12-lead ECG A resting ECG may not con \201 rm the diagnosis but can point towards ischaemi c heart disease. The presence of T-wave inversion (2 mm) or Q waves suggests previous myoca rdial injury. The presence of ST depres- sion and, to a lesser extent, T-wave inversion dur ing pain is a marker of ischaemia, and patients with these signs should be further investig ated. If ST-segment deviation is observed at rest, an acute coronary syndrome must be exclu ded. 12-lead ECG can also help identify other causes of chest pain (LVH, arrhythmia, perica rditis). Tests for inducible ischaemia Tests such as exercise ECG, stress echocardiography (ECHO), o r myo- cardial perfusion scanning are a useful adjunct to con \201 rm the diagnosis and ai d management. Management Lifestyle : Stop smoking. Encourage daily aerobic exercise within limits of exer cise capacity. Look at occupational needs and advise adjustment if symptom level not compat ible. Advise healthy diet, collaborating with dieticians if required. Aspirin : (75 mg/24 h) In all cases unless active peptic ulcer disease or bleeding diathesi s. Those with past peptic ulcer disease may take a gastro- protective agent such as a H 2 a ntagonist or proton pump inhibitor. Anti-anginals : B-blockers: 1st line (e.g. atenolol 25 \200\223100 mg od or metoprolol 25 \200\22350 mg tds). Start on suspicion of IHD. Avoid onl y if contraindicated (asthma with con \201 rmed B-agonist response (mortality improved in patients with angina and concomitant chronic obstructive pulmonary disease (COPD) if they c an tolerate the reduced peak expiratory \202 ow rate (PEFR)), uncontrolled severe LV dysf unction, bradycardia, coronary artery spasm). Calcium antagonists : (e.g. amlodipine 5 \200\22310 mg od or diltiazem MR 90 \200\223180 mg bd) if B -blocker contraindicated. Nitrates : (e.g. GTN spray) Used for control of breakth rough angina. Long-acting nitrates (e.g. isosorbide mononitrate MR 60 \200\223120 mg od) ar e a useful addition to B -blockers for prevention of attacks. Statins : Reduce mortality by approximately one-third in all risk groups. However, the underlying risk of events must be taken into account when considering starting the drug because absolute risk reduction in y oung patients with low-risk IHD may be very small, with a possible harm of myositis, hepati c failure, and reduced compliance with other medications. ANGINA PECTORIS 253 Chest pain clinics Rapid-access or open-access chest pain clinics have transformed the prim ary and secondary care interface for UK patients since their incorpo- ration into the Natio nal Service Framework. They have facilitated the shift of care of stable angina from genera list to specialist, and increased rates of angiography and revascularization. It is not kno wn if this has an effect on mortality but it has certainly prioritized cardiac care and rat es of diagnosis of IHD. The clinics usually involve a standardized referral form, which can be used by either a general practitioner (GP) or hospital physician. The emphasis is on early exclusion of non-cardiac disease and risk strati \201 cation for IHD. Thus, in the \201 rst visit, the patient would see a specialist, perform an exercise test, and have baseline risk factors estimated. At the end of the consultation, the patien t will be reassured that there is a low likelihood of IHD or will begin the path of treatme nt of risk factors and symptoms, ultimately leading to revascularization if required. 