FIBRINOLYTIC THERAPY

1. FIBRINOLYTIC THERAPY (Thrombolytic Therapy)

2. OBJECTIVES • Identify the indications for use in AMI • Identify the indications for use in acute non-hemorrhagic stroke • Have knowledge of patient selection criteria • Have an enlarged scope of knowledge with regard to fibrinolytics

3. INTRODUCTION • The goal of fibrinolytic therapy is to dissolve occlusive clots. • Thrombus occlusion leads to cessation of blood flow to the affected area leading to oxygen deprivation and tissue damage distal to the occlusion, leading to irreversible damage and possibly death.

4. THROMBOGENESIS Activation of coagulation cascade Traumatized tissue Production of fibrinogen Thrombin Fibrin Fibrin strands cross-link and trap red blood cells and platelets Clot is formed

5. FIBRINOLYSIS Convert to Plasmin Plasminogen activation Fibrin clot

6. Fibrinolytic therapy in AMI • Clot can be dissolved • Institute early • Limits infarct size • Preserve myocardial function • Decrease mortality and morbidity

7. Patient selection criteria • Continuous CP lasting at least 30 min • Symptom onset within 12 hours • ST elevation in 2 contiguous leads • CP unrelieved by NTG or nifedipine • No absolute contraindications present • Initiation of therapy can be prompt

8. Absolute Contraindications • Any hx of intracranial hemorrhage • Known intracranial neoplasm or AV malformation • Suspected aortic dissection • Active bleeding

9. Obtain orders Explain to pt and family Obtain informed consent Baseline labs and diagnostic tests At least 2 IV lines Gather equipment: Phillips monitor Zoll at bedside Ambu bag ready Suction Crash cart nearby Infusion pumps (3) General pre-fibrinolytic procedures

11. Tenecteplase (TNK) • Binds to fibrin and converts plasminogen to plasmin • Decreases circulating fibrinogen and plasminogen

12. TNK • Weight based • One dose • Reconstitute TNK vile with 10cc sterile H2O • Gently swirl • Give single bolus over 5 seconds • Maximum dose 50MG

13. TNK-Adverse reactions • Bleeding-internal or superficial • Reperfusion arrhythmias • Allergic rxn • Coronary artery re-occlusion

14. Surface Bleeding • Establish all peripheral IV sites prior to fibrinolytic infusion • Avoid IM injections • Monitor all venous and arterial sites frequently • Apply direct pressure to all bleeding for a minimum of 30 min. or homeostasis achieved

15. Coronary Artery Reperfusion • Normalization of the ST segment • Resolution of the CP or ischemic symptoms • Reperfusion arrhythmias • May not have any of the above

16. Reperfusion Arrhythmias Bradycardia V- tach Heart Blocks

17. Eftifibatide (Integrilin) • A cyclic amino acid that binds to the platelet receptor glycoprotein GP IIb/IIIa of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen • Used in combination with heparin and ASA

18. Integrilin • Weight based dosing, use insert chart • Initial bolus 180mcg/kg-single dose over 1-2 minutes • Infusion of 2mcg/kg/min. Glass 100 ml bottle. Need vented spike • Refrigerated • Option of low dose renal dose

19. Compatible With…

20. Tissue Plasminogen Activator (Activase,t-PA) • Activase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin • Then initiates local fibrinolysis • Give within 3 hours of stroke s/s

21. Indications for MI • Lysis of thrombi obstruction in the coronary arteries • Reduction of infarct size • Improvement of ventricular function • Reduction of incidence of CHF

22. Indications for stroke • Improve neurologic recovery • Reduce incidence of disability

23. t-PA Reconstitution • Open Activase powder and 100cc sterile H2o • Using piercing pin, push into Activase vial • Attach sterile water bottle to top • Allow the entire contents of water to flow down , invert gently

24. t-PA Administration • Use a separate IV line, use IV pump • Dosing different for stroke, pulmonary emboli, CVAD occlusions, and AMI • STROKE-0.9 mg/kg IV over one hour. With 10% of the dose given IV push over one minute • Max dose is 90mg

25. T-PA for MI • 100 mg over 90 min. • Bolus 15mg over 2 min. • Then 50 mg over 30 min. • Infuse last 35 mg over 60 min.

26. Heparin • Combines with other factors in the blood to inhibit the conversion of prothrombin to thrombin, and fibrinogen to fibrin • Adhesiveness of platelets is reduced • Well-established clots are not dissolved, growth is prevented and newer clots may be resolved

27. Heparin • Compatible with NTG and morphine at Y-site • Antidote – Protamine sulfate

28. Nitroglycerin • A vascular smooth –muscle relaxant and vasodilator. • Affects arterial and venous beds • Reduces myocardial O2 consumption, preload and afterload

29. Glass bottle, vented spike IV pump required. Given as mcg/min Usually 10-30mcg, titrate to pain Lasts only 3-5 minutes Compatible at Y-site with morphine and t-PA,heparin Side effects: abdominal pain, allergic rxn, dizzy, HA, low BP Nitroglycerin Administration

30. Metoprolol (Lopressor) • Cardioselective adrenergic blocking agent • Reduces incidence of recurrent MI • Reduces size of the infarct and the incidence of fatal arrhythmias • Lasts 4 hours • Contraindicated in HR < 45

31. Lopressor Administration • Five milligrams at five minute intervals to a total dose of 15 mg • Monitor rhythm, BP and HR between all doses • Hold for SBP less than 100 • Compatible at Y-site with morphine

32. Concurrent Drugs Aspirin NTG sublingual Lidocaine Nifedipine

33. Door to drug time is 30 minutes