MANAGEMENT (Table 9.1) The choice of treatment for ACS largely depends on an assessment of the risk of immediate extensive myocardial

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1 242 INTENSIVE CARE a I II III AVR AVL AVF V 1 V 2 V 3 V 4 V 5 V 6 Fig. 9.1 Electrocardiogram (ECG) changes in myocardial infarction and evolution of ECG changes in ST-segment elevation myocardial infarction (STEMI). (a) An acute anterolateral myocardial infarction shown by a 12-lead ECG. Note the ST segment elevation in leads I, AVL and V 2 V 6. The T wave is inverted in leads I, AVL and V 3 V 6. Pathological Q waves are seen in leads V 2 V 6. (b) An acute inferior wall myocardial infarction shown by a 12-lead ECG. Note the raised ST segment and Q waves in the inferior leads (II, III and AVF). The additional T- wave inversion in V 4 and V 5 probably represents anterior wall ischaemia. Adapted from Kumar P, Clark M 2005 Clinical Medicine 6E Elsevier with permission. b I II III AVR AVL AVF V 1 V 2 V 3 V 4 V 5 V 6 metabolic disturbances; drug toxicity; pericarditis; left ventricular hypertrophy; normal variant; Wolff Parkinson White syndrome and conduction defects. Cardiac-specific troponin I and troponin T are highly sensitive and specific early markers of myocardial injury. Levels start to rise within 3 4 hours after MI and remain raised for 4 10 days. If the initial troponin assay is negative a repeat determination should be performed 9 12 hours later. Measurement of creatinine kinase (CK)-MB levels is less specific but may be useful for monitoring the course of established MI. It is important to appreciate that a positive cardiac troponin (> 0.1 ng/ml) does not differentiate between the various causes of myocardial injury and that troponin levels are raised in many other conditions, including sepsis, renal failure, pulmonary embolism and cerebrovascular accident (Ammann et al., 2004). New markers of myocardial injury such as myeloperoxidase and glutathione peroxidase 1 are becoming available. Echocardiography can be useful for identifying wall motion abnormalities (which support the diagnosis) and assessing the severity of left ventricular impairment, as well as for the diagnosis of specific complications such as mitral regurgitation, ventricular septal defect, pericardial effusion and myocardial rupture. Echocardiography may also detect alternative diagnoses such as aortic dissection, pericarditis or pulmonary embolism (see Chapter 4). MANAGEMENT (Table 9.1) The choice of treatment for ACS largely depends on an assessment of the risk of immediate extensive myocardial

2 Myocardial ischaemia, cardiopulmonary resuscitation and management of arrhythmias 243 c Before Minutes afterwards Hours afterwards Days afterwards β-blockade to reduce myocardial oxygen demand (unless contraindicated); treat pulmonary oedema (see Chapters 7 and 8). Treatment can be given prior to hospital admission by trained health care professionals using strict guidelines. 3-hydroxy- 3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor agents (statins) are routinely administered to patients with ACS. These agents may stabilize the plaque, improve vascular and myocardial remodelling and, when given early, reduce the incidence of further cardiovascular events. The treatment of STEMI (or MI with new/presumed new LBBB) aims to restore the blood supply to myocardium that has not been irreversibly damaged. Clinical trials have confirmed the efficacy of early reperfusion therapy in reducing infarct size, complications and mortality from MI (GUSTO Angiographic Investigators, 1993; Zijlstra et al., 1993). Reperfusion should be achieved as soon as possible after the onset of chest pain. Coronary reperfusion may be achieved by percutaneous coronary intervention (PCI) or thrombolysis. In this situation coronary artery surgery is usually reserved for the complications of MI. An early invasive strategy also seems to be associated with sustained benefit in moderate- to high-risk patients with non-st-elevation ACS (Lagerqvist et al., 2006). Weeks afterwards Fig. 9.1 (c) Electrocariographic evolution of myocardial infarction (STEMI). After the first few minutes the T waves become tall, pointed and upright and there is ST-segment elevation. After the first few hours the T waves invert, the R- wave voltage is decreased and Q waves develop. After a few days the ST segment returns to normal. After weeks or months the T wave may return to upright but the Q wave remains. Adapted from Kumar P, Clark M 2005 Clinical Medicine 6E Elsevier with permission. damage or further coronary