254 CHAPTER 5 Coronary artery disease Acute coronary syndromes Acute coronary syndrome (ACS) is an operational term used to descr ibe a constellation of symptoms resulting from acute myocardial ischaemia. An ACS resulting in myocardial injury is termed myocardial infarction (MI). ACS includes the diagnosis of u nstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segmen t elevation myo- cardial infarction (STEMI). The term ACS is initially generally, assigned by ancillary/triage personnel on initial contact with the patient. Guidelines for identi \201 cation of ACS are summarized in Table 5.7 on b NSTEMI/UA: risk strati \201 cation, p. 295. De \201 nition The current nomenclature divides ACS into two major groups, on the basis of delivered treatment modalities (see Fig. 5.12): \200 STEMI \200\224 an ACS where patien ts present with chest discomfort and ST-segment elevation on ECG. This group of patients mu st undergo reperfusion therapy on presentation NSTEMI and UA \200\224 ACS where patients present with ischaemic chest discomfort associat ed with transient or permanent non-ST-elevation ischaemic ECG changes. If there is biochemi cal evidence of myocardial injury, the condition is termed NSTEMI, and in the absence if bi ochemical myocardial injury the condition is termed UA (see b Non-ST elevation myocardial i nfarction (NSTEMI)/unstable angina (UA), p. 290). This group of patients is not treated wit h thrombolysis. Initial management of ACS \200 All patients with suspected ACS should be placed in an env ironment with continuous ECG monitoring and de \201 brillation capacity. The referring doctor should be instructed to give aspirin (300 mg PO if no contraindication s) and not to give any IM injections (causes a rise in total creatine kinase (CK) and risk of bleeding with thrombolysis/ anticoagulation). Immediate assessment should include: \200 rapid examination to exclude hypotension, note the presence of murmurs, and identify and treat acute pulmonary oedema secure intravenous (IV) access \200 12-lead ECG should be obtained and reported within 10 minutes. Give: \200 oxygen (initially only 28 % if history of COPD) \200 diamorphine 2 .5 \200\22310 mg IV prn for pain relief \200 metoclopramide 10 mg IV for nausea \200 GT N spray 2 puffs/unless hypotensive Take blood for: \200 FBC/U&E \200\224 Supplement K + to keep it at 4 \200\2235 mmol/L \200 glucose: may be i acutely post-MI, even in non-diab etic patients, and re \202 ects a stress-catecholamine response and may resolve without tr eatment biochemical markers of cardiac injury (see b STEMI: diagnosis, p. 258). ACUTE CORONARY SYNDROMES 255 lipid pro \201 le \200\224 total cholesterol, LDL, HDL, triglycerides; serum cholesterol and HDL remain close to baseline for 24 \200\22348 hours but fall thereafter an d take (cid:2)8 weeks to return to baseline. Portable CXR will assess cardiac size and pulmonary oedema and exclude mediastinal enlargement. General examination should include peripheral pulses, fundoscopy, and abdominal examination for organomegaly and aortic aneurysm. Conditions mimicking pain in ACS \200 Pericarditis \200 Dissecting aortic aneurysm \200 Pulmonary embolism \200 Oesophageal re \202 ux, spasm or rupture \200 Biliary tr act disease \200 Perforated peptic ulcer \200 Pancreatitis Acute coronary syndromes No ST elevation ST elevation No enzyme rise NSTEMI Unstable angina NQ-MI QwMI Fig. 5.12 Nomenclature of ACS: patients with ACS may present with or without ST elevation o n the ECG. The majority of patients with ST elevation (large arrows) ultimately develop Q-w ave MI (QwMI), whereas a minority (small arrow) develop a non-Q-wave MI (NQ-MI). Patients w ithout ST-elevation are experiencing either UA or an NSTEMI, depending on the absence or pr esence of cardiac enzymes (e.g. troponin) detected in the blood. Adapted and reproduced wit h permission from Antman EM, Braunwald E (1997). Acute myocardial infarction. In Braunwald EB (ed). Heart Disease: a textbook of cardiovascular medicine . Philadelphia, PA WB Saunder s. 256 CHAPTER 5 Coronary artery disease ST elevation myocardial infarction (STEMI) Patients with an ACS who have ST-segment elevati on/left bundle branch block (LBBB) on their presenting ECG bene \201 t signi \201 cantly from immediate reperfusion, and are treated as one group under the term ST elevation myocar dial infarction (STEMI). Presentation \200 