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Pre-hospital thrombolysis is associated with mortality reduction and prognosis improvement in patients with ST-elevation myocardial infarction Class n.7 [email protected] 1 Introdução à Medicina 2008/2009 Introduction Acute myocardial infarction (AMI) • Destruction of myocardial tissue resulting from inadequate supply of oxygen to the heart muscle. LCA – left coronary artery; RCA – right coronary artery; 1 – Occlusion; 2 – Myocardial infarction. 2 And how can this happen? 1.http://www.emedicine.com/emerg/TOPIC327.HTM Atherosclerosis (formation of plaques in blood vessels) Narrowing of the lumen Artery Stenosis Thrombi formation 3 2.http://www.emedicine.com/emerg/TOPIC831.HTM Thrombus • Formed usually by platelets, fibrin, red and white blood cells and are attached to a plate or in alignment with it. • Release thromboxane A2, serotonin and thrombin, all vasoconstrictor substances that lead to a vicious cycle of recurring occlusion. 4 2.http://www.emedicine.com/emerg/TOPIC831.HTM Thrombosis of coronary arteries Rupture of plaques or fragmentation, followed by subsequent release of the material. Formation of a "buffer" platelet; Liberation from the material of the plate, thromboplastin which will activate the clotting; Obstruction of the vascular lumen components of the plate; 5 AMI 2.http://www.emedicine.com/emerg/TOPIC831.HTM AMI Diagnosis • Signs and symptoms; • Biochemical data; How should we react? • ECG alterations (ST-elevation). 6 http://www.emedicine.com/emerg/TOPIC327.HTM Identify the signals Activate the National Institute of Medical Emergencies (112) Reduction of injuries and consequent harm to the patient “Time is myocardium” 7 Signs and Symptoms • Retrosternal discomfort ; • Discomfort in one or both arms, neck, the jaw, on the back or epigastrium; • Dyspnea ( breathing difficulty); • Diaphoresis (excessive sweating), nausea and vomiting. 8 1.http://www.emedicine.com/emerg/TOPIC327.HTM ECG An electrocardiogram is a noninvasive transthoracic graphic produced by an electrocardiograph, which records the electrical activity of the heart over time. 9 Normal ECG Schematic representation of normal ECG 3.http://www.ecglibrary.com/ ECG with ST-elevation The typical ST segment duration is usually around 0.08 sec (80 ms). An elevation of >1mm and longer than 80 milliseconds may indicate myocardial infarction. Schematic ECG with St-elevation 10 ECG showing ST-segment elevation (orange) and reciprocal changes (blue) in the inferior leads. 3.http://www.ecglibrary.com/ Treatment • In acute myocardial infarction with ST-segment elevation the best treatment is reperfusion in the first 2 hours after the onset of symptoms. Reperfusion 11 Pharmacologic al Mechanical Thrombolytic therapy Angioplasty 4. ACC/AHA Guidelines for the management of patients with STelevation myocardial infarction. 5. JAMA, 287(15): 1943–1951. Thrombolytic therapy • Treatment given intravenously allowing the opening of the coronary artery; • The thrombolysis consists in the dissolution of the fibrin clot that blocks thrombus included in the coronary artery. 12 4. ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction. 5. JAMA, 287(15): 1943–1951. American College of Cardiology and American Heart Association Recommendations (Guidelines) • ACC and AHA recognize that “most benefit in seen in those treated soonest with thrombolytics after the onset of symptoms.” • Their analysis of published studies “has shown significant reduction (range 15 to 20%) in early mortality with pre-hospital treatment.” • ACC and AHA think that “must be interpreted with caution” because in the analyzed studies “time to treatment was not randomized”. However, they consider results “as an additional indirect support for the initiation of fibrinolytic treatment”. • ´ACC and AHA also indicate that administration of thrombolytics is contraindicated in certain cases (Aortic dissection, knowing bleeding disorder, ischemic stroke, central nervous system damage or neoplasm,…) 13 4. ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction Background 14 • Time to thrombolysis remains a key modifiable determinant of mortality in ST-elevation myocardial infarction. Despite many years of medical advances, the time from symptom onset to thrombolysis has remained at large unchanged, with a median of 2.5–3 h.6 • A pre-hospital treatment strategy when compared with in-hospital thrombolysis may reduce time to thrombolysis with a subsequent reduce of in-hospital mortality and complications. 