events (Bertrand et al., 2002; Van der Werf et al., 2003) (Table 9.2). Immediate management should include general measures combined with treatment to relieve symptoms, limit myocardial damage and reduce the risk of cardiac arrest: oxygen in high concentrations via a facemask; aspirin 300 mg (chewed) as soon as possible: can be combined with clopidogrel (300 mg p.o. loading dose then 75 mg p.o. daily) and low-molecularweight heparin; nitroglycerine as sublingual glyceryl trinitrate (0.3 1 mg) repeated, unless the patient is hypotensive; continuous ECG monitoring: obtain 12-lead ECG; establish venous access and obtain blood for biochemical markers, full blood count, biochemistry, lipids, glucose; morphine or diamorphine titrated intravenously, avoiding oversedation and respiratory depression; consider an antiemetic if nausea is present; Percutaneous coronary intervention PCI, performed within 90 minutes if possible, is the preferred reperfusion therapy in interventional cardiology centres with the available expertise, especially if more than 3 hours have elapsed since the onset of chest pain. Percutaneous transluminal coronary angioplasty (PTCA) performed within 12 hours of the onset of STEMI is associated with a lower risk of death or reinfarction when compared to thrombolysis (Keeley et al., 2003). Rates of reintervention, hospital readmission and recurrent ischaemia may also be lower with PTCA than with thrombolysis. The superiority of PCI in this situation is largely attributable to a reduction in the incidence of recurrent MI. Stenting of the coronary arteries during primary PCI seems to reduce the need for repeat target vessel revascularization but does not appear to influence mortality. It is unclear whether the use of drug-eluting stents is advantageous in patients with acute MI (Laarman et al., 2006; Spaulding et al., 2006). A recent trial (Fernandez- Aviles et al., 2004) suggests that PCI is safe, and improves clinical outcome at 1 year even when performed following thrombolysis. There is some evidence to suggest that atrial natriuretic peptide can reduce infarct size in patients undergoing reperfusion treatment (Kitakaze et al., 2007). Thrombolysis Thrombolysis is most effective when administered within 6 hours of STEMI or new LBBB MI, whereas the benefits are limited when treatment is delayed for more than 12 hours (Fibrinolytic Therapy Trialists Collaborative Group, 1994). Older patients benefit less from thrombolysis, perhaps because of their increased risk of cerebrovascular accident.

3 244 INTENSIVE CARE Table 9.1 Pharmacological therapy in acute coronary syndromes Drug Dose Notes Oxygen 35 50% Check ABG in severe COPD Antiplatelet Aspirin mg chewable or soluble aspirin, then 75 mg p.o. daily Give PPI to those with dyspepsia history Clopidogrel 300 mg p.o. loading dose, then 75 mg p.o. daily Caution: increased risk of bleeding; avoid if CABG planned Analgesia Diamorphine mg i.v. Prescribe with antiemetic (e.g., metoclopramide 10 mg i.v.) Myocardial energy consumption β-blockers e.g. Atenolol 5 mg i.v. repeated after 15 min, then mg p.o. daily or Metoprolol 5 mg i.v. repeated to a maximum of 15 mg, then mg p.o. twice daily Avoid in asthma, heart failure, hypotension, bradyarrhythmias Coronary vasodilatation Glyceryl trinitrate 2 10 mg/h i.v./buccal or sublingual Maintain systolic BP above 90 mmhg Plaque stabilization/ventricular remodeling HMG-CoA reductase inhibitors (statins) ACE inhibitors e.g. Simvastatin mg p.o. daily Pravastatin mg p.o. daily Atorvastatin 80 mg p.o. daily e.g. Ramipril mg p.o. daily Lisinopril 5 10 mg p.o. daily PLUS FOR NON-ST-ELEVATION MYOCARDIAL INFARCTION (NSTEMI) Antithrombin Low-molecular-weight Enoxaparin 1 mg/kg s.c. twice daily heparins Glycoprotein IIb/IIIa inhibitors Abciximab 250 mcg/kg i.v. bolus then 125 nanogram/kg per min up to 10 mcg/min i.v. for 12 h Eptifibatide 180 mcg/kg i.v. bolus, then 2 mcg/kg per min i.v. for 72 h Tirofiban 400 nanogram/kg per min i.v. for 30 min, then 100 nanogram/kg per min for h PLUS FOR ST-ELEVATION MYOCARDIAL INFARCTION (STEMI) Thrombolysis Combine with dietary advice and modification Monitor renal function If coronary intervention likely within 24 h Indicated in high-risk patients managed without coronary intervention or during PCI Indicated in high-risk patients managed without coronary intervention or during PCI Streptokinase units i.v. over 60 min Antibodies appear after 4 days. It should not therefore be used after this time Drug doses are for adult patients with normal renal or hepatic function and without specific contraindications.