Chest pain is usually similar in nature to angina, but of greater sever ity, longer duration and not relieved by sublingual GTN. Associated features include: nausea and vomiting, sweating, breathlessness, and extreme distress. The pains may be atypical (e.g. epigastric), or radiate to the back. \200 Individuals wit h diabetes, or hypertension, and the elderly may suffer painless ( \200\230silent \200\231 infarcts) and/or atypical infarction . Presenting features include breathlessness from acut e pulmonary oedema, syncope or coma from dysrrhythmias, acute confusional states (mania/psy chosis), diabetic hyperglycaemic crises, hypotension/cardiogenic shock, and central nervous system (CNS) manifestations resembling stroke, secondary to sudden reduction in cardiac ou tput and peripheral embolization. Management Diagnosis is normally made on presentation, followed by rapid stablization to en sure institution of reperfusion therapy without delay. This is in con- trast to NSTEMI/UA w here diagnosis may evolve over period of 24 \200\22372 hours (see b Non-ST elevation myocar dial infarction (NSTEMI)/unstable angina (UA), p. 290). The management principles of the va rious stages are outlined below and expanded subsequently. \200 Stabilizing measures are generally similar for all ACS patients (see b STEMI: general measures, p. 262): \200 all patients with suspected STEMI should ha ve continuous ECG monitoring in an area with full resuscitation facilities patients should receive immediate aspirin 300 mg PO (if no contraindications), analgesia, a nd oxygen; secure IV access rapid examination to exclude hypotension, note the presence of murmurs, and identify and tr eat acute pulmonary oedema. Right ventricular function (RVF) out of proportion to left vent ricular function (LVF) suggests RV infarction (see b Right ventricular infarction, p. 272) blood for FBC, biochemical pro \201 le, markers of cardiac injury, lipid pro \201 le, glucose, and portable CXR. Diagnosis must be made on the basis of history, ECG (ST elevation/ new LBBB), and biochemical markers of myocardial injury. ( NB: if ECG changes are diagnosti c, reperfusion must not be delayed to wait for biochemical markers). ST ELEVATION MYOCARDIAL INFARCTION (STEMI) 257 Treatment \200 General medical measures (see b STEMI: general measures, p. 262). \200 R eperfusion ((see b STEMI: reperfusion therapy (thrombolysis) and STEMI: reperfusion by primary PCI, p. 264 \200\2239). All patients with STEMI should be admitted to the coronary care unit (CCU). Discharge and risk prevention. Factors associated with a poor prognosis \200 Age > 70 years \200 Previous MI or chroni c stable angina \200 Anterior MI or right ventricular infarction \200 LV failure at pre sentation \200 Hypotension (and sinus tachycardia) at presentation \200 Diabetes mellit us \200 Mitral regurgitation (acute) \200 Ventricular septal defect 258 CHAPTER 5 Coronary artery disease STEMI: diagnosis This is based on a combination of history, ECG, and biochemical markers of cardiac injury . In practice, history and ECG changes are normally diag- nostic, resulting in immediate reperfusion/medical treatment. Biochemical markers of cardiac injury usually become available later and help to recon- \201 rm the diagnosis, as well as to provide pr ognostic information (magni- tude of rise). ECG changes \200 ST segment elevation occurs within minutes and may last for up to 2 weeks. ST elevation of (cid:2) 2 mm in adjacent chest leads and (cid:2) 1 mm in adjacent limb leads is necessary to ful \201 l thrombolysis criteria. Persisting ST elevation after 1 month suggests formation of LV aneurysm. The infarction site can be localized from ECG c hanges as indicated in the box opposite. Pathological Q waves indicate signi \201 cant abnormal electrical conduction, but are not synonymous with irreversible myocardial damage. In the context of a \200\230transmural inf arction \200\231, it may take