. 25 How ? • Any cardioselective ß-blocker (such as atenolol, bisoprolol, or metoprolol) is probably an acceptable choice. • Preoperative dose is titrated to achieve a resting heart rate between 50 and 60 beats/min • In those patients in whom ß-blocker therapy is going to be discontinued after discharge, the dose should be tapered slowly to avoid acute withdrawal symptoms. 26 References • H.-J. Priebe. Perioperative myocardial infarction—aetiology and prevention. Br J Anaesth 95:3-17, 2005 • The Task Force on Beta-Blockers of the European Society of Cardiology. Expert consensus document on ß-adrenergic receptor blockers. Eur Heart J 25:1341-62, 2004. • ACC/AHA 2006 Guideline Update on Perioperative Cardiovascular Evaluation for Noncardiac Surgery: Focused Update on Perioperative Beta-Blocker Therapy. Circulation 113;2662-2674, 2006. • Miller. Anesthesia 2006 27