4 Myocardial ischaemia, cardiopulmonary resuscitation and management of arrhythmias 245 Table 9.1 Continued Drug Dose Notes Alteplase Or Tenecteplase Or Reteplase 15 mg i.v. bolus, then 50 mg over 30 min and 35 mg over 60 min mg i.v. bolus according to weight ( mcg/kg) 10 units i.v. bolus repeated after 30 min Dose modification if < 65 kg or 6 12 h post-mi Prescribe heparin for at least 24 h (consult product literature) Prescribe heparin for at least 24 h (consult product literature) Prescribe heparin for 48 h (consult product literature) ABG, arterial blood gases; ACE, angiotensin-converting enzyme; BP, blood pressure; CABG, coronary artery bypass grafting; COPD, chronic obstructive pulmonary disease; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; LMW, PCI, percutaneous coronary intervention; PPI, proton pump inhibitor. Drug doses are for adult patients with normal renal or hepatic function and without specific contraindications. Table 9.2 The thrombolysis in myocardial infarction (TIMI) risk score for acute coronary syndromes Risk factor Score Age > 65 1 More than three coronary artery disease risk factors: hypertension, hyperlipidaemia, family history, diabetes, smoking 1 Known coronary artery disease (coronary angiography stenosis > 50%) 1 Aspirin use in the last 7 days 1 Severe angina (more than two episodes of rest pain in 24 hours) 1 ST deviation on ECG (horizontal ST depression or transient ST elevation > 1 mm) 1 Elevated cardiac markers (CK-MB or troponin) 1 Total score Rate of death/mi in 14 days (%) Rate of death/mi/urgent revascularization (%) CK-MB, creatine kinase MB; ECG, electrocardiogram; MI, myocardial infarction. The death rate from MI can be reduced by prompt reperfusion therapy (door to needle time < 20 minutes). Streptokinase is the agent most commonly used worldwide. Recombinant tissue-type plasminogen activator (rt-pa) achieves higher reperfusion rates but is more expensive than streptokinase and is associated with a higher risk of stroke. Some use rt-pa in preference to streptokinase in patients less than 50 years old with anterior MI, in those with hypotension and in patients who have previously received streptokinase. Recombinant t-pa appears to be considerably more effective than streptokinase if it can be given within 4 hours of the onset of chest pain. Double-bolus reteplase and singlebolus tenecteplase facilitate rapid administration of fibrinolytic therapy and can be used for pre-hospital fibrinolysis. If the patient fails to reperfuse within minutes (as demonstrated by 50% reduction in the extent of ST-segment elevation), re-thrombolysis or referral for rescue coronary angioplasty is indicated. Thrombolysis should be accompanied by aspirin therapy, which in STEMI should be combined with clopidogrel.

5 246 INTENSIVE CARE Table 9.3 Contraindications to thrombolysis Absolute contraindications Haemorrhagic stroke or stroke of unknown origin at any time Ischaemic stroke in preceding 6 months Central nervous system damage or neoplasms Recent major trauma/surgery/head injury (within preceding 3 weeks) Gastrointestinal bleeding within the last month Known bleeding disorder Aortic dissection Relative contraindications Transient ischaemic attack in preceding 6 months Oral anticoagulant therapy Pregnancy or within 1 week postpartum Non-compressible puncture wounds Traumatic resuscitation Refractory hypertension (systolic blood pressure > 180 mmhg) Advanced liver disease Infective endocarditis Heparin is recommended adjunctive therapy with alteplase, reteplase or tenecteplase to prevent re-thrombosis but not with streptokinase. Unfractionated heparin is preferred in patients receiving tenecteplase. The contraindications to thrombolysis are listed in Table 9.3. Low-risk patients with non-st-segment elevation ACS (no recurrence of chest pain during observation, normal ECG or minor T-wave changes only, normal troponin on the initial assay and at 6 12 hours post admission) can be managed with oral aspirin and/or clopidogrel, β-blockers and nitrates (Chen, 2005; Yusuf et al., 2001). Glycoprotein (GP) IIb/IIIa platelet receptor inhibitors (e.g. abciximab, eptifibatide, tirofiban) are of most benefit in troponin-positive patients with diabetes scheduled for coronary intervention. Patients with NSTEMI should be given low-molecular-weight heparin. Subsequent management Delayed coronary revascularization is recommended for high-risk patients with ACS who have not been adequately revascularized acutely and low-risk patients in whom an exercise or dobutamine stress test proves positive. Those with single-vessel