hours or days to develop and usually remains inde \201 nitel y. In the standard leads, the Q wave should be (cid:2) 25 % of the R wave, 0.04 s in durati on, with negative T waves. In the precordial leads, Q waves in V 4 should be > 0.4 mV (4 sm all squares) and in V 6 > 0.2 mV (2 small squares), in the absence of LBBB (QRS width <0.1 s or 3 small squares). \200 ST-segment depression (ischaemia at distance) in a second ter ritory (in patients with ST-segment elevation) is secondary to ischaemia in a territory oth er than the area of infarction (often indicative of multivessel disease), or reciprocal ele ctrical phenomena. Overall, it implies a poorer prognosis. PR-segment elevation/depression and alterations in the contour of the P wave are generally indicative of atrial infarction. Most patients will also have abnormal atrial rhythms such as AF/ \202 utter, wandering atrial pacemaker, and AV nodal rhythm. T-wave inversion may be immediate or delayed, and generally persists after the ST elevation has resolved. Non-diagnostic changes , but ones that may be ischaemic, include new LBBB or right bundle branch block (RBBB), tachyarrhythmias, transient tall peaked T waves o r T-wave inversion, axis shift (extreme left or right), or AV block. Biochemical markers of cardiac injury Serial measurements evaluating a temporal rise and fa ll should be obtained to allow a more accurate diagnosis. CK and CK-MB from a skeletal musc le source tend to remain elevated for a greater time period in comparison to a cardiac sour ce. STEMI: DIAGNOSIS 259 Conditions that may mimic ECG changes of a STEMI \200 Left or right ventricular hypertrop hy \200 LBBB or left anterior fasciculate block \200 Wolff \200\223Parkinson \200\223Wh ite syndrome \200 Pericarditis or myocarditis \200 Cardiomyopathy (hypertrophic or dila ted) \200 Trauma to myocardium \200 Cardiac tumors (primary and metastatic) \200 Pulm onary embolus \200 Pneumothorax \200 Intracranial hemorrhage \200 Hyperkalaemia \200 Cardiac sarcoid or amyloid \200 Pancreatitis. Localization of infarcts from ECG changes Anterior ST elevation and/or Q waves in V 1 \200\223V 4 /V 5 ST elevation and/or Q waves in V 1 \200\223V 3 Anteroseptal ST elevation and/or Q waves in V 1 \200\223V 6 and I and aVL Anterolateral ST elevation and/or Q waves in V 5 \200\223V 6 and T-wave inversion/ST elevation/Q waves i n I and aVL Lateral ST elevation and/or Q waves in II, III, aVF, and V 5 \200\223V 6 (sometimes I and aVL) Inferolateral Inferior ST elevation and/or Q waves in II, III and aVF ST elevation and/or Q waves in II, III, aVF, V 1 \200\223V 3 Inferoseptal Tall R waves in V 1 \200\223V 2 with ST depression in V 1 \200\223V 3 ; T waves remain up right in V 1 \200\223V 2 . This can be con \201 rmed with an oesophageal lead if availabl e (method similar to a nasogastric (NG) tube). Usually occurs in conjunction with an inferi or or lateral infarct. True posterior RV infarction ST segment elevation in the right precordial leads (V 3R \200\223V 4R ). Usually found in conjunction with inferior infarction. This may only be present in the early hours of infarc tion. Creatine kinase \200 Levels twice the upper-limit of normal are taken as being abnormal. \200 Serum levels rise within 4 \200\2238 hours post-STEMI and fall to normal within 3 \200\2234 days. The peak level occurs at about 24 hours but may be earlier (12 hou rs) and higher in patients who have had reperfusion (thrombolysis or PCI). 