1-year mortality seems also to be reduced.6,7,8 Time till thrombolysis is a key factor in the reduction of injuries and harm to the patient. 6. European Heart Journal. 2006 May; 27(10):1146-1152; 7. Circulation. 2004 Oct 5; 110(14):1909-15; 8. European Heart Journal. 2008 October; [Epub ahead of print]. Problem • There are sparse and scatter data on the impact of pre-hospital thrombolysis (PHT) in real-life patients with ST-elevation myocardial infarction. Sometimes this data is even contradictory.9,10 Therefore it is difficult to evaluate the impact of PHT and how it reduces time to thrombolysis, complications and mortality. • In response to this problem, we will try to reunite the able information about this problematic and use it to find if PHT and the consequent reduction of till thrombolysis can really reduce complications and mortality. 15 9. Emergency Medicine Journal 2004; 21:625–629; 10. Heart 2002;88:583–586. Study Aim and Question PHT PHT Develop a study that could lead us to an answer the question: 16 Is PHT beneficial in terms of morbidity and mortality on patients with ST-elevation myocardial infarction? Objectives Determine if pre-hospital thrombolysis is associated with reduction in early and late (1 year) cardiovascular mortality in patients with ST elevation myocardial infarction. Evaluate if pre-hospital trombolysis is associated with prognosis improvement such as: hospital stay, left ventricular ejection fraction, reenfartion rates, reenfartion readmission rates. Determine if pre-hospital thrombolysis performed by non medical teams is associated with and increase in complication rates. 17 Methods • Systematic review of prospective cohort studies and posterior metanalysis. • If possible, we will also include clinical trials about PHT. Studies will be chosen according to the following criteria of inclusion and exclusion: 18 Inclusion Exclusion 1. Study type: Clinical trials and Cohort studies only; 2. Studies Aim: Studies that evaluate the efficacy of PHT; 3. Thrombolytic type: New generation thrombolytics; 4. Follow-ups till 1 year. 1. Study language: Non-english studies; 2. Thrombolytic type: 1st generation thrombolytics. Query (sketch) • Databases: • Keywords: Medline; 2. Scopus; 3. ISI Web of Knowledge. 1. 1. 2. 3. 4. 5. 19 Acute Myocardial Infarction (MeSH); Pre-hospital thrombolysis (MeSH); Alteplase, Reteplase OR Tecneplase; Treatment delay; Mortality (MeSH). References 20 1. Drew Evan Fenton et al. Myocardial Infarction [Internet]. New York: eMedicine Clinical Knowledge Base; [updated Oct 10, 2008].Available from: http://www.emedicine.com/emerg/TOPIC327.HTM 2. José G Cabañas et al. Thrombolytic Therapy [Internet]. New York: eMedicine Clinical Knowledge Base; [updated Jun 22, 2006].Available from: http://www.emedicine.com/emerg/TOPIC831.HTM 3. Dean Jenkins, Stephen Gerred. ECG Library [internet] [updated Oct 12, 2002]. http://www.ecglibrary.com. 4. American College of Cardiology (ACC) and American Heart Association (AHA) (2004). ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction. Report of the ACC/AHA Task Force on Practice Guidelines. 5. Aversano T, et al. Thrombolytic therapy vs. primary percutaneous coronary intervention for myocardial infarction in patients presenting to hospitals without on-site cardiac surgery. JAMA 2002 April 7; 287(15): 1943–1951. Available from References 21 6. Erik Björklund, Ulf Stenestrand, Johan Lindbäck, et al. Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction. European Heart Journal 2006 May; 27(10):114652. 7. Danchin N, Blanchard D, Steg PG, et al. Impact of pre-hospital thrombolysis for acute myocardial infarction on 1-year outcome: results from the French Nationwide USIC 2000 Registry. Circulation 2004 Oct 5;110(14):1909-15. 8. Danchin N, Durand E, Blanchard D. Pre-hospital thrombolysis in perspective. Overview of current guidelines and data from trials and registries on the best perfusion approach for acute MI with STelevation. European Heart Journal 2008 Oct 23. [Epub ahead of print] References 9. S Goodacre, A-M Kelly, D Kerr. Potential impact of interventions to reduce times to thrombolysis. Emergency Medicine Journal 2004 Sep;21(5):625-9. 10. J Wilkinson, K Foo, N Sekhri, J Cooper, et al. Interaction between arrival time and thrombolytic treatment in determining early outcome of acute myocardial infarction. Heart 2002 Dec;88(6):583-6. 22