disease are normally treated with PCI, whereas patients with left main stem lesions or triple-vessel disease may be best managed by surgical coronary artery bypass grafting. Surgery may also be indicated in those with complex coronary lesions. Coronary stenting may stabilize the disrupted coronary plaque and reduces restenosis rates compared to PTCA alone. The incidence of complications associated with coronary intervention can be reduced by preprocedure clopidogrel and periprocedure GP IIb/IIIa inhibitors. Such an interventional approach significantly reduces mortality, as well as reducing the rate of MI, recurrent angina and hospital readmission. Patients with increased troponin levels benefit most. Preventive strategies Secondary prevention involves antithrombotic therapy with low-dose aspirin (75 mg daily), preservation of left ventricular function with an angiotensin-converting enzyme inhibitor, β-blockade and, for those with angina, oral nitrates. Cholesterol reduction strategies, including low-fat, highfibre diet and regular exercise, will complement cholesterol suppression by statins. In those with diabetes blood glucose levels must be strictly controlled. Effective control of blood pressure, maintenance of optimal body weight and removal of avoidable risk factors such as smoking contribute to a reduction in the risk of future coronary events, cardiorespiratory collapse and death. Complications These include: cardiac failure/cardiogenic shock; myocardial rupture/aneurysmal dilatation; ventricular septal defect; mitral regurgitation; cardiac arrhythmias; conduction disturbances; post-mi pericarditis and Dressler s syndrome. The Killip classification can be used to assess patients with heart failure post MI: Killip I no crackles and no third heart sound Killip II crackles in < 50% of the lung fields or a third heart sound Killip III crackles in > 50% of the lung fields Killip IV cardiogenic shock. Prognosis The risk of death following STEMI can be predicted using the TIMI score (Table 9.4) (Chesebro et al., 1987). CARDIORESPIRATORY ARREST Millions of people around the world have learned the fundamentals of cardiopulmonary resuscitation (CPR). Instructions are available on the internet at org. Readers interested in refreshing their knowledge of advanced CPR can access or For up-to-date posters of the algorithms for basic and advanced life support, go to edu. Recent evidence suggests that cardiac-only resuscitation

6 References pp Bertrand ME, Simoons ML, Fox K, et al. (2002) Management of acute coronary syndromes in patients presenting without persistent ST segment elevation. European Heart Journal 23: Chen Z (2005) COMMIT/CCS-2: Clopidogrel and metopralol in myocardial infarction trial/second Chinese cardiac study the clopidogrel arm. Available online at: Chesebro JH, Knatterud G, Roberts R, et al. (1987) Thrombolysis in myocardial infarction (TIMI) Trial phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76: Fernandez-Aviles F, Alonso JJ, Castro- Beiras A, et al. (2004) Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet 364: Fibrinolytic Therapy Trialists Collaborative Group (1994) Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 343: GUSTO Angiographic Investigators (1993) The effects of tissue plasminogen activator, streptokinase or both on coronary-artery patency, ventricular function and survival after acute myocardial infarction. New England Journal of Medicine 329: Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361: Kitakaze M, Asakura M, Kim J, et al. and the J-WIND investigators (2007) Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet 370: Lagerqvist B, Husted S, Kontny F, et al. (2006) 5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-st-elevation acute coronary syndrome: a follow-up study. Lancet 368: Laarman GJ, Suttorp MJ, Dirksen MT, et al. (2006) Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. New England Journal of Medicine 355: Spaulding C, Henry P, Teiger E, et al. (2006) Sirolimus-eluting versus uncoated stents in acute myocardial infarction. New England Journal of Medicine 355: Van der Werf F, Ardissino D, Betriu A, et al. (2003) Management of acute myocardial infarction in patients presenting with ST segment elevation. European Heart Journal 24: Yusuf S, Zhao F, Mehta SR, et al. (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New England Journal of Medicine 345: Zijlstra F, de Boer MJ, Hoorntje JC, et al. (1993) A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. New England Journal of Medicine 328: Extracts 2008 Elsevier Limited. All rights reserved.