260 CHAPTER 5 Coronary artery disease False-positive rates of 715 % occur in patients with alcohol intoxication, muscle disease o r trauma, vigorous exercise, convulsions, IM injections, hypothyroidism, pulmonary embolism (PE), and thoracic outlet syndrome. CK-MB isoenzyme is more speci \201 c for myocardial disease. Levels may be elevated despit e a normal total CK. However, CK-MB is also present in small quantities in other tissues (s keletal muscle, tongue, diaphragm, uterus, and prostate) and trauma or surgery may lead to false-positive results. If there is doubt about myocardial injury with CK-MB levels obtaine d, a cardiac troponin must be measured. Cardiac troponins (TnT, TnI) \200 Both TnT and TnI are highly sensitive and speci \201 c markers of cardiac injury. Serum levels start to rise by 3 hours post-MI, and elevation may persist up to 7 \200\22314 days. This is advantageous for diagnosis of late MI. In most STEMI cases, the diagnosis can be made using a combination of the clinical picture and serial CK/CK-MB levels. In the event of normal CK-MB levels and suspected non-cardiac s ources of CK, troponins can be used. Troponins can also be elevated in non-ischaemic myocyte damage such as myocarditis, cardiomyopathy, and pericarditis. Other markers There are multiple other markers, but with increasing clinical availability o f troponins, measurements are not recommended. These include aspartate transaminase (AST) ( rise 18 \200\22336 hours post-MI) and lactate dehydrogenase (LDH) (rise 24 \200\22336 hours post-MI). The time course of the various markers is shown in Fig. 5.13 . STEMI: DIAGNOSIS 261 Fig. 5.13 Graph of the appearance of cardiac markers in the blood versus time of onset of s ymptoms. Adapted with permission from Wu AH et al. (1999). Clin Chem 45: 1104 \200\22321. P eak A : early release of myoglobin or CK-MB isoforms after AMI. Peak B : cardiac troponin a fter AMI. Peak C : CK-MB after AMI. Peak D : Cardiac troponin after unstable angina. Adapte d with permission from Wu AH et al. (1999). Clin Chem 45: 1104 \200\22321. 262 CHAPTER 5 Coronary artery disease STEMI: general measures 1. Immediate stabilizing measures are as outlined on b Acute corona ry syndromes, p. 254 for all ACS. 2. Control of cardiac pain: diamorphine 2.5 \200\22310 mg IV is the drug of choice and may be repeated to ensure adequa te pain relief, unless there is evidence of emerging toxicity (hypotension, respiratory dep ression). Nausea and vomiting should be treated with metoclopramide (10 mg IV) or a phenoth iazine oxygen to be administered at 2 \200\2235 L/min for at least 2 \200\2233 hours. Hypoxaemia is frequently seen post-MI due to ventilation \200\223perfusion abnormalities se condary to LVF. In patients with refractory pulmonary oedema, continuous positive airways p ressure (CPAP), or via formal endotracheal intubation may be necessary. Beware of CO 2 rete ntion in patients with COPD nitrates may lessen pain and can be given, providing the patient is not hypotensive (sublin gual or intravenous). They need to be used cautiously in inferior STEMI, especially with RV infarction, as venodilation may impair RV \201 lling and precipitate hypotension. Nitrat e therapy has no effect on mortality (fourth International Study of Infarct Survival (ISIS- 4)). 3. Correction of electrolytes : both low potassium and magnesium may be arrhythmogenic and must be supplemented, especially in the context of arrhythmias. 4. Strategies to limit infarct size (B-blockade, ACE-I and reperfusion). B-blockade \200 Early B-blockade in limiting infarct size and reducing mortality and early malignant arrhyt hmias. All patients (including primary PCI and thrombolysis patients) should have early B-b lockade, but those with the following features will bene \201 t most: \200 hyperdynamic state (sinus tachycardia, iBP) \200 ongoing or recurrent pain/reinfarction \200 tachyar rhythmias such as AF. Absolute contraindications : HR<60 bpm, SBP < 100 mmHg, moderate to severe heart failure, A V conduction defect, severe airways disease. Relative contraindications : asthma, current use of calcium-channel blocker and/or B-blocke r, severe peripheral vascular disease with critical limb ischaemia, large inferior MI invol ving the right ventricle. Use short-acting agent IV initially (metoprolol 1 \200\2232 mg at a time repeated at 1 \200\2232 minute intervals to a maximum dose of 15 \200\22320 mg) under conti nuous ECG and BP monitoring. Aim for a pulse rate of 60 bpm and SBP 100 \200\223110 mmHg. I f haemodynamic stability continues 15 \200\22330 minutes after last IV dose, start metoprol ol 50 mg tds. Esmolol is an ultra-short-acting IV B-blocker, which may be tried if there is concern whether the patient will tolerate B-blockers. STEMI: GENERAL MEASURES 263 ACE inhibitors After receiving aspirin, B-blockade (if appropriate), and reperfusion, all p atients with STEMI/LBBB infarction should receive an ACE-I within the \201 rst 24 hours o f presentation. \200 Patients with high-risk/large infarcts, particularly with an anterio r STEMI, a previous MI, elderly population, heart failure, and impaired LV function on imagin g (ECHO) will bene \201 t most. The effect of ACE-I appears to be a class effect: use the drug you are familiar with (e.g. ramipril 1.25 mg od). 264 CHAPTER 5 Coronary artery disease STEMI: reperfusion therapy (thrombolysis) Rapid reperfusion is the cornerstone of current m anagement of STEMI and is marked by normalization of ST segments on ECG. Primary PCI and th rom- bolysis are the main reperfusion modalities. The best long-term outcome is achieved wi th primary PCI. Reperfusion occurs in 50 \200\22370 % of patients who receive thrombolysis within 4 hours o f onset of pain (cf. 720 % of controls). As with primary PCI, thrombolysis also results in reduced mortality, LV dysfunction, heart failure, cardiogenic shock, and arrhythmias. Howev er, the magnitude of the bene \201 ts obtained is smaller. Furthermore, patients must unde rgo cardiac catheterization to delineate their coronary anatomy before revascularization (a chieved at the same time with primary PCI). Time is once again of paramount importance, and thrombolysis should be administered as soon as possible. Indications for thrombolysis \200 Typical history of cardiac pain within previous 12 hour s and ST elevation in two contiguous ECG leads ( > 1 mm in limb leads or > 2 mm in V 1 \200\223V 6 ). Cardiac pain with new/presumed new LBBB on ECG. \200 If ECG is equivocal on arrival, repe at at 15 \200\22330 minute intervals to monitor progression. Thrombolysis should not be given if the ECG is normal, or there is isolated ST depression ( must exclude true posterior infarct), or ST elevation with no preceding history of pain. Timing of thrombolysis \200 Greatest bene \201 t is achieved with early thrombolysis (es pecially if given within 4 hours of onset of \201 rst pain). Patients presenting between 12 and 24 hours from onset of pain should be thrombolysed only with persisting symptoms and ST-segment elevation. Elderly patients ( > 65 years) presenting within the 12 \200\22324 hour time period with symptoms are best managed by primary PCI, as thrombolysis has demonstrated increased cardiac rupture. Patients presenting within 12 \200\22324 hours from onset of pain, whose clinical picture appears to have settled, should be managed initially as an NSTEMI, followe d by early catheterization. Choice of thrombolytic agent \200 This is partly determined by local thrombolysis strateg y. \200 Allergic reactions and episodes of hypotension are greater with streptokinase (SK). Bolus agents are easier and quicker to administer, with a decrease in drug errors in comparison to \201 rst-generation infusions. STEMI: REPERFUSION THERAPY (THROMBOLYSIS) 265 Recombinant tissue plasminogen activator (rt-PA) has a greater reperfusion capacity and a marginally higher 30-day survival bene \201 t than SK, but an i ncreased risk of hemorrhage. More recent rt-PA derivatives have a higher 90-minute TIMI-III (Thrombolysis in Myocardial Infarction) \202 ow rate, but similar 30-day mortality bene \201 t to rt-PA. A rt-PA derivative should be considered for any patient with: \200 large anterior MI espe cially if within 4 hours of onset \200 previous SK therapy or recent streptococcal infect ion \200 hypotension (systolic BP<100 mmHg) \200 low risk of stroke (age <55 years, sys tolic BP <144 mmHg) \200 reinfarction during hospitalization where immediate PCI faciliti es are not available. The characteristics of the major thrombolytic agents are on b p. 266. Patients with greatest bene \201 t from thrombolysis \200 Anterior infarct \200 Marked ST elevation \200 Age > 75 years \200 Impaired LV function or LBBB, hypotensive \200 Systolic BP <100 mmHg \200 Patients presenting within 1 hour of onset of pain Complications of thrombolysis \200 Bleeding is seen in up to 10 % of patients. Most bleed s are minor, at sites of vascular puncture. Local pressure is suf \201 cient but occasionally transfusion may be required. In extreme cases, SK may be reversed by tranexamic acid (10 mg/kg slow IV infusion). Hypotension during the infusion is common with SK. Lay the patient supine and slow/stop infusion until the blood pressure rises. Treatment with cautious (100 \200\223500 mL) \202 uid challenges may be required, especially in inferior/RV infarction . Hypotension is not an allergic reaction and does not warrant treatment as such. Allergic reactions are common with SK and include a low-grade fever, rash, nausea, headache s, and \202 ushing. Give hydrocortisone 100 mg IV with chlorphenamine 10 mg IV. Intracranial hemorrhage is seen in 70.3 % of patients treated with SK and 70.6 % with rt-PA. Reperfusion arrhythmias (most commonly a short, self-limiting run of idioventricular rhythm ) may occur as the metabolites are washed out of the ischaemia tissue. See b Ventricular ta chyarrhythmias post-MI, p. 284, for management. Systemic embolization may occur from lysis of thrombus within the left atrium, LV, or aortic aneurysm. Absolute contraindications to thrombolysis \200 Active internal bleeding \200 Suspected aortic dissection 266 CHAPTER 5 Coronary artery disease Recent head trauma and/or intracranial neoplasm \200 Previous haemorrhagic stroke at any time \200 Previous ischaemic stroke within the past 1 year \200 Previous allergic react ion to \201 brinolytic agent \200 Trauma and/or surgery within the past 2 weeks at risk of bleeding. Relative contraindications to thrombolysis \200 Trauma and/or surgery more than 2 weeks p reviously \200 Severe uncontrolled hypertension (BP > 180/110 mmHg) \200 Non-haemorrhag ic stroke over 1 year ago \200 Known bleeding diathesis, or current use of anticoagulatio n within therapeutic range (international normalized ratio (INR) 2 or over) Signi \201 cant liver or renal dysfunction \200 Prolonged ( > 10 min) cardiopulmonary re suscitation \200 Prior exposure to SK (especially previous 6 \200\2239 months) \200 Pre gnancy or post partum \200 Lumbar puncture within previous 1 month \200 Menstrual bleed ing or lactation \200 History of chronic severe hypertension \200 Non-compressible vasc ular punctures (e.g. subclavian central venous lines). Doses and administration of thrombolytic agents Streptokinase (SK) \200 Give as 1.5 million units in 100 mL normal saline IV over 1 hour. \200 There is no indication for routine heparinization after SK, as there is no clear mo rtality bene \201 t and there is a small increase in risk of hemorrhage. Recombinant tissue-type plasminogen activator (rt-PA, alteplase) \200 The GUSTO (Global U tilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries ) trial suggested the \200\230front-loaded \200\231 or accelerated rt-PA (alteplase) is th e most effective dosage regimen. Give 15 mg bolus IV then 0.75 mg/kg over 30 min (not to exceed 50 mg), then 0.5 mg/kg over 60 min (not to exceed 35 mg). This should be followed by IV heparin (see text). Reteplase \200 Give two IV bolus doses of 10 units 10 minutes apart. Tenecteplase \200 Give as injection over 10 seconds at 30 \200\22350 mg according to body weight (500 \200\223600 mcg/kg). \200 Maximum dose is 50 mg. APSAC (anistreplase) \200 Give as an IV bolus of 30 mg over 2 \200\2235 minutes. This page